Effect of Glimepiride on Serum Adiponectin Level in Subjects With Type 2 Diabetes

doi:10.2337/diacare.26.7.2215

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Letters: Observations
Letter

Effect of Glimepiride on Serum Adiponectin Level in Subjects With Type 2 Diabetes

Shoichiro Nagasaka, MD¹, Ataru Taniguchi, MD², Yoshitaka Aiso, MD³, Toshimitsu Yatagai, MD¹, Tomoatsu Nakamura, MD¹, Yoshikatsu Nakai, MD⁴, Mitsuo Fukushima, MD⁵, Akira Kuroe, MD² and Shun Ishibashi, MD¹

¹ Division of Endocrinology and Metabolism, Jichi Medical School, Tochigi, Japan
² Division of Diabetes, Kansai-Denryoku Hospital, Osaka, Japan
³ Aiso Clinic, Tokyo, Japan
⁴ College of Medical Technology, Kyoto University, Kyoto, Japan
⁵ Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan

Address correspondence to Shoichiro Nagasaka, MD, Division of Endocrinology and Metabolism, Jichi Medical School, Yakushiji 3311-1, Minamikawachi, Tochigi 329-0498, Japan. E-mail: sngsk{at}jichi.ac.jp.

Sulfonylurea is known to lower glucose levels by stimulatingpancreatic insulin secretion. Glimepiride, a new agent of sulfonylurea,is unique in that the glucose-lowering efficacy is similar butthe ability to stimulate insulin secretion is lower in comparisonwith conventional sulfonylureas such as glibenclamide, glipizide,and gliclazide (1). Thus, glimepiride is hypothesized to havegreater extrapancreatic effect, such as an improvement in insulinresistance (1). The previous report by Muller et al. (1) supportsthe hypothesis that insulin-resistant diabetic KK-Ay mice canbe well controlled by glimepiride, but not by glibenclamideand gliclazide. Glimepiride is reported to increase insulin-stimulatedglycogen synthesis in cultured human skeletal muscle cells.Very recently, Tsunekawa et al. (2) clearly demonstrated thatglimepiride actually increases insulin sensitivity in type 2diabetic patients. They also proposed that the increase in insulinsensitivity might be associated with increased adiponectinemia.Here we report our data regarding the effects of glimepirideon insulinemia, insulin sensitivity, and serum adiponectin levelsin type 2 diabetic subjects. In addition, the effects of glimepirideare compared with those achieved by metformin, which has beenproven to have little effect on body weight during glycemiccontrol.

A total of 28 Japanese patients with type 2 diabetes (19 menand 9 women, aged 59 ± 2 years [mean ± SE], BMI26.5 ± 0.8 kg/m²) were investigated before and aftertreatment with glimepiride. The treatment duration was 3 months,and the daily dose of glimepiride was 1.9 ± 0.2 mg (range1.0–3.0). Changes in indices were analyzed by Wilcoxon’ssign-rank test. After the treatment, fasting plasma glucose(166 ± 7 vs. 147 ± 7 mg/dl, P = 0.009) and HbA_1c(7.9 ± 0.3 vs. 7.4 ± 0.2%, P = 0.006) levels fellsignificantly. Both fasting insulin (11.7 ± 1.5 vs. 9.4± 1.0 µU/ml, P = 0.007) and homeostasis model assessmentfor insulin resistance (HOMA-IR) (3) (5.0 ± 0.8 vs. 3.8± 0.6, P = 0.005) decreased, suggesting an ameliorationof insulin resistance. Serum adiponectin concentration, measuredby Linco RIA kits (St. Charles, MO), increased significantly(22.1 ± 2.7 vs. 28.5 ± 2.8 µg/ml, +29%,P = 0.015), whereas no significant change was observed in BMI(26.5 ± 0.9 vs. 26.5 ± 0.8 kg/m², P = 0.748).There was also no change in serum concentrations of total (214± 6 vs. 210 ± 6 mg/dl, P = 0.125) and HDL (54± 3 vs. 53 ± 3 mg/dl, P = 0.438) cholesterol andtriglyceride (123 ± 10 vs. 120 ± 10 mg/dl, P =0.387) before and after the treatment.

In a separate group of type 2 diabetic patients matched withthe glimepiride group for sex, age, BMI, glycemia, and insulinemia(seven men and five women, aged 58 ± 3 years, and BMI25.7 ± 0.7 kg/m²), the effect of metformin (daily dose750 mg) was evaluated. Three months of the metformin treatmentalso decreased both fasting glucose (159 ± 4 to 135 ±4 mg/dl, P = 0.006) and HbA_1c (7.9 ± 0.2 to 7.1 ±0.2%, P = 0.013) levels. In contrast to the glimepiride treatment,fasting insulin (12.4 ± 2.0 vs. 13.8 ± 4.3 µU/ml,P = 0.689) and HOMA-IR (4.8 ± 0.7 vs. 4.1 ± 1.0,P = 0.695) remained unchanged, whereas serum adiponectin concentrationwas increased slightly but significantly (18.7 ± 3.0vs. 20.6 ± 3.3 µg/ml, +10%, P = 0.034). No significantchange was observed in BMI and serum lipid concentrations (datanot shown).

Our present finding supports the notion that one of the glucose-loweringmechanisms of glimepiride is to improve insulin resistance.In accordance with a recent article (2), the glimepiride treatmentincreased serum adiponectin levels without affecting BMI. Inthe present study, serum adiponectin levels were also increasedby the treatment of metformin, which, unlike insulin-sensitizingthiazolidinediones, is known to not affect circulating adiponectinconcentration (4). Therefore, it seems possible that the increasein adiponectinemia by the glimepiride treatment could be, inpart, due to an effect of glycemic control per se. Another differencebetween the glimepiride and metformin groups is the change ininsulinemia; fasting insulin was decreased in the former groupand unchanged in the latter. Since insulin seems to suppressexpression and secretion of adiponectin in both in vitro andin vivo studies (5,6), the decrease in insulinemia by glimepiridemay conversely increase circulating adiponectin concentration.

We agree that the improvement in glycemic control, insulinemia,and adiponectinemia by glimepiride is of potential benefit todecrease risk factors of atherosclerosis in type 2 diabeticpatients. The mechanisms of the increased adiponectinemia byglimepiride may be complex and multifactorial. It also remainsto be elucidated whether conventional sulfonylureas would increaseadiponectinemia in subjects with type 2 diabetes.

References

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Tsunekawa T, Hayashi T, Suzuki Y, Matsui-Hirai H, Kano H, Fukatsu A, Nomura N, Miyazaki A, Iguchi A: Plasma adiponectin plays an important role in improving insulin resistance with glimepiride in elderly type 2 diabetic patients. Diabetes Care 26:285–289, 2003[Abstract/Free Full Text]
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