Plasma adiponectin plays an important role in improving insulin resistance with glimepiride in elderly type 2 diabetic subjects.
OBJECTIVE
We investigated the effect of glimepiride, a third-generation sulfonylurea hypoglycemic agent, on insulin resistance in elderly patients with type 2 diabetes, in connection with plasma adiponectin and 8-epi-prostagrandin F2alpha (8-epi-PGF2alpha), an oxidative stress marker.


METHODS
A total of 17 elderly patients with type 2 diabetes received 12 weeks of treatment with glimepiride. Homeostasis assessment model of insulin resistance (HOMA-IR), homeostasis assessment model of beta-cell function, HbA(1c), C-peptide in 24-h pooled urine (urine CPR), and plasma concentrations of 8-epi-PGF2alpha, tumor necrosis factor-alpha (TNF-alpha), plasminogen activator inhibitor type 1, and adiponectin were measured at various times. The metabolic clearance rate of glucose (MCR-g) was also assessed by a hyperinsulinemic-euglycemic clamp.


RESULTS
After 8 weeks of glimepiride treatment, significant reductions were observed in HbA(1c) (from 8.4 +/- 1.9 to 6.9 +/- 1.0%), HOMA-IR (from 2.54 +/- 2.25 to 1.69 +/- 0.95%), and plasma TNF-alpha concentrations (from 4.0 +/- 2.0 to 2.6 +/- 2.5 pg/ml). MCR-g was significantly increased from 3.92 +/- 1.09 to 5.73 +/- 1.47 mg. kg(-1). min(-1). Plasma adiponectin increased from 6.61 +/- 3.06 to 10.2 +/- 7.14 micro g/ml. In control subjects, who maintained conventional treatment, no significant changes were observed in any of these markers.


CONCLUSIONS
Glimepiride remarkably improved insulin resistance, suggested by a significant reduction in HOMA-IR, an increase in MCR-g, and a reduction in HbA(1c) without changing extrapancreatic beta-cell function and urine CPR. Increased plasma adiponectin and decreased plasma TNF-alpha may underlie the improvement of insulin resistance with glimepiride.
Tsunekawa
Taku
T
Department of Geriatrics, Nagoya University Graduate School of Medicine, Japan.
Hayashi
Toshio
T
Suzuki
Yusuke
Y
Matsui-Hirai
Hisako
H
Kano
Hatsuyo
H
Fukatsu
Akiko
A
Nomura
Noriko
N
Miyazaki
Asaka
A
Iguchi
Akihisa
A
D052242:Adiponectin; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology*; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000097:blood; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007333:Insulin Resistance; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011506:Proteins / Q000032:analysis*; D013453:Sulfonylurea Compounds / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D052242:Adiponectin; D007004:Hypoglycemic Agents; D036341:Intercellular Signaling Peptides and Proteins; D017395:Plasminogen Activator Inhibitor 1; D011506:Proteins; D013453:Sulfonylurea Compounds; D014409:Tumor Necrosis Factor-alpha; C075750:8-epi-prostaglandin F2alpha; C057619:glimepiride; D015237:Dinoprost