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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.

Recent molecular phylogenetic analyses of scleractinian corals have resulted in the discovery of cryptic lineages. To understand species diversity in corals, these lineages need to be taxonomically defined. In the present study, we report the discovery of a distinct lineage obscured by the traditional morphological variation of Fungia fungites. This taxon exists as two distinct morphs: attached and unattached. Molecular phylogenetic analyses using mitochondrial COI and nuclear ITS markers as well as morphological comparisons were performed to clarify their phylogenetic relationships and taxonomic positions. Molecular data revealed that F. fungites consists of two genetically distinct clades (A and B). Clade A is sister to a lineage including Danafungia scruposa and Halomitra pileus, while clade B formed an independent lineage genetically distant from these three species. The two morphs were also found to be included in both clades, although the attached morph was predominantly found in clade A. Morphologically, both clades were statistically different in density of septal dentation, septal number, and septal teeth shape. These results indicate that F. fungites as presently recognized is actually a species complex including at least two species. After checking type specimens, we conclude that specimens in clade A represent true F. fungites with two morphs (unattached and attached) and that all of those in clade B represent an unknown species and genus comprising an unattached morph with only one exception. These findings suggest that more unrecognized taxa with hitherto unnoticed morphological differences can be present among scleractinian corals.

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.

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

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

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.

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.

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.

AIMS To prospectively investigate the association between the number of prescribed drugs and the fracture risk in patients with type 2 diabetes. METHODS Japanese participants with type 2 diabetes (n = 4,706; 2,755 men, 1,951 postmenopausal women; mean age, 66 years) were followed for a median of 5.3 years and grouped on the basis of the number of prescribed drugs at baseline. The main outcomes were fractures at any anatomic site and fragility fractures (fractures at hip and spine sites). RESULTS During follow-up, any fracture occurred in 662 participants. The overall age- and sex-adjusted fracture incidence rates per 1,000 person-years were 21.2 (0-2 drugs), 28.1 (3-5 drugs), 37.7 (6-8 drugs), and 44.0 (≥9 drugs) (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.

Mushroom corals are reef corals of the family Fungiidae, which live in the tropical and subtropical Indo-Pacific region. Recently, most species of this family have been revised taxonomically based on morphological and molecular analyses. However, the phylogenetic position of Cycloseris hexagonalis ( Milne Edwards and Haime, 1848 ) has not been analyzed and remains unclear. This species is believed to show allometric growth by changing its corallum shape from hexagonal in juveniles to irregularly circular with an undulated corallum margin in mature individuals. However, these morphological changes have not been monitored and their genetic basis has not been confirmed. In the present study morphological and molecular phylogenetic analyses were performed to evaluate the identity of the morpho-types in C. hexagonalis and to clarify the phylogenetic and taxonomic position of the species. In the morphological analysis, we used 20 specimens of C. hexagonalis collected from around Iriomote Island, Okinawa, Japan, and identified four morphotypes. Moreover, the molecular phylogenetic analyses using mitochondrial COI and nuclear ITS markers showed that all morpho-types of C. hexagonalis together form an independent clade, indicating that they are all conspecific. Molecular phylogenetic comparison between this species and other fungiids revealed that the clade of C. hexagonalis is clearly distant from the Cycloseris clade as well as from clades representing other genera in the Fungiidae. Considering these data, we establish a monotypic new genus, Sinuorota, to accommodate C. hexagonalis.