The Unitarian Hypothesis for the aetiology of diabetes mellitus.
Over the years, several clinical syndromes have been described in diabetes mellitus. Although world opinion has settled somewhat on the main two types, the debate continues as to how the 'formes frustes' syndromes fit in and what if any implications there are for the accepted aetiology of the disease. Type 1, insulin dependent diabetes mellitus, results from pancreatic inadequacy as a result of a variety of insults such as autoimmune attack, toxic damage, etc. Insulin administration is at the core of the therapeutic approach. Type 2, non insulin dependent diabetes mellitus, results from reduced responsiveness of the target tissues to insulin and as such, an insulin resistance syndrome is described. Lifestyle adjustment and oral hypoglycaemic agents are the mainstay of therapy. Over the years, however, insulin insufficiency will develop in most cases and insulin therapy required in order to achieve normoglycaemia. The aetiology of these main two types has been maintained to be distinct from each other and as such types 1 and 2 are described as two separate developmental conditions. Furthermore, the variant patterns, such as malnutrition related, drug induced, intermittent or phasic insulin requiring, gestational, temporary, stress related, etc., all present a challenge as to how they fit in aetiologically. The Unitarian Hypothesis, by presenting this overall cascade of biochemical and physiological interactions, brings a logic which embraces the points of entry of a variety of insults, all of which can lead to the clinical picture of hyperglycaemia and its attendant adverse outcomes. The hypothesis buttresses the belief that nature - the genetic predisposition which directs potential antibody development; and nurture - the environmental influences such as nutritional status (over- or under-), infective and toxic attack, can aggravate or initiate aspects of the cascade of reactions leading to hyperglycaemia. The causative agents functioning internally within the cascade are imputed to be free radicals, oxidizing molecular species and antibodies and the corollary to this overview concept would be that a situation that minimizes the genesis and accumulation of these three agents would minimize the development of diabetes mellitus. Currently the debate is rife about the use of free radical scavengers and antioxidants in the treatment and prevention of diabetes mellitus. The verdict is still out on this approach. Our research on rootcrops such as yams and cassava, staple foods in tropical countries, indicates the presence of cyanoglycosides such as linamarin, which on digestion yields cyanide radicals. These radicals are pancreatotoxic especially in the undernourished state. Dog models however, have shown that free radical scavengers such as riboflavin, Vitamin B(2), is protective against this toxic damage. Further, scientific investigations have clearly demonstrated the role of antibody attack and have been able to ward off the appearance of type 1 diabetes mellitus in susceptible individuals, by the early use of immunosuppressive therapy such as cyclosporin. Thus the Unitarian Hypothesis demonstrates how all types of clinical syndromes being described in diabetes mellitus are not necessarily variants of a specific illness but rather manifestations of a central process of membrane damage-->antibody response-->insulin inadequacy (quantitatively or qualitatively); and the future intervention in containing this disease may well lie in focusing on preservation of the integrity of the body's cell membranes.