FEMORAL SUBCUTANEOUS LMNA (LAMIN A/C) GENE EXPRESSION CORRELATES WITH VISCERAL AND HEPATIC ADIPOSITY AND CIRCULATING INTERLEUKIN-6 IN ASIAN INDIAN TYPE 2 DIABETES MELLITUS: A CASE-CONTROL CORRELATION STUDY

Abstract

LMNA-encoded lamin A/C proteins restrain adipogenic differentiation by sequestering SREBP1 and C/EBPα at the nuclear periphery, and lamin A/C in macrophages independently drives NF-κB-mediated transcription of interleukin-6 (IL-6) and other pro-inflammatory genes; whether femoral (thigh) subcutaneous LMNA expression, a depot not previously distinguished by diabetes status at the group level in Asian Indians, nonetheless tracks systemic adiposity, ectopic fat, and the circulating inflammatory profile has not been examined. In this case-control study of 40 Asian Indian patients with type 2 diabetes mellitus (T2DM) and 40 non-diabetic controls undergoing femur surgery at a tertiary care centre in Jaipur, India, absolute LMNA expression was measured by quantitative RT-PCR in femoral subcutaneous adipose tissue, and Pearson correlation coefficients were calculated between LMNA expression and anthropometric, lipid, glycaemic, adipocytokine, DEXA-derived body-composition, and MRI-derived abdominal and hepatic fat parameters, separately within the diabetic and non-diabetic groups. In diabetics, LMNA expression correlated strongly and positively with circulating IL-6 (r=0.80) and negatively with MRI-derived abdominal visceral fat (r=−0.64) and subcutaneous fat (r=−0.67); no anthropometric, lipid, or glycaemic correlation reached significance. In non-diabetics, LMNA correlated positively with hepatic fat (r=0.89), trunk-to-limb fat mass ratio (r=0.70), HDL-C (r=0.62), VLDL-C (r=0.49), TNF-α (r=0.41), triglycerides (r=0.33), and the trunk:leg fat ratio (r=0.32), and negatively with total body fat percentage (r=−0.29) and fat mass/height² (r=−0.25). The relationship between peripheral LMNA expression and the metabolic phenotype thus appears reorganised, rather than simply absent, in T2DM: the physiological coupling with adiposity and lipid handling seen in non-diabetics is lost, and a disease-specific coupling with circulating IL-6 emerges. These hypothesis-generating findings, from a previously unreported correlation analysis of an existing cohort, warrant replication with per-subject macrophage phenotyping and protein-level validation.