Regional differences in frailty among older adults with type 2 diabetes: a multicenter cross-sectional study in Japan.

BACKGROUND: Social environment may broadly impact multifaceted frailty; however, how environmental differences influence frailty in older adults with diabetes remains unclear. This study aimed to investigate regional differences in frailty in urban and rural areas among older adults with diabetes. METHODS: This cross-sectional study was conducted as part of the frailty prevention program for older adults with diabetes study. Older adults aged 60-80 years who could independently perform basic activities of daily living (ADLs) were enrolled sequentially. Trained nurses obtained patient background, complications, body weight, body composition, blood tests, grip strength, frailty assessment, and self-care score results. Regional differences in frailty were evaluated using logistic and multiple linear regression analyses. RESULTS: This study included 417 participants (269 urban and 148 rural). The prevalence of robustness was significantly lower in rural areas than in urban areas (29.7% vs. 43.9%, p = 0.018). Living in rural areas was associated with frailty (odds ratio [OR] 2.55, 95% confidence interval [CI] 1.38-4.71) and pre-frailty (OR 2.10, 95%CI 1.30-3.41). Lower instrumental ADL (B 0.28, standard error [SE] 0.073) and social ADL (B 0.265, SE 0.097) were characteristics of rural residents. CONCLUSIONS: Regional differences in frailty were observed. Older adults with diabetes living in rural areas have a higher risk of frailty owing to a decline in instrumental and social ADLs. Social environment assessment and intervention programs that include communication strategies to enable care and social participation across environments are crucial to the effective and early prevention of frailty.

Relationship Between Frailty and Diabetic Pharmacologic Therapy in Older Adults with Type 2 Diabetes: A Cross-Sectional Study.

BACKGROUND: Older adults with diabetes mellitus require drug treatment considering their frailty, cognitive function, and hypoglycemia. OBJECTIVE: We investigated the association between diabetic pharmacologic therapy and both diabetic complications and frailty across eight diabetes-specific outpatient clinics nationwide. METHODS: Participants (aged 60-80 years) who had type 2 diabetes and did not require nursing care were included in the study. Basic attributes, patient background, complications, hypoglycemic status, body weight, body composition, blood tests, grip strength, and Kihon Checklist (a frailty index) and self-care scores were obtained. Descriptive statistics, t-test, chi-square test, and regression analyses were employed for evaluation. RESULTS: Overall, 417 participants were included (224 men, 193 women, mean age 70.1 ± 5.4 years, diabetes duration 14.9 ± 10.9 years, body mass index 24.5 ± 3.8, glycated hemoglobin 7.22 ± 0.98%, proportion of individuals with frailty and prefrailty, 19.9% and 41.0%, respectively). All drugs were used more frequently in prefrailty conditions. Each diabetes medication was related to complications, body composition, and frailty, as follows: sulfonylurea (lower hypoglycemia); glinide (severe hypoglycemia, retinopathy, weaker grip strength, high Kihon Checklist score, decreased physical activities); alpha-glucosidase inhibitors (no association); biguanide (high body mass index, high body fat, stronger grip strength); thiazolidinedione (decreased instrumental activities of daily living); dipeptidyl-peptidase-4 inhibitors (no association); sodium-glucose cotransporter 2 inhibitors; retinopathy, high body mass index and Kihon Checklist score, and depressive mood); glucagon-like peptide-1 receptor agonists (high body mass index and body fat and poor nutritional status); and insulin preparations (hypoglycemia, retinopathy, neuropathy, nephropathy, cardiovascular diseases, weaker grip strength, and high Kihon Checklist score and physical inactivity). CONCLUSIONS: Some formulations, such as glinide, sodium-glucose cotransporter 2 inhibitors, and insulin, are associated with an increased frequency of frailty, warranting careful and individualized diabetes treatment.

Impact of diabetes mellitus on postoperative outcomes in individuals with non-small-cell lung cancer: A retrospective cohort study.

OBJECTIVES: Studies showing that individuals with non-small cell lung cancer (NSCLC) and diabetes mellitus (DM) have reported poor outcomes after pulmonary resection with varying results. Therefore, we investigated the clinical impact of preoperative DM on postoperative morbidity and survival in individuals with resectable NSCLC. PATIENTS AND METHODS: Data of individuals who underwent pulmonary resection for NSCLC from 2000 to 2015 were extracted from the database of Kyoto University Hospital. The primary endpoint was the incidence of postoperative complications, and secondary endpoints were postoperative length of hospital stay and overall survival. The survival rate was analyzed using the Kaplan-Meier method. RESULTS: A total of 2,219 patients were eligible for the study. The median age of participants was 67 years. Among them, 39.5% were women, and 259 (11.7%) presented with DM. The effect of DM on the incidence of postoperative complications and postoperative length of hospital stay was not significant. Although the 5-year survival rates were similar in both patients with and without DM (80.2% versus 79.4%; p = 0.158), those with DM who had a hemoglobin A1c level ≥ 8.0% had the worst survival. CONCLUSIONS: In individuals with resectable NSCLC, preoperative DM does not influence the acute phase postoperative recovery. However, poorly controlled preoperative DM could lead to low postoperative survival rates.

Overeating Risk in Overweight Young Women Is Divided into Two Types According to Appetite and Eating Behavior.

Background: The problem of obesity in young women leads to future chronic diseases, effects on reproductive health, and next-generation obesity. Thus, it is necessary to provide effective support for these women's behavioral change. The purpose of this study was to evaluate dietary-related indicators to clarify the appetite and eating behavior problems among young women. Methods: Healthy women 18-39 years of age were enrolled. Interoceptive awareness (IA) was quantified using a heartbeat perception task score. Eating behavior was examined in three ways: Three-Factor Eating Questionnaire (TFEQ), visual analog scales of subjective appetite sensations, and a food consumption test. Results: In all, 15 participants who were overweight and 50 with normal weight were analyzed. The overweight women were clustered into two groups according to the heartbeat perception task score: a low-score group (women with overweight who have low IA [OW-LOW]) and high-score group (women with overweight who have high IA [OW-HIGH]). The OW-LOW group had significantly smaller intermeal changes in hunger score compared with women with normal weight. The disinhibition score on the TFEQ for the OW-HIGH group was significantly higher than the normal-weight women, and the prospective consumption score in the fasting condition was significantly higher in women with normal weight and a high heartbeat perception task score. Conclusions: Overweight young women were characterized into two groups with different appetite and eating behavior, which is connected to the risk of overeating. An appetite characteristic is associated with a high risk of obesity among the normal-weight population. Individualized interventions tailored to the IA levels may help in improving and preventing obesity.

Nutrition-related factors associated with waiting list mortality in patients with interstitial lung disease: A retrospective cohort study.

Japanese patients with interstitial lung disease (ILD) sometimes die waiting for lung transplantation (LTx) because it takes about 2 years to receive it in Japan. We evaluated nutrition-related factors associated with waiting list mortality. Seventy-six ILD patients were hospitalized in Kyoto University Hospital at registration for LTx from 2013 to 2015. Among them, 40 patients were included and analyzed. Patient background was as follows: female, 30%; age, 50.3 ± 6.9 years; body mass index, 21.1 ± 4.0 kg/m2 ; 6-minute walk distance (6MWD), 356 ± 172 m; serum albumin, 3.8 ± 0.4 g/dL; serum transthyretin (TTR), 25.3 ± 7.5 mg/dL; and C-reactive protein, 0.5 ± 0.5 mg/dL. Median observational period was 497 (range 97-1015) days, and median survival time was 550 (95% CI 414-686) days. Survival rate was 47.5%, and mortality rate was 38.7/100 person-years. Cox analyses showed that TTR (HR 0.791, 95% CI 0.633-0.988) and 6MWD (HR 0.795, 95% CI 0.674-0.938) were independently correlated with mortality and were influenced by body fat mass and leg skeletal muscle mass, respectively. It is suggested that nutritional markers and exercise capacity are important prognostic markers in waitlisted patients, but further study is needed to determine whether nutritional intervention or exercise can change outcomes.

Sex-related differences in frailty factors in older persons with type 2 diabetes: a cross-sectional study.

BACKGROUND: This cross-sectional study aimed to describe sex-related differences in diabetes-specific factors underlying the development of frailty in older persons with type 2 diabetes. METHODS: Older persons aged 60-80 years were sequentially enrolled. Frailty and sarcopenia were evaluated using the validated Kihon checklist (KCL) and Asian Working Group for Sarcopenia algorithm, respectively. Physical function and characteristics were measured by trained nurses independently. RESULTS: This study included 213 participants. The mean age, body mass index (BMI), and glycated hemoglobin (HbA1c) level were 70.4 years, 24.3 kg/m2, and 7.4%, respectively. Prevalence of frailty was higher in women. Social and cognitive functions were lower in the prefrailty stage, while physical function was lower in the frailty stage, although there was no decrease in skeletal muscle mass. After adjustment for age, the KCL score was significantly associated with peripheral neuropathy, diet score, and coronary artery disease (CAD); frailty, with CAD and inoccupation; prefrailty, with diet score; and sarcopenia, with living alone in men. Meanwhile, the KCL score was significantly associated with living alone and skeletal muscle percentage; prefrailty, with peripheral neuropathy; and sarcopenia, with diabetes duration, LDL-cholesterol level, diet score, and irregular lifestyle in women. CONCLUSIONS: Sex differences in the risk factors of frailty should be considered when selecting preventive strategies for older persons with type 2 diabetes, early in the prefrailty stage. In particular, it is important to evaluate social participation and diet therapy in men and skeletal muscle mass and psychosocial function in women.

Sphingosine kinase 1-interacting protein is a dual regulator of insulin and incretin secretion.

Our previous study demonstrated that sphingosine kinase 1-interacting protein (SKIP, or Sphkap) is expressed in pancreatic ß-cells, and depletion of SKIP enhances glucose-stimulated insulin secretion. We find here that SKIP is also expressed in intestinal K- and L-cells and that secretion of gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) as well as insulin are significantly increased, and blood glucose levels are decreased in SKIP-deficient (SKIP-/-) mice compared with those in wild-type mice. Plasma triglyceride (Tg), LDL cholesterol, and mRNA levels of proinflammatory cytokines in adipose tissues, livers, and intestines were found to be significantly decreased in SKIP-/- mice. The phenotypic characteristics of SKIP-/- mice, including adiposity and attenuation of basal inflammation, were abolished by genetic depletion of GIP. The improvement of glucose tolerance and lipid profiles in SKIP-/- mice were cancelled by GLP-1 receptor antagonist exendin-(9-39) treatment. In summary, depletion of SKIP ameliorates glucose tolerance by enhancing secretion of insulin and incretins, improves lipid metabolism, and reduces basal inflammation levels. Thus, inhibition of SKIP action may emerge as a new option for treatment of type 2 diabetes mellitus with metabolic dysfunction.-Liu, Y., Harashima, S., Wang, Y., Suzuki, K., Tokumoto, S., Usui, R., Tatsuoka, H., Tanaka, D., Yabe, D., Harada, N., Hayashi, Y., Inagaki, N. Sphingosine kinase 1-interacting protein is a dual regulator of insulin and incretin secretion.

Long-Term Effect of the Color Record Method in Self-Monitoring of Blood Glucose on Metabolic Parameters in Type 2 Diabetes: A 2-Year Follow-up of the Color IMPACT Study.

INTRODUCTION: This article evaluates the potential long-term effect of two different color indication methods for self-monitoring of blood glucose (SMBG), the color record (CR) and color display (CD), on metabolic parameters in insulin-treated type 2 diabetes in a post-intervention period. METHODS: 101 participants with type 2 diabetes who completed the Color IMPACT study were enrolled in a 2-year comparison follow-up study. Participants continued SMBG with their usual diabetes care. The study outcomes were differences in change in HbA1c levels, blood pressure (BP), body weight and lipid profiles between the CR and non-CR arms and the CD and non-CD arms during a 1- and 2-year period of the study. RESULTS: 98 participants were analyzed. Reductions in HbA1c levels, systolic BP and low-density lipoprotein cholesterol levels were maintained in the CR arm by - 0.40% (95% CI: - 0.73 to - 0.06, p = 0.020), -1 3.2 mmHg (95% CI: - 24.1 to - 2.3, p = 0.019), - 11.4 mg/dl (95% CI: - 18.1 to - 4.6, p = 0.001), respectively, in a 1-year period. However, HbA1c and BP returned to the baseline levels during an additional 1-year period. In contrast, there were no significant changes in outcome in the CD arm during the study period. CONCLUSION: Intervention promoting self-action such as the color record method in SMBG sustains a beneficial effect on metabolic parameters after the intervention. This long-term effect is helpful for people with type 2 diabetes to manage their diabetes ABCs (HbA1c, BP, cholesterol) and to prevent diabetic complications. TRIAL REGISTRATION: UMIN clinical trials registry identifier, UMIN000006865.

Canagliflozin for the treatment of type 2 diabetes: a comparison between Japanese and non-Japanese patients.

INTRODUCTION: Canagliflozin, a sodium-glucose co-transporter-2 (SGLT2) inhibitor, improves various cardiometabolic parameters. Although canagliflozin was originally discovered in Japan, no comprehensive summary of its effects in Japanese patients has been reported. As differences exist in the pathologic features of diabetes between Japanese and non-Japanese populations, it is important to consolidate Japanese data for canagliflozin. Areas covered: The authors summarize Japanese clinical trial and post-marketing surveillance data for canagliflozin, and make comparisons with non-Japanese data. They also consider the therapeutic potential of canagliflozin in Japanese patients by presenting results from the CANagliflozin cardioVascular Assessment Study (CANVAS) Program. Expert opinion: In Japanese patients, canagliflozin 100 mg, administered as monotherapy or combination therapy, improved blood glucose, body weight, and blood pressure, and was well tolerated; the efficacy and safety profiles were comparable to previous clinical studies in other countries. In the CANVAS Program, canagliflozin reduced major cardiovascular events, and although Japan was not included in this program, canagliflozin may have cardiovascular benefits in Japanese patients, in whom control of multiple risk factors is important for preventing diabetic complications. Patients with high cardiovascular risk often have multiple comorbidities, so it is important to consider the risk-benefit balance of using SGLT2 inhibitors in individual patients.

Cross-cultural comparison of predictors for self-care behaviors in patients with type 2 diabetes.

The aim of the present study was to evaluate how culture moderates the behavioral and psychosocial predictors of diabetes self-care activities. Patients with type 2 diabetes were recruited in the outpatient department at two sites: Kyoto University hospital in Japan and the Christiana Care Health System in the USA. The data were collected by survey using questionnaires including questions on the frequency of self-care activities, behavioral and psychosocial predictors, and other background information from 149 Japanese patients and 48 American patients. The cultural impact was observed by multiple regression analyses with interaction terms on the association between emotional support and self-care activities in diet in female patients. The findings of the present study serve as an example of how cultural context can affect patients with diabetes, and lead to a better understanding of culturally sensitive behavioral intervention.

Efficacy and safety of canagliflozin as add-on therapy to a glucagon-like peptide-1 receptor agonist in Japanese patients with type 2 diabetes mellitus: A 52-week, open-label, phase IV study.

Sodium-glucose co-transporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RAs) are antihyperglycaemic agents with weight-lowering effects. The efficacy and safety of the SGLT2 inhibitor canagliflozin as add-on therapy in Japanese patients with type 2 diabetes mellitus (T2DM) and inadequate glycaemic control with a GLP-1RA (≥12 weeks) were evaluated in this phase IV study. Patients received canagliflozin 100 mg once daily for 52 weeks. Efficacy endpoints included change in glycated haemoglobin (HbA1c), fasting plasma glucose (FPG), body weight, systolic blood pressure (SBP) and HDL cholesterol from baseline to week 52. Safety endpoints included adverse events (AEs), hypoglycaemia and laboratory tests. Of the 71 patients treated with canagliflozin, 63 completed the study. At 52 weeks, HbA1c was significantly reduced from baseline (-0.70%; paired t test, P < .001). Significant changes were also observed in FPG (-34.7 mg/dL), body weight (-4.46%), SBP (-7.90 mm Hg), and HDL cholesterol (7.60%; all P < .001). The incidence of AEs, adverse drug reactions and hypoglycaemia was 71.8%, 32.4% and 9.9%, respectively. All hypoglycaemic events were mild. These findings suggest that the long-term combination of canagliflozin with a GLP-1RA is effective and well tolerated in Japanese patients with T2DM.

Whole-exome sequencing in a Japanese family with highly aggregated diabetes identifies a candidate susceptibility mutation in ADAMTSL3.

AIMS: The aim of this study was to clarify the genetic background of a family with multiple cases of diabetes accompanied by absolute insulin deficiency using whole-exome sequencing (WES). METHODS: In a Japanese family, WES was performed in four affected members with absolute insulin deficiency and two unaffected members. We focused on variants that were predicted to be disease-causing by bioinformatics and were shared by all of the four affected members but were not present in the two unaffected members. We assumed that the familial clustering of diabetes was caused by rare variants excluding those with allele frequency of more than 0.01 in the 1000 Genomes Project, the Human Genetic Variation Database, or a cohort of 105 normoglycemic controls in Japan. The rare variants were then genotyped in 2102 Japanese without diabetes and 119 Japanese with diabetes. RESULTS: Among the variants detected by WES and predicted to be disease-causing, 16 variants shared by all of the four of the affected members and not present in the two unaffected members were confirmed to be rare. Genotyping of the 16 rare variants revealed that only A137T in ADAMTSL3 (rs181914721) was observed more frequently in the 119 subjects with diabetes than in the 105 normoglycemic controls, and the allele frequency of the variant was significantly higher in the 119 subjects with diabetes than in another cohort of 2102 Japanese without diabetes. CONCLUSIONS: We propose that A137T in ADAMTSL3 is a candidate mutation for susceptibility to diabetes in this family and in the Japanese population.

Long-term efficacy and safety of canagliflozin in combination with insulin in Japanese patients with type 2 diabetes mellitus.

AIM: The aim of this study was to assess the long-term efficacy and safety of canagliflozin as add-on therapy in Japanese patients with type 2 diabetes mellitus who had inadequate glycaemic control with insulin. MATERIALS AND METHODS: The study comprised a 16-week, double-blind period in which patients were randomized to either placebo (P; N = 70) or canagliflozin (100 mg, CAN; N = 76), followed by a 36-week open-label period in which all patients received canagliflozin. The efficacy endpoints included the change in HbA1c from baseline to end of treatment. The safety endpoints were adverse events, hypoglycaemic events, and laboratory test values. RESULTS: The changes from baseline (mean ± standard deviation, last observation carried forward) in the P/CAN and CAN/CAN groups, respectively, were -1.09% ± 0.85% and -0.88% ± 0.86% for HbA1c, -1.40% ± 2.54% and -2.14% ± 2.75% for body weight, and 7.84% ± 14.37% and 8.91% ± 10.80% for HOMA2-%B (all, P < .001). Adverse events occurred in 85.1% of the P/CAN group and 92.0% of the CAN/CAN group. Hypoglycaemic events occurred in 43.3% and 54.7%, respectively. All hypoglycaemic events were mild in severity and insulin dose reduction decreased the incidence rate of hypoglycaemic events. Post-hoc ordinal logistic modelling/logistic modelling showed that lower serum C-peptide at Week 0 was a risk factor for hypoglycaemia in both the P and CAN groups in the double-blind period as well as in the canagliflozin all-treatment period. CONCLUSIONS: This study demonstrates the long-term efficacy and safety of canagliflozin combined with insulin in Japanese patients.

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.

Bullous pemphigoid associated with dipeptidyl peptidase-4 inhibitors: A report of five cases.

Bullous pemphigoid (BP) is an autoimmune blistering skin disorder. Recently, BP induced by dipeptidyl peptidase-4 (DPP-4) inhibitors has been a concern. Although DPP-4 inhibitors are commonly used in the Asian population because of their safety and efficacy, BP associated with DPP-4 inhibitors is sometimes seen in clinical settings. Here, we report five Japanese cases of BP associated with the agents. In the present cases, BP occurred in older adults using four different DPP-4 inhibitors, which showed various clinical manifestations in terms of latency period for BP, sex, glycemic control and diabetes duration. Withdrawal of DPP-4 inhibitors was effective in improving BP, and achieved remission even in cases requiring oral steroid administration and intravenous immunoglobulin therapy. Clinicians should note the importance of early diagnosis of this clinical condition and initiate prompt withdrawal of DPP-4 inhibitors.

Prognostic factors and outcomes in Japanese lung transplant candidates with interstitial lung disease.

OBJECTIVE: Young patients with advanced interstitial lung disease (ILD) are potential candidates for cadaveric lung transplantation. This study aimed to examine clinical features, outcomes, and prognostic factors in Japanese ILD patients awaiting lung transplantation. METHODS: We investigated the clinical features and outcomes of 77 consecutive candidates with ILD who were referred to Kyoto University Hospital and subsequently actively listed for lung transplant in the Japan Organ Transplant Network between 2010 and 2014. RESULTS: Of the 77 candidates, 33 had idiopathic pulmonary fibrosis (IPF) and 15 had unclassifiable ILD. During the observational period, 23 patients (30%) received lung transplantations and 49 patients (64%) died before transplantation. Of the 33 patients with IPF, 13 (39%) had a family history of ILD and 13 (39%) had an "inconsistent with usual interstitial pneumonia pattern" on high-resolution computed tomography (HRCT). The median survival time from registration was 16.7 months, and mortality was similar among patients with IPF, unclassifiable ILD, and other ILDs. Using a multivariate stepwise Cox proportional hazards model, 6-min walking distance was shown to be an independent prognostic factor in candidates with ILD (per 10 m, hazard ratio (HR): 0.97; 95% confidence interval (CI): 0.95-0.99, p<0.01), while lower body mass index (HR: 0.83; 95% CI: 0.72-0.95, p < 0.01) independently contributed to mortality in patients with IPF. CONCLUSIONS: Japanese patients with ILD awaiting transplantation had very poor outcomes regardless of their specific diagnosis. A substantial percentage of IPF patients had an atypical HRCT pattern. 6-min walking distance in ILD patients and body mass index in IPF patients were independent predictors of mortality.

Physical activity level significantly affects the survival of patients with end-stage lung disease on a waiting list for lung transplantation.

PURPOSE: Our objective was to investigate the factors predicting the survival of patients on the waiting list for lung transplantation (LT) during the waiting period, with a special emphasis on the physical activity level. METHODS: The study included 70 patients with end-stage pulmonary disease who were on the waiting list for LT at Kyoto University Hospital. We examined the association between the baseline characteristics, including the body mass index and body composition, serum albumin, serum C-reactive protein (CRP), steroid administration, physical activity level (calculated by the food frequency questionnaire) and survival during the waiting period using Kaplan-Meier curves and Cox proportional hazard regression models. RESULTS: A physical activity level of ≤1.2 was correlated with significantly decreased survival (1-year survival: 68 vs. 90.9%, p = 0.0089), with a hazard ratio (HR) of 2.24 (95% confidence interval (CI) 1.22-4.19, p = 0.0001). Hypo-albumin (HR 2.024, 95% CI 1.339-6.009, p = 0.004), a high level of CRP (HR 2.551, CI 1.229-4.892, p = 0.02), and the administration of steroids (HR 2.258, CI 1.907-5.032, p = 0.024) were also significant predictors of survival. CONCLUSIONS: Low levels of physical activity during the waiting period for LT led to decreased survival times among LT candidates.

Sphingosine kinase 1-interacting protein is a novel regulator of glucose-stimulated insulin secretion.

Glucose-stimulated insulin secretion (GSIS) is essential in keeping blood glucose levels within normal range. GSIS is impaired in type 2 diabetes, and its recovery is crucial in treatment of the disease. We find here that sphingosine kinase 1-interacting protein (SKIP, also called Sphkap) is highly expressed in pancreatic ß-cells but not in α-cells. Intraperitoneal glucose tolerance test showed that plasma glucose levels were decreased and insulin levels were increased in SKIP-/- mice compared to SKIP+/+ mice, but exendin-4-enhanced insulin secretion was masked. GSIS was amplified more in SKIP-/- but exendin-4-enhanced insulin secretion was masked compared to that in SKIP+/+ islets. The ATP and cAMP content were similarly increased in SKIP+/+ and SKIP-/- islets; depolarization-evoked, PKA and cAMP-mediated insulin secretion were not affected. Inhibition of PDE activity equally augmented GSIS in SKIP+/+ and SKIP-/- islets. These results indicate that SKIP modulates GSIS by a pathway distinct from that of cAMP-, PDE- and sphingosine kinase-dependent pathways.

Severe underweight decreases the survival rate in adult lung transplantation.

PURPOSE: The body mass index (BMI) before lung transplantation (LT) is a benchmark of the post-LT survival. The aim of the study is to determine the BMI inadequate for the post-LT survival. METHODS: We examined the survival after LT in patients grouped into the following BMI categories: <18.5 kg/m2 (underweight), 18.5-24.9 kg/m2 (normal weight), 25-29.9 kg/m2 (overweight), and ≥30.0 kg/m2 (obese) according to the World Health Organization (WHO) criteria. A more detailed categorization was made for further evaluation of the underweight group: mild (17.0 ≤ BMI < 18.5 kg/m2) and severely underweight (BMI <17.0 kg/m2). RESULTS: There was no statistically significant difference in the post-LT survival between underweight and normal-weight patients (5-year survival: 78.7 vs. 76.1%). Patients with BMI <17.0 kg/m2 had a worse prognosis than those with 17.0 ≤ BMI < 18.5 kg/m2 (5-year survival: 70.3 vs. 90.0%). CONCLUSIONS: Standard BMI categorization per the WHO criteria is inadequate for determining the post-LT survival, especially in underweight patients. For the nutritional evaluation of underweight pre-LT patients, BMI <17.0 kg/m2 should be used instead of BMI <18.5 kg/m2.

A Large Difference in Dose Timing of Basal Insulin Introduces Risk of Hypoglycemia and Overweight: A Cross-Sectional Study.

INTRODUCTION: Basal insulin should be injected at the same time each day, but people with diabetes sometimes mistime their injections. It is not known whether irregular daily dose timing affects diabetes-related factors. We report here our evaluation of the effects of deviations from a regular dosing schedule on glycemic control and hypoglycemia on patients treated with long-acting insulin (insulin glargine U100). We also consider the effects of ultra-long-acting insulin (insulin degludec) in this context. METHODS: Nineteen individuals with type 1 diabetes and 58 with type 2 diabetes were enrolled. Demographic data on all participants were retrieved from their medical records. Variation in dose timing was determined as the difference between the time of the earliest mistimed dose and the time of the latest mistimed dose, for each participant, over a 2-week period. All participants completed the Summary of Diabetes Self-Care Activities questionnaire, Problem Areas in Diabetes scale and 5-Item World Health Organization Well-being Index. Glargine U100 was switched to degludec in those individuals with type 2 diabetes who achieved inadequate glycemic control or suffered from frequent hypoglycemic episodes or who required two injections per day, and changes in hemoglobin A1c level and frequency of hypoglycemic episodes during the 12-week period were compared. RESULTS: A greater difference in dose timing was related to a higher frequency of hypoglycemic episodes and overweight in persons with type 2 diabetes. Smoking, drinking and living alone were independently associated with a greater difference in dose timing. Insulin degludec decreased the frequency of hypoglycemia and improved glycemic control in participants whose dose mistiming was >120 min. CONCLUSION: Fixed dose timing should be employed for basal insulin, as a larger difference in dose timing worsens diabetes-related factors. Insulin degludec improved glycemic control and lowered the hypoglycemia rate in persons with more irregular dose timing.