Relative contribution of muscle and liver insulin resistance to dysglycemia in postmenopausal overweight and obese women: A MONET group study

Abstract

Objectives: The relative contribution of muscle and liver insulin resistance (IR) in the development of dysglycemia and metabolic abnormalities is difficult to establish. The present study aimed to investigate the relative contribution of muscle IR vs. liver IR to dysglycemia in non-diabetic overweight or obese postmenopausal women and to determine differences in body composition and cardiometabolic indicators associated with hepatic or muscle IR.

Material and methods: Secondary analysis of 156 non-diabetic overweight or obese postmenopausal women. Glucose tolerance was measured using an oral glucose tolerance test. Whole-body insulin sensitivity (IS) was determined as glucose disposal rate during a euglycemic-hyperinsulinemic clamp. Muscle and liver IR have been calculated using Abdul-Ghani et al. OGTT-derived formulas. Participant's body compositions as well as cardiometabolic risk indicators were also determined.

Results: Overall, 57 (36.5%) of patients had dysglycemia, among them 25 (16.0%); 21 (13.5%); 11 (7.1%) had impaired fasting glycemia, impaired glucose tolerance and combined glucose intolerance respectively. Fifty-three (34.0%) participants were classified as combined IS while on the opposite 51 participants (32.7%) were classified as combined IR and 26 (16.7%) participants had either muscle IR or liver IR. For similar body mass index and total fat mass, participants with liver IR were more likely to have lower whole-body IS, dysglycemia and higher visceral fat, liver fat index, triglycerides and alanine aminotransferase than participants with muscle IR.

Conclusion: In the present study, the presence of liver IR is associated with a higher prevalence of dysglycemia, ectopic fat accumulation and metabolic abnormalities than muscle IR.

Keywords: Glucose homeostasis; Homéostasie du glucose; Insulinorésistance hépatique; Insulinorésistance musculaire; Liver insulin resistance; Muscle insulin resistance; Obesity; Obésité.