Effect of Progressive Weight Loss on Lactate Metabolism: A Randomized Controlled Trial

Maria Chondronikola, Faidon Magkos, Jun Yoshino, Adewole L Okunade, Bruce W Patterson, Michael J Muehlbauer, Christopher B Newgard, Samuel Klein, Maria Chondronikola, Faidon Magkos, Jun Yoshino, Adewole L Okunade, Bruce W Patterson, Michael J Muehlbauer, Christopher B Newgard, Samuel Klein

Abstract

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 [6,6-2 H2 ]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.

Trial registration: ClinicalTrials.gov NCT01299519.

Conflict of interest statement

Disclosure: The authors declare no conflict of interest.

© 2018 The Obesity Society.

Figures

Figure 1. CONSORT diagram of the study
Figure 1. CONSORT diagram of the study
Flow of participants through screening procedures, baseline testing, randomization into weight loss and weight maintenance, and post-intervention testing. Adopted from ref. (10).
Figure 2. Interrelationship between plasma lactate concentration…
Figure 2. Interrelationship between plasma lactate concentration ([LAC]) and glucose kinetics
(A) Relationship between fasting [LAC] and the glucose rate of appearance (Ra) into plasma. (B) Relationship between fasting [LAC] and the relative increase in glucose rate of disappearance (Rd) during a hyperinsulinemic-euglycemic clamp procedure. (C) Relationship between the relative change in [LAC] and the relative increase in glucose Rd during a hyperinsulinemic-euglycemic clamp procedure.
Figure 3. Effect of moderate (5%) weight…
Figure 3. Effect of moderate (5%) weight loss on plasma lactate concentration ([LAC]) during postabsorptive conditions and a hyperinsulinemic-euglycemic clamp procedure
(A) Fasting [LAC] before and after weight maintenance and 5% weight loss. *Value significantly different from corresponding weight maintenance value, interaction p=0.009 evaluated by using two-way repeated measures ANOVA. (B) Change in [LAC] induced by a hyperinsulinemic-euglycemic clamp procedure before and after weight maintenance and 5% weight loss. **Value different from corresponding weight maintenance value, interaction p=0.06 evaluated by using one-way repeated measures ANOVA. (C) Relationship between the relative change in fasting [LAC]pl with the relative change in glucose rate of appearance (Ra). (D) Relationship between the relative change in fasting [LAC] with the relative change in insulin sensitivity [assessed as the percent increase in glucose rate of disappearance during a hyperinsulinemic-euglycemic clamp procedure].
Figure 4. Effect of progressive weight loss…
Figure 4. Effect of progressive weight loss on plasma lactate concentration ([LAC])
(A) Fasting [LAC] before and after progressive weight loss (evaluated by using one-way repeated measures ANOVA, p=0.002; linear effect of time, p=0.006). (B) Change in [LAC] during a hyperinsulinemic-euglycemic clamp procedure before and after progressive weight loss (evaluated by using one-way repeated measures ANOVA, p=0.016; linear effect of time, p=0.006). *Value significantly different from Pre value, p <0.05.

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