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Hyperglycemia increases the incidence of congenital malformations. Tight control of blood sugar prior to conception (goal A1C <7%) is important (1).
Women with microalbuminuria during the 1st trimester are at increased risk for preeclampsia and preterm delivery.
A safe pregnancy is possible with vaginal delivery of a term baby. Close monitoring of blood sugar during labor is important.
Many drugs used to treat diabetic complications are relatively/absolutely contraindicated in pregnancy.
EPIDEMIOLOGY
- Age of onset peaks between 5 and 7 years of age and again around puberty; rapid decline in incidence after adolescence.
- Slightly more common in males than females
- Overall incidence is increasing worldwide.
- More cases are diagnosed in the autumn and winter than in spring and summer.
Incidence
- 18/100,000 per year in the United States (0 to 60/100,000 worldwide) (2)
- Average lifetime prevalence risk of T1DM in the general population is 0.4%.
- Racial predilection for whites
- African Americans have lowest overall incidence.
Pediatric Considerations
Although onset is usually before the age of 19 years, T1DM can occur for the first time in patients who are well into their 30s.
Young children are more likely to present in diabetic ketoacidosis (DKA) due to atypical presentation and because they may not express thirst or obtain fluids as readily as older children or adults.
ETIOLOGY AND PATHOPHYSIOLOGY
- Genetic predisposition is thought to exist.
- Alteration in immunologic integrity, placing the β-cell at special risk for inflammatory damage
- Autoantibodies present in >90% of patients at presentation: glutamic acid decarboxylase (GAD), insulinoma-associated autoantigen 2 (IA2A), zinc transporter 8 (ZnT8A), and insulin (IAA) (2)
- Associated environmental triggers (none have been verified):
- Vitamin D deficiency
- Infant feeding practices (short-term breastfeeding, early exposure to complex proteins)
- Viruses (e.g., enteroviruses, retroviruses)
- Environmental toxins
- Various epigenetic modifications of gene expression (DNA methylation, histone modifications, and micro-RNA dysregulation) have been noted, further suggesting a role between genetics and environment in the development of T1DM (3).
Genetics
- T1DM is a polygenic disorder with 40+ loci known to affect susceptibility to the disease (2).
- Genes located on major histocompatibility complex (MHC) on chromosome 6 provide about half of the genetic susceptibility leading to T1DM risk (2).
- HLA class II shows the strongest association with T1DM risk, but class I MHCs also affect risk (2).
RISK FACTORS
- Certain human leukocyte antigen (HLA) types, MHC classes, and autoantibodies (2)
- Increased susceptibility to T1DM is inheritable (3):
- Only 10-15% of newly diagnosed T1DM patients have a positive family history of T1DM.
- Among autoimmune conditions, T1DM has the highest concordance rates in monozygotic twins.
- Average prevalence risk of T1DM in children of patients with T1DM is ~6%.
- Relative risk for siblings of patients with T1DM is about 15%.
- See environmental triggers above (2).
COMMONLY ASSOCIATED CONDITIONS
- Autoimmune diseases, such as celiac disease, vitamin B12 deficiency, and hypothyroidism
- T1DM can also be seen as part of autoimmune polyendocrine syndromes.
DIAGNOSIS
DIFFERENTIAL DIAGNOSIS
- Benign renal glycosuria
- Glucose intolerance
- Type 2 diabetes
- Consider monogenic diabetes if
- Diabetes diagnosed before 6 months of age.
- Strong family history of diabetes without classic features of type 2 diabetes
- Mild fasting hyperglycemia
- Nonobese diabetic child with negative autoantibodies
- Secondary diabetes
- Pancreatic disease (chronic pancreatitis, cystic fibrosis, hereditary hemochromatosis)
- Endocrine-associated diabetes: acromegaly, Cushing syndrome, pheochromocytoma, glucagonoma, neuroendocrine tumors
- Drug- or chemical-induced glucose intolerance: glucocorticosteroids, HIV protease inhibitors, atypical antipsychotics, tacrolimus, cyclosporine
- Acute poisonings (salicylate poisoning can cause hyperglycemia and glycosuria, and may mimic DKA)
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
- *Criteria for the diagnosis of diabetes (1)[C]:
- Fasting glucose ≥126 mg/dL (7.0 mmol/L)
- Random of ≥200 mg/dL (11.1 mmol/L) in a patient with classic symptoms of hyperglycemia
- Oral glucose tolerance test; plasma glucose ≥200 mg/dL 2 hours after a glucose load of 1.75 g/kg (max dose 75 g)
- Glycated hemoglobin (HbA1c) level ≥6.5%
- *In the absence of unequivocal hyperglycemia, results should be confirmed by repeat testing.
- Other tests to consider:
- Serum electrolytes, especially in sicker patients who may have ketoacidosis
- Urinalysis for glucose, ketones, and microalbuminuria
- Pancreatic autoantibodies
- Islet cell, IAA, GAD, IA2A, and ZnT8A
- CBC (WBC count and hemoglobin may be elevated)
- C-peptide insulin level if needed to differentiate from type 2 diabetes
Test Interpretation
Inflammatory changes, lymphocytic infiltration around the islets of Langerhans, or islet cell loss
HISTORY
- Polyuria and polydipsia (4)[C]
- Polyuria may present as nocturia, bedwetting, or incontinence in a previously continent child.
- Polyuria may be difficult to appreciate in diaper-clad children.
- Weight loss 10-30%
- Often almost devoid of body fat at diagnosis due to hypovolemia and increased catabolism
- Prolonged or recurrent candidal infection, usually in the diaper area
- Increased fatigue, lethargy, muscle cramps
- Abdominal discomfort, nausea
- Vision changes, such as blurriness
- Altered school or work performance
TREATMENT
GENERAL MEASURES
- Overall control of carbohydrate metabolism for all pediatric age ranges (1)[C]
- Before meals, strive for blood glucose levels in range of 90 to 1,300 mg/dL (5.0 to 7.2 mmol/L)
- Bedtime/overnight: 90 to 150 mg/dL (5.0 to 8.3 mmol/L)
- A1c goal: <7.5% across all pediatric age groups
- A1c <7.0% is reasonable if achieved without excessive hypoglycemia.
- Very tight control might be dangerous in young children due to risk of repeated hypoglycemia.
- Adult A1c goal: <7.0% (1)[B]
- A1c <6.5% reasonable in select individuals (1)[C].
- Less stringent A1c goals (such as <8%) may be appropriate for others (1)[B].
- Normal growth and development and overall good health (asymptomatic) (4)[C]:
- Reach optimal height for genetic potential.
- Appropriate and timely pubertal maturation
- Coping psychosocial development: normal school or work attendance and performance; normal goals/career plans. Screen children ≥10 years of age annually for depression.
- Prevent acute complications, including the following:
- Hypoglycemic insulin reactions
- Ketoacidosis
- Delay or prevent chronic end-organ complications
MEDICATION
- Most type 1 diabetes patients will require some form of insulin supplementation, either multiple-dose insulin injections or continuous subcutaneous insulin infusion (1)[A].
- Types of insulin (1)[C]:
- Long-acting insulin analogues: insulin glargine (Lantus) and insulin detemir (Levemir). These should not be mixed with other insulins in the same syringe.
- Intermediate-acting insulin (NPH)-Humulin N or Novolin N-can be mixed with other insulins
- Short-acting (regular) insulin: Novolin R or Humulin R
- Very rapid-acting insulin analogues: insulin lispro (Humalog), insulin aspart (Novolog), and insulin glulisine (Apidra)
First Line
- Flexible intensive insulin therapy is the gold standard.
- Multiple dose insulin (MDI) or continuous subcutaneous insulin infusion (CSII) have equal efficacy (1)[B].
- Total initial dose is 0.2 to 0.4 U/kg/day for insulin-na ¯ve patients (will often need 0.6 to 0.7 U/kg/day)
- 40-60% of total dose given as basal insulin, with the rest as bolus insulin
- MDI regimen (1)[A],(5)[C]:
- Basal, long-acting insulin once or twice a day
- Prandial, short-acting insulin based on number of carbohydrate portions (e.g., 1:10, meaning 1 U of insulin for every 10 g of carbohydrate to be eaten)
- Correctional short-acting mealtime insulin based on premeal blood glucose level (subtract target blood glucose level and divided by sensitivity factor)
- Administration of the mealtime insulin before a meal may be more efficacious than during or after the meal.
- CSII regimen:
- May use regular insulin or rapid-acting insulin analogues
- Basal insulin is infused continuously at a preset rate, and bolus doses are given with meals as above.
Second Line
- Twice-daily injections with NPH along with regular or rapid-acting insulin
- Not physiologic, but lower cost and fewer injections may improve adherence in the less-motivated patient.
- Premixed insulin available as NPH/regular (Novolin or Humulin 70/30) or NPH/rapid-acting insulin (e.g., Novolog 75/25 Mix or Humulin 75/25 Mix) (5)[C]
- Pancreatic transplantation is usually reserved for patients with end-stage renal failure, who may receive kidney-pancreatic transplants at the same time.
- Oral hypoglycemics not indicated in type 1 diabetes (except in obese patients, who may have a combination of type 1 and type 2): Metformin (Glucophage)
INPATIENT CONSIDERATIONS
Newly diagnosed type 1 diabetics may require hospitalization during initiation of insulin therapy.
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
- Normal; full participation in sports activities
- Regular aerobic exercise is recommended.
Patient Monitoring
- BP monitoring at every office visit. If elevated, consider an ACE inhibitor or an angiotensin receptor blocker; avoid in pregnancy (1)[C].
- Monitor height, weight, and sexual maturation (in children) (5)[C].
- Daily home blood glucose monitoring with home blood glucose meter: Blood tests should be done at least 4 to 6 times daily (more frequently in pump patients) for optimal monitoring.
- Quarterly measurement of HbA1c
- Annual screenings (1)[C]:
- Microalbuminuria for earliest signs of possible nephropathy
- Ophthalmology exam (after 3 to 5 years of diabetes, also depending on glycemic control); annually thereafter
- Annual lipid profile, thyroid levels, blood chemistries, CBC
- Annual influenza vaccine in patients ≥6 months of age
- Pneumococcal polysaccharide vaccine to all patients ≥2 years
- Hepatitis B vaccination to unvaccinated adults aged 19 to 59 years
DIET
- American Diabetic Association diet: http://www.diabetes.org/food-and-fitness/food/
- Carbohydrate counting using insulin-to-carbohydrate ratio with all meals and snacks; allows patient flexibility in eating and ability to eat almost anything
PROGNOSIS
- Initial remission or honeymoon phase with decreased insulin needs and easier control, usually 3 to 6 months
- Current prognosis for reduced life expectancy:
- Increasing longevity and quality of life with careful blood glucose monitoring, improvement in insulin delivery regimens, and appropriate glycemic control
COMPLICATIONS
- Microvascular disease (retinopathy, nephropathy, neuropathy)
- Hyperlipidemia
- Macrovascular disease (coronary and cerebral artery disease)
- Chronic foot ulcers/amputations
- Hypoglycemia
- DKA
- Excessive weight gain
- Increased risk for preeclampsia and preterm delivery
- Driving mishaps
- Psychological problems of chronic disease
REFERENCES
11 American Diabetes Association. Standards of medical care in diabetes. Diabetes Care. 2015;38(Suppl 1):S77-S79.22 Atkinson MA, Eisenbarth GS, Michels AW. Type 1 diabetes. Lancet. 2014;383(9911):69-82.33 Stankov K, Benc D, Draskovic D. Genetic and epigenetic factors in etiology of diabetes mellitus type 1. Pediatrics. 2013;132(6):1112-1122.44 Silverstein J, Klingensmith G, Copeland K, et al. Care of children and adolescents with type 1 diabetes: a statement of the American Diabetes Association. Diabetes Care. 2005;28(1):186-212.55 Mooradian AD, Bernbaum M, Albert SG. Narrative review: a rational approach to starting insulin therapy. Ann Intern Med. 2006;145(2):125-134.
ADDITIONAL READING
- Cox DJ, Ford D, Gonder-Frederick L, et al. Driving mishaps among individuals with type 1 diabetes: a prospective study. Diabetes Care. 2009;32(12):2177-2180.
- Gillett MJ. International Expert Committee report on the role of the A1c assay in the diagnosis of diabetes: Diabetes Care 2009;32(7):1327-1334. Clin Biochem Rev. 2009;30(4):197-200.
- Husebye ES, Anderson MS. Autoimmune polyendocrine syndromes: clues to type 1 diabetes pathogenesis. Immunity. 2010;32(4):479-487.
SEE ALSO
Diabetes Mellitus, Type 2; Diabetic Ketoacidosis
CODES
ICD10
- E10.9 Type 1 diabetes mellitus without complications
- E10.8 Type 1 diabetes mellitus with unspecified complications
- E10.69 Type 1 diabetes mellitus with other specified complication
- E10.29 Type 1 diabetes mellitus w oth diabetic kidney complication
- E10.628 Type 1 diabetes mellitus with other skin complications
- 10.43 Type 1 diabetes w diabetic autonomic (poly)neuropathy
- E10.339 Type 1 diab w moderate nonprlf diab rtnop w/o macular edema
- E10.341 Type 1 diab w severe nonprlf diabetic rtnop w macular edema
- E10.22 Type 1 diabetes mellitus w diabetic chronic kidney disease
- E10.41 Type 1 diabetes mellitus with diabetic mononeuropathy
- E10.618 Type 1 diabetes mellitus with other diabetic arthropathy
- E10.329 Type 1 diab w mild nonprlf diabetic rtnop w/o macular edema
- E10.49 Type 1 diabetes w oth diabetic neurological complication
- E10.649 Type 1 diabetes mellitus with hypoglycemia without coma
- E10.331 Type 1 diab w moderate nonprlf diab rtnop w macular edema
- E10.21 Type 1 diabetes mellitus with diabetic nephropathy
- E10.319 Type 1 diabetes mellitus with unspecified diabetic retinopathy without macular edema
- E10.321 Type 1 diab w mild nonprlf diabetic rtnop w macular edema
- E10.11 Type 1 diabetes mellitus with ketoacidosis with coma
- E10.641 Type 1 diabetes mellitus with hypoglycemia with coma
- E10.65 Type 1 diabetes mellitus with hyperglycemia
- E10.311 Type 1 diabetes w unsp diabetic retinopathy w macular edema
- E10.40 Type 1 diabetes mellitus with diabetic neuropathy, unsp
- E10.359 Type 1 diabetes w prolif diabetic rtnop w/o macular edema
- E10.610 Type 1 diabetes mellitus w diabetic neuropathic arthropathy
- E10.36 Type 1 diabetes mellitus with diabetic cataract
- E10.42 Type 1 diabetes mellitus with diabetic polyneuropathy
- E10.621 Type 1 diabetes mellitus with foot ulcer
- E10.10 Type 1 diabetes mellitus with ketoacidosis without coma
- E10.349 Type 1 diab w severe nonprlf diab rtnop w/o macular edema
- E10.59 Type 1 diabetes mellitus with oth circulatory complications
- E10.630 Type 1 diabetes mellitus with periodontal disease
- E10.51 Type 1 diabetes w diabetic peripheral angiopath w/o gangrene
- E10.351 Type 1 diabetes w prolif diabetic rtnop w macular edema
- E10.622 Type 1 diabetes mellitus with other skin ulcer
- E10.638 Type 1 diabetes mellitus with other oral complications
- E10.44 Type 1 diabetes mellitus with diabetic amyotrophy
- E10.620 Type 1 diabetes mellitus with diabetic dermatitis
- E10.39 Type 1 diabetes w oth diabetic ophthalmic complication
- E10.52 Type 1 diabetes w diabetic peripheral angiopathy w gangrene
- 250.01 Diabetes mellitus without mention of complication, type I [juvenile type], not stated as uncontrolled
ICD9
- 250.01 Diabetes mellitus without mention of complication, type I [juvenile type], not stated as uncontrolled
- 250.03 Diabetes mellitus without mention of complication, type I [juvenile type], uncontrolled
- 250.91 Diabetes with unspecified complication, type I [juvenile type], not stated as uncontrolled
- 250.11 Diabetes with ketoacidosis, type I [juvenile type], not stated as uncontrolled
- 250.41 Diabetes with renal manifestations, type I [juvenile type], not stated as uncontrolled
- 250.51 Diabetes with ophthalmic manifestations, type I [juvenile type], not stated as uncontrolled
- 250.81 Diabetes with other specified manifestations, type I [juvenile type], not stated as uncontrolled
- 250.61 Diabetes with neurological manifestations, type I [juvenile type], not stated as uncontrolled
- 250.71 Diabetes with peripheral circulatory disorders, type I [juvenile type], not stated as uncontrolled
SNOMED
- 46635009 Diabetes mellitus type 1 (disorder)
- 313435000 Type I diabetes mellitus without complication
- 420270002 Ketoacidosis in type I diabetes mellitus (disorder)
- 421893009 Renal disorder associated with type I diabetes mellitus (disorder)
- 426907004 Small vessel disease due to type 1 diabetes mellitus (disorder)
- 421165007 Diabetic oculopathy associated with type I diabetes mellitus (disorder)
- 421468001 neurological disorder associated with type I diabetes mellitus (disorder)
CLINICAL PEARLS
- Polyuria may present as nocturia, bedwetting, or incontinence in a previously continent child.
- Young children are more likely to present in DKA because they may not express thirst or obtain fluids as readily as older children or adults.
- Onset usually before the age of 19 years, but type 1 diabetes can present in patients who are well into their 30s.