Type 2 diabetes in East Asians is characterized primarily by β‐cell dysfunction, and with less adiposity and less insulin resistance compared with that in Caucasians. Such pathophysiological differences can determine the appropriate therapeutics for the disease. Incretins, glucose‐dependent insulinotropic polypeptide and glucagon‐like peptide‐1, are secreted in response to meal ingestion, and enhance insulin secretion glucose‐dependently. Incretin‐based drugs, dipeptidyl peptidase‐4 inhibitors (DPP‐4i) and glucagon‐like peptide‐1 receptor agonists, that ameliorate β‐cell dysfunction with limited hypoglycemia risk are now widely used in type 2 diabetes management. Recent meta‐analyses of clinical trials on DPP‐4i and glucagon‐like peptide‐1 receptor agonists found that the drugs were more effective in Asians, most likely because of amelioration of β‐cell dysfunction. In addition, we found increased glycated hemoglobin‐lowering effects of DPP‐4i to be associated with intake of fish in type 2 diabetes, which suggests that dietary customs of East Asians might also underlie the greater efficacy of DPP‐4i. Despite the limited risk, cases of severe hypoglycemia were reported for DPP‐4i/sulfonylureas combinations. Importantly, hypoglycemia was more frequent in patients also receiving glibenclamide or glimepiride, which activate exchange protein directly activated by cyclic adenosine monophosphate 2, a critical mediator of incretin signaling, and was less frequent in patients receiving gliclazide, which does not activate exchange protein directly activated by cyclic adenosine monophosphate 2. Prevention of insulin‐associated hypoglycemia by DPP‐4i has gained attention with regard to the enhancement of hypoglycemia‐induced glucagon secretion by insulinotropic polypeptide, but remains to be investigated in East Asians. Despite the safety issues, which are paramount and must be carefully monitored, the incretin‐based drugs could have potential as a first choice therapy in East Asian type 2 diabetes patients.

Aims/hypothesisInvestigation of dietary therapy for diabetes has focused on meal size and composition; examination of the effects of meal sequence on postprandial glucose management is limited. The effects of fish or meat before rice on postprandial glucose excursion, gastric emptying and incretin secretions were investigated.MethodsThe experiment was a single centre, randomised controlled crossover, exploratory trial conducted in an outpatient ward of a private hospital in Osaka, Japan. Patients with type 2 diabetes (n = 12) and healthy volunteers (n = 10), with age 30–75 years, HbA1c 9.0% (75 mmol/mol) or less, and BMI 35 kg/m2 or less, were randomised evenly to two groups by use of stratified randomisation, and subjected to meal sequence tests on three separate mornings; days 1 and 2, rice before fish (RF) or fish before rice (FR) in a crossover fashion; and day 3, meat before rice (MR). Pre- and postprandial levels of glucose, insulin, C-peptide and glucagon as well as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide were evaluated. Gastric emptying rate was determined by 13C-acetate breath test involving measurement of 13CO2 in breath samples collected before and after ingestion of rice steamed with 13C-labelled sodium acetate. Participants, people doing measurements or examinations, and people assessing the outcomes were not blinded to group assignment.ResultsFR and MR in comparison with RF ameliorated postprandial glucose excursion (AUC−15–240 min-glucose: type 2 diabetes, FR 2,326.6 ± 114.7 mmol/l × min, MR 2,257.0 ± 82.3 mmol/l × min, RF 2,475.6 ± 87.2 mmol/l × min [p < 0.05 for FR vs RF and MR vs RF]; healthy, FR 1,419.8 ± 72.3 mmol/l × min, MR 1,389.7 ± 69.4 mmol/l × min, RF 1,483.9 ± 72.8 mmol/l × min) and glucose variability (SD−15–240 min-glucose: type 2 diabetes, FR 1.94 ± 0.22 mmol/l, MR 1.68 ± 0.18 mmol/l, RF 2.77 ± 0.24 mmol/l [p < 0.05 for FR vs RF and MR vs RF]; healthy, FR 0.95 ± 0.21 mmol/l, MR 0.83 ± 0.16 mmol/l, RF 1.18 ± 0.27 mmol/l). FR and MR also enhanced GLP-1 secretion, MR more strongly than FR or RF (AUC−15–240 min-GLP-1: type 2 diabetes, FR 7,123.4 ± 376.3 pmol/l × min, MR 7,743.6 ± 801.4 pmol/l × min, RF 6,189.9 ± 581.3 pmol/l × min [p < 0.05 for FR vs RF and MR vs RF]; healthy, FR 3,977.3 ± 324.6 pmol/l × min, MR 4,897.7 ± 330.7 pmol/l × min, RF 3,747.5 ± 572.6 pmol/l × min [p < 0.05 for MR vs RF and MR vs FR]). FR and MR delayed gastric emptying (Time50%: type 2 diabetes, FR 83.2 ± 7.2 min, MR 82.3 ± 6.4 min, RF 29.8 ± 3.9 min [p < 0.05 for FR vs RF and MR vs RF]; healthy, FR 66.3 ± 5.5 min, MR 74.4 ± 7.6 min, RF 32.4 ± 4.5 min [p < 0.05 for FR vs RF and MR vs RF]), which is associated with amelioration of postprandial glucose excursion (AUC−15–120 min-glucose: type 2 diabetes, r = −0.746, p < 0.05; healthy, r = −0.433, p < 0.05) and glucose variability (SD−15–240 min-glucose: type 2 diabetes, r = −0.578, p < 0.05; healthy, r = −0.526, p < 0.05), as well as with increasing GLP-1 (AUC−15–120 min-GLP-1: type 2 diabetes, r = 0.437, p < 0.05; healthy,...

Aims/Introduction:  The effectiveness of incretin‐based therapies in Asian type 2 diabetes requires investigation of the secretion and metabolism of glucose‐dependent insulinotropic polypepide (GIP) and glucagon‐like peptide 1 (GLP‐1). Plasma extractions have been suggested to reduce variability in intact GLP‐1 levels among individuals by removing interference that affects immunoassays, although no direct demonstration of this method has been reported. We have evaluated the effects of ethanol and solid‐phase extractions on incretin immunoassays. We determined incretin levels during meal tolerance tests in Japanese patients with type 2 diabetes and characterized predictors for incretin secretion.Materials and Methods:  Japanese patients with type 2 diabetes (23 anti‐diabetic drug‐naïve and 18 treated with sulfonylurea [SU] alone) were subjected to meal tolerance tests, and incretin levels were determined by immunoassays with or without extraction.Results:  Intact GLP‐1 levels determined by an intact GLP‐1 immunoassay with ethanol and solid‐phase extractions were lower than those determined without extraction. Intact GLP‐1 levels determined by the extractions were highly correlated with each other, much more so than the levels with and without extraction. Total GLP‐1 was unaffected by extractions, showing that extractions remove interference only in the case of intact GLP‐1. Incretin secretion after meal ingestion was similar between drug‐naïve and SU‐treated patients. Fasting and postprandial GLP‐1 levels were correlated positively with fasting free fatty acids and negatively with dipeptidyl peptidase‐4 activity.Conclusions:  Ethanol and solid‐phase extractions remove interference for intact GLP‐1 immunoassay. SU showed little effect on incretin secretion. GLP‐1 and GIP secretion were predicted by different factors. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2011.00141.x, 2012)