Metabolic effects of suppression of nonesterified fatty acid levels with acipimox in obese NIDDM subjects.
NEFAs characteristically are elevated in obese NIDDM patients in both the basal state and after insulin. This elevation might aggravate glycemic control both by decreasing peripheral glucose disposal (glucose-fatty acid cycle), and by increasing HGO. Thus, lowering plasma NEFA levels might improve carbohydrate metabolism. We therefore measured HGO and fuel use (by indirect calorimetry) both in the basal state and during the last 30 min of a hyperinsulinemic clamp (0.025U.kg-1.h-1) in 8 obese NIDDM patients (BMI 34.8 +/- 1.0 kg/m2) after complete overnight suppression of plasma NEFA levels with acipimox, a new nicotinic acid analogue. After acipimox, mean basal plasma NEFA and glycerol levels were lower than control values (0.11 +/- 0.02 vs. 0.65 +/- 0.04 mM, P < 0.001; and 16 +/- 3 vs. 68 +/- 7 microM, P = 0.004, respectively) and were accompanied by a fall in lipid oxidation (acipimox vs. placebo: 16.1 +/- 1.2 vs. 38.8 +/- 2.4 mg.m-2 x min-1; P < 0.001) and a rise in glucose oxidation (91.1 +/- 6.2 vs. 54.1 +/- 9.0 mg.m-2 x min-1; P = 0.002). Basal HGO and fasting plasma glucose levels were lower (94.1 +/- 9.2 vs. 118.5 +/- 9.5 mg.m-2 x min-1, P = 0.01; and 8.3 +/- 1.2 vs. 9.8 +/- 1.2 mM; P < 0.001), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Fulcher
G R
GR
Department of Medicine, Medical School, University of Newcastle Upon Tyne, United Kingdom.
Walker
M
M
Catalano
C
C
Agius
L
L
Alberti
K G
KG
D020155:3-Hydroxybutyric Acid; D000409:Alanine / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood; D003920:Diabetes Mellitus / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005260:Female; D015309:Glucose Clamp Technique; D005990:Glycerol / Q000097:blood; D006801:Humans; D006885:Hydroxybutyrates / Q000097:blood; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D007773:Lactates / Q000097:blood; D008297:Male; D008875:Middle Aged; D009765:Obesity; D011719:Pyrazines / Q000494:pharmacology*; D011773:Pyruvates / Q000097:blood; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D006885:Hydroxybutyrates; D000960:Hypolipidemic Agents; D007328:Insulin; D007773:Lactates; D011719:Pyrazines; D011773:Pyruvates; D014280:Triglycerides; D002784:Cholesterol; C027696:acipimox; D000409:Alanine; D005990:Glycerol; D020155:3-Hydroxybutyric Acid