Lean Diabetes: A Unique form of Diabetes

1 Jul, 22

Introduction

The incidence of unique form of diabetes among individuals with low body mass index (BMI; <19 kg/m²) has been long recognized. Formally classified as “malnutrition-related diabetes mellitus” (MRDM) by the World Health Organization (WHO), this form of diabetes has a high prevalence in low- and middle-income countries (LMICs). The WHO withdrew the MRDM category from diabetes classification in 1999, nevertheless; a substantial amount of data continued to support this unique and fairly prevalent form of diabetes. A correct assessment of patients’ metabolic defects may aid clinicians to appropriately tailor the clinical management in such patients.

Aim

To define the metabolic characteristics of individuals affected with MRDM

Patients Profile

Patients with lower socioeconomic status (SES) and low BMI (BMI up to 19.5 kg/m²) (n=73)
All patients were males from India (age; 19–45 years) with diabetes duration of at least 1 year and having moderate glycemic control (HbA1c 8–10%) and without micro- or macrovascular complications.
Patients with “low BMI diabetes” (LD; n=20) in whom all forms of diabetes were excluded, were compared with demographically matched groups of patients with type 1 diabetes mellitus (T1DM; n=15), type 2 diabetes mellitus (T2DM; n=13), and a group of individuals without diabetes (lean non-DM; n=16, overweight non-DM; 9).

Methods

Study Design

Cross-sectional study to characterise a subtype of diabetes

Assessments

Study participants underwent anthropometric assessments including BMI, waist circumference, and waist-to-hip ratio measurement and were classified as; lean, non-obese or obese as per the 2013 the “National Institute for Health and Care Excellence” guidelines.
Laboratory assessments included lipid profile, HbA1c, blood glucose measurements, challenged C-peptide levels, and GAD-65/IA-2 antibody assays.
Study participants underwent genetic screening for maturity-onset diabetes of the young (MODY) and lipodystrophy
Hepatic and peripheral insulin sensitivities were assessed using a 6-hour “stepped” euglycemic hyperinsulinemic pancreatic clamp study
Hepatic and myocellular lipid contents were assessed with 1H-nuclear magnetic resonance spectroscopy
Insulin secretion was assessed with standard mixed meal tolerance test
Whole body composition for body fat percentage, fat mass, lean mass, and truncal fat was assessed using a DEXA scanner

Results

Individuals in the LD group had a lower total insulin secretory response as compared with the lean non-DM and the T2DM group.
Individuals in the LD group also had significantly lower endogenous glucose production (EDP) when compared with patients in the T2DM group (Table 1).
Individuals in the LD group had a significantly higher insulin-stimulated glucose uptake as compared with the patients in the T2DM group (R_d, peripheral insulin sensitivity), suggesting lower peripheral insulin resistance (Table 1).

Table 1: Comparison of various parameters in the study groups

Parameter	LD Group	T2DM Group	P value
Insulin Secretory response (Total AUC)	383.0	839.5	<0.05
EDP (mg/kg.min)	0.5	0.84	<0.05
Insulin-stimulated Glucose Uptake (mg/kg.min)	10.1	4.2	<0.001

Individuals in the LD group had a significantly higher insulin resistance, as compared with the lean non-DM group. Individuals in the LD group also had significantly higher glucose levels at all time points as compared with the lean non-DM group.
Patients in the LD groups also had significantly lower visceral adipose tissue and hepatocellular lipids as compared with patients in the T2DM group.

Conclusions

This was a first-of-its kind study that comprehensively characterized insulin secretion, hepatic and peripheral insulin sensitivity, whole body composition, etc. in individuals with LD.
The study demonstrated that the cardinal physiologic feature of LD was a defect in insulin secretory capacity as opposed to insulin resistance.
Individuals from LMICs with LD had a unique metabolic profile, suggesting towards a distinct entity that warrants further investigation.

Diabetes Care 2022;45:1428–1437.