Miglitol, α-glycosidase inhibitor, reduces visceral fat accumulation and cardiovascular risk factors in subjects with the metabolic syndrome: A randomized comparable study
Introduction
The metabolic syndrome is a cluster of common cardiovascular risk factors including hypertension, glucose intolerance, dyslipidemia and visceral fat obesity [1], [2], [3]. The notion has been proposed that visceral fat obesity is the central element in this syndrome and could be causally involved in clustering of the other components [4]. Actually, losing 5–10% of body weight was shown to reduce the traditional cardiovascular risks [5], [6]. Currently ongoing are clinical trials that use health-promoting lifestyle interventions, new drugs and even surgery, which are all aimed at weight loss, reduction in disease manifestations, and improved outcomes [5], [6].
Two placebo-controlled randomized trials using α-glycosidase inhibitors revealed that acarbose and voglibose, respectively, improved postprandial hyperglycemia and reduced the risk of development of type 2 diabetes in patients with impaired glucose tolerance (IGT) [7], [8]. Meta-analysis of seven randomized, double-blind, placebo-controlled acarbose studies [Meria7] showed that acarbose prevents myocardial infarction and cardiovascular diseases in type 2 diabetic patients [9]. Noteworthy was the fact that acarbose reduced body weight and body mass index in the diabetic patients, accompanied by improvement in glycemic, triglyceride and systolic blood pressure controls. These observations suggest that inhibition of postprandial hyperglycemia by α-glycosidase inhibitors may be a therapeutic strategy for reducing risks for diabetes, hypertension, dyslipidemia and cardiovascular diseases in patients with high-risk obesity such as the metabolic syndrome. Selective inhibition of α-glycosidase enzymes delays carbohydrate digestion in the small intestine and reduces the postprandial rise in plasma glucose. Such profiles could avoid enhanced insulin requirement/hyperinsulinemia and might be protecting from visceral fat accumulation. But, such notion of α-glycosidase inhibitors on fat remodeling has never been elucidated.
In this open-label, prospective, randomized study, patients with the metabolic syndrome were treated either by life style modification (LSM) or LSM with miglitol, and visceral fat distribution and glucose/insulin profiles were evaluated.
Section snippets
Subjects
Participants visited our hospital by self-referral or by recommendation for further check-up of life-style related disease at local center screening (Diabetes and Life-style Related Disease Center, Tomishiro Central Hospital). The studied subjects included men and women aged between 34 and 69 years with the metabolic syndrome, defined according to the 2005 IDF guideline [2]. In the IDF criteria, subjects to be defined as metabolic syndrome have abdominal obesity (modified Japanese criteria,
Baseline characteristics
A total of 111 patients were enrolled, with 56 randomized to LSM group and 55 to LSM + miglitol group, and 50 of LSM and 48 of LSM + miglitol were available for analysis (Fig. 1). Baseline characteristics did not differ between the two groups: LSM group included 39 male and 17 female with a mean age of 55 ± 12 years, and LSM + miglitol group included 38 male and 17 female with a mean age of 54 ± 10 years. At baseline before treatment, body weight, BMI, waist circumference, blood pressure and heart rate
Discussions
Our study indicated that miglitol, in contrast to LSM alone, profoundly decreases body weight, BMI and waist circumference in patients with the metabolic syndrome. In addition, data provide evidence that body weight reduction by miglitol is closely correlated with a reduction in visceral adiposity and also with improvement in indices of insulin resistance. Finally, the reduction in visceral adiposity was accompanied by overall improvement in metabolic derangements such as glucose intolerance,
Acknowledgments
This study supported by grants from the Ministry of Education, Culture, Sports, Science and Technology, the Ministry of Health, Labour and Welfare (MHLW), and the Suzuken Memorial Foundation. We deeply thank Ms. Hiroe Shinjo, Ms. Saeko Nakamura, Ms. Ayano Tajima and Ms. Rie Shiroma for dedicated secretarial assistance, Ms. Tokiko Kinjo and Ms. Kaori Ichimatsu for experienced nutritional counseling and Dr. Hideaki Tanaka, Dr. Yoshinao Uezu, and Dr. Yoshiki Shiohira for encouragement and valuable
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