Glimepiride in type 2 diabetes mellitus Thai patients.

This study aimed to confirm the efficacy of glimepiride given once daily in the treatment of Thai type 2 diabetic patients and to find out the optimum dosage for Thai patients. The patients were enrolled at the diabetic clinics of 5 hospitals (Rajavithi, Chulalongkorn, Pramongkutklao, Siriraj and Theptarin Hospitals). All patients started glimepiride 1 mg once daily and escalated to 2, 3, 4 and until 6 mg every 4 weeks if fasting plasma glucose (FPG) exceeded 140 mg/dL. Subjects were 60 females and 29 males with an average age of 52.2 +/- 10.0 years. Mean BMI was 25.5 +/- 3.8 kg/m2. Fifty seven patients (64.0%) were drug naïve and thirty two patients (36.0%) had been previously treated with oral hypoglycemic agents. Seventy three per cent of the drug naïve and 37 per cent of the previously treated patients could be controlled with 1-2 mg of glimepiride once daily. At the twelfth week of treatment, mean fasting plasma glucose decreased from 224.6 to 156.6 mg/dL (30% reduction) and mean HbA1c decreased from 10.0 to 7.5 per cent (25% reduction). At the end of the study 49.4 per cent of the patients had HbA1c < 7.0 per cent, 21.3 per cent had HbA1c 7.0-8.0 per cent and 29.3 per cent had HbA1c > 8.0 per cent. Adverse events that were probably or possibly related to the drug were reported in 5 patients (5.6%). Three of them were hypoglycemia and two patients had skin rash. All hypoglycemic episodes were mild. Glimepiride was indicated to be safe. There were no clinically significant changes in clinical laboratory values, physical examinations and vital signs. In conclusion, glimepiride was efficacious and safe in type 2 diabetes Thai patients and 1-2 mg of glimepiride appeared to be a sufficient dose for most newly diagnosed type 2 diabetic patients.

Heart rate/stroke volume relationship during upright exercise in long-term diabetics.

The changes in stroke volume (SV) during upright exercise were studied in 20 insulin-dependent diabetics (IDDM) and 20 age- and sex-matched controls. None of the diabetics had any cardiovascular symptoms. In addition, tests of autonomic function were conducted in the diabetics, assessing changes in heart rate (HR) during deep breathing and the Valsalva maneuver. During exercise the SV in the controls gradually increased and then remained essentially unchanged until maximum HR was achieved. Seven of the diabetics failed to sustain an initial increase in SV (fall > 15%), eight showed a "delayed" increase in SV, and the remaining five demonstrated an increasing SV over the range from rest to peak exercise. Abnormal autonomic function results were found during deep breathing (four diabetics) and the Valsalva maneuver (four diabetics). Findings indicate that cardiac function could be abnormal in IDDM without evidence of autonomic dysfunction. This abnormality could be due to a specific cardiomyopathy.

Insulin action is altered in hyperthyroidism.

We have assessed insulin action in five hyperthyroid patients, pre- and post-radioactive iodine therapy using oral glucose tolerance tests, monocyte insulin binding and dose response curves generated with the euglycemic clamp technique. All patients had become euthyroid after radioactive iodine therapy with a decline in the plasma free T4 index level from 278 +/- 43 to 105 +/- 9. Fasting glucose was modestly, but significantly elevated in the thyrotoxic patients compared to when they were rendered euthyroid (p less than 0.05). Oral glucose tolerance tests showed no difference in either glucose or insulin values after the glucose load. Insulin receptor binding and affinity were similar regardless of their thyroid status. Hepatic glucose production in the basal state was elevated in the thyrotoxic patients, 61 +/- 5 mg/M2/min vs 49 +/- 3 mg/M2/min (p less than 0.05). At the lowest level of insulin infusion no difference in glucose disposal was found. At maximum insulin concentrations the glucose disposal rate was enhanced in the thyrotoxic patients, 686 +/- 19 vs 567 +/- 26 mg/M2/min (p less than 0.01). These results indicate that higher fasting glucose levels may result from increased hepatic glucose production in thyrotoxicosis, but as indicated by the oral glucose tolerance tests, this defect in insulin action is usually of minor significance. However, insulin responsiveness measured at pharmacological insulin levels is augmented in thyrotoxicosis.

Assessment of value of glycosylated albumin and protein in detection of gestational diabetes.

There is a recognized need for the early detection of gestational diabetes, and a single blood test, if reliable, would be advantageous. Because serum albumin and total protein are glycosylated and have short life spans, we investigated the usefulness of glycosylated albumin and glycosylated protein in the detection of gestational diabetes. We studied five groups, each with 20 subjects: nonpregnant and pregnant controls, nonpregnant and pregnant insulin-dependent diabetic (IDDM) patients, and gestational diabetic patients. All patients with no history of diabetes had an oral glucose tolerance test to define their carbohydrate status. Our results showed that percent glycosylated albumin and percent glycosylated protein were significantly elevated in both groups of IDDM patients compared with the other groups. However, gestational diabetic patients had glycosylated albumin and glycosylated protein values similar to those of both control groups. Both glycosylated albumin and glycosylated protein correlated well with HbA1c determinations. Thus, glycosylated albumin and glycosylated protein may be a good index of glycemic control, but they are of little value in the diagnosis of gestational diabetes because of a lack of sensitivity: 8 and 3% for glycosylated albumin and glycosylated protein, respectively.

Insulin action does not change during the menstrual cycle in normal women.

Normal women have alterations in carbohydrate metabolism during pregnancy and when taking oral contraceptives, and clinical observations suggest that diabetic women need more insulin during menstruation. We, therefore, studied insulin action in normal women during the menstrual cycle in the follicular, luteal, and menstrual phases. Glucose tolerance was similar at all three times. Specific insulin receptor binding to monocytes did not change during the menstrual cycle. Euglycemic insulin clamp studies at four different insulin infusion rates (15, 40, 120, and 240 mU/M2 X min) showed no differences in insulin sensitivity or responsiveness throughout the menstrual cycle, and hepatic glucose output did not change. These studies suggest that if insulin action is impaired during menstruation in diabetic women it is because of factors that are not detected in normal women.