Low bodyweight Type 2 diabetes in India: Clinical characteristics and pathophysiology

Low body weight Type 2 DM/Type 2 DM-lean is a distinct clinical entity that is neither related clinically or pathophysiologically to LADA nor former fruste of Type 1DM, having absence of markers for autoimmune destruction of β-cells and good insulin and C-peptide reserve for a prolonged period of life. They constitute an independent variant of Type 2 DM with inherent peculiarities of insulin kinetics in the liver along with altered profile and behaviour of key enzymes related to carbohydrate metabolism which are marked by excess extraction of insulin in hepatic bed, hyperactive cytochrome system and non-supressible glucokinase activity. These peculiarities are reflected in the peripheral circulation as states of low circulating levels of insulin, hyperglycemia, dyslipidemia without low high density lipoprotein cholesterol (HDLc), raised triglycerides (Tg), low levels of plasma homocysteine and BMI below 19 make these diabetics less prone to develop macrovascular disease. Peripheral neuropathy and the consequences of poor glycemic control such as increased succeptibility to infections and endothelial dysfunction manifesting as proteinuria dominate the clinical picture. In view of more of infective complications and coexistent severe hyperglycemia (glucose toxicity) many of these diabetics may not respond to OHA adequately at the initiation of therapy. However, due presence of insulin resistance and good β-cell reserve for insulin, despite of lean habitus, most of them respond well to OHA for long periods of life, as may be comparable with any other phenotype of Type 2 diabetes. The insulin resistance observed in Type 2 DM-lean is not consequent to anthropometric parameters like central obesity and WHR as these diabetics are lean with poor fat depot and thus it could be an integral part of the pathogenic mechanism of Type 2 DM per se.