An Atypical Form of Diabetes Among Individuals With Low BMI

Abstract

Objective: Diabetes among individuals with low BMI (<19 kg/m2) has been recognized for >60 years as a prevalent entity in low- and middle-income countries (LMICs) and was formally classified as "malnutrition-related diabetes mellitus" by the World Health Organization (WHO) in 1985. Since the WHO withdrew this category in 1999, our objective was to define the metabolic characteristics of these individuals to establish that this is a distinct form of diabetes.

Research design and methods: State-of-the-art metabolic 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: a group with type 1 diabetes (T1D), a group with type 2 diabetes (T2D), and a group without diabetes. Insulin secretion was assessed by C-peptide deconvolution. Hepatic and peripheral insulin sensitivity were analyzed with stepped hyperinsulinemic-euglycemic pancreatic clamp studies. Hepatic and myocellular lipid contents were assessed with 1H-nuclear magnetic resonance spectroscopy.

Results: The total insulin secretory response was lower in the LD group in comparison with the lean group without diabetes and the T2D group. Endogenous glucose production was significantly lower in the LD group than the T2D group (mean ± SEM 0.50 ± 0.1 vs. 0.84 ± 0.1 mg/kg · min, respectively; P < 0.05). Glucose uptake was significantly higher in the LD group in comparison with the T2D group (10.1 ± 0.7 vs. 4.2 ± 0.5 mg/kg · min; P < 0.001). Visceral adipose tissue and hepatocellular lipids were significantly lower in LD than in T2D.

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

Figure 1

Schematic representation of the euglycemic-hyperinsulinemic clamp procedure. GH, growth hormone.

Figure 2

A: Insulin secretion AUC in response to MMTT across groups. B: Glucose levels during MMTT across groups. Data are presented as mean ± SEM. Asterisks indicate values that are significantly different for LD vs. T1D and T2D groups (*P < 0.05; **P < 0.01; ***P < 0.001).

Figure 3

Clamp studies. A: EGP. B: Glucose uptake (R_d) during the clamp studies. C: Average glucose level during two steady states in each group. D: Average atom percent excess (APE) during two steady states in each group. Values are presented as mean ± SEM. Asterisks indicate values that are significantly different when compared to the LD group (*P < 0.05).