Metabolic consequences of sustained suppression of free fatty acids by acipimox in patients with NIDDM.
To examine whether overnight suppression of free fatty acid levels reduces hepatic glucose production, 20 NIDDM patients were given a slow-release formulation of the antilipolytic agent acipimox, in a double-blind crossover manner at bedtime for 4 wk. During acipimox treatment, serum free fatty acid concentrations were suppressed between 2400 and 0600 by 64% (P < 0.001), but no reduction in hepatic glucose production was observed (2.16 +/- 0.16 vs. 2.23 +/- 0.16 mg.kg-1 x min-1, acipimox vs. placebo). In contrast, from 0800 to 2000 a sustained 50% rise occurred in serum free fatty acids (P < 0.001). As a consequence, the 24-h area under the free fatty acid curve was similar during both treatment periods. In the morning, the rise in free fatty acid concentration occurred despite identical serum acipimox concentrations as those measured at midnight, when free fatty acid levels were suppressed. Although energy expenditure was higher (P < 0.05) during periods of elevated free fatty acid levels, the sums of energy expenditure measured in the morning and in the evening were similar during the acipimox and placebo periods. To exclude that the free fatty acid rise was caused by administration of acipimox only once at bedtime, additional experiments were performed administering acipimox every 2 h for 4 days. Despite similar acipimox concentration on day 1 and day 4 of this frequent dosing regimen, the free fatty acid concentrations were significantly higher on day 4 compared with day 1 (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Saloranta
C
C
Third Department of Medicine, Helsinki University Hospital, Finland.
Taskinen
M R
MR
Widen
E
E
Härkönen
M
M
Melander
A
A
Groop
L
L
D001786:Blood Glucose / Q000032:analysis; D002151:Calorimetry; D002851:Chromatography, High Pressure Liquid; D002940:Circadian Rhythm / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005230:Fatty Acids, Nonesterified / Q000097:blood* / Q000378:metabolism / Q000502:physiology*; D005260:Female; D005934:Glucagon / Q000097:blood; D005947:Glucose / Q000032:analysis / Q000378:metabolism; D005990:Glycerol / Q000097:blood; D013006:Growth Hormone / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D000960:Hypolipidemic Agents / Q000097:blood / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011719:Pyrazines / Q000097:blood / Q000627:therapeutic use*; D013997:Time Factors
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D000960:Hypolipidemic Agents; D007328:Insulin; D011719:Pyrazines; D013006:Growth Hormone; D005934:Glucagon; D005947:Glucose; C027696:acipimox; D005990:Glycerol; D006854:Hydrocortisone