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Mar.25.2021

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
  • Children with type 1 diabetes typically present with polyuria, polydipsia, and unexplained weight loss
  • Children typically have an elevated glucose level, varying degrees of acidosis, and positive pancreatic islet autoantibodies findings
  • Initial treatment of severe hyperglycemia includes correction of fluid deficits and electrolyte abnormalities, insulin administration, dosing adjustments, and diabetes education
  • Monitoring for comorbidities and complications is a key component of comprehensive diabetes care for patients with type 1 diabetes
  • 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

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
  • Insulin dependence is lifelong

Classification

  • Immune-mediated diabetes r1
    • Caused by autoimmune destruction of pancreatic β-cells
    • Accounts for the majority of patients with type 1 diabetes mellitus, but only 5% to 10% of all patients with diabetes r1
    • Defined by 1 or more autoimmune markers, which include islet cell autoantibodies and autoantibodies to insulin, GAD65 (glutamate decarboxylase 2), tyrosine phosphatases IA-2 and IA-2β, and ZnT8 (SLC30A8, a zinc transporter related to insulin secretion)
  • Idiopathic diabetes (type 1B) r1
    • Type 1 diabetes mellitus with nonimmune basis for pancreatic β-cell destruction
    • Permanent insulinopenia without immunologic evidence of β-cell autoimmunity or HLA association
    • Mainly occurs in patients with African or Asian ancestry, and accounts for a minority of patients with type 1 diabetes
  • Stages r1r2
    • 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
    • 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

Diagnosis

Clinical Presentation

History

  • Patient typically presents abruptly with severe hyperglycemia and/or in state of DKA c1
    • Approximately one-third of children in the United States present with DKA r3c2d1
  • Most common presenting symptoms r4
    • 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 r4
    • 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 r5

Physical examination

  • Findings are unremarkable, except in severe hyperglycemia with DKA
    • Kussmaul respiration: high respiratory rate and large tidal volume of each breath c21c22
    • Altered mental status: disoriented, semicomatose, or rarely comatose c23c24c25c26c27c28c29c30
    • Signs of dehydration: orthostatic hypotension, tachycardia, and poor skin turgor c31c32c33c34c35c36c37c38
    • Fruity odor to the breath, caused by ketosis c39c40

Causes and Risk Factors

Causes

  • Autoimmune (most common cause in childhood) c41
    • 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 individuals
      • Symptoms and signs of diabetes occur when more than 80% of β-cells are destroyed r6
  • Idiopathic c42
    • Pancreatic β-cell failure that occurs without autoimmune destruction

Risk factors and/or associations

Age
  • Can occur at any age; however, the large majority of patients present before age 18 years r7c43
Genetics
  • Risk of type 1 diabetes is conferred by 2 susceptible haplotypes in the region of the HLA complex in the class II region r8c44
    • 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) r9
    • 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 r10
      • 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 r11
  • Familial clustering r12c45
    • 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 r13
      • Monozygotic twins have a cumulative concordance rate of 65%,r14whereas dizygotic twins have a concordance rate of 6% to 10%r12
      • Offspring of affected mothers have a 2% to 3% risk, whereas offspring of affected fathers have a 7% risk r12
  • Neonatal (congenital) diabetes
    • Most mutations that cause diabetes in the first 6 months of life are dominantly inherited r1
    • Most common pathologic variants associated with disease involve Kir6.2 subunit (KCNJ11) and SUR1 subunit (ABCC8) of the β-cell potassium ATP channel r1
    • Second most common cause involves pathologic variants of the insulin gene (INS) r1
Ethnicity/race
  • Incidence and prevalence are highest in non-Hispanic White people r12r15c46c47c48c49
    • In the United States, incidence is increasing at greater rate in racial/ethnic minority youth compared with White populations r16
  • Incidence is highest in Finland, Sardinia, Sweden, northern Europe, North America, and Australasia; lowest incidence is in East Asia and Southeast Asia r17
  • Most patients with idiopathic (type 1B) diabetes are of Asian or African descent r1c50c51c52c53
Other risk factors/associations
  • Coexistent autoimmune disorders c54
    • Thyroid disease c55
      • Autoimmune hypothyroidism occurs in approximately 15% to 30% of children and adolescents with type 1 diabetes r18c56
      • 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 r19c57
    • Celiac disease c58
      • 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 type 1A diabetes mellitus (4%-9%) compared with the general population (0.3%-1%) r18
      • Autoantibodies indicative of celiac disease include IgA antitissue transglutaminase and antiendomysial antibodies
    • Autoimmune polyendocrine syndrome type 1r20(OMIM #240300)r21c59
      • Autosomal dominant or recessive disorder caused by mutations in the AIRE gene
      • Type 1 diabetes occurs in 4% to 18% of cases r20
      • Syndrome also includes mucocutaneous candidiasis, hypoparathyroidism, and Addison disease
    • X-linked immunodysregulation, polyendocrinopathy, and enteropathy (OMIM #304790)r22c60
      • X-linked recessive disease caused by mutations in the FOXP3 gene encoding forkhead box P3
      • Affects only boys, and is characterized by severe neonatal autoimmunity that leads to death in infancy
    • Autoimmune polyendocrine syndrome type 2r20(OMIM %269200)r23c61
      • 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 r20
      • 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 r24c62
  • Season of birth r25
    • Higher prevalence among those born in April through July c63c64
    • Lower prevalence among those born in November through February c65c66
  • Birth size
    • Being born large for gestational age is a risk factor for type 1 diabetes; independent of maternal BMI and diabetes status r26
  • Season of onset
    • Higher incidence of onset from late autumn through early spring compared with the rest of the year c67
  • Vitamin D deficiency and insufficiency is common at onset of type 1 diabetes in children r27c68

Diagnostic Procedures

Primary diagnostic tools

  • Elements of history and physical examination are highly suggestive of diabetes, but biochemical parameters are mandatory for the diagnosis of diabetes c69
    • When a child presents with symptomatic laboratory-confirmed severe hyperglycemia, a diagnosis of diabetes is secured
    • Under all other circumstances, 1 of 4 laboratory methods are used to establish the diagnosis
      • Additionally, when a child presents asymptomatically and a routine urinalysis shows glucosuria or ketonuria, confirmatory laboratory tests are required
    • Laboratory diagnosis requires confirmation of 2 tests (same or different type of confirmatory tests), unless a clear clinical diagnosis exists (eg, patient in a hyperglycemic crisis or with classic symptoms of hyperglycemia and a random plasma glucose measurement of at least 200 mg/dL) r1
  • Confirmatory laboratory test results include: r1
    • Fasting (no caloric intake for at least 8 hours) plasma glucose measurement of 126 mg/dL or higher
    • Random plasma glucose measurement of 200 mg/dL or higher when classic symptoms of hyperglycemia or hyperglycemic crisis are present
    • Hemoglobin A1C measurement 6.5% or higher
    • 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)
  • Pancreatic islet autoantibodies and C-peptide levels are useful laboratory studies for determining diabetes type classification when there is uncertainty about type 1 status r1
  • Initial diagnostic assessment of comorbidities at time of diagnosis r1
    • Measure blood pressure, fasting lipid panel, and urinary albumin excretion
    • American Diabetes Association provides a complete list of comprehensive medical evaluation components to cover at initial evaluation r28
  • Additional baseline laboratory tests recommended at diagnosis to screen for associated diseases include: r28
    • Estimated GFR/creatinine clearance
    • Lipid panel (after glucose control has been established)
    • TSH, antithyroid peroxidase, and antithyroglobulin antibodies (soon after glycemic control has been established)
    • Celiac antibody panel (soon after diagnosis)
      • 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

Laboratory

  • Fasting glucose measurement c70
    • Diagnostic thresholds are as follows: r1
      • 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 r1
    • In absence of unequivocal hyperglycemia, another abnormal test result from either the same specimen or a separate sample is required to confirm diagnosis r1
  • Random glucose measurement c71
    • Diagnostic threshold is 200 mg/dL (11.1 mmol/L) or greater when signs or symptoms of hyperglycemia are present r1
  • Hemoglobin A1C r1c72
    • Diagnostic threshold is 6.5% or greater
    • 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)r29 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 r15
      • 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 and only plasma blood glucose criteria should be used to diagnose diabetes; such conditions may 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
      • A second abnormal test result from either the same specimen or a separate sample is required to confirm diagnosis in absence of unequivocal hyperglycemia
  • Oral glucose tolerance test c73
    • Technically, can be used to make a diagnosis of diabetes mellitus, but not especially useful when type 1 diabetes is suspected in a child
  • Pancreatic islet autoantibodies r13c74
    • Type 1 diabetes is defined by presence of 1 or more autoantibodies against islet cell antigens (commercial laboratory assays measure all four) r1
      • 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 r30r31
        • 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 r30r31
      • 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 r30r31
      • Autoantibodies to insulin
        • Must be measured before or within 2 weeks of initiating insulin therapy r31
        • Detected in over 50% to 90% of patients with newly diagnosed disease r30r31
  • C-peptide c75
    • 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 r32
    • A frankly low level or complete absence of C-peptide is indicative of type 1 diabetes r33
    • 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 r34

Other diagnostic tools

  • Genetic testing r1
    • Genetic testing for neonatal diabetes is indicated for any child with diabetes diagnosed in the first 6 months of life
    • Testing should include at a minimum mutational analysis of genes encoding the Kir6.2 subunit (KCNJ11) and SUR1 subunit (ABCC8) of the β-cell potassium-ATP channel, and the gene encoding insulin (INS)

Differential Diagnosis

Most common

  • Type 2 diabetes mellitus c76d2
    • 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 r1
    • 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 r33
      • Fasting C-peptide level greater than 3 nanograms/mL after several months of therapy is highly suggestive of type 2 diabetes r35
  • Monogenic diabetes mellitus r36c77
    • Set of disorders that cause β-cell dysfunction and impaired insulin secretion, with onset of hyperglycemia in youth r37
    • Prevalence of 1% to 2% in pediatric diabetes population r38
    • Consider in children with the following findings: r36
      • Diabetes diagnosed within the first 6 months of life r1
      • Strong family history of diabetes but without typical features of type 2 diabetes (ie, nonobese, low-risk ethnic group)
      • Mild fasting hyperglycemia (100-150 mg/dL [5.5-8.5 mmol/L]), especially if young and nonobese r36
      • Diabetes with negative autoantibodies results and without signs of obesity or insulin resistance
    • 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--2021. Diabetes Care. 44(suppl 1):S15-33, 2021; 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 AsianAllAll, 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 autoantibodies+ (80%-90%)− (less than 1%)− (less than 10%)
    Acanthosis nigricans− − − (matches general population)+ (86%)
    Obesity− (matches general population)+/− (varies by population)− (uncommon)+ (very common, more than 90%)

Cystic fibrosis–related diabetes r39c78

  • Diabetes occurs in 20% of adolescents with cystic fibrosis, and it is typically discovered through screening measures r39
  • 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 the basis of patient's known history of cystic fibrosis

Treatment

Goals

  • Goals of initial management r32
    • 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
    • Aim for optimal glycemic control
      • Hemoglobin A1C target level is less than 7% in children younger than 19 years r40
        • More strict goal of less than 6.5% is suggested if it can be achieved without excessive hypoglycemia or other negative impacts
        • More relaxed glycemic targets (greater than 7.5%) are suggested for children who cannot articulate hypoglycemic symptoms, experience hypoglycemia unawareness, lack advanced insulin delivery or monitoring technology, or cannot check blood glucose level regularly
      • Target goals for measurements from self-monitoring of blood glucose level r41
        • Preprandial goal: 90 to 130 mg/dL (5-7.2 mmol/L)
        • Bedtime and overnight: 90 to 150 mg/dL (5-8.3 mmol/L)
        • Before exercise: 90 to 250 mg/dL (5-13.9 mmol/L) r40
      • Ambulatory glucose profile targets (continuous glucose monitoring)
        • Greater than 70% of time in range of 70 to 180 mg/dL r42r43
      • Minimize hypoglycemia (especially important for children younger than 6 years) r40
      • Avoid extreme fluctuations in blood glucose
    • 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 r40
        • In adolescents aged 13 years or older, below 120/80 mm Hg r40
      • Reference ranges for age, sex, and height and appropriate methods for measurement are available from the American Academy of Pediatrics r44
    • Lipids
      • Goal is an LDL-C value lower than 100 mg/dL r40

Disposition

Admission criteria

New diagnosis

  • Consider the following factors when deciding to admit patient for new diagnosis of diabetes: r32
    • 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: r45
    • DKA
    • Random glucose measurement is 250 mg/dL or greater
    • Hemoglobin A1C greater than 9%
  • Ongoing clinical trials are studying the ideal setting in which to deliver care of patient with newly diagnosed type 1 diabetes who is not acutely ill r46
    • Available data suggest that when adequate resources for home management are available, outcomes such as acute complications, long-term metabolic control, behavioral problems, and psychosocial issues are comparable when initial care occurs in the outpatient versus inpatient setting r47

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: r48
    • 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 r40
  • 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 10 years or older, or puberty has started (whichever is earlier), and child has had diabetes for 3 to 5 years r40
  • 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 r40

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 r32
  • Second priority is to provide basic diabetes education and self-management training for the child (age and developmentally appropriate) and other caregivers r32

Chronic management of children with type 1 diabetes consists of several components, which together constitute a comprehensive treatment plan r40

  • Intensive insulin therapy r43
  • Glucose monitoring r43
  • Age-appropriate diabetes education r28
  • Medical nutrition therapy r49
  • Ongoing assessment and treatment of comorbidities and complications r40

Insulin therapy

  • Intensive insulin therapy to simulate a physiologic pattern of insulin secretion is standard of care r50r51
  • Successful management requires balancing insulin replacement with carbohydrate intake and physical activity
  • Intensive insulin therapy consists of insulin delivery using 1 of 2 methods r51
    • Multiple (3-4 per day) daily injections, which combine rapid and long-acting insulin analogues, or
    • 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
  • Most children with newly diagnosed disease start with a regimen of multiple daily injections; some may transition to continuous subcutaneous insulin infusion thereafter
  • Both methods of insulin delivery require adjustment of the insulin dose depending on the preprandial glucose levels, dietary intake, and physical activity

Glucose monitoring r43

  • Blood glucose self-monitoring is essential to determine basal and prandial insulin needs, prevent hypoglycemia, and to assess response to changes in insulin dosing
  • Methods for self-monitoring of blood glucose include capillary blood glucose testing using a glucometer or continuous glucose monitoring
  • If self-monitoring, children and adolescents should monitor glucose levels up to 6 to 10 times per day
  • Consider continuous glucose monitoring in all children and adolescents r40
    • 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 r52
    • Intermittently scanned continuous glucose monitors (in lieu of self-monitoring of blood glucose levels) 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 r52

Diabetes education r49

  • 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 and continues with a series of formal sessions with a diabetes educator during the initial 3 months of diagnosis, then annually thereafter

Medical nutrition therapy

  • Individualized nutrition counseling, provided by a registered dietitian, is recommended for all patients r40
  • Monitoring carbohydrate intake (ie, carbohydrate counting or experience-based estimation) is an important aspect in achieving optimal glycemic control r40
  • 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 r40

Drug therapy

  • Insulin c79
    • General principles r53
      • Initial insulin therapy with either multiple daily injections or continuous subcutaneous insulin infusion requires comprehensive education
        • Multiple daily injections r53
          • Basal insulin is given as an injection of long- or intermediate-acting insulin analogues, while meal-related glucose excursions are treated with bolus injections of rapid-acting insulin analogues
        • Continuous subcutaneous insulin infusion r53
          • 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
        • Insulin analogues are preferred both for multiple daily injections and continuous subcutaneous insulin infusion; no clinically significant differences have been shown among the various analogues available in the pediatric population r54
      • For either mode of insulin delivery, 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
      • Safety and effectiveness of a prescribed insulin regimen depend on frequent self-monitoring of blood glucose and/or a continuous glucose monitoring system to avoid hypoglycemia and glucose variability
      • Regardless of the mode of insulin delivery, regularly review and modify insulin doses based on consideration of individual factors (eg, exercise, pubertal status) and daily pattern of blood glucose
    • Initial strategy at the time of a new diagnosis in insulin-naive patients is as follows:
      • Starting doses vary widely, with higher doses usually necessary after a patient has stabilized from DKA
      • Suggested starting total daily doses r55
        • Prepubertal children: 0.25 to 0.5 units/kg/day
        • Pubertal children: 0.5 to 0.75 units/kg/day
        • Postpubertal children: 0.25 to 0.5 units/kg/day
      • Divide total daily insulin into bolus and prandial portions r55
        • Basal insulin glargine should be 25% to 30% of the total dose in toddlers and 40% to 50% in older children
        • Remaining portion of the total daily dose is provided as bolus insulin
      • Typical maintenance total daily doses r50
        • During the partial remission "honeymoon" phase, the total daily insulin dose is usually less than 0.5 units/kg/day
        • Prepubertal children (outside the partial remission phase) usually require a total daily insulin dose of 0.7 to 1 units/kg/day
        • During puberty, total daily insulin requirements can reach as high as 1 to 2 units/kg/day
      • Optimal dose of insulin maximizes glycemic control without causing frequent or severe hypoglycemia, and on a practical level, can only be determined empirically with frequent blood glucose monitoring and insulin adjustments
  • Basal insulins c80c81c82c83
    • Basal insulin is designed to ideally provide enough insulin to maintain euglycemia between meals and overnight r56
    • 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 r57
    • Detemir insulin
      • Insulin Detemir (Recombinant) Solution for injection; Children and Adolescents 2 to 17 years: Insulin requirements highly variable and must be individualized based on patient factors and insulin regimen. During partial remission phase, total combined daily insulin requirement often less than 0.5 units/kg/day. Prepubertal children (outside the partial remission phase) usually require 0.7 to 1 unit/kg/day. During puberty, insulin requirement is often between 1 to 2 units/kg/day. Use insulin detemir in combination with rapid-acting insulin as part of a basal-bolus regimen; approximately 30% to 45% (sometimes 50% when insulin analogs are used) should be basal insulin, the rest should be adjusted doses for prandial insulin. Alternatively, administer one-third to one-half of total daily insulin requirements subcutaneously 1 to 2 times/day as insulin detemir. Titrate dosage to achieve blood glucose and A1C goals. For once daily dosing, give dose with evening meal or at bedtime. For twice daily dosing, give 1 dose in the morning; give the second dose 12 hours after the morning dose, with the evening meal, or at bedtime. Conversion of insulin glargine or NPH insulin to insulin detemir is 1:1. Adjust to response; concurrent rapid- or short-acting insulin dosages or timing may need adjusted.
    • Glargine insulin
      • Insulin Glargine Solution for injection; Children and Adolescents 6 to 17 years: Insulin requirements highly variable and must be individualized based on patient factors and insulin regimen. During partial remission phase, total combined daily insulin requirement often less than 0.5 units/kg/day. Prepubertal children (outside the partial remission phase) usually require 0.7 to 1 unit/kg/day. During puberty, insulin requirement often between 1 to 2 units/kg/day. Use insulin glargine in combination with rapid-acting insulin as part of a basal-bolus regimen; approximately 30% to 45% (sometimes 50% when insulin analogs are used) should be basal insulin, the rest should be adjusted doses for prandial insulin. Alternatively, initially administer one-third of the total daily insulin requirements/dose subcutaneously once daily. Titrate to blood glucose control and A1C goals in conjunction with a rapid- or short-acting insulin. Give the dose at the same time every day, at any time. No dose chage is necessary for conversion from once daily NPH insulin. For conversion from twice-daily NPH, reduce the total daily dose of NPH insulin (or other twice daily basal insulin) by 20% and give once daily. When transferring from once-daily Toujeo to once-daily Lantus, Basaglar, or Semglee, the recommended initial Lantus, Basaglar, or Semglee dose is 80% of the Toujeo dose that is being discontinued. Adjust to patient response; concurrent rapid- or short-acting insulin dosages or timing may need to be adjusted.
    • NPH insulin
      • Insulin Suspension Isophane (NPH) (Recombinant) Suspension for injection; Infants, Children, and Adolescents: Insulin requirements highly variable and must be individualized based on patient factors and insulin regimen. During partial remission phase, total combined daily insulin requirement often less than 0.5 units/kg/day. Prepubertal children (outside the partial remission phase) usually require 0.7 to 1 unit/kg/day. During puberty, insulin requirement is often between 1 to 2 units/kg/day. Use isophane insulin in combination with rapid-acting insulin as part of a basal-bolus regimen; approximately 30% to 45% (sometimes 50% when insulin analogs are used) should be basal insulin, the rest should be adjusted doses for prandial insulin. Isophane insulin is given once daily before bed or divided into a twice daily regimen given 30 to 60 minutes before a meal.
  • Prandial insulins r58c84c85c86c87c88
    • Prandial doses (rapid-acting analogues or regular insulin) are used to limit glucose excursions that occur after meals or snacks
    • Regular insulin
      • Insulin Regular (Recombinant) Solution for injection; Infants, Children, and Adolescents: Insulin requirements highly variable; must be individualized based on patient and insulin regimen. During partial remission phase, total combined daily insulin requirement often less than 0.5 units/kg/day. Prepubertal children (outside the partial remission phase) usually require 0.7 to 1 unit/kg/day. During puberty, insulin requirement often between 1 and 2 units/kg/day. Use regular insulin in combination with intermediate- or long-acting insulin. Depending on the type of insulin used as the basal insulin, approximately 30% to 45% (sometimes 50% when insulin analogs are used) should be basal insulin, with the remainder divided into 3 to 4 prandial regular insulin boluses. Administer pre-meal doses of regular insulin approximately 20 to 30 minutes prior to a meal.
    • Aspart insulin
      • Insulin Aspart (Recombinant) Solution for injection; Children and Adolescents 2 to 17 years: Insulin requirements highly variable; must be individualized based on patient and insulin regimen. During partial remission phase, total combined daily insulin requirement often less than 0.5 units/kg/day. Prepubertal children (outside the partial remission phase) usually require 0.7 to 1 unit/kg/day. During puberty, insulin requirement often between 1 to 2 units/kg/day. Use insulin aspart in combination with intermediate- or long-acting insulin. Depending on the type of insulin used as the basal insulin, approximately 30% to 45% (sometimes 50% when insulin analogs are used) should be basal insulin, with the remainder divided into 3 to 4 prandial rapid-acting insulin boluses. Administer insulin aspart immediately before a meal (i.e., meal starts within 5 to 10 minutes after injection).
    • Lispro insulin
      • Insulin Lispro Solution for injection; Children and Adolescents 3 to 17 years: Insulin requirements highly variable; must be individualized based on patient and insulin regimen. During partial remission phase, total combined daily insulin requirement often less than 0.5 units/kg/day. Prepubertal children (outside the partial remission phase) usually require 0.7 to 1 unit/kg/day. During puberty, insulin requirement often between 1 to 2 units/kg/day. Use insulin lispro in combination with intermediate- or long-acting insulin. Depending on the type of insulin used as the basal insulin, approximately 30% to 45% (sometimes 50% when insulin analogs are used) should be basal insulin, with the remainder divided into 3 to 4 prandial rapid-acting insulin boluses. Administer insulin lispro 15 minutes before or immediately after a meal.
    • Glulisine insulin
      • Insulin Glulisine Solution for injection; Children and Adolescents 4 to 17 years: Insulin requirements highly variable; must be individualized based on patient and insulin regimen. During partial remission phase, total combined daily insulin requirement often less than 0.5 units/kg/day. Prepubertal children (outside the partial remission phase) usually require 0.7 to 1 unit/kg/day. During puberty, insulin requirement often between 1 to 2 units/kg/day. Use insulin glulisine in combination with intermediate- or long-acting insulin. Depending on the type of insulin used as the basal insulin, approximately 30% to 45% (sometimes 50% when insulin analogs are used) should be basal insulin, with the remainder divided into 3 to 4 prandial rapid-acting insulin boluses. Administer insulin glulisine within 15 minutes before or 20 minutes after starting a meal.
  • Rapid-acting insulin analogues for continuous subcutaneous insulin infusion devices r58
    • Aspart insulin
      • Insulin Aspart (Recombinant) Solution for injection; Children and Adolescents 2 to 17 years: When used in an external insulin pump via continuous subcutaneous insulin infusion (CSII), individualize dosing to the patient's age and metabolic needs. Therapy is provided by a professional team trained in CSII therapy and capable of supporting patient care continuously (i.e., 24-hours/7 days-a-week).
    • Lispro insulin
      • Insulin Lispro Solution for injection; Children and Adolescents 3 to 17 years: When used in an external insulin pump via continuous subcutaneous insulin infusion (CSII), individualize dosing to the patient's age and metabolic needs. Use Admelog or Humalog 100 units/mL only. Do NOT administer Humalog 200 units/mL using a continuous subcutaneous infusion pump. Therapy is provided by a professional team trained in CSII therapy and capable of supporting patient care continuously (i.e., 24-hours/7 days-a-week).
    • Glulisine insulin
      • Insulin Glulisine Solution for injection; Children and Adolescents 4 to 17 years: When used in an external insulin pump via continuous subcutaneous insulin infusion (CSII), individualize dosing to the patient's age and metabolic needs. Therapy is provided by a professional team trained in CSII therapy and capable of supporting patient care continuously (i.e., 24-hours/7 days-a-week).
  • Glucagon for severe hypoglycemia c89
    • Glucagon Hydrochloride Solution for injection; Infants and Children weighing less than 25 kg and Children younger than 6 years with unknown weight: 0.5 mg IM, IV, or subcutaneously once; may repeat a 0.5 mg dose using a new kit if there has been no response after 15 minutes.
    • Glucagon Hydrochloride Solution for injection; Children and Adolescents weighing 25 kg or more and Children 6 years and older with unknown weight: 1 mg IM, IV, or subcutaneously once; may repeat a 1 mg dose using a new kit if there has been no response after 15 minutes.
  • Common insulin preparations and approximate action profiles.Data from European Medicines Agency: Fiasp, INN-insulin aspart. Annex 1: summary of product characteristics. European Medicines Agency website. Published February 3, 2017. Updated April 27, 2018. Accessed June 17, 2019. https://www.ema.europa.eu/en/documents/product-information/fiasp-epar-product-information_en.pdf ; and 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.
    Type of insulinOnsetPeakDuration
    Ultra-rapid-acting
    Aspart (Fiasp)15 to 20 minutes1 to 3 hours3 to 5 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 c90

  • Replace volume deficits with normal saline IV fluids at a rate not to exceed 1.5 to 2 times the usual daily maintenance requirement r48

Blood glucose monitoring r59c91

  • 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) r59
    • May be needed up to 6 to 10 times per day r60
    • Recommended times for testing include 2 to 3 hours after meals; before, during, and after strenuous exercise; during intercurrent illness; and periodically between 12 AM and 4 AM r60
    • 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 as 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 with 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 r51
      • 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 r40r61r62
      • As a general rule, adolescents and young adults (aged 13-24 years) are least likely to use the devices with regularity, and thus do not achieve hemoglobin A1C reductions as significant as either younger children or adults
    • Indications r59
      • Most professional societies recommend real-time continuous glucose monitoring systems in children under the following circumstances:
        • Severe hypoglycemia
        • Hypoglycemia unawareness
    • Contraindications
      • Relative: unwillingness to use glucometer to guide insulin dosing
  • Intermittently scanned (flash) continuous glucose monitoring r60r63
    • 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;r40limited data show that the device has accuracy similar to standard continuous glucose monitor devices and lower rates of hypoglycemiar64
    • Main disadvantage is that it does not provide alarms for hypoglycemia or hyperglycemia

Diabetes education and self-management training r40c92c93

  • 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 r49c94

  • 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 r55
  • 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 r55
    • Total recommended caloric intake is based on size
    • Ideal macronutrient distribution is individualized;r49 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 Ramadanr65 and during intercurrent illnessr66

Immunizations r58

  • Annual influenza vaccine for children with diabetes who are aged 6 months or older c95
  • Pneumococcal polysaccharide vaccine for children with diabetes aged 2 years or older c96
  • Routine childhood vaccinations in accordance with recommended CDC vaccination schedulesr67c97

Other lifestyle issues c98

  • Discourage smoking (including e-cigarettes) in young people who do not smoke and encourage smoking cessation in those who do r40d3
  • Limit exposure to cigarette smoke in the home
  • Instruct patients to wear medical alert bracelet

Physical activity c99

  • 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) r49
    • Participation in physical activity with duration of at least 60 minutes significantly reduces hemoglobin A1C r68
    • Encourage muscle and bone strengthening activities at least 3 times weekly r49
  • 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 r69
  • Strategies to prevent exercise-induced hypoglycemia include: r70
    • Aim for minimum blood glucose level of 95 to 250 mg/dL at the start of exercise r40
      • If initial blood glucose levels are less than 95 mg/dL, delay physical activity and consume sufficient carbohydrates until blood glucose level is within appropriate preexercise range r40r69
    • Adjust insulin and/or carbohydrate intake
      • Reduce prandial insulin dose for meal or snack preceding exercise r40
      • Increase carbohydrate intake before exercise r40
      • Reduce basal insulin rates on continuous subcutaneous insulin infusion device by about 10% to 50% or more or suspend for 1 to 2 hours during exercise r40
      • Reduce basal insulin rate or long-acting insulin dose by approximately 20% after exercise to mitigate delayed exercise-induced hypoglycemia r40
    • 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 r40
      • For more strenuous and prolonged activities, instruct patient to consume 0.5 to 1.5 g carbohydrates/kg for each hour of strenuous activity r69
      • Monitor blood glucose during periods of continuous physical activity about every 30 minutes as well as 15 minutes after completion of exercise and at bedtime r69
      • 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 r71
      • 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 r71
      • If not already used, consider initiating a combined insulin pump/continuous glucose monitor system, particularly one with a low glucose threshold–suspend feature r69
  • Strategies to prevent hyperglycemia include:
    • In the presence of preexercise hyperglycemia, check for ketonuria
      • If glucose is greater than 250 mg/dL or ketones findings are positive, postpone vigorous exercise r69
    • If significant hyperglycemia occurs after exercise (usually from high-intensity exercise and increased catecholamine production), cautiously administer a small rapid-acting bolus of insulin r69

Behavioral and psychosocial aspects of care r40

  • Assess for psychosocial issues and family stress that may impact diabetes management; provide referrals to trained mental health providers when indicated
  • 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: r72

  • Diabetes care in the school setting r73
  • Care of young children with diabetes in the child care setting r74
  • Insulin access and affordability r75
  • Diabetes and driving r76
  • Diabetes and employment r77
  • Diabetes care in correctional institutions r78
Procedures
Continuous subcutaneous insulin infusion (insulin pump) therapy r79r80c100c101c102c103c104
General explanation
  • Mechanically driven insulin delivery technology in which a catheter is placed subcutaneously to provide a continuous infusion of rapid-acting insulin
  • 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
  • A newly available hybrid closed-loop system integrates an insulin pump and continuous glucose monitor and uses an algorithm that is capable of determining insulin needs based on sensor values r81
    • 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
Indication
  • Suggested indications vary among different professional societies
  • American Diabetes Associationr51 and International Society for Pediatric and Adolescent Diabetesr50 both recommend that continuous subcutaneous insulin infusion is a suitable option 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: r79
    • 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 r82

Complications r83

  • Cutaneous irritation or infection
  • Mechanical failures of software or hardware (eg, insulin leaking, screen fading, battery damage)
  • Catheter problems (eg, occlusion, bubbles, kinking)
Contraindications
  • Hybrid closed-loop system should not be used in: r81
    • 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 r84
  • 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 r85
  • 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 r86r87r88

During the COVID-19 pandemic, telehealth should be used for sick day management and routine diabetes care

Comorbidities

  • Hypertension r40c105
    • Measure blood pressure at each office visit
    • Encourage adolescents with diabetes to use ambulatory blood pressure monitoring periodically r44
    • Normative blood pressure values and threshold for diagnosing elevated blood pressure are now lower than previous classifications r44r89
      • High normal blood pressure is systolic or diastolic blood pressure in 90th to 95th percentile for age, sex, and height, or 120/80 to 139/89 mm Hg in adolescents aged 13 years or older confirmed on 3 separate visits r44
      • Hypertension is systolic or diastolic blood pressure in 95th percentile or higher for age, sex, and height, or 140/90 mm Hg or greater in adolescents aged 13 years or older confirmed on 3 separate visits r44
    • Initial treatment for high normal blood pressure is aimed at lifestyle modifications of altering diet, increasing exercise, and controlling weight r40
      • Consider pharmacologic treatment of hypertension if target blood pressure is not reached with 3 to 6 months of using lifestyle methods r40
    • 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 140/90 mm Hg or greater in adolescents aged 13 years or older) r40
      • ACE inhibitors or angiotensin receptor blockers (alternatively) are preferred in children with diabetes and hypertension r40
      • Use of an ACE inhibitor and statin are not recommended for primary prevention of microvascular complications since available data do not demonstrate reduction in albuminuria or progression of retinopathy r90
    • 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 r40
  • Dyslipidemia c106
    • Dyslipidemia is a risk factor for atherosclerotic cardiovascular disease in type 1 diabetes
    • Initial therapy consists of both: r40
      • Optimizing glucose control (which can improve lipid values but not normalize them), and r91
      • 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 about 10% calories from monounsaturated fats r40
    • 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 r40
  • Cardiovascular disease r92c107
    • Cardiovascular events generally do not occur during childhood, but atherosclerotic process begins during childhood in diabetes r93
      • Age and hemoglobin A1C level are strongest risk factors for a major atherosclerotic event or any cardiovascular disease in type 1 diabetes r94
      • Cardiovascular risk reduction involves optimizing glycemic control and managing other cardiovascular risk factors (eg, maintaining healthy body weight, physical activity, healthy diet, treating hypertension) r93
  • Autoimmune conditions c108
    • Assess for presence of thyroid dysfunction and celiac disease soon after diagnosis and if symptoms develop
      • Autoimmune thyroiditis c109
        • Most common autoimmune disorder associated with diabetes, occurring in 15% to 30% of children and adolescents with type 1 diabetes r18
        • Assess TSH level soon after diagnosis and metabolic stabilization, and obtain tests for antithyroid peroxidase and antithyroglobulin antibodies r95
        • If TSH levels are within reference range, consider rechecking every 1 to 2 years or sooner if the patient has positive thyroid antibodies or develops symptoms suggestive of thyroid dysfunction, thyromegaly, abnormal growth rate, or unexplained glycemic variation r40
      • Celiac disease r96c110
        • Gluten-sensitive enteropathy that occurs in approximately 2% to 16% of patients with type 1 diabetes r40
        • Higher prevalence in patients with type 1 diabetes, family history of celiac disease, younger age, and associated thyroid autoimmunity r96
        • Children may be asymptomatic or 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 r96
        • 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 r40
          • Obtain IgA tissue transglutaminase antibodies in patients with documentation of normal total serum IgA levels; 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 r40
        • Treat patients with confirmed celiac disease using gluten-free diet in consultation with a dietitian experienced in managing both diabetes and celiac disease r40
      • 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 c111c112c113c114c115
        • A heightened awareness for their presence is advisable, but routine screening of asymptomatic children is not recommended r40
  • 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 r97
    • 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 r98
    • 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) r99
    • 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 r97
  • Psychosocial issues c116
    • Psychosocial distress is common, owing to burdens of diabetes management throughout childhood and adolescence r40c117c118
      • The term diabetes distress refers to the duress of constant behavioral demands (eg, medication dosing, frequency, and titration; monitoring blood glucose, food intake and eating patterns; physical activity) of diabetes self-management r100
      • Occurs in approximately one-third of adolescents with diabetes r101
      • Monitor for diabetes distress routinely (Diabetes Distress Scaler102) beginning at age 7 or 8 years,r40 and refer patient to diabetes education or a behavioral health provider if areas of diabetes care are impacted r100
    • Rates of depression are higher in youth with type 1 diabetes compared with those of youth without the disease r103c119
      • Annually screen youth for depression using depression screening tools r100r104
      • Consider screening for depression with any changes in medical status, including development of new complications r100
    • 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 r103c120
    • 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: r100
        • 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 r40
  • Eating disorders c121
    • Higher incidence in youth with type 1 diabetes compared with that of children without diabetes
    • Disturbed eating behaviors, coupled with unhealthy weight control behaviors, correlate with worse glycemic control r105
      • Insulin omission and insulin underdosing are the most common and serious weight control behaviors and are associated with increased morbidity and mortality r106
      • 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,r107 particularly when hyperglycemia and weight loss are unexplained r40

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 r50
      • Increase insulin to carbohydrate ratios to estimate prandial doses r58
  • 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 r108
      • Discuss risks of fetal malformations, maternal complications, and diabetes in offspring for women with reproductive potential
        • Major malformations are caused by hyperglycemia during the first 8 weeks of gestation and account for 50% of perinatal mortality r109
        • Fetal complications later in pregnancy arise from fetal hyperinsulinemia secondary to maternal hyperglycemia, leading to macrosomia r109
      • Discuss contraceptives for all girls of childbearing potential r40
    • Transition to adulthood
      • Adolescents should gradually assume greater responsibility for diabetes management
      • Begin to prepare youth for transition in early adolescence r40
      • 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 r40r110
  • Adolescent pregnancy r109
    • Most pregnancies in adolescents with type 1 diabetes are unplanned; referral to high-risk obstetrics specialist is routine
    • Glycemic goals in pregnancy are more stringent
      • American Association of Clinical Endocrinologists targets r58
        • Hemoglobin A1C less than 6% during pregnancy
        • Preprandial, bedtime, and overnight glucose levels: 60 to 99 mg/dL
        • Peak postprandial blood glucose level: 100 to 129 mg/dL
      • American Diabetes Association targets r108
        • Hemoglobin A1C level: ideal value is 6% or lower (may use target of less than 7% in patients with frequent hypoglycemia)
        • Fasting blood glucose of less than 95 mg/dL
        • 1-hour postprandial blood glucose less than 140 mg/dL or 2-hour postprandial blood glucose 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
      • Self-monitoring of blood glucose 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 r108
      • 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 5 mg daily 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
    • Consider prescribing low-dose aspirin (100-162 mg/day) starting at the end of the first trimester to lower risk of preeclampsia r108

Monitoring

  • American Diabetes Association provides a complete list of comprehensive medical evaluation components to cover at annual examination and each follow-up visit r28
    • Periodically reassess the following:
      • Diabetes self-management and support r40
      • Educational needs and training for those providing care for child (eg, day care providers, school personnel) r40
      • Growth and development
        • Measure height and weight at each visit, or on quarterly basis r15
        • Calculate BMI percentile and corresponding BMI-for-age percentile on quarterly basis r111
        • Regularly check injection sites and technique
      • Glycemic control
        • Self-monitoring of blood glucose is essential for optimal management
          • Inverse relationship exists between frequency of blood glucose monitoring and hemoglobin A1C levels r112
          • Recommended frequency of blood glucose self-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) r59
            • 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 r15r59r60
          • 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 r43
            • 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% r40r43
            • Precise range for a given child's glucose parameters is somewhat individualized; general goal is target range of 70 to 180 mg/dL r43
            • Continuous glucose monitoring metrics are recommended to be used in conjunction with hemoglobin A1C values whenever possible r40
        • 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 r1r113
          • Recommended measurement includes: r43
            • 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 is less than 7.5%; individualization of target goal may be necessary based on needs and situation of family and patient r40
        • Monitor blood or urine ketone levels in the setting of prolonged hyperglycemia or acute illness r15r60
          • 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 r28
          • 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 r40
      • Comorbidities
        • Hypertension
          • Measure blood pressure at each routine visit r40
        • Dyslipidemia
          • Perform initial lipid testing when initial glycemic control has been achieved and patient is at least 2 years old; subsequent testing should be performed at ages 9 to 11 years if initial LDL-C is 100 mg/dL or lower r40
            • 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);r40monitor annually if level is abnormalr15
        • 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 r40
          • If patient develops autoimmune hypothyroidism and takes thyroid hormone replacement, measure periodically to maintain TSH within reference range
        • Celiac disease
          • Repeat screening within 2 years of initial screening at the time of diagnosis; follow-up with screening every 5 years or more frequently in patients with symptoms concerning for celiac disease, or in patients with first-degree relative with celiac disease r40
            • Obtain IgA tissue transglutaminase antibodies (with documentation of normal total serum IgA levels) or IgG to tissue transglutaminase 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 r40
          • Monitor children and adolescents, along with their parents, for signs of diabetes distress during routine follow-up care r100
          • Screen for depression and anxiety quarterly
          • For teenagers, assess use of alcohol, tobacco, illicit drugs, and contraception as needed
          • Monitor for eating disorders in patients around age 10 to 12 years with validated screening tool and when hyperglycemia and/or weight loss are unexplained r40
      • Complications
        • Nephropathy
          • Measure urinary albumin-creatinine ratio (from a spot urine sample) once child has had diabetes for 5 years starting at puberty or age 10 years, whichever is earlier, and then annually thereafter r40
          • Obtain estimated GFR as needed based on clinical status, age, duration of diabetes, and therapy r40
        • 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 r40
          • Less-frequent examinations (every 4 years) may be acceptable with the advice of an eye care professional r40
          • Other recommendations suggest initial ophthalmologic examination beginning 5 years after diagnosis and annually thereafter r114
        • Neuropathy
          • Visual foot examination annually in older children to educate regarding importance of foot care r40
          • Consider annual comprehensive foot examination to assess for peripheral neuropathy at start of puberty or at least 10 years old (whichever is earlier) once diabetes has been established for 5 years r40
            • Assessment includes history and monofilament testing with pinprick, temperature, or vibration sensation tests

Complications and Prognosis

Complications

  • Acute
    • DKA (diabetic ketoacidosis) r115c122d1
      • Life-threatening condition marked by hyperglycemia, metabolic acidosis, and ketonemia
      • 30% of new-onset diabetes cases in children present as DKA r116
      • COVID‐19 infection may precipitate severe metabolic complications of diabetes including DKA, which may be the initial presentation of new-onset diabetes r117
      • 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 r117r118
      • Signs and symptoms include polyuria, polydipsia, polyphagia, weight loss, weakness, abdominal pain, nausea, vomiting, Kussmaul respirations, and acetone breath
      • 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 r119
    • Treatment-related hypoglycemia
      • Thresholds r120
        • At a glucose level of less than or equal to 70 mg/dL, 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 developmental and age-dependent; limitations of infants and toddlers to detect or report symptoms may demand more frequent monitoring r40
      • Frequent, severe, and/or nocturnal hypoglycemia require adjustment in insulin doses r63
      • 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 r40
      • Immediate treatment of severe hypoglycemia requires administration of rapidly absorbed glucose, glucagon, and IV glucose with treatment based on the severity of the hypoglycemia
  • Chronic
    • Microvascular complications r121c123c124c125c126
      • 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 r15
        • Nephropathy r121c127c128c129c130
          • 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 r121
            • Modestly elevated albumin excretion: 30 to 299 mg/g albumin-creatinine ratio (in a spot urine sample) r121
            • Persistent abnormal microalbumin excretion: requires documentation of 2 of 3 consecutive abnormal values obtained on different days over a 6-month period r40
            • Test confounders include exercise within 24 hours, infection, fever, congestive heart failure, marked hyperglycemia, menstruation, and severe hypertension r121
          • In addition to strict glycemic control, blood pressure control (less than 130/80 mm Hg in the setting of albuminuria) 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) r40
        • Retinopathy c131c132c133c134
          • 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 r40
          • Measures to reduce risk or slow progression of diabetic retinopathy include optimal control of glycemia, blood pressure, and serum lipid levels r121
        • Neuropathy r121c135c136c137c138
          • Neurologic complications rarely occur during childhood
          • Measures to prevent or delay onset of diabetic neuropathy include optimizing glycemic control
    • Macrovascular complications c139
      • Cardiovascular disease r92c140
        • Coronary artery disease is main cause of death in persons with type 1 diabetes c141
        • 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 r94
        • 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 r94
        • Addressing other individual risk factors for atherosclerotic cardiovascular disease to reduce the likelihood of harmful events is especially important in diabetes r99
        • 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 c142
    • 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) r40
    • Obesity is as common in children and adolescents with type 1 diabetes as in those without diabetes r40
    • 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 r122
    • All-cause and cardiovascular-related mortality rates are at least twice as high as those for matched controls r123
    • 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 r124
    • 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 r124

Screening and Prevention

Screening

At-risk populations

  • First-degree relatives have an 8- to 15-fold increased risk of type 1 diabetes r125c143
  • Second-degree relatives have a 2-fold increased risk of type 1 diabetes r125

Screening tests

  • Measuring islet autoantibodies in relatives of patients with type 1 diabetes may identify those who are at risk for developing disease r2c144
    • General population screening of first-degree relatives of those with type 1 diabetes is not universally recommended, but it is available in clinical research trials

Prevention

  • There are no known effective lifestyle measures or pharmacologic interventions that delay or prevent type 1 diabetes r126c145
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