Insulin resistance in obesity is associated with elevated basal lactate levels and diminished lactate appearance following intravenous glucose and insulin.
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 [SI] 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 SI 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 SI and basal lactate levels (r = -.56). Moreover, a significant and positive relationship was found between SI 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, SI 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Lovejoy
J
J
Department of Medicine, Emory University School of Medicine, Atlanta, GA.
Newby
F D
FD
Gebhart
S S
SS
DiGirolamo
M
M
D000328:Adult; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007275:Injections, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology*; D007333:Insulin Resistance; D007773:Lactates / Q000097:blood*; D019344:Lactic Acid; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009765:Obesity / Q000097:blood*
D007328:Insulin; D007773:Lactates; D019344:Lactic Acid