The effect of sensitisation to insulin with pioglitazone on fasting and postprandial lipid metabolism, lipoprotein modification by lipases, and lipid transfer activities in type 2 diabetic patients.
OBJECTIVE
Insulin resistance is thought to be central to the pathogenesis of diabetic dyslipidaemia. We hypothesised that improving insulin sensitivity would improve fasting and postprandial triglyceride metabolism in patients with type 2 diabetes. To this aim we studied fasting and postprandial lipaemia in type 2 diabetic patients before and after sensitisation to insulin with pioglitazone, compared with that observed in patients on an insulin-providing regime.


METHODS
In a double-blind placebo-controlled protocol, 22 patients with type 2 diabetes were randomly allocated to receive either pioglitazone (45 mg/day) or glibenclamide (5 mg/day), for a 20-week period. Fasting and postprandial lipid metabolism were investigated at baseline and at the end of the treatment period. A group of non-diabetic subjects was also studied.


RESULTS
Compared with glibenclamide treatment, pioglitazone treatment decreased fasting triglyceride, glucose and insulin levels and the homeostasis model assessment score of insulin resistance. Decreased fasting triglyceride after pioglitazone treatment was due to reduced VLDL triglyceride, particularly VLDL-2. Lipoprotein lipase activity was unchanged by pioglitazone treatment but hepatic lipase showed a significant decrease. Pioglitazone treatment lowered total postprandial triglyceride, as well as chylomicron- and chylomicron-remnant retinyl palmitate levels to normal. Glucose disposal improved but remained abnormal.


CONCLUSIONS
Insulin sensitisation with pioglitazone has major effects in restoring postprandial lipaemia to normal, while also correcting fasting hypertriglyceridaemia; both factors may have consequences for atherogenic risk in diabetes.
Al Majali
K
K
Royal Free and University College Medical School, Department of Medicine, 5th Floor Jules Thorn Institute, Middlesex Hospital, Mortimer St, London W1N 8AA, UK.
Cooper
M B
MB
Staels
B
B
Luc
G
G
Taskinen
M-R
MR
Betteridge
D J
DJ
D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism*; D004032:Diet; D004224:Diterpenes; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006262:Health; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D050356:Lipid Metabolism / Q000187:drug effects*; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008074:Lipoproteins / Q000378:metabolism*; D008099:Liver / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D000077205:Pioglitazone; D000084562:Retinyl Esters; D045162:Thiazolidinediones / Q000494:pharmacology* / Q000627:therapeutic use; D014280:Triglycerides / Q000097:blood; D014801:Vitamin A / Q000031:analogs & derivatives / Q000097:blood
D001786:Blood Glucose; D004224:Diterpenes; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D008074:Lipoproteins; D000084562:Retinyl Esters; D045162:Thiazolidinediones; D014280:Triglycerides; D014801:Vitamin A; C014794:retinol palmitate; D008071:Lipoprotein Lipase; D000077205:Pioglitazone