Comparison of the Hypoglycemic Effect of Acarbose Monotherapy in Patients With Type 2 Diabetes Mellitus Consuming an Eastern or Western Diet: A Systematic Meta-analysis

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 A_1c (HbA_1c) 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 HbA_1c levels in the Eastern (P = 0.20) and Western (P = 0.10) diet groups was similar to that of sulfonylureas, and HbA_1c 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 HbA_1c 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 HbA_1c 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.

Introduction

In recent years, the guidelines of the American Diabetes Association¹ and the Association of American Clinical Endocrinologists² have reached a consensus on the comprehensive management of patients with diabetes mellitus (DM), especially with regard to glycemic control. The Steno-2 study3, 4, 5 found that intensive multifactorial interventions could significantly reduce the rates of cardiovascular mortality (43%) and cardiovascular events (41%) in patients with DM, but the success rates for other clinical targets differed markedly. Successful blood pressure and blood lipid reduction rates were high, as indicated by decreased total cholesterol levels in 75% of patients, triglyceride levels in 60%, diastolic pressure in 75%, and systolic blood pressure in 50%, but the reduction of hemoglobin A_1c (HbA_1c) was less successful (<20% of patients achieved the target of 6.5%), indicating that glucose control remains a key challenge in diabetes treatment. The United Kingdom Prospective Diabetes Study6, 7, 8, 9, 10, 11 confirmed that HbA_1c levels were reduced by 1% in patients with newly diagnosed type 2 DM (T2DM) after intensive intervention; diabetes-related mortality decreased by 21%, and rates of related complications decreased significantly (myocardial infarction by 14%, stroke by 12%, and heart failure by 16%); rates of pathological capillary changes were decreased by 37% and cataract extractions by 19%, and the incidence and mortality rates of peripheral vascular disease were decreased by 43%. Thus, although effective control of HbA_1c levels in patients with DM may reduce the incidence of these complications, this target has proved difficult to achieve.

α-Glucosidase inhibitors (AGIs), principally acarbose, are commonly used oral hypoglycemic agents in Eastern Asia. AGIs primarily target α-glucosidase in the small intestine, where it decomposes nonabsorbable complex carbohydrates into absorbable monosaccharides. Acarbose is a competitive and reversible inhibitor of small intestinal brush border glucosidase, thereby blocking the degradation of starch and sucrose and prolonging the absorption rate of glucose and fructose in the alimentary tract. Via this effect, it reduces blood glucose concentrations, especially postprandial levels. The Study to Prevent Non–Insulin-Dependent Diabetes Mellitus12, 13, 14 and the Meta-Analysis of Risk Improvement under Acarbose¹⁵ confirmed that acarbose has a hypoglycemic effect in patients with abnormal glycometabolism, as well as a role in preventing cardiovascular events. However, because of its mechanism of action, dietary starch content might alter the hypoglycemic effect of acarbose.

Diets evolve over time, and income, prices, individual preferences and beliefs, and cultural traditions, as well as geographic, environmental, social, and economic factors, all interact in a complex manner to shape dietary consumption patterns. Thus, eating patterns differ among countries and regions. Factor analysis has been used to identify 2 major eating patterns: the Eastern and Western patterns.¹⁶ The Eastern pattern is characterized by higher intakes of whole grains, legumes, vegetables, fruits, and fish, whereas the Western pattern is characterized by higher intakes of processed meat, red meat, butter, high-fat dairy products, eggs, and refined grains.¹⁶ According to national food consumption (proportions of foods in average diets) data provided by the Food and Agriculture Organization of the United Nations, most inhabitants of Asian and African countries follow a Eastern diet, whereas the inhabitants of Europe and North America adhere to a Western diet.¹⁷ However, rapid economic growth, urbanization, and globalization have spurred a marked shift in Asian diets away from cereals and toward the Western pattern of increased consumption of animal and dairy products, fats, and oils.¹⁸

Consumption of animal products has increased rapidly in developing countries since the 1980s. Although per capita consumption of these products has increased in East and Southeast Asia, with 2.4% to 5.6% annual growth in total calories obtained from animal products, the absolute contribution to the diet remained less than 25% in most countries through 2005.¹⁹ In most Asian countries, at least 50% to 60% of total calories are still obtained from cereals.²⁰

Because starch comprises a higher proportion of total calories in Eastern than in Western diets, the hypoglycemic effect of AGIs might be greater in consumers of an Eastern diet. Studies of the efficacy and safety of acarbose in countries throughout the world have yielded different results with respect to HbA_1c levels: the Precose Resolution of Optimal Titration to Enhance Current Therapies study in the United States²¹ found that HbA_1c levels were reduced by ∼0.7%, and German²² and Italian²³ studies have reported reductions of 1.8% and 0.14%, respectively. In comparison, studies conducted in China, both on the mainland and Taiwan,24, 25, 26 have reported reductions of 1% to 1.5%. However, these studies all had several confounding factors that compromised the strength of the evidence, and no study has directly compared HbA_1c reductions due to acarbose in patients with T2DM consuming Eastern and Western diets.

A search of various databases for reports of patients consuming a Western diet identified numerous controlled clinical trials of the hypoglycemic effect of acarbose monotherapy conducted in Europe, the United States, and other Western countries. Most studies of acarbose in patients consuming an Eastern diet have been conducted in China, with fewer studies performed in Japan, South Korea, India, and other Asian countries. We identified even fewer relevant studies of patients consuming a Mediterranean diet, which has received much recent attention. Thus, this meta-analysis aimed to evaluate whether the reduction in HbA_1c level achieved with acarbose monotherapy in patients with T2DM differed between consumers of Eastern and Western diets.