PREDICTORS OF WHOLE-BODY INSULIN SENSITIVITY ACROSS AGES AND ADIPOSITY IN ADULT HUMANS.

PREDICTORS OF WHOLE-BODY INSULIN SENSITIVITY ACROSS AGES AND ADIPOSITY IN ADULT HUMANS.

J Clin Endocrinol Metab. 2015 Dec 28;:jc20152892

Authors: Lalia AZ, Dasari S, Johnson ML, Robinson MM, Konopka AR, Distelmaier K, Port JD, Glavin MT, Esponda RR, Nair KS, Lanza IR

Abstract
CONTEXT: Numerous factors are purported to influence insulin sensitivity including age, adiposity, mitochondrial function, and physical fitness. Univariate associations cannot address the complexity of insulin resistance syndrome or the interrelationship among potential determinants.
OBJECTIVE: To identify significant independent predictors of insulin sensitivity across a range of age and adiposity in humans.
DESIGN, SETTING AND PARTICIPANTS: Peripheral and hepatic insulin sensitivity were measured by two stage hyperinsulinemic-euglycemic clamps in 116 men and women (19-78 years). Insulin-stimulated glucose disposal (GIR), the suppression of endogenous glucose production during hyperinsulinemia (EGPSUP), and HOMA-IR were tested for associations with 11 potential predictors. Abdominal subcutaneous fat (AFSQ), visceral fat (AFVISC), intrahepatic lipid (IHL) and intramyocellular lipid (IMCL) were quantified by magnetic resonance imaging and spectroscopy. Skeletal muscle mitochondrial respiratory capacity (State 3), coupling efficiency (RCR) and reactive oxygen species production (ROS) were evaluated from muscle biopsies. Aerobic fitness was measured from whole-body maximum oxygen uptake (VO2 peak), and metabolic flexibility (ΔRQ) was determined using indirect calorimetry.
RESULTS: Multiple regression analysis revealed that AFVISC (p<0.0001) and IHL (p=0.002) were independent negative predictors of peripheral insulin sensitivity, while VO2 peak (p=0.0007) and IMCL (p=0.023) were positive predictors. Mitochondrial capacity and efficiency were not independent determinants of peripheral insulin sensitivity. The EGPSUP model of hepatic insulin sensitivity revealed % fat (p<0.0001) and AFVISC (p=0.001) as significant negative predictors. Modeling HOMA-IR identified AFVISC (p<0.0001), VO2 peak (p=0.001), and IMCL (p=0.01) as independent predictors.
CONCLUSION: The reduction in insulin sensitivity observed with aging is driven primarily by age-related changes in the content and distribution of adipose tissue and is independent of muscle mitochondrial function or chronological age.

PMID: 26709968 [PubMed - as supplied by publisher]

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