Handbook of Genetic Counseling/Diabetes Mellitus

Diabetes Mellitus

Genetic etiology of the condition

 * Diabetes mellitus is characterized by hyperglycemia and relative or absolute deficiency of insulin. It is one of the most common chronic disorders, affecting 5-10% of the adult population in the western hemisphere. There are two types of diabetes. Type 1 is insulin-dependent diabetes mellitus (IDDM) and represents about 10% of all cases. It results from the destruction of the Beta cells of the pancreas, which is an auto-immune process. Type 2 is non-insulin-dependent diabetes mellitus (NIDDM) and represents around 90% of the cases. It has a poorly defined pathogenesis, but may cause resistance due to a decrease in insulin receptors and interact with outside factors such as obesity.
 * Inheritance: the genetics of diabetes mellitus is complex, with multifactorial inheritance indicating an interaction of both genetic and environmental factors. The disease itself is not inherited; rather it is a susceptibility to the disease. (Type 2 has a greater genetic component.)
 * Risk factors: family history, obesity, lack of exercise, age over 30. Ethnic backgrounds of African American, Latino, Native American, and Asian have twice the risk for developing diabetes than Caucasians.

Incidence and carrier frequency

 * Type 1 (IDDM) has an incidence of about 1 in 200 Caucasians and usually manifests early in life. Risk to sibling is 6% and risk to offspring is 2.5%. The male gender may have an influence on predisposition.
 * Type 2 (NIDDM) has a recurrence risk to siblings and offspring for over disease of 5-10%, while there is a recurrence risk for abnormal glucose tolerance of 15-25%.
 * Diabetes mellitus frequently accompanies the symptoms of Fredriech's Ataxia. This appears to be the case in this family. Therefore, Mr. and Mrs. R's offspring may be at a lower risk.

Clinical features

 * In both types, insulin deficiency leads to hyperglycemia which is responsible for complications like microvascular (retinopathy and nephropathy) and macrovascular disease (atherosclerosis).
 * Type 1: The typical patient is a thin, ketosis-prone juvenile who requires insulin to live. It usually occurs in childhood, adolescence, and early adulthood with acute onset of polyuria, polydipsia, weight loss, severe hyperglycemia, and ketoacidosis.
 * Type 2: The typical patient is an overweight adult whose diabetes can be managed by diet or oral medication (although they may receive insulin.) It is usually much less dramatic and presents in an overweight person later in life. Symptoms include tiredness, frequent urination, thirst, blurred vision, and frequent infections with slow-healing sores.
 * During pregnancy, the need for insulin is often increased (diabetogenic).

Age of onset, natural history, and life span

 * It is important to note that either type can occur at any age, although Type 1 is usually younger (before 30) while Type 2 is usually older (after 40).
 * Manifestations can range from asymptomatic glucose intolerance, to acute medical emergencies, to chronic complications.

Testing

 * Blood tests: elevation of plasma glucose (fasting level of at least 140 mg/dl)
 * Urinalysis for glucose and ketone bodies
 * Glucose tolerance tests/insulin assays
 * Molecular analysis of HLA genes (IDDM)

Surveillance, management, and treatment options

 * Insulin, dietary management, and oral hypoglycemic agents, exercise
 * Eye exams and podiatry care is important
 * In pregnancy, there is a dose-response effect where the better the glycemic control in the first trimester, the lower the risk of birth defects in the fetus.

Differential diagnoses

 * Gestational Diabetes: have an insulin resistance . . . the pancreas is working correctly, but the tissue is resistant . . . first recognized during pregnancy (screened at 24-28 weeks) and then usually returns to normal. Teratogenic effect seems to increase when insulin is required during the third trimester (in 20-30% of the women) and if control it is poor during the first trimester.
 * Two types: Type 1 - must have insulin along with diet control
 * Type 2 - can control blood sugars by diet alone
 * Risk factors: family history of diabetes, advanced maternal age (AMA), obesity, and a history of macrosomia.
 * Up to 50% of women with gestational diabetes may develop overt diabetes in 5-8 years following their pregnancy.
 * Diabetes is associated with a number of genetic syndromes (over 60).

Psychosocial issues

 * The risk for a major congenital malformation in the infant of a diabetic mother is estimated to be two to three times greater than the general population.
 * Risks to the mother include miscarriage, pre-eclampsia, and caesarian delivery while risks to the fetus include congenital anomalies (caudal regression, NTDs, renal and cardiac abnormalities), macrosomia, hydramnios, and perinatal morbidity or mortality
 * Various community resources and support groups (some web based).

Resources

 * Creasy and Resnik. (1994) Maternal-Fetal Medicine: Principles and Practices, 3rd Ed. WB Saunders Co: Philadelphia.
 * Robinson A and Linden MG. (1993) Clinical Genetics Handbook, 2nd Ed. Blackwell Science Pub: Boston.
 * Schulman JD and Simpson JL. (1981) Genetic Diseases in Pregnancy: Maternal Effects and Fetal Outcomes. Academic Press: New York.
 * Thompson MW, McInnes RR, Willard HF. (1991) Thompson & Thompson Genetics in Medicine, 5th Ed. WB Saunders Co: Philadelphia.