The aim of the present study was to try to examine the intrinsic effects of acarbose on the secretion of incretins in drug-naive patients with newly diagnosed T2DM. Results showed that no significant difference was observed in the OGTT group before and after administering acarbose. In the MMT group, postprandial levels of plasma glucose, insulin, glucagon at 15 min, glucagon AUC, GIP levels at 30 min, and GIP AUC were decreased after receiving acarbose with a mixed meal, but GLP-1 levels and GLP-1 AUC did not change. These results suggest that the influence of acarbose on incretin levels is related to the types of carbohydrate being consumed in patients with T2DM.
Inhibitors of α-glucosidase (such as acarbose) are known to delay the intestinal hydrolysis of oligo- and disaccharides, mainly in the upper half of the small intestine, by binding competitively and in a dose-dependent manner to α-glucosidase, reducing their intestinal absorption, but acarbose has no direct effect on the absorption of glucose . As a result, after taking 75 g glucose, the OGTT group in this study did not present significant changes in the levels of plasma glucose with the administration of acarbose. Furthermore, the results showed no difference in the levels of incretins and insulin in the OGTT group after administering acarbose, indicating that acarbose had no direct effect on the secretion of incretins from L and K cells after the 75 g glucose load.
In the present study, after acarbose, the MMT group did not present significant difference in GLP-1, but the levels at 30 min and the AUC of GIP were decreased significantly. These findings are inconsistent with those of other studies. Indeed, GLP-1 secretion is dependent on both the size and the nutrient composition of the meal . Vilsboll et al.  demonstrated that the incretin responses were significantly higher in the group receiving a large meal compared with those receiving a small meal in lean patients with type 1 diabetes mellitus and obese patients with T2DM (520 kcal vs. 260 kcal). Meal sizes of 400–550 kcal have failed to demonstrate that acarbose could enhance GLP-1 secretion [14, 20]. A previous study has shown that miglitol, a first-generation α-glucosidase inhibitor, induced an enhanced GLP-1 release with an ordinary meal of 720 kcal in obese women with T2DM . In another study using oral sucrose, patients with poorly controlled T2DM also showed a prolonged and enhanced secretion of GLP-1 after administration of acarbose . In the present study, the meal size was 370 kcal and was designed to represent the characteristic Chinese meal. It included 74 % carbohydrates, 7 % protein, and 19 % fat [23, 24], which might not be sufficient to stimulate the secretion of GLP-1 even with the administration of acarbose. However, factors such as the inclusion criteria of subjects (duration of diabetes, severity of diabetes complications, combined medications, and the degree of obesity and insulin resistance) might influence incretin secretion. In the present study, patients were newly diagnosed with T2DM and were slightly overweight (BMI of 25.5 ± 1.1 kg/m2), and they had no history of antidiabetic drugs or chronic complications of diabetes. Therefore, GLP-1 might not yet be impaired severely in these patients. In addition, subjects in this study received a single dose of acarbose, which was different from other studies. Indeed, Zheng et al.  reported that a 24-week treatment with acarbose significantly increased the levels of GLP-1 in newly diagnosed T2DM patients. The β cells function and insulin sensitivity can be improved by the elimination of glucotoxicity, which can affect the secretion of incretins directly and indirectly . Glycemic control after the 24-week administration of acarbose may contribute in part to the restoration of the GLP-1 secretion defect. However, no significant changes were found in GLP-1 levels with the single dose of acarbose.
Recent studies of inhibitors of α-glucosidase (acarbose and miglitol) in patients with T2DM have indicated that these drugs can reduce the levels of GIP [20, 25, 26]. GIP is released from K cells in the duodenum, which can be stimulated through the absorption of carbohydrates and fat . Studies have shown that the secretion of GIP increases significantly after the excessive ingestion of nutrients, indicating that GIP plays an important role in the development of obesity and insulin resistance induced by a high-calorie diet . The present study showed that the GIP and glucagon levels decreased after a mixed meal in patients with new diagnosed T2DM by treatment with single dose acarbose.
It is known that the secretion and activation of incretins are impaired in patients with T2DM , and this dysfunction can be observed even in the early stage of glucose metabolism disorders . Incretin dysfunction is not necessarily a characteristic unique to T2DM because several studies reported no GLP-1 deficiency in the early stage of abnormal glucose tolerance, suggesting that incretin deficiency could be the consequence of T2DM development [30, 31]. In addition, patients with long duration of diabetes and poor response of glucagon to glucose stimulation may present GLP-1 dysfunction . A previous study showed that acarbose decreased GLP-1 levels in patients with T2DM . In the present study, subjects were newly diagnosed with diabetes and had a mean HbA1c of 7.3 ± 0.4 % and a mean BMI of about 25 kg/m2, which may explain why no difference was found in GLP-1 levels between healthy subjects and patients with T2DM. A possible explanation is the fact that the effect of meals on GLP-1 secretion is negligible in East Asians, as well as GLP-1 secretion after OGTT . Additional study is necessary to address this issue.
On the other hand, GIP levels were increased significantly at 60 min during OGTT in patients with T2DM compared with controls. The present study also showed that insulin levels in the early phase were reduced while GIP was relatively high, suggesting that the biological action of GIP on stimulating glucose-dependent insulin secretion was impaired. Such phenomenon was demonstrated in a previous study of patients with T2DM, in whom GIP levels were normal or increased but the insulinotropic response was diminished substantially . As for the present study, the differences in GIP between the controls and patients with T2DM may suggest that the early changes in T2DM development may occur earlier than the changes in GLP-1 levels.
OGTT is a load of pure glucose. Since acarbose delays the hydrolysis of polysaccharides and disaccharides but has no effect on the direct absorption of glucose, acarbose had no effect on the OGTT parameters . On the other hand, since the mixed meal contained polysaccharides and disaccharides, acarbose delayed their hydrolysis, resulting in changes in incretins. These results are supported by a previous study that showed some effects of a single dose acarbose after a meal tolerance test .
This study has several limitations. First, the number of subjects was probably not sufficient to provide definitive evidence of the effect of acarbose on incretins. Indeed, the effects of acarbose on incretins may be subtle, leading to differences that cannot be detected using a small sample size. In addition, variations in the methods used to measure incretin levels may confound the detection of differences, particularly with a small sample size. Secondly, the controls were not perfectly matched to the patients. Finally, the generalisability of these results may be limited by the particularities of the T2DM observed in Chinese . Indeed, T2DM in Chinese is characterized by a rapid increase in prevalence due to the Westernized lifestyle changes, as well as specific genetic characteristics that result in low insulin secretory capacity in East Asians . Further study is still necessary to determine adequately the effects of acarbose on the metabolism of incretins.