Incomplete suppression of hepatic glucose production in non‐insulin dependent diabetes mellitus measured with [6,6^‐2H²]glucose enriched glucose infusion during hyperinsulinaemic euglycaemic clamps

Abstract

We have minimized methodological errors in the isotope dilution technique by using stable isotope, [6,6-2H2]glucose, thus avoiding the problem of contamination of tritiated glucose tracers and, by maintaining a constant plasma tracer enrichment have reduced error due to mixing transients. Using these modifications we have calculated hepatic glucose production in 20 patients with non-insulin-dependent diabetes mellitus during low (1 mU kg-1 min-1) and high (8 mU kg-1 min-1) dose insulin infusions. Mean fasting hepatic glucose production was 14.2 +/- 0.8 mumol kg-1 min-1. This suppressed by only 68% to 4.6 +/- 0.8 mumol kg-1 min-1 during the low-dose insulin infusion (plasma insulin 0.85 +/- 0.05 nmol l-1) and did not suppress further during the high-dose insulin infusion (plasma insulin 14.55 +/- 0.83 nmol l-1). Hepatic glucose production was significantly higher than zero throughout the study. Thus, we have found that minimization of known errors in the isotope dilution technique results in physiologically plausible and significantly positive values for hepatic glucose production indicating that the liver is resistant to insulin in patients with non-insulin-dependent diabetes mellitus.

Cortisol clearance and associations with insulin sensitivity, body fat and fatty liver in middle-aged men

“…2 H-labelled glucose infusion ( 6;6 À 2 H 2 Â Ã glucose; 170 mg, 1.7 mg/min; Cambridge Isotopes, Cambridge, MA, USA) was infused at the same time to determine hepatic insulin sensitivity, measured by insulin-mediated suppression of endogenous glucose production [16,17]. The M value of insulin sensitivity was defined as the glucose infusion rate during the final 30 min of the test in mg kg −1 min −1 .…”

Differential effects of fatness, fitness and physical activity energy expenditure on whole-body, liver and fat insulin sensitivity

“…An infusion of deuterated glucose was given at the same time to estimate hepatic insulin sensitivity measured by insulin-mediated suppression of endogenous glucose production [21,22]. Deuterium-labelled glucose was used as a steady-state infusion for 150 min prior to commencing the insulin infusion and was continued throughout the clamp.…”

Non-esterified fatty acid concentrations are independently associated with hepatic steatosis in obese subjects

“…Hepatic insulin sensitivity was determined by insulin-mediated suppression of endogenous glucose production [20,29]. Subjects attended the Clinical Research Facility at 08:00 hours, having abstained from vigorous exercise for 48 h and having fasted from 22:00 hours the night before.…”

“…The clamp continued for 3 h, with blood samples taken at half-hour intervals until the final 30 min, when samples were taken at intervals of 5-10 min for determination of whole-body glucose disposal. A modified version of the equations formulated by Steele [29] was used to calculate total rate of appearance (R a ) of glucose, endogenous glucose production and rate of disappearance (R d ) of glucose. The tracer to tracee ratio (TTR) was calculated as the ratio of the two areas from the mass spectrometry data.…”

“…TTR and plasma glucose values were smoothed using the method of optical segments [30]. For the Steele equations, 65% was used as the effective fraction and 0.22 l/kg as the distribution volume of glucose to calculate R a and R d [29,31]. Endogenous glucose production was measured as insulin-mediated suppression of glucose output in the early part of the clamp and was expressed as percentage suppression 60 min after commencing the insulin infusion, when suppression was linear to this time point.…”