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Constipation was shown to be associated with higher risk of end-stage kidney disease or incident chronic kidney disease, although evidence in diabetic patients is lacking. The objective of the present study was to examine the association between constipation and diabetic kidney disease (DKD). In total, 4826 Japanese outpatients with type 2 diabetes were classified according to presence or absence of constipation (defecation frequency

Aims/Introduction The incidence of severe hypoglycemia and its risk factors including an insulin‐sensitizing adipokine, adiponectin, were prospectively investigated in Japanese patients with type 1 or insulin‐treated type 2 diabetes. Materials and Methods A total of 207 participants with type 1 diabetes (mean age 55 years) and 1,396 with insulin‐treated type 2 diabetes (mean age 65 years) from the local diabetes registry were followed for 5 years (follow‐up rate 99%). Severe hypoglycemia was defined as events requiring the assistance of others for recovery from hypoglycemia. Results The incidence of severe hypoglycemia was 9.2 per 100 person‐years in those with type 1 diabetes, and 2.3 per 100 person‐years in those with insulin‐treated type 2 diabetes, respectively. For type 1 diabetes, the risk was significant in those with a history of severe hypoglycemia within the previous year, slow eating and higher serum adiponectin (the highest vs the lowest in quartile hazard ratio 2.36, 95% confidence interval 1.22–4.69). For insulin‐treated type 2 diabetes, the risk included age ≥65 years, history of severe hypoglycemia within the previous year, alcohol consumption ≥60 g/day, larger insulin dose and higher serum adiponectin (the highest vs the lowest in quartile, hazard ratio 2.95, 95% confidence interval 1.22–4.69). For all participants, the incidence of severe hypoglycemia increased along with serum adiponectin (age‐ and sex‐adjusted hazard ratio 1.65 per 1 standard deviation increase of log serum adiponectin, 95% confidence interval 1.45–1.87). Conclusions The incidence of severe hypoglycemia was prospectively determined, and the association between severe hypoglycemia and higher serum adiponectin was observed in Japanese patients with type 1 and insulin‐treated type 2 diabetes., The incidence of severe hypoglycemia was prospectively determined in Japanese patients with type 1 and insulin‐treated type 2 diabetes. The development of severe hypoglycemia was associated with higher serum adiponectin level.

Aims/Introduction Patients with type 2 diabetes mellitus have an increased hip fracture risk. We investigated the relationship between hip fracture and all‐cause death in patients with type 2 diabetes in comparison with cardiovascular disease (CVD) or end‐stage renal disease (ERSD). Materials and Methods In total, 4,923 Japanese participants with type 2 diabetes (mean age 65 years, 2,790 men, 2,133 women) were followed for a median of 5.3 years (follow‐up rate 99.5%). We evaluated the associations between the presence of hip fracture (n = 110), upper limb fracture (n = 801), CVD (n = 1,344), ESRD (n = 104) and all‐cause death by logistic regression analysis. Results A total of 309 participants died during follow up. Multivariate‐adjusted odds ratios (ORs) for all‐cause mortality were significantly higher in participants with hip fractures than those without hip fractures (OR 2.67, 95% confidence interval [CI] 1.54–4.41), whereas the ORs for upper limb fracture were not significant. The ORs for all‐cause mortality were significantly higher in participants with CVD than those without CVD (OR 1.78, 95% CI, 1.39–2.70) and ESRD (OR 2.36, 95% CI 1.32–4.05). The ORs for all‐cause mortality of hip fracture were not affected by further adjustment for CVD and ESRD (OR 2.74, 95% CI 1.58–4.54). The cause of death was infection (40.0%), malignant neoplasm (25.0%) and CVD (15.0%) among participants with hip fracture. Conclusions Hip fractures were associated with an increased risk of death among Japanese patients with type 2 diabetes, independently of CVD and ESRD., Hip fracture is associated with increased mortality in the general population, although few studies have investigated the impact of hip fractures on the risk of death in patients with type 2 diabetes who also have a higher prevalence of fatal diseases, such as cardiovascular disease, renal disease or malignant neoplasia. In this study, the presence of hip fracture was associated with an increased risk of death among Japanese patients with type 2 diabetes, independently of cardiovascular disease and end‐stage renal disease. It should be emphasized that hip fracture is a critical event in the aging population of patients with type 2 diabetes.

Epidemiological data regarding diabetic kidney disease are accumulated insufficiently in Japan. We prospectively investigated the incidence of end-stage renal disease (ESRD) and risk factors for progression of renal dysfunction in Japanese patients with type 2 diabetes. 4904 participants with type 2 diabetes (mean age 65 years, mean estimated glomerular filtration rate (eGFR) 75 mL/min/1.73 m2, proportion of eGFR

AIM The impact of glycaemic control on fracture risk is controversial, which may be due to the possible presence of hypoglycaemia. The aim of this study was to separately investigate the impacts of severe hypoglycaemia and poor glycaemic control on fracture risk in people with type 2 diabetes. METHODS Overall, 4706 Japanese participants (2755 men and 1951 postmenopausal women) with type 2 diabetes (mean age 66 years) were followed prospectively (a median of 5.3 years; follow-up rate, 97.6%), and were stratified by severe hypoglycaemia status and glycaemic control. The primary outcome was fractures at any anatomic site. RESULTS Fractures occurred in 662 participants (249 men and 413 women). The age- and sex-adjusted incidence rates (expressed per 1000 person-years) were: 71.2 (multiple episodes of severe hypoglycaemia), 43.1 (one episode), 25.2 [HbA1c

Constipation was shown to be associated with higher risk of end-stage kidney disease or incident chronic kidney disease, although evidence in diabetic patients is lacking. The objective of the present study was to examine the association between constipation and diabetic kidney disease (DKD).In total, 4826 Japanese outpatients with type 2 diabetes were classified according to presence or absence of constipation (defecation frequency 3 times/week and/or taking laxative medication). DKD was defined as presence of decreased estimated glomerular filtration rate (eGFR 60 ml/min/1.73 mCompared with participants without constipation, the age- and sex-adjusted odds ratio for presence of DKD was 1.58 (95% confidence interval 1.38-1.82) for those with constipation. This association persisted following adjustment for potential confounding factors. Decreased defecation frequency and laxative use were also significantly associated with higher prevalence of DKD. Overall, these findings were identical even when decreased eGFR and albuminuria were separately analyzed.Constipation was associated with higher likelihood of DKD in patients with diabetes, suggesting the importance of clinical assessment of constipation to identify patients at high risk of progression of kidney disease.

We prospectively investigated the association of urinary tubule injury markers with estimated glomerular filtration rate (eGFR) decline in Japanese patients with type 2 diabetes.Urinary kidney injury molecule 1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), liver-type fatty-acid-binding protein (L-FABP), and urinary albumin-to creatinine ratio (UACR) were measured in 2,685 participants with type 2 diabetes. Renal outcomes were ≥ 30% decline in eGFR from the baseline and annual eGFR decline for 5 years.In normoalbuminuric participants, no tubular markers were associated with ≥ 30% decline in eGFR or annual eGFR changes. In those with UACR ≥ 30 mg/gCr, hazard ratios for ≥ 30% eGFR decline were 1.37 (95% confident interval (CI) 1.07-1.75) for urinary KIM-1 (1.5 µg/gCr), 1.46 (95% CI 1.13-1.66) for urinary NGAL (16.4 µg/gCr), and 1.26 (95% CI 0.94-1.66) for urinary L-FABP (12.5 µg/gCr), 2.61 (95% CI 1.64-4.17) for the combination of 3 tubular markers above the cutoff after multivariable adjustments including UACR and eGFR.The current study demonstrated that urinary tubule injury markers and their combination were significant predictors for the future eGFR decline in those with type 2 diabetes and albuminuria independently of UACR and eGFR. Urinary tubular markers may be useful to identify high-risk patients with albuminuria.

IntroductionThe impact of consuming green tea or coffee on mortality in patients with diabetes is controversial. We prospectively investigated the impact of each beverage and their combination on mortality among Japanese patients with type 2 diabetes.Research design and methodsIn all, 4923 patients (2790 men, 2133 women) with type 2 diabetes (mean age, 66 years) were followed prospectively (median, 5.3 years; follow-up rate, 99.5%). We evaluated the amount of green tea and coffee consumed using self-administered questionnaires.ResultsDuring the follow-up period, 309 participants died. The consumption of green tea, coffee, and a combination of the beverages was associated with reduced all-cause mortality. Multivariable-adjusted hazard ratios (95% CIs) for green tea were as follows: none 1.0 (referent); 0.85 (0.60–1.22) for ≤1 cup/day; 0.73 (0.51–1.03) for 2–3 cups/day; 0.60 (0.42–0.85) for ≥4 cups/day; and P for trend, 0.002. For coffee, they were: none 1.0 (referent); 0.88 (0.66–1.18) for ConclusionsHigher consumption of green tea and coffee was associated with reduced all-cause mortality: their combined effect appeared to be additive in patients with type 2 diabetes.

Aims We prospectively investigated the incidence of stroke and its subtypes, risk factors and prognosis in Japanese patients with type 2 diabetes. Methods A total of 4,875 participants with type 2 diabetes (mean age 65.4 years, male 57%, previous stroke 10%) were investigated for the development of stroke for 5 years. Risk factors were evaluated using multivariable adjusted Cox proportional models. Results The incidence rates per 1,000 person-years were 6.7 for new-onset stroke (ischemic 5.5, hemorrhagic 1.2) and 22.7 for recurrent stroke (ischemic 18.8, hemorrhagic 3.8), respectively. Ischemic stroke was significantly associated with age, male, reduced regular physical activity, HbA1c, diabetic kidney disease and previous stroke. Lacunar infarction was significantly associated with obesity, reduced regular physical activity, HbA1c and diabetic kidney disease, whereas atherothrombotic stroke was significantly associated with age, reduced intake of dietary fiber, reduced regular physical activity, HbA1c and previous stroke. Recurrent stroke was significantly associated with depressive symptom. Thirty-day and one-year survival was 76% and 64% for hemorrhagic stroke, and 96% and 91% for ischemic stroke, respectively. Conclusions The current study reemphasized the importance of glycemic control and lifestyle modification such as regular physical exercise for stroke prevention in patients with type 2 diabetes.

Background Although statins deteriorate glucose metabolism, their glucose-lowering effects have emerged in some situations. Here, we assessed whether these effects are a consequence of statins’ interaction with paraoxonase (PON)1 enzyme polymorphism. Methods Adult Japanese type 2 diabetes patients (n = 3798) were enrolled in a cross-sectional study. We used Q192R polymorphism of the PON1 gene as a representative single-nucleotide polymorphism and focused on the effects of the wild-type Q allele, in an additive manner. For patients with and without statin therapy, the associations of this allele with fasting plasma glucose (FPG), HbA1c, C-peptide, HOMA2-%β, and HOMA2-IR were investigated separately using a linear regression model, and were compared between groups by testing interactions. Sensitivity analyses were performed using propensity score to further control the imbalance of characteristics between groups. Results Among patients with statin therapy, there were linear associations of the number of Q alleles with decreased FPG and HbA1c, and with increased serum C peptide and HOMA2-%β (all P

Little is known about the combined effects of unhealthy lifestyle behaviors on glycemia. The objective of this study was to examine the association between combined modifiable lifestyle and glycemic control, as well as markers of insulin resistance and secretion. In total, 4,870 patients with type 2 diabetes were sorted by lifestyle scores. Scores were determined by summing the number of unhealthy lifestyle factors that showed a significant association with hemoglobin A1c (HbA1c) (current smoking, decreased dietary fiber intake, eating quickly, inadequate sleep duration, and obesity). The associations between lifestyle score and hemoglobin A1c (HbA1c), homeostasis model assessment of insulin resistance (HOMA2-IR), and β-cell function (HOMA2-%B) were cross-sectionally analyzed. HbA1c increased progressively with increases in lifestyle score (p for trend

Aims Constipation has been shown to be associated with a higher risk of diabetes. However, few studies have evaluated the relationship between defecation frequency, one of the major symptoms of constipation, and glycemic control in patients with diabetes. The aim of the present study was to determine the relationship between defecation frequency and HbA1c in patients with diabetes. Methods We determined the relationship between defecation frequency and HbA1c in 5029 patients with diabetes in the Fukuoka Diabetes Registry, a multi-center prospective cohort study conducted in diabetes specialist outpatient clinic (mean age 64.9 years, men 55%). Participants were classified according to their defecation frequency: ≥7, 3– Results Low defecation frequency was linearly associated with high HbA1c, with mean levels of 7.41% (95% confidence interval, 7.37–7.44%), 7.54% (7.49–7.60%) and 7.63% (7.52–7.74%) for patients with defecation frequencies of ≥7 times/week, 3– Conclusions The present study suggests the importance of assessing defecation frequency in the management of diabetes.

Cigarette smoking is an important modifiable risk factor for lifestyle diseases. The smoking rate remains high, and the prevalence of diabetes mellitus is increasing in Asian countries; however, few studies have examined the effects of smoking on chronic kidney disease (CKD) in Asian diabetic patients. The aim of the present study was to investigate the association between smoking and its cessation with CKD and its components in patients with type 2 diabetes. A total of 2770 Japanese male patients with type 2 diabetes aged ⩾20 years were divided according to the amount of cigarette smoking and the years since cessation. The associations with CKD, the urinary albumin-creatinine ratio (UACR) and the estimated glomerular filtration rate (eGFR) were cross-sectionally examined. The proportions of CKD and the mean UACR dose-dependently increased with increases in both the number of cigarettes per day and the Brinkman index compared with the never smokers. The creatinine-based eGFR also increased with increases in the amount of smoking, whereas the cystatin C-based eGFR decreased, and their average did not significantly change. These parameters exhibited inverse associations with the years after smoking cessation compared with the association with the amount of smoking. A dose-dependent association of active smoking and a graded inverse association of the years since quitting with CKD enhance the merit of smoking cessation in patients with type 2 diabetes.

BACKGROUND: Although the association between type 2 diabetes and cancer has been reported, few epidemiological studies have been conducted in Japanese patients whose leading cause of death is cancer. We prospectively studied the incidence of site-specific cancer, risk factors for developing cancer, cancer death, and survival in Japanese patients with type 2 diabetes. METHODS: We followed 4923 participants (mean age, 65 years) with type 2 diabetes attending an outpatient diabetes clinic for a median of 5.3 years (follow-up rate, 99.0%). RESULTS: During the follow-up period, cancer occurred in 450 participants (incidence rate, 22.3/1000 person-years in men and 12.2/1000 person-years in women). In men, prostate cancer was the most common cancer (4.3/1000 person-years), colorectal cancer was the second (3.6/1000 person-years), and gastric cancer was the third (3.3/1000 person-years). In women, colorectal cancer was the most common cancer (2.6/1000 person-years), gastric cancer was the second (2.0/1000 person-years), and breast cancer was the third (1.4/1000 person-years). Smoking, male sex, low-density lipoprotein cholesterol, family history of cancer, and reduced intake of isoflavone daidzein were significant risk factors for developing cancer using multivariable Cox proportional hazards models. The leading cancer death was lung cancer in men and pancreatic cancer in women. The survival was the best for prostate cancer and the worst for pancreatic cancer (2-year cancer-specific survival 95.4%, 30.0%, respectively). CONCLUSIONS: Since the leading cause of death in patients with type 2 diabetes is cancer in Japan, clinicians should be aware of epidemiological data regarding cancer besides diabetic complications.

Aims Sarcopenia is involved in the pathogenesis of increased fracture risk associated with diabetes. The serum creatinine to cystatin C (Cr/CysC) ratio has been reported as a surrogate marker for muscle mass. We aimed to prospectively investigate the relationship between the Cr/CysC ratio and fracture risk. Methods We followed 1911 postmenopausal women and 2689 men with type 2 diabetes (mean age, 66 years) for a median of 5.3 years, and divided into Cr/CysC ratio quartiles by sex. The primary outcome was fragility fractures and the secondary outcome was any fracture. Results Fragility fractures occurred in 192 participants, and any fracture occurred in 645 participants. Multivariate-adjusted hazard ratios (95% CI) for fragility fractures were 2.15 (1.19–3.88) (Q1), 1.63 (0.89–2.98) (Q2), 1.34 (0.72–2.51) (Q3) and 1.0 (ref.) (Q4) in postmenopausal women, and 1.75 (0.64–4.50) (Q1), 2.09 (0.83–5.26) (Q2), 1.56 (0.58–4.18) (Q3) and 1.0 (ref.) (Q4) in men. Those for any fracture were 1.46 (1.07–1.98) (Q1), 1.33 (0.98–1.81) (Q2), 1.40 (1.03–1.88) (Q3) and 1.0 (ref.) (Q4) in postmenopausal women, and 2.33 (1.54–3.54) (Q1), 2.02 (1.54–3.04) (Q2), 1.13 (0.71–1.78) (Q3) and 1.0 (ref.) (Q4) in men. Conclusions A lower Cr/CysC ratio is a significant risk factor for fractures in patients with type 2 diabetes.

Aims/Introduction A younger age at menarche is associated with obesity and type 2 diabetes in adult life. The impact of early‐onset menarche on obesity and glycemic control in type 2 diabetes has not been investigated. The present study examined the relationship between age at menarche and obesity and glycemic control in type 2 diabetes. Materials and Methods A total of 2,133 patients with type 2 diabetes aged ≥20 years were divided into groups according to age at menarche (≤11, 12, 13, 14 and ≥15 years). A retrospective cohort study examined the association of menarcheal age with adiposity and hemoglobin A1c. Results Age at menarche was inversely associated with body mass index (BMI) and abdominal circumference (P < 0.001). Each 1‐year decrease in age at menarche was associated with a 0.25‐kg/m2 and 0.6‐cm increase in BMI and abdominal circumference, respectively, using a multivariate‐adjusted model. Odds ratios for obesity and abdominal obesity significantly increased in participants with age at menarche ≤11 years after multivariable adjustments when age at menarche of 13 years was used as the reference (odds ratio 1.95, 95% CI 1.33–2.88, odds ratio 1.95, 95% CI 1.32–2.87, respectively). Younger age at menarche was significantly associated with higher hemoglobin A1c (P < 0.001); however, the association was not statistically significant after adjusting for BMI. Conclusions Age at menarche of ≤11 years was associated with obesity after adjusting for confounding factors, and poor glycemic control associated with high BMI in type 2 diabetes. Age at menarche should be considered during clinical assessments.

OBJECTIVE There is growing evidence that weight loss is associated with increased fracture risk in the general population. As patients with diabetes often lose weight intentionally or unintentionally, we aimed to investigate prospectively the relationship between weight loss from maximum body weight and fracture risk. RESEARCH DESIGN AND METHODS A total of 4,706 Japanese participants with type 2 diabetes (mean age 66 years), including 2,755 men and 1,951 postmenopausal women, were followed for a median of 5.3 years and were divided according to weight loss from maximum weight: RESULTS During the follow-up period, fragility fractures occurred in 198 participants. The age- and sex-adjusted incidence rates per 1,000 person-years in all participants were 6.4 ( CONCLUSIONS The current study demonstrates that ≥20% body weight loss from maximum weight is a significant risk factor for fragility fractures in patients with type 2 diabetes, especially in men.

Aims Although diabetic foot ulcer (DFU) is a serious diabetic complication, there have been no large-scale epidemiological studies of DFU in Japan. We prospectively investigated the incidences of DFU and limb amputation, the risk for developing DFU, and mortality in Japanese patients with type 2 diabetes. Methods We followed 4870 participants (mean age, 65 years) with type 2 diabetes attending an outpatient diabetes clinic for a median of 5.3 years (follow-up rate, 97.7%). The primary outcome was the development of DFU. Results During the follow-up period, DFU occurred in 74 participants (incidence rate, 2.9/1000 person-years) and limb amputation in 12 (incidence rate, 0.47/1000 person-years). DFU recurrence was observed in 21.4% of participants with history of DFU. History of DFU, chronic kidney disease (estimated glomerular filtration rate Conclusions Incidences of DFU and limb amputation were 0.3% and 0.05% per year in this Japanese cohort, respectively. Mortality significantly increased approximately 2-fold in those with DFU and/or history of DFU compared with those without.

Serum adiponectin has been reported to impact upon fracture risk in the general population. Although type 2 diabetes is associated with increased fracture risk, it is unclear whether serum adiponectin predicts fractures in individuals with type 2 diabetes. The aim of the study was to prospectively investigate the relationship between serum adiponectin and fracture risk in individuals with type 2 diabetes. In this study, data was obtained from The Fukuoka Diabetes Registry, a multicentre prospective study designed to investigate the influence of modern treatments on the prognoses of patients with diabetes mellitus. We followed 4869 participants with type 2 diabetes (mean age, 65 years), including 1951 postmenopausal women (defined as self-reported amenorrhea for >1 year) and 2754 men, for a median of 5.3 years. The primary outcomes were fractures at any site and major osteoporotic fractures (MOFs). During the follow-up period, fractures at any site occurred in 682 participants, while MOFs occurred in 277 participants. Age-adjusted HRs (95% CIs) of any fracture and MOFs for 1 SD increment in log e -transformed serum adiponectin were 1.27 (1.15, 1.40) and 1.35 (1.17, 1.55) in postmenopausal women and 1.22 (1.08, 1.38) and 1.40 (1.15, 1.71) in men, respectively. HRs (95% CIs) of MOFs for hyperadiponectinaemia (≥ 20 μg/ml) were 1.72 (1.19, 2.50) in postmenopausal women and 2.19 (1.23, 3.90) in men. The per cent attributable risk of hyperadiponectinaemia for MOFs was as high as being age ≥70 years or female sex. Higher serum adiponectin levels were significantly associated with an increased risk of fractures at any site and with an increased risk of MOFs in individuals with type 2 diabetes, including postmenopausal women.

Sleep duration is suggested to be associated with adverse health outcomes. However, few studies are available on the impact of sleep duration on metabolic syndrome in patients with diabetes, who were at high risk for cardiovascular diseases (CVD). The objective of the present study was to examine the associations of sleep duration with metabolic syndrome and insulin resistance, a major pathophysiologic feature of metabolic syndrome, in patients with type 2 diabetes.A total of 4402 Japanese patients with type 2 diabetes aged ≥20years were divided into 5 groups according to self-reported sleep duration: less than 5.5h, 5.5-6.4h, 6.5-7.4h, 7.5-8.4h, and more than 8.5h. The associations of sleep duration with metabolic syndrome and other cardiovascular risk factors were examined cross-sectionally.The proportions of patients who had metabolic syndrome increased significantly in both patients with shorter and longer sleep duration compared with those with 6.5-7.4h of sleep (P for quadratic trend0.001). This U-shaped association remained significant after adjustment for potential confounders, including total energy intake, current smoking, current drinking and depressive symptoms. Each component of metabolic syndrome also showed similar trends. Furthermore, sleep duration had a quadratic association with homeostasis model assessment of insulin resistance and high sensitivity C-reactive protein.Sleep duration was shown to have a U-shaped relationship with metabolic syndrome and insulin resistance, independent of potential confounders, and therefore may be an important modifiable risk factor for CVD prevention in patients with type 2 diabetes.

There is little information about the predictive ability of cystatin C-based estimated glomerular filtration rates (eGFRCys) for all-cause mortality in Asian populations. We compared the discriminatory ability of eGFRCys for all-cause mortality with that of creatinine-based estimated glomerular filtration rates (eGFRCr) in Japanese patients with type 2 diabetes. A total of 4869 participants were classified into four categories (eGFR ≤29, 30–59, 60–89, and ≥90 ml/min/1.73 m2) by eGFRCr and eGFRCys, and followed up for a median of 3.3 years. 150 deaths were identified. The multivariable-adjusted risk of all-cause mortality was significantly increased in eGFRCr ≤29 ml/min/1.73 m2 compared with eGFRCr ≥90 ml/min/1.73 m2 [hazard ratio (HR) 2.4 (95 % confidence interval (95 % CI) 1.2–5.0)], whereas it was significantly increased in eGFRCys 59 ml/min/1.73 m2 or lower [30–59 ml/min/1.73 m2, HR 1.9 (95 % CI 1.1–3.5); ≤29 ml/min/1.73 m2, HR 5.8 (95 % CI 2.8–12.0)]. Comparing eGFRCys with eGFRCr, the proportions of participants reclassified to lower and higher eGFR stages were 6.3 and 28.8 %, respectively. The multivariable-adjusted HRs for all-cause mortality were 1.8 (95 % CI 1.1–2.9) and 0.7 (95 % CI 0.4–1.1), respectively. The C statistic of the model including eGFRCys and other risk factors was significantly increased compared with the model including eGFRCr. The net reclassification improvement and the integrated discrimination improvement were significantly positive. Our findings suggest that eGFRCys has a stronger association with all-cause mortality and is superior to eGFRCr for predicting all-cause mortality in Japanese patients with type 2 diabetes.

Objective Cigarette smoking is an important modifiable risk factor for cardiovascular diseases. However, the effect of smoking and its cessation on glycemic control in diabetic patients has not been fully examined yet. The aim of the present study was to examine the association of smoking status with glycemic level and markers of insulin resistance and secretion in patients with type 2 diabetes mellitus. Research Design and Methods A total of 2,490 Japanese male patients with type 2 diabetes mellitus aged ≥20 years were divided according to smoking status, amount of cigarettes smoked and years since quitting. The associations with glycemic level and markers of insulin resistance and secretion were examined cross-sectionally. Results HbA1c levels increased progressively with increases in both number of cigarettes per day and pack-years of cigarette smoking compared with never smokers (P for trend = 0.001 and

OBJECTIVE: Few studies have so far investigated the impact of sleep duration on chronic kidney disease in diabetic patients. The objective of the present study was to examine the relationship between sleep duration and albuminuria in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: A total of 4,870 Japanese type 2 diabetic patients ≥20 years of age were divided into six groups according to self-reported sleep duration: less than 4.5 hours, 4.5-5.4 hours, 5.5-6.4 hours, 6.5-7.4 hours, 7.5-8.4 hours and more than 8.5 hours. The association between sleep duration and urinary albumin-creatinine ratio (UACR) was examined cross-sectionally. RESULTS: Both short and long sleep durations were significantly associated with higher UACR levels and higher proportions of patients with albuminuria (≥30 mg/g) and macroalbuminuria (≥300 mg/g) compared with a sleep duration of 6.5-7.4 hours (P for quadratic trend

Medical nutrition therapy plays a critical role in the prevention and treatment of type 2 diabetes. However, appropriate measures of eating behaviours, such as eating rate, have not yet been clearly established. The aim of the present study was to examine the associations among eating rate, obesity and cardiovascular risk factors.A total of 7,275 Japanese individuals aged ≥40 years who had normal fasting glucose levels, impaired fasting glucose or diabetes were divided into four groups according to self-reported eating rate: slow, medium, relatively fast and very fast. The associations between eating rate and various cardiovascular risk factors were investigated cross-sectionally.The proportions of participants who were obese or who had elevated waist circumference levels increased progressively with increases in eating rate (p for trend0.001), regardless of glucose tolerance status. These associations remained significant after adjustment for potential confounders, namely, age, sex, total energy intake, dietary fibre intake, current smoking, current drinking and regular exercise (p for trend0.001). Blood pressure and lipid levels also tended to increase in association with eating rate. HbA(1c) rose significantly as eating rate increased, even after multivariate adjustment, including BMI, in diabetic patients on insulin therapy (p = 0.02), whereas fasting plasma glucose did not increase significantly.Our findings suggest that eating rate is associated with obesity and other cardiovascular risk factors and therefore may be a modifiable risk factor in the management of cardiovascular risk factors and diabetes.

Este trabalho avalia de maneira detalhada diferentes parâmetros para a definição de níveis de homogeneidade e heterogeneidade em sistemas computacionais distribuídos. O objetivo é analisar a eficiência da métrica GH - Grau de Heterogeneidade - em relação a diferentes perspectivas. Métricas encontradas na literatura e benchmarks de código aberto (reconhecidos pela comunidade científica) são utilizados para quantificar a heterogeneidade do sistema computacional. A métrica GH também é empregada no AMIGO, um ambiente de escalonamento real, para analisar a sua utilização em algoritmos de escalonamento de processos. Os principais resultados obtidos neste trabalho são: a comprovação da estabilidade da métrica GH para determinar o grau de heterogeneidade de plataformas computacionais distribuídas, o uso da métrica GH com sucesso em um ambiente de escalonamento real e o desenvolvimento de um algoritmo de escalonamento adaptativo. Sub-produtos deste trabalho são: um levantamento dos principais benchmarks com código aberto e livre disponíveis na literatura, os quais podem ser utilizados em trabalhos futuros no grupo de pesquisa e a continuidade do desenvolvimento do ambiente de escalonamento AMIGO This work evaluates several parameters in a detailed way for the definition of homogeneity and heterogeneity levels in distributed computing systems. The objective is to analise the GH metric efficiency (heterogeneity degree) according to different perspectives. Metrics found in the literature and open source benchmarks (recognized by the scientific community) are both used to quantify the heterogeneity of the computational system. The GH metric is also employed in the AMIGO, a real scheduling environment, in order to evaluate its use in process scheduling algorithms. The main results obtained in this work are: the verification of the GH metric stability for determining the heterogeneity degree of distributed computing platforms; the use of the GH metric with success in a real scheduling environment and the development of an adaptive scheduling algorithm. By-products of this work are: the highlighting of the main benchmarks with open source available in the literature, which can be used in future works by the research group and the continuity of the development of the AMIGO

Aldehyde dehydrogenase 2 (ALDH2) detoxifies aldehyde produced during ethanol metabolism and oxidative stress. A genetic defect in this enzyme is common in East Asians and determines alcohol consumption behaviors. We investigated the impact of genetically determined ALDH2 activity on diabetic microvascular and macrovascular complications in relation to drinking habits in Japanese patients with type 2 diabetes mellitus. An ALDH2 single-nucleotide polymorphism (rs671) was genotyped in 4,400 patients. Additionally, the relationship of clinical characteristics with ALDH2 activity (ALDH2 *1/*1 active enzyme activity vs. *1/*2 or *2/*2 inactive enzyme activity) and drinking habits (lifetime abstainers vs. former or current drinkers) was investigated cross-sectionally (n = 691 in *1/*1 abstainers, n = 1,315 in abstainers with *2, n = 1,711 in *1/*1 drinkers, n = 683 in drinkers with *2). The multiple logistic regression analysis for diabetic complications was adjusted for age, sex, current smoking habits, leisure-time physical activity, depressive symptoms, diabetes duration, body mass index, hemoglobin A1c, insulin use, high-density lipoprotein cholesterol, systolic blood pressure and renin-angiotensin system inhibitors use. Albuminuria prevalence was significantly lower in the drinkers with *2 than that of other groups (odds ratio [95% confidence interval (CI)]: *1/*1 abstainers as the referent, 0.94 [0.76–1.16] in abstainers with *2, 1.00 [0.80–1.26] in *1/*1 drinkers, 0.71 [0.54–0.93] in drinkers with *2). Retinal photocoagulation prevalence was also lower in drinkers with ALDH2 *2 than that of other groups. In contrast, myocardial infarction was significantly increased in ALDH2 *2 carriers compared with that in ALDH2 *1/*1 abstainers (odds ratio [95% CI]: *1/*1 abstainers as the referent, 2.63 [1.28–6.13] in abstainers with *2, 1.89 [0.89–4.51] in *1/*1 drinkers, 2.35 [1.06–5.79] in drinkers with *2). In summary, patients with type 2 diabetes and ALDH2 *2 displayed a lower microvascular complication prevalence associated with alcohol consumption but a higher macrovascular complication prevalence irrespective of alcohol consumption.

Objective Although many studies have investigated the clinical characteristics of patients with diabetes with depression in Western populations, there is a lack of information regarding other ethnicities. We studied the association between clinical characteristics and depressive symptoms in Japanese patients with type 2 diabetes. Methods A total of 4218 Japanese patients with type 2 diabetes who were not taking antidepressants were divided into four groups according to the Center for Epidemiologic Studies Depression Scale (CES-D) score. The relationship between the severity of depressive symptoms and clinical parameters was examined cross-sectionally. Results After multivariate adjustments, the severity of depressive symptoms was significantly associated with body mass index, leisure-time physical activity, current smoking, sleep duration, sucrose intake, skipping breakfast, insulin use, severe hypoglycemia, dysesthesia of both feet, history of foot ulcer, photocoagulation, ischemic heart disease, and stroke. ORs for severe hypoglycemia increased significantly with the CES-D score in 2756 sulfonylurea and/or insulin-treated patients after multivariate adjustment including age, sex, duration of diabetes, glycated hemoglobin, insulin use, self-monitoring of blood glucose, leisure-time physical activity, skipping breakfast, dysesthesia of both feet, ischemic heart disease, and stroke (CES-D score ≤9, referent; 10–15, OR 1.64; 16–23, OR 2.09; ≥24, OR 3.66; p for trend Conclusions Severe hypoglycemia was positively associated with the severity of depressive symptoms in Japanese patients with type 2 diabetes independent of glycemic control, insulin therapy, lifestyle factors, and diabetic complications. As both severe hypoglycemia and depression are known risk factors for morbidity and mortality in patients with diabetes, clinicians should be aware of this association. UMIN Clinical Trial Registry 000002627.