Risako Yamamoto

Gut Dysbiosis and Detection of “Live Gut Bacteria” in Blood of Japanese Patients With Type 2 Diabetes

OBJECTIVE Mounting evidence indicates that the gut microbiota are an important modifier of obesity and diabetes. However, so far there is no information on gut microbiota and “live gut bacteria” in the systemic circulation of Japanese patients with type 2 diabetes. RESEARCH DESIGN AND METHODS Using a sensitive reverse transcription–quantitative PCR (RT-qPCR) method, we determined the composition of fecal gut microbiota in 50 Japanese patients with type 2 diabetes and 50 control subjects, and its association with various clinical parameters, including inflammatory markers. We also analyzed the presence of gut bacteria in blood samples. RESULTS The counts of the Clostridium coccoides group, Atopobium cluster, and Prevotella (obligate anaerobes) were significantly lower (P < 0.05), while the counts of total Lactobacillus (facultative anaerobes) were significantly higher (P < 0.05) in fecal samples of diabetic patients than in those of control subjects. Especially, the counts of Lactobacillus reuteri and Lactobacillus plantarum subgroups were significantly higher (P < 0.05). Gut bacteria were detected in blood at a significantly higher rate in diabetic patients than in control subjects (28% vs. 4%, P < 0.01), and most of these bacteria were Gram-positive. CONCLUSIONS This is the first report of gut dysbiosis in Japanese patients with type 2 diabetes as assessed by RT-qPCR. The high rate of gut bacteria in the circulation suggests translocation of bacteria from the gut to the bloodstream.

Combination of the Framingham Risk Score and Carotid Intima-Media Thickness Improves the Prediction of Cardiovascular Events in Patients With Type 2 Diabetes

OBJECTIVE The aim of this study was to investigate whether carotid intima-media thickness (IMT) and brachial-ankle pulse wave velocity (baPWV) add value to the Framingham risk score (FRS) in predicting the development of cardiovascular diseases (CVDs) in type 2 diabetic patients with a negative history of CVD. RESEARCH DESIGN AND METHODS Type 2 diabetic patients (n = 783) were retrospectively recruited and followed for CVD. RESULTS During a 5.4-year follow-up period, 85 incidences of CVD were recorded (10.9%). After adjustment for conventional arterial risk factors, multivariate analysis with the Cox proportional hazards model identified IMT, but not baPWV, as a significant determinant of CVD. In addition, the combination of FRS with IMT, but not with baPWV, improved the prediction of CVD. CONCLUSIONS Carotid IMT is a significant predictor of CVD in asymptomatic type 2 diabetic patients, and the combination of FRS and IMT improves the prediction of CVD in these patients.

Association between atherosclerosis and newly classified chronic kidney disease stage for Japanese patients with type 2 diabetes

Using a new estimated glomerular filtration rate (eGFR) equation, we undertook a retrospective chart review to investigate the clinical significance of chronic kidney disease (CKD) stage for atherosclerosis in 653 Japanese patients with type 2 diabetes that were followed from January 2004 to December 2006 at Juntendo University Hospital. Diabetic patients with CKD stage 2 or 3 detected in 2004 or before had more history of cardiovascular disease (CVD) compared with those patients without CKD [ischemic heart disease (IHD): 25% vs. 9.3%, P<0.01 and stroke: 17.6% vs. 10.5%, P<0.05]. In Addition, the incidence of CVD through the observation period tended to increase with progression of CKD stage (0.9% in stage 0, 3.2% in stage 1 or 2, and 3.4% in stage > or =3, P=0.056), and patients with eGFR<75 had a higher incidence of IHD (2.5% vs. 0.3%) and IHD or Stroke (3.3% vs. 0.7%) compared with those who had eGFR > or =75. Patients with urinary albumin excretion rate (UACR) > or =20mg/g Cr also had a higher incidence of IHD or stroke compared to patients with UACR<20 (3.5% vs. 0.6%). In conclusion, diabetic patients with eGFR<75 and/or UACR > or =20 might be a high-risk population for CVD.

Morningness–eveningness questionnaire score correlates with glycated hemoglobin in middle-aged male workers with type 2 diabetes mellitus

‘Morningness’ and ‘eveningness’ represent the sleep–wake patterns of the circadian rhythm might also affect glycemic control in patients with type 2 diabetes. The aim of this study was to examine the relationship between the morningness–eveningness trait and metabolic parameters.

Effects of sitagliptin on ectopic fat contents and glucose metabolism in type 2 diabetic patients with fatty liver: A pilot study

Recent data have shown that ectopic fat accumulation in the liver worsens hepatic glucose metabolism, suggesting that fatty liver in patients with type 2 diabetes is a therapeutic target. Glucagon‐like peptide (GLP)‐1 improves fatty liver, but the effect of dipeptidyl peptidase‐4 inhibitor on fatty liver is still unclear. The present pilot study determined the effects of 12‐week treatment with sitagliptin, a dipeptidyl peptidase‐4 inhibitor, on liver fat content in type 2 diabetes with fatty liver. We also evaluated intramyocellular lipid (IMCL) and glucose kinetics during oral glucose tolerance test (OGTT) before and after the treatment.

Carotid intima-media thickness progression predicts cardiovascular events in Japanese patients with type 2 diabetes

AIMS The aim of this retrospective study was to investigate the relationship between progression of carotid intima-media thickness (cIMT) and cardiovascular events in Japanese patients with type 2 diabetes mellitus (T2DM) and free of history of cardiovascular events. METHODS Patients with T2DM (n=342) without history of cardiovascular events whose cIMT was assessed more than twice by ultrasonography were recruited and followed up for cardiovascular events. RESULTS During a mean follow-up of 7.6 years, 56 (16.4%) cardiovascular events (27 coronary events and 29 cerebrovascular events) were recorded. Multivariate analysis with the Cox proportional hazard model identified cIMT progression as a significant determinant of cardiovascular events, with a hazard ratio (HR) of 2.24 (95% confidence interval; CI, 1.25-4.03, P<0.01), in addition to baseline cIMT. The Kaplan-Meier curves also showed significantly higher event rate in patients with high cIMT progression compared with those with low cIMT progression (log-rank χ(2)=6.65; P<0.01). Furthermore, the combination of high baseline cIMT and high cIMT progression was a significant predictor of cardiovascular events. CONCLUSION Our findings suggest that cIMT progression, in addition to baseline cIMT, is a predictor of cardiovascular events in patients with T2DM without history of cardiovascular events, and that the combination of cIMT progression and baseline cIMT has a strong predictive power for such events.

Reliability and validity of the Japanese version of the Diabetes Quality-Of-Life questionnaire for Japanese patients with type 2 diabetes mellitus

ObjectiveQuality of life (QOL) is recognized as an important medical outcome. The aim of this study was to test the validity and reliability of the Japanese version of the Diabetes Quality-Of-Life (J-DQOL) questionnaire originally developed by the Diabetes Control and Complications Trial.Patients and methodsThe standard procedure for cross-culture adaptation was followed to develop the Japanese version of the J-DQOL. After linguistic validation, reliability was assessed by evaluating the test–retest reliability and internal consistency. Validity was also assessed by examining the floor and ceiling effects, factor structure, and construct validity.ResultsThe responses of 298 of 319 patients with type 2 diabetes who volunteered to answer the questionnaire were analyzed. The J-DQOL and its four scales had high degrees of internal consistency (Cronbach’s alpha, 0.73–0.91) and test–retest reliability (intraclass correlation coefficients, 0.66–0.86). Floor effects were found in the categories of worry about social/vocational issues and diabetes. Also, factor analysis indicated that the J-DQOL structure was not completely consistent with that of the original DQOL. Construct validity was confirmed by relative correlation between J-DQOL scores only and certain components of the Diabetes Treatment Satisfaction Questionnaire, the Well-being Questionnaire, and the Beck Depression Inventory measures.ConclusionsThis study confirmed the reliability of the J- DQOL questionnaire and indicates that DQOL for Japanese patients with type 2 diabetes mellitus is not valid for assessing QOL, especially with regard to worry domains.

Comparison of effects of cilnidipine and azelnidipine on blood pressure, heart rate and albuminuria in type 2 diabetics with hypertension: A pilot study.

Previous studies reported that both cilnidipine and azelnidipine have a renoprotective effect compared with amlodipine. The aim of this study was to compare the effects of cilnidipine and azelnidipine on blood pressure, heart rate and albuminuria. An open‐label prospective crossover trial was carried out. We recruited 19 type 2 diabetics treated with amlodipine (5 mg/day) at least for 12 weeks. At study entry, amlodipine was changed to cilnidipine (10 mg/day) or azelnidipine (16 mg/day) and each administered for 16 weeks. Then, the drugs were switched and the treatment was continued for another 16 weeks. Despite no differences in 24‐h blood pressure and heart rate between cilnidipine and azelnidipine, treatment with cilnidipine resulted in a greater reduction in urinary albumin:creatinine ratio than azelnidipine. Our results suggested that cilnidipine is more efficient in reducing albuminuria than azelnidipine independent of its blood pressure lowering effect in type 2 diabetic patients with hypertension. This trial was registered with UMIN (no. 000007201).

Effects of alcohol abstinence on glucose metabolism in Japanese men with elevated fasting glucose: A pilot study

It has been demonstrated that moderate alcohol consumption provides protection against the development of type 2 diabetes. However, several other reports suggested that moderate alcohol intake may increase the risk of type 2 diabetes in non-obese Japanese. The aim of present study was to investigate the effect of 1-week alcohol abstinence on hepatic insulin sensitivity and fasting plasma glucose (FPG) in non-obese Japanese men. We recruited 8 non-obese Japanese men with mildly elevated FPG and drinking habits alcohol (mean frequency; 5.6 ± 2.5 times/week, mean alcohol consumption; 32.1 ± 20.0 g/day). Before and after the 1-week alcohol abstinence, we used the 2-step hyperinsulinemic-euglycemic clamp to measure endogenous glucose production (EGP) and insulin sensitivity (IS) in muscle and liver. One-week alcohol abstinence significantly reduced both FPG by 7% (from 105.5 ± 11.7 to 98.2 ± 7.8 mg/dl, P < 0.01) and fasting EGP by 6% (from 84.1 ± 4.2 to 77.6 ± 1.6 mg/m2 per min, P < 0.01), respectively. Two–step clamp study showed that alcohol abstinence significantly improved hepatic-IS, but not muscle-IS. In conclusion, one week alcohol abstinence improved hepatic IS and FPG in non-obese Japanese men with mildly elevated FPG and drinking habits alcohol.