Efficacy of acarbose in Chinese subjects with impaired glucose tolerance
Introduction
Diabetes is a major global health problem and an increasing cause of morbidity and mortality [1]. Impaired glucose tolerance (IGT), the metabolic stage intermediate between normal glucose homeostasis and diabetes, is clinically significant as a major risk factor for Type 2 diabetes [2] and cardiovascular disease (CVD) [3], [4]; it is part of a cluster of risk factors called the metabolic syndrome which includes obesity, hypertension and dyslipidaemia [5]. All these disorders are associated with insulin resistance and hyperinsulinaemia.
According to estimates [1], a 134% increase in diabetic adults is anticipated in China by 2025. An annual incidence rate of 15.7% was reported in the Chinese Da Qing study for the IGT control group [6] and an increased frequency of CVD and its risk factors was also shown in Da Qing IGT subjects [7]. As IGT incidence will probably increase with rising living standards in China, various intervention strategies should be tested.
The α-glucosidase inhibitor acarbose has shown beneficial effects on postprandial hyperglycaemia and hyperlipidaemia in Type 2 diabetic patients. These effects have been shown to be sustained during long-term therapy of up to 5 years duration [8], [9]. Furthermore, it has been proven that acarbose is well tolerated in Asian patients [10], [11], [12]. In addition, a study in Japanese Type 2 diabetic patients demonstrated that α-glucosidase inhibitors were more effective in conjunction with a diet rich in carbohydrates [13], although this topic is still in debate [14], [15]. For these reasons, acarbose might be an especially suitable agent for the Chinese population whose traditional diet is mainly composed of carbohydrates.
As there is evidence that Type 2 diabetes starts as a postprandial disease [16], [17], [18], [19], significant improvement in the surrogate parameters postprandial blood glucose and serum insulin in IGT subjects should then be able to prevent disease progression.
This study investigated the efficacy of acarbose to improve postprandial blood glucose and serum insulin profiles in Chinese IGT subjects.
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Subjects and methods
The study was designed as a multicentre, double-blind, placebo-controlled, randomised parallel group comparison of acarbose and placebo. Subjects were recruited by five centres in the mainland of China; after obtaining written informed consent, the subjects were screened using the oral glucose tolerance test (75 g glucose) to determine if IGT defined according to WHO criteria (2 h-postprandial plasma glucose ≥140 mg/dl <200 mg/dl and fasting plasma glucose <125 mg/dl) was present. Further
Results
Of the 261 subjects randomised to the two treatment arms, three subjects did not receive double-blind study medication and were subsequently excluded from the safety analysis (acarbose n=126, placebo n=132). Six individuals were not valid for the ITT analysis (252 subjects; acarbose n=125, placebo n=127) and 247 subjects completed the study. Table 1 summarises the baseline demographic characteristics for the ITT population. The treatment arms compared well for all parameters; there was a small
Discussion
The development of Type 2 diabetes is usually preceded by a prediabetic phase of glucose levels above normal but below the diabetic threshold. There are many IGT subjects who present with elevated postprandial blood glucose concentrations but normal fasting values. Heine et al. [16] showed that the 2 h-postprandial blood glucose value was a significant predictor of progression from IGT to Type 2 diabetes. Other studies have also provided evidence [17], [18], [19]. The DECODE study also showed
Acknowledgements
The technical help of Dr Wen Wu, Medical Department of Bayer Healthcare Beijing, is gratefully acknowledged. This study was supported by Bayer AG, Leverkusen, Germany.
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