Insulin-Sensitive Obesity: Prospective and Interventional Studies

Abstract

BACKGROUND: Individuals with metabolically healthy/insulin-sensitive obesity (MHO/Obsen) have been shown to have a comparable metabolic profile to lean individuals. However, longitudinal change in metabolic parameters in those with MHO/Obsen has not been comprehensively delineated with the gold-standard measure of insulin-sensitivity, the hyperinsulinaemic-euglycaemic clamp. The response of MHO/ Obsen cohorts to weight loss is also unclear. This study investigates the metabolic changes in the Obsen phenotype over time and in response to weight loss.

METHODS: A cohort of 124 individuals was carefully phenotyped 6 years ago and categorised into lean, overweight/obese insulin-sensitive (Obsen) or resistant (Obres, using gender based median insulin-sensitivity cut-offs) and type 2 diabetes mellitus (T2DM). Sixty-nine participants were followed up in this study. A subcohort (n = 13) also underwent a 16-week caloric restriction intervention. A comprehensive assessment of metabolic health, including insulin sensitivity (using hyperinsulinaemic-euglcyaemic clamp), body fat composition, serum/plasma metabolic markers, energy metabolism and lifestyle parameters, was performed.

RESULTS: There was an increase in total body fat, visceral adipose tissue mass, blood pressure and adipose tissue insulin resistance and a decrease in resting metabolic rate in the whole cohort over 6 years. Insulin sensitivity appeared to decrease over time in Obsen compared to the other groups. Physical activity increased and sugar intake decreased in Obres and T2DM. Saturated fat and trans-fat intake increased in the Obsen group. Insulin sensitivity in the 6 years prior to weight loss was inversely correlated to the change in insulin sensitivity induced by weight loss. Insulin sensitivity immediately prior to weight loss was inversely correlated to the change in resting metabolic rate induced by weight loss.

CONCLUSION: Obsen is not an enduring phenotype over 6 years. Hence, clinical intervention should target all individuals with overweight/obesity, irrespective of apparent metabolic health. However, further investigation into the role that insulin sensitivity plays in the response to weight loss is required to ensure optimum management in Obsen individuals.