Metabolic effects of troglitazone therapy in type 2 diabetic, obese, and lean normal subjects.
OBJECTIVE
To characterize metabolic effects of troglitazone in type 2 diabetic, obese, and lean subjects, and examine the effects of troglitazone 2-3 weeks after discontinuation.


METHODS
Nine type 2 diabetic, nine obese, and nine lean subjects underwent baseline metabolic studies including an 8-h meal-tolerance test (MTT) and a 5-h glucose clamp. Subjects then received troglitazone (600 mg/day) for 12 weeks and subsequently had repeat metabolic studies. Diabetic subjects remained off hypoglycemic agents for 2-3 weeks and then underwent a 5-h glucose clamp.


RESULTS
In diabetic subjects, fasting plasma glucose was reduced (P<0.05) and insulin-stimulated glucose disposal (Rd) was enhanced by treatment (P<0.02). The area under the MTT 8-h plasma glucose curve declined with therapy (P<0.001), and its change was positively correlated with the improvement in Rd (r = 0.75, P<0.05). There was also a positive correlation between the change in fasting hepatic glucose output (HGO) and the change in fasting plasma glucose with treatment (r = 0.92, P<0.001). Discontinuation of therapy for 2-3 weeks did not significantly affect fasting plasma glucose or insulin-stimulated glucose Rd. In obese subjects, insulin-stimulated glucose Rd improved with therapy (P<0.001), allowing for maintenance of euglycemia by lower plasma insulin concentrations (P<0.05). In lean subjects, an increase in fasting HGO (P<0.001) and glucose clearance (P<0.01) was observed.


CONCLUSIONS
Troglitazone lowers fasting and postprandial plasma glucose in type 2 diabetes by affecting both fasting HGO and peripheral insulin sensitivity. Its effects are evident 2-3 weeks after discontinuation. In obese subjects, its insulin sensitizing effects suggest a role for its use in the primary prevention of type 2 diabetes.
Frias
J P
JP
Division of Endocrinology and Metabolism, University of California, San Diego, La Jolla 92093, USA.
Yu
J G
JG
Kruszynska
Y T
YT
Olefsky
J M
JM
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D002096:C-Peptide / Q000097:blood; D002784:Cholesterol / Q000097:blood; D002839:Chromans / Q000494:pharmacology / Q000627:therapeutic use*; D003920:Diabetes Mellitus / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000378:metabolism*; D013844:Thiazoles / Q000494:pharmacology / Q000627:therapeutic use*; D045162:Thiazolidinediones; D000077288:Troglitazone
D001786:Blood Glucose; D002096:C-Peptide; D002839:Chromans; D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D007328:Insulin; D013844:Thiazoles; D045162:Thiazolidinediones; D002784:Cholesterol; D000077288:Troglitazone; D005947:Glucose