Improved Glycemic Control and Lipid Profile in a Randomized Study of Pioglitazone Compared with Acarbose in Patients with Type 2 Diabetes Mellitus

Objective: To assess the efficacy of pioglitazone treatment in comparison with that of acarbose treatment in patients with type 2 diabetes mellitus. Participants and methods: In this randomized, parallel-group, open-label study patients were assigned to treatment with either pioglitazone (n = 129) or acarbose (n = 136). During a 1-week run-in patients commenced an individualized dietary regimen which was maintained throughout the study. Patients received the assigned study medication for 26 weeks. Serum glycosylated hemoglobin (HbA_1c) levels, insulin resistance and lipid profiles were determined at baseline and at endpoint. Results: Mean HbA_1c was reduced from 8.98 ± 1.20% to 7.82 ± 1.95% with pioglitazone treatment and from 9.03 ± 1.32% to 8.55 ± 1.96% with acarbose treatment during the 26-week study. The change from baseline to endpoint was significantly greater for pioglitazone compared with acarbose when analyzed for all patients (p < 0.001) and for those who had (p = 0.009) or had not (p < 0.001) received previous medication for diabetes mellitus. Compared with acarbose, pioglitazone produced a significantly greater decrease in fasting glucose, insulin and insulin resistance (p < 0.001 for each). Triglycerides were decreased by 71.1 ± 184.1 mg/dl with pioglitazone compared with 38.1 ± 171.3 mg/dl with acarbose (p = 0.001 for difference between groups). High density lipoprotein (HDL)-cholesterol level was increased by 7.8 ± 10.2 mg/dl with pioglitazone compared with a decrease of 0.8 ± 24.1 mg/dl with acarbose (p < 0.001). While serum low density lipoprotein (LDL)-cholesterol levels remained unchanged with both treatment regimens, the decrease from baseline in very low density lipoprotein (VLDL)-cholesterol was significantly greater with pioglitazone than with acarbose (p < 0.04). Pioglitazone decreased systolic blood pressure by 5.6 ± 17.7mm Hg compared with a 0.4 ± 18.4mm Hg increase during acarbose treatment (p < 0.001). Pioglitazone caused a significantly greater decrease compared with acarbose in serum levels of γ-glutamyl aminotransferase (p < 0.001) and alanine aminotransferase (p = 0.004). Conclusions: Six months of pioglitazone treatment decreased insulin resistance and improved glycemic control to a significantly greater extent than acarbose treatment. Pioglitazone was also associated with a significantly improved lipid profile, suggesting a reduction in risk of coronary heart disease.     

Effect of acarbose on platelet-derived microparticles, soluble selectins, and adiponectin in diabetic patients

Platelet-derived microparticles (PDMP), selectins, and adiponectin play an important role in the development of atherosclerosis in diabetes. Acarbose has been shown to have a beneficial effect on postprandial hyperglycemia in diabetic patients. However, its influence on PDMP, selectins, and adiponectin in these patients is poorly understood. We investigated the effect of acarbose on circulating levels of PDMP, selectins, and adiponectin in patients with type 2 diabetes. Acarbose (300 mg/day) was administered for 3 months. Levels of PDMP, sP-selectin, sL-selectin, and adiponectin were measured by ELISA at baseline and after 1 and 3 months of treatment. The levels of PDMP, sP-selectin, and sL-selectin were higher in diabetic patients than in hypertensive patients (PDMP; 35.1 ± 34.2 vs. 53.3 ± 56.7 U/ml, P < 0.05: sP-selectin; 134 ± 52 vs. 235 ± 70 ng/dl, P < 0.01: sL-selectin; 569 ± 183 vs. 805 ± 146 ng/ml, P < 0.05), while there were no significant differences between hypertensive and hyperlipidemic patients. Before acarbose treatment, the adiponectin level of diabetic patients was lower than that of hypertensive patients. Acarbose therapy significantly decreased the plasma PDMP level relative to baseline. Acarbose also caused a significant decrease of sP-selectin and sL-selectin. On the other hand, acarbose therapy led to a significant increase of adiponectin after 3 months of administration compared with baseline (adiponectin: diabetes versus hypertension, 3.61 ± 1.23 vs. 5.87 ± 1.92 μg/ml, P < 0.05; diabetes versus controls, 2.81 ± 0.95 vs. 6.13 ± 1.24 μg/ml, P < 0.01). Twelve of the 30 diabetic patients had a history of thrombotic complications. Furthermore, the reduction of PDMP and selectins during acarbose therapy was significantly greater in the thrombotic group (12 of 30) than in the nonthrombotic group (18 of 30) of diabetic patients. Acarbose may be beneficial for primary prevention of atherothrombosis in patients with type 2 diabetes. However, it requires a large clinical trial to test this hypothesis.     

Effects of combination of insulin and acarbose compared with insulin and gliclazide in type 2 diabetic patients

In this prospective study we aimed to compare insulin plus acarbose with insulin plus gliclazide with respect to their effect on insulin requirement, lipid profiles and body mass index (BMI) while achieving good glycemic control. Forty patients with type 2 diabetes mellitus who were on conventional insulin therapy (subcutaneous insulin therapy consisting of regular and NPH insulin, two times a day) were included in the study. They were randomized to double blind treatment with insulin in combination with gliclazide or acarbose for 6 months. For both groups, acceptable glycemic control was achieved at the end of study period. The mean HbA_1c levels decreased from 8.32±0.26 to 7.13±0.18% in acarbose group and 8.6±0.15 to 7.48±0.21% in the gliclazide group. The difference between groups was not significant (P 0.29). In the acarbose group, total cholesterol and LDL concentration decreased significantly while other parameters did not change. In the gliclazide group, HDL levels decreased significantly from 46.6±2.48 mg/dl to 41.3±2.09 mg/dl (P 0.001) BMI increased significantly from 27.60±1.21 kg/m² to 28.69±1.26 kg/m². (P 0.003) Total daily insulin dose was not changed in the acarbose group significantly, but increased from 42.6±2.73 to 49.27±3.58 U/day, which was significant in gliclazide group of (P 0.016). In the acarbose group, there were no significant differences between responders and nonresponders with respect to fasting and stimulated C-peptide, HbA_1c levels and baseline BMI values. But in the gliclazide group, baseline BMI values were significantly higher in the nonresponding group compared to responders (P 0.02). In conclusion, combination of insulin with acarbose can be a good alternative for type 2 diabetic patients on insulin therapy; seems more beneficial than combination with gliclazide; may have advantage of achieving good glycemic control without increasing insulin dose and BMI; also may have the advantage of providing a decrease in LDL level, which are all important to prevent atherosclerosis. Received: 29 January 1999 / Accepted in revised form: 19 May 1999     

Efficacy and safety of voglibose in comparison with acarbose in type 2 diabetic patients.

We performed a randomized crossover open comparative study to evaluate the efficacy and safety of voglibose and acarbose in 30 patients with type 2 diabetes who were not well controlled with diet therapy. There was no significant reduction of FBG with either voglibose or acarbose at 4 and 8 weeks after treatment. The 1 h postprandial blood glucose (PPBG) level was significantly decreased from 224.9+/-42.8 to 204.1+/-37.6 (P=0.005) and 206.1+/-38.9 mg/dl (P=0.038) after voglibose therapy at 4 and 8 weeks, respectively. Significant decrease was also obtained after acarbose treatment from 228.3+/-37.4 to 182.7+/-35.5 (P<0.001) and 186.6+/-36.1 mg/dl (P<0.001). The decrease of 1 h PPBG was associated with a significant fall of serum insulin concentration. HbA(1c) levels were also significantly decreased from 7.07+/-1.21 to 6.83+/-1.11 (P=0.017) and 6.79+/-1.33% (P=0.036) after voglibose and 6.98+/-0.98 to 6.70+/-1.04 (P<0.001) and 6.59+/-1.04% (P<0.001) after acarbose at 4 and 8 weeks. In contrast to voglibose, treatment with acarbose significantly decreased the 2 h PPBG at 4 and 8 weeks and the 2 h postprandial serum insulin concentration at 8 weeks. Adverse drug events were more commonly reported in acarbose-treated patients (P<0.05). Increased flatulence was observed in 56.7 and 90% of the patients taking voglibose and acarbose, respectively, while abdominal distention was noted in 10 and 16.7%. Significantly decreased body weights of 0.9 and 0.8 kg were recorded at 8 weeks after voglibose and acarbose therapy, respectively. We conclude that both voglibose (0.2 mg) and acarbose (100 mg) thrice daily significantly decreased HbA(1c), PPBG and postprandial insulin levels. At these dose levels, voglibose was associated with less gastrointestinal side effects and slightly less efficacy for postprandial glucose reduction.     

Hyperlipidemia in Iranian liver transplant recipients: prevalence and risk factors

Background Hyperlipidemia is a metabolic complication after liver transplantation (LT). The aim of this study was to investigate the prevalence and risk factors for developing hyperlipidemia in patients who underwent LT in the Shiraz Organ Transplantation Center. Methods Our patients were 170 liver recipients who underwent LT from 1994 to 2006 in the Organ Transplantation Center of the Shiraz University of Medical Sciences. To perform this study we administered questionnaires, including information about age, sex, body mass index (BMI), underlying liver disease, graft type, immunosuppressive medications, and serum levels of triglycerides and cholesterol, before and 6 months after LT. Serum triglyceride and cholesterol levels were considered elevated if they were >150 mg/dl and >250 mg/dl, respectively. Data were analyzed with SPSS software. Results There were 108 male and 62 female patients, with a mean age of 31.4 ± 13.3 years, and the mean duration of follow-up was 25.9 ± 23.5 months. The average pretransplant serum triglyceride and cholesterol (mean of individual means) levels were 104.6 ± 73.2 and 109.5 ± 51.5 mg/dl, respectively, and the average posttransplant levels were 230.1 ± 131 and 185 ± 77 mg/dl, respectively. Six months after LT, 119 (70%) and 26 (15.3%) patients developed hypertriglyceridemia and hypercholesterolemia, respectively. Age, sex, BMI, and underlying liver disease were not predictors of hypertriglyceridemia or hypercholesterolemia (P > 0.05). Posttransplant hypertriglyceridemia was significantly more common in patients receiving tacrolimus than in those receiving cyclosporine (P = 0.040), but posttransplant hypercholesterolemia had no significant correlation with type of immune suppression (P > 0.05). Conclusions Hyperlipidemia was common after LT, and hypertriglyceridemia was more common than hypercholesterolemia. Among all risk factors, tacrolimus therapy was correlated with development of hypertriglyceridemia after LT.     

Long-Term Effects of Intestinal Alpha-Glucosidase Inhibition on Postprandial Glucose,Pancreatic and Gut Hormone Responses and Fasting Serum Lipids in Diabetics on Sulphonylureas

Seventeen non-insulin-dependent diabetics poorly controlled by diet and sulphonylurea drugs took part in a long-term (20–52 weeks) trial of the effect of an alpha-glucosidase inhibitor (acarbose 100 mg thrice daily) on postprandial glycaemic and gastro-entero-pancreatic hormone responses. Patients were assessed before, during, and after the trial period with identical 2.2 MJ mixed test meals plus placebo or acarbose 100 mg, and sulphonylurea therapy was continued throughout. Acarbose administration reduced the integrated postprandial plasma responses of glucose to 58 ± 10% (mean ± SEM, p < 0.001), insulin to 61 ± 10% (p < 0.01) and gastric inhibitory polypeptide to 45 ± 8% (p < 0.001) of control values, increased the enteroglucagon response to 152 ± 26% (p < 0.001) of control and slightly prolonged the postprandial release of motilin. Recorded glycosuria was significantly (p < 0.01) reduced throughout the treatment period. The effects of acarbose on postprandial glycaemic and endocrine responses remained approximately constant throughout the trial period, and responses returned to pre-treatment values within 2 days of stopping treatment.     

Comparison of vildagliptin and acarbose monotherapy in patients with Type 2 diabetes: a 24-week,double-blind,randomized trial

Aims To compare the efficacy and tolerability of the dipeptidyl peptidase-4 inhibitor, vildagliptin, with the alpha glucosidase inhibitor, acarbose, in drug-naive patients with Type 2 diabetes. Methods This multi-centre, randomized, double-blind, parallel-arm study compared the efficacy and tolerability of vildagliptin (100 mg daily, given as 50 mg twice daily, n = 441) and acarbose (up to 300 mg daily, given as three equally divided doses, n = 220) during 24-week treatment in drug-naive patients with Type 2 diabetes. Results Monotherapy with vildagliptin or acarbose decreased glycated haemoglobin (HbA_1c) (baseline ≈ 8.6%) to a similar extent during 24-week treatment. The adjusted mean change from baseline to end-point (AMΔ) in HbA_1c was −1.4 ± 0.1% and −1.3 ± 0.1% in patients receiving vildagliptin and acarbose, respectively, meeting the statistical criterion for non-inferiority (upper limit of 95% confidence interval for between-treatment difference ≤ 0.4%). The decrease in fasting plasma glucose was similar with acarbose (−1.5 ± 0.2 mmol/l) and vildagliptin (−1.2 ± 0.1 mmol/l). Body weight did not change in vildagliptin-treated patients (−0.4 ± 0.1 kg) but decreased in acarbose-treated patients (−1.7 ± 0.2 kg, P < 0.001 vs. vildagliptin). The proportion of patients experiencing any adverse event (AE) was 35% vs. 51% in patients receiving vildagliptin or acarbose, respectively; gastrointestinal AEs were significantly more frequent with acarbose (25.5%) than vildagliptin (12.3%, P < 0.001). No hypoglycaemia was reported for either group. Conclusions Vildagliptin is effective and well tolerated in patients with Type 2 diabetes, demonstrating similar glycaemic reductions to acarbose, but with better tolerability.     

Outpatient treatment of juvenile-onset diabetes with a preprogrammed portable subcutaneous insulin infusion system

Seven patients with juvenile-onset, insulin-dependent diabetes (aged 13 to 32 years) were continuously treated for 12 to 32 weeks while out of the hospital in their usual environment with a portable, batterypowered infusion pump which delivers insulin subcutaneously in basal (between-meal) doses with pulse dose increments before meals. Mean blood glucose levels (237 ± 28 mg/dl during conventional insulin therapy) fell to 105 ± 5 mg/dl after four weeks of pump treatment (p < 0.01) and were maintained at 80 to 104 mg/dl as pump treatment was continued beyond eight weeks. Glycosylated hemoglobin levels (16.0 ± 1.5 per cent before pump therapy) also fell within two weeks (p < 0.01) reaching normal values (9.9 ± 0.3) after eight weeks of pump therapy. Mean plasma cholesterol and triglyceride levels were elevated during conventional therapy and fell to normal after pump treatment. After the first month of pump treatment, only minor adjustments in insulin dose (< 5 per cent of total daily dose) were made. No episode of mechanical pump failure occurred during the 1,110 patient-days of treatment. Overinsulinization and underinsulinization due to human error were relatively rare (four and six episodes, respectively) and failed to result in symptoms of hypo- or hyperglycemia. All patients performed their usual home, work or school activities during pump treatment. We conclude that normalization or near normalization of blood glucose levels can be achieved with a portable subcutaneous insulin infusion system when continuously used to treat patients with juvenile-onset, insulindependent diabetes outside the hospital for three to eight months.     

A randomized controlled trial of acarbose in hepatic encephalopathy.

BACKGROUND & AIMS: Hepatic encephalopathy in cirrhosis is contributed to by toxic products deriving from the proteolytic bacterial flora-related degradation of dietary nitrogen substances. Acarbose is a novel hypoglycemic agent acting through the inhibition of glucose absorption in the gut and the promotion of intestinal saccharolytic bacterial flora at the expense of proteolytic flora. We assessed whether acarbose exerts a beneficial effect on hepatic encephalopathy and on postprandial hyperglycemia in cirrhotic patients with low-grade hepatic encephalopathy and type 2 diabetes mellitus. METHODS: One hundred seven cirrhotic patients with grade 1-2 hepatic encephalopathy and type 2 diabetes mellitus were randomized to acarbose 100 mg 3 times daily or placebo for 8 weeks; after a 2-week washout period, treatments were switched, and patients were followed for 8 more weeks. Ammonia blood levels, Reitan's number connection test, intellectual function, fasting and postprandial glucose levels, glycated hemoglobin values, and C peptide values were determined 2 weeks before and 4, 8, 11, 14, and 18 weeks after treatment. RESULTS: (1) Acarbose significantly decreased ammonia blood levels and improved Reitan's test score and intellectual function score compared with placebo (P < .01). (2) Acarbose caused a 33% decrease in fasting glucose level and an approximately 50% decrease in postprandial glucose level compared with placebo (P < .01). (3) Acarbose significantly lowered glycated hemoglobin values and postprandial C peptide compared with baseline values, whereas placebo did not. (4) No change in biochemical parameters of liver function was observed after acarbose treatment. CONCLUSIONS: Acarbose is a safe and effective drug in cirrhotic patients with low-grade hepatic encephalopathy and type 2 diabetes mellitus.     

Plasma homocysteine status in patients with ankylosing spondylitis

Homocysteine (Hcy), a sulfur-containing amino acid, is eliminated through B vitamins-dependent pathways. Hyperhomocysteinemia has been found to be an independent risk factor for atherosclerotic cardiovascular, cerebrovascular, and peripheral vascular diseases. Recently, psoriasis, lupus, and rheumatoid arthritis were reported to be associated with hyperhomocysteinemia. This study was aimed to evaluate the changes of plasma Hcy level before and after sulfasalazine and MTX therapy in patients with ankylosing spondylitis (AS). One hundred and two patients with AS and ten normal controls were enrolled in the cross-sectional case-control study. Fasting plasma Hcy levels were determined by ELISA kits (IMX, Abbott). Hcy levels were compared to their Bath AS disease activity index (BASDAI) and the usage of sulfasalazine and/or MTX. Active disease was defined by BASDAI as more than 3 in a 10-cm scale with ESR >20 mm/h. For those patients with plasma Hcy ≥15 μmol/l, a perspective trial of daily supplement of vitamin B-12 0.5 mg, B-6 50 mg, and folic acid 5 mg for 2 weeks were also tested for the efficacy. Plasma Hcy level increased significantly in AS patients under sulfasalazine (10.4±3.8 μmol/l, p<0.05), MTX (11.9±4.7, p<0.05) and sulfasalazine/MTX combination treatment (11.2±2.6, p<0.05) compared with normal controls (8.6±1.2 μmol/l) and AS patients without DMARD(9.4± 2.6μmol/l). No correlation between disease activity and plasma Hcy level was found. Daily supplement of vitamin B-12 0.5 mg, B-6 50 mg, and folic acid 5 mg can lower Hcy level in 2 weeks (32.3±24.0 vs 15.6±11.1 μmol/l, p=0.007). Plasma homocysteine level did significantly increase in AS patients under sulfasalazine or MTX treatment. B-vitamins should be considered as a routine supplementation for patients who underwent sulfasalazine and/or MTX treatment. Further longitudinal studies are required to confirm the conclusions.     

Serum ferritin and transferrin saturation in patients with chronic alcoholic and non-alcoholic liver diseases

Abstract. Objectives. To compare serum ferritin concentration and transferrin saturation in patients with alcoholic and non-alcoholic chronic liver diseases. Design. Concecutive patients with liver diseases. Setting. The department of internal medicine in a teaching hospital. Subjects. Three hundred and twelve patients with different liver diseases concecutively admitted between 1987 and 1992. Interventions. None. Main outcome measures. Fasting serum iron, transferrin and ferritin. Results. Serum ferritin was increased above 200 μg L^?1 in all 18 patients with haemochromatosis (range 310–6500 μg L^?1), in 64 of 111 alcoholics (58%) and in 30 of 137 (22%) with chronic non-alcoholic liver diseases (P < 0.01). Twelve of 111 alcoholics (11%) had serum ferritin above 1000 μg L^?1 compared with one of 137 (0.7%) with chronic non-alcoholic liver diseases. In 13 alcoholics who abstained after admission, serum ferritin decreased from 1483 μg L¹ ± 1134 to 388 μg L^?1 ± 237 (P < 0.001) after 1 1/2 to 6 weeks. The transferrin saturation was increased above 62% in 13 of 18 patients (72%) with haemochromatosis, in 16 of 105 alcoholics (15.2%) and in three of 132 (2.3%) with chronic non-alcoholic liver disease (P < 0.01). Conclusion. Serum ferritin is more frequently elevated in abusing patients with alcoholic liver disease than in patients with other chronic liver diseases such as autoimmune liver diseases and hepatitis C. Because serum ferritin decreases rapidly during abstinence, the measurement of ferritin for the detection of haemochromatosis in patients abusing alcohol should be postponed until the patients are abstaining. Most of the patients with increased serum ferritin have normal transferrin saturation values which can be used to separate them from haemochromatosis.     

Impact of non‐alcoholic fatty liver disease on microalbuminuria in patients with prediabetes and diabetes

Background: It is unknown whether microalbuminuria is associated with non‐alcoholic fatty liver disease (NAFLD) among patients with prediabetes and type 2 diabetes mellitus (DM). This study investigated the association of NAFLD with microalbuminuria among patients with prediabetes and diabetes. Methods: We evaluated 1361 subjects who had an abnormal oral glucose tolerance test (OGTT) on routine screening. All participants were divided into two groups, prediabetes and newly diagnosed type 2 DM, and the association of NAFLD with metabolic parameters on microalbuminuria was analysed. Results: The patients with NAFLD had higher prevalence rates of microalbuminuria (6.3% vs 19%; P= 0.001 in prediabetes, 4.5% vs 32.6%; P < 0.001 in diabetes) and also had a greater albumin‐to‐creatinine ratio (14.6 ± 52.0 µg/mg Cr vs 27.7 ± 63.9 µg/mg Cr; P= 0.051 in prediabetes, 11.4 ± 21.4 µg/mg Cr vs 44.7 ± 76.4 µg/mg Cr; P < 0.001 in diabetes) than those without NAFLD. The logistic regression analysis showed that NAFLD was associated with increased rates of microalbuminuria (odds ratio 3.66; 95% confidence interval (CI) 1.31–10.20, P= 0.013 in prediabetes, odds ratio 5.47; 95% CI 1.01–29.61, P= 0.048 in diabetes), independently of age, sex, body mass index, waist circumference, liver enzymes, lipid profiles, HbA1c, insulin resistance as estimated by homeostasis model assessment, hypertension, smoking status and the metabolic syndrome. Conclusions: The results of our study revealed a strong relationship between microalbuminuria and NAFLD in the patients with prediabetes and newly diagnosed diabetes. Further studies are required to confirm whether NAFLD is a predictor of the development of microalbuminuria in patients with prediabetes and diabetes.     

Effects of 4 weeks’ administration of pramlintide, a human amylin analogue, on glycaemia control in patients with IDDM: effects on plasma glucose profiles and serum fructosamine concentrations

Summary The effects of 4 weeks' administration of pramlintide, an analogue of the human hormone amylin, on blood glucose control in 215 patients with insulin-dependent diabetes mellitus were examined in a 4-week, randomized, double-blind, placebo-controlled, parallel-group trial. Pramlintide was administered subcutaneously prior to meals in four dosing regimens: 30 μg four times per day (breakfast, lunch, dinner, and evening snack), 30 μg three times per day (breakfast, lunch and dinner [BLD]), 30 μg three times per day (breakfast, dinner and evening snack [BDS]), and 60 μg twice per day (breakfast and dinner). After 4 weeks of pramlintide 30 μg four times per day administration, there was a statistically significant reduction in the mean 24 h plasma glucose concentration when compared to placebo (– 1.4 ± 0.5 vs 0.3 ± 0.5 μmol/l, p = 0.009). Serum fructosamine concentrations were reduced 62 ± 10 μmol/l in the pramlintide 30 mg four times per day group, 43 ± 7 μmol/l in the pramlintide 30 μg three times per day (BLD) group, 47 ± 6 μmol/l in the pramlintide 30 μg three times per day (BDS) group, 46 ± 7 μmol/l in the pramlintide 60 μg twice per day group, and 29 ± 8 μmol/l by placebo. The incidence of hypoglycaemia was not different in any pramlintide group compared to the placebo group. Nausea, the most frequent adverse event, subsided after the first week of treatment in the majority of patients. In conclusion, pramlintide improved blood glucose control over a 4-week period without increased hypoglycaemia and was well tolerated. Future studies using a longer period of pramlintide administration with assessment of HbA_1c as the measurement of glycaemic control are warranted. [Diabetologia (1997) 40: 1278–1285] Received: 3 January 1997 and in revised form: 2 May 1997     

格列吡嗪控释片对2型糖尿病患者血管内皮功能的影响

目的　探讨格列吡嗪控释片对2型糖尿病患者血管内皮功能的影响。方法　76例2型糖尿病者,经2周洗脱期后,随机分为两组。一组4 0例应用格列吡嗪控释片;另一组36例应用格列本脲。根据达到目标血糖调整药物剂量,单药未能达标者加用阿卡波糖,治疗期12周。每位患者均采用高分辨率超声显像法,分别于治疗前后各进行一次右肱动脉血管内皮功能检测。结果　格列本脲组治疗前后肱动脉内径基础值、反应性充血及含服硝酸甘油后肱动脉内径变化,均无显著性差异[(3. 70±0 . 5 7)mm对(3 .72±0 . 5 9)mm ,(5 . 4 6±0 .82 ) %对(5 .70±0 .84 ) % ,(2 0 . 5±5 . 0 ) %对(2 0 . 1±5 . 1) % ,P >0 .0 5 ]。格列吡嗪控释片组治疗前后肱动脉内径基础值、含服硝酸甘油后肱动脉内径的变化,也无显著性差异[(3 .72±0 . 6 2 )mm对(3 .73±0 . 6 3)mm ,(19. 8±5. 5 ) %对(19. 9±5 . 8) % ,P >0 . 0 5 ];但反应性充血引起肱动脉内径变化,治疗前后具有非常显著性差异[(5. 6 7±0 .79) %对(9. 4 6±3 .81) % ,P <0 . 0 1]。结论　格列吡嗪控释片可能改善2型糖尿病者的血管内皮功能。     

Lipid peroxidation in nicotinamide-deficient and nicotinamide-supplemented rats with streptozotocin-induced diabetes

Reactive oxygen species have been related to the pathogenesis of various diseases, including diabetes mellitus. Nicotinamide has been used for the prevention of the diabetogenic effects of streptozotocin (STZ) in animals. In the present study we assessed the effect of diets with deficient, normal or 17-fold supplemented nicotinamide concentrations on the rate of lipopoeroxidation in animals with STZ-induced diabetes. Male Wistar rats were divided into three groups kept on one of the diets for six weeks: DD, diabetic rats on a nicotinamide-deficient diet; DN, diabetic rats on a normal nicotinamide diet; and DS, diabetic rats on a nicotinamide-supplemented diet. During the fourth week of the experiment all animals were fasted for 24 hours and injected into the tail vein with a single STZ dose (40 mg/kg weight). Eight animals from each of the six groups were then sacrificed 24 hours, 1 week and 2 weeks after STZ injection. Mean pancreatic thiobarbituric acid reactive substances (TBARS) (nmol/mg tissue) were significantly lower in the DS group (p < 0.05) compared to the DN and DD groups at 24 hours and during the first week. Hepatic TBARS concentrations (nmol/mg protein) did not differ between groups. Mean hepatic reduced glutathione (GSH) levels were significantly higher (46.76 ± 12.33 nmol/mg protein) in the DS group compared to the DD (32.90 ± 6.70) and DN (24.55 ± 6.41) groups, but only after the 24-hour period. Hepatic vitamin E consumption (Μg/g tissue) was considerable in the groups not supplemented with nicotinamide, whereas vitamin E levels were unchanged in the supplemented group. In contrast, plasma vitamin E levels were decreased in the normal and supplemented groups after 1 and 2 weeks. A higher N-methylnicotinamide excretion (μg/ 24 hours) occurred in the supplemented group. We conclude that, after induction of diabetes with STZ, nicotinamide supplementation protected from the damage caused by the toxic action of STZ, promoting lower lipid peroxidation. Received: 27 September 1999 / Accepted in revised form: 3 March 2000     

Efficacy of combined use of miglitol in Type 2 diabetes patients receiving insulin therapy-placebo-controlled double-blind comparative study

Combination therapy with an α-glucosidase inhibitor and insulin is commonly performed for type 2 diabetes mellitus. We conducted a placebo-controlled double-blind comparative study to investigate the efficacy of combination therapy with miglitol and insulin. The patients with T2DM on insulin therapy were randomly assigned to either a miglitol treatment group (Group M) or a placebo group (Group P) and treated for 12 weeks. Meal tolerance tests were conducted at the observation period, week 0 and week 12 of the treatment period. Mean values of decrease in 1-h- and 2-h postprandial plasma glucose level were significantly larger in Group M than in Group P (60.3 ± 70.1 mg/dl vs. −5.1 ± 68.2 mg/dl (P < 0.001)), as was HbA1c as well (0.36 ± 0.66% vs. −0.03 ± 0.56% (P < 0.001)). Adverse events included abdominal distension and flatulence, which were significantly more frequent in Group M. The frequency of nocturnal hypoglycemia events tended to be reduced in Group M. Combined use of insulin and miglitol is useful for postprandial glucose regulation and improves glycemic control.     

Metformin reduces thyrotropin levels in obese, diabetic women with primary hypothyroidism on thyroxine replacement therapy

Context It has been reported that metformin might modify thyroid hormone economy. In two retrospective studies, initiation of treatment with metformin caused suppression of TSH to subnormal levels. Objective To prospectively evaluate if administration of metformin to obese, diabetic patients with primary hypothyroidism on stable thyroxine replacement doses modifies TSH levels. Patients and methods Eight obese, diabetic postmenopausal women with primary hypothyroidism participated in the study. They received 1,700 mg of metformin daily for 3 months. Weight, TSH, free T4, and free T3 levels were measured at baseline, 3 months after metformin initiation and 3 months after its withdrawal. Results After 3 months of on metformin, mean TSH was significantly lower than basal TSH (3.11 ± 0.50 μUI/ml vs. 1.18 ± 0.36 μUI/ml; P = 0.01). Mean TSH 3 months after metformin withdrawal was 2.21 ± 0.37 μUI/ml, significantly higher than TSH after metformin (P = 0.05), but not different from basal TSH. Mean fT4 level increased during metformin administration (basal fT4: 1.23 ± 0.06 ng/dl, fT4 after metformin: 1.32 ± 0.04 ng/dl; P = ns), and decreased after its withdrawal (fT4 3 months after metformin withdrawal: 1.15 ± 0.05 ng/dl; vs. 3 months after metformin, P = 0.04; vs. basal; P = ns). Conclusions In obese, diabetic patients with primary hypothyroidism on thyroxine replacement treatment, short-term metformin administration is associated with a significant fall in TSH.     

Correlation between pancreatic endocrine and exocrine function and characteristics of pancreatic endocrine function in patients with diabetes mellitus owing to chronic pancreatitis

Summary Conclusion Pancreatic endocrine capacities are remarkably disturbed in patients with pancreatic diabetes owing to calcific pancreatitis as opposed to those owing to noncalcific pancreatitis. Insulin secretion in calcific pancreatitis resembled, that in insulin-dependent diabetes mellitus (IDDM), whereas insulin secretion in noncalcific pancreatitis resembled that in non-IDDM (NIDDM). The involvements of acinar cell and ductal cell function closely correlate with endocrine function (insulin and glucagon secretions) in chronic pancreatitis (pancreatic diabetes). Background We sought to clarify the differences of pancreatic endocrine function between pancreatic diabetes and primary diabetes, and to verify the correlations between pancreatic exocrine and endocrine dysfunction in patients with chronic pancreatitis. Methods Urinary C-peptide (CPR) excretion and fasting plasma glucagon levels in patients with pancreatic diabetes owing to calcific pancreatitis (19 cases) and owing to noncalcific pancreatitis (14 cases) were studied in comparison with those in patients with insulin-dependent diabetes mellitus (IDDM, 23 cases), noninsulin-dependent diabetes (NIDDM, 18 cases), and in healthy controls (11 cases). In addition, pancreatic exocrine function was investigated in patients with chronic pancreatitis (calcific and noncalcific) and in healthy controls. The correlation between pancreatic exocrine and endocrine function was studied. Results The urinary CPR excetion in controls was 94.9±20.5 μg/d. The urinary CPR excretion in calcific pancreatitis was 12.8±7.4 μg/d and it resembled that in IDDM (9.4±5.8 μg/d). The urinary CPR excretion in noncalcific pancreatitis was 41.5±30.1 μg/d, being similar to that in NIDDM (49.3±21.0 μg/d). The plasma glucagon level in calcific pancreatitis was 64.1±15.9 ρg/mL, which was significantly lower than the values in IDDM (111.2±50.2 ρg/mL) and NIDDM (96.7±21.9 ρg/mL). The plasma glucagon level in calcific and noncalcific pancreratitis (88.4±29.6 ρg/mL) were significantly lower than that in controls (12.9±21.6 ρg/mL). The residual capacities of acinar cells and ductal cells were strongly correlated with urinary CPR excretion and plasma glucagon concentration.     

2型糖尿病患者血清脂蛋白(a)水平及其与冠心病的关系

目的　探讨 2型糖尿病患者血清脂蛋白 (a) [Lp(a) ]水平及其与冠心病的关系。方法　选择 90例 2型糖尿病及 6 8例健康对照者测定其血清Lp(a)、总胆固醇 (TC)、甘油三酯 (TG)、高密度脂蛋白胆固醇 (HDL C)水平 ;计算低密度脂蛋白胆固醇 (LDL C)水平及TC、TG、LDL C与HDL C比值。结果　 (1)糖尿病组血清Lp(a)水平与对照组比较差异无显著性意义 (P >0 .0 5 )。 (2 )将 2型糖尿病患者分为糖尿病伴冠心病和单纯糖尿病亚组后发现 :①糖尿病伴冠心病亚组血清Lp(a)水平明显高于单纯糖尿病亚组 [(2 3.78± 2 3.73)mg/dlvs (13.31± 10 .6 6 )mg/dl;P <0 .0 1]及对照组 [(2 3.78± 2 3.73)mg/dlvs (16 .2 8± 17.95 )mg/dl;P <0 .0 5 ];②糖尿病伴冠心病亚组血清Lp(a)水平与LDL C呈正相关关系 (r =0 .32 16 ,P <0 .0 5 )。结论　 2型糖尿病患者血清Lp(a)水平增高可能与冠心病发病有密切关系。