Diabetes Mellitus Type 1 in Children

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

• 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

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: ^r2r29
  • 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
    • Hemoglobin A1C measurement of 6.5% or higher ^c85
    • Fasting plasma glucose level of 126 mg/dL or higher (no caloric intake for at least 8 hours before blood draw) ^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 ^r30r31
  • 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
• Additional baseline laboratory tests recommended at diagnosis to screen for associated diseases include the following: ^r30r31
  • 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) ^c97c98c99
  • 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 ^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)^r32 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 ^r14r29c105
  • Type 1 diabetes is defined by presence of 1 or more autoantibodies against islet cell antigens (commercial laboratory assays measure all 4) ^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 ^r33r34
      • 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 more than 30% to 70% of patients with newly diagnosed disease ^r33r34
    • 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 ^r33r34
    • Autoantibodies to insulin
      • Must be measured before or within 2 weeks of starting insulin therapy ^r33
      • Detected in more than 50% to 90% of patients with newly diagnosed disease ^r33r34
  • Absence of pancreatic autoantibodies does not rule out type 1 diabetes ^r35
    • Up to 10% of patients with new-onset type 1 diabetes have been found to have no islet antibodies in White European study populations ^r35
    • Pancreatic autoantibody titers diminish over time, which can produce false-negative results ^r36
• C-peptide ^r35c106
  • 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 ^r37
  • A frankly low level or complete absence of C-peptide is indicative of type 1 diabetes ^r38
  • 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 ^r39

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

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 ^r35
    • Lower BMI, unintentional weight loss, ketoacidosis, and severe hyperglycemia at presentation also favor type 1 diabetes ^r35
    • 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 ^r38
    • Fasting C-peptide level greater than 3 nanograms/mL after several months of therapy is highly suggestive of type 2 diabetes ^r40
• Monogenic diabetes mellitus ^r41c109
  • Set of disorders that cause β-cell dysfunction and impaired insulin secretion, with onset of hyperglycemia in youth ^r42
  • Prevalence of 1% to 2% in pediatric diabetes population ^r43
  • Consider in children with the following findings: ^r41
    • 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 ^r41
    • 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.

  Characteristic	Immune-mediated type 1 diabetes	Idiopathic type 1 diabetes	Monogenic diabetes	Type 2 diabetes
  Prevalence
  In children with diabetes (overall)	Most cases of type 1 diabetes in children, but 5% to 10% of all diabetes	10% or higher in African-American children	1% to 6%	Approximately 12%
  Ethnicity	All, White populations at highest risk (30%-60% lower in African-American populations)	African-American and Asian populations	All	All, minority groups at highest risk in North America
  Onset
  Typical age at onset in children	Throughout childhood and adolescence but may occur into eighth or ninth decade of life	Pubertal	Typically younger than 35 years	Puberty (mean age, 13.5 years)
  Onset	Acute severe	Acute severe	Gradual	Insidious to severe
  DKA at onset	Approximately 32% in United States (up to 80% globally)	Episodic	Not typical	5% to 20%
  Heredity
  Affected relative	3% to 10%	More than 75%	50% to 90%	Up to 90%
  Inheritance	Polygenic	Autosomal dominant	Autosomal dominant	Polygenic
  HLA-DR3/4 association	Present	Absent	Absent	Absent
  Insulin status
  Insulin (C-peptide) secretion	Reduced or absent	Variably reduced	Variably reduced	Varies (up 85% impairment at time of diagnosis)
  Insulin sensitivity	Normal when controlled	Normal	Normal	Reduced
  Insulin dependence	Lifelong	Intermittent	Variable	Variable
  Associated features
  Islet autoantibodies	80%-90%	Absent	Less than 1%	Less than 10%
  Acanthosis nigricans	Matches general population	Matches general population	Matches general population	86%
  Obesity	Matches general population	Varies by population	Uncommon	More than 90%

Admission criteria

New diagnosis

• Consider the following factors when deciding to admit patient for new diagnosis of diabetes: ^r37
  • 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: ^r48
  • 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 ^r49
  • No patients randomized to home management required hospital admission during start of treatment
  • 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

Recommendations for specialist referral

• A multidisciplinary treatment team of specialists with experience managing pediatric diabetes is ideal for care coordination ^r31
• Refer all patients to pediatric endocrinologist for guidance on start 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 ^r31
• 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 ^r31

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 insulin	Onset	Peak	Duration
    Ultra-rapid-acting
    Aspart (Fiasp)	15 to 20 minutes	1.5 to 2.25 hours	5 to 7 hours
    Rapid-acting
    Aspart (Novolog)	15 to 30 minutes	1 to 3 hours	3 to 5 hours
    Lispro (Humalog)	15 to 30 minutes	1 to 3 hours	3 to 5 hours
    Glulisine (Apidra)	15 to 30 minutes	1 to 3 hours	3 to 5 hours
    Short-acting
    Regular insulin	30 to 60 minutes	2 to 4 hours	5 to 8 hours
    Intermediate-acting
    NPH	2 to 4 hours	4 to 8 hours	12 to 18 hours
    Long-acting
    Detemir (Levemir)	2 to 4 hours	None	12 to 24 hours
    Glargine (Lantus)	2 to 4 hours	None	Up to 24 hours
    Degludec (Tresiba)	2 to 4 hours	None	More 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 ^r50

Blood glucose monitoring ^r63c132

• 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) ^r63
  • 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 ^r64
  • 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 ^r65r66r67
    • 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 ^r31r51
    • Other professional societies recommend real-time continuous glucose monitoring systems in children with type 1 diabetes under the following circumstances: ^r63
      • 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 ^r64r68
  • 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 ^r31
  • 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 ^r69
  • Not all models provide alarms for hypoglycemia or hyperglycemia ^r70

Diabetes education and self-management training ^r31c133c134

• 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; 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 ^r52c135

• 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;^r52 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
  • Fat and protein composition of meals is also of importance because higher fat and protein content can be associated with early hypoglycemia and delayed postprandial fluctuations in blood glucose ^r31
• 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 Ramadan^r71 and during intercurrent illness^r72

Immunizations ^r73

• 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 schedules^r74c138
  • 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 ^r31c140d4
• 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) ^r52
  • Exercise is essential to mitigation of cardiometabolic risk factors in children and adolescents with type 1 diabetes ^r75
  • Regular physical activity lowers hemoglobin A1C by 0.3% to 0.5%, depending on baseline level and amount of physical activity ^r75
  • Physical activity improves insulin sensitivity ^r75
  • Regular exercise lowers the risk of premature all-cause and cardiovascular mortality ^r75
• Encourage muscle and bone strengthening activities at least 3 times weekly ^r31r52
• 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 ^r76
• Strategies to prevent exercise-induced hypoglycemia include: ^r75
  • Aim for blood glucose level of 126 to 180 mg/dL before physical activity and exercise ^r31
    • If initial blood glucose levels are below goal, delay physical activity and consume sufficient carbohydrates until blood glucose level is within appropriate preexercise range ^r31r76
  • Adjust insulin and/or carbohydrate intake ^r31
    • Reduce prandial insulin dose for meal or snack preceding exercise
    • Increase carbohydrate intake before exercise
    • 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
    • Reduce basal insulin rate or long-acting insulin dose by approximately 20% after exercise to mitigate delayed exercise-induced hypoglycemia
  • 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 ^r31
    • For more strenuous and prolonged activities, instruct patient to consume 0.5 to 1.5 g carbohydrates/kg for each hour of strenuous activity ^r76
    • 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 ^r76
    • 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 ^r75
    • 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 ^r75
    • Use of a combined insulin pump/continuous glucose monitoring system, particularly one with a low glucose threshold–suspend feature, is strongly recommended ^r57
• 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 ^r31
• If significant hyperglycemia occurs after exercise (usually from high-intensity exercise and increased catecholamine production), cautiously administer a small rapid-acting bolus of insulin ^r76

Behavioral and psychosocial aspects of care ^r31

• Assess for psychosocial issues and family stress that may affect diabetes management; provide referrals to trained mental health practitioners 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: ^r77

• Diabetes care in the school setting ^r78r79
• Care of young children with diabetes in the child care setting ^r80
• Managing diabetes in preschoolers ^r81
• Insulin access and affordability ^r82
• Diabetes and driving ^r83
• Diabetes and employment ^r84
• Diabetes care in correctional institutions ^r85

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

Comorbidities

• Hypertension ^r31c147
  • Measure blood pressure at each office visit
  • Encourage adolescents with diabetes to use ambulatory blood pressure monitoring periodically ^r47
  • Normative blood pressure values and thresholds for diagnosing elevated blood pressure and hypertension are now lower than in previous classifications ^r31r47
    • Elevated blood pressure (previously termed "prehypertension") is either of the following confirmed on 3 separate visits: ^r47
      • 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: ^r47
      • Systolic or diastolic blood pressure in 95th percentile or higher for age, sex, and height
      • 130/80 mm Hg or higher 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 ^r31
    • Consider pharmacologic treatment of hypertension if target blood pressure is not reached within 3 to 6 months of using lifestyle methods ^r31
    • Ambulatory blood pressure monitoring is strongly encouraged for these patients
  • 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 higher in adolescents aged 13 years or older) ^r31
    • ACE inhibitors or angiotensin receptor blockers (alternatively) are preferred in children with diabetes and hypertension ^r31
    • Use of an ACE inhibitor with statin is not recommended for primary prevention of microvascular complications because available data do not show reduction in albuminuria or progression of retinopathy ^r104
  • Goal blood pressure levels are those that are consistently below 90th percentile for age, sex, and height, or below 130/80 mm Hg in adolescents aged 13 years or older ^r31
• Dyslipidemia ^c148
  • Dyslipidemia is a risk factor for atherosclerotic cardiovascular disease in type 1 diabetes
  • Initial therapy consists of both of the following: ^r31
    • Optimizing glucose control (which can improve lipid values but not normalize them) ^r105
    • 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 ^r31
  • 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 ^r31
    • Goal of therapy is to achieve LDL cholesterol value less than 100 mg/dL ^r31
• Cardiovascular disease ^r106c149
  • Cardiovascular events generally do not occur during childhood, but atherosclerotic process begins during childhood in diabetes ^r107
    • Age and hemoglobin A1C level are strongest risk factors for a major atherosclerotic event or any cardiovascular disease in type 1 diabetes ^r108
    • Cardiovascular risk reduction involves optimizing glycemic control and managing other cardiovascular risk factors (eg, maintaining healthy body weight, physical activity, healthy diet, treating hypertension) ^r107
• 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 ^r109r110
      • 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 ^r31
    • Celiac disease ^r111c152
      • Gluten-sensitive enteropathy that occurs in approximately 2% to 16% of patients with type 1 diabetes ^r31
      • Higher prevalence in patients with type 1 diabetes, family history of celiac disease, younger age, and associated thyroid autoimmunity ^r111
      • 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 ^r111
      • 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 ^r31
        • 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 in asymptomatic children given potential challenges of recommended dietary restrictions for patients with both diabetes and celiac disease ^r31
      • Treat patients with confirmed celiac disease using gluten-free diet in consultation with a dietitian experienced in managing both diabetes and celiac disease ^r31
    • 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 ^r31
• 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 with overweight or obesity, respectively ^r112
  • 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 ^r113
  • 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) ^r114
  • 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 ^r112
• Psychosocial issues ^c158
  • Psychosocial distress is common, owing to burdens of diabetes management throughout childhood and adolescence ^r31c159c160
    • 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) ^r115
    • Occurs in approximately one-third of adolescents with diabetes ^r116
    • Routinely monitor for diabetes distress (Diabetes Distress Scale^r117) beginning at age 7 or 8 years^r31 and refer patient to diabetes education or a behavioral health practitioner if areas of diabetes care are affected ^r115
  • Rates of depression are higher in youth with type 1 diabetes compared with youth without the disease ^r118c161
    • Annually screen youth for depression using depression screening tools ^r115r119
    • Consider screening for depression with any changes in medical status, including development of new complications ^r115
  • 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 ^r118c162
  • 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 practitioner for evaluation and treatment in the following situations: ^r115
      • 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 ^r109
• Eating disorders ^c163
  • Approximately one-fourth of adolescents are at risk of diabetes-specific eating disorder ^r120
  • Disturbed eating behaviors, coupled with unhealthy weight control behaviors, correlate with worse glycemic control ^r121
    • 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 ^r120r122
    • 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,^r123 particularly when hyperglycemia and weight loss are unexplained ^r31

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 XXXX^r54
    • Increase insulin to carbohydrate ratios to estimate prandial doses ^r73
• 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 ^r124
    • 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 ^r125
      • Fetal complications later in pregnancy arise from fetal hyperinsulinemia secondary to maternal hyperglycemia, leading to macrosomia ^r125
    • Discuss contraceptives with all female patients with childbearing potential ^r31
  • Transition to adulthood
    • Adolescents should gradually assume greater responsibility for diabetes management
    • Begin to prepare youth for transition in early adolescence ^r109
    • 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 ^r109r126
• Adolescents who are pregnant ^r125
  • 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 ^r73
      • 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 ^r124
      • 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 ^r124
    • 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 ^r124

At-risk populations

• First-degree relatives of patients with type 1 diabetes have an 8- to 15-fold increased risk of type 1 diabetes ^r144c185
• Second-degree relatives have a 2-fold increased risk of type 1 diabetes ^r144

Screening tests

• Measuring islet autoantibodies in relatives of patients with type 1 diabetes may identify those who are at risk for developing disease ^r3
  • Younger age at seroconversion (particularly age younger than 3 years), greater number of diabetes-related autoantibodies, and presence of autoantibodies against islet antigen 2 are associated with more rapid progression to clinical type 1 diabetes ^r145
• In patients in whom multiple islet autoantibodies are identified
  • Monitor for disease progression with HbA1C approximately every 6 months and 75-g oral glucose tolerance test annually; can individualize frequency of monitoring
  • Consider referral to a specialized center for evaluation and/or consideration of a clinical trial or therapy aimed at delaying development of clinical diabetes
• 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 ^r146
• General population screening of first-degree relatives of those with type 1 diabetes is not universally recommended but has potential benefits ^r146r147
  • Identification and education of families with children at high risk for developing type 1 diabetes while in a presymptomatic 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