Beta-Cell Secretory Function in Recent-Onset Type 2 Diabetes Mellitus: A Comparative Study Across Body Mass Index Categories

TL;DR

This study compares beta-cell function and insulin resistance in lean, normal, and overweight type 2 diabetes patients, finding that overweight individuals have higher beta-cell activity and insulin resistance.

Contribution

The study provides new insights into beta-cell secretory function differences in lean versus overweight type 2 diabetes patients.

Findings

Overweight T2DM patients had significantly higher HOMA2-%B and HOMA2-IR values compared to lean and normal-weight patients.

Lean and normal-weight T2DM patients exhibited lower beta-cell secretory function.

Abdominal obesity was associated with higher insulin resistance and preserved beta-cell function.

Abstract

Introduction: A section of type 2 diabetes mellitus (T2DM) patients have normal/lean body weight as opposed to classic diabetic patients who are generally overweight. The relative role of insulin resistance and beta-cell secretory defect in lean-/normal-weight T2DM patients as compared to patients of overweight body type needs further inquiry.

Methods: This cross-sectional study, conducted in family health centres across North Kerala, included 120 T2DM patients aged ≥30 years with a disease duration of ≤5 years. Participants were stratified into lean-weight, normal-weight, and overweight groups based on body mass index (BMI), with 40 patients randomly selected per group from an initial cohort of 829 screened patients. Coupled fasting serum glucose and insulin levels were estimated after an eight-hour overnight fasting serum sample. The homeostasis model assessment 2-measure of insulin resistance (HOMA2-IR) and homeostasis model assessment 2-measure of beta-cell secretion (HOMA2-%B) were then calculated using these measures with the help of the HOMA2 calculator. Data analysis was performed using RStudio Version 2023.06.1+524 (Posit Software, Boston, MA, USA).

Results: In the study population, comparison across three body weight categories revealed that waist circumference (WC), hip circumference, fasting insulin, HOMA2-IR, and HOMA2-%B differed significantly among them. Mean HOMA2-%B values were lower in lean-weight (27.38±22.18) and normal-weight (30.0±24.7) patients and highest in the overweight group (46.9±26.3). Similarly, HOMA2-IR was markedly elevated in overweight individuals (1.28±0.65) compared to lean-weight (0.72±0.55) and normal-weight (0.73±0.56) groups. Post hoc Tukey HSD analysis confirmed that only the overweight category patients had a statistically significant difference for these variables from the other two groups. Patients with abdominal obesity, defined by South Asian WC cut-offs, had significantly higher HOMA2-IR and HOMA2-%B values than those without. Regression analysis indicated that a 10% increase in BMI was associated with a 16.04% rise in HOMA2-%B and a 19.34% rise in HOMA2-IR. Female patients show 41.55% higher HOMA2-%B and 31.78% higher HOMA2-IR than males. Each additional year in age of onset of diabetes predicts a 1.71% rise in HOMA2-%B with no significant impact on insulin resistance.

Conclusion: Lean- or normal-weight diabetic patients have lower beta-cell secretion compared to overweight/obese patients. Also, patients with abdominal obesity exhibit higher insulin resistance with better preserved beta-cell function compared to those without. Also, patients with a younger age of onset of diabetes have comparatively lower beta-cell reserve compared to those developing diabetes at an older age.

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