TY - JOUR

T1 - Effect of progressive weight loss on lactate metabolism

T2 - A randomized controlled trial

AU - Chondronikola, Maria

AU - Magkos, Faidon

AU - Yoshino, Jun

AU - Okunade, Adewole L

AU - Patterson, Bruce W

AU - Muehlbauer, Michael J

AU - Newgard, Christopher B

AU - Klein, Samuel

N1 - © 2018 The Obesity Society.

PY - 2018

Y1 - 2018

N2 - Objective: Lactate is an intermediate of glucose metabolism that has been implicated in the pathogenesis of insulin resistance. This study evaluated the relationship between glucose kinetics and plasma lactate concentration ([LAC]) before and after manipulating insulin sensitivity by progressive weight loss.Methods: Forty people with obesity (BMI = 37.9 ± 4.3 kg/m2 ) were randomized to weight maintenance (n = 14) or weight loss (n = 19). Subjects were studied before and after 6 months of weight maintenance and before and after 5%, 11%, and 16% weight loss. A hyperinsulinemic-euglycemic clamp procedure in conjunction with [6,6-2H2]glucose tracer infusion was used to assess glucose kinetics.Results: At baseline, fasting [LAC] correlated positively with endogenous glucose production rate (r = 0.532; P = 0.001) and negatively with insulin sensitivity, assessed as the insulin-stimulated glucose disposal (r = -0.361; P = 0.04). Progressive (5% through 16%) weight loss caused a progressive decrease in fasting [LAC], and the decrease in fasting [LAC] after 5% weight loss was correlated with the decrease in endogenous glucose production (r = 0.654; P = 0.002) and the increase in insulin sensitivity (r = -0.595; P = 0.007).Conclusions: This study demonstrates the interrelationships among weight loss, hepatic and muscle glucose kinetics, insulin sensitivity, and [LAC], and it suggests that [LAC] can serve as an additional biomarker of glucose-related insulin resistance.

AB - Objective: Lactate is an intermediate of glucose metabolism that has been implicated in the pathogenesis of insulin resistance. This study evaluated the relationship between glucose kinetics and plasma lactate concentration ([LAC]) before and after manipulating insulin sensitivity by progressive weight loss.Methods: Forty people with obesity (BMI = 37.9 ± 4.3 kg/m2 ) were randomized to weight maintenance (n = 14) or weight loss (n = 19). Subjects were studied before and after 6 months of weight maintenance and before and after 5%, 11%, and 16% weight loss. A hyperinsulinemic-euglycemic clamp procedure in conjunction with [6,6-2H2]glucose tracer infusion was used to assess glucose kinetics.Results: At baseline, fasting [LAC] correlated positively with endogenous glucose production rate (r = 0.532; P = 0.001) and negatively with insulin sensitivity, assessed as the insulin-stimulated glucose disposal (r = -0.361; P = 0.04). Progressive (5% through 16%) weight loss caused a progressive decrease in fasting [LAC], and the decrease in fasting [LAC] after 5% weight loss was correlated with the decrease in endogenous glucose production (r = 0.654; P = 0.002) and the increase in insulin sensitivity (r = -0.595; P = 0.007).Conclusions: This study demonstrates the interrelationships among weight loss, hepatic and muscle glucose kinetics, insulin sensitivity, and [LAC], and it suggests that [LAC] can serve as an additional biomarker of glucose-related insulin resistance.

KW - Adult

KW - Female

KW - Glucose Clamp Technique/methods

KW - Humans

KW - Insulin Resistance/physiology

KW - Lactates/metabolism

KW - Male

KW - Weight Loss/physiology

U2 - 10.1002/oby.22129

DO - 10.1002/oby.22129

M3 - Journal article

C2 - 29476613

VL - 26

SP - 683

EP - 688

JO - Obesity

JF - Obesity

SN - 1930-7381

IS - 4

ER -