What Causes Diabetes?

Type 1 diabetes mellitus results from autoimmune destruction of the insulin-producing β cells in the pancreatic islets. Numerous genes play a role in type 1 diabetes, although their exact function is still unclear. Environmental factors, such as viral infections and stress, may also contribute to the development of the disease. In type 2 diabetes mellitus, the initial insulin resistance and subsequent relative insulin deficiency result in abnormal glucose metabolism and its consequences. Obese individuals in particular are thought to have insulin resistance before development of relative insulin deficiency. Symptoms of diabetes occur in type 2 diabetes when insulin secretion is inadequate to overcome insulin resistance. Type 2 diabetes is emerging as an important pediatric problem, reflecting the epidemic of obesity in the industrialized world. In the United States, 10% to 40% of children with newly diagnosed diabetes have type 2 disease, with regional variation based on the prevalence of obesity and other risk factors, including race.

How Do Type 1 and Type 2 Diabetes Differ?

Distinguishing type 1 diabetes from type 2 diabetes is important and may present a diagnostic dilemma in children. Although there is a genetic component to type 1 diabetes, a family history of diabetes is positive in only 1 of 10 patients. By contrast, the family history in type 2 diabetes is usually more prominent. Both type 1 and type 2 diabetes cause polyuria and polydipsia. Type 1 diabetes has mainly nonspecific physical findings, including dehydration, weight loss, and, rarely, growth failure. Type 2 diabetes is strongly associated with obesity as a component of the metabolic syndrome and may have additional findings, including acanthosis nigricans, hypertension, hyperlipidemia, and, in females, polycystic ovary syndrome. Table 60-1 lists the features of both types of diabetes.

Table 60-1 Characteristics of Type 1 and Type 2 Diabetes Mellitus

How Is Blood Glucose Used to Diagnose Diabetes?

The following blood glucose findings are diagnostic of diabetes:

Impaired fasting glucose or impaired glucose tolerance implies a significant risk of developing diabetes. Impaired fasting glucose is defined as glucose levels of 100 to 125 mg/dl in fasting patients. Impaired glucose tolerance is defined as 2-hour glucose levels of 140 to 199 mg/dl on the 75-g oral glucose tolerance test. The oral glucose tolerance test is not recommended for routine clinical use to screen for the diagnosis.

How Is Type 1 Diabetes Diagnosed?

Type 1 diabetes becomes clinically apparent when excessive thirst and urination develop, along with increased appetite, enuresis, weight loss, and fatigue. If symptoms are not recognized, the child may become markedly dehydrated and progress to diabetic ketoacidosis (DKA). Rarely, an asymptomatic patient will be identified because of glucosuria on a routine urinalysis. Diagnosis of diabetes is based on hyperglycemia. Glucosuria, with or without ketonuria, also is diagnostic.

How Is Type 2 Diabetes Diagnosed in Children?

Type 2 diabetes is increasing in prevalence among obese children and adolescents. Risk factors include a family history of type 2 diabetes, a body mass index above the 95th percentile for age, physical inactivity, hypertension, and low levels of high-density lipoprotein cholesterol. Populations at high risk include African-Americans, Latinos, Native Americans, and Asian-Pacific Islanders. The typical patient with type 2 diabetes is an obese adolescent with acanthosis nigricans who may be asymptomatic or may have polyuria, polydipsia, and sometimes dehydration. Evaluation of such a patient should include inquiry into the family history and a screening test for blood glucose level. Referral of obese patients to pediatric endocrinologists for evaluation, diagnosis, and treatment of type 2 diabetes has increased markedly.

How Is Diabetes Managed?

The goal in diabetes management is to delay or prevent complications by maintaining the best possible degree of blood glucose control. Most newly diagnosed diabetic children have type 1 diabetes and thus require insulin. Blood glucose levels must be monitored closely at home to allow adjustments of insulin dosages. Management must include discussion of nutrition, physical activity, psychobehavioral issues, and the continuous changes of childhood and adolescence. For type 2 diabetes, the initial treatment may include insulin, but this can usually be replaced with oral hypoglycemic agents and dietary control, with additional management similar to that for the type 1 diabetic. Efforts to improve lifestyle, eating behavior, and activity may be appropriate.

What Are the Guidelines for Blood Glucose Control?

The principal goal of home blood glucose monitoring is to maintain blood glucose within the age-specific target range. In practice, tight blood glucose control is difficult, and most patients have frequent excursions both below and above the target range (Table 60-2). Effectiveness of the treatment regimen and adherence by the patient are assessed by regular blood glucose determinations. All blood test results should be recorded in a log that is reviewed at each clinic visit so that insulin or oral medication doses may be adjusted. Approximately every 3 months, glycosylated hemoglobin (HbA_1c) should be measured to assess chronic blood glucose control.

Table 60-2 Target Ranges for Blood Glucose Control

How Is Insulin Used to Treat Type 1 Diabetes?

Treatment depends on whether the patient has type 1 diabetes or type 2 diabetes. On occasion, the distinction cannot be made and it is usually safest to begin treatment with insulin. Type 1 diabetes is always treated with insulin. Short-acting and long-acting insulins are typically injected alone or in combinations three or more times daily. You must be aware of the speed of onset and the duration of action of each commonly used type of insulin (Table 60-3). Increasing numbers of adolescents and young children are now using external insulin pumps for continuous subcutaneous insulin infusion. The pump delivers short-acting insulin at a basal rate during the day and night and as a bolus whenever needed to correspond to a meal. Patients learn to match the amount of insulin to the carbohydrate content of the food they are about to eat.

Table 60-3 Insulin and Its Actions

What Medications Are Used for Type 2 Diabetes?

Type 2 diabetes is treated with oral medications and sometimes with insulin. Commonly used oral hypoglycemic agents and their mechanisms of action are listed in Table 60-4.

Table 60-4 Oral Hypoglycemic Agents

What Are the Consequences of Poor Diabetic Control?

Retinopathy, nephropathy, and both peripheral and autonomic neuropathy result from chronic poor control. Beginning approximately 5 years after the diagnosis of diabetes, all patients should have ophthalmologic evaluations yearly. Ongoing assessment of growth and blood pressure are important. In addition, a yearly urinalysis should be done to detect the presence of microalbuminuria. Recognition that complications may occur is important if they are to be detected early. It is also important to remember that intensive treatment of hyperglycemia with insulin or oral hypoglycemic agents prevents or delays all of these complications. Nutritional management and attention to emotional and behavioral issues are crucial.

When Does Diabetic Ketoacidosis Occur in Diabetes?

Diabetic ketoacidosis (DKA) is the most dangerous acute complication and may occur during an acute illness because of relative insulin deficiency or insulin resistance. Profound hyperglycemia, metabolic anion gap acidosis, and severe dehydration may lead to life-threatening shock. Patients and their parents need to know about signs and symptoms of DKA. Fever, upper respiratory infection, headache, abdominal pain, diarrhea, nausea, vomiting, and increased rate of breathing should raise the concern of DKA. In adolescence, DKA commonly results from omission of insulin in a setting of psychobehavioral conflict.