Islets Β Cell Response and Glucose Homeostasis in Low Body Weight Type 2 Diabetes

Abstract

Introduction: Low body weight Type 2 Diabetes Mellitus (LB T2 DM) is not a distinct clinical entity that is related clinically or pathophysiologically to latent autoimmune diabetes in adults (LADA) nor to Type 1DM, have 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 behavior of key enzymes related to carbohydrate metabolism which are marked by excess extraction of insulin in the hepatic bed, hyperactive cytochrome system and non-suppressible glucokinase activity. These peculiarities are reflected in the peripheral circulation as low circulating insulin levels and severe persistent hyperglycemia despite fairly preserved β cell reserve for insulin. Peripheral persistent hyperglycemia could be the likely cause for higher prevalence of peripheral neuropathy, infections and endothelial cell dysfunction. In view of higher prevalence of infective complications and coexistent severe hyperglycemia, many of these diabetics may not respond to Oral Anti diabetic Drugs (OAD) adequately at the initiation of therapy. However, due to existence of insulin resistance and good β-cell reserve for insulin, despite of lean habitus, glucose homeostasis and normo glycemia is often maintained with OAD for long periods of life, as may be comparable with any other phenotype of Type 2 DM. The insulin resistance observed in LB T2 DM is not related to anthropometric parameters like central obesity and Waist Hip Ratio (WHR). Conclusion: LB T2DM are variant of classical (obese) Type 2 DM where the lean habitus is neither consequent to under nutrition, having low circulating insulin levels, nor due to autoimmune β-cell destruction but have inherent metabolic aberrations in hepatic bed extracting more insulin causing low circulating insulin levels. They do have peripheral insulin resistance. The management although akin to classical Type 2 DM, biguanides are avoided, the complications profile are visibly different from the Type 2 DM seen in the West.