Non-insulin-dependent diabetes in young Indians : a clinical and biochemical study.

Abstract

One of the earliest recorded references to polyuria is found in the Papyrus Ebers (1500 BC) and much later the occurrence of "honey urine" was noted by an ancient Hindu physician, Sushrutha, in old Indian Sanskrit (400 BC). However, the first good clinical description of the disease is ascribed to Celsus, although the name "diabetes" was introduced by Aretaeus of Cappadocia. The body of knowledge which has accumulated since these early recordings to the present state of the art reflects a most impressive sojourn, punctuated by many milestones, each adding impetus to future attempts in a relentless endeavour to unravel the aetiopathogenesis of this common malady. However, this "sweet evil" (diabetes) remains an enigma in many ways. There is little doubt today that there are 2 major types of diabetes: juvenile onset diabetes, presently known as insulin-dependent diabetes mellitus (IDDM) and maturity onset diabetes, referred to as non-insulin dependent diabetes mellitus (NIDDM). In NIDDM aggregation of HLA types, evidence of cell mediated immunity and the presence of circulating islet cell antibodies, which are characteristically associated with IDDM, are not found. There is also a vast difference in concordance of diabetes in the co-twins between the two types of diabetes suggesting that a different mixture of genetic and environmental factors is operative in the pathogenesis of these two types of diabetes. In I960, Fajans and Conn drew attention to the existence of a form of diabetes with an onset before the age of 35 years. Their patients showed a substantial improvement in glucose tolerance when treated with an oral hypoglycaemic agent, tolbutamide. Subsequent to this report numerous studies from various parts of the world confirmed this entity of non-insulin dependent diabetes in the young (NIDDY) in White Caucasians. There are, however, several different syndromes presenting as mild carbohydrate intolerance in the first two to three decades of life. The classical form of NIDDY is a mild non-insulin requiring form of diabetes in which the disorder is inherited as a dominant trait; there is little progression of glucose intolerance, if any, with time, and the diabetes is rarely accompanied by vascular complications. This subtype of diabetes is referred to as MODY (maturity onset diabetes in the young) and thus constitutes a subset under the broad umbrella of NIDDY. However, recently compelling evidence for heterogeneity within MODY has been presented. This evidence is based on the prevalence of certain HLA antigens, insulin responses to oral glucose, occurrence of vascular complications, progression of hyperglycaemia to the stage of insulin requirement and failure to demonstrate autosomal dominant inheritance in some families studied. In the South African Indian population which has a high prevalence of diabetes, Campbell was the first to draw attention to NIDDY in Indians more than two decades ago. Since this initial report, nobody has really studied NIDDY in any depth in South Africa and certainly not in the Indian population. NIDDY in the local Indian population is of particular interest for the obvious reason that diagnostic and management problems arise daily in a population with a high prevalence of non-insulin dependent diabetes. It is vital that the clinical features, endocrine and associated biochemical aberrations be known in detail if this condition is to be managed appropriately and adequately. A study of these aspects therefore became the primary task of this thesis. To pre-empt any challenge that patients were not really diabetic, the strict criteria of the W.H.O. for the diagnosis of diabetes were chosen. It should therefore be borne in mind throughout this study that a group of rather severe diabetics were selected by design. The patients studied represent the rather extreme end of the spectrum. But, in the event, this selection proved advantageous in that it covered an unstudied part of the spectrum and some light could be shed on the natural history of the disorder. In the long term the purpose was to prepare the ground for what must become the thrust of future studies, namely the biochemical pathogenesis of NIDDM. If it is true that some forms of NIDDY are inherited dominantly, existing techniques should make it possible to identify a gene(s) locus and if this is done the biochemical basis of this disorder must be identifiable. In the present study direct examination of these aspects were not undertaken, but an attempt was certainly made to pinpoint those biochemical abnormalities which are perhaps primary or central to the whole disorder.