Pioglitazone decreases fasting and postprandial endogenous glucose production in proportion to decrease in hepatic triglyceride content.
OBJECTIVE
Hepatic triglyceride is closely associated with hepatic insulin resistance and is known to be decreased by thiazolididinediones. We studied the effect of pioglitazone on hepatic triglyceride content and the consequent effect on postprandial endogenous glucose production (EGP) in type 2 diabetes.


METHODS
Ten subjects with type 2 diabetes on sulfonylurea therapy were treated with pioglitazone (30 mg daily) for 16 weeks. EGP was measured using a dynamic isotopic methodology after a standard liquid test meal both before and after pioglitazone treatment. Liver and muscle triglyceride levels were measured by (1)H magnetic resonance spectroscopy, and intra-abdominal fat content was measured by magnetic resonance imaging.


RESULTS
Pioglitazone treatment reduced mean plasma fasting glucose and mean peak postprandial glucose levels. Fasting EGP decreased after pioglitazone treatment (16.6 +/- 1.0 vs. 12.2 +/- 0.7 micromol . kg(-1) . min(-1), P = 0.005). Between 80 and 260 min postprandially, EGP was twofold lower on pioglitazone (2.58 +/- 0.25 vs. 1.26 +/- 0.30 micromol . kg(-1) . min(-1), P < 0.001). Hepatic triglyceride content decreased by approximately 50% (P = 0.03), and muscle (anterior tibialis) triglyceride content decreased by approximately 55% (P = 0.02). Hepatic triglyceride content was directly correlated with fasting EGP (r = 0.64, P = 0.01) and inversely correlated to percentage suppression of EGP (time 150 min, r = -0.63, P = 0.02). Muscle triglyceride, subcutaneous fat, and visceral fat content were not related to EGP. CONCLUSIONS Reduction in hepatic triglyceride by pioglitazone is very closely related to improvement in fasting and postprandial EGP in type 2 diabetes.
Ravikumar
Balasubramanian
B
Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, U.K.
Gerrard
Jean
J
Dalla Man
Chiara
C
Firbank
Michael J
MJ
Lane
Annette
A
English
Philip T
PT
Cobelli
Claudio
C
Taylor
Roy
R
D050153:Abdominal Fat / Q000033:anatomy & histology / Q000378:metabolism; D000328:Adult; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D001835:Body Weight; D002096:C-Peptide / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D005215:Fasting / Q000502:physiology; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005934:Glucagon / Q000097:blood; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D008099:Liver / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism; D010084:Oxidation-Reduction; D000077205:Pioglitazone; D019518:Postprandial Period / Q000187:drug effects / Q000502:physiology; D013453:Sulfonylurea Compounds / Q000008:administration & dosage; D045162:Thiazolidinediones / Q000008:administration & dosage*; D014280:Triglycerides / Q000378:metabolism*
D001786:Blood Glucose; D002096:C-Peptide; D005230:Fatty Acids, Nonesterified; D005934:Glucagon; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D000077205:Pioglitazone; D013453:Sulfonylurea Compounds; D045162:Thiazolidinediones; D014280:Triglycerides; C517652:hemoglobin A1c protein, human