Acute metabolic and hormonal responses to the inhibition of lipolysis in non-obese patients with non-insulin-dependent (type 2) diabetes mellitus: effects of acipimox.
1. Increased rates of fatty acid oxidation are frequently observed in patients with non-insulin-dependent diabetes mellitus and may contribute to hyperglycaemia by both decreasing peripheral glucose disposal and, more importantly, by increasing the rate of gluconeogenesis and therefore hepatic glucose output. Despite this relationship between lipid and carbohydrate metabolism, fasting glucose concentrations do not fall acutely in patients with non-insulin-dependent diabetes mellitus when plasma non-esterified fatty acid concentrations and lipid oxidation rates are decreased, questioning the importance of this interaction to glycaemic control. We have therefore measured the acute changes that occur 120-150 min after administration of 500 mg of the antilipolytic agent acipimox in eight non-obese male patients with non-insulin-dependent diabetes mellitus. 2. After administration of acipimox, lipolysis was inhibited as reflected by lower plasma non-esterified fatty acid (0.05 +/- 0.02 versus 0.55 +/- 0.05 mmol/l, P less than 0.001) and blood glycerol (8 +/- 1 versus 56 +/- 8 mumol/l, P less than 0.001) concentrations. The lipid oxidation rate was decreased (0.63 +/- 0.05 versus 1.02 +/- 0.08 mg min-1 kg-1, P less than 0.001), whereas there was a significant increase in the carbohydrate oxidation rate (1.93 +/- 0.17 versus 1.22 +/- 0.18 mg min-1 kg-1, P = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)
Fulcher
G R
GR
Department of Medicine, University of Newcastle-upon-Tyne, U.K.
Walker
M
M
Catalano
C
C
Farrer
M
M
Alberti
K G
KG
D020155:3-Hydroxybutyric Acid; D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D004837:Epinephrine / Q000097:blood; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005934:Glucagon / Q000097:blood; D005990:Glycerol / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D006885:Hydroxybutyrates / Q000097:blood; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008066:Lipolysis / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D011719:Pyrazines / Q000494:pharmacology*
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D006885:Hydroxybutyrates; D000960:Hypolipidemic Agents; D011719:Pyrazines; D005934:Glucagon; C027696:acipimox; D005990:Glycerol; D020155:3-Hydroxybutyric Acid; D006854:Hydrocortisone; D009638:Norepinephrine; D004837:Epinephrine