The role of diminished beta cell reserve and insulin resistance in secondary sulfonylurea failure of type 2 diabetes mellitus.

INTRODUCTION: The correction of hyperglycemia by insulin treatment has been shown to ameliorate beta cell function and insulin sensitivity in SU failure patients, and there also appears to have disparity between tests of beta cell function among these patients. The objectives of this study were to determine beta cell secretory reserve and insulin resistance of secondary SU failure type 2 diabetic patients who had fairly good glycemic control compared with those who were SU responsive and the disparity of beta cell responses to glucose and non-glucose stimuli were examined in these two groups. SUBJECTS AND METHOD: Eight secondary SU failure, insulin-treated and 11 SU responsive type 2 diabetic patients who were matched for age, degree of obesity, duration of diabetes as well as HbAlc were studied. Intravenous glucagon and oral glucose tolerance tests (OGTT) as well as short intravenous insulin tolerance test using arterialized venous blood were randomly performed on separate occasions to assess beta cell secretory reserve and insulin sensitivity, respectively. RESULTS: Basal (0.37+/-0.05 (SEM) vs 0.80+/-0.14 nmol/l; p=0.02) and stimulated c-peptide levels (0.66+0.08 vs 1.16+/-0.14 nmol/l; p=0.007) after glucagon as well as basal (0.46+/-0.06 vs 0.73+/-0.10 nmol/l; p=0.046) and maximal c-peptide responses (1.41+/-0.14 vs 1.97+/-0.14 nmol/l; p=0.021) to glucose stimulation were significantly lower in SU failure than SU responsive patients. However, the incremental changes of c-peptide over basal after glucagon (0.29+/-0.06 vs 0.37+/-0.09 nmol/l) and glucose (AUC: 36.9+/-7.6 vs 47.9+/-4.5 nmol/l/h) were not different between both groups. There were strong positive relationships between basal and stimulated c-peptide responses to glucagon (r=0.818; p=0.002) and glucose (r=0.85; p=0.001) in SU responsive patients but these relationships were not as strong in SU failure patients (r=0.682; p=0.062 and r=0.41; p=NS, respectively). Insulin sensitivity did not differ between the two groups. CONCLUSION: This study demonstrated that decreased basal, but not stimulated, insulin secretion was possibly a major factor associated with secondary SU failure in type 2 diabetic patients. With comparable glycemic control, there was no disparate beta cell responses to glucose and glucagon in patients with or without secondary SU failure.

The utility of conventional dipsticks for urinary protein for screening of microalbuminuria in diabetic patients.

The demonstration that microalbuminuria is predictive of overt diabetic nephropathy has created a demand for the routine measurement of urinary albumin in diabetic patients. We assessed the sensitivity, specificity, positive and negative predictive values of the conventional dipsticks for urinary protein (Ames Multistix, Bayer Diagnostic, Australia) as the screening test for microalbuminuria in diabetic patients compared with Micral-Test II (Boehringer Mannheim, Germany). Radioimmunoassay for albumin was taken as standard for comparison. With the urinary albumin concentration of 20 mg/L as a discriminating level of microalbuminuria, Micral-Test II had a sensitivity of 98.8 per cent and a specificity of 68.6 per cent whereas Ames Multistix had lower sensitivity but higher specificity. If urinary albumin concentration of 60 mg/L was used instead as a discriminating level of microalbuminuria, none of Ames Multistix by visual reading and only 5 of 32 (15.6%) of those by reflectance photometer had false negative results. By visual reading, the sensitivity of Ames Multistix was increased from 68.1 to 100 per cent with the drop in specificity from 85.7 to 50.2 per cent. On the other hand, the sensitivity was increased from 37.4 to 84.4 per cent but the specificity was maintained if reflectance photometer was used. In conclusion, Ames Multistix was less sensitive than Micral-Test II in detection of urinary albumin concentration above 20 mg/L. At higher urinary albumin concentration above 60 mg/L which indicates a clinically significant microalbuminuria, the sensitivity of Ames Multistix was increased to 100 per cent. Ames Multistix which is much less expensive than Micral-Test II, can be used as the screening test for significant microalbuminuria in clinical practice particularly in cases having financial problems.

Effect of acarbose in treatment of type II diabetes mellitus: a double-blind, crossover, placebo-controlled trial.

This study evaluated the efficacy of acarbose in improvement of metabolic control in patients with fairly, well controlled non-insulin-dependent diabetes mellitus (NIDDM). Fifteen patients with mean age and duration of diabetes of 57.5 +/- 2.6 (SE) and 7.5 +/- 1.5 years, respectively were recruited and completed our study protocol. This study was a double-blind, crossover, placebo-controlled design consisting of two twelve-week treatments of acarbose and placebo separated by an eight-week washout period. Acarbose was effective in lowering of 1-hour and 2-hour postprandial plasma glucose from 251.7 +/- 10.7 and 205.3 +/- 9.1 mg/dl to 197.4 +/- 7.0 (p = 0.001) and 181.5 +/- 8.5 mg/dl (p = 0.03), respectively. Fasting plasma glucose was slightly decreased but without significant change, from 150.8 +/- 7.3 to 140.8 +/- 6.1 mg/dl (p = 0.07). Overall glycemic control tended to improve during the study period as indicated by the falling of HbA1c levels from 7.7 +/- 0.4 to 7.0 +/- 0.2 per cent (p = 0.05). Serum C-peptide both fasting and postprandial as well as serum lipids were not affected by acarbose. Almost half of the patients treated with acarbose had mild and tolerable gastrointestinal adverse effects. In conclusion, acarbose, as combined therapy with other oral hypoglycemic agents, was effective in improvement of glycemic control particularly postprandial hyperglycemia in fairly, well controlled NIDDM patients with mild and acceptable adverse effects.

Effect of pravastatin in treatment of hypercholesterolemia in non-insulin-dependent diabetes patients.

To evaluate the efficacy of pravastatin in treatment of hypercholesterolemia in non-insulin-dependent diabetes patients, a 6-month trial of once daily 10 mg-pravastatin was studied in 30 patients with fairly, well controlled non-insulin-dependent diabetes mellitus. For 27 patients who completed the study, serum total cholesterol and low-density lipoprotein cholesterol were significantly lower 16.7 +/- 2.3 and 20.2 +/- 3.3% from 286.7 +/- 5.9 and 198.6 +/- 7.2 mg/dl at before to 232.6 +/- 7.9 and 147.8 +/- 6.4 mg/dl at 4th week and 237.8 +/- 6.4 and 155.0 +/- 5.8 mg/dl at 24th week after treatment with pravastatin, respectively (P < 0.00001). Serum triglyceride level was decreased from 194.7 +/- 16.8 mg/dl to 175.0 +/- 16.8 mg/dl at 4th week and 176.6 +/- 14.1 mg/dl at 24th week and serum high-density lipoprotein cholesterol level was slightly increased from 45.4 +/- 2.8 mg/dl to 48.2 +/- 2.5 mg/dl at 4th week and 47.5 +/- 2.6 mg/dl at 24th week of pravastatin treatment, respectively (P > 0.05). There was no serious adverse effect except acute hepatitis in one patient who recovered spontaneously after drug withdrawal. Once daily 10 mg-pravastatin in effective in the treatment of hypercholesterolemia in patients with non-insulin-dependent diabetes mellitus.

Thyroid function test in patient with acute-severe-nonthyroidal illnesses.

Patients with acute-severe-nonthyroidal illnesses had FT4 and T3 values below the normal range with the magnitude of change greater for T3 than FT4. Some patients had depressed and some had elevated TSH values. In the recovery phase, FT4 levels appeared to rise before T3 levels and TSH exhibited an exaggerated increase. These results are consistent with other studies which suggest that dysfunction of the hypothalamic-pituitary-thyroid axis may be associated with anomalous results for thyroid function test parameters in patients with acute-severe-nonthyroidal illnesses. This anomaly should be given due consideration when interpreting results of thyroid function test parameters in such patients.