Treating postprandial hyperglycemia does not appear to delay progression of early type 2 diabetes: the Early Diabetes Intervention Program.
ABSTRACT Postprandial hyperglycemia characterizes early type 2 diabetes. We investigated whether ameliorating postprandial hyperglycemia with acarbose would prevent or delay progression of diabetes, defined as progression to frank fasting hyperglycemia, in subjects with early diabetes (fasting plasma glucose [FPG] <140 mg/dl and 2-h plasma glucose > or =200 mg/dl).
Two hundred nineteen subjects with early diabetes were randomly assigned to 100 mg acarbose t.i.d. or identical placebo and followed for 5 years or until they reached the primary outcome (two consecutive quarterly FPG measurements of > or =140 mg/dl). Secondary outcomes included measures of glycemia (meal tolerance tests, HbA(1c), annual oral glucose tolerance tests [OGTTs]), measures of insulin resistance (homeostasis model assessment [HOMA] of insulin resistance and insulin sensitivity index from hyperglycemic clamps), and secondary measures of beta-cell function (HOMA-beta, early- and late-phase insulin secretion, and proinsulin-to-insulin ratio).
Acarbose significantly reduced postprandial hyperglycemia. However, there was no difference in the cumulative rate of frank fasting hyperglycemia (29% with acarbose and 34% with placebo; P = 0.65 for survival analysis). There were no significant differences between groups in OGTT values, measures of insulin resistance, or secondary measures of beta-cell function. In a post hoc analysis of subjects with initial FPG <126 mg/dl, acarbose reduced the rate of development of FPG > or =126 mg/dl (27 vs. 50%; P = 0.04).
Ameliorating postprandial hyperglycemia did not appear to delay progression of early type 2 diabetes. Factors other than postprandial hyperglycemia may be greater determinants of progression of diabetes. Alternatively, once FPG exceeds 126 mg/dl, beta-cell failure may no longer be remediable.
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ABSTRACT: BACKGROUND: Because of its mechanism of action, the starch content of a diet might alter the hypoglycemic effect of acarbose. OBJECTIVE: We aimed to determine whether differences in this hypoglycemic effect existed between individuals consuming Eastern and Western diets with significantly different starch contents, a systematic meta-analysis of studies comparing acarbose with placebo or other hypoglycemic agents in patients with type 2 diabetes mellitus (T2DM) was performed. METHODS: Records were retrieved from the Cochrane clinical controlled trials, MEDLINE, EMBASE, Wanfang, Chinese Technical Periodicals, and ongoing trials databases, and full texts and reference lists were screened. Because no study has directly compared patients consuming different types of diet, fixed- and random-effect models were used to indirectly compare the hypoglycemic effect of acarbose monotherapy with that of placebo and/or comparator drugs in patients with T2DM consuming an Eastern (Eastern Asia) or Western (including Europe and North America) diet. RESULTS: A total of 46 studies were included in the meta-analysis. The results revealed that, compared with placebo, hemoglobin A1c (HbA1c) levels were reduced to a significantly greater extent (1.02%) in the Eastern diet (mean [SD], 1.54% [2.00%]) than in the Western diet (mean [SD], 0.52% [1.20%]) P < 0.00001). The ability of acarbose to reduce HbA1c levels in the Eastern (P = 0.20) and Western (P = 0.10) diet groups was similar to that of sulfonylureas, and HbA1c levels were reduced significantly more (0.39%; P < 0.00001) in the Eastern than in the Western diet group. The ability of acarbose to reduce HbA1c levels was similar to those of metformin and nateglinide/repaglinide, but a comparison of its efficacy with different diets was difficult because of the inclusion of few studies in these categories. Analysis of all included studies revealed that acarbose achieved a greater absolute reduction of HbA1c levels in the Eastern diet (mean [SD], 1.26% [1.20%]) than in the Western diet (mean [SD], 0.62% [1.28%]; P < 0.00001) group. However, the poor quality of Eastern diet trials may have affected the outcomes of the meta-analysis. CONCLUSION: The hypoglycemic effect of acarbose is superior in patients with T2DM consuming an Eastern diet than in those consuming a Western diet and is similar to that of sulfonylureas, metformin, and glinide drugs.Clinical Therapeutics 04/2013; · 2.23 Impact Factor
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ABSTRACT: To compare the efficacy of glycemic control and insulin secretion of alpha glucosidase inhibitors (AGI) on type 2 diabetes patients between Asian and Caucasian. The MEDLINE®, EMBASE®, CENTRAL were searched and qualified studies in Asian and Caucasian population comparing AGI treatment with placebo or other oral anti-diabetic drugs in type 2 diabetic patients were included. Totally 58 qualified studies were included. When AGI treatment was compared with placebo, a significant difference in HbA1c decline from baseline favoring AGI treatment was found in Asian (weighted mean difference (WMD), -0.50%; 95% CI, -0.66% to -0.34%) and in Caucasian a significant difference in HbA1c decline favoring AGI treatment was also found (WMD, -0.68%; 95% CI, -0.76% to -0.60%). In Asian, fasting plasma glucose was reduced with AGI treatment compared with placebo (WMD, -0.53 mmol/L; 95% CI, -0.91 to -0.14 mmol/L) and in Caucasian there was also a significant difference in FPG changes favoring AGI therapy (WMD, -0.88 mmol/L; 95% CI, -1.00 to -0.77 mmol/L). Studies in Asian showed a significant difference in fasting insulin changes favoring AGI treatment (WMD, -0.78 uU/ml; 95% CI, -0.96 to -0.59 uU/ml). While in Caucasian fasting insulin was decreased without significance with AGI treatment (WMD-1.24 uU/ml; 95% CI, -2.51 to 0.04 uU/ml). Body weight was decreased with AGI treatment in Asian (WMD, -1.00 kg; 95% CI, -1.69 to -0.31 kg) and was also decreased with AGI treatment in Caucasian (WMD, -0.73 kg; 95% CI, -1.13 to -0.33 kg). According to results from this meta-analysis, the efficacy in glucose lowering, body weight reduction and insulin secretion decreasing of AGI treatment in Asian were comparable with those in Caucasian.PLoS ONE 01/2013; 8(11):e79421. · 3.53 Impact Factor
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ABSTRACT: Prediabetes, a high-risk state for future development of diabetes, is prevalent globally. Abnormalities in the incretin axis are important in the progression of B-cell failure in type 2 diabetes. Incretin based therapy was found to improve B cell mass and glycaemic control in addition to having multiple beneficial effects on the systolic and diastolic blood pressure, weight loss in addition to their other beneficial effects on the liver and cardiovascular system. In prediabetes, several well-designed preventive trials have shown that lifestyle and pharmacologic interventions such as metformin, thiazolidinediones (TZD), acarbose and, nateglinide and orlistat, are effective in reducing diabetes development. In recent small studies, incretin based therapy (DPP IV inhibitors and GLP-1 agonists) have also been extended to patients with prediabetes since it was shown to better preserve B-cell function and mass in animal studies and in clinical trials and it was also shown to help maintain good long term metabolic control. Because of the limited studies and clinical experience, their side effects and costs currently guidelines do not recommend incretin-based therapies as an option for treatment in patients with prediabetes. With future clinical trials and studies they may be recommended for patients with impaired fasting glucose or impaired glucose tolerance.Primary Care Diabetes. 01/2014;