Basal and insulin mediated VLDL-triglyceride kinetics in type 2 diabetic men

Lars P Sørensen, Iben R Andersen, Esben Søndergaard, Lars C Gormsen, Ole Schmitz, Jens S Christiansen, Søren Nielsen, Lars P Sørensen, Iben R Andersen, Esben Søndergaard, Lars C Gormsen, Ole Schmitz, Jens S Christiansen, Søren Nielsen

Abstract

Objective: Increased very-low-density lipoprotein triglycerides (VLDL-TG) concentration is a central feature of diabetic dyslipidemia. The objective was to compare basal and insulin mediated VLDL-TG kinetics, oxidation, and adipose tissue storage in type 2 diabetic and healthy (nondiabetic) men.

Research design and methods: Eleven type 2 diabetic and 11 healthy men, matched for BMI and age, were included. Ex vivo-labeled VLDL-TG tracers, blood and breath samples, fat biopsies, indirect calorimetry, and body composition measures were applied to determine VLDL-TG kinetics, VLDL-TG fatty acids (FA) oxidation, and storage in regional adipose tissue before and during a hyperinsulinemic euglycaemic clamp.

Results: VLDL-TG secretion was significantly greater in diabetic compared with healthy men (basal: 86.9 [31.0] vs. 61.9 [30.0] μmol/min, P = 0.03; clamp: 60.0 [26.2] vs. 34.2 [17.9] μmol · min⁻¹, P = 0.01). The insulin mediated suppression of VLDL-TG secretion was significant in both groups. VLDL-TG clearance was lower in diabetic men (basal: 84.6 [32.7] vs. 115.4 [44.3] ml · min⁻¹, P = 0.08; clamp: 76.3 [30.6] vs. 119.0 [50.2] ml · min⁻¹, P = 0.03). During hyperinsulinemia fractional VLDL-TG FA oxidation was comparable, but in percentage of energy expenditure (EE), significantly higher in diabetic men. Basal VLDL-TG storage was similar, but significantly greater in abdominal compared with leg fat.

Conclusions: Increased VLDL-TG in type 2 diabetic men is caused by greater VLDL-TG secretion and less so by lower VLDL-TG clearance. The ability of hyperinsulinemia to suppress VLDL-TG secretion appears preserved. During hyperinsulinemia VLDL-TG FA oxidation is significantly increased in proportion of EE in type 2 diabetic men. Greater basal abdominal VLDL-TG storage may help explain the accumulation of upper-body fat in insulin-resistant individuals.

Trial registration: ClinicalTrials.gov NCT01037647.

Figures

FIG. 1.
FIG. 1.
Study protocol.
FIG. 2.
FIG. 2.
Glucose infusion rate during the hyperinsulinemic clamp (A), concentrations of glucose (B), triglycerides (TG) (C), VLDL-TG (D), FFA (E), and insulin (F) in the basal state and during the hyperinsulinemic clamp. *P < 0.05 between groups (60–120 min and 360–420 min). Black circles, healthy subjects; open (white) circles, type 2 diabetic subjects. Data are presented as mean ± SEM.
FIG. 3.
FIG. 3.
VLDL-TG–specific activity (A), VLDL-TG secretion rate (B), VLDL-TG clearance rate (C), VLDL-TG concentration (D), and VLDL-TG/VLDL-ApoB-100 ratio (E) in the VLDL-TG SA steady state periods. Black circles and bars, healthy subjects; open (white) circles and bars, type 2 diabetic subjects. Data are mean ± SEM.
FIG. 4.
FIG. 4.
Breath 14CO2 SA steady state was reached in the clamp period, but not in the basal period (A). Therefore, only VLDL-TG FA oxidation data from the clamp period are illustrated and analyzed statistically. VLDL-TG FA oxidation expressed as fraction of secretion (B) and as oxidation rate (fractional oxidation × VLDL-TG secretion rate) (C). VLDL-TG FA oxidation as fraction of EE (D). Black circles and bars, healthy subjects; open (white) circles and bars, type 2 diabetic subjects. Data are mean ± SEM.
FIG. 5.
FIG. 5.
Storage of VLDL-TG FA in abdominal (A and B) and leg (C and D) subcutaneous adipose tissue expressed as fraction of VLDL-TG secretion (A and C) and as storage rate (fraction storage × VLDL secretion rate) (B and D). Black bars, healthy subjects; white bars, type 2 diabetic subjects. Data are presented as mean ± SEM.

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