S100 Genes are Highly Expressed in Peripheral Leukocytes of Type 2 Diabetes Mellitus Patients Treated with Dietary Therapy.

BACKGROUND AND OBJECTIVES: We demonstrated that the mRNA induction of S100s in rat peripheral leukocytes by severe hyperglycemia was reduced by inhibiting postprandial hyperglycemia. Here, we compared inflammatory gene expression in peripheral leukocytes between type 2 diabetes mellitus (T2DM) patients undergoing dietary therapy alone and healthy volunteers, and between T2DM patients undergoing dietary therapy alone and those undergoing such therapy in combination with drug therapy using the α-glucosidase inhibitor miglitol. METHODS: T2DM patients who had undertaken dietary therapy alone or in combination with drug therapy using miglitol for ≥ 8 weeks and healthy volunteers were subjected to a meal tolerance test and glucose concentration, neutrophil elastase concentration, and mRNA expression analyses of peripheral leukocytes by microarray and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) immediately before and 180 min after a meal. RESULTS: Blood glucose concentrations 60 min after a meal were lower in T2DM patients with dietary + miglitol therapy than in those with dietary therapy alone. Neutrophil elastase concentrations at 60 and 120 min after a meal were lower in T2DM patients with dietary + miglitol therapy than in those with dietary therapy alone. Expression levels of S100A8 in a fasting state and S100A6, S100A8, and S100A9 180 min after a meal were higher in T2DM patients with dietary therapy alone than in healthy volunteers. Expression levels of S100A12 in a fasting state and 180 min after a meal were higher in T2DM patients with dietary therapy alone than in T2DM patients with dietary + miglitol therapy. CONCLUSIONS: S100 genes were more highly expressed in T2DM patients with dietary therapy than in healthy volunteers.

Add-on therapy with anagliptin in Japanese patients with type-2 diabetes mellitus treated with metformin and miglitol can maintain higher concentrations of biologically active GLP-1/total GIP and a lower concentration of leptin.

Metformin, α-glucosidase inhibitors (α-GIs), and dipeptidyl peptidase 4 inhibitors (DPP-4Is) reduce hyperglycemia without excessive insulin secretion, and enhance postprandial plasma concentration of glucagon-like peptide-1 (GLP-1) in type-2 diabetes mellitus (T2DM) patients. We assessed add-on therapeutic effects of DPP-4I anagliptin in Japanese T2DM patients treated with metformin, an α-GI miglitol, or both drugs on postprandial responses of GLP-1 and glucose-dependent insulinotropic polypeptide (GIP), and on plasma concentration of the appetite-suppressing hormone leptin. Forty-two Japanese T2DM patients with inadequately controlled disease (HbA1c: 6.5%-8.0%) treated with metformin (n=14), miglitol (n=14) or a combination of the two drugs (n=14) received additional treatment with anagliptin (100mg, p.o., b.i.d.) for 52 weeks. We assessed glycemic control, postprandial responses of GLP-1 and glucose-dependent insulinotropic polypeptide (GIP), and on plasma concentration of leptin in those patients. Add-on therapy with anagliptin for 52 weeks improved glycemic control and increased the area under the curve of biologically active GLP-1 concentration without altering obesity indicators. Total GIP concentration at 52 weeks was reduced by add-on therapy in groups treated with miglitol compared with those treated with metformin. Add-on therapy reduced leptin concentrations. Add-on therapy with anagliptin in Japanese T2DM patients treated with metformin and miglitol for 52 weeks improved glycemic control and enhanced postprandial concentrations of active GLP-1/total GIP, and reduce the leptin concentration.

Effects of sitagliptin or mitiglinide as an add-on to acarbose on daily blood glucose fluctuations measured by 72 h subcutaneous continuous glucose monitoring in Japanese patients with type 2 diabetes: a prospective randomized study.

OBJECTIVE: Postprandial hyperglycemia and blood glucose fluctuations increase the risk of macroangiopathy in patients with type 2 diabetes mellitus (T2DM). However, few studies have examined the effects of oral hypoglycemic drugs on blood glucose fluctuations in daily life. METHODS: Twenty-nine T2DM patients treated with acarbose were randomized to receive either sitagliptin (14 patients) or mitiglinide (15 patients) together with acarbose for 4 weeks. Patients were then switched to a combination of 10 mg mitiglinide and 0.2 mg voglibose for 4 weeks. All patients wore a continuous glucose monitoring (CGM) device for 5 - 7 days in week 3 of each treatment period. RESULTS: The percentage of blood glucose levels in the hyperglycemic range, blood glucose indices derived from 24-h CGM profiles and the glycemic parameters (HbA1c, glycated albumin and fasting plasma glucose) were significantly improved by adding sitagliptin or mitiglinide to ongoing acarbose therapy. These parameters also tended to improve in the mitiglinide/voglibose combination period. CONCLUSION: Daily blood glucose fluctuations were significantly improved by adding sitagliptin or mitiglinide to acarbose, and improved after switching to the mitiglinide/voglibose combination. Larger controlled studies are needed to verify the effects of adding sitagliptin or mitiglinide to acarbose on glucose fluctuations.

Cotreatment with the α-glucosidase inhibitor miglitol and DPP-4 inhibitor sitagliptin improves glycemic control and reduces the expressions of CVD risk factors in type 2 diabetic Japanese patients.

OBJECTIVE: In this study, we examined whether inhibition of postprandial hyperglycemia by combination therapy with two drugs for reducing postprandial hyperglycemia, i.e., α-glucosidase inhibitor miglitol and dipeptidyl peptidase (DPP)-4 inhibitor sitagliptin, improves glycemic control and reduces the risk of cardiovascular disease (CVD) development. MATERIALS/METHODS: We enrolled 32 type 2 diabetic Japanese patients with hemoglobin A1c (HbA1c) levels ranging from 6.9% to 10.5%, who had been treated for at least 2 months with 50mg miglitol (t.i.d.) or 50 mg sitagliptin (q.d.). Following a monotherapy period with either miglitol (Group-M) or sitagliptin (Group-S) for 1 month, the patients were subjected to combination therapy with sitagliptin and miglitol for 3 months. Meal tolerance tests were performed at the end of the monotherapy and combination therapy. RESULTS: Combination therapy for 3 months after monotherapy reduced HbA1c (changes: Group-M: -1.3%±0.7%, P<0.001; Group-S: -0.6%±0.5%, P<0.001) and glycoalbumin levels and increased 1,5-anhydroglucitol concentrations in the blood. In the meal tolerance tests, circulating active glucagon-like peptide-1 levels were elevated in both groups, while active glucose-dependent insulinotropic polypeptide levels were reduced by combination therapy in the group with add-on miglitol therapy. The plasma protein concentrations of interleukin (IL)-8 and adhesion molecules (sE-selectin and sVCAM-1) were reduced by switching to the combination therapy, in particular with the add-on miglitol therapy. CONCLUSIONS: Our results suggest that combination therapy with miglitol and sitagliptin improves glycemic control and reduces the circulating protein concentrations of IL-8, sE-selectin, and sVCAM-1 in type 2 diabetic Japanese patients.