Methylation pattern of urinary DNA as a marker of kidney function decline in diabetes.

INTRODUCTION: Renal tubular injury contributes to the decline in kidney function in patients with diabetes. Cell type-specific DNA methylation patterns have been used to calculate proportions of particular cell types. In this study, we developed a method to detect renal tubular injury in patients with diabetes by detecting exfoliated tubular cells shed into the urine based on tubular cell-specific DNA methylation patterns. RESEARCH DESIGN AND METHODS: We identified DNA methylation patterns specific for human renal proximal tubular cells through compartment-specific methylome analysis. We next determined the methylation levels of proximal tubule-specific loci in urine sediment of patients with diabetes and analyzed correlation with clinical variables. RESULTS: We identified genomic loci in SMTNL2 and G6PC to be selectively unmethylated in human proximal tubular cells. The methylation levels of SMTNL2 and G6PC in urine sediment, deemed to reflect the proportion of exfoliated proximal tubular cells due to injury, correlated well with each other. Methylation levels of SMTNL2 in urine sediment significantly correlated with the annual decline in estimated glomerular filtration rate. Moreover, addition of urinary SMTNL2 methylation to a model containing known risk factors significantly improved discrimination of patients with diabetes with faster estimated glomerular filtration rate decline. CONCLUSIONS: This study demonstrates that patients with diabetes with continual loss in kidney function may be stratified by a specific DNA methylation signature through epigenetic urinalysis and provides further evidence at the level of exfoliated cells in the urine that injury of proximal tubular cells may contribute to pathogenesis of diabetic kidney disease.

Societal Marketing in the Treatment of Type 2 Diabetes Mellitus: A Longitudinal Questionnaire Survey for Michelin-Starred Restaurants in Japan.

Numerous dietary recommendations have been made for the prevention and treatment of diabetes. However, many people with diabetes regard healthy dietary behavior as wearisome and have difficulty adhering to nutrition therapy. We, therefore, conducted a questionnaire survey concerning the restaurants that serve meals suitable for people with diabetes. We first aimed to determine the number of restaurants that were aware of the need to create special menus for people with diabetes. Second, we aimed to encourage restaurants' serving of tasty, healthy food and promote easier social living for people with diabetes. We conducted our questionnaire survey every year from 2008 to 2013 on the availability of special menus for people with diabetes at restaurants listed in Michelin Guide Tokyo. We succeeded in increasing the proportion of restaurants offering special meals for people with diabetes from 6.7% (10 of 150 restaurants) in 2008 to 13.2% (32 of 242 restaurants) in 2013. As a result of the diabetes pandemic, the market for goods and services catering to people with diabetes is increasing. Diabetologists need to inform and support the food industry to produce foods that are suitable for people with diabetes and promote the serving of such foods by restaurants. This represents a new approach in the prevention and treatment of type 2 diabetes.

Practical guidance for treatment of patients with diabetes using flash glucose monitoring: a pilot study.

BACKGROUND: Flash glucose monitoring (FGM) is a factory-calibrated, blood glucose measuring sensor system for patients with diabetes. We aimed to investigate the correlation between the sensor glucose (SG) value obtained using an FGM device and the traditional self-monitoring of blood glucose (SMBG) value. METHODS: In 30 patients with diabetes under insulin treatment, SG and SMBG values were measured for 2 weeks, and the correlation between the values was analyzed. RESULTS: The mean number of accumulated measurements of SG values was 1223.2 ± 193.0, whereas that of the SMBG values was 49.2 ± 21.3. Although SG and SMBG values showed a favorable correlation (R2 = 0.8413), SG values were lower than SMBG values by an average of 7.9 ± 29.8 mg/dL. The correlation patterns fell into four types: low type (SG values lower than SMBG values; n = 12), high type (SG values higher than SMBG values; n = 3), cross type (the slope of the two regression lines crossed at a certain measurement value; n = 14), and matching type (the values overlapped; n = 1). CONCLUSIONS: Recognition of the characteristic correlation patterns between SG and SMBG values is indispensable for certified diabetes educators to provide appropriate treatment guidance to patients with diabetes.

The current status of treatment-related severe hypoglycemia in Japanese patients with diabetes mellitus: A report from the committee on a survey of severe hypoglycemia in the Japan Diabetes Society.

Despite great strides in pharmacotherapy for diabetes, there is increasing concern over the risk of hypoglycemia in patients with diabetes receiving pharmacotherapy as they become increasingly older. This has prompted the Japan Diabetes Society (JDS) to initiate a survey on the current status of severe hypoglycemia in clinical settings. In July 2015, following approval from the JDS Scientific Survey/Research Ethics Committee, the JDS extended an invitation to executive educators, who represented a total of 631 healthcare facilities accredited by the JDS for diabetes education, to participate in the proposed survey. Of these, those who expressed their willingness to participate in the survey were sent an application form required for obtaining ethical approval at these healthcare facilities and were then asked, following approval, to enter relevant clinical data on an unlinked, anonymous basis in a web-based registry. The current survey was fully funded by the JDS Scientific Survey/Research Committee. A case registry (clinical case database) was launched after facility-specific information (healthcare facility database) was collected from all participating facilities and after informed consent was obtained from all participating patients. With severe hypoglycemia defined as the "presence of hypoglycemic symptoms requiring assistance from another person to treat and preferably venous plasma glucose levels at onset/diagnosis of disease or at presentation clearly less than 60 mg/dL (capillary whole blood glucose, less than 50 mg/dL)", the current survey was conducted between April 1, 2014 and March 31, 2015, during which facility-specific information was collected from a total of 193 facilities with a total of 798 case reports collected from 113 facilities. Of the 193 respondent facilities, 149 reported having an emergency department as well, with the median number of patients who required emergency transportation services to reach these facilities totaling 4,962 annually, of which those with severe hypoglycemia accounted for 0.34% (17). The respondent facilities accommodated a total of 2,237 patients with severe hypoglycemia annually, with the number of patients thus accommodated being 6.5 patients per site. A total of 1,171 patients were admitted for severe hypoglycemia, with the number of patients thus admitted being 4.0 per site, who accounted for 52.3% of all patients visiting annually for severe hypoglycemia. A review of the 798 case reports collected during the survey revealed that 240, 480 and 78 patients had type 1 diabetes, type 2 diabetes, and other types of diabetes, respectively; those with type 2 diabetes were shown to be significantly older (median [interquartile range], 77.0 [68.0-83.0]) than those with type 1 diabetes (54.0 [41.0-67.0]) (P < 0.001); and the BMI was shown to be significantly higher for those with type 2 diabetes (22.0 [19.5-24.8] kg/m2 ) than for those with type 1 diabetes (21.3 [18.9-24.0] kg/m2 ) (P = 0.003). It was also found that the median estimated glomerular filtration rate (eGFR) was significantly lower among those with type 2 diabetes (50.6 mL [31.8-71.1]/min/1.73 m2 ) than among those with type 1 diabetes (73.3 [53.5-91.1] mL/min/1.73 m2 ) (P < 0.001). Again, the median HbA1c value at onset of severe hypoglycemia was shown to be 7.0 (6.3-8.1)% among all patients examined, 7.5 (6.9-8.6)% among those with type 1 diabetes, and 6.8 (6.1-7.6)% among those with type 2 diabetes, with the HbA1c value at onset of hypoglycemia being significantly lower among those with type 2 diabetes (P < 0.001). Antecedent symptoms of severe hypoglycemia were shown to be present, absent and unknown in 35.5, 35.6, and 28.9% of all patients, respectively, with the incidence of symptomatic hypoglycemia being significantly lower among those with type 1 diabetes (41.0%) than among those with type 2 diabetes (56.9%). The antidiabetic agents used in those with type 2 diabetes were insulin preparations (292 patients including 29 receiving concomitant sulfonylureas [SUs]) (60.8%), SUs (159 insulin-naïve patients) (33.1%), and no insulin preparations or SUs (29 patients) (6.0%). Of the 798 patients surveyed, 296 patients (37.2%) were shown to have required emergency transportation services for severe hypoglycemia before. Thus, the survey revealed, for the first time, the current status of treatment-related severe hypoglycemia in Japan and clearly highlights the acute need for implementing preventive measures against hypoglycemia not only through education on hypoglycemia but through optimization of antidiabetic therapy for those at high risk of severe hypoglycemia or those with a history of severe hypoglycemia.

The current status of treatment-related severe hypoglycemia in Japanese patients with diabetes mellitus: a report from the committee on a survey of severe hypoglycemia in the Japan Diabetes Society.

Despite great strides in pharmacotherapy for diabetes, there is increasing concern over the risk of hypoglycemia in patients with diabetes receiving pharmacotherapy as they become increasingly older. This has prompted the Japan Diabetes Society (JDS) to initiate a survey on the current status of severe hypoglycemia in clinical settings. In July 2015, following approval from the JDS Scientific Survey/Research Ethics Committee, the JDS extended an invitation to executive educators, who represented a total of 631 health-care facilities accredited by the JDS for diabetes education, to participate in the proposed survey. Of these, those who expressed their willingness to participate in the survey were sent an application form required for obtaining ethical approval at these health-care facilities and were then asked, following approval, to enter relevant clinical data on an unlinked, anonymous basis in a Web-based registry. The current survey was fully funded by the JDS Scientific Survey/Research Committee. A case registry (clinical case database) was launched after facility-specific information (healthcare facility database) was collected from all participating facilities and after informed consent was obtained from all participating patients. With severe hypoglycemia defined as the "presence of hypoglycemic symptoms requiring assistance from another person to treat and preferably venous plasma glucose levels at onset/diagnosis of disease or at presentation clearly less than 60 mg/dL (capillary whole blood glucose, less than 50 mg/dL)", the current survey was conducted between April 1, 2014 and March 31, 2015, during which facility-specific information was collected from a total of 193 facilities with a total of 798 case reports collected from 113 facilities. Of the 193 respondent facilities, 149 reported having an emergency department as well, with the median number of patients who required emergency transportation services to reach these facilities totaling 4962 annually, of which those with severe hypoglycemia accounted for 0.34% (17). The respondent facilities accommodated a total of 2237 patients with severe hypoglycemia annually, with the number of patients thus accommodated being 6.5 patients per site. A total of 1171 patients were admitted for severe hypoglycemia, with the number of patients thus admitted being 4.0 per site, who accounted for 52.3% of all patients visiting annually for severe hypoglycemia. A review of the 798 case reports collected during the survey revealed that 240, 480, and 78 patients had type 1 diabetes, type 2 diabetes, and other types of diabetes, respectively; those with type 2 diabetes were shown to be significantly older [median (interquartile range), 77.0 (68.0-83.0)] than those with type 1 diabetes [54.0 (41.0-67.0)] (P < 0.001); and the BMI was shown to be significantly higher for those with type 2 diabetes [22.0 (19.5-24.8) kg/m2] than for those with type 1 diabetes [21.3 (18.9-24.0) kg/m2] (P = 0.003). It was also found that the median estimated glomerular filtration rate (eGFR) was significantly lower among those with type 2 diabetes [50.6 mL (31.8-71.1)/min/1.73 m2] than among those with type 1 diabetes [73.3 (53.5-91.1) mL/min/1.73 m2] (P < 0.001). Again, the median HbA1c value at onset of severe hypoglycemia was shown to be 7.0 (6.3-8.1)% among all patients examined, 7.5 (6.9-8.6)% among those with type 1 diabetes, and 6.8 (6.1-7.6)% among those with type 2 diabetes, with the HbA1c value at onset of hypoglycemia being significantly lower among those with type 2 diabetes (P < 0.001). Antecedent symptoms of severe hypoglycemia were shown to be present, absent, and unknown in 35.5, 35.6, and 28.9% of all patients, respectively, with the incidence of symptomatic hypoglycemia being significantly lower among those with type 1 diabetes (41.0%) than among those with type 2 diabetes (56.9%). The antidiabetic agents used in those with type 2 diabetes were insulin preparations (292 patients including 29 receiving concomitant sulfonylureas [SUs]) (60.8%), SUs (159 insulin-naïve patients) (33.1%), and no insulin preparations or SUs (29 patients) (6.0%). Of the 798 patients surveyed, 296 patients (37.2%) were shown to have required emergency transportation services for severe hypoglycemia before. Thus, the survey revealed, for the first time, the current status of treatment-related severe hypoglycemia in Japan and clearly highlights the acute need for implementing preventive measures against hypoglycemia, not only through education on hypoglycemia but also through optimization of antidiabetic therapy for those at high risk of severe hypoglycemia or those with a history of severe hypoglycemia.

The Effect of Novel Glucose Monitoring System (Flash Glucose Monitoring) on Mental Well-being and Treatment Satisfaction in Japanese People with Diabetes.

INTRODUCTION: FreeStyle Libre (Abbot Diabetes Care Ltd) has been launched as a novel glucose monitoring system called flash glucose monitoring (FGM) in Europe. Several reports are becoming available on its usefulness and safety. To date, however, reports from Asian countries have not been made available. In this study, we evaluated its usefulness in Japanese people with diabetes in terms of its mental well-being and patient satisfaction outcomes. METHODS: Individuals with type 1 and 2 diabetes treated with insulin were enrolled, and they performed self-monitoring of blood glucose. All participants were subjected to FGM for 14 days and compared for changes in mental well-being using the WHO-Five Well-Being Index (WHO-5) (1998 version) as well as in patient satisfaction using the Diabetes Treatment Satisfaction Questionnaire (DTSQ) before and after implementation of FGM. RESULTS: The study included a total of 80 subjects (type 1/2 diabetes, 57/23). The WHO-5 scores were significantly improved from 15.5 ± 4.1 at baseline to 17.2 ± 4.5 after implementation of FGM (P < 0.001); the DTSQ scores also were significantly improved from 24.8 ± 6.0 to 26.7 ± 5.2 (P = 0.001). In type 1 diabetes, both the WHO-5 and DTSQ scores were significantly improved from baseline (P = 0.001, P = 0.001), while neither the WHO-5 scores nor the DTSQ scores were improved in type 2 diabetes. CONCLUSIONS: The study results suggest that FGM has the potential to improve mental well-being and treatment satisfaction among individuals with type 1 diabetes.

Clinical significance of serum complement factor 3 in patients with type 2 diabetes mellitus.

AIMS: Although serum complement factor 3 (C3) is an acute phase reactant mainly synthesized in the liver, several recent studies have shown high C3 gene expression in adipose tissue (AT). However, the relationship between C3 and AT levels has not been fully clarified in type 2 diabetes mellitus (T2DM) patients. METHODS: A total of 164 T2DM patients (109men and 55 women) participated in this cross-sectional study. A computed tomography scan was performed to measure visceral, subcutaneous, and total AT. The correlation between these factors and C3 levels was examined using Pearson's correlation analysis. A multivariate regression model was used to assess an independent determinant associated with C3 levels after adjusting the explanatory variables (i.e., all ATs [visceral, subcutaneous, and total], and clinical features [sex, age, body mass index, waist circumference, glycated hemoglobin, duration of diabetes, systolic blood pressure, diastolic blood pressure, aspartate aminotransferase levels, alanine aminotransferase levels, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, log(triglyceride levels), estimated glomerular filtration rate, and log(high-sensitivity C-reactive protein levels)]). RESULTS: Serum C3 levels were correlated with visceral, subcutaneous, and total AT among both men (r=0.505, p<0.001; r=0.545, p<0.001; r=0.617, p<0.001, respectively) and women (r=0.396, p=0.003; r=0.517, p<0.001; r=0.548, p<0.001, respectively). In the multivariate regression model, the association between total AT and C3 levels remained significantly positive (ß=0.490, p<0.001). CONCLUSIONS: Serum C3 levels are associated with visceral, subcutaneous, and total AT in T2DM patients. Furthermore, C3 levels seem to be a marker for overall adiposity rather than regional adiposity.

Factors affecting consultation length in a Japanese diabetes practice.

AIMS: Sufficient consultation time is important for establishing good doctor-patient relationship. We examined the factors that affect consultation length in Japanese diabetes practice. METHODS: This was a cross-sectional study performed at a diabetes clinic in central Tokyo, Japan. Regular diabetes consultations of 1197 patients with 22 physicians were analyzed. Consultation time and clinical characteristics were obtained from the electronic records. A negative binomial model, which included patient and physician characteristics, was constructed to examine the association of the variables with consultation length. RESULTS: Of the 1197 patients (mean age, 66; women, 25%; type 1 diabetes, 10%), the mean consultation time was 10.1min. In the multivariate model, longer consultation time was recorded in patients with type 1 diabetes, higher glycated hemoglobin (HbA1c), use of insulin injections, and use of hypnotics/anxiolytics. The consultation time was longer in patients with HbA1c of ⩾7.0 to <8.0% (⩾53 to <64mmol/mol), ⩾8.0 to <9.0% (⩾64 to <75mmol/mol) and ⩾9.0% (⩾75mmol/mol), compared to those with HbA1c of <7.0% (<53mmol/mol) with the ratios of 1.03 (95% confidence interval (CI)=0.96-1.10), 1.16 (95% CI=1.07-1.26) and 1.17 (95% CI=1.06-1.29), respectively. Body mass index was also associated with long consultation. Older and female physicians provided longer consultation. CONCLUSIONS: Clinical consultation length in diabetes practice was associated with certain patient and physician characteristics. The findings can be used for making diabetes consultation more efficacious, which could eventually lead to the provision of the most appropriate consultation time for individual patients.

Diabetes Affects Length of Stay and Hospital Costs for Elderly Patients with Pneumonia: An Analysis of a Hospital Administrative Database.

OBJECTIVE: The present study investigated the association of having diabetes with length of stay and hospital costs for elderly patients with pneumonia who were admitted to an acute-care hospital in Japan. METHODS: Based on the inpatient administrative claims database of an acute-care hospital in central Tokyo between 2010 and 2013, 753 patients aged ≥ 65 years who were admitted to the hospital presenting with pneumonia and discharged alive were analyzed. The association was analyzed using a negative binomial model, having adjusted for age, sex, body mass index, dyspnea grade, functional evaluation of feeding, use of mechanical ventilation, and use of renal replacement therapy. A log-linear regression model adjusted for the same variables was used in the analysis of hospital costs. RESULTS: Of the 753 patients (mean age, 82.5 years; men, 58.2%), 225 patients had diabetes. The negative binomial regression revealed that those with diabetes had a 1.19 times longer length of stay (95% CI = 1.06-1.33) compared to those without. The log-linear regression revealed that hospital costs were 1.14 times higher (95% CI = 1.04-1.25) in patients with diabetes. CONCLUSION: The presence of diabetes significantly correlated with longer length of stay and higher hospital costs for elderly patients with pneumonia.

Diabetic Microangiopathy Is an Independent Predictor of Incident Diabetic Foot Ulcer.

AIM: To determine the diabetic foot ulcer incidence and examine its association with microangiopathy complications, including diabetic retinopathy (DR) and albuminuria (Alb), in type 2 diabetes patients. METHODS: This was a retrospective cohort study of 1,305 patients with type 2 diabetes who were assigned to the following groups: Category 1, normoalbuminuria without DR (n = 712); Category 2, Alb without DR (n = 195); Category 3, normoalbuminuria with DR (n = 185); and Category 4, Alb with DR (n = 213). Cox proportional hazard models were used to compare the risks of developing diabetic foot ulcers across the categories. RESULTS: During 14,249 person-years of follow-up, 50 subjects developed diabetic foot ulcers, with incidence rates of 1.6/1,000, 1.5/1,000, 3.4/1,000, and 12.5/1,000 person-years in Categories 1, 2, 3, and 4, respectively. After adjusting for the presence of diabetic neuropathy and macroangiopathy, the hazard ratios and 95% confidence intervals (CIs) for the risk of diabetic foot ulcer development were 0.66 (95% CI, 0.18-2.36), 1.72 (95% CI, 0.67-4.42), and 3.17 (95% CI, 1.52-6.61) in Categories 2, 3, and 4, respectively, compared with Category 1. CONCLUSION: The presence of DR and Alb significantly increases the risk of diabetic foot ulcer development.

Efficacy and safety of liraglutide monotherapy compared with metformin in Japanese overweight/obese patients with type 2 diabetes.

There is little information on direct comparison between metformin and glucagon-like peptide-1 (GLP-1) receptor agonists in the Asian population. This study examined the efficacy and safety of liraglutide monotherapy compared with metformin monotherapy in overweight/obese Japanese patients with type 2 diabetes (T2DM). The study was a 24-week, open-labeled, randomized controlled study. Overweight or obese patients with T2DM aged 20-75 years with suboptimal glycemic control were randomized to liraglutide or metformin monotherapy. The primary endpoint was change in HbA1c at week 24. Secondary endpoints included changes in daily glycemic profile, body weight, incidence of hypoglycemia and other adverse events. The study, which was originally planned to enroll 50 subjects in each group, was ended with insufficient recruitment. A total of 46 subjects completed the study, and analysis was conducted in this cohort. Reduction in HbA1c at week 24 was comparable between the metformin (n = 24) and liraglutide (n = 22) groups (-0.95 ± 0.80% vs. -0.80 ± 0.88%, p = 0.77), while the liraglutide group reached maximal reduction more rapidly than did the metformin group. There was no significant difference in weight gain or incidence of hypoglycemia between the groups. Diarrhea was more frequent in the metformin group, while constipation was more frequent in the liraglutide group. There was no significant difference in treatment satisfaction between the groups. In conclusion, liraglutide and metformin monotherapy showed similar reduction in HbA1c during 24 weeks, with no difference in weight gain or incidence of hypoglycemia in overweight or obese Japanese patients with T2DM.

Past Obesity as well as Present Body Weight Status Is a Risk Factor for Diabetic Nephropathy.

Aims. We analyzed the prevalence of nephropathy according to past body weight status in Japanese subjects with type 2 diabetes because the influence of past obesity on diabetic complications is not certain. Methods. We examined the prevalence of nephropathy in 2927 subjects with type 2 diabetes mellitus according to current BMI and maximum BMI in the past. We defined "current obesity" as BMI on hospitalization of 25 or more, "previous obesity" as BMI on hospitalization of less than 25 and self-reported maximum BMI in the past of 25 or more, and "continuously lean" as maximum BMI of less than 25. Results. The prevalence of nephropathy was significantly higher in subjects with current obesity (40.6%) or previous obesity (35.6%) than in those who were continuously lean (24.3%) (P < 0.017). In logistic regression analysis, previous obesity, as well as current obesity, was a significant risk factor for nephropathy, independent of sex, age, disease duration, hypertension, dyslipidemia, HbA1c, and diabetic retinopathy. Conclusions. Obesity in the past, as well as the present body weight status, was a risk factor for diabetic nephropathy.

Baseline and 1-year interim follow-up assessment of Japanese patients initiating insulin therapy who were enrolled in the cardiovascular risk evaluation in people with type 2 diabetes on insulin therapy study: an international, multicenter, observational study.

BACKGROUND: The Cardiovascular Risk Evaluation in people with type 2 Diabetes on Insulin Therapy (CREDIT) study is an international, multicenter, observational study designed to assess metabolic parameters and cardiovascular risk of patients with type 2 diabetes mellitus (T2DM) on insulin therapy. The present report summarizes results at baseline and 1-year follow-up for the cohort of Japanese patients. METHODS: Male and female patients (n = 511), aged >40 years, with T2DM for >1 year, treated with insulin therapy for ≥1 month and <6 months were eligible for participation in the study. Glycemic and lipid parameters, duration of diabetes, diabetic complications, oral antidiabetic medications, and all hypoglycemic episodes were recorded. Effectiveness was assessed based on changes in clinical parameters and attainment of target HbA1c levels. Safety was evaluated based on episodes of hypoglycemia and weight gain. RESULTS: At baseline, the mean ± SD duration of diabetes was 11.8 ± 8.8 years. Microvascular and macrovascular diabetic complications were present in 83.4% and 25.1% of patients, respectively. At the 1-year follow-up, significant improvements were observed in mean HbA1c (10.3 ± 2.0% vs. 7.5 ± 1.3%, P < .001), fasting plasma glucose (217.3 ± 80.8 mg/dL vs. 139.0 ± 48.7 mg/dL, P < .001), and postprandial plasma glucose levels (296.1 ± 96.0 mg/dL vs. 178.2 ± 68.6 mg/dL, P < .001) compared with baseline. Mean total cholesterol (P < .001), low-density lipoprotein cholesterol (P < .001), triglycerides (P < .01), and diastolic blood pressure (P < .01) also significantly decreased. Good glycemic control (HbA1c < 7.0%) was achieved in 40% of patients at the 1-year follow-up. Glycemic control tended to be better in patients with lower baseline HbA1c levels (P < .01). Patients with a shorter duration of diabetes were more likely to achieve glycemic control and discontinue insulin for diabetes control at the 1-year follow-up (P < .05 for trend). Symptomatic hypoglycemic episodes occurred in 21.8% of patients over 6 to 12 months. CONCLUSIONS: Our results suggest that insulin treatment is an effective and safe therapeutic option in Japanese patients with T2DM, and earlier insulin initiation might be associated with better glycemic control.

Histopathological characteristics of stenosing flexor tenosynovitis in diabetic patients and possible associations with diabetes-related variables.

PURPOSE: To compare the histopathological findings of stenosing flexor tenosynovitis (SFTS) in diabetic patients with those in nondiabetic patients and to analyze the predominant characteristics of SFTS in diabetic patients by statistical methods. METHODS: We included 63 patients (63 specimens) who underwent excision of A1 pulleys for SFTS. A total of 38 patients (38 digits) were diabetic and 25 (25 digits) were nondiabetic. We obtained specimens from the proximal one-third of each A1 pulley and analyzed them by histological and immunohistochemical methods. After we identified the predominant histopathological characteristics of SFTS in patients with diabetes, we performed multiple logistic regression analysis to examine the possible associations between the histopathological characteristics and diabetes-related variables. RESULTS: We divided histopathological findings into 3 types in both diabetic and nondiabetic groups. Types 1 and 2 showed fibrocartilage metaplasia including fibrocartilage-like cells surrounded by basophilic extracellular substances. Type 2 was characterized by the presence of granulation tissue in the middle layer, which was not recognized in type 1. The granulation tissue contained newly formed microvessels, stromal cells, a small number of inflammatory cells, and extracellular matrix that showed myxomatous degeneration. Type 3 showed a decrease in fibrocartilage-like cells with surrounding extracellular eosinophilic substances, which was similar to hyaline degeneration. The histopathological features of type 2 were found in 68% of the diabetic group and in 28% of the nondiabetic group. This difference was statistically significant. The findings of type 2 were significantly associated with the severity of diabetic retinopathy and hemoglobin A1c values in the diabetic group. CONCLUSIONS: Type 2 findings were more frequent in the diabetic group than in the nondiabetic group. A pathomechanism to accelerate neovascularization and hypercellularity in the granulation tissue in the middle layer of A1 pulley may exist, especially in diabetic patients with severe retinopathy and poorly controlled hyperglycemia.

Risk for future diabetes among individuals with high-normal glycemia at 40 years of age.

OBJECTIVE: The present study investigated the risk for future diabetes among individuals with high-normal glycemia (fasting plasma glucose (FPG) of 100-109 mg/dL) in an early middle-aged population. METHODS: We retrospectively observed a workplace cohort all aged 40 and followed the incidence of diabetes according to the FPG levels at baseline. A total of 901 non-diabetic males were included in the analysis. The 10-year cumulative incidence of diabetes was calculated. The hazard ratios of developing diabetes were calculated using a Cox proportional hazards regression. RESULTS: The proportions of those with high-normal glycemia and impaired fasting glucose (IFG) (FPG of 110-125 mg/dL) at baseline were 21.5% and 4.7%. The 10-year cumulative incidence of diabetes was 14.7% and 48.9%, respectively, in these individuals. After adjustment for possible confounders, the hazard ratios of developing diabetes among individuals with high-normal glycemia and IFG were 5.2 (95% CI=2.4-11.2) and 21.3 (95% CI=9.2-49.5) relative to those with an FPG of <90 mg/dL. CONCLUSION: High-normal glycemia is a risk for future diabetes even in the relatively young and healthy workplace population. Although the relative risk is much higher in those with IFG, the absolute number of incident diabetes developing from those with high-normal glycemia seems to be considerable given the prevalence of this condition.