Insulin resistance in obesity is associated with elevated basal lactate levels and diminished lactate appearance following intravenous glucose and insulin

doi:10.1016/0026-0495(92)90185-D

Metabolism

Volume 41, Issue 1, January 1992, Pages 22-27

https://doi.org/10.1016/0026-0495(92)90185-D Get rights and content

Abstract

Lactate metabolism is altered in obesity. Increasing obesity is associated with increased blood lactate levels after an overnight fast. In contrast, we have recently shown a marked decrease in the capacity for acute lactate generation in obese subjects following an oral glucose load, which we postulated might be linked to altered insulin sensitivity. In the present study, we systematically analyzed the relationship between insulin sensitivity (the Sensitivity Index [S₁] derived using the minimal model), body mass index (BMI), and glucose, insulin, and lactate levels in the basal state and following intravenous (IV) glucose and insulin administration in lean and obese subjects. The results showed that S₁ and BMI were inversely related, as expected. Insulin sensitivity was more tightly associated with glucose, insulin, and lactate levels (both basal and integrated) than obesity per se. A significant inverse relationship was found between S₁ and basal lactate levels (r = −.56). Moreover, a significant and positive relationship was found between S₁ and incremental lactate area under the curve (reflecting acute lactate production) (r = .41). In a multiple regression analysis to separate the independent effects of obesity (BMI) and insulin sensitivity, after adjusting for age, sex, and race, S₁ accounted for 34% of the variance in basal lactate and 24% of the variance in incremental lactate area. Obesity independently accounted for 10% of the variance in basal lactate and 11% of the variance in incremental lactate area, neither of which were statistically significant. We conclude that elevations in basal lactate are associated with the development of insulin resistance. Furthermore, the ability to produce lactate acutely in response to a glucose and insulin challenge is reduced with progressively increased insulin resistance. Diminished insulin sensitivity appears to have a greater influence on alterations in glucose, insulin, and lactate that the degree of obesity per se.

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^☆: Supported in part by National Institutes of Health Grants No. 1-F32-DK08264 (J.L.) and 5-R01-DK39326 (M.D.G.), by General Clinical Research Center Public Health Service Grant No. M01-RR-00039, and by a grant from the American Institute for Cancer Research.

¹: Dr Lovejoy's current address is Pennington Biomedical Research Center, 6400 Perkins Rd, Baton Rouge, LA 70808-4124.

View full text

Insulin resistance in obesity is associated with elevated basal lactate levels and diminished lactate appearance following intravenous glucose and insulin☆

Abstract

Am J Clin Nutr

Lancet

Metabolism

Metabolism

Metabolism

Metabolism

Biology of regional body fat distribution: Relationship to non-insulin-dependent diabetes mellitus

Diabetes Metab Rev

Lactate release in isolated rat adipocytes: Influence of cell size, glucose concentration, insulin and epinephrine

Horm Metab Res

In vitro insulin resistance of human adipocytes isolated from subjects with noninsulin-dependent diabetes mellitus

J Clin Invest

Glucose uptake in human adipose tissue

Metabolism

Blood lactate levels in human obesity

Int J Obesity

The effects of obesity and maturity-onset diabetes mellitus on l(+) lactic acid metabolism

Clin Sci

Lactate generation following glucose ingestion: Relation to obesity, carbohydrate tolerance and insulin sensitivity

Int J Obesity

Quantitative estimation of insulin sensitivity

Am J Physiol

Classification and diagnosis of diabetes mellitus and other categories of glucose tolerance

Diabetes

Minimal model analysis of IVGTT-derived insulin sensitivity in diabetic subjects

J Clin Endocrinol Metab