medwireNews: Researchers have characterized an atypical form of diabetes in Indian men with low BMI, which has a unique metabolic profile setting it apart from type 1 and type 2 diabetes.
Meredith Hawkins (Albert Einstein College of Medicine, New York, USA) and co-authors explain that cases of diabetes in individuals with a BMI below 19 kg/m2 have previously been reported in low- and middle-income countries (LMICs), and this condition was recognized as “malnutrition-related diabetes mellitus (MRDM)” by the World Health Organization (WHO) in 1985.
The WHO subsequently withdrew this category in 1999, “due to lack of substantial evidence” that malnutrition causes diabetes, but later epidemiologic data “continued to support this entity as a unique and fairly prevalent form of diabetes,” the researchers add.
To investigate the condition further, Hawkins et al carried out a comprehensive metabolic study of 20 Asian Indian men who met the WHO criteria for MRDM and after having all known forms of diabetes ruled out by immunogenetic analysis were categorized as having “low BMI diabetes.” Their metabolic profile was compared with that of demographically matched individuals with type 1 (n=15) or type 2 (n=13) diabetes, and lean (n=16) or overweight (n=9) people without diabetes.
“Only male participants were included in the study to minimize sex-specific variability and on the basis of the male predominance of MRDM,” note Hawkins et al in Diabetes Care.
The team’s analysis demonstrated that reduced insulin secretory capacity is “the cardinal physiologic feature” of low BMI diabetes. They say that both the first-phase insulin secretory response and the total insulin secretory response – measured using C-peptide deconvolution during a mixed-meal tolerance test (MMTT) – were significantly lower in people with low BMI diabetes relative to those with type 2 diabetes or without diabetes. However, low BMI diabetes was associated with higher insulin secretion when compared with type 1 diabetes.
In contrast to the insulin secretion results, individuals with low BMI diabetes had significantly lower average scores on the Matsuda index (a measure of hepatic and peripheral insulin sensitivity), disposition index, and insulinogenic index during the MMTT than those with type 2 diabetes, reflecting greater insulin sensitivity in the low BMI diabetes group. The HOMA insulin resistance score was significantly higher in people with low BMI diabetes versus controls in the lean no diabetes group.
Hawkins et al also measured insulin action during hyperinsulinemic–euglycemic pancreatic clamp, finding a significantly lower rate of endogenous glucose production in people with low BMI diabetes than those with type 2 diabetes (0.50 vs 0.84 mg/kg per min), “suggesting comparatively less hepatic insulin resistance,” they say. In addition, people with low BMI diabetes had significantly higher insulin-stimulated glucose uptake relative to those with type 2 diabetes (10.1 vs 4.2 mg/kg per min).
These findings emphasize that low BMI diabetes “is unlikely to be a subtype of [type 2 diabetes],” write the authors.
Finally, body composition analysis demonstrated that total lean body mass was significantly lower in the low BMI diabetes group compared with all the other groups. Visceral adipose tissue (VAT) volume and subcutaneous adipose tissue (SAT) volumes were significantly reduced in people with low BMI diabetes compared with those in the type 2 diabetes or overweight no diabetes groups, but VAT-to-SAT ratio was significantly higher in the low BMI diabetes than the type 1 diabetes or lean no diabetes groups.
Summarizing their results, Hawkins et al say that their study is “the first to demonstrate that [low BMI diabetes] individuals in LMICs have a unique metabolic profile, suggesting that this is a distinct entity that warrants further investigation.”
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Diabetes Care 2022; 45: 1428–1437