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Diabetes mellitus type 1 in children

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Oct.16.2023

Diabetes Mellitus Type 1 in Children

Synopsis

Key Points

  • Diabetes mellitus type 1 is a chronic metabolic disease characterized by hyperglycemia and absolute insulin deficiency secondary to destruction of pancreatic β-cells
  • Type 1 diabetes accounts for most cases of diabetes diagnosed in childhood
  • Children with type 1 diabetes typically present abruptly with severe hyperglycemia and/or in state of DKA
  • Children typically have an elevated glucose level, varying degrees of acidosis, and positive pancreatic islet autoantibodies findings
  • History and physical examination can suggest diabetes, but biochemical parameters are required for diabetes diagnosis; specific testing for pancreatic islet autoantibodies and C-peptide level can help differentiate diabetes type and confirm a diagnosis of type 1 disease
  • Differential diagnosis for type 1 diabetes in children includes type 2 diabetes and monogenic diabetes; children with cystic fibrosis may also have an associated form of diabetes
  • Initial treatment of severe hyperglycemia includes correction of fluid deficits and electrolyte abnormalities, insulin administration, dosing adjustments, and diabetes education
  • Initial treatment of severe hypoglycemia includes administration of rapidly absorbed glucose (oral), glucagon (IM or intranasal), and/or IV glucose, depending on patient's ability to use oral route
  • Comprehensive chronic management for children with type 1 diabetes includes intensive insulin therapy, glucose monitoring, age-appropriate diabetes education, lifestyle management including medical nutrition therapy, and ongoing assessment and treatment of associated comorbidities and complications
  • Most common acute complication associated with type 1 diabetes is DKA; in children, this may be associated with cerebral edema—the most common cause of death
  • Chronic complications associated with type 1 diabetes include cardiovascular disease, nephropathy, and retinopathy
  • Type 1 diabetes is associated with increased risk of mortality in children and adolescents

Urgent Action

  • DKA and severe treatment-related hypoglycemia are life-threatening complications and must be treated emergently
  • In any child with known diabetes who presents with altered mental status, check glucose level and correct any hypoglycemia immediately
  • If patient is severely hyperglycemic, correct volume deficits, electrolyte abnormalities, and administer insulin
  • Identify and treat any associated infections

Pitfalls

  • Failure to consider diabetes in a child with new-onset enuresis, weight loss, or poor school performance can delay diagnosis, leading to ketoacidosis
  • Failure to consider cerebral edema in a child with DKA and altered mental status may result in death
  • Children with overweight or obesity are at risk for type 2 diabetes, but they can also develop type 1 diabetes

Terminology

Clinical Clarification

  • Diabetes mellitus type 1 is a chronic metabolic disease characterized by hyperglycemia and absolute insulin deficiency secondary to destruction of pancreatic β-cells r1
  • People with diabetes mellitus type 1 have complete, lifelong dependence on exogenous insulin to regulate blood glucose levels r1

Classification

  • Immune-mediated diabetes r2
    • Type 1 diabetes caused by progressive cell-mediated autoimmune destruction of pancreatic β-cells
    • Accounts for most cases of type 1 diabetes mellitus, but only 5% to 10% of all cases of diabetes r2
    • Defined by presence of autoimmune markers, including autoantibodies to the following: GAD65 (glutamate decarboxylase 2), insulin, the tyrosine phosphatases IA-2 and IA-2β, and the zinc transporter protein ZnT8 (SLC30A8, a transporter related to insulin secretion)
  • Specific types of diabetes due to other causes r2
    • Monogenic diabetes, which includes neonatal diabetes and maturity-onset diabetes of the young; less than 5% of all cases of diabetes
    • Diseases of the exocrine pancreas, such as cystic fibrosis and pancreatitis
    • Drug- or chemical-induced diabetes
    • Idiopathic type 1 diabetes, characterized by permanent insulinopenia but absence of antibodies against β-cells; mainly occurs in patients with African or Asian ancestry and accounts for a minority of patients with type 1 diabetes
  • Stages r2r3
    • Stage 1: presymptomatic; normoglycemic in the presence of β-cell autoimmunity as evidenced by development of 2 or more type 1 diabetes–associated islet autoantibodies; fasting glucose and glucose tolerance within reference range
    • Stage 2: presymptomatic; progresses to glucose intolerance or dysglycemia (impaired fasting glucose), also in the presence of β-cell autoimmunity
    • Stage 3: onset of symptomatic disease as defined by standard criteria; overt hyperglycemia; autoantibodies may become absent

Diagnosis

Clinical Presentation

History

  • Patient typically presents abruptly with severe hyperglycemia and/or in state of DKA c1
    • Approximately 30% to 40% of children present with DKA; rates have increased over time r4c2d1
  • Most common presenting symptoms r5
    • Polyuria c3
    • Polydipsia c4
    • Nocturia c5
    • Polyphagia c6
    • Unexplained weight loss c7
  • Less common symptoms at presentation
    • Nausea or vomiting c8c9
    • Abdominal pain c10
    • Fatigue c11
    • Blurred vision c12
  • Commonly missed scenarios in children r5
    • Onset of enuresis in a previously toilet-trained child c13
    • Perineal candidiasis, especially in prepubertal girls c14c15
    • Chronic weight loss or failure to gain weight in a growing child c16c17
    • Irritability and deteriorating school performance c18c19
    • Recurrent skin infections c20
  • Rarely, type 1 diabetes is discovered presymptomatically when metabolic abnormalities are mild (incidental glucosuria), but this is more likely to occur in adults r6c21

Physical examination

  • Findings are unremarkable, except in severe hyperglycemia with DKA
    • Kussmaul respiration: high respiratory rate and large tidal volume of each breath c22c23
    • Altered mental status: disoriented, semicomatose, or rarely comatose c24c25c26c27c28c29c30c31
    • Signs of dehydration: orthostatic hypotension, tachycardia, and poor skin turgor c32c33c34c35c36c37c38c39
    • Fruity odor to the breath, caused by ketosis c40c41

Causes and Risk Factors

Causes

  • Autoimmune (most common cause in childhood) c42
    • T cell–mediated autoimmune disease characterized by selective destruction of pancreatic β-cells
    • Islet cell antibodies, produced in response to an environmental trigger, destroy pancreatic β-cells in genetically susceptible persons
      • Although it is commonly held that signs of diabetes occur when more than 80% of β-cells are destroyed, some studies have concluded that this is often an overestimate and that even a 40% reduction is sufficient to produce symptoms in some persons r7
  • Idiopathic c43
    • Pancreatic β-cell failure that occurs without autoimmune destruction c44
    • Strong inheritance pattern r2

Risk factors and/or associations

Age
  • Type 1 diabetes accounts for most cases of diabetes diagnosed in childhood r8c45
  • Can occur at any age; up to 25% to 50% of people with type 1 diabetes present in adulthood r8c46
Sex
  • Approximately equal distribution between males and females overall r9c47c48
Genetics
  • Risk of type 1 diabetes is conferred by 2 susceptible haplotypes in the region of the HLA complex in the class II region r10c49
    • Specific HLA DR/DQ alleles associated with type 1 diabetes include DRB1*03:01-DQB1*02:01 (DR3/DQ2) or DRB1*04:01-DQB1*03:02 (DR4/DQ8) r11c50c51
    • While a large proportion of people with type 1 diabetes carry a susceptible haplotype, only a small proportion of people in the general population with this susceptible haplotype actually develop the disease
      • 40% to 50% of familial clustering in type 1 diabetes is due to the susceptible haplotype in the HLA complex r12
      • Remaining proportion of familial clustering caused by genetic susceptibility is associated with variations at numerous other loci (more than 50), each of which accounts for a modest impact on risk r13
  • Familial clustering r9c52
    • Having a first-degree relative with type 1 diabetes carries a 5% lifetime risk of developing the disease, compared with a 0.3% risk in the general population r14
      • Monozygotic twins have a cumulative concordance rate of 65%,r15 whereas dizygotic twins have a concordance rate of 6% to 10%r9c53c54
      • Offspring of affected mothers have a 2% to 3% risk, whereas offspring of affected fathers have a 7% risk r9
  • Neonatal (congenital) diabetes
    • Most sequence variants that cause diabetes in the first 6 months of life are dominantly inherited r2
    • The most common of such disease-associated variants involve the Kir6.2 subunit (KCNJ11) and SUR1 subunit (ABCC8) of the β-cell ATP-sensitive potassium channel r2c55
    • The second most common of such disease-associated variants are in INS, the insulin gene r2
Ethnicity/race
  • Incidence and prevalence are highest in non-Hispanic White people r9r16c56c57c58c59
    • In the United States, incidence is increasing at greater rate in racial/ethnic minority youth compared with White populations r17
  • Incidence is highest in Finland, Sardinia, Sweden, northern Europe, North America, and Australasia; lowest incidence is in East Asia and Southeast Asia r18
  • Most patients with idiopathic diabetes are of Asian or African descent r2c60c61c62c63
Other risk factors/associations
  • Clustering with other autoimmune disorders associated with genetic susceptibility r9c64
    • Thyroid disease c65
      • Autoimmune hypothyroidism occurs in approximately 15% to 30% of children and adolescents with type 1 diabetes r19c66
      • Hyperthyroidism is much less common (approximately 0.5% of children with type 1 diabetes), but it occurs at higher frequency than in the general population r20c67
    • Celiac disease c68
      • Symptoms include diarrhea, weight loss, abdominal pain, bloating, chronic fatigue, malnutrition due to malabsorption, and unexplained hypoglycemia or erratic blood glucose levels
      • Occurs more frequently in children or adolescents with immune-mediated type 1 diabetes mellitus (4%-9%) compared with the general population (0.3%-1%) r19
      • Autoantibodies indicative of celiac disease include IgA antitissue transglutaminase and antiendomysial antibodies
    • Autoimmune polyendocrine syndrome type 1r21(OMIM #240300)r22c69
      • Autosomal dominant or recessive disorder caused by sequence variants in the AIRE gene (autoimmune regulator)
      • Type 1 diabetes occurs in 4% to 18% of cases r21
      • Syndrome also includes mucocutaneous candidiasis, hypoparathyroidism, and Addison disease
    • X-linked immunodysregulation, polyendocrinopathy, and enteropathy (OMIM #304790)r23c70c71c72c73
      • X-linked recessive disease caused by sequence variants in the FOXP3 gene (encoding forkhead box P3) c74
      • Affects only boys, and is characterized by severe neonatal autoimmunity that leads to death in infancy
    • Autoimmune polyendocrine syndrome type 2r21(OMIM #269200)r24c75
      • Rare disorder of unknown molecular basis; susceptibility is linked to class II alleles within the major histocompatibility complex
      • Approximately 60% of patients with this syndrome develop type 1 diabetes r21
      • Clinical components, which also include Addison disease and autoimmune thyroid disease, most often evolve in the third decade of life, but they can present in childhood
  • Recurrent viral respiratory tract infections during the first 6 months of life are associated with slightly increased risk r25c76
  • Season of birth r26
    • Higher prevalence among those born in April through July c77c78
    • Lower prevalence among those born in November through February c79c80
  • Birth size
    • Being born large for gestational age is a risk factor for type 1 diabetes; independent of maternal BMI and diabetes status r27c81
  • Season of onset
    • Higher incidence of onset from late autumn through early spring compared with the rest of the year c82
  • Vitamin D deficiency and insufficiency is common at onset of type 1 diabetes in children r28c83

Diagnostic Procedures

Primary diagnostic tools

  • History and physical examination can suggest diabetes, but biochemical parameters are required for a diagnosis c84
  • Laboratory confirmation of diabetes can be achieved with either of the following: r2
    • 2 diagnostic test results from among the following 3 tests, using the same or 2 different types of tests and the same or 2 different test samples:
      • Fasting plasma glucose level of 126 mg/dL or higher (no caloric intake for at least 8 hours before blood draw) c85
      • Hemoglobin A1C measurement of 6.5% or higher c86
      • 2-hour plasma glucose measurement of 200 mg/dL or higher during an oral glucose tolerance test (rarely used for patients with type 1 diabetes mellitus) c87c88
    • One random plasma glucose measurement of 200 mg/dL or higher when classic symptoms of hyperglycemia or hyperglycemic crisis are present
  • Pancreatic islet autoantibodies and C-peptide levels are useful laboratory studies for determining diabetes type classification when there is uncertainty about type 1 status r2c89
  • Initial diagnostic assessment of comorbidities at time of diagnosis r29r30
    • Measure blood pressure, fasting lipid panel, and urinary albumin excretion c90c91c92
    • American Diabetes Association provides complete lists of comprehensive medical evaluation components to cover at initial evaluation r29r30
  • Additional baseline laboratory tests recommended at diagnosis to screen for associated diseases include: r29r30
    • Lipid panel (after glucose control has been established for those aged 2 years or older) c93
    • Liver function tests c94
    • Spot urinary albumin to creatinine ratio (at puberty or after age 10 years, whichever is earlier, and diabetes duration of 5 years) c95
    • Estimated GFR/creatinine clearance c96
    • TSH, antithyroid peroxidase, and antithyroglobulin antibodies (soon after diagnosis) r29c97c98c99
    • Celiac antibody panel (soon after diagnosis) r29
      • Obtain IgA tissue transglutaminase antibodies in patients with documented total serum IgA levels within reference range; obtain IgG to tissue transglutaminase and deamidated gliadin antibodies in IgA-deficient patients c100

Laboratory

  • Fasting glucose measurement c101
    • Diagnostic thresholds are as follows: r2
      • Fasting glucose reference range: less than 100 mg/dL (less than 5.6 mmol/L)
      • Impaired fasting glucose: 100 to 125 mg/dL (5.6-6.9 mmol/L)
      • Diabetes mellitus: 126 mg/dL (7 mmol/L) or greater
    • Fasting requires no caloric intake for at least 8 hours r2
    • In absence of unequivocal symptomatic hyperglycemia, diabetes diagnosis must be confirmed by another abnormal test result; can be the same or different type of test and can be from the same or different test samples r2
  • Random glucose measurement c102
    • A single measurement of 200 mg/dL (11.1 mmol/L) or greater when signs or symptoms of hyperglycemia are present confirms diagnosis of diabetes r2
    • Many children with type 1 diabetes will present with severe symptomatic hyperglycemia or DKA, thus fulfilling this criterion
  • Hemoglobin A1C r2c103
    • Diagnostic threshold is 6.5% or greater
    • In absence of unequivocal symptomatic hyperglycemia, diabetes diagnosis must be confirmed by another abnormal test result; can be the same or different type of test and can be from the same or different test samples
    • Indirect measure of average glycemic control over 2 to 3 months and is used to monitor overall level of control
    • Strongly predictive for complications
    • Perform hemoglobin A1C testing using method certified by NGSP (sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases)r31 and standardized to the Diabetes Control and Complications Trial assay (to avoid misdiagnosis or missed diagnosis)
    • Limitations
      • Measurement of 6.5% or greater is a highly specific—but not sensitive—early indicator of disease compared with diabetes diagnosed by oral glucose tolerance test or asymptomatic hyperglycemia r16
      • Marked discordance between measured hemoglobin A1C and plasma glucose levels raises the possibility of assay interference
        • Consider using an assay without interference or plasma blood glucose criteria to diagnose diabetes if marked discordance exists
      • Relationship between hemoglobin A1C and glycemia may be altered by certain conditions; in these contexts, only plasma blood glucose criteria should be used to diagnose diabetes. Such conditions include:
        • Those associated with increased RBC turnover (eg, recent blood loss, transfusion, hemolysis)
        • Hemoglobinopathies (eg, sickle cell disease)
        • Anemia
        • Pregnancy (second and third trimesters, postpartum period)
        • HIV
        • Hemodialysis or erythropoietin therapy
      • Hemoglobin A1C levels may vary with patients' race/ethnicity; Black patients may have higher levels than non-Hispanic White patients despite similar fasting and 2-hour postprandial glucose levels
  • Oral glucose tolerance test c104
    • Technically, can be used to make a diagnosis of diabetes mellitus, but not especially useful when type 1 diabetes is suspected in a child
    • Many children with type 1 diabetes present with DKA or symptomatic hyperglycemia, rendering glucose challenge unnecessary
  • Pancreatic islet autoantibodies r14c105
    • Type 1 diabetes is defined by presence of 1 or more autoantibodies against islet cell antigens (commercial laboratory assays measure all four) r2
      • Autoantibodies against a glutamic acid decarboxylase isoform (GAD2, alias GAD65)
        • Most widely available and best characterized test
        • Detected in 50% to 80% of patients with type 1 diabetes r32r33
        • Seroconversion usually precedes onset of clinical manifestations of disease, and result remains positive thereafter
      • Autoantibodies against certain protein tyrosine phosphatases that are cell membrane autoantigens, including on islet cells (ie, PTPRN and PTPRN2, alias IA-2 and IA-2β, respectively)
        • Detected in over 30% to 70% of patients with newly diagnosed disease r32r33
      • Autoantibodies against a zinc transporter protein (SLC30A8, alias ZnT8) (solute carrier family 30 member 8)
        • Test is largely available in research settings
        • Detected in 50% to 70% of patients with newly diagnosed disease r32r33
      • Autoantibodies to insulin
        • Must be measured before or within 2 weeks of initiating insulin therapy r33
        • Detected in over 50% to 90% of patients with newly diagnosed disease r32r33
    • Absence of pancreatic autoantibodies does not rule out type 1 diabetes r34
      • Up to 10% of patients with new-onset type 1 diabetes have been found to have no islet antibodies in White European study populations r34
      • Pancreatic autoantibody titers diminish over time, which can produce false-negative results r35
  • C-peptide r34c106
    • Surrogate marker for insulin secretion
    • Can be obtained if islet autoantibodies are absent and diabetes type remains unclear
    • Use of C-peptide level to aid in classification is most useful when done several months or even 1 year after diagnosis because of the possibility that levels measured soon after diagnosis can be low owing to glucotoxicity r36
    • A frankly low level or complete absence of C-peptide is indicative of type 1 diabetes r37
    • Detectable C-peptide does not entirely exclude type 1 diabetes; some residual C-peptide secretion occurs in a significant proportion of patients in the first few years after diagnosis r38

Other diagnostic tools

  • Genetic testing r2
    • Genetic testing for neonatal diabetes is indicated for any child with diabetes diagnosed in the first 6 months of life
    • Testing should include, at minimum, mutational analysis of genes encoding the Kir6.2 subunit (KCNJ11) and SUR1 subunit (ABCC8) of the β-cell ATP-sensitive potassium channel, and the INS gene (encoding insulin) c107

Differential Diagnosis

Most common

  • Type 2 diabetes mellitus c108d2
    • Typical features include obesity, insulin resistance, and strong family history of type 2 diabetes
    • Patients exhibit marked insulin resistance or, alternatively, insulin needs resolve
    • Differentiated from type 1 diabetes on basis of clinical course and pancreatic islet autoantibodies
      • Clinical course of type 1 diabetes is characterized by ongoing, absolute insulin requirement that is lifelong, whereas insulin dependency in type 2 diabetes is absent or develops later
      • Positive pancreatic islet autoantibodies finding usually indicates type 1 diabetes r2
      • Initial diabetes diagnosis in children favors type 1 diabetes; type 2 diabetes is more likely after age 35 years r34
      • Lower BMI, unintentional weight loss, ketoacidosis, and severe hyperglycemia at presentation also favor type 1 diabetes r34
      • Type 2 diabetes most often responds to noninsulin antihyperglycemic agents early in the course of disease (eg, metformin, glyburide)
    • C-peptide levels are helpful for distinguishing type 1 from type 2 diabetes, but the measurement is most useful several months to a year after therapy begins, allowing for the resolution of any glucotoxicity
      • Most patients with type 1 diabetes have an undetectable or low C-peptide level r37
      • Fasting C-peptide level greater than 3 nanograms/mL after several months of therapy is highly suggestive of type 2 diabetes r39
  • Monogenic diabetes mellitus r40c109
    • Set of disorders that cause β-cell dysfunction and impaired insulin secretion, with onset of hyperglycemia in youth r41
    • Prevalence of 1% to 2% in pediatric diabetes population r42
    • Consider in children with the following findings: r40
      • Diabetes diagnosed within the first 6 months of life r2
      • Strong family history of diabetes suggesting autosomal dominant inheritance r2
      • Mild fasting hyperglycemia (100-150 mg/dL [5.5-8.5 mmol/L]), especially if young and without obesity r40
      • Diabetes with negative autoantibodies results and without signs of obesity or insulin resistance r2
    • Differentiated from type 1 or type 2 diabetes with genetic testing
  • Characteristics of types of primary diabetes in children and adolescents.Data from Chiang JL et al: Type 1 diabetes in children and adolescents: a position statement by the American Diabetes Association. Diabetes Care. 41(9):2026-44, 2018; American Diabetes Association: 2. Classification and diagnosis of diabetes: Standards of Medical Care in Diabetes--2022. Diabetes Care. 45(suppl 1):S17-38, 2022; and Mayer-Davis EJ et al: ISPAD clinical practice consensus guidelines 2018: definition, epidemiology, and classification of diabetes in children and adolescents. Pediatr Diabetes. 19(suppl 27):7-19, 2018.
    CharacteristicImmune-mediated type 1 diabetesIdiopathic type 1 diabetesMonogenic diabetesType 2 diabetes
    Prevalence
    In children with diabetes (overall)Most cases of type 1 diabetes in children, but 5% to 10% of all diabetes10% or higher in African-American children1% to 6%Approximately 12%
    EthnicityAll, White populations at highest risk (30%-60% lower in African-American populations)African-American and Asian populationsAllAll, minority groups at highest risk in North America 
    Onset
    Typical age at onset in childrenThroughout childhood and adolescence, but may occur into 8th or 9th decade of lifePubertalTypically younger than 35 yearsPuberty (mean age, 13.5 years)
    OnsetAcute severeAcute severeGradualInsidious to severe
    DKA at onsetApproximately 32% in United States (up to 80% globally)EpisodicNot typical5% to 20%
    Heredity
    Affected relative3% to 10%More than 75%50% to 90%Up to 90%
    InheritancePolygenicAutosomal dominant Autosomal dominantPolygenic
    HLA-DR3/4 associationPresentAbsentAbsentAbsent
    Insulin status
    Insulin (C-peptide) secretionReduced or absentVariably reducedVariably reducedVaries (up 85% impairment at time of diagnosis)
    Insulin sensitivityNormal when controlledNormalNormalReduced
    Insulin dependence Lifelong Intermittent VariableVariable
    Associated features
    Islet autoantibodies80%-90%AbsentLess than 1%Less than 10%
    Acanthosis nigricansMatches general populationMatches general populationMatches general population86%
    ObesityMatches general populationVaries by populationUncommonMore than 90%

Cystic fibrosis–related diabetes r43c110d3

  • Diabetes occurs in 20% of adolescents with cystic fibrosis, and it is typically discovered through screening measures r43
  • Results primarily from insulin deficiency but is also marked by high degree of insulin resistance
  • Hyperglycemia can be transient and dependent on any acute illness, inflammation, bowel function, or use of medication that promotes glucose intolerance
  • Differentiation from type 1 diabetes is usually made on basis of patient's known history of cystic fibrosis

Treatment

Goals

  • Goals of initial management r36
    • Correct fluid and electrolyte imbalances
    • Stabilize metabolic state with insulin
    • Provide basic diabetes education and self-management training for child and caregivers
  • Goals of chronic management
    • Realize that all glycemic goals are individualized based on the child's current life circumstances and may change over time
    • Aim for optimal glycemic control
      • Hemoglobin A1C target level less than 7% is appropriate for most children r29
        • A goal of less than 6.5% is reasonable for selected children if it can be achieved without excessive hypoglycemia or other negative impacts on well-being, or undue burden of care
        • In light of improved glucose monitoring and insulin delivery systems, current International Society for Pediatric and Adolescent Diabetes guidelines no longer recommend that risk of severe hypoglycemia justifies setting a hemoglobin A1C target over 7% for most patients, outside of resource-limited settings r44
        • American Diabetes Association guidelines state that less stringent A1C goals (eg, less than 8%) may be appropriate for children who experience severe hypoglycemia or have a limited life expectancy, or where the harms of treatment are perceived to be greater than the benefits r29
      • Target goals for measurements from glucometer
        • Preprandial, bedtime and overnight goal: 70 to 126 mg/dL (3.9-7 mmol/L) r1
        • Postprandial peak: 180 mg/dL (10 mmol/L) r1
        • Before physical activity and exercise: 126 to 180 mg/dL (7-10 mmol/L) r29
      • Ambulatory glucose profile targets (continuous glucose monitoring) r45
        • Note: spending 70% of time in range corresponds to hemoglobin A1C of 7%
        • Time in range (70-180 mg/dL): more than 70% or more than 16 hours and 48 minutes
        • Time below range (54-69 mg/dL): less than 4% or less than 1 hour
        • Time below range (less than 54 mg/dL): less than 1% or less than 15 minutes
        • Time above range (181-250 mg/dL): less than 25% (less than 4 hours)
        • Time above range (more than 250 mg/dL): less than 5% (less than 1 hour and 12 minutes)
        • Glycemic variability (%coefficient of variation): 36% or less
        • Percentage of time continuous glucose monitoring is active: 70% of data from 14 days
      • Minimize hypoglycemia (especially important for children younger than 6 years) r29
      • Avoid extreme fluctuations in blood glucose level
    • Maintain normal growth and development
    • Minimize risk of acute and chronic complications
  • Cardiovascular goals
    • Blood pressure
      • Consistently below 90th percentile for age, sex, and height r29
        • In adolescents aged 13 years or older, below 120/80 mm Hg r29
      • Reference ranges for age, sex, and height and appropriate methods for measurement are available from the American Academy of Pediatrics r46
    • Lipids
      • Goal is an LDL-C value lower than 100 mg/dL r29

Disposition

Admission criteria

New diagnosis

  • Consider the following factors when deciding to admit patient for new diagnosis of diabetes: r36
    • Severity of metabolic derangements
    • Family psychosocial circumstances
    • Resources available at the treatment center and experience in managing newly diagnosed children in an outpatient setting
  • New diagnosis of diabetes usually requires inpatient admission under the following circumstances: r47
    • DKA
    • Random glucose measurement 250 mg/dL or greater
    • Hemoglobin A1C greater than 9%
  • A large, multicenter, controlled trial (DECIDE) randomized clinically well children younger than 17 years with newly diagnosed type 1 diabetes to initial management at home or in hospital r48
    • No patients randomized to home management required hospital admission during treatment initiation
    • There were no significant differences in measures of blood glucose control, psychological outcomes, or serious adverse events during the 2 year follow-up

Established diagnosis

  • Failure to control diabetes as outpatient, when insulin adjustment and monitoring cannot be reliably and safely managed at home
Criteria for ICU admission
  • Any patient with severe DKA or the following: r49
    • Altered mental status
    • Consider for children younger than 5 years; strongly consider for children younger 2 years
    • pH less than 7.15 or bicarbonate level less than 5 mEq/L
    • Hemodynamic instability

Recommendations for specialist referral

  • A multidisciplinary treatment team of specialists with experience managing pediatric diabetes is ideal for care coordination r29
  • Refer all patients to pediatric endocrinologist for guidance on initiation and modifications of insulin regimen
  • Refer all patients to registered dietitian trained in the care of children and adolescents with type 1 diabetes
  • Refer to ophthalmologist to evaluate for retinopathy once child is aged 11 years or older, or puberty has started (whichever is earlier), and child has had diabetes for 3 to 5 years r29
  • Refer to nephrologist for management of diabetic nephropathy, as determined by development of modestly elevated urinary albumin excretion
  • Refer to mental health professional (clinical psychologist or social worker) for guidance on psychosocial issues, including diabetes-related family conflict and stress r29

Treatment Options

Initial management of children with newly diagnosed type 1 diabetes

  • For acutely ill children who present with severe hyperglycemia, the first priority is to treat dehydration, replace electrolytes, correct any acidemia, and administer insulin r36
  • Second priority is to provide basic diabetes education and self-management training for the child (age- and developmentally appropriate) and other caregivers r36

Long-term management of chronic disease in children with type 1 diabetes consists of several components, which together constitute a comprehensive treatment plan r29

  • Intensive insulin therapy r50
  • Glucose monitoring r50
  • Age-appropriate diabetes education r30
  • Lifestyle management including medical nutrition therapy r51
  • Ongoing assessment and treatment of comorbidities and complications r29

Insulin therapy

  • Intensive insulin therapy to simulate a physiologic pattern of insulin secretion is standard of care r52r53
  • Intensive insulin therapy consists of insulin delivery using 1 of 2 methods r53
    • Multiple (3-4 per day) daily injections, which combine basal and prandial insulin r54
      • Basal insulin is given as an injection of long- or intermediate-acting insulin, while meal-related glucose excursions are treated with bolus injections of rapid-acting insulin analogues or regular insulin
        • Basal insulin is designed to ideally provide enough insulin to maintain euglycemia between meals and overnight r55
        • Prandial doses (rapid-acting analogues or regular insulin) are used to limit glucose excursions that occur after meals or snacks
      • Injected insulin may be given via syringes or insulin pens
        • Modern insulin pens labeled as smart pens are linked to mobile apps that record the concurrent glucose level from a continuous glucose monitor. Use of smart pens has been associated with better glycemic control and reduce hypoglycemic events r56r57r58
    • Continuous subcutaneous insulin infusion (ie, insulin pump), which provides rapid-acting insulin through a catheter that is inserted into subcutaneous tissue of the anterior abdominal wall r54
      • Rapid-acting insulin analogue is typically used in the device
      • Provides a 24-hour preselected but adjustable basal rate of rapid-acting insulin, along with patient-activated mealtime bolus doses
      • Modern day insulin pump advances include sensor-augmentation; automated suspension of insulin delivery at low glucose thresholds; predictive low-glucose suspension, which reduces or stops insulin delivery based on input from linked continuous glucose monitors; and automated insulin delivery systems that assess the rate of change and increase or decrease insulin delivery without patient input (the latter are also known as hybrid closed-loop systems) r1r57
    • Most children with newly diagnosed disease start with a regimen of multiple daily injections; some may transition to continuous subcutaneous insulin infusion thereafter
    • Insulin analogues are preferred for both multiple daily injections and continuous subcutaneous insulin infusion; no clinically significant differences have been found among the various analogues available in the pediatric population r59
    • Both methods of insulin delivery require adjustment of the insulin dose depending on the preprandial glucose levels, dietary intake, and physical activity
      • At meals, a dose of rapid insulin is estimated based on preprandial blood glucose level and anticipated carbohydrate intake using individualized ratios of carbohydrate to insulin
    • Initial insulin therapy with either multiple daily injections or continuous subcutaneous insulin infusion requires comprehensive education
  • Safety and effectiveness of a prescribed insulin regimen depend on frequent blood glucose monitoring and/or a continuous glucose monitoring system to avoid hypoglycemia and glucose variability
  • Premixed insulin products are not recommended except in limited situations, such as when an adolescent refuses injections, a caregiver has limited math abilities, or a caregiver cannot mix insulin products r60

Glucose monitoring r50

  • Blood glucose monitoring is essential to determine basal and prandial insulin needs, to prevent hypoglycemia, and to assess response to changes in insulin dosing
  • Methods for monitoring blood glucose include capillary blood glucose testing using a glucometer or continuous glucose monitoring
  • If self-monitoring with a glucometer, children and adolescents may need to check capillary blood glucose levels up to 6 to 10 times per day, including before meals and snacks, at bedtime, and periodically in situations such as exercise, driving, or presence of hypoglycemic symptoms
  • Consider continuous glucose monitoring for all children and adolescents with type 1 diabetes who are capable of using the device safely, either independently or with caregiver assistance r29r50
    • Real-time continuous glucose monitors are a useful tool to lower and/or maintain hemoglobin A1C and/or reduce hypoglycemia in children with diabetes who are treated with insulin (eg, multiple daily injections, continuous subcutaneous insulin infusion); daily use is recommended r61
    • Intermittently scanned continuous glucose monitors may lower hemoglobin A1C and/or reduce hypoglycemia in children with diabetes who are treated with insulin; recommended frequency of scanning is at a minimum of once every 8 hours r61

Diabetes education r29r51

  • Purpose is to enable the patient to acquire the knowledge and skills necessary to make informed day-to-day management decisions and perform diabetes self-care
  • Begins at diagnosis with a series of formal sessions with a certified diabetes educator and continues longitudinally with periodic reassessment
  • Should be individualized, culturally sensitive, and developmentally appropriate

Medical nutrition therapy

  • Individualized nutrition counseling, provided by a registered dietitian, is recommended for all patients r29
  • Monitoring carbohydrate intake (ie, carbohydrate counting or experience-based estimation) is an important aspect in achieving optimal glycemic control r29
  • Nutrition counseling occurs as part of initial education and generally requires a series of sessions in the first several months after the diagnosis
  • Annually scheduled reorientations are ideal, with young children requiring more frequent reevaluations r29

Drug therapy

  • Insulin c111
    • Initial strategy at the time of a new diagnosis in insulin-naïve patients is as follows:
      • Starting doses vary widely, with higher doses usually necessary after a patient has stabilized from DKA
      • Divide total daily insulin into basal and prandial portions r8
      • Optimal dose of insulin maximizes glycemic control without causing frequent or severe hypoglycemia, and on a practical level, it can be determined empirically only with frequent blood glucose monitoring and insulin adjustments
    • Basal insulin c112c113c114c115
      • Degludec insulin
        • Insulin Degludec Solution for injection; Children and Adolescents: 30% to 45% of the total daily insulin dose subcutaneously once daily, initially. Adjust dose based on metabolic needs, blood glucose, and glycemic control goal. Use short-acting, prandial insulin to satisfy the remainder of the daily insulin requirements. The typical starting total daily insulin dose is 0.25 to 0.5 unit/kg/day for prepubertal or postpubertal children and 0.5 to 0.75 unit/kg/day during puberty. The typical maintenance total daily insulin dose is often less than 0.5 unit/kg/day during the partial remission phase, 0.7 to 1 unit/kg/day for prepubertal children outside the partial remission phase, and 1 to 2 units/kg/day during puberty.
      • Detemir insulin c116
        • Insulin Detemir (Recombinant) Solution for injection; Children and Adolescents 2 to 17 years: 30% to 45% of the total daily insulin dose subcutaneously once daily or divided twice daily, initially. Adjust dose based on metabolic needs, blood glucose, and glycemic control goal. Use short-acting, prandial insulin to satisfy the remainder of the daily insulin requirements. The typical starting total daily insulin dose is 0.25 to 0.5 unit/kg/day for prepubertal or postpubertal children and 0.5 to 0.75 unit/kg/day during puberty. The typical maintenance total daily insulin dose is often less than 0.5 unit/kg/day during the partial remission phase, 0.7 to 1 unit/kg/day for prepubertal children outside the partial remission phase, and 1 to 2 units/kg/day during puberty.
      • Glargine insulin c117
        • Insulin Glargine Solution for injection; Children and Adolescents 6 to 17 years: 30% to 45% of the total daily insulin dose subcutaneously once daily, initially. Adjust dose based on metabolic needs, blood glucose, and glycemic control goal. Use short-acting, prandial insulin to satisfy the remainder of the daily insulin requirements. The typical starting total daily insulin dose is 0.25 to 0.5 units/kg/day for prepubertal or postpubertal children and 0.5 to 0.75 units/kg/day during puberty. The typical maintenance total daily insulin dose is often less than 0.5 unit/kg/day during the partial remission phase, 0.7 to 1 unit/kg/day for prepubertal children outside the partial remission phase, and 1 to 2 units/kg/day during puberty.
      • NPH insulin (isophane insulin) c118
        • Insulin Suspension Isophane (NPH) (Recombinant) Suspension for injection; Infants, Children, and Adolescents: 30% to 45% of the total daily insulin dose subcutaneously once daily or divided twice daily, initially. Adjust dose based on metabolic needs, blood glucose, and glycemic control goal. Use short-acting, prandial insulin to satisfy the remainder of the daily insulin requirements. The typical starting total daily insulin dose is 0.25 to 0.5 unit/kg/day for prepubertal or postpubertal children and 0.5 to 0.75 unit/kg/day during puberty. The typical maintenance total daily insulin dose is often less than 0.5 unit/kg/day during the partial remission phase, 0.7 to 1 unit/kg/day for prepubertal children outside the partial remission phase, and 1 to 2 units/kg/day during puberty.
    • Prandial insulin c119c120c121c122c123
      • Short-acting insulin
        • Regular insulin c124
          • Insulin Regular (Recombinant) Solution for injection; Infants, Children, and Adolescents: 55% to 70% of the total daily insulin dose subcutaneously divided 2 to 3 times daily approximately 30 minutes before meals, initially. Adjust dose based on metabolic needs, blood glucose, and glycemic control goal. Use intermediate or long-acting basal insulin to satisfy the remainder of the daily insulin requirements. The typical starting total daily insulin dose is 0.25 to 0.5 unit/kg/day for prepubertal or postpubertal children and 0.5 to 0.75 unit/kg/day during puberty. The typical maintenance total daily insulin dose is often less than 0.5 unit/kg/day during the partial remission phase, 0.7 to 1 unit/kg/day for prepubertal children outside the partial remission phase, and 1 to 2 units/kg/day during puberty.
      • Rapid-acting insulin analogue
        • Aspart insulin c125
          • Insulin Aspart (Recombinant) Solution for injection; Children and Adolescents 2 to 17 years: 55% to 70% of the total daily insulin dose subcutaneously divided 5 to 10 minutes before meals, initially. Adjust dose based on metabolic needs, blood glucose, and glycemic control goal. Use intermediate or long-acting basal insulin to satisfy the remainder of the daily insulin requirements. The typical starting total daily insulin dose is 0.25 to 0.5 unit/kg/day for prepubertal or postpubertal children and 0.5 to 0.75 unit/kg/day during puberty. The typical maintenance total daily insulin dose is often less than 0.5 unit/kg/day during the partial remission phase, 0.7 to 1 unit/kg/day for prepubertal children outside the partial remission phase, and 1 to 2 units/kg/day during puberty.
        • Glulisine insulin c126
          • Insulin Glulisine Solution for injection; Children and Adolescents 4 to 17 years: 55% to 70% of the total daily insulin dose subcutaneously divided 15 minutes before or within 20 minutes after start of meals, initially. Adjust dose based on metabolic needs, blood glucose, and glycemic control goal. Use intermediate or long-acting basal insulin to satisfy the remainder of the daily insulin requirements. The typical starting total daily insulin dose is 0.25 to 0.5 unit/kg/day for prepubertal or postpubertal children and 0.5 to 0.75 unit/kg/day during puberty. The typical maintenance total daily insulin dose is often less than 0.5 unit/kg/day during the partial remission phase, 0.7 to 1 unit/kg/day for prepubertal children outside the partial remission phase, and 1 to 2 units/kg/day during puberty.
        • Lispro insulin c127
          • Insulin Lispro Solution for injection; Children and Adolescents 3 to 17 years: 55% to 70% of the total daily insulin dose subcutaneously divided 15 minutes before or immediately after meals, initially. Adjust dose based on metabolic needs, blood glucose, and glycemic control goal. Use intermediate or long-acting basal insulin to satisfy the remainder of the daily insulin requirements. The typical starting total daily insulin dose is 0.25 to 0.5 unit/kg/day for prepubertal or postpubertal children and 0.5 to 0.75 unit/kg/day during puberty. The typical maintenance total daily insulin dose is often less than 0.5 unit/kg/day during the partial remission phase, 0.7 to 1 unit/kg/day for prepubertal children outside the partial remission phase, and 1 to 2 units/kg/day during puberty.
      • Ultra rapid-acting insulin analogue
        • Aspart insulin
          • Insulin Aspart (Recombinant) Solution for injection; Children and Adolescents 2 to 17 years: 55% to 70% of the total daily insulin dose subcutaneously divided at the start of or within 20 minutes after starting meals, initially. Adjust dose based on metabolic needs, blood glucose, and glycemic control goal. Use intermediate or long-acting basal insulin to satisfy the remainder of the daily insulin requirements. The typical starting total daily insulin dose is 0.25 to 0.5 unit/kg/day for prepubertal or postpubertal children and 0.5 to 0.75 unit/kg/day during puberty. The typical maintenance total daily insulin dose is often less than 0.5 unit/kg/day during the partial remission phase, 0.7 to 1 unit/kg/day for prepubertal children outside the partial remission phase, and 1 to 2 units/kg/day during puberty.
    • Rapid-acting insulin analogue for continuous subcutaneous insulin infusion devices
      • Rapid-acting insulin analogue
        • Aspart insulin c128
          • Insulin Aspart (Recombinant) Solution for injection; Children 2 to 6 years: 30% to 35% of the total daily insulin dose by continuous subcutaneous infusion by insulin pump. Bolus mealtime and correction insulin dose by pump based on insulin-to-carbohydrate ratio and/or insulin sensitivity factor and target glucose 5 to 10 minutes before meals. Adjust basal dose based on overnight, fasting, or daytime glucose outside of activity of bolus doses. The typical starting total daily insulin dose is 0.25 to 0.5 unit/kg/day for prepubertal or postpubertal children and 0.5 to 0.75 unit/kg/day during puberty. The typical maintenance total daily insulin dose is often less than 0.5 unit/kg/day during the partial remission phase, 0.7 to 1 unit/kg/day for prepubertal children outside the partial remission phase, and 1 to 2 units/kg/day during puberty.
          • Insulin Aspart (Recombinant) Solution for injection; Children and Adolescents 7 to 17 years: 50% of the total daily insulin dose by continuous subcutaneous infusion by insulin pump. Bolus mealtime and correction insulin dose by pump based on insulin-to-carbohydrate ratio and/or insulin sensitivity factor and target glucose 5 to 10 minutes before meals. Adjust basal dose based on overnight, fasting, or daytime glucose outside of activity of bolus doses. The typical starting total daily insulin dose is 0.25 to 0.5 unit/kg/day for prepubertal or postpubertal children and 0.5 to 0.75 unit/kg/day during puberty. The typical maintenance total daily insulin dose is often less than 0.5 unit/kg/day during the partial remission phase, 0.7 to 1 unit/kg/day for prepubertal children outside the partial remission phase, and 1 to 2 units/kg/day during puberty.
        • Glulisine insulin c129
          • Insulin Glulisine Solution for injection; Children 4 to 6 years: 30% to 35% of the total daily insulin dose by continuous subcutaneous infusion by insulin pump. Bolus mealtime and correction insulin dose by pump based on insulin-to-carbohydrate ratio and/or insulin sensitivity factor and target glucose 15 minutes before or within 20 minutes after starting meals. Adjust basal dose based on overnight, fasting, or daytime glucose outside of activity of bolus doses. The typical starting total daily insulin dose is 0.25 to 0.5 unit/kg/day for prepubertal or postpubertal children and 0.5 to 0.75 unit/kg/day during puberty. The typical maintenance total daily insulin dose is often less than 0.5 unit/kg/day during the partial remission phase, 0.7 to 1 unit/kg/day for prepubertal children outside the partial remission phase, and 1 to 2 units/kg/day during puberty.
          • Insulin Glulisine Solution for injection; Children and Adolescents 7 to 17 years: 50% of the total daily insulin dose by continuous subcutaneous infusion by insulin pump. Bolus mealtime and correction insulin dose by pump based on insulin-to-carbohydrate ratio and/or insulin sensitivity factor and target glucose 15 minutes before or within 20 minutes after starting meals. Adjust basal dose based on overnight, fasting, or daytime glucose outside of activity of bolus doses. The typical starting total daily insulin dose is 0.25 to 0.5 unit/kg/day for prepubertal or postpubertal children and 0.5 to 0.75 unit/kg/day during puberty. The typical maintenance total daily insulin dose is often less than 0.5 unit/kg/day during the partial remission phase, 0.7 to 1 unit/kg/day for prepubertal children outside the partial remission phase, and 1 to 2 units/kg/day during puberty.
        • Lispro insulin c130
          • Insulin Lispro Solution for injection; Children 3 to 6 years: 30% to 35% of the total daily insulin dose by continuous subcutaneous infusion by insulin pump. Bolus mealtime and correction insulin dose by pump based on insulin-to-carbohydrate ratio and/or insulin sensitivity factor and target glucose 15 minutes before or immediately after meals. Adjust basal dose based on overnight, fasting, or daytime glucose outside of activity of bolus doses. The typical starting total daily insulin dose is 0.25 to 0.5 unit/kg/day for prepubertal or postpubertal children and 0.5 to 0.75 unit/kg/day during puberty. The typical maintenance total daily insulin dose is often less than 0.5 unit/kg/day during the partial remission phase, 0.7 to 1 unit/kg/day for prepubertal children outside the partial remission phase, and 1 to 2 units/kg/day during puberty.
          • Insulin Lispro Solution for injection; Children and Adolescents 7 to 17 years: 50% of the total daily insulin dose by continuous subcutaneous infusion by insulin pump. Bolus mealtime and correction insulin dose by pump based on insulin-to-carbohydrate ratio and/or insulin sensitivity factor and target glucose 15 minutes before or immediately after meals. Adjust basal dose based on overnight, fasting, or daytime glucose outside of activity of bolus doses. The typical starting total daily insulin dose is 0.25 to 0.5 unit/kg/day for prepubertal or postpubertal children and 0.5 to 0.75 unit/kg/day during puberty. The typical maintenance total daily insulin dose is often less than 0.5 unit/kg/day during the partial remission phase, 0.7 to 1 unit/kg/day for prepubertal children outside the partial remission phase, and 1 to 2 units/kg/day during puberty.
      • Ultra rapid-acting insulin analogue
        • Insulin aspart
          • Insulin Aspart (Recombinant) Solution for injection; Children 2 to 6 years: 30% to 35% of the total daily insulin dose by continuous subcutaneous infusion by insulin pump. Bolus mealtime and correction insulin dose by pump based on insulin-to-carbohydrate ratio and/or insulin sensitivity factor and target glucose at the start of or within 20 minutes after starting meals. Adjust basal dose based on overnight, fasting, or daytime glucose outside of activity of bolus doses. The typical starting total daily insulin dose is 0.25 to 0.5 unit/kg/day for prepubertal or postpubertal children and 0.5 to 0.75 unit/kg/day during puberty. The typical maintenance total daily insulin dose is often less than 0.5 unit/kg/day during the partial remission phase, 0.7 to 1 unit/kg/day for prepubertal children outside the partial remission phase, and 1 to 2 units/kg/day during puberty.
          • Insulin Aspart (Recombinant) Solution for injection; Children and Adolescents 7 to 17 years: 50% of the total daily insulin dose by continuous subcutaneous infusion by insulin pump. Bolus mealtime and correction insulin dose by pump based on insulin-to-carbohydrate ratio and/or insulin sensitivity factor and target glucose at the start of or within 20 minutes after starting meals. Adjust basal dose based on overnight, fasting, or daytime glucose outside of activity of bolus doses. The typical starting total daily insulin dose is 0.25 to 0.5 unit/kg/day for prepubertal or postpubertal children and 0.5 to 0.75 unit/kg/day during puberty. The typical maintenance total daily insulin dose is often less than 0.5 unit/kg/day during the partial remission phase, 0.7 to 1 unit/kg/day for prepubertal children outside the partial remission phase, and 1 to 2 units/kg/day during puberty.
    • Common insulin preparations and approximate action profiles.Chiang JL et al: Type 1 diabetes in children and adolescents: a position statement by the American Diabetes Association. Diabetes Care. 41(9):2026-44, 2018; Novo Nordisk Inc.: FIASP® (Insulin Aspart) Injection, for Subcutaneous or Intravenous Use. Highlights of Prescribing Information. Accessdata.fda.gov website. Updated June 2023. Accessed October 7, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/208751s020lbl.pdf
      Type of insulinOnsetPeakDuration
      Ultra-rapid-acting
      Aspart (Fiasp)15 to 20 minutes1.5 to 2.25 hours5 to 7 hours
      Rapid-acting
      Aspart (Novolog)15 to 30 minutes1 to 3 hours3 to 5 hours
      Lispro (Humalog)15 to 30 minutes1 to 3 hours3 to 5 hours
      Glulisine (Apidra)15 to 30 minutes1 to 3 hours3 to 5 hours
      Short-acting
      Regular insulin30 to 60 minutes2 to 4 hours5 to 8 hours
      Intermediate-acting
      NPH2 to 4 hours4 to 8 hours12 to 18 hours
      Long-acting
      Detemir (Levemir)2 to 4 hoursNone12 to 24 hours
      Glargine (Lantus)2 to 4 hoursNoneUp to 24 hours
      Degludec (Tresiba)2 to 4 hoursNoneMore than 24 hours

Nondrug and supportive care

Fluid administration to correct dehydration c131

  • Replace volume deficits with normal saline IV fluids at a rate not to exceed 1.5 to 2 times the usual daily maintenance requirement r49

Blood glucose monitoring r62c132

  • Point of care testing technology in which a small volume of capillary blood is placed on a test strip and inserted into a glucometer, providing a real-time digital display of blood glucose level
  • Indicated for all children with type 1 diabetes; introduced at diagnosis
  • Recommended testing frequency is a minimum of 4 blood glucose tests per day (before meals and at bedtime) r62
    • May be needed up to 6 to 10 times per day, including before meals and snacks, at bedtime, and as needed in specific situations such as exercise, driving, or presence of hypoglycemic symptoms r63
    • Mealtime testing results are used to determine prandial doses of insulin
  • School employees and caregivers should be knowledgeable about blood glucose monitoring and should be equipped with all necessary supplies
  • Real-time continuous glucose monitoring
    • Testing technology in which a catheter with a glucose oxidase sensor is placed subcutaneously to measure and record interstitial glucose concentrations and provide a real-time display of glucose levels
    • Personal continuous glucose monitoring devices are available either as stand-alone devices or combined with an insulin pump
      • Combined continuous subcutaneous insulin infusion and glucose monitoring systems (ie, sensor-augmented pump) function to deliver insulin and sample interstitial fluid glucose levels but do not automatically provide bolus doses
      • Combined continuous subcutaneous insulin infusion and glucose monitoring systems with threshold suspension functionality halt insulin delivery for up to 2 hours when the sensor glucose value reaches a predetermined lower threshold; this is a safety measure against an impending hypoglycemic event
    • Glucometric data analysis by the health care professional is used to adjust insulin doses
    • Overall, use of continuous glucose monitoring has a favorable balance of benefits (improved control) against any potential harms, especially in children with frequent hypoglycemia and/or hypoglycemia unawareness
      • Benefits of continuous glucose monitoring are proportional to adherence to wearing the device and are realized when data from the devices are reviewed for patterns to make thoughtful insulin dosage adjustments on a periodic basis r53
      • Continuous glucose monitoring, when used properly in conjunction with insulin therapy, is a useful tool to lower and/or maintain hemoglobin A1C levels and/or reduce hypoglycemia r64r65r66
      • As a general rule, adolescents and young adults (aged 13-24 years) are least likely to use the devices with regularity, and thus they often do not achieve hemoglobin A1C reductions as substantial as those in either younger children or adults
    • Indications
      • American Diabetes Association recommends offering continuous glucose monitoring to all youths with type 1 diabetes who are capable of using the device safely, either independently or with caregiver assistance r29r50
      • Other professional societies recommend real-time continuous glucose monitoring systems in children with type 1 diabetes under the following circumstances: r62
        • Frequent episodes of severe hypoglycemia, particularly nocturnal
        • Hypoglycemia unawareness
    • Contraindications
      • Relative: unwillingness to use glucometer to guide insulin dosing
  • Intermittently scanned (flash) continuous glucose monitoring r63r67
    • An alternative glucose-sensing device that does not require calibration (and is thus simpler and more attractive to users)
    • Displays present, 8-hour historic, and trend glucose data when scanned by the user with a near-field scanner
    • Intermittently scanned continuous glucose monitoring, when used properly with insulin therapy, may be useful to replace self-monitoring of blood glucose r29
    • A recent meta-analysis found that flash glucose monitoring did not lower hemoglobin A1c compared to self-monitoring of blood glucose, but did increase time in range and decreased number of hypoglycemic episodes r68
    • Not all models provide alarms for hypoglycemia or hyperglycemia r69

Diabetes education and self-management training r29c133c134

  • Family education and involvement is particularly important for optimal diabetes management in children and adolescents
    • Diabetes care team should encourage developmentally appropriate parental involvement in managing the patient's diabetes care tasks
  • Education is ideally provided with sensitivity to the age and developmental stage of the patient, with regard to approach and content delivered
    • For preschoolers, direct education toward the parents and primary caregivers; whereas, for most adolescents, direct education primarily toward the patient
  • To be effective, educational interventions need to be ongoing, with frequent in-person and telephone contact (improves hemoglobin A1C levels and decreases hospitalization rates for acute diabetes complications)
  • Counseling topics include the importance of optimizing blood glucose, lipid, and blood pressure treatment; encouragement to participate in regular exercise; and avoidance of smoking
  • Educational content is based on life stages and individualized to the patient's needs

Medical nutrition therapy r51c135

  • All patients with type 1 diabetes should receive nutrition counseling sessions that include both the patient and parents/caregivers
  • No special nutritional requirements for a child with type 1 diabetes, other than those for optimal growth and development r8
  • Registered dietitian constructs an individualized food plan with recommendations regarding daily caloric intake, division of calories between meals and snacks, meal composition, and macronutrient distribution r8
    • Total recommended caloric intake is based on size
    • Ideal macronutrient distribution is individualized;r51 general target includes a macronutrient distribution comprising approximately 55% carbohydrate, 30% fat, and 15% protein
    • Dietitian provides guidance on selection of type and amounts of carbohydrates, which are the primary determinants of insulin needs
      • Carbohydrate content should be approximately 70% complex, aiming for high fiber content with limited intake of sucrose or highly refined sugars
    • Ideally, dietary fats are polyunsaturated and from vegetable sources
  • Dietitian also educates patients and families on how to perform carbohydrate counting, as well as the impact that different types of carbohydrates exert on blood glucose levels and how these foods interact with exercise and insulin
  • Consider food preferences, as well cultural and ethnic diets
  • Consistent eating patterns with regular carbohydrate intake are advisable, although rare exceptions for excesses are permissible
  • Guidelines are available to guide management of diabetes in children and adolescents during fasting for Ramadanr70 and during intercurrent illnessr71

Immunizations r72

  • Annual influenza vaccine for children with diabetes who are aged 6 months or older c136
  • Pneumococcal polysaccharide vaccine for children with diabetes aged 2 years or older c137
  • Routine childhood vaccinations in accordance with recommended CDC vaccination schedulesr73c138
    • Since mid-2022, this includes COVID-19 vaccination for ages 6 months and older

Other lifestyle issues c139

  • Discourage smoking (including e-cigarettes) in young people who do not smoke and encourage smoking cessation in those who do r29c140d4
  • Limit exposure to cigarette smoke in the home
  • Instruct patients to wear medical alert bracelet

Physical activity c141

  • Encourage engagement in at least 60 minutes of moderate to vigorous aerobic physical activity daily (same recommendations for physical activity for all children, independent of a diagnosis of diabetes) r51
    • Exercise is essential to mitigation of cardiometabolic risk factors in children and adolescents with type 1 diabetes r74
    • Regular physical activity lowers hemoglobin A1C by 0.3%-0.5%, depending on baseline level and amount of physical activity r74
    • Physical activity improves insulin sensitivity r74
    • Regular exercise lowers the risk of premature all-cause and cardiovascular mortality r74
  • Encourage muscle and bone strengthening activities at least 3 times weekly r51
  • Inform patients that anaerobic exercise or high-intensity activity can result in hyperglycemia immediately after start of exercise; also, aerobic activity increases the risk of hypoglycemia during and after exercise r75
  • Strategies to prevent exercise-induced hypoglycemia include: r74
    • Aim for blood glucose level of 126 to 180 mg/dL before physical activity and exercise r29
      • If initial blood glucose levels are below goal, delay physical activity and consume sufficient carbohydrates until blood glucose level is within appropriate preexercise range r29r75
    • Adjust insulin and/or carbohydrate intake
      • Reduce prandial insulin dose for meal or snack preceding exercise r29
      • Increase carbohydrate intake before exercise r29
      • Reduce basal insulin rates on continuous subcutaneous insulin infusion device by approximately 10% to 50% or more or suspend for 1 to 2 hours during exercise r29
      • Reduce basal insulin rate or long-acting insulin dose by approximately 20% after exercise to mitigate delayed exercise-induced hypoglycemia r29
    • Monitor glucose frequently before, during, and after exercise
      • Have blood glucose testing supplies and sources of simple carbohydrate readily available to prevent and treat hypoglycemia r29
      • For more strenuous and prolonged activities, instruct patient to consume 0.5 to 1.5 g carbohydrates/kg for each hour of strenuous activity r75
      • Monitor blood glucose during periods of continuous physical activity approximately every 30 minutes as well as 15 minutes after completion of exercise and at bedtime r75
      • Detailed guideline recommendations are available outlining initial recommendations for general insulin therapy, carbohydrate consumption, and glucose sensor thresholds for patients using continuous glucose monitoring systems r74
      • Consider use of remote monitor (eg, mobile application) to watch continuous glucose monitoring system in real time during exercise to assess and respond to glycemic changes during activity r74
      • Use of a combined insulin pump/continuous glucose monitoring system, particularly one with a low glucose threshold–suspend feature, is strongly recommended r56
  • Marked hyperglycemia (glucose level of 350 mg/dL or more) before exercise should prompt delay of physical activity; presence of insulin deficiency and ketosis should be evaluated r29
  • If significant hyperglycemia occurs after exercise (usually from high-intensity exercise and increased catecholamine production), cautiously administer a small rapid-acting bolus of insulin r75

Behavioral and psychosocial aspects of care r29

  • Assess for psychosocial issues and family stress that may impact diabetes management; provide referrals to trained mental health providers when indicated
  • Encourage family involvement in diabetes management for children and adolescents, individualized to developmental appropriateness
  • Factors like food security, housing stability, health literature, financial constraints, and social support should be considered and incorporated in treatment planning
  • Consider assessing social adjustment (peer relationships) and school performance to determine if further evaluation is needed

Various diabetes advocacy position statements are available from the American Diabetes Association, including the following: r76

  • Diabetes care in the school setting r77r78
  • Care of young children with diabetes in the child care setting r79
  • Managing diabetes in preschoolers r80
  • Insulin access and affordability r81
  • Diabetes and driving r82
  • Diabetes and employment r83
  • Diabetes care in correctional institutions r84

When appropriate, telehealth should be used for sick day management and routine diabetes care

Procedures
Continuous subcutaneous insulin infusion (insulin pump) therapy r85r86c142c143c144c145c146
General explanation
  • Mechanically driven insulin delivery technology in which a catheter is placed subcutaneously to provide a continuous infusion of rapid-acting insulin; recently, a tubeless pump system that attaches directly to the body gained FDA approvalr87
  • Provided as a preset basal rate with operator-driven periodic boluses; basal delivery rate can be programmed to vary throughout the day
  • A sensor-augmented pump is a continuous subcutaneous insulin infusion device combined with a continuous glucose monitoring feature
    • A pump with threshold suspension functionality temporarily halts delivery of insulin when interstitial glucose levels fall below a set threshold
    • Sensor-augmented pumps with threshold suspension functionality are ideal for patients with frequent nocturnal hypoglycemia, recurrent severe hypoglycemia, or hypoglycemia unawareness
  • Automated insulin delivery systems combine an insulin pump, a continuous glucose monitor, and an algorithm that adjusts insulin delivery; multiple hybrid closed-loop devices have been approved by the FDA r61r88
    • Pump automatically adjusts delivery of basal insulin based on glucose values as determined by the continuous glucose monitor, without requiring intervention from the user; it automatically increases, decreases, and suspends insulin delivery in response to continuous glucose monitoring
    • Patients still must enter carbohydrate intake and periodically calibrate sensor, hence the "hybrid" closed-loop designation
      • Fully closed-loop systems requiring no user input are under development but not yet commercially available r89
    • Care givers should be aware that do-it-yourself systems that combine a continuous glucose monitor and an insulin pump with a controller and an algorithm are widely used
      • One such system that uses a phone-based app was recently approved by the FDA r90
  • Comparison of outcomes using multiple daily insulin injections versus continuous subcutaneous insulin infusion shows that the latter is associated with slightly lower hemoglobin A1C levels,r91less DKA,r92 and improved quality of lifer86
  • Use of continuous subcutaneous insulin infusion is associated with reduction in all-cause and cardiovascular mortality when compared with multiple daily insulin injections r93
Indication
  • Suggested indications vary among different professional societies
  • American Diabetes Associationr53r29 and International Society for Pediatric and Adolescent Diabetesr52 both recommend continuous subcutaneous insulin infusion as a possible alternative to multiple daily injections of insulin for all pediatric patients with type 1 diabetes
  • American Association of Clinical Endocrinologists suggests consideration of continuous subcutaneous insulin infusion therapy for children with type 1 diabetes under the following circumstances: r86
    • Elevated hemoglobin A1C levels on injection therapy
    • Frequent, severe hypoglycemia
    • Widely fluctuating glucose levels
    • Microvascular complications and/or risk factors for macrovascular complications
  • Hybrid closed-loop systems are intended for patients aged 14 years or older with type 1 diabetes r94

Complications r95

  • Cutaneous irritation or infection
  • Mechanical failures of software or hardware (eg, insulin leaking, screen fading, battery damage)
  • Catheter problems (eg, occlusion, bubbles, kinking)
Contraindications
  • Do not use hybrid closed-loop system in: r96
    • Anyone younger than 7 years
    • Patients who require less than a total daily insulin dose of 8 units/day; requires a minimum of 8 units/day to operate safely
Interpretation of results
  • Insulin pumps equipped with predictive threshold-suspend features appear to reduce hypoglycemia 2-fold (compared to standard sensor-augmented pumps without suspension feature) without deterioration in glycemic control r97
  • Hybrid closed-loop systems have been shown to be safe during in-home use by adolescents (and adults), to provide reductions in hypoglycemia and hyperglycemia, and to result in lower hemoglobin A1C values r98
  • Children and adolescents using a closed-loop system maintained glucose levels in the target range for a greater percentage of time than those using sensor-augmented insulin pumps r99r100r101
  • A recent large randomized trial found that a hybrid closed-loop system significantly improved glycemic control without increasing time spent in hypoglycemia even for very young children (aged 1 to 7 years) with type 1 diabetes, indicating promise for future use in this population r102

Comorbidities

  • Hypertension r29c147
    • Measure blood pressure at each office visit
    • Encourage adolescents with diabetes to use ambulatory blood pressure monitoring periodically r46
    • Normative blood pressure values and thresholds for diagnosing elevated blood pressure and hypertension are now lower than in previous classifications r29r46
      • Elevated blood pressure (previously termed "prehypertension") is either of the following confirmed on 3 separate visits: r46
        • Systolic or diastolic blood pressure in 90th to less than 95th percentile for age, sex, and height
        • 120 to 129 mm Hg systolic and less than 80 mm Hg diastolic in adolescents aged 13 years or older
      • Confirmed hypertension is either of the following confirmed on 3 separate visits: r46
        • Systolic or diastolic blood pressure in 95th percentile or higher for age, sex, and height
        • 130/80 mm Hg or greater in adolescents aged 13 years or older
    • Initial treatment for patients with high-normal blood pressure is aimed at lifestyle modifications of altering diet, increasing exercise, and controlling weight r29
      • Consider pharmacologic treatment of hypertension if target blood pressure is not reached with 3 to 6 months of using lifestyle methods r29
      • Ambulatory blood pressure monitoring is strongly encouraged for these patients r29
    • Consider starting pharmacologic treatment in addition to lifestyle modification in patients with hypertension (blood pressure at 95th percentile or greater for age, sex, and height, or 130/80 mm Hg or greater in adolescents aged 13 years or older) r29
      • ACE inhibitors or angiotensin receptor blockers (alternatively) are preferred in children with diabetes and hypertension r29
      • Use of an ACE inhibitor with statin is not recommended for primary prevention of microvascular complications because available data do not demonstrate reduction in albuminuria or progression of retinopathy r103
    • Goal blood pressure levels are those that are consistently below 90th percentile for age, sex, and height, or below 120/80 mm Hg in adolescents aged 13 years or older r29
  • Dyslipidemia c148
    • Dyslipidemia is a risk factor for atherosclerotic cardiovascular disease in type 1 diabetes
    • Initial therapy consists of both: r29
      • Optimizing glucose control (which can improve lipid values but not normalize them), and r104
      • Medical nutrition therapy to limit the amount of calories from fat to 25% to 30%, saturated fat to less than 7%, cholesterol less than 200 mg/day, avoidance of trans fats, and approximately 10% calories from monounsaturated fats r29
    • Pharmacotherapy with a statin is recommended for children aged 10 years or older if, after attempting therapeutic lifestyle change, LDL-C level remains higher than 160 mg/dL or LDL-C level remains higher than 130 mg/dL when the patient has 1 or more cardiovascular disease risk factors r29
      • Goal of therapy is to achieve LDL cholesterol value less than 100 mg/dL r29
  • Cardiovascular disease r105c149
    • Cardiovascular events generally do not occur during childhood, but atherosclerotic process begins during childhood in diabetes r106
      • Age and hemoglobin A1C level are strongest risk factors for a major atherosclerotic event or any cardiovascular disease in type 1 diabetes r107
      • Cardiovascular risk reduction involves optimizing glycemic control and managing other cardiovascular risk factors (eg, maintaining healthy body weight, physical activity, healthy diet, treating hypertension) r106
  • Autoimmune conditions c150
    • Assess for presence of thyroid dysfunction and celiac disease soon after initial diabetes diagnosis and if symptoms develop
      • Autoimmune thyroiditis c151
        • Most common autoimmune disorder associated with diabetes, occurring in 15% to 30% of children and adolescents with type 1 diabetes r19
        • Assess TSH level soon after initial diabetes diagnosis and metabolic stabilization, and obtain tests for anti–thyroid peroxidase and antithyroglobulin antibodies r29r108
        • If TSH levels are within reference range, consider rechecking every 1 to 2 years or more frequently if the patient has positive thyroid antibodies or develops symptoms suggestive of thyroid dysfunction, thyromegaly, abnormal growth rate, or unexplained glycemic variation r29
      • Celiac disease r109c152
        • Gluten-sensitive enteropathy that occurs in approximately 2% to 16% of patients with type 1 diabetes r29
        • Higher prevalence in patients with type 1 diabetes, family history of celiac disease, younger age, and associated thyroid autoimmunity r109
        • Children may be asymptomatic or may present with the following symptoms: weight loss, poor growth, anemia, dermatitis herpetiformis, bone and muscle pains, abdominal pain, diarrhea, constipation, mouth ulcers, bloating, and gas r109
        • Screen all children with type 1 diabetes at diagnosis; repeat screening within 2 years of diagnosis and then again after 5 years; consider more frequent screening in children with suggestive symptoms or first-degree relative with celiac disease r29
          • Obtain IgA tissue transglutaminase antibodies in patients with documentation of total serum IgA levels within reference range; obtain IgG to tissue transglutaminase and deamidated gliadin antibodies in IgA-deficient patients
        • Some experts suggest confirming celiac disease diagnosis with small-bowel biopsy, given potential challenges of recommended dietary restrictions for patients with both diabetes and celiac disease r29
        • Treat patients with confirmed celiac disease using gluten-free diet in consultation with a dietitian experienced in managing both diabetes and celiac disease r29
      • Other autoimmune conditions
        • Conditions that occur more commonly in children with type 1 diabetes include Addison disease (primary adrenal insufficiency), autoimmune hepatitis, autoimmune gastritis, dermatomyositis, and myasthenia gravis c153c154c155c156c157
        • A heightened awareness of the risk of such conditions is advisable, but routine screening of asymptomatic children is not recommended r29
  • Overweight and obesity
    • Children with overweight or obesity are at risk for type 2 diabetes, but they can also develop type 1 diabetes
    • Approximately 15% and 25% of children with type 1 diabetes in the United States are overweight or obese, respectively r110
    • Intensive diabetes management can make weight control challenging, although most series have found that overweight or obese body habitus is associated with higher hemoglobin A1C levels r111
    • Overweight or obese body habitus in youth with type 1 diabetes has negative implications for glycemic control, insulin resistance, and cardiovascular risk factors (eg, hypertension, dyslipidemia) r112
    • Suggested strategies for limiting weight gain include avoidance of excessive caloric intake, selecting more nutritious foods, encouraging regular physical activity, advising reduced screen time, and eliminating snacks r110
  • Psychosocial issues c158
    • Psychosocial distress is common, owing to burdens of diabetes management throughout childhood and adolescence r29c159c160
      • The term diabetes distress refers to the duress of constant behavioral demands of diabetes self-management (eg, medication dosing, frequency, and titration; monitoring blood glucose, food intake and eating patterns; physical activity) r113
      • Occurs in approximately one-third of adolescents with diabetes r114
      • Monitor for diabetes distress routinely (Diabetes Distress Scaler115) beginning at age 7 or 8 years,r29 and refer patient to diabetes education or a behavioral health provider if areas of diabetes care are impacted r113
    • Rates of depression are higher in youth with type 1 diabetes compared with youth without the disease r116c161
      • Annually screen youth for depression using depression screening tools r113r117
      • Consider screening for depression with any changes in medical status, including development of new complications r113
    • Comorbid anxiety complicates management of diabetes by mimicking symptoms of hypoglycemia; patient may also have fear of hypoglycemia that leads to intentionally maintaining blood glucose above healthy target levels r116c162
    • Mental health comorbidities can reduce adherence to treatment, which ultimately increases risk for long-term complications and reduces quality of life
      • Refer children or adolescents to a mental health provider for evaluation and treatment in the following situations: r113
        • Diabetes distress persists even after tailored diabetes education
        • Positive screening result for depression, eating disorder, or anxiety; suspicion for a serious mental illness; or fear of hypoglycemia
        • Repeated hospitalizations for DKA, intentionally omitting insulin, or declining to perform self-care behaviors (eg, injecting insulin, monitoring blood glucose)
    • Assess food security, housing stability/homelessness, health literacy, financial barriers, and social/community support and apply pertinent information to treatment decisions r29
  • Eating disorders c163
    • Approximately one-fourth of adolescents are at risk of diabetes-specific eating disorder r118
    • Disturbed eating behaviors, coupled with unhealthy weight control behaviors, correlate with worse glycemic control r119
      • Insulin omission or insulin underdosing (diabulimia) to lose weight is the most common and serious weight control behavior and is associated with increased morbidity and mortality r118r120
      • Consider reevaluating treatment regimen if symptoms of disordered eating behavior are evident
    • Screen for disordered eating behaviors in patients between the ages of 10 and 12 years with available screening tools,r121 particularly when hyperglycemia and weight loss are unexplained r29

Special populations

  • Patients in pubertal stage
    • Puberty is a state of relative insulin resistance and therefore insulin requirements increase substantially
    • Anticipate increases in basal and prandial insulin doses
      • Basal insulin requirements typically range from 1 to 2 units/kg/day r52
      • Increase insulin to carbohydrate ratios to estimate prandial doses r72
  • Older adolescents
    • Motor vehicle operation issues
      • Counsel adolescents to test blood glucose before driving, to carry a source of glucose, and to discontinue driving if symptoms of hypoglycemia occur; document this counseling in the record
    • Preconception counseling r122
      • Discuss risks of fetal malformations, maternal complications, and diabetes in offspring for female patients with reproductive potential
        • Major malformations are caused by hyperglycemia during the first 8 weeks of gestation and account for 50% of perinatal mortality r123
        • Fetal complications later in pregnancy arise from fetal hyperinsulinemia secondary to maternal hyperglycemia, leading to macrosomia r123
      • Discuss contraceptives with all female patients with childbearing potential r29
    • Transition to adulthood
      • Adolescents should gradually assume greater responsibility for diabetes management
      • Begin to prepare youth for transition in early adolescence r29
      • Start a transition plan at least 1 year in advance of transferring over to adult health care to prepare for issues related to insurance, obtaining diabetes supplies, affective disorders, reproductive health, substance use, and identifying an adult care physician r29r124
  • Adolescents who are pregnant r123
    • Most pregnancies in adolescents with type 1 diabetes are unplanned; referral to a high-risk obstetrics specialist is routine
    • Glycemic goals in pregnancy are more stringent
      • American Association of Clinical Endocrinologists targets r72
        • Hemoglobin A1C less than 6% during pregnancy
        • Preprandial glucose levels 95 mg/dL or less
        • Postprandial blood glucose level less than 140 mg/dL at 1 hour and less than 120 mg/dL at 2 hours
        • Should spend more than 70% of time in target range of 63 to 140 mg/dL
      • American Diabetes Association targets r122
        • Hemoglobin A1C level: ideal value is 6% or lower (may use target of less than 7% in patients with frequent hypoglycemia)
        • Fasting blood glucose level of less than 95 mg/dL
        • 1-hour postprandial blood glucose level less than 140 mg/dL or 2-hour postprandial blood glucose level less than 120 mg/dL
    • Pregnancy changes maternal insulin sensitivity, which results in altered insulin requirements
      • First trimester insulin requirements are typically lower, whereas second and third trimester requirements are typically higher, owing to increasing insulin resistance
      • Shift in allocation of total daily insulin
        • Increase proportion of insulin given with meals
        • Reduce dose of insulin given as basal proportion
      • Blood glucose monitoring may be required 10 or more times per day to achieve glucose targets while avoiding hypoglycemia
        • During pregnancy, both preprandial and postprandial blood glucose testing are required to achieve glycemic targets r122
      • Continuous glucose monitoring does not affect maternal or neonatal outcomes, but this technology may be useful for pregnant patients with preexisting type 1 diabetes who have unstable glucose levels and frequent hypoglycemia
    • Prescribe folic acid and prenatal vitamin as soon as pregnancy is confirmed
    • Perform fetal ultrasonography in first trimester to evaluate gestational age
    • Withdraw ACE inhibitors, angiotensin receptor antagonists, diuretics, and statins
    • Refer for baseline ophthalmologic examination in first trimester, and monitor every trimester as indicated by degree of retinopathy
    • Prescribe low-dose aspirin starting at end of first trimester to lower risk of preeclampsia r122

Monitoring

  • American Diabetes Association provides a complete list of comprehensive medical evaluation components to cover at annual examination and at each follow-up visit r30
    • Periodically reassess the following:
      • Diabetes self-management and support r29
      • Educational needs and training for those providing care for child (eg, day care providers, school personnel) r29
      • Growth and development
        • Measure height and weight at each visit, or on quarterly basis r16
        • Calculate BMI percentile and corresponding BMI-for-age percentile on quarterly basis r125
        • Regularly check injection sites and technique
      • Glycemic control
        • Blood glucose monitoring is essential for optimal management
          • Inverse relationship exists between frequency of blood glucose monitoring and hemoglobin A1C levels r126
          • Recommended frequency of blood glucose monitoring is determined on an individual basis according to blood glucose lability and likelihood of hypoglycemia
            • Minimum frequency of testing suggested is 4 times per day (premeal and at bedtime) r62
            • Testing at other times (eg, 2 hours after meals; overnight; before, during, and after exercise) can provide more information about glucose trends and aid in refining insulin doses r16r62r63
          • Blood glucose data are analyzed by treating physician to identify hyperglycemic and hypoglycemic trends, which are then used to adjust insulin dosing
          • Use of metrics obtained from a continuous glucose monitoring device may improve overall assessment of glycemic control; allows precise assessment of time with glucose in target range and frequency of hypoglycemia r50
            • Continuous glucose monitoring metrics are recommended to be used in conjunction with hemoglobin A1C values whenever possible r29
            • A 14-day continuous glucose monitoring assessment of time in range and glucose management indicator can serve as a surrogate for A1C for use in clinical management r50
            • Uncertainty exists surrounding ideal target time in range for children; general goal is a time in range greater than 70% with time below range less than 4% r29
            • Precise range for a given child's glucose parameters is somewhat individualized; general goal is target range of 70 to 180 mg/dL r29
        • Hemoglobin A1C serves as an indicator of long-term glycemic control
          • Also serves as correlate for risk of diabetes complications; lower hemoglobin A1C in adolescence and young adulthood is associated with a lower risk and rate of microvascular and macrovascular complications r2r127
          • Recommended measurement includes: r50
            • At least twice yearly in patients meeting treatment goals (stable glycemic control)
            • At least quarterly and as needed in patients whose therapy has recently changed and/or who are not meeting glycemic goals
          • Target goal hemoglobin A1C less than 7% is appropriate for many children; individualization of target goal may be necessary based on needs and situation of family and patient r29r44
        • Monitor blood or urine ketone levels in the setting of prolonged hyperglycemia or acute illness r16r63
          • Aids in determining whether adjustments to treatment and referral for urgent care are necessary
        • Follow-up visits with diabetes educators should occur at least every 3 to 6 months initially, individualized to the patient r30
          • Discuss self-care behaviors, physical activity, and daily routines
          • Inquire about frequency, severity, and circumstances surrounding hypoglycemic events
          • Review blood glucose monitoring data to identify patterns and trends in relation to insulin dosing and meals
          • Monitoring of carbohydrate intake (eg, carbohydrate counting, experience-based estimation) is an important aspect in achieving glycemic control r29
      • Comorbidities
        • Hypertension
          • Measure blood pressure at each routine visit r29
        • Dyslipidemia
          • Perform initial lipid testing when initial glycemic control has been achieved and patient is aged at least 2 years; perform subsequent testing at ages 9 to 11 years if initial LDL-C is 100 mg/dL or lower r29
            • Initial testing may be done with a nonfasting, non-HDL-C level with confirmatory testing using a fasting lipid panel
            • Lipid profile may be repeated every 3 years if LDL-C values are within the accepted risk level (less than 100 mg/dL);r29monitor annually if level is abnormalr16
        • Autoimmune thyroid disease
          • Annual thyroid examination with TSH measurement every 1 to 2 years or sooner if patient has positive thyroid antibodies or develops symptoms suggestive of thyroid dysfunction r29
          • If patient develops autoimmune hypothyroidism and takes thyroid hormone replacement, measure periodically to maintain TSH level within reference range
        • Celiac disease
          • Repeat screening within 2 years of initial screening (at time of diagnosis); provide follow-up with screening every 5 years or more frequently in patients with symptoms concerning for celiac disease, or in patients with a first-degree relative with celiac disease r29
            • Obtain IgA tissue transglutaminase antibodies (with documentation of total serum IgA levels within reference range) or IgG tissue transglutaminase antibodies and deamidated gliadin antibodies in IgA-deficient patients
        • Psychosocial issues
          • Monitor for psychosocial issues and family stress that may impact management (during routine follow-up care) r29
          • Monitor children and adolescents, along with their parents, for signs of diabetes distress (during routine follow-up care) r113
          • Screen for depression and anxiety quarterly
          • For teenagers, assess use of alcohol, tobacco, illicit drugs, and contraception as needed
          • Monitor for eating disorders (with a validated screening tool) in patients around age 10 to 12 years and when hyperglycemia and/or weight loss are unexplained r29
      • Complications
        • Nephropathy
          • Measure urinary albumin-creatinine ratio (from a spot urine sample, preferably a morning sample) once child has had diabetes for 5 years starting at puberty or at age 10 years, whichever is earlier, and then annually thereafter r29
          • Obtain estimated GFR as needed based on clinical status, age, duration of diabetes, and therapy r29
        • Retinopathy
          • Obtain initial dilated retinal and comprehensive eye examinations once patient is at least 11 years old or pubertal (whichever is earlier) and has had diabetes diagnosis for 3 to 5 years, then every 2 years thereafter r29r128
          • Less-frequent examinations (every 4 years) may be acceptable with the advice of an eye care professional r29
          • Other recommendations suggest initial ophthalmologic examination beginning 5 years after diagnosis and annually thereafter r129
        • Neuropathy
          • Visual foot examination at each visit with older children to educate regarding importance of foot care r29
          • Consider annual comprehensive foot examination to assess for peripheral neuropathy at start of puberty or at age 10 years (whichever is earlier) once diabetes has been established for 5 years r29
            • Assessment includes history and monofilament testing with pinprick, temperature, or vibration sensation tests

Complications and Prognosis

Complications

  • Acute
    • DKA (diabetic ketoacidosis) r130c164d1
      • Life-threatening condition marked by hyperglycemia, metabolic acidosis, and ketonemia
      • Signs and symptoms include polyuria, polydipsia, polyphagia, weight loss, weakness, abdominal pain, nausea, vomiting, Kussmaul respirations, and acetone breath
      • 30% of new-onset diabetes cases in children present as DKA r131
      • COVID-19 considerations
        • COVID‐19 infection may precipitate severe metabolic complications of diabetes including DKA, which may be the initial presentation of new-onset diabetes r132
        • Delays in diagnosis of diabetes and seeking care for diabetes‐related emergencies owing to fear of exposure to COVID‐19 may result in more severe DKA at presentation r132r133
      • Treat with fluid resuscitation, insulin, electrolyte replacement, and correction of precipitating factors
      • Cerebral edema is the major complication; it causes 20% of all deaths from DKA occurring in children r134
    • Treatment-related hypoglycemia
      • Thresholds r135
        • At a glucose level of 70 mg/dL or lower, hypoglycemia is sufficiently low to require treatment with fast-acting carbohydrate and dose adjustment of insulin
        • At a glucose level of less than 54 mg/dL, hypoglycemia is considered serious and clinically significant
        • Severe hypoglycemia associated with severe cognitive impairment does not have a specific numerical threshold, but this category is reserved for any hypoglycemic event that requires external assistance for recovery
      • Recognition is developmentally and age-dependent; limitations of infants and toddlers to detect or report symptoms may demand more frequent monitoring r29
      • Frequent, severe, and/or nocturnal hypoglycemia require adjustment in insulin doses r67
      • In young children, severe hypoglycemia may lead to cognitive deficits; thus, if hypoglycemia is frequent, blood glucose targets may need to be relaxed for this age group r29
      • Immediate treatment of severe hypoglycemia requires administration of rapidly absorbed glucose (oral), glucagon (IM or intranasal), and/or IV glucose, with treatment based on severity of hypoglycemia, level of consciousness, and ability of child to ingest oral glucose r136r137
  • Chronic
    • Microvascular complications r29r128r138c165c166c167c168
      • Intensive diabetes therapy aimed at achieving near-normal glycemia reduces the development of microvascular complications in type 1 diabetes
      • Rarely occurs before puberty or in children with diabetes duration less than 2 years, but does occur after puberty or in children with diabetes duration of 5 to 10 years r16
        • Nephropathy r29r138c169c170c171c172
          • Elevated albumin excretion rate is usually first finding; persistence predicts progression to gross proteinuria within 6 to 14 years
            • Reference range: less than 30 mg/g albumin-creatinine ratio r138
            • Modestly elevated albumin excretion: 30 to 299 mg/g albumin-creatinine ratio (in a spot urine sample) r138
            • Persistent abnormal microalbumin excretion: requires documentation of 2 of 3 consecutive abnormal values obtained on different days over a 6-month period r29
            • Test confounders include exercise within 24 hours, infection, fever, congestive heart failure, marked hyperglycemia, menstruation, and severe hypertension r138
          • In addition to strict glycemic control, blood pressure control is essential to reduce the risk or slow progression of nephropathy
          • Consider treatment with ACE inhibitor (or angiotensin receptor blocker) for nonpregnant patients with persistently abnormal microalbumin excretion (greater than 30 mg/g) r29
        • Retinopathy c173c174c175c176
          • Highly specific vascular complication of diabetes, with prevalence strongly correlated to duration of diabetes and level of glycemic control
          • Refer to ophthalmologist for an initial dilated retinal and comprehensive eye examination once the child is at least 11 years old or pubertal (whichever is earlier) and has had diagnosis of diabetes for 3 to 5 years r29
          • Measures to reduce risk or slow progression of diabetic retinopathy include optimal control of glycemia, blood pressure, and serum lipid levels r128
        • Neuropathy r128c177c178c179c180
          • Neurologic complications rarely occur during childhood
          • Measures to prevent or delay onset of diabetic neuropathy include optimizing glycemic control
    • Macrovascular complications c181
      • Cardiovascular disease r105c182
        • Coronary artery disease is main cause of death in persons with type 1 diabetes c183
        • Cardiovascular events generally do not occur during childhood, but the atherosclerotic process begins during childhood in patients with diabetes
          • Age and hemoglobin A1C level are the strongest risk factors for a major atherosclerotic event or for any cardiovascular disease in patients with type 1 diabetes r107
        • A period of intensive diabetes management at an early stage of the disease is associated with beneficial effects on the long-term occurrence of cardiovascular disease r107
        • Addressing other individual risk factors for atherosclerotic cardiovascular disease to reduce the likelihood of harmful events is especially important in diabetes r112
        • Lifestyle measures to reduce risk include achieving blood pressure and weight control, smoking cessation or avoidance, and consuming a balanced diet that is rich in fruits and vegetables, low in saturated fat and sodium, and enriched in whole grains
    • Abnormal growth c184
      • Poor growth and delay in pubertal and skeletal maturation may result from chronic undertreatment with insulin, resulting in poor diabetes control or development of comorbidity (eg, depression, thyroid disease, celiac disease) r29
      • Obesity is as common in children and adolescents with type 1 diabetes as in those without diabetes r29
      • Maintain normal physical growth to include regular gains in height and weight, as well as normal timing of the onset and magnitude of the pubertal growth spurt
        • If patient is not growing appropriately according to nomograms:
          • Alter insulin dosing and control
          • Consider coexistence or development of comorbidity (eg, hypothyroidism, celiac disease)
          • Reassess nutritional status and refine dietary counseling

Prognosis

  • Type 1 diabetes is associated with increased risk of mortality
    • Excess mortality in childhood- or adolescent-diagnosed type 1 diabetes is apparent across countries worldwide r139
    • All-cause and cardiovascular-related mortality rates are at least twice as high as those for matched controls r140
    • Excess risk of death from any cause and death from cardiovascular causes appears to vary by glycemic control, with the risk for death rising as hemoglobin A1C levels increase r141
    • Over the long term, an initial period of intensive diabetes therapy (duration of 6.5 years) is associated with a modestly lower all-cause mortality rate when compared with conventional therapy r141

Screening and Prevention

Screening

At-risk populations

  • First-degree relatives have an 8- to 15-fold increased risk of type 1 diabetes r142c185
  • Second-degree relatives have a 2-fold increased risk of type 1 diabetes r142

Screening tests

  • Measuring islet autoantibodies in relatives of patients with type 1 diabetes may identify those who are at risk for developing disease r3
  • A combined analysis of 3 large, prospective studies found that screening for islet autoantibodies in children at elevated risk for type 1 diabetes at age 10 years and followed to age 18 had a 90% sensitivity and 66% positive predictive value for later development of the disease r143
    • General population screening of first-degree relatives of those with type 1 diabetes is not universally recommended, but has potential benefits r143r144
      • Identification and education of families with children at high-risk for developing type 1 diabetes while in a pre-symptomatic phase may prevent a more severe initial disease presentation (eg, DKA)
      • Early identification of high-risk children provides an opportunity to use therapies that delay onset of clinical diabetes

Prevention

  • The time delay between appearance of autoantibodies and the complete destruction of insulin-producing β-cells presents an opportunity for intervention and is an active area of pharmacologic research r144c186
    • Teplizumab is the only drug approved by the FDA to delay the onset of stage 3 type 1 diabetes mellitus; approval is for children and adults aged 8 years or older with stage 2 type 1 diabetes mellitus r145
      • Teplizumab is a monoclonal antibody that binds to CD3 molecules on the surface of CD4+ and CD8+ lymphocytes that are responsible for the loss of pancreatic β-cells; administered as a single 14-day treatment course r146
        • Teplizumab Solution for injection; Children and Adolescents 8 to 17 years: 65 mcg/m2/dose IV once daily on day 1, then 125 mcg/m2/dose IV once daily on day 2, then 250 mcg/m2/dose IV once daily on day 3, then 500 mcg/m2/dose IV once daily on day 4, and then 1,030 mcg/m2/dose IV once daily on days 5 through 14.
      • In a pivotal randomized trial in patients with stage 2 type 1 diabetes, 45% of treated patients were later diagnosed with stage 3 diabetes, compared to 72% of placebo patients. The mid-range time to develop stage 3 diabetes was 50 months in the treated group versus 25 months for the placebo group r147
      • In clinical trials, adverse events have been mild and of short duration r146
Sperling MA et al: Current management of glycemia in children with type 1 diabetes mellitus. N Engl J Med. 386(12):1155-64, 202235320645ElSayed NA et al: 2. Classification and diagnosis of diabetes: Standards of Care in Diabetes-2023. Diabetes Care. 46(Suppl 1):S19-S40, 202336507649Insel RA et al: Staging presymptomatic type 1 diabetes: a scientific statement of JDRF, the Endocrine Society, and the American Diabetes Association. Diabetes Care. 38(10):1964-74, 201526404926Cherubini V et al: Temporal trends in diabetic ketoacidosis at diagnosis of paediatric type 1 diabetes between 2006 and 2016: results from 13 countries in three continents. Diabetologia. 63(8):1530-41, 202032382815Couper J et al: Phases of diabetes in children and adolescents. Pediatr Diabetes. 10(suppl 12):13-6, 200919754614Elding Larsson H et al: Children followed in the TEDDY study are diagnosed with type 1 diabetes at an early stage of disease. Pediatr Diabetes. 15(2):118-26, 201424034790Klinke DJ 2nd: Extent of beta cell destruction is important but insufficient to predict the onset of type 1 diabetes mellitus. PLoS One. 3(1):e1374, 200818167535Kliegman RM et al: Diabetes mellitus. In: Kliegman RM et al, eds: Nelson Textbook of Pediatrics. 21st ed. Elsevier; 2020:3019-52.e4Maahs DM et al: Epidemiology of type 1 diabetes. Endocrinol Metab Clin North Am. 39(3):481-97, 201020723815Bonnefond A et al: Rare and common genetic events in type 2 diabetes: what should biologists know? Cell Metab. 21(3):357-68, 201525640731Michels A et al: Prediction and prevention of type 1 diabetes: update on success of prediction and struggles at prevention. Pediatr Diabetes. 16(7):465-84, 201526202050Noble JA et al: Genetics of the HLA region in the prediction of type 1 diabetes. Curr Diab Rep. 11(6):533-42, 201121912932Onengut-Gumuscu S et al: Fine mapping of type 1 diabetes susceptibility loci and evidence for colocalization of causal variants with lymphoid gene enhancers. Nat Genet. 47(4):381-6, 201525751624Chiang JL et al: Type 1 diabetes through the life span: a position statement of the American Diabetes Association. Diabetes Care. 37(7):2034-54, 201424935775Redondo MJ et al: Concordance for islet autoimmunity among monozygotic twins. N Engl J Med. 359(26):2849-50, 200819109586Chiang JL et al: Type 1 diabetes in children and adolescents: a position statement by the American Diabetes Association. Diabetes Care. 41(9):2026-44, 201830093549Divers J et al: Trends in incidence of type 1 and type 2 diabetes among youths--selected counties and Indian reservations, United States, 2002-2015. MMWR Morb Mortal Wkly Rep. 69(6):161-5, 202032053581Tuomilehto J et al: Update on worldwide trends in occurrence of childhood type 1 diabetes in 2020. Pediatr Endocrinol Rev. 17(suppl 1):198-209, 202032208564Triolo TM et al: Additional autoimmune disease found in 33% of patients at type 1 diabetes onset. Diabetes Care. 34(5):1211-3, 201121430083Dost A et al: Hyperthyroidism in 276 children and adolescents with type 1 diabetes from Germany and Austria. Horm Res Paediatr. 84(3):190-8, 201526202175Kakleas K et al: Associated autoimmune diseases in children and adolescents with type 1 diabetes mellitus (T1DM). Autoimmun Rev. 14(9):781-97, 201526001590Autoimmune Polyendocrine Syndrome, Type I, With or Without Reversible Metaphyseal Dysplasia; APS1. Online Mendelian Inheritance in Man. OMIM website. Johns Hopkins University. Updated July 5, 2022. Edited July 6, 2022. Accessed October 7, 2023. https://www.omim.org/entry/240300https://www.omim.org/entry/240300Immunodysregulation, Polyendocrinopathy, and Enteropathy, X-linked; IPEX. Online Mendelian Inheritance in Man. OMIM website. Johns Hopkins University. Updated November 6, 2014. Edited August 8, 2023. Accessed October 7, 2023. https://www.omim.org/entry/304790https://www.omim.org/entry/304790Autoimmune Polyendocrine Syndrome, Type II; APS2. Online Mendelian Inheritance in Man. OMIM website. Johns Hopkins University. Updated April 10, 2007. Edited May 12, 2014. Accessed October 7, 2023. https://www.omim.org/entry/269200https://www.omim.org/entry/269200Beyerlein A et al: Infections in early life and development of type 1 diabetes. JAMA. 315(17):1899-1901, 201627139064Kahn HS et al: Association of type 1 diabetes with month of birth among U.S. youth: the SEARCH for Diabetes in Youth study. Diabetes Care. 32(11):2010-5, 200919675199Lindell N et al: Size for gestational age affects the risk for type 1 diabetes in children and adolescents: a Swedish national case-control study. Diabetologia. ePub, 202133544169Feng R et al: Lower serum 25 (OH) D concentrations in type 1 diabetes: a meta-analysis. Diabetes Res Clin Pract. 108(3):e71-5, 201525836943ElSayed NA et al: 14. Children and adolescents: Standards of Care in Diabetes-2023. Diabetes Care. 46(Suppl 1):S230-53, 202336507640ElSayed NA et al: 4. Comprehensive medical evaluation and assessment of comorbidities: Standards of Care in Diabetes-2023. Diabetes Care. 46(Suppl 1):S49-S67, 202336507651NGSP: NGSP website. Updated 2022. Accessed October 7, 2023. http://ngsp.org/http://ngsp.org/Lampasona V et al: Islet autoantibodies. Curr Diab Rep. 16(6):53, 201627112957Simmons KM et al: Islet Autoantibody Testing: Current Utility, Future Prospects in Predicting and Diagnosing Type 1 Diabetes. Clinical Laboratory News. American Association for Clinical Chemistry website. Published July 1, 2017. Accessed October 7, 2023. https://www.aacc.org/publications/cln/articles/2017/july/islet-autoantibody-testing-predicting-and-diagnosing-type-1-diabeteshttps://www.aacc.org/publications/cln/articles/2017/july/islet-autoantibody-testing-predicting-and-diagnosing-type-1-diabetesHolt RIG et al: The management of type 1 diabetes in adults: a consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia. 64(12):2609-52, 202134590174Tridgell DM et al: Interaction of onset and duration of diabetes on the percent of GAD and IA-2 antibody-positive subjects in the type 1 diabetes genetics consortium database. Diabetes Care. 34(4):988-93, 201121330643Wolfsdorf JI et al: Management of diabetes in children. In: Jameson JL et al, eds: Endocrinology: Adult and Pediatric. 7th ed. Saunders; 2016:854-82Jones AG et al: The clinical utility of C-peptide measurement in the care of patients with diabetes. Diabet Med. 30(7):803-17, 201323413806Davis AK et al: Prevalence of detectable C-peptide according to age at diagnosis and duration of type 1 diabetes. Diabetes Care. 38(3):476-81, 201525519448Cho MJ et al: Fasting serum C-peptide is useful for initial classification of diabetes mellitus in children and adolescents. Ann Pediatr Endocrinol Metab. 19(2):80-5, 201425077090Hattersley A et al: The diagnosis and management of monogenic diabetes in children and adolescents. Pediatr Diabetes. 10(suppl 12):33-42, 200919754616Carmody D et al: A clinical guide to monogenic diabetes. In: Weiss RE et al, eds: Genetic Diagnosis of Endocrine Disorders. 2nd ed. Academic Press; 2016:21-30Pihoker C et al: Prevalence, characteristics and clinical diagnosis of maturity onset diabetes of the young due to mutations in HNF1A, HNF4A, and glucokinase: results from the SEARCH for Diabetes in Youth. J Clin Endocrinol Metab. 98(10):4055-62, 201323771925O'Shea D et al: Cystic fibrosis related diabetes. Curr Diab Rep. 14(8):511, 201424915888de Bock M et al: ISPAD Clinical Practice Consensus Guidelines 2022: Glycemic targets and glucose monitoring for children, adolescents, and young people with diabetes. Pediatr Diabetes. 23(8):1270-6, 202236537523Battelino T et al: Clinical targets for continuous glucose monitoring data interpretation: recommendations from the International Consensus on Time in Range. Diabetes Care. 42(8):1593-603, 201931177185Flynn JT et al: Clinical practice guideline for screening and management of high blood pressure in children and adolescents. Published corrections appear in Pediatrics. 140(6):e20173035 and Pediatrics. 142(3):e20181739. Pediatrics. 140(3):e20171904, 201728827377Lowes L et al: Management of newly diagnosed diabetes: home or hospital? Arch Dis Child. 89(10):934-7, 200415383437Gregory JW et al: Effectiveness of home or hospital initiation of treatment at diagnosis for children with type 1 diabetes (DECIDE trial): a multicentre individually randomised controlled trial. BMJ Open. 9(12):e032317, 201931796486Wolfsdorf JI et al: Diabetic ketoacidosis and hyperglycemic hyperosmolar state. Pediatr Diabetes. 15(suppl 20):154-79, 201425041509ElSayed NA et al: 6. Glycemic targets: Standards of Care in Diabetes-2023. Diabetes Care. 46(Suppl 1):S97-S110, 202336507646ElSayed NA et al: 5. Facilitating positive health behaviors and well-being to improve health outcomes: Standards of Care in Diabetes-2023. Diabetes Care. 46(Supple 1):S68-S96, 202336507648Danne T et al: ISPAD clinical practice consensus guidelines 2018: insulin treatment in children and adolescents with diabetes. Pediatr Diabetes. 19(suppl 27):115-35, 201829999222ElSayed NA et al: 9. Pharmacologic approaches to glycemic treatment: Standards of Care in Diabetes-2023. Diabetes Care. 46(Suppl 1):S140-57, 202336507650Malik FS et al: Insulin therapy in children and adolescents with type 1 diabetes. Paediatr Drugs. 16(2):141-50, 201424458650Nathan DM: Diabetes: advances in diagnosis and treatment. JAMA. 314(10):1052-62, 201526348754Adolfsson P et al: Improved glycemic control observed in children with type 1 diabetes following the introduction of smart insulin pens: a real-world study. Diabetes Ther. 13(1):43-56, 202234748170Kesavadev J et al: Evolution of insulin delivery devices: from syringes, pens, and pumps to DIY artificial pancreas. Diabetes Ther. 11(6):1251-69, 202032410184Jendle J et al: Smart insulin pens are associated with improved clinical outcomes at lower cost versus standard-of-care treatment of type 1 diabetes in Sweden: a cost-effectiveness analysis. Diabetes Ther. 12(1):373-88, 202133306169Philotheou A et al: Comparable efficacy and safety of insulin glulisine and insulin lispro when given as part of a basal-bolus insulin regimen in a 26-week trial in pediatric patients with type 1 diabetes. Diabetes Technol Ther. 13(3):327-34, 201121291333Beck JK et al: Outpatient management of pediatric type 1 diabetes. J Pediatr Pharmacol Ther. 20(5):344-57, 201526472948ElSayed NA et al: 7. Diabetes technology: Standards of Care in Diabetes-2023. Diabetes Care. 46(Suppl 1):S111-27, 202336507635Bailey TS et al: American Association of Clinical Endocrinologists and American College of Endocrinology 2016 outpatient glucose monitoring consensus statement. Endocr Pract. 22(2):231-61, 201626848630Marks BE et al: Monitoring of pediatric type 1 diabetes. Front Endocrinol (Lausanne). 11:128, 202032256447Dicembrini I et al: Effects of real-time continuous glucose monitoring in type 1 diabetes: a meta-analysis of randomized controlled trials. Acta Diabetol. 58(4):401-10, 202132789691Wong JC et al: Real-time continuous glucose monitoring among participants in the T1D Exchange clinic registry. Diabetes Care. 37(10):2702-9, 201425011947Gurnurkar S et al: Evaluation of hemoglobin A1c before and after initiation of continuous glucose monitoring in children with type 1 diabetes mellitus. J Pediatr Endocrinol Metab. ePub, 202133618445Iqbal A et al: Recent updates on type 1 diabetes mellitus management for clinicians. Diabetes Metab J. 42(1):3-18, 201829504302Liang B et al: Efficacy of flash glucose monitoring in type 1 and type 2 diabetes: a systematic review and meta-analysis of randomised controlled trials. Front Clin Diabetes Healthc. 3:849725, 202236992733Oriot P et al: Intermittent-scanned continuous glucose monitoring with low glucose alarms decreases hypoglycemia incidence in middle-aged adults with type 1 diabetes in real-life setting. J Diabetes Complications. 37(2):108385, 202336603333Deeb A et al: ISPAD clinical practice consensus guidelines: fasting during Ramadan by young people with diabetes. Pediatr Diabetes. 21(1):5-17, 202031659852Laffel LM et al: ISPAD clinical practice consensus guidelines 2018: sick day management in children and adolescents with diabetes. Pediatr Diabetes. 19(suppl 27):193-204, 201830079506Blonde L et al: American Association of Clinical Endocrinology clinical practice guideline: developing a diabetes mellitus comprehensive care plan-2022 Update. Endocr Pract. 28(10):923-1049, 202235963508CDC: Child and Adolescent Immunization Schedule by Age: Recommendations for Ages 18 Years or Younger, United States, 2023. CDC website. Last reviewed April 27, 2023. Accessed October 7, 2023. https://www.cdc.gov/vaccines/schedules/hcp/imz/child-adolescent.html#addendum-childhttps://www.cdc.gov/vaccines/schedules/hcp/imz/child-adolescent.html#addendum-childAdolfsson P et al: ISPAD Clinical Practice Consensus Guidelines 2022: Exercise in children and adolescents with diabetes. Pediatr Diabetes. 23(8):1341-72, 202236537529Nadella S et al: Management of diabetes mellitus in children and adolescents: engaging in physical activity. Transl Pediatr. 6(3):215-24, 201728795013ElSayed NA et al: 17. Diabetes advocacy: Standards of Care in Diabetes-2023. Diabetes Care. 46(Suppl 1):S279-80, 202336507643American Diabetes Association: Guidelines for the Use of Continuous Glucose Monitors (CGM) and Sensors in the School Setting. ADA website. Updated September 10, 2018. Accessed October 7, 2023. https://www.diabetes.org/sites/default/files/2019-06/CGM%20guidelines.pdfhttps://www.diabetes.org/sites/default/files/2019-06/CGM%20guidelines.pdfJackson CC et al: Diabetes care in the school setting: a position statement of the American Diabetes Association. Diabetes Care. 38(10):1958-63, 201526404925Siminerio LM et al: Care of young children with diabetes in the child care setting: a position statement of the American Diabetes Association. Diabetes Care. 37(10):2834-42, 201425249671Sundberg F et al: ISPAD Clinical Practice Consensus Guidelines 2022: Managing diabetes in preschoolers. Pediatr Diabetes. 23(8):1496-1511, 202236537520Cefalu WT et al: Insulin Access and Affordability Working Group: conclusions and recommendations. Diabetes Care. 41(6):1299-311, 201829739814American Diabetes Association: Diabetes and driving. Diabetes Care. 37(suppl 1):S97-103, 201424357217American Diabetes Association: Diabetes and employment. Diabetes Care. 37(suppl 1):S112-7, 201424357206American Diabetes Association: Diabetes management in correctional institutions. Diabetes Care. 37(suppl 1):S104-11, 201424357205Grunberger G et al: American Association of Clinical Endocrinologists and American College of Endocrinology 2018 position statement on integration of insulin pumps and continuous glucose monitoring in patients with diabetes mellitus. Endocr Pract. 24(3):302-8, 201829547046Grunberger G et al: American Association of Clinical Endocrinology clinical practice guideline: the use of advanced technology in the management of persons with diabetes mellitus. Endocr Pract. 27(6):505-37, 202134116789Aleppo G et al: Improvements in glycemic outcomes in 4738 children, adolescents, and adults with type 1 diabetes initiating a tubeless insulin management system. Diabetes Ther. 14(3):593-610, 202336763329Peacock S et al: A Systematic review of commercial hybrid closed-loop automated insulin delivery systems. Diabetes Ther. 14(5):839-55, 202337017916Templer S: Closed-loop insulin delivery systems: past, present, and future directions. Front Endocrinol (Lausanne). 13:919942, 202235733769US Food and Drug Administration: FDA Roundup: January 24, 2023. USFDA website. Published January 24, 2023. Accessed October 7, 2023. https://www.fda.gov/news-events/press-announcements/fda-roundup-january-24-2023https://www.fda.gov/news-events/press-announcements/fda-roundup-january-24-2023Yeh HC et al: Comparative effectiveness and safety of methods of insulin delivery and glucose monitoring for diabetes mellitus: a systematic review and meta-analysis. Ann Intern Med. 157(5):336-47, 201222777524Karges B et al: Association of insulin pump therapy vs insulin injection therapy with severe hypoglycemia, ketoacidosis, and glycemic control among children, adolescents, and young adults with type 1 diabetes. JAMA. 318(14):1358-66, 201729049584Steineck I et al: Insulin pump therapy, multiple daily injections, and cardiovascular mortality in 18,168 people with type 1 diabetes: observational study. BMJ. 350:h3234, 201526100640FDA: Summary of Safety and Effectiveness Data (SSED). Automated Insulin Dosing Device System, Single Hormone. MiniMed 670G System. Premarket Approval Application (PMA) Number P160017/S031. FDA website. Updated June 21, 2018. Accessed October 7, 2023. https://www.accessdata.fda.gov/cdrh_docs/pdf16/P160017S031B.pdfhttps://www.accessdata.fda.gov/cdrh_docs/pdf16/P160017S031B.pdfRoss PL et al: Clinical review: insulin pump-associated adverse events in adults and children. Acta Diabetol. 52(6):1017-24, 201526092321Foerster V et al: A hybrid closed-loop insulin delivery system for the treatment of type 1 diabetes. In: Canadian Agency for Drugs and Technologies in Health, ed: CADTH Issues in Emerging Health Technologies. Canadian Agency for Drugs and Technologies in Health; 2016https://www.ncbi.nlm.nih.gov/books/NBK476442/Abraham MB et al: Reduction in hypoglycemia with the predictive low-glucose management system: a long-term randomized controlled trial in adolescents with type 1 diabetes. Diabetes Care. 41(2):303-10, 201829191844Garg SK et al: Glucose outcomes with the in-home use of a hybrid closed-loop insulin delivery system in adolescents and adults with type 1 diabetes. Diabetes Technol Ther. 19(3):155-63, 201728134564Breton MD et al: A randomized trial of closed-loop control in children with type 1 diabetes. N Engl J Med. 383(9):836-45, 202032846062Kanapka LG et al: Extended use of the Control-IQ closed-loop control system in children with type 1 diabetes. Diabetes Care. 44(2):473-8, 202133355258Isganaitis E et al: Closed-loop insulin therapy improves glycemic control in adolescents and young adults: outcomes from the International Diabetes Closed-Loop Trial. Diabetes Technol Ther. ePub, 202133216667Ware J et al: Randomized trial of closed-loop control in very young children with type 1 diabetes. N Engl J Med. 386(3):209-19, 202235045227Marcovecchio ML et al: ACE inhibitors and statins in adolescents with type 1 diabetes. N Engl J Med. 377(18):1733-45, 201729091568Maahs DM et al: Glucose control predicts 2-year change in lipid profile in youth with type 1 diabetes. J Pediatr. 162(1):101-7.e1, 201322795314de Ferranti SD et al: Type 1 diabetes mellitus and cardiovascular disease: a scientific statement from the American Heart Association and American Diabetes Association. Diabetes Care. 37(10):2843-63, 201425114297de Ferranti SD et al: Cardiovascular risk reduction in high-risk pediatric patients: a scientific statement from the American Heart Association. Circulation. 139(13):e603-34, 201930798614Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Research Group: Risk factors for cardiovascular disease in type 1 diabetes. Diabetes. 65(5):1370-9, 201626895792Bilimoria KY et al: Autoimmune thyroid dysfunction in children with type 1 diabetes mellitus: screening guidelines based on a retrospective analysis. J Pediatr Endocrinol Metab. 16(8):1111-7, 200314594171Hill ID et al: Guideline for the diagnosis and treatment of celiac disease in children: recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr. 40(1):1-19, 200515625418DuBose SN et al: Obesity in youth with type 1 diabetes in Germany, Austria, and the United States. J Pediatr. 167(3):627-32.e4, 201526164381Nansel TR et al: Cross-sectional and longitudinal relationships of body mass index with glycemic control in children and adolescents with type 1 diabetes mellitus. Diabetes Res Clin Pract. 100(1):126-32, 201323339757Maahs DM et al: Cardiovascular disease risk factors in youth with diabetes mellitus: a scientific statement from the American Heart Association. Circulation. 130(17):1532-58, 201425170098Young-Hyman D et al: Psychosocial care for people with diabetes: a position statement of the American Diabetes Association. Published corrections appear in Diabetes Care. 40(2):287, 2017 and Diabetes Care. 40(5):726, 2017. Diabetes Care. 39(12):2126-40, 201627879358Hagger V et al: Diabetes distress among adolescents with type 1 diabetes: a systematic review. Curr Diab Rep. 16(1):9, 201626748793Polonsky WH et al: Assessing psychosocial distress in diabetes: development of the diabetes distress scale. Diabetes Care. 28(3):626-31, 200515735199Ducat L et al: The mental health comorbidities of diabetes. JAMA. 312(7):691-2, 201425010529Corathers SD et al: Improving depression screening for adolescents with type 1 diabetes. Pediatrics. 132(5):e1395-402, 201324127480Tarçın G et al: Diabetes-specific eating disorder and possible associated psychopathologies in adolescents with type 1 diabetes mellitus. Eat Weight Disord. 28(1):36, 202337029851Young V et al: Eating problems in adolescents with type 1 diabetes: a systematic review with meta-analysis. Diabet Med. 30(2):189-98, 201322913589Goebel-Fabbri AE et al: Insulin restriction and associated morbidity and mortality in women with type 1 diabetes. Diabetes Care. 31(3):415-9, 200818070998Markowitz JT et al: Brief screening tool for disordered eating in diabetes: internal consistency and external validity in a contemporary sample of pediatric patients with type 1 diabetes. Diabetes Care. 33(3):495-500, 201020032278ElSayed NA et al: 15. Management of diabetes in pregnancy: Standards of Care in Diabetes-2023. Diabetes Care. 46(Suppl 1):S254-66, 202336507645Codner E et al: Contraception, and pregnancy in adolescents with type 1 diabetes: a review. Pediatr Diabetes. 13(1):108-23, 201221995767Peters A et al: Diabetes care for emerging adults: recommendations for transition from pediatric to adult diabetes care systems: a position statement of the American Diabetes Association, with representation by the American College of Osteopathic Family Physicians, the American Academy of Pediatrics, the American Association of Clinical Endocrinologists, the American Osteopathic Association, the Centers for Disease Control and Prevention, Children with Diabetes, the Endocrine Society, the International Society for Pediatric and Adolescent Diabetes, Juvenile Diabetes Research Foundation International, the National Diabetes Education Program, and the Pediatric Endocrine Society (formerly Lawson Wilkins Pediatric Endocrine Society). Diabetes Care. 34(11):2477-85, 201122025785CDC: BMI Percentile Calculator for Child and Teen. CDC website. Reviewed September 14, 2023. Accessed October 7, 2023. https://www.cdc.gov/healthyweight/bmi/calculator.htmlhttps://www.cdc.gov/healthyweight/bmi/calculator.htmlMiller KM et al: Evidence of a strong association between frequency of self-monitoring of blood glucose and hemoglobin A1c levels in T1D exchange clinic registry participants. Diabetes Care. 36(7):2009-14, 201323378621The Diabetes Control and Complications Trial Research Group: The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 329(14):977-86, 19938366922ElSayed NA et al: 12. Retinopathy, neuropathy, and foot care: Standards of Care in Diabetes-2023. Diabetes Care. 46(Suppl 1):S203-15, 202336507636Flaxel CJ et al: Diabetic retinopathy Preferred Practice Pattern. Ophthalmology. 127(1):P66-145, 202031757498Fayfman M et al: Management of hyperglycemic crises: diabetic ketoacidosis and hyperglycemic hyperosmolar state. Med Clin North Am. 101(3):587-606, 201728372715Scibilia J et al: Why do children with diabetes die? Acta Endocrinol Suppl (Copenh). 279:326-33, 19863096039Priyambada L et al: ISPAD clinical practice consensus guideline: diabetic ketoacidosis in the time of COVID-19 and resource-limited settings--role of subcutaneous insulin. Pediatr Diabetes. 21(8):1394-402, 202032935435Lawrence C et al: Increased paediatric presentations of severe diabetic ketoacidosis in an Australian tertiary centre during the COVID-19 pandemic. Diabet Med. 38(1):e14417, 202133020999Finberg L: Fluid management of diabetic ketoacidosis. Pediatr Rev. 17(2):46, 52, 19968775891International Hypoglycaemia Study Group: Glucose concentrations of less than 3.0 mmol/L (54 mg/dL) should be reported in clinical trials: a joint position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 40(1):155-7, 201727872155Battelino T et al: Dasiglucagon, a next-generation ready-to-use glucagon analog, for treatment of severe hypoglycemia in children and adolescents with type 1 diabetes: results of a phase 3, randomized controlled trial. Pediatr Diabetes. 22(5):734-41, 202133934456Lowe RN et al: Intranasal glucagon: a new way to treat hypoglycemic emergencies. Ann Pharmacother. 54(8):780-7, 202032052651ElSayed NA et al: 11. Chronic kidney disease and risk management: Standards of Care in Diabetes-2023. Diabetes Care. 46(Suppl 1):S191-S202, 202336507634Morgan E et al: Excess mortality in type 1 diabetes diagnosed in childhood and adolescence: a systematic review of population-based cohorts. Acta Diabetol. 52(4):801-7, 201525585594Lind M et al: Glycemic control and excess mortality in type 1 diabetes. N Engl J Med. 371(21):1972-82, 201425409370Writing Group for the DCCT/EDIC Research Group et al: Association between 7 years of intensive treatment of type 1 diabetes and long-term mortality. JAMA. 313(1):45-53, 201525562265Parkkola A et al: Extended family history of type 1 diabetes and phenotype and genotype of newly diagnosed children. Diabetes Care. 36(2):348-54, 201323033245Ghalwash M et al: Islet autoantibody screening in at-risk adolescents to predict type 1 diabetes until young adulthood: a prospective cohort study. Lancet Child Adolesc Health. 7(4):261-8, 202336681087Nagy G et al: New therapeutic approaches for type 1 diabetes: disease-modifying therapies. World J Diabetes. 13(10):835-50, 202236312000Provention Bio, Inc.: Tzield™ (Teplizumab-mzwv) Injection, for Intravenous Use. Highlights of Prescribing Information. Accessdata.fda.gov website. Updated November 2022. Accessed October 7, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761183Orig1s000lbl.pdfhttps://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761183Orig1s000lbl.pdfMisra S et al: Teplizumab: type 1 diabetes mellitus preventable? Eur J Clin Pharmacol. 79(5):609-16, 202337004543Herold KC et al: An anti-CD3 antibody, teplizumab, in relatives at risk for type 1 diabetes. N Engl J Med. 381(7):603-13, 201931180194
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