Relationship between the efficacy of oral antidiabetic drugs and clinical features in type 2 diabetic patients (JDDM38).

AIMS/INTRODUCTION: We carried out an observational cohort study to examine the relationship between the efficacy of oral antidiabetic drugs and clinical features in type 2 diabetics. MATERIALS AND METHODS: We analyzed the CoDiC(®) database of the Japan Diabetes Data Management Study Group across 67 institutions in Japan. In a total of 3,698 drug-naïve patients who were initiated with metformin, dipeptidyl peptidase-4 inhibitor (DPP-4i) or sulfonylurea (SU) from 2007 to 2012, we evaluated body mass index (BMI) and hemoglobin A1c (HbA1c). The patients were stratified according to their clinical features, and matched using a propensity score to adjust for baseline factors. RESULTS: HbA1c was reduced with all drugs, with the largest effect elicited by DPP-4i and the smallest by SU (P = 0.00). HbA1c increased with SU after 6 months in the patients stratified by an age-of-onset of <50 years (P = 0.00). BMI increased with SU in the patients stratified by a BMI of <25 (P = 0.00), and decreased with metformin in the patients with a BMI >25 (P = 0.00). The reduction in HbA1c was larger in patients with HbA1c of ≥8%, compared with that in patients with HbA1c of <8% (P = 0.00). HbA1c during the study period was higher in patients who were added to or swapped with other drug(s), than in patients continued on the original drug (P = 0.00). CONCLUSIONS: The effect on bodyweight and glycemic control differed among metformin, DPP-4i and SU, and the difference was associated with clinical features.

Effects of epalrestat, an aldose reductase inhibitor, on diabetic neuropathy and gastroparesis.

OBJECTIVE: Diabetic patients with severe autonomic nervous disorder show delayed gastric emptying accompanied by diabetic gastroparesis, which decreases the electric activity of the stomach associated with gastric motility. It is reported that epalrestat, an aldose reductase inhibitor, is useful for treating diabetic neuropathy. Therefore, we evaluated whether this drug improves the decreased gastric motility in diabetic patients. METHODS: The present study evaluated the electrogastrograms (EGG) and autonomic nervous activity in 15 healthy volunteers (N group), and in 15 diabetic patients before and after the administration of epalrestat (DM group). Autonomic nervous activity was evaluated by spectral analysis of heart rate variability. The EGGs were recorded before and after oral administration of epalrestat (3 months or more) in the DM group. RESULTS: The dominant frequency of EGG was 3 cycles/min (cpm) in the N group. However, these 3 cpm waves disappeared with bradygastria, and postprandial increases in the peak powers of EGG were not observed in the DM group. Both the amplitude of 3 cpm waves and the postprandial peak powers were significantly increased after the administration of epalrestat. The parameters of autonomic nervous activities (LF power, HF power, and the LF/HF ratio) were significantly lower in the DM group before the administration of epalrestat than in the N group. However, these parameters were improved after the administration of epalrestat. CONCLUSION: Since gastroparesis is a form of diabetic dysautonomia, complication by gastroparesis may influence blood sugar control and the absorbance of oral antidiabetics. Epalrestat significantly increased the amplitude of 3 cpm waves on EGG and improved the spectral analytical parameters of heart rate variability. These findings suggest that epalrestat is useful for the treatment of diabetic gastroparesis.

Does coronary artery stenting for acute myocardial infarction improve left ventricular overloading at the chronic stage?

In the present study, we evaluated whether stenting is useful for cardiac overloading, using ANP, BNP, and (99m)Tc-tetrofosmin myocardial scintigraphy. It has been reported that coronary artery stenting is useful for cardiac functions for acute myocardial infarction (AMI). The subjects were 110 patients with AMI successfully treated by direct angioplasty. These patients were subgrouped into two groups: the S group (underwent stenting; 54 patients) and the P group (underwent POBA alone; 56 patients). Extent scores reflecting decreased myocardial blood flow were calculated at myocardial areas showing a radioactivity count of less than (-)2 x standard deviations compared to the database of normal subjects.The ratio of extent scores to defect scores (extent/defect ratio) was compared between the P and S groups. Both ANP and BNP levels in the S group were lower than in the P group at the chronic stage (1 and 3 months after reperfusion therapy). Moreover, the end-diastolic volume index from the left ventriculography 3 months after reperfusion therapy was significantly larger in the P than the S group. The extent/defect ratio was significantly lower in the P group (2.8 +/- 0.2) than the S group (3.5 +/- 0.3), suggestive of a microcirculation disorder. These results suggest that cardiac overloading and left ventricular remodeling are decreased more by stenting than by POBA alone, probably because stenting prevents decreased myocardial blood flow around the infarct myocardium.

High-sensitivity C-reactive protein and left ventricular remodeling in patients with acute myocardial infarction.

Inflammatory cytokines are suspected to play an important role in the pathophysiology of left ventricular (LV) remodeling. We investigated whether high-sensitivity C-reactive protein (CRP) (hs-CRP) is a predictor for LV remodeling in patients with acute myocardial infarction (AMI) with successful reperfusion, and also whether such a situation can be avoided by the administration of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB). The subjects were 139 patients with an initial attack of anterior myocardial infarction successfully treated by reperfusion therapy. They were randomly divided into the following two groups: an angiotensin (AG) group (91 patients treated with ACEI/ARB) and a NON-AG group (48 patients not treated with ACEI/ARB). Levels of hs-CRP, creatine kinase, human atrial natriuretic polypeptide, brain natriuretic peptide (BNP), fasting blood glucose, serum lipids, fibrinogen, fibrin degradation product, prothromloin time, and activated partial thromboplastin time were measured immediately after 1, 2, 3, and 7 days, and 1 months after the onset of AMI. ACEI or ARB administration lowered hs-CRP levels and prevented the development of LV remodeling. Peak CRP levels significantly correlated with BNP levels during the acute stage (r = +0.54, P < 0.0001), end-diastolic volume index (r = +0.78, P < 0.0001), end-systolic volume index (r = +0.36, P = 0.0405), ejection fraction (r = -0.45, P = 0.0052), left ventricular end-diastolic diameter (r = +0.61, P < 0.0001), cardiac output (r = -0.52, P = 0.0005), cardiac index (r = -0.41, P = 0.0099), and systolic pulmonary arterial pressure (r = +0.48, P = 0.0017) 1 month after the onset of AMI in the NON-AG group but not in the AG group. Logistic multivariate analysis revealed that peak CRP alone was an independent risk factor for the development of LV remodeling in the NON-AG group (odds ratio = 1.79, P = 0.002). These results suggest that hs-CRP is a useful factor for predicting LV remodeling. Furthermore, ACEI or ARB administration to AMI patients showing increased hs-CRP levels during the early stage of the disease could prevent LV remodeling.

Acute myocardial infarction in a 35-year-old postpartum woman.

A 35-year-old postpartum woman was transferred to our emergency room because of severe precordial pain on the 49th day after delivery. Her ECG up on admission showed ST elevations in leads II, III, and aVF, and an emergency coronary angiography (CAG) demonstrated thrombosis in segment #1 and obstruction in segment #2 of the right coronary artery. Although percutaneous transluminal coronary angioplasty (PTCA) was performed immediately to dilate the stenotic and obstructive regions with balloons, it was not possible to achieve sufficient coronary blood flow TIMI grade 3 coronary blood flow was restored, however, through intracoronary thrombolysis. Three months after the onset of acute myocardial infarction (AMI), no significant stenosis was detected by CAG. However, a later CAG showed that the administration of acetylcholine induced spasm at the entrance and in segments # 2 and #4 of the right coronary artery. In our patient, the presence of both a vasospastic tendency and thrombophilia might have been a leading cause of the AMI, and this finding may be useful in determining future therapeutic tactics for postpartum AMI.