Lean diabetes mellitus: An emerging entity in the era of obesity

Abstract

Much has been published on the characteristics of type 2 diabetes mellitus and its association with the epidemic of obesity. But relatively little is known about the incidence of lean diabetes, progression of disease and fate of the patients with low-normal body mass index (< 25). Studies in developing countries have shown that the clinical characteristics of these patients include history of childhood malnutrition, poor socioeconomic status, relatively early age of onset and absence of ketosis on withdrawal of insulin. In the United States, recent studies showed that the lean, normal weight diabetes is not rare especially among minority populations. They showed that these patients are mainly males, have higher prevalence of insulin use indicating rapid beta cell failure. They might have increased total, cardiovascular and non cardiovascular mortality when compared to obese diabetic patients. In this review, the epidemiologic and clinical features of lean diabetes are presented. The potential causal mechanisms of this emerging diabetes type that may include genetic, autoimmune, acquired and behavioral factors are discussed. The need for studies to further elucidate the causation as well as specific prevention and treatment of lean diabetes is emphasized.

Keywords: Beta cell failure; Ketosis resistant diabetes of young; Lean diabetes; Obesity paradox; Sarcopenic obesity.

Figure 1

Pathogenetic model of development of lean type 2 diabetes. In the obese individuals the diabetes develops once the beta cell cannot cope with the insulin resistance conferred by the growing obesity. In the lean diabetes the early failure of the beta cells results in development of diabetes at much lower insulin resistance. It might be speculated that in individual with similar beta cell dysfunction but lower insulin resistance (lower weight) diabetes might not develop. NGT: Normal glucose tolerance; IGT: Impaired glucose tolerance; T2DM: Type 2 diabetes; Modified from Weyer et al. J Clin Invest 1999; 104: 787–794.