Nocturnal and postprandial free fatty acid kinetics in normal and type 2 diabetic subjects: effects of insulin sensitization therapy.
Whether free fatty acid (FFA) rate of appearance (R(a)) is increased in type 2 diabetes is controversial. To characterize nocturnal and postprandial abnormalities in FFA kinetics and to determine the effects of treatment with insulin sensitizers on lipolysis, we measured palmitate R(a) in control subjects (n = 6) and individuals with poorly controlled, sulfonylurea-treated type 2 diabetes (HbA(1c) = 8.7 +/- 0.2%, n = 20), the latter before and at the end of 12 weeks of treatment with troglitazone (600 mg/day, n = 4), metformin ( approximately 2,000 mg/day, n = 8), or placebo (n = 8). Subjects consumed a standard breakfast at 0800 h. Results in control subjects and type 2 diabetic subjects were compared at baseline. Integrated nocturnal FFA R(a) (AUC(1:00-8:00 A.M.)) was approximately 50% higher in type 2 diabetic subjects than in control subjects (29.4 +/- 3.0 vs. 19.4 +/- 3.9 mmol. m(-2). 7 h(-1), respectively, P < 0.05), whereas postprandial palmitate R(a) (AUC(0-240 min)) was almost threefold higher in type 2 diabetic subjects than in control subjects (14.2 +/- 1.7 vs. 5.3 +/- 1.0 mmol. m(-2). 4 h(-1), respectively, P < 0.01). After troglitazone treatment, nocturnal palmitate R(a) did not change, but postprandial palmitate R(a) decreased by approximately 30% (P < 0.05). Palmitate kinetics did not change with metformin or placebo treatment. In summary, nocturnal and postprandial FFA R(a) is increased in type 2 diabetes. Postprandial lipolysis appears to be preferentially improved by thiazolidinediones compared with nocturnal lipolysis.
Miles
John M
JM
Mid-America Heart Institute of Saint Luke's Hospital, University of Missouri-Kansas City, Kansas City, MO, USA. miles.john@mayo.edu
Wooldridge
David
D
Grellner
Wayne J
WJ
Windsor
Sheryl
S
Isley
William L
WL
Klein
Samuel
S
Harris
William S
WS
D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D002096:C-Peptide / Q000097:blood; D002839:Chromans / Q000627:therapeutic use; D002940:Circadian Rhythm; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy*; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005260:Female; D005502:Food; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D007700:Kinetics; D008066:Lipolysis; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D010919:Placebos; D013844:Thiazoles / Q000627:therapeutic use; D045162:Thiazolidinediones; D000077288:Troglitazone
D001786:Blood Glucose; D002096:C-Peptide; D002839:Chromans; D005230:Fatty Acids, Nonesterified; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin; D010919:Placebos; D013844:Thiazoles; D045162:Thiazolidinediones; D000077288:Troglitazone