Serum high-molecular weight adiponectin decreases abruptly after an oral glucose load in subjects with normal glucose tolerance or impaired fasting glucose, but not those with impaired glucose tolerance or diabetes mellitus.

Adiponectin exists in the blood as 3 forms, which are a trimer, a hexamer, and a high-molecular weight (HMW) form. We investigated whether circulating HMW adiponectin levels were altered by oral glucose or fat ingestion. Forty male subjects underwent a 75-g oral glucose loading test (OGTT), and 11 healthy subjects (5 women and 6 men) received a fat loading test. Serum levels of HMW and total adiponectin were measured during the OGTT and the fat loading test. The fat loading test was performed for at least 8 hours. Among the 40 male subjects, 11 had normal glucose tolerance (NGT), 9 had impaired fasting glucose (IFG), 11 had impaired glucose tolerance, and 9 had diabetes mellitus (DM). In all 40 subjects, the serum total adiponectin level did not change significantly, whereas serum HMW adiponectin decreased significantly after a glucose load and reached 92.2% of the basal level at 120 minutes after the OGTT (P < .01). The HMW to total adiponectin ratio decreased significantly from 0.47 +/- 0.15 at baseline to 0.43 +/- 0.13 at 120 minutes after a glucose load (P < .05). Serum HMW adiponectin measured at 120 minutes after the OGTT decreased significantly to 86.0% and 85.6% of the basal level in subjects with NGT or IFG, respectively (both P < .01). In subjects with impaired glucose tolerance or DM, however, serum HMW adiponectin did not change. The area under the curve for insulin at 30 minutes after a glucose load during the OGTT was significantly larger in subjects with NGT or IFG than in those with DM (P < .05). In addition, the insulinogenic index (DeltaI(0-30)/DeltaG(0-30)) was significantly higher in subjects with NGT or IFG than in those with DM (P < .001). Percentage changes in serum HMW adiponectin of the baseline at 120 minutes correlated negatively with those in serum insulin (r = -0.468, P = .0023), but not plasma glucose, of the baseline at 30 minutes in 40 subjects. On the other hand, serum triglycerides increased significantly after an oral fat load in 11 healthy subjects; but neither serum total nor HMW adiponectin changed. In conclusion, serum HMW adiponectin (but not total adiponectin) decreased rapidly after glucose loading in subjects with NGT or IFG; and the decrease of HMW adiponectin may be associated with an increase of serum insulin at 30 minutes.

Low-dose pioglitazone increases serum high molecular weight adiponectin and improves glycemic control in Japanese patients with poorly controlled type 2 diabetes.

We investigated the effects of low-dose pioglitazone (7.5mg/day) on serum high molecular weight (HMW) adiponectin and fluid retention (estimated from hematocrit) in 14 male and 16 female patients with type 2 diabetes. All of them were being treated with sulfonylureas and had poor glycemic control. Patients were given 7.5 mg/day of pioglitazone and were followed for 12 weeks at monthly intervals. In all 30 patients, HbA1c was significantly decreased after 12 weeks of treatment with pioglitazone (8.2+/-0.7% vs. 7.4+/-0.8%, P<0.0001). Serum HMW adiponectin increased markedly from 5.2 (2.4, 8.6) microg/ml at baseline to 9.8 (4.1, 12.6) microg/ml at the end of pioglitazone treatment (P<0.0001). When the changes were evaluated separately for each sex, diabetic men showed no increase of body weight or BMI after treatment, while HbA1c decreased significantly, and did Hct. Serum HMW adiponectin increased significantly after treatment. In diabetic women, neither body weight nor BMI increased after treatment with pioglitazone, as was the case for the men. HbA1c decreased significantly, and did Hct. Serum HMW adiponectin increased significantly after treatment. In conclusion, low-dose pioglitazone therapy could significantly improved glycemic control and markedly increased serum HMW adiponectin in both male and female Japanese patients with type 2 diabetes.