Increased Lactate Release per Fat Cell in Normoglycemic First-Degree Relatives of Individuals with Type 2 Diabetes

Abstract

The aim of this study was to examine subcutaneous lactate production in the relatives of individuals with type 2 diabetes. Therefore, we recruited seven healthy first-degree relatives of type 2 diabetic patients and seven pairwise, matched, healthy control subjects without any heredity for diabetes. All subjects were studied with a euglycemic insulin clamp at ∼600 pmol/l, abdominal subcutaneous microdialysis, and 133Xe clearance. Furthermore, a subcutaneous needle biopsy was performed to determine fat cell size. In the fasting state, interstitial lactate was 40% higher in relatives than in control subjects (P = 0.043), but net lactate production was similar in both groups. However, during the insulin clamp, interstitial lactate (2.50 ± 0.29 vs. 1.98 ± 0.26 mmol/l, P = 0.018), interstitial-arterial lactate concentration difference (1.08 ± 0.30 vs. 0.53 ± 0.24 mmol/l, P = 0.028), and net lactate release per fat cell (10.9 ± 3.7 vs. 2.8 ± 1.3 fmol · cell-1 · min-1, P = 0.018) were increased in the relatives. We conclude that first-degree relatives of type 2 diabetic patients may have an enhanced net lactate release per fat cell in abdominal subcutaneous tissue. This could suggest a pathological regulation in adipose tissue that is of importance for the metabolic defects known in type 2 diabetic relatives.