Glimepiride and Serum Adiponectin Level in Type 2 Diabetic Subjects: Response to Nagasaka et al.

We read with interest the article by Nagasaka et al. (1) reporting that glimepiride, a new agent of sulfonylurea, has an increasing effect on circulating adiponectin concentration, which may play a role in mediating insulin sensitivity. The authors demonstrated that serum adiponectin concentration increased significantly from 22.1 ± 2.7 to 28.5 ± 2.8 μg/ml after 3 months’ glimepiride treatment. However, their baseline level of serum adiponectin was markedly higher than that of the Japanese type 2 diabetic subjects reported by Tsunekawa et al. (2) (22.1 ± 2.7 vs. 6.61 ± 3.06 μg/ml) in spite of higher BMI (26.5 ± 0.9 vs. 21.2 ± 2.2 kg/m²) and greater homeostasis model assessment of insulin resistance (5.0 ± 0.8 vs. 2.54 ± 2.25), although both groups measured serum adiponectin levels with Linco radioimmunoassay kits (St. Charles, MO).

Recently, Hara et al. (3) reported the association between single nucleotide polymorphism (SNP) 276 of the adiponectin gene and plasma adiponectin levels, showing that the G allele at position 276 was linearly associated with lower plasma adiponectin levels (G/G: 10.4 ± 0.85 μg/ml; G/T: 13.7 ± 0.87 μg/ml; and T/T: 16.6 ± 2.24 μg/ml) in Japanese subjects with higher BMIs. Here, we measured serum adiponectin concentrations by human adiponectin enzyme-linked immunosorbent assay kits (Otsuka Pharmaceutical, Tokyo, Japan) in Japanese diabetic patients and investigated the influence of SNP 276 of the adiponectin gene. A total of 101 type 2 diabetic subjects (70 men and 31 women, aged 55.5 ± 8.7 years) were studied (data are means ± SD). Twenty-eight subjects (20 men and 8 women, aged 55.2 ± 6.5 years) had been treated with glimepiride (daily dosage 1.5 ± 0.6 mg) and 31 subjects (22 men and 9 women, aged 60.2 ± 6.3 years) with gliclazide (daily dosage 39.3 ± 18.4 mg) for >6 months. The remaining 42 subjects (28 men and 14 women, aged 51.4 ± 10.3 years) had been treated with diet therapy alone and without any hypoglycemic agents. BMI (glimepiride group: 24.6 ± 3.4 kg/m²; gliclazide group: 24.3 ± 3.1; and diet group: 24.5 ± 5.3), HbA_1c (glimepiride group: 7.2 ± 1.2%; gliclazide group: 6.7 ± 0.5; and diet group: 6.8 ± 1.4), homeostasis model assessment of insulin resistance (glimepiride group: 3.3 ± 2.3; gliclazide group: 2.5 ± 1.4; and diet group: 3.1 ± 2.0), and serum lipid levels (data not shown) were not significantly different among the groups. Serum adiponectin levels in subjects with glimepiride (5.34 ± 2.82 μg/ml) and gliclazide (5.38 ± 2.61 μg/ml) were significantly lower than that of the diet group (7.31 ± 4.87 μg/ml). The G allele frequency of SNP 276 of the adiponectin gene was 0.70. The serum adiponectin levels were not different among the genotypes at position 276 of the adiponectin gene (G/G, n = 54 [53.5%]: 6.43 ± 5.54 μg/ml; G/T, n = 34 [33.7%]: 6.31 ± 4.25 μg/ml; and T/T, n = 13 [12.8%]: 5.70 ± 2.00 μg/ml). After various treatments were started, SNP 276 of the adiponectin gene did not associate with significantly different serum adiponectin levels.

Again, the serum adiponectin levels after glimepiride therapy reported by Nagasaka et al. (1) were quite higher than our results. Although cautious interpretation of our results is necessary because the present study is cross-sectional and the number of subjects is small, multiple factors such as glycemic control per se, obesity (4), polymorphisms of the adiponectin gene (3), or peroxisome proliferator–activated receptor-γ2 gene (5) may affect serum adiponectin concentration. In addition, therapy with sulfonylureas, such as glimepiride (1) and gliclazide, is a possible affecting factor for serum adiponectin level. Prospective and large-scale studies are needed to clarify the interactions between environmental factors or therapeutic interventions and genetic factors on serum adiponectin concentrations.