Basics
Description
Type 1 diabetes is an autoimmune disorder that causes pancreatic β-cell destruction. This destruction leads to insulin deficiency that results in hyperglycemia and disrupts energy storage and metabolism. Severe insulin deficiency can lead to ketosis, acidosis, dehydration, shock, and death. �
Epidemiology
- Most common endocrine disorder of childhood
- More common in whites of Northern European descent
Incidence
- Annual U.S. incidence is ~19/100,000 in children 10-19 years old.
- Incidence of type 1 diabetes is rising by 3% per year but faster in young children.
Prevalence
- Prevalence of type 1 diabetes in youth 0-19 years in United States is ~2/1,000.
- Note: At least 2% of diabetes in children may be due to maturity onset diabetes of youth (MODY) or other genetic forms.
Risk Factors
Genetics
- Increased susceptibility to type 1 diabetes associated with HLA region of chromosome 6, 5-fold greater risk with MHC antigen types DR3 and DR4
- MODY is a group of autosomal dominant syndromes of partial insulin deficiency due to monogenic defects of pancreatic development or insulin secretion; they comprise a small fraction of childhood diabetes.
Pathophysiology
- Loss of pancreatic β cells results in insulin deficiency, leading to hyperglycemia, and predominance of catabolic processes.
- Hyperglycemia causes hyperosmolality, polyuria, and damage to small blood vessels.
- Catabolic processes produce ketosis, weight loss, and metabolic acidosis.
Etiology
- Type 1 diabetes
- An environmental trigger (likely viral) induces expression of antigens on β-cell surface.
- Recruitment of cytotoxic lymphocytes
- Production of anti-insulin and anti-islet cell antibodies (including GAD65, ICA512, ZnT8)
- Progressive inflammatory, autoimmune loss of β-cell mass results in insulin deficiency.
- The autoimmune destruction of β cells is more likely in genetically susceptible persons.
Commonly Associated Conditions
- Autoimmune thyroid disease
- Hashimoto (hypothyroidism) more common than Graves (hyperthyroidism)
- Celiac disease
- More rarely other autoimmune diseases, such as alopecia areata, rheumatoid arthritis
- Depression
- After prolonged hyperglycemia: vascular complications:
- Microvascular
- Nephropathy
- Retinopathy
- Neuropathy
- (See "Patient Monitoring"� for screening recommendations)
- Macrovascular
- Peripheral vascular disease
- Cardiovascular disease
Diagnosis
History
- Duration of symptoms prior to diagnosis varies by age: may be days in toddlers, months in adolescents.
- Polyuria, nocturia, and enuresis are related to hyperglycemia >180 mg/dL.
- Polydipsia: due to polyuria, hyperosmolality
- Polyphagia: appetite amplified by loss of calories from glycosuria; this is often absent.
- Weight loss: dehydration, loss of calories
- Malaise, nausea, vomiting, abdominal pain, hyperventilation, lethargy due to ketosis, acidosis, electrolyte depletion, hyperosmolality
- MODY is usually asymptomatic.
Physical Exam
- Weight loss common at presentation of type 1 diabetes.
- Candidal vaginitis and balanitis common in young children with type 1 diabetes
- In ketoacidosis: dehydration, hyperventilation
Diagnostic Tests & Interpretation
Lab
- Diagnosis based on BG level:
- Fasting BG ≥126 mg/dL, random BG ≥200 mg/dL, or 2-hour BG ≥200 mg/dL on oral glucose tolerance test (OGTT), and exclusion of stress hyperglycemia
- Asymptomatic hyperglycemia requires repeat confirmation.
- Glycosuria may be intermittent.
- Ketonuria may occur with both types 1 and 2.
- With presence of ketonuria or ketosis, DKA should be ruled out by checking serum bicarbonate.
- HgbA1c reflects BG levels of previous 2-3 months and is nearly always elevated at diagnosis of both types.
- GAD, islet cell, ZnT8, and/or insulin autoantibodies are positive in most persons with type 1 diabetes at onset (85-90%)
- In some patients presenting with hyperglycemia and ketosis, not possible to distinguish type 1 from type 2 until the course over several months has been followed
Differential Diagnosis
- MODY
- Type 2 diabetes (in obese pubertal youth)
- UTI (polyuria)
- Renal glycosuria
- Stress-related hyperglycemia
- Drug-induced hyperglycemia (steroids)
- Psychogenic polydipsia
- Pneumonia (in DKA)
- Sepsis (in DKA)
- Acute surgical abdomen (in ketoacidosis)
Treatment
Medication
(See insulin regimens under "General Measures."�) Insulin is required to treat type 1 diabetes. �
- Insulins:
- Rapid-acting analogs:
- Aspart (Novolog), lispro (Humalog), glulisine (Apidra)
- Onset of action 5-15 minutes, peak action 60-90 minutes, and duration 2-5 hours
- Short-acting
- Regular insulin-used for IV delivery, can be used for SC injection
- Onset of action when given SC-30-60 minutes, peak action-2-3 hours, duration-6-9 hours
- Intermediate-acting
- NPH (Humulin N, Novolin N)
- Onset 1-2 hours, peak action 3-8 hours, duration 12-15 hours
- Use is less common when long-acting analogs available.
- Long-acting analogs
- Detemir (Levemir), glargine (Lantus)
- Onset-3-4 hour, no significant peak, duration 20-24 hours
- Other long-acting analogs under investigation but are not FDA-approved in 2014 including insulin degludec, which is approved for use in the European Union
Additional Treatment
General Measures
- Insulin is given as a fixed or flexible regimen.
- TDD-calculated by adding up all short- and long-acting insulin given over 24 hours-usually ~0.7-1.2 U/kg/24 h; choose higher range for ketoacidosis presentation, obesity, and puberty.
- Doses may decline during "honeymoon period."�
- Fixed insulin regimens require fewer shots but consistent schedule and eating.
- Historically, common fixed regimen is split-mixed: 2/3 of TDD in morning (1/3 as short-acting and 2/3 long-acting), and 1/3 of TDD in evening (with 1/2 as short-acting and 1/2 as long-acting), either at dinner or split between dinner and bedtime.
- Flexible insulin regimens consist of basal insulin plus a short-acting bolus for every carbohydrate meal and for high blood sugar.
- Basal dosing
- 40-50% of TDD is given as 1 injection of a long-acting insulin such as glargine (Lantus) or detemir (Levemir).
- Sometimes, these long-acting insulins are split into twice daily doses given ~12 hours apart.
- Boluses of short-acting insulin (lispro or aspart) are given for meals and snacks based on carbohydrate content and BGs.
- Carbohydrate coverage (grams of carbohydrate covered by 1 unit) can be estimated by dividing the TDD to 500.
- Hyperglycemia coverage ("corrective dose"�) can be estimated by dividing the TDD to 1,800 to find how much 1 unit of insulin may lower blood sugar.
- Another flexible method uses SC insulin infusion by pump that administers a continuous basal infusion.
- Patient gives manually administered bolus doses of rapid-acting analog insulin at mealtimes and corrective doses.
- Dosing guidelines are similar.
Ongoing Care
Patient Monitoring
- Regular appointments with diabetes specialist every 3 months to assess management:
- HgbA1c assessment at each visit (with generally recommended goal of <7.5% for children)
- Is diabetes interfering with emotional health, family relationships, school attendance, athletic activities, or social development?
- Is family minimizing hospitalization risks from hypoglycemia or DKA with appropriate adjustment of insulin, recognition of lows, glucagon availability, ketone testing, and telephone contact?
- Is family reducing long-term complication risk by keeping HgbA1c lower and by avoiding or treating other risk factors?
- Exam: growth, weight, blood pressure, thyromegaly, liver size, pubertal status, injection/infusion sites, feet, skin lesions
- Meet with nutritionist periodically/as needed to reassess meal plan.
- Meet with psychologist or social worker as needed to address psychosocial issues.
- Regular screening for long-term complications:
- Annual urine for microalbumin after 12 years of age, 3-5 years diabetes duration
- Periodic lipid profile, thyroid screening (T4, TSH or TSH and thyroid antibodies), celiac screen
- Annual eye exam to detect early retinopathy after 10 years of age, 3-5 years diabetes duration
Diet
- Dietary education for type 1 diabetes is directed toward healthy distribution and matching of carbohydrate intake with insulin action:
- Recommended distribution of calories: 55% from carbohydrates (mostly complex); 30% from fats; 15% from protein
- Fixed insulin regimens require snacks spaced between meals and before bedtime.
- Carbohydrate counting is essential for flexible insulin regimens and helpful for maintaining consistency for fixed regimens.
- Reduction of saturated and trans fats, rapidly digested carbohydrates, and salt may be beneficial in both types of diabetes.
Patient Education
- Home BG monitoring at least 6 times per day. Many patients will need to test more frequently: before meals, when feeling hypoglycemic or ill.
- Insulin injection and site rotation
- Oral carbohydrate for mild hypoglycemia; glucagon 0.5-1 mg IM for severe hypoglycemia (lower dose given in children <20 kg)
- Activity:
- Frequent exercise reduces BG and insulin requirements in both types of diabetes.
- Exercise may require extra carbohydrate intake or reduced insulin doses to prevent hypoglycemia in type 1 diabetes.
- Detecting or preventing hypoglycemia during or after physical exercise
- Diet: carbohydrate counting
- Prevention: checking urine for ketones when blood sugar is high or child feels ill; extra insulin for ketones
Complications
- DKA: most common cause of hospitalization and death in type 1 diabetes in childhood. See "Diabetic Ketoacidosis."�
- Hypoglycemia
- This most common acute complication. Limits achievable glycemic control
- If severe, may cause seizure, unconsciousness
- Long-term harm may be reduced by better glycemic control:
- Nephropathy: Microalbuminuria and hypertension are 1st manifestations before adulthood.
- Retinopathy: Blood vessel changes may occur in childhood but not vision loss.
- Neuropathy: diminished nerve conduction velocity common; paresthesias are earliest symptoms.
- Vasculopathy: Large vessel disease begins in childhood, but clinical effects occur in adults.
- Prenatal harm to infants of diabetic mothers: Birth defects occur early, large size late.
- Growth failure (Mauriac syndrome) and delayed sexual maturation
- Depression, family stress, higher divorce rate
Alert
DKA should be treated in the emergency department or inpatient setting. The risk for morbidity and mortality due to cerebral edema or other complications of DKA is high. �
Additional Reading
- American Diabetes Association. Clinical practice recommendations: 2013. Diabetes Care. 2013;36(Suppl 1):S1.
- Atkinson �MA, Eisenbarth �GS, Michels �AW. Type 1 diabetes. Lancet. 2014;383(9911):69-82. �[View Abstract]
- Chiang �JL, Kirkman �MS, Laffel �LM, Type 1 Diabetes Sourcebook Authors. Type 1 diabetes through the lifespan: a position statement of the American Diabetes Association. Diabetes Care. 2014;37(7):2034-2054. �[View Abstract]
- Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study Group, Tamborlane �WV, Beck �RW, Bode �BW, et al. Continuous glucose monitoring and intensive treatment of type 1 diabetes. N Engl J Med. 2008;359(14):1464-1476. �[View Abstract]
- Nguyen �TM, Mason �KJ, Sanders �CG, et al. Targeting blood glucose management in school improves glycemic control in children with poorly controlled type 1 diabetes mellitus. J Pediatr. 2008;153(4):575-578. �[View Abstract]
- Steinke �JM, Mauer �M, International Diabetic Nephropathy Study Group. Lessons learned from studies of the natural history of diabetic nephropathy in young type 1 diabetic patients. Pediatr Endocrinol Rev. 2008;5(Suppl 4):958-963. �[View Abstract]
Codes
ICD09
- 250.01 Diabetes mellitus without mention of complication, type I [juvenile type], not stated as uncontrolled
- 250.91 Diabetes with unspecified complication, 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
ICD10
- E10.9 Type 1 diabetes mellitus without complications
- E10.8 Type 1 diabetes mellitus with unspecified complications
- E10.21 Type 1 diabetes mellitus with diabetic nephropathy
- E10.319 Type 1 diabetes mellitus with unspecified diabetic retinopathy without macular edema
- E10.59 Type 1 diabetes mellitus with oth circulatory complications
- E10.69 Type 1 diabetes mellitus with other specified complication
- E10.40 Type 1 diabetes mellitus with diabetic neuropathy, unsp
SNOMED
- 46635009 Diabetes mellitus type 1 (disorder)
- 313435000 Type I diabetes mellitus without complication
- 421893009 Renal disorder associated with type I diabetes mellitus (disorder)
- 420789003 Diabetic retinopathy associated with type I diabetes mellitus (disorder)
- 426907004 Small vessel disease due to type 1 diabetes mellitus (disorder)
- 421468001 neurological disorder associated with type I diabetes mellitus (disorder)
- 421365002 peripheral circulatory disorder associated with type I diabetes mellitus (disorder)
FAQ
- Q: What is the risk of diabetes in a sibling or child of a person with type 1 diabetes?
- A: It is 5-10% in 1st-degree relatives (siblings, offspring) and 40-50% in identical twins.
- Q: What are the newest management tools?
- A: Continuous glucose sensors allow patients to avoid symptomatic high and low glucoses by detecting trends, to see the outcome of management decisions, and to reduce the risk of severe nocturnal hypoglycemia. Insulin pumps using data from sensors are in development ("artificial pancreas"� systems). A pump with a feature to suspend insulin delivery for low glucose detected by sensor is now available.