1. Diabetes Mellitus

2. Diabetes mellitus is characterized by hyperglycemia and glycosuria and is an endpoint of a few disease processes

3. The most common type occurring in childhood is DM1, which is caused by auto-immune destruction of the insulin-producing beta cells (islets) of the pancreas. Patients with DM1 have permanent insulin deficiency and require insulin. Type 2 diabetes mellitus (DM2) is less common in children and results from insulin resistance and relative insulin deficiency, usually with obesity.

4. A diagnosis of diabetes mellitus is made if a fasting serum glucose concentration is greater than 126 mg/dL or a 2-hour postprandial serum glucose concentration is greater than 200 mg/dL on two separate occasions. A patient is considered glucose intolerant if fasting serum glucose concentrations are greater than 110 mg/dL but less than 126 mg/dL and if 2-hour post-prandial values are greater than 140 mg/dL but less than 200 mg/dL

5. Sporadic hyperglycemia occurs in children, usually in the setting of an intercurrent illness. When the hyperglycemic episode is clearly related to an illness or other physiologic stress, the probability of incipient diabetes is small (<5%). Sporadic hyperglycemia occurring without a clear precipitating physiologic stress is of more concern because diabetes develops in at least 30%

7. INSULIN-DEPENDENT (TYPE 1) DIABETES MELLITUS

8. DM1 results from the autoimmune destruction of the insulin-producing beta cells (islets) of the pancreas. In addition to the presence of diabetes susceptibility genes, an unknown environmental insult presumably occurs to trigger the autoimmune destruction. A variety of cross-sectional, retrospective, and prospective studies have produced conflicting data regarding a host of environmental factors and their etiologic role in DM1. These include cow's milk feeding before age 2 years and viral infectious agents (coxsackie B virus, cytomegalovirus, mumps, and rubella).

9. NON-INSULIN-DEPENDENT (TYPE 2) DIABETES MELLITUS

10. DM2 can occur as the result of various pathophysiologic processes; however, the most common form results from peripheral insulin resistance with failure of the pancreas to maintain compensatory hyperinsu-linemia

11. of DM2 also can occur in children
of DM2 also can occur in children. Maturity-onset diabetes of youth (MODY) comprises a group of dominantly inherited forms of relatively mild diabetes. Insulin resistance does not occur in these patients; instead the primary abnormality is an insufficient insulin secretory response to glycemic stimulation

12. DM2 was thought to be uncommon in childhood; the prevalence of this disorder in children is increasing in parallel with the increased prevalence of childhood obesity. The prevalence is highest in children of ethnic groups with a high prevalence of DM2 in adults, including Native Americans, Hispanic Americans, and African Americans. Obesity, the metabolic syndrome, and a family history of DM2 are risk factors.

13. The diagnosis of DM2 may be suspected on the basis of polyuria and polydipsia and in a background of the metabolic syndrome. Differentiating DM2 from DM1 in children sometimes can be challenging. The possibility of DM2 should be considered in patients who are obese, have a strong family history of DM2, have other characteristics of the metabolic syndrome and acanthosis nigricans on physical examination, or have absence of antibodies to beta cell antigens at the time of diagnosis of diabetes.

14. Acanthosis nigricans is a dermatologic manifestation of hyperinsulinism that presents as hyperkeratotic pigmentation in the nape of the neck and in flexural areas. Although ketoacidosis occurs far more commonly in DM1, it also can occur in patients with DM2 under conditions of physiologic stress and cannot be used as an absolute differentiating factor. The diagnosis of DM2 can be confirmed by evaluation of insulin or C-peptide responses to stimulation with oral carbohydrate.

15. DM2 is the result of a combination of insulin resistance and insulin hyposecretion. Asymptomatic patients with mildly elevated glucose values (slightly >126 mg/dL for fasting or slightly >200 mg/dL for random glucose) may be managed initially with lifestyle modifications, including nutrition therapy (dietary adjustments) and increased exercise. Exercise has been shown to decrease insulin resistance

16. The most common treatment is either metformin or one of the thiazolidinediones. A rare side effect of metformin is lactic acidosis, which occurs mainly in patients with compromised renal function. The most common side effect is gastrointestinal upset. If ketonuria or ketoacidosis occurs, insulin treatment is necessary at first, but may be switched within weeks to oral medications. Insulin can be used in children with DM2, but may lead to continued weight gain. Oral drugs may be used as combinations

17. As in adults, significant lifestyle modifications, such as improved eating habits and increased exercise, have a role in preventing or decreasing the morbidity of DM2.