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 ^r6

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

• 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 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 ^c42
  • Pancreatic β-cell failure that occurs without autoimmune destruction

Risk factors and/or associations

Primary diagnostic tools

• History and physical examination can suggest diabetes, but biochemical parameters are required for a diagnosis of diabetes ^c69
• Laboratory confirmation of diabetes can be achieved with either of the following: ^r2
  • 2 diagnostic test results from among the following 3 tests, using the same or 2 different types of tests and the same or 2 different test samples:
    • Fasting plasma glucose level of 126 mg/dL or higher (no caloric intake for at least 8 hours before blood draw)
    • Hemoglobin A1C measurement of 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)
  • 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 ^r2
• Initial diagnostic assessment of comorbidities at time of diagnosis ^r2
  • Measure blood pressure, fasting lipid panel, and urinary albumin excretion
  • American Diabetes Association provides complete lists of comprehensive medical evaluation components to cover at initial evaluation ^r29r30
• Additional baseline laboratory tests recommended at diagnosis to screen for associated diseases include: ^r29r30
  • Lipid panel (after glucose control has been established for those aged 2 years or older)
  • Liver function tests
  • Spot urinary albumin to creatinine ratio (at puberty or after age 10 years, whichever is earlier, and diabetes duration of 5 years)
  • Estimated GFR/creatinine clearance
  • TSH, antithyroid peroxidase, and antithyroglobulin antibodies (soon after diagnosis) ^r29
  • Celiac antibody panel (soon after diagnosis) ^r29
    • Obtain IgA tissue transglutaminase antibodies in patients with documented total serum IgA levels within reference range; obtain IgG to tissue transglutaminase and deamidated gliadin antibodies in IgA-deficient patients

Laboratory

• Fasting glucose measurement ^c70
  • 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 ^c71
  • 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 ^r2c72
  • Diagnostic threshold is 6.5% or greater
  • In absence of unequivocal symptomatic hyperglycemia, diabetes diagnosis must be confirmed by another abnormal test result; can be the same or different type of test and can be from the same or different test samples
  • Indirect measure of average glycemic control over 2 to 3 months and is used to monitor overall level of control
  • Strongly predictive for complications
  • Perform hemoglobin A1C testing using method certified by NGSP (sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases)^r31 and standardized to the Diabetes Control and Complications Trial assay (to avoid misdiagnosis or missed diagnosis)
  • Limitations
    • Measurement of 6.5% or greater is a highly specific—but not sensitive—early indicator of disease compared with diabetes diagnosed by oral glucose tolerance test or asymptomatic hyperglycemia ^r16
    • Marked discordance between measured hemoglobin A1C and plasma glucose levels raises the possibility of assay interference
      • Consider using an assay without interference or plasma blood glucose criteria to diagnose diabetes if marked discordance exists
    • Relationship between hemoglobin A1C and glycemia may be altered by certain conditions; in these contexts, only plasma blood glucose criteria should be used to diagnose diabetes. Such conditions include:
      • Those associated with increased RBC turnover (eg, recent blood loss, transfusion, hemolysis)
      • Hemoglobinopathies (eg, sickle cell disease)
      • Anemia
      • Pregnancy (second and third trimesters, postpartum period)
      • HIV
      • Hemodialysis or erythropoietin therapy
    • Hemoglobin A1C levels may vary with patients' race/ethnicity; Black patients may have higher levels than non-Hispanic White patients despite similar fasting and 2-hour postprandial glucose levels
• Oral glucose tolerance test ^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
  • Many children with type 1 diabetes present with diabetic ketoacidosis or symptomatic hyperglycemia, rendering glucose challenge unnecessary
• Pancreatic islet autoantibodies ^r14c74
  • Type 1 diabetes is defined by presence of 1 or more autoantibodies against islet cell antigens (commercial laboratory assays measure all four) ^r2
    • Autoantibodies against a glutamic acid decarboxylase isoform (GAD2, alias GAD65)
      • Most widely available and best characterized test
      • Detected in 50% to 80% of patients with type 1 diabetes ^r32r33
      • Seroconversion usually precedes onset of clinical manifestations of disease, and result remains positive thereafter
    • Autoantibodies against certain protein tyrosine phosphatases that are cell membrane autoantigens, including on islet cells (ie, PTPRN and PTPRN2, alias IA-2 and IA-2β, respectively)
      • Detected in over 30% to 70% of patients with newly diagnosed disease ^r32r33
    • Autoantibodies against a zinc transporter protein (SLC30A8, alias ZnT8) (solute carrier family 30 member 8)
      • Test is largely available in research settings
      • Detected in 50% to 70% of patients with newly diagnosed disease ^r32r33
    • Autoantibodies to insulin
      • Must be measured before or within 2 weeks of initiating insulin therapy ^r32
      • Detected in over 50% to 90% of patients with newly diagnosed disease ^r32r33
  • Absence of pancreatic autoantibodies does not rule out type 1 diabetes ^r34
    • Up to 10% of patients with new-onset type 1 diabetes have been found to have no islet antibodies, in White European study populations ^r34
    • Pancreatic autoantibody titers diminish over time, which can produce false-negative results ^r35
• C-peptide ^r34c75
  • Surrogate marker for insulin secretion
  • Can be obtained if islet autoantibodies are absent, and diabetes type remains unclear
  • Use of C-peptide level to aid in classification is most useful when done several months or even 1 year after diagnosis because of the possibility that levels measured soon after diagnosis can be low owing to glucotoxicity ^r36
  • A frankly low level or complete absence of C-peptide is indicative of type 1 diabetes ^r37
  • Detectable C-peptide does not entirely exclude type 1 diabetes; some residual C-peptide secretion occurs in a significant proportion of patients in the first few years after diagnosis ^r38

Other diagnostic tools

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

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 ^r2
    • Initial diabetes diagnosis in children favors type 1 diabetes; type 2 diabetes is more likely after age 35 years ^r34
    • Lower BMI, unintentional weight loss, ketoacidosis, and severe hyperglycemia at presentation also favor type 1 diabetes ^r34
    • Type 2 diabetes most often responds to noninsulin antihyperglycemic agents early in the course of disease (eg, metformin, glyburide)
  • C-peptide levels are helpful for distinguishing type 1 from type 2 diabetes, but the measurement is most useful several months to a year after therapy begins, allowing for the resolution of any glucotoxicity
    • Most patients with type 1 diabetes have an undetectable or low C-peptide level ^r37
    • Fasting C-peptide level greater than 3 nanograms/mL after several months of therapy is highly suggestive of type 2 diabetes ^r39
• Monogenic diabetes mellitus ^r40c77
  • Set of disorders that cause β-cell dysfunction and impaired insulin secretion, with onset of hyperglycemia in youth ^r41
  • Prevalence of 1% to 2% in pediatric diabetes population ^r42
  • Consider in children with the following findings: ^r40
    • Diabetes diagnosed within the first 6 months of life ^r2
    • Strong family history of diabetes suggesting autosomal dominant inheritance ^r2
    • Mild fasting hyperglycemia (100-150 mg/dL [5.5-8.5 mmol/L]), especially if young and without obesity ^r40
    • Diabetes with negative autoantibodies results and without signs of obesity or insulin resistance ^r2
  • Differentiated from type 1 or type 2 diabetes with genetic testing

• Characteristics of types of primary diabetes in children and adolescents.

  Data from Chiang JL et al: Type 1 diabetes in children and adolescents: a position statement by the American Diabetes Association. Diabetes Care. 41(9):2026-44, 2018; American Diabetes Association: 2. Classification and diagnosis of diabetes: Standards of Medical Care in Diabetes--2022. Diabetes Care. 45(suppl 1):S17-38, 2022; and Mayer-Davis EJ et al: ISPAD clinical practice consensus guidelines 2018: definition, epidemiology, and classification of diabetes in children and adolescents. Pediatr Diabetes. 19(suppl 27):7-19, 2018.

  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	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 8th or 9th 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%)	−	− (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%)

Admission criteria

New diagnosis

• Consider the following factors when deciding to admit patient for new diagnosis of diabetes: ^r36
  • Severity of metabolic derangements
  • Family psychosocial circumstances
  • Resources available at the treatment center and experience in managing newly diagnosed children in an outpatient setting
• New diagnosis of diabetes usually requires inpatient admission under the following circumstances: ^r47
  • DKA
  • Random glucose measurement 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 ^r48
  • 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 ^r49

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 ^r29
• Refer all patients to pediatric endocrinologist for guidance on initiation and modifications of insulin regimen
• Refer all patients to registered dietitian trained in the care of children and adolescents with type 1 diabetes
• Refer to ophthalmologist to evaluate for retinopathy once child is aged 10 years or older, or puberty has started (whichever is earlier), and child has had diabetes for 3 to 5 years ^r29
• Refer to nephrologist for management of diabetic nephropathy, as determined by development of modestly elevated urinary albumin excretion
• Refer to mental health professional (clinical psychologist or social worker) for guidance on psychosocial issues, including diabetes-related family conflict and stress ^r29

Drug therapy

• Insulin ^c79
  • General principles ^r56
    • Initial insulin therapy with either multiple daily injections or continuous subcutaneous insulin infusion requires comprehensive education
      • Multiple daily injections ^r56
        • 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
        • Injected insulin may be given via syringes or insulin pens
          • Modern insulin pens labeled as smart pens are linked to mobile apps that record the concurrent glucose level from a continuous glucose monitor. Use of smart pens has been associated with better glycemic control and reduce hypoglycemic events ^r57r58r59
      • Continuous subcutaneous insulin infusion ^r56
        • Rapid-acting insulin analogue is typically used in the device
        • Provides a 24-hour preselected but adjustable basal rate of rapid-acting insulin, along with patient-activated mealtime bolus doses
        • Modern day insulin pump advances include sensor-augmentation, automated suspension of insulin delivery at low glucose thresholds, predictive low-glucose suspension which reduces or stops insulin delivery based on input from linked continuous glucose monitors, and automated insulin delivery systems that assess the rate of change and increase or decrease insulin delivery without patient input (the latter are also known as hybrid closed-loop systems) ^r1r58
      • Insulin analogues are preferred for both multiple daily injections and continuous subcutaneous insulin infusion; no clinically significant differences have been found among the various analogues available in the pediatric population ^r60
    • 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 blood glucose monitoring 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 ^r8
      • 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 ^r8
      • 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 ^r53
      • 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, it can be determined empirically only 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 ^r61
  • 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 ^r62
  • 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 (isophane insulin suspension)
    • 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 ^{r63c84c85c86c87c88}
  • 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 ^r63
  • 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 dose 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. May repeat dose 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 September 23, 2021. Accessed August 1, 2022. 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 insulin	Onset	Peak	Duration
  Ultra-rapid-acting
  Aspart (Fiasp)	15 to 20 minutes	1 to 3 hours	3 to 5 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 ^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 ^r50

Blood glucose monitoring ^r64c91

• 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) ^r64
  • 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 hypoglycemic symptoms ^r51r65
  • 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 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 ^r54
    • 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 ^r66r67r68
    • 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 ^r29r51
    • Other professional societies recommend real-time continuous glucose monitoring systems in children with type 1 diabetes under the following circumstances: ^r64
      • 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 ^r65r69
  • 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;^r29limited data show that the device has accuracy similar to standard continuous glucose monitor devices and lower rates of hypoglycemia^r70
  • Main disadvantage is that it does not provide alarms for hypoglycemia or hyperglycemia

Diabetes education and self-management training ^r29c92c93

• 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 ^r52c94

• 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
• 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 ^r63

• 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 schedules^r73c97
  • Since mid-2022, this includes COVID-19 vaccination for ages 6 months and older

Other lifestyle issues ^c98

• Discourage smoking (including e-cigarettes) in young people who do not smoke and encourage smoking cessation in those who do ^r29d3
• 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) ^r52
  • Participation in physical activity with duration of at least 60 minutes significantly reduces hemoglobin A1C ^r74
  • Encourage muscle and bone strengthening activities at least 3 times weekly ^r52
• Inform patients that anaerobic exercise or high-intensity activity can result in hyperglycemia immediately after start of exercise; also, aerobic activity increases the risk of hypoglycemia during and after exercise ^r75
• Strategies to prevent exercise-induced hypoglycemia include: ^r76
  • Aim for blood glucose level of 126 to 180 mg/dL before physical activity and exercise ^r29
    • If initial blood glucose levels are below goal, delay physical activity and consume sufficient carbohydrates until blood glucose level is within appropriate preexercise range ^r29r75
  • Adjust insulin and/or carbohydrate intake
    • Reduce prandial insulin dose for meal or snack preceding exercise ^r29
    • Increase carbohydrate intake before exercise ^r29
    • Reduce basal insulin rates on continuous subcutaneous insulin infusion device by about 10% to 50% or more or suspend for 1 to 2 hours during exercise ^r29
    • Reduce basal insulin rate or long-acting insulin dose by approximately 20% after exercise to mitigate delayed exercise-induced hypoglycemia ^r29
  • Monitor glucose frequently before, during, and after exercise
    • Have blood glucose testing supplies and sources of simple carbohydrate readily available to prevent and treat hypoglycemia ^r29
    • For more strenuous and prolonged activities, instruct patient to consume 0.5 to 1.5 g carbohydrates/kg for each hour of strenuous activity ^r75
    • Monitor blood glucose during periods of continuous physical activity about every 30 minutes as well as 15 minutes after completion of exercise and at bedtime ^r75
    • Detailed guideline recommendations are available outlining initial recommendations for general insulin therapy, carbohydrate consumption, and glucose sensor thresholds for patients using continuous glucose monitoring systems ^r77
    • 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 ^r77
    • If not already used, consider initiating a combined insulin pump/continuous glucose monitoring system, particularly one with a low glucose threshold–suspend feature ^r75
• Marked hyperglycemia (glucose level of 350 mg/dL or more) before exercise should prompt delay of physical activity; presence of insulin deficiency and ketosis should be evaluated ^r29
• If significant hyperglycemia occurs after exercise (usually from high-intensity exercise and increased catecholamine production), cautiously administer a small rapid-acting bolus of insulin ^r75

Behavioral and psychosocial aspects of care ^r29

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

Various diabetes advocacy position statements are available from the American Diabetes Association, including the following: ^r78

• Diabetes care in the school setting ^r79r80
• Care of young children with diabetes in the child care setting ^r81
• Insulin access and affordability ^r82
• Diabetes and driving ^r83
• Diabetes and employment ^r84
• Diabetes care in correctional institutions ^r85

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

Comorbidities

• Hypertension ^r29c105
  • Measure blood pressure at each office visit
  • Encourage adolescents with diabetes to use ambulatory blood pressure monitoring periodically ^r46
  • Normative blood pressure values and thresholds for diagnosing elevated blood pressure and hypertension are now lower than in previous classifications ^r29r46
    • Elevated blood pressure (previously termed "prehypertension") is either of the following confirmed on 3 separate visits: ^r46
      • Systolic or diastolic blood pressure in 90th to less than 95th percentile for age, sex, and height
      • 120 to 129 mm Hg systolic and less than 80 mm Hg diastolic in adolescents aged 13 years or older
    • Confirmed hypertension is either of the following confirmed on 3 separate visits: ^r46
      • Systolic or diastolic blood pressure in 95th percentile or higher for age, sex, and height
      • 130/80 mm Hg or greater in adolescents aged 13 years or older
  • Initial treatment for high-normal blood pressure is aimed at lifestyle modifications of altering diet, increasing exercise, and controlling weight ^r29
    • Consider pharmacologic treatment of hypertension if target blood pressure is not reached with 3 to 6 months of using lifestyle methods ^r29
    • Ambulatory blood pressure monitoring is strongly encouraged for these patients ^r29
  • Consider starting pharmacologic treatment in addition to lifestyle modification in patients with hypertension (blood pressure at 95th percentile or greater for age, sex, and height, or 130/80 mm Hg or greater in adolescents aged 13 years or older) ^r29
    • ACE inhibitors or angiotensin receptor blockers (alternatively) are preferred in children with diabetes and hypertension ^r29
    • Use of an ACE inhibitor with statin is not recommended for primary prevention of microvascular complications, because available data do not demonstrate reduction in albuminuria or progression of retinopathy ^r100
  • Goal blood pressure levels are those that are consistently below 90th percentile for age, sex, and height, or below 120/80 mm Hg in adolescents aged 13 years or older ^r29
• Dyslipidemia ^c106
  • Dyslipidemia is a risk factor for atherosclerotic cardiovascular disease in type 1 diabetes
  • Initial therapy consists of both: ^r29
    • Optimizing glucose control (which can improve lipid values but not normalize them), and ^r101
    • 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 ^r29
  • Pharmacotherapy with a statin is recommended for children aged 10 years or older if, after attempting therapeutic lifestyle change, LDL-C level remains higher than 160 mg/dL or LDL-C level remains higher than 130 mg/dL when the patient has 1 or more cardiovascular disease risk factors ^r29
    • Goal of therapy is to achieve LDL cholesterol value less than 100 mg/dL ^r29
• Cardiovascular disease ^r102c107
  • Cardiovascular events generally do not occur during childhood, but atherosclerotic process begins during childhood in diabetes ^r103
    • Age and hemoglobin A1C level are strongest risk factors for a major atherosclerotic event or any cardiovascular disease in type 1 diabetes ^r104
    • Cardiovascular risk reduction involves optimizing glycemic control and managing other cardiovascular risk factors (eg, maintaining healthy body weight, physical activity, healthy diet, treating hypertension) ^r103
• Autoimmune conditions ^c108
  • Assess for presence of thyroid dysfunction and celiac disease soon after initial diabetes 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 ^r19
      • Assess TSH level soon after initial diabetes diagnosis and metabolic stabilization, and obtain tests for anti–thyroid peroxidase and antithyroglobulin antibodies ^r29r105
      • 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 ^r29
    • Celiac disease ^r106c110
      • Gluten-sensitive enteropathy that occurs in approximately 2% to 16% of patients with type 1 diabetes ^r29
      • Higher prevalence in patients with type 1 diabetes, family history of celiac disease, younger age, and associated thyroid autoimmunity ^r106
      • 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 ^r106
      • Screen all children with type 1 diabetes at diagnosis; repeat screening within 2 years of diagnosis and then again after 5 years; consider more frequent screening in children with suggestive symptoms or first-degree relative with celiac disease ^r29
        • Obtain IgA tissue transglutaminase antibodies in patients with documentation of 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 ^r29
      • Treat patients with confirmed celiac disease using gluten-free diet in consultation with a dietitian experienced in managing both diabetes and celiac disease ^r29
    • Other autoimmune conditions
      • Conditions that occur more commonly in children with type 1 diabetes include Addison disease (primary adrenal insufficiency), autoimmune hepatitis, autoimmune gastritis, dermatomyositis, and myasthenia gravis ^{c111c112c113c114c115}
      • A heightened awareness of the risk of such conditions is advisable, but routine screening of asymptomatic children is not recommended ^r29
• Overweight and obesity
  • Children with overweight or obesity are at risk for type 2 diabetes, but they can also develop type 1 diabetes
  • Approximately 15% and 25% of children with type 1 diabetes in the United States are overweight or obese, respectively ^r107
  • 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 ^r108
  • 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) ^r109
  • 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 ^r107
• Psychosocial issues ^c116
  • Psychosocial distress is common, owing to burdens of diabetes management throughout childhood and adolescence ^r29c117c118
    • The term diabetes distress refers to the duress of constant behavioral demands of diabetes self-management (eg, medication dosing, frequency, and titration; monitoring blood glucose, food intake and eating patterns; physical activity) ^r110
    • Occurs in approximately one-third of adolescents with diabetes ^r111
    • Monitor for diabetes distress routinely (Diabetes Distress Scale^r112) beginning at age 7 or 8 years,^r29 and refer patient to diabetes education or a behavioral health provider if areas of diabetes care are impacted ^r110
  • Rates of depression are higher in youth with type 1 diabetes, compared with youth without the disease ^r113c119
    • Annually screen youth for depression using depression screening tools ^r110r114
    • Consider screening for depression with any changes in medical status, including development of new complications ^r110
  • 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 ^r113c120
  • 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: ^r110
      • Diabetes distress persists even after tailored diabetes education
      • Positive screening result for depression, eating disorder, or anxiety; suspicion for a serious mental illness; or fear of hypoglycemia
      • Repeated hospitalizations for DKA, intentionally omitting insulin, or declining to perform self-care behaviors (eg, injecting insulin, monitoring blood glucose)
  • Assess food security, housing stability/homelessness, health literacy, financial barriers, and social/community support and apply pertinent information to treatment decisions ^r29
• Eating disorders ^c121
  • Higher incidence in youth with type 1 diabetes, compared with youth without diabetes
  • Disturbed eating behaviors, coupled with unhealthy weight control behaviors, correlate with worse glycemic control ^r115
    • Insulin omission and insulin underdosing are the most common and serious weight control behaviors and are associated with increased morbidity and mortality ^r116
    • 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,^r117 particularly when hyperglycemia and weight loss are unexplained ^r29

Special populations

• Patients in pubertal stage
  • Puberty is a state of relative insulin resistance and therefore insulin requirements increase substantially
  • Anticipate increases in basal and prandial insulin doses
    • Basal insulin requirements typically range from 1 to 2 units/kg/day ^r53
    • Increase insulin to carbohydrate ratios to estimate prandial doses ^r63
• 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 ^r118
    • 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 ^r119
      • Fetal complications later in pregnancy arise from fetal hyperinsulinemia secondary to maternal hyperglycemia, leading to macrosomia ^r119
    • Discuss contraceptives with all female patients with childbearing potential ^r29
  • Transition to adulthood
    • Adolescents should gradually assume greater responsibility for diabetes management
    • Begin to prepare youth for transition in early adolescence ^r29
    • Start a transition plan at least 1 year in advance of transferring over to adult health care to prepare for issues related to insurance, obtaining diabetes supplies, affective disorders, reproductive health, substance use, and identifying an adult care physician ^r29r120
• Adolescents who are pregnant ^r119
  • 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 ^r63
      • 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 ^r118
      • 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 ^r118
    • 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
  • Prescribe low-dose aspirin starting at end of first trimester, to lower risk of preeclampsia ^r118

At-risk populations

• First-degree relatives have an 8- to 15-fold increased risk of type 1 diabetes ^r138c143
• Second-degree relatives have a 2-fold increased risk of type 1 diabetes ^r138

Screening tests

• Measuring islet autoantibodies in relatives of patients with type 1 diabetes may identify those who are at risk for developing disease ^r3c144
  • 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