Plasma Lactate Levels Increase during Hyperinsulinemic Euglycemic Clamp and Oral Glucose Tolerance Test

Abstract

Insulin resistance, which plays a central role in the pathogenesis of type 2 diabetes (T2D), is an early indicator that heralds the occurrence of T2D. It is imperative to understand the metabolic changes that occur at the cellular level in the early stages of insulin resistance. The objective of this study was to determine the pattern of circulating lactate levels during oral glucose tolerance test (OGTT) and hyperinsulinemic euglycemic clamp (HIEC) study in normal nondiabetic subjects. Lactate and glycerol were determined every 30 minutes during OGTT and HIEC on 22 participants. Lactate progressively increased throughout the HIEC study period (P < 0.001). Participants with BMI < 30 had significantly higher mean M-values compared to those with BMI ≥ 30 at baseline (P < 0.05). This trend also continued throughout the OGTT. In addition, those with impaired glucose tolerance test (IGT) had significantly higher mean lactate levels compared to those with normal glucose tolerance (P < 0.001). In conclusion, we found that lactate increased during HIEC study, which is a state of hyperinsulinemia similar to the metabolic milieu seen during the early stages in the development of T2D.

Brain insulin resistance in type 2 diabetes and Alzheimer disease: concepts and conundrums

“…The relative contribution of this shuttle as a neuronal fuel source compared with neuronal glucose uptake via glucose transporters is still debated, although it is clear that neurons can use lactate to fuel oxidative phosphorylation and generate ATP during periods of high energy demand 87 . Hyperinsulinaemia is reported to increase peripheral lactate levels, which in turn could affect the net flux of lactate across the BBB and affect energy metabolism within the brain 88 ; therefore, the effect of insulin levels on lactate could have implications for brain functioning. Astrocytes bind insulin with high affinity 89 and express IRS1, IRS2 and downstream signalling molecules AKT and MAPK.…”

Detection of Early Disease Risk Factors Associated with Metabolic Syndrome: A New Era with the NMR Metabolomics Assessment

“…Lactate metabolism is directly implicated in the gluconeogenesis, indirectly in the TCA cycle and in the respiratory chain, which are metabolic pathways implicated in carbohydrate metabolism [114]. Changes in plasma lactate during an oral glucose tolerance test (OGTT) are inversely correlated with fasting insulin, indicating that IR can be reflected through this metabolite response to a glucose challenge [115,116]. Lactate homeostasis is related to glucose metabolism and, therefore, diseases associated with glucose disruption, as MetS, obesity or diabetes, are associated with disturbed lactate metabolism [114,117].…”

Lactate, a Neglected Factor for Diabetes and Cancer Interaction

“…Barnett et al proposed that diabetes-associated hyperlactatemia might be an early change in the time course of the disease [39]. Recently, Berhane et al [40] demonstrated that lactate production progressively rises during hyperinsulinemic euglycemic clamp study, a condition of hyperinsulinemia similar to the early stages in the development of T2DM. Intriguingly, similar previous studies also report elevated lactate concentrations during the early stages of diabetes, prediabetes, and the hyperinsulinemia condition.…”

“…In addition, the postprandially nonoxidative glycolysis is elevated in these patients relative to healthy controls and blood lactate level rises under this condition [36]. Insulin resistance plays a vital role in the pathogenesis of T2DM [46] and can be used as an early marker for the disease [40]. Under the insulin resistant condition, high levels of insulin promote glycolysis through activating two rate limiting enzymes, namely, phosphofructokinase and pyruvate dehydrogenase [47].…”

“…Some studies suggest that augmented lactate levels in obesity, which might play a significant role in glucose transport and metabolism, profoundly influence insulin sensitivity [49]. Its high plasma level might be an early indication of the beginning of insulin resistance and can be utilized to identify a state of insulin resistance [40]. In addition, in HIV-infected patients treated with nucleoside reverse transcriptase inhibitors, both resting and postexercise levels of lactate are associated with insulin resistance in skeletal muscle [50].…”