11 - Class II histocompatibility genes and diabetes

Summary

Introduction

Diabetes mellitus, a syndrome characterized by insufficient insulin secretion, hyperglycemia, and a propensity to develop universal microangiopathy, neuropathy and atherosclerosis, is a common condition affecting 2–4% of all Caucasians (Panzram & Zabel-Langenning, 1981). Insulin-dependent diabetes (IDDM) makes up 10–15% of all diabetes and is characterized by a selective B-cell destruction, very low if any insulin secretion, absolute requirement for exogenous insulin and often a young age of onset (although cases do occur at all ages). Microvascular disease becomes clinically evident 10–20 years after diagnosis of IDDM and constitutes a major cause of death, due to resulting renal insufficiency (Rossini & Chick, 1980). While improvements in treatment, such as intensive insulin and pump therapies, continue to be developed, and experimental treatment such as pancreatic transplantation and immunotherapy are proposed (Lacy et al., 1981; Rossini, 1983), a major goal must be prevention of the group of disorders we currently label as IDDM. At this time of clinical presentation, the majority of the IDDM diabetic pancreatic B-cells have undergone irreversible destruction (Cahill & McDevitt, 1981). Thus it is likely that potential interventions will have their greatest success if applied before the onset of clinically recognized disease, as has been demonstrated by immunologic interventions in appropriate animal models (Like et al., 1983). To accomplish this major goal of prevention, we must better understand the natural history, etiopathogenesis, and genetic susceptibility to IDDM, and develop accurate methods to detect genetically susceptible individuals in the population at large before the onset of clinically recognized disease.