|Title||Predictors of Whole-Body Insulin Sensitivity Across Ages and Adiposity in Adult Humans.|
|Publication Type||Journal Article|
|Year of Publication||2016|
|Authors||Lalia, AZ, Dasari, S, Johnson, ML, Robinson, MM, Konopka, AR, Distelmaier, K, Port, JD, Glavin, MT, Esponda, RRuiz, K Nair, S, Lanza, IR|
|Journal||J Clin Endocrinol Metab|
|Date Published||2016 Feb|
|Keywords||Adiposity, Adult, Aged, Aging, Anaerobic Threshold, Blood Glucose, Female, Glucose Clamp Technique, Homeostasis, Humans, Hyperinsulinism, Insulin Resistance, Intra-Abdominal Fat, Lipid Metabolism, Liver, Male, Middle Aged, Mitochondria, Muscle, Muscle, Skeletal, Predictive Value of Tests, Reactive Oxygen Species, Subcutaneous Fat, Young Adult|
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 or the interrelationship among potential determinants.
OBJECTIVE: The objective of the study was 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 (aged 19-78 y). Insulin-stimulated glucose disposal, the suppression of endogenous glucose production during hyperinsulinemia, and homeostatic model assessment of insulin resistance were tested for associations with 11 potential predictors. Abdominal subcutaneous fat, visceral fat (AFVISC), intrahepatic lipid, and intramyocellular lipid (IMCL) were quantified by magnetic resonance imaging and spectroscopy. Skeletal muscle mitochondrial respiratory capacity (state 3), coupling efficiency, and reactive oxygen species production were evaluated from muscle biopsies. Aerobic fitness was measured from whole-body maximum oxygen uptake (VO2 peak), and metabolic flexibility was determined using indirect calorimetry.
RESULTS: Multiple regression analysis revealed that AFVISC (P < .0001) and intrahepatic lipid (P = .002) were independent negative predictors of peripheral insulin sensitivity, whereas VO2 peak (P = .0007) and IMCL (P = .023) were positive predictors. Mitochondrial capacity and efficiency were not independent determinants of peripheral insulin sensitivity. The suppression of endogenous glucose production during hyperinsulinemia model of hepatic insulin sensitivity revealed percentage fat (P < .0001) and AFVISC (P = .001) as significant negative predictors. Modeling homeostatic model assessment of insulin resistance identified AFVISC (P < .0001), VO2 peak (P = .001), and IMCL (P = .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.
|Alternate Journal||J. Clin. Endocrinol. Metab.|
|PubMed Central ID||PMC4880121|
|Grant List||R01 DK041973 / DK / NIDDK NIH HHS / United States |
AG009531 / AG / NIA NIH HHS / United States
R01 DK059615 / DK / NIDDK NIH HHS / United States
T32DK007352 / DK / NIDDK NIH HHS / United States
T32 DK007198 / DK / NIDDK NIH HHS / United States
P30 DK050456 / DK / NIDDK NIH HHS / United States
KL2 TR000136 / TR / NCATS NIH HHS / United States
DK041973 / DK / NIDDK NIH HHS / United States
U24 DK100469 / DK / NIDDK NIH HHS / United States
DK50456 / DK / NIDDK NIH HHS / United States
UL1 TR000135 / TR / NCATS NIH HHS / United States
KL2 TR-000136 / TR / NCATS NIH HHS / United States
T32 DK007352 / DK / NIDDK NIH HHS / United States
R01 AG009531 / AG / NIA NIH HHS / United States
U24DK100469 / DK / NIDDK NIH HHS / United States
R56 DK041973 / DK / NIDDK NIH HHS / United States