Type 1 Diabetes Mellitus

Joseph Wolfsdorf, MB, BCh
Professor of Pediatrics, Harvard Medical School, Boston, MA

Katharine Garvey, MD, MPH
Instructor of Pediatrics, Harvard Medical School, Boston, MA

Definition/Key Clinical Features
Differential Diagnosis
Best Tests
Best Therapy
Best References

Definition/Key Clinical Features

Absolute deficiency of insulin from destruction of pancreatic beta cells
Polyuria, polydipsia, weight loss despite normal food intake, fatigue, and blurred vision

Typically occur 2– 12 wk before diagnosis

Family history increases susceptibility

Complications
· Acute Life-Threatening Complication

Ketoacidosis
Hypoglycemia

Chronic Complications

Retinopathy
Nephropathy
Neuropathy
Increased risk of cardiovascular disease, including myocardial infarction and stroke
Chronic complications delayed or reduced by intensive treatment

Differential Diagnosis

Insulin deficiency secondary to chronic pancreatitis or pancreatectomy
Gestational diabetes mellitus

In first trimester, likely to be presentation of type 1 or 2 diabetes precipitated by pregnancy
In second or third trimester, often remits after delivery but increases risk of future diabetes

Drug-induced hyperglycemia

Primarily from glucocorticoids in high doses

Best Tests

Diagnosis usually evident from history
Random blood glucose level > 200 mg/dL
Urine for glucose and ketone
Hemoglobin A_1c (HbA_1c )

Best Therapy*

Daily self-management by the patient, many lifestyle adaptations
Frequent contact with physician

Illness, unusual stress, ketosis requires consultation

Insulin Replacement

Schedules and doses individualized according to blood glucose levels and carbohydrate content of meals

Blood glucose self-testing

Before each meal
Periodically 1–2 hr after meals
Before and after intensive exercise
Occasionally at 3 am
Frequently during illness

HbA1c measurement twice a year (four times a year if glycemic goals not met; monthly during pregnancy)
Test for ketoacids in urine or blood during illness
Anticipated meal carbohydrate intake
American Diabetes Association goals

Preprandial capillary whole blood glucose levels: 70–130 mg/dL
Postprandial peak capillary whole blood glucose levels: < 180 mg/dL
HbA1c values < 7.0% (nondiabetic range ~ 4.0–6.0%)
Goals difficult to achieve with current therapeutic tools

Long-acting insulin (~ 50% of total daily dose) to provide 24-hour basal supply, plus short-acting insulin before meals (dose based on premeal BG level and carbohydrate content of meal)
Average total daily dose = 0.6–0.7 units per kg body weight
Insulin requirements increased by weight gain and increased caloric intake and during adolescence, late pregnancy, illness, stress

Insulin delivery

Subcutaneous injection in the abdomen, hips, buttocks, anterior thighs, posterior aspect of upper arms

Continuous subcutaneous insulin infusion (CSII) via external pump

Use rapid-acting insulin analogue or regular insulin
Provides more predictable insulin absorption, smooth basal delivery, and optimal coverage for meals

Insulin Preparations

Short acting

Regular, crystalline zinc insulin (CZI)

Onset of action: 0.5– 1.0 hr
Duration of action: 5– 8 hr
Peak action: 2– 3 hr

Rapid acting

Lispro, aspart, glulisine

Onset of action: 5– 15 min
Duration of action: 3– 5 hr
Peak action: 0.5– 1.5 hr

Intermediate acting

Onset of action: 2– 4 hr
Duration of action: 10– 16 hr
Peak action: 4– 10 hr

Long acting

Detemir

Onset of action: 2– 4 hr
Duration of action: 16– 20 hr
Peak action: variable modest peak: 6– 14 hr

Glargine

Onset of action: 2– 4 hr
Duration of action: 20– 24 hr
Peak action: no peak

Pramlintide (synthetic amylin analogue)

Adjunct to insulin for patients who fail to achieve glycemic control with insulin alone

Inject subcutaneously before meals
Dose: 15 µ g initially; titrate upward as necessary to 30– 60 µ g
Reduce preprandial insulin by 50% initially

Lifestyle Measures

Diet controlled for carbohydrate intake and tailored to activity levels
Exercise regimen to maintain lean muscle mass

Diabetic Emergencies

Ketoacidosis

Caused by insulin deficiency resulting in extremely high plasma glucose and ketoacid levels
Symptoms: nausea, vomiting, dehydration, hyperventilation, altered mentation or decreased consciousness
Treatment: 0.9% saline IV immediately for volume repletion; potassium repletion; rapid-acting insulin, 0.1 U/kg/hr IV after serum potassium rises to 4.0 mEq/L, if below normal initially

Hypoglycemia

Caused by missed meals, insulin dosage errors, exercise, alcohol, drugs
Symptoms: palpitations, tremulousness, anxiety, sweating, blurred vision, dizziness; can cause confusion, seizures, coma
Treatment: 15 g simple carbohydrates p.o.; glucagon 1 mg SC or IM

Best References

Diabetes Control and Complications Trial Research Group. N Engl J Med 1993;329:977. [PMID 8366922]

Diagnosis and classification of diabetes mellitus. Diabetes Care 2011;34 Suppl 1:S62-9. [PMID 21193628]

Hirsch IB. Insulin analogues. N Engl J Med 2005;352:174–83. [PMID 15647580]

Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN. Hyperglycemic crises in adult patients with diabetes. Diabetes Care 2009;32:1335-43. [PMID 19564476]

Standards of medical care in diabetes--2011. Diabetes Care 2011;34 Suppl 1:S11–61. [PMID 21525493]

* To obtain additional drug information, click on the DrugInfo tab in the left column, or click on the following link: http://search.medscape.com/drug-reference-search?queryText=

January 2012