An Atypical Form of Diabetes Among Individuals With Low BMI

Background: Diabetes among low body mass index (BMI < 19 kg/m2) individuals has been recognized for over 60 years as a prevalent entity in low- and middle-income countries (LMICs), and was formally classified as Malnutrition-Related Diabetes Mellitus (MRDM) by the World Health Organization (WHO) in 1985. Since the WHO withdrew this category in 1999, definitive metabolic characterization of these individuals is essential to establish that this is a distinct form of diabetes.

Methods: State-of-the-artmetabolic studies were used to characterize Indian individuals with ”Low BMI Diabetes”( LD) in whom all known forms of diabetes were excluded by immunogenetic analysis. They were compared with demographically-matched groups: type 1 diabetes (T1D), type 2 diabetes (T2D), and non-diabeticsInsulin secretion was assessed by C-peptide deconvolution. Hepatic and peripheral insulin sensitivity were analyzed using stepped hyperinsulinemic-euglycemic pancreatic clamp studies. Hepatic and myocellular lipid contents were assessed by 1H-nuclear-magnetic-resonance-spectroscopy.

Results: The total insulin secretory response was lower in the LD group when compared to the lean non-diabetic group and the T1D group. Endogenous glucose production (EGP) was significantly lower in the LD group than the T2D group (0.50±0.1 vs. 0.84±0.1 mg/kg.min, p<0.05). Glucose uptake was significantly higher in the LD group when compared to T2D (10.1±0.7 vs. 4.2±0.5 mg/kg.min, p<0.001). Visceral adipose tissue (VAT) and hepatocellular lipids (HCL) were significantly lower in LD than in T2D.

Conclusions: These studies are the first to demonstrate that low BMI individuals with diabetes in LMICs have a unique metabolic profile suggesting that this is a distinct entity that warrants further investigation.