25-Hydroxyvitamin D Is Associated with Islet Homeostasis in Type-2 Diabetic Patients with Abdominal Obesity.

OBJECTIVE: Islet α cells input is essential for insulin secretion from ß cells. The present study aims to investigate the association between 25-hydroxyvitamin D [25(OH)D] and islet function homeostasis in type-2 diabetes (T2D) patients. METHODS: A total of 4670 T2D patients from seven communities in Shanghai, China were enrolled. The anthropometric indices, biochemical parameters, serum 25(OH)D, and islet function [including C-peptide (C-p) and glucagon] were measured. RESULTS: The fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), glucagon, and C-p levels exhibited a significantly decreasing trend in T2D patients as the 25(OH)D levels increased. Next, the population was divided into two groups: abdominal obesity and non-abdominal obesity groups. After adjustment, the 25(OH)D level was found to be associated with HbA1c, glucagon, and homeostasis model assessment of ß (HOMA-ß) in the non-abdominal obesity group. There was a significant relationship between 25(OH)D and HbA1c, glucagon, HOMA-IR, baseline insulin or C-p in the abdominal obesity group. In the abdominal obesity group, the ordinary least squares (OLS) regression and quantile regression revealed that 25(OH) D was obviously associated with glucagon and fasting C-p levels. In the abdominal obesity group, the moderate analysis revealed a significant interaction effect of 25(OH)D and glucagon on C-p (P=0.0124). Furthermore, the conditional indirect effect of 25(OH)D on the glucagon/C-p ratio was significantly lower at 1 standard deviation (SD) below the mean (P=0.0002), and lower at the mean of the course of diabetes (P=0.0007). CONCLUSION: 25(OH)D was found to be negatively correlated to glucagon and C-p in T2D patients with abdominal obesity. The 25(OH)D influenced C-p in part by influencing glucagon. The effect of 25(OH)D on the glucagon/C-p ratio in T2D patients with abdominal obesity, in terms of islet homeostasis, is influenced by the course of diabetes.

FSH may mediate the association between HbA1c and bone turnover markers in postmenopausal women with type 2 diabetes.

INTRODUCTION: Recent studies in postmenopausal women have found associations of follicle-stimulating hormone (FSH) levels with both glucose metabolism and bone turnover. The objective of the study was to investigate whether FSH may contribute to suppressed bone turnover markers (BTMs) in postmenopausal women with type 2 diabetes (T2D). MATERIALS AND METHODS: 888 postmenopausal women with T2D, 352 nondiabetes (prediabetes plus normoglycemia) were included from the METAL study. HbA1c, sex hormones, 25-hydroxy vitamin D (25(OH)D), serum procollagen type I N-terminal propeptide (P1NP), and ß-C-terminal telopeptide (ß-CTX) were measured. RESULTS: P1NP and ß-CTX decreased in postmenopausal T2D women compared with nondiabetes controls (both p < 0.001). The major factors responsible for the changes in P1NP were HbA1c (ß = - 0.050, p < 0.001), 25(OH)D (ß = - 0.003, p = 0.006), FSH (ß = 0.001, p = 0.044) and metformin (ß = - 0.109, p < 0.001), for ß-CTX were HbA1c (ß = - 0.049, p < 0.001), body mass index (BMI) (ß = - 0.011, p = 0.005), 25(OH)D (ß = - 0.003, p = 0.003), FSH (ß = 0.002, p = 0.022) and metformin (ß = - 0.091, p = 0.001) in postmenopausal T2D women based on multivariate regression analysis. With the increase in HbA1c, FSH decreased significantly (p for trend < 0.001). Mediation analysis demonstrated that FSH partly mediated the suppression of LnP1NP and Lnß-CTX by HbA1c (ß = - 0.009 and - 0.010, respectively), and Lnß-CTX by BMI (ß = - 0.015) when multiple confounders were considered (all p < 0.05). CONCLUSION: HbA1c was the crucial determinant contributing to the suppression of BTMs. FSH might play a novel mediation role in BTM suppression due to HbA1c or BMI.

Cardiovascular and renal burdens of metabolic associated fatty liver disease from serial US national surveys, 1999-2016.

BACKGROUND: Non-communicable chronic diseases have become the leading causes of disease burden worldwide. The trends and burden of "metabolic associated fatty liver disease" (MAFLD) are unknown. We aimed to investigate the cardiovascular and renal burdens in adults with MAFLD and non-alcoholic fatty liver disease (NAFLD). METHODS: Nationally representative data were analyzed including data from 19,617 non-pregnant adults aged ≥20 years from the cross-sectional US National Health and Nutrition Examination Survey periods, 1999 to 2002, 2003 to 2006, 2007 to 2010, and 2011 to 2016. MAFLD was defined by the presence of hepatic steatosis plus general overweight/obesity, type 2 diabetes mellitus, or evidence of metabolic dysregulation. RESULTS: The prevalence of MAFLD increased from 28.4% (95% confidence interval 26.3-30.6) in 1999 to 2002 to 35.8% (33.8-37.9) in 2011 to 2016. In 2011 to 2016, among adults with MAFLD, 49.0% (45.8-52.2) had hypertension, 57.8% (55.2-60.4) had dyslipidemia, 26.4% (23.9-28.9) had diabetes mellitus, 88.7% (87.0-80.1) had central obesity, and 18.5% (16.3-20.8) were current smokers. The 10-year cardiovascular risk ranged from 10.5% to 13.1%; 19.7% (17.6-21.9) had chronic kidney diseases (CKDs). Through the four periods, adults with MAFLD showed an increase in obesity; increase in treatment to lower blood pressure (BP), lipids, and hemoglobin A1c; and increase in goal achievements for BP and lipids but not in goal achievement for glycemic control in diabetes mellitus. Patients showed a decreasing 10-year cardiovascular risk over time but no change in the prevalence of CKDs, myocardial infarction, or stroke. Generally, although participants with NAFLD and those with MAFLD had a comparable prevalence of cardiovascular disease and CKD, the prevalence of MAFLD was significantly higher than that of NAFLD. CONCLUSIONS: From 1999 to 2016, cardiovascular and renal risks and diseases have become highly prevalent in adults with MAFLD. The absolute cardiorenal burden may be greater for MAFLD than for NAFLD. These data call for early identification and risk stratification of MAFLD and close collaboration between endocrinologists and hepatologists.

Association between blood cadmium and vitamin D levels in the Yangtze Plain of China in the context of rapid urbanization.

BACKGROUND: China has experienced rapid urbanization in the past 30 years. We aimed to report blood cadmium level (BCL) in the rapidly urbanized Yangtze Plain of China, and explore the association between BCL and 25-hydroxyvitamin D (25(OH)D). METHODS: Our data source was the Survey on Prevalence in East China for Metabolic Diseases and Risk Factors (SPECT-China) cross-sectional study (ChiCTR-ECS-14005052, www.chictr.org). We enrolled 3234 subjects from 12 villages in the Yangtze Plain. BCLs were measured by atomic absorption spectrometry. 25(OH)D was measured with a chemiluminescence assay. RESULTS: A total of 2560 (79.2%) subjects were diagnosed with vitamin D deficiency. The median (interquartile range) BCL was 1.80 µg/L (0.60-3.42) for men and 1.40 µg/L (0.52-3.10) for women. In women, mean 25(OH)D concentrations were inversely associated with BCL (0.401, 95% confidence interval: -0.697 to -0.105 nmol/L lower with each doubling of the BCL) after adjustment for age, educational status, current smoking, body mass index, diabetes, and season. However, there was no significant difference in 25(OH)D across the BCL tertiles for men. CONCLUSIONS: BCL in Chinese residents in the Yangtze Plain were much higher than that in developed countries. An inverse association between BCL and 25(OH)D was found in general Chinese women after multivariable adjustment. Future prospective cohort and animal studies are warranted to resolve the direction and temporality of these relationships, and to elucidate the exact mechanisms involved.

Relationship between Free Thyroxine and Islet Beta-cell Function in Euthyroid Subjects.

Thyroid hormones have a specific effect on glucose-induced insulin secretion from the pancreas. We aimed to investigate the association between euthyroid hormones and islet beta-cell function in general population and non-treated type 2 diabetes mellitus (T2DM) patients. A total of 5089 euthyroid participants (including 4601 general population and 488 non-treated T2DM patients) were identified from a cross-sectional survey on the prevalence of metabolic diseases and risk factors in East China from February 2014 to June 2016. Anthropometric indices, biochemical parameters, and thyroid hormones were measured. Compared with general population, non-treated T2DM patients exhibited higher total thyroxine (TT4) and free thyroxine (FT4) levels but lower ratio of free triiodothyronine (T3):T4 (P<0.01). HOMA-ß had prominently negative correlation with FT4 and positive relationship with free T3:T4 in both groups even after adjusting for age, body mass index (BMI) and smoking. When analyzed by quartiles of FT4 or free T3:T4, there were significantly decreased trend of HOMA-ß going with the higher FT4 and lower free T3:T4 in both groups. Linear regression analysis showed that FT4 but not FT3 and free T3:T4 was negatively associated with HOMA-ß no matter in general population or T2DM patients, which was independent of age, BMI, smoking, hypertension and lipid profiles. FT4 is independently and negatively associated with islet beta-cell function in euthyroid subjects. Thyroid hormone even in reference range could play an important role in the function of pancreatic islets.

Shifts in the Bacterial Community of Supragingival Plaque Associated With Metabolic-Associated Fatty Liver Disease.

Metabolic-associated fatty liver disease (MAFLD), also known as the hepatic manifestation of metabolic disorders, has become one of the most common chronic liver diseases worldwide. The associations between some oral resident microbes and MAFLD have been described. However, changes to the oral microbial community in patients with MAFLD remain unknown. In this study, variations to the supragingival microbiota of MAFLD patients were identified. The microbial genetic profile of supragingival plaque samples from 24 MAFLD patients and 22 healthy participants were analyzed by 16S rDNA sequencing and bioinformatics analysis. Clinical variables, including indicators of insulin resistance, obesity, blood lipids, and hepatocellular damage, were evaluated with laboratory tests and physical examinations. The results showed that the diversity of the supragingival microbiota in MAFLD patients was significantly higher than that in healthy individuals. Weighted UniFrac principal coordinates analysis and partial least squares discriminant analysis showed that the samples from the MAFLD and control groups formed separate clusters (Adonis, P = 0.0120). There were 27 taxa with differential distributions (linear discriminant analysis, LDA>2.0) between two groups, among which Actinomyces spp. and Prevotella 2 spp. were over-represented in the MAFLD group with highest LDA score, while Neisseria spp. and Bergeyella spp. were more abundant in the control group. Co-occurrence networks of the top 50 abundant genera in the two groups suggested that the inter-genera relationships were also altered in the supragingival plaque of MAFLD patients. In addition, in genus level, as risk factors for the development of MAFLD, insulin resistance was positively correlated with the abundances of Granulicatella, Veillonella, Streptococcus, and Scardovia, while obesity was positively correlated to the abundances of Streptococcus, Oslenella, Scardovia, and Selenomonas. Metagenomic predictions based on Phylogenetic Investigation of Communities by Reconstruction of Unobserved States revealed that pathways related to sugar (mainly free sugar) metabolism were enriched in the supragingival plaque of the MAFLD group. In conclusion, as compared to healthy individuals, component and interactional dysbioses were observed in the supragingival microbiota of the MAFLD group.

Let-7g inhibits synthesis of estradiol by downregulating activity of aromatase in JEG3 cells.

BACKGROUND: Increased production of estrogen in human placenta during pregnancy closely associates with parturition. Aromatase, encoded by CYP19A1 gene, is an enzyme critical for biosynthesis of estrogen. Despite numerous efforts in the past few decades ascribed to characterizing the mechanisms of transcriptional control of aromatase, the posttranscriptional control of CYP19A1 remains poorly understood. OBJECTIVE: In this study, we sought to investigate the role of microRNA, let-7g, in posttranscriptional regulation of aromatase in human trophoblast choriocarcinoma cell line, JEG3. METHODS AND RESULTS: We show that the expression of let-7g was downregulated in JEG3 cell line, but upregulated in primary term trophoblast; conversely, aromatase was upregulated in JEG3 but downregulated in primary trophoblast. We further show that let-7g antagomirs and mimics increased and decreased aromatase expression, respectively; and let-7g directly targeted 3'-untranslated region of CYP19A1 mRNA by using dual luciferase assay. Using ELISA, we also demonstrate that let-7g antagomirs and mimics robustly increased and decreased production of estradiol, respectively. DISCUSSION: Our results suggest that aromatase expression is regulated at multiple molecular layers in the placenta. These results further suggest that JEG3 cell line is a valuable tool to study additional mechanisms associated with human birth.

Ectopic thyroids have lower computed tomography attenuation values than orthotopic thyroids.

PURPOSE: To determine whether ectopic thyroid had the same computed tomography (CT) value as orthotopic thyroid. METHODS: Twenty-one patients with 23 ectopic thyroids and 23 controls with orthotopic thyroids underwent CT scans and were included in this retrospective study. The CT images were reviewed in a blinded fashion by two radiologists. Independent-Samples T-test was used for comparison of CT attenuation values between two groups. RESULTS: Ectopic thyroids had significantly lower non-enhanced attenuation (91.04 ± 5.97 Hounsfield Units vs. 106.56 ± 4.06 Hounsfield Units, P = 0.038) and contrast-enhanced attenuation (141.32 ± 6.42 Hounsfield Units vs. 169.82 ± 4.30 Hounsfield Units, P = 0.001) values than orthotopic thyroids. CONCLUSIONS: Ectopic thyroids have lower CT attenuation values than orthotopic thyroids probably due to the structural or functional abnormalities. The dysgenesis and pathological changes of the ectopic thyroids may contribute to functional deficiency which finally leads to decrease of the CT attenuation values.

Low vitamin D levels and non-alcoholic fatty liver disease, evidence for their independent association in men in East China: a cross-sectional study (Survey on Prevalence in East China for Metabolic Diseases and Risk Factors (SPECT-China)).

Recent studies have suggested an association between vitamin D and non-alcoholic fatty liver disease (NAFLD); however, some results are subject to debate. This study was carried out to evaluate the correlation between NAFLD and vitamin D in men and women in East China. The data were obtained from a cross-sectional study that focused on the health and metabolic status of adults in sixteen areas of East China. According to ultrasonic assessments, the patients were divided into normal and NAFLD groups. Demographic characteristics and biochemical measurements were obtained. Binary logistic regression analysis was used to explore the association. In total, 5066 subjects were enrolled, and 2193 (43·3 %) were diagnosed with NAFLD; 84·56 % of the subjects showed vitamin D deficiency. Subjects with high vitamin D levels had a lower prevalence of NAFLD, particularly male subjects. Within the highest quartile of vitamin D levels, the prevalence of NAFLD was 40·8 %, whereas the lowest quartile of vitamin D levels showed a prevalence of 62·2 %, which was unchanged in women across the vitamin D levels. Binary logistic analysis showed that decreased vitamin D levels were associated with an increased risk of NAFLD (OR 1·54; 95 % CI 1·26, 1·88). This study suggests that vitamin D levels are significantly associated with NAFLD and that vitamin D acts as an independent factor for NAFLD prevalence, particularly in males in East China. Vitamin D interventional treatment might be a new target for controlling NAFLD; elucidating the mechanism requires further research.

Impact of potentially inappropriate medication and continuity of care in a sample of Taiwan elderly patients with diabetes mellitus who have also experienced heart failure.

AIMS: Continuity of care (COC) and potentially inappropriate medication (PIM) can affect the elderly healthcare outcome. We evaluated the COC and PIM effects in older diabetes mellitus (DM) patients with heart failure (HF). METHODS: The Longitudinal Health Insurance Database of 2005 was multiple-year claim data collected from 2005 to 2010 in Taiwan. There were both 823 DM and non-DM subjects aged 65 years and older in this observational study. The COC index and 2012 Beers criteria were applied to evaluate the COC and HF-PIM in older DM patients with heart failure. The dependent variables were either hospital admissions or emergency department visits. Generalized estimating equation was used to adjust all covariates. RESULTS: During 2005-2010, the rate of HF-PIM in the elderly DM group was 86.1%, the mean COC index was 0.28 ± 0.19, the admission rate was 31.9% and the emergency department rate was 38.8 %. Lower COC index was associated with HF-PIM and HF-PIM duration in older DM patients with HF. Lower COC index was associated with hospitalizations (OR 0.07, 95% CI 0.05-0.11) and ED visits (OR 0.10, 95% CI 0.07-0.13), but HF-PIM was not significant. The duration of HF-PIM was related with poor health outcomes over 90 and 180 days for hospitalization and emergency department visit, respectively. CONCLUSION: Among elderly DM patients with HF, COC had positive effects on healthcare outcomes. Improving COC and reducing PIM duration for elderly DM patients with HF seems warranted. Geriatr Gerontol Int 2016; 16: 1117-1126.

Adherence to self-care behavior and glycemic effects using structured education.

AIMS/INTRODUCTION: The purpose of the present study was to examine glycemic control in suboptimally controlled type 2 diabetes provided by a structured education group using the Diabetes Conversation Map™ (CM™) vs usual care in a university-based hospital primary care clinic. MATERIALS AND METHODS: This was a randomized, pragmatic clinical trial. Patients with type 2 diabetes were randomly assigned to structured education or usual care groups. The primary outcome was the difference in the mean change of glycated hemoglobin (HbA1c) from baseline to 12 months. Secondary outcomes included the percentage achieving therapeutic HbA1c goal and self-behavioral changes. RESULTS: A total of 245 patients were randomly assigned to two groups (CM™ group n = 121; usual care group, n = 116). The absolute reduction of HbA1c was significantly greater in the CM™ group at 3 and 6 months (Δ = -0.59% and Δ = -1.13%, P < 0.01), but the difference was no longer statistically significant at 9 and 12 months (Δ = -0.43% and Δ = -0.49%), based on an intention-to-treat analysis. A per-protocol analysis showed the significant change was maintained at 12 months (Δ = -0.67%). In the intervention group, greater percentages of patients achieved their American Association of Diabetes Educators Self-Care Behaviours™ framework (AADE7) behavioral goals at 3 months, in particular being active, problem-solving, reducing risk and health coping. CONCLUSIONS: In type 2 diabetic patients with suboptimally controlled glucose, there were greater improvements in glucose control and self-care behavioral goals in those who underwent the CM™ education program compared with outcomes achieved in patients receiving usual care.

DPP-4 Inhibitor Linagliptin Attenuates Aß-induced Cytotoxicity through Activation of AMPK in Neuronal Cells.

AIM: It is now clear that insulin signaling has important roles in regulation of neuronal functions in the brain. Dysregulation of brain insulin signaling has been linked to neurodegenerative disease, particularly Alzheimer's disease (AD). In this regard, there is evidence that improvement of neuronal insulin signaling has neuroprotective activity against amyloid ß (Aß)-induced neurotoxicity for patients with AD. Linagliptin is an inhibitor of dipeptidylpeptidase-4 (DPP-4), which improves impaired insulin secretion and insulin downstream signaling in the in peripheral tissues. However, whether the protective effects of linagliptin involved in Aß-mediated neurotoxicity have not yet been investigated. METHODS: In the present study, we evaluated the mechanisms by which linagliptin protects against Aß-induced impaired insulin signaling and cytotoxicity in cultured SK-N-MC human neuronal cells. RESULTS: Our results showed that Aß impairs insulin signaling and causes cell death. However, linagliptin significantly protected against Aß-induced cytotoxicity, and prevented the activation of glycogen synthase kinase 3ß (GSK3ß) and tau hyperphosphorylation by restoring insulin downstream signaling. Furthermore, linagliptin alleviated Aß-induced mitochondrial dysfunction and intracellular ROS generation, which may be due to the activation of 5' AMP-activated protein kinase (AMPK)-Sirt1 signaling. This upregulation of Sirt1 expression was also observed in diabetic patients with AD coadministration of linagliptin. CONCLUSIONS: Taken together, our findings suggest linagliptin can restore the impaired insulin signaling caused by Aß in neuronal cells, suggesting DPP-4 inhibitors may have therapeutic potential for reducing Aß-induced impairment of insulin signaling and neurotoxicity in AD pathogenesis.

The Diabetes Shared Care Program and Risks of Cardiovascular Events in Type 2 Diabetes.

OBJECTIVE: The Diabetes Shared Care Program (DSCP) is an integrated diabetes care model designed to increase the quality of diabetes care in Taiwan. The efficacy of this program is unknown. Therefore, we evaluated whether participating patients had reduced risks of cardiovascular events, including coronary heart disease, stroke, and all-cause mortality. METHODS: All 120,000 diabetes patients' data in this retrospective cohort study were obtained from Taiwan's National Health Insurance Research Database. DSCP participants received integrated care from a physician, diabetes educator, and dietitian. Otherwise, non-DSCP participants visited a physician without instruction from a diabetes educator or dietitian. We followed these patients until the first hospitalizations due to cardiovascular events. The Kaplan-Meier method was used to estimate the survival curves, and the Cox proportional hazards model was applied to determine the risk of cardiovascular events. RESULTS: A total of 4458 participants and 4458 matched controls were enrolled in this study. Mean age of both participants and nonparticipants was 56 years. DSCP participants had significantly lower risks of cardiovascular events (hazard ratio [HR] 0.86; 95% confidence interval [CI], 0.78-0.95), including stroke (HR 0.84; 95% CI, 0.73-0.98) and all-cause mortality (HR 0.78; 95% CI, 0.63-0.95), compared with nonparticipants. Older age, male, history of hypertension, chronic lung disease, and prescription for insulin secretagogues or insulin tended to have higher cardiovascular risks. Nevertheless, the following drugs reduced the cardiovascular risks: biguanides, alpha-glucosidase inhibitors, and thiazolidinediones. CONCLUSIONS: Participation in the DSCP was associated with lower risks of cardiovascular events, stroke, and all-cause mortality.

Effects of hypoxic exercise training on microRNA expression and lipid metabolism in obese rat livers.

To investigate the effects of hypoxic exercise training on microRNA (miRNA) expression and the role of miRNA expression in regulating lipid metabolism, 20 dietary-induced obese SD rats were divided into a normoxic sedentary group (N, n=10) and a hypoxic exercise training group (H, n=10). After four weeks, measurements were taken of body weight, body length, fat mass, serum lipid concentration, miRNAs differentially expressed in rat liver, and gene and protein expression levels of peroxisome proliferator activated receptor α (PPARα), fatty acid synthetase (FAS), and carnitine palmitoyl transferase 1A (CPT1A) in rat liver. Body weight, Lee's index, fat mass, fat/weight ratio, and serum levels of total cholesterol (TC) and high density lipoprotein cholesterol (HDL-C) were all significantly lower in the H group than in the N group (P<0.01). Six miRNAs expressed significantly differently in the liver (P<0.05). Specifically, expression levels of miR-378b were significantly lower in the H group than in the N group (P<0.05). Compared with the normoxic sedentary group, hypoxic exercise training resulted in a lower ratio of FAS mRNA to CPT1A mRNA (P<0.05), as well as lower CPT1A protein levels (P<0.01), while a higher ratio of FAS to CPT1A protein levels (P<0.01) was observed. In conclusion, hypoxic training may elevate the resistance of high fat diet induced obesity in rats by reducing the expression of miR-378b, and decrease the fatty acid mitochondrial oxidation in obese rat livers by decreasing the protein expression of CPT1A and increasing the protein expression ratio of FAS/CPT1A.

Diabetes-related avoidable hospitalizations in Taiwan.

BACKGROUND: An avoidable hospitalization (AH) is a condition that could have been prevented through effective treatment in outpatient care. Diabetes is often referred to as an ambulatory care-sensitive condition, and its associated hospitalizations are often referred to as avoidable hospitalizations. There are limited data on avoidable hospitalizations for individuals with diabetes in Taiwan. METHOD: We used the National Health Interview Survey (NHIS) dataset to obtain diabetes-related avoidable hospitalizations for subjects aged above 12 years. We included data from 20,826 subjects who had completed the interview between 2004 and 2005. Data were collected from a total of 15,574 people, who had agreed to link their health information to the Taiwan National Health Insurance Research Database, including basic demographic variables, inpatient or outpatient medical events, admission date, discharge date, and diagnosis. The 1005 individuals who self-reported having diabetes or had at least 1 hospitalization or 2 physician service claims for diabetes mellitus with an ICD-9 diagnosis of 250 were included in the analysis. We divided those with diagnosis of diabetes into two groups: never hospitalized and hospitalized. The never hospitalized group served as the control group. We further identified hospitalized subjects with long-term complications due to diabetes (PQI-3) that included ICD-CM codes 250.4-250.9. RESULTS: The mean ages of patients with diabetes-related long-term complications in the hospitalized and never hospitalized groups were 65 years and 58 years, respectively (p-value<0.01). More than half (52%) of the patients with diabetes-related long-term complications had a body mass index (BMI) lower than 24. The hospitalized group also had lower educational status compared with that of patients in the never hospitalized group (equal to or lower than elementary school, 63% vs. 50%; junior high school, 23% vs. 14%; equal or higher than senior high school, 14% vs. 36%). Furthermore, hospitalized patients tended to have lower household monthly income, were unmarried, and did not have private medical insurance. There were no significance differences in ethnic composition between the groups. Interestingly, patients with frequent retinal examination, and those with lower body mass index had higher frequency of avoidable hospitalization (p<0.01). CONCLUSION: We found that the following factors were associated with a higher frequency of avoidable hospitalization among patients with type 2 diabetes: elderly, male, lower body mass index, lower household income, non-exercise, higher disease comorbidity, and frequent retinal examination.

Automatic functional analysis of left ventricle in cardiac cine MRI.

RATIONALE AND OBJECTIVES: A fully automated left ventricle segmentation method for the functional analysis of cine short axis (SAX) magnetic resonance (MR) images was developed, and its performance evaluated with 133 studies of subjects with diverse pathology: ischemic heart failure (n=34), non-ischemic heart failure (n=30), hypertrophy (n=32), and healthy (n=37). MATERIALS AND METHODS: The proposed automatic method locates the left ventricle (LV), then for each image detects the contours of the endocardium, epicardium, papillary muscles and trabeculations. Manually and automatically determined contours and functional parameters were compared quantitatively. RESULTS: There was no significant difference between automatically and manually determined end systolic volume (ESV), end diastolic volume (EDV), ejection fraction (EF) and left ventricular mass (LVM) for each of the four groups (paired sample t-test, α=0.05). The automatically determined functional parameters showed high correlations with those derived from manual contours, and the Bland-Altman analysis biases were small (1.51 mL, 1.69 mL, -0.02%, -0.66 g for ESV, EDV, EF and LVM, respectively). CONCLUSIONS: The proposed technique automatically and rapidly detects endocardial, epicardial, papillary muscles' and trabeculations' contours providing accurate and reproducible quantitative MRI parameters, including LV mass and EF.

Identifying a novel mutation of CYP17A1 gene from five Chinese 17α-hydroxylase/17, 20-lyase deficiency patients.

Mutations of CYP17A1 gene could cause complete or partial, combined or isolated 17α-hydroxylase/17,20-lyase enzyme deficiencies (17OHD). We intended to investigate the CYP17A1 mutation in five unrelated patients and analyze its possible influence on phenotype of an atypical 17OHD patient presented with micropenis, hypertension and intermittent hypokalemia. Steroid hormones were assayed in these patients. A novel missense mutation (c.1169C>G, p. Thr390Arg) located in exon 7 was detected in one of the patients. Homozygous c. 985_987delinsAA, p. Tyr329fs mutation was found in two patients, while compound heterozygous mutations (c. 985_987delinsAA, p. Tyr329fs/c. 932-939 del, p. Val311fs and c. 287G>A, p. Arg96Gln/c. 985_987delinsAA, p. Tyr329fs) were found in two other patients, respectively. Then, steric model analysis of CYP17A1 showed that the novel mutation T390R changed the local structure as well as the electrostatic potential of the nearby beta sheet. Finally, site-directed mutagenesis and in vitro expression were used to analyze the activity of novel mutant CYP17A1. It indicated the T390R mutant retained part of enzyme activity, which was consistent to the clinical features. In conclusion, we identified a novel missense mutation of CYP17A1 gene from a patient with micropenis, hypertension and intermittent hypokalemia, which varied from other four patients. It also expanded our understanding of genotype-phenotype correlation of the disease.

Identification of a novel mutation in CYP17A1 gene.

17α-hydroxylase/17,20-lyase deficiency (17OHD) is a rare autosomal recessive genetic disease that is characterized by low-renin hypertension, hypokalemia, and abnormal development of the genitalia. Mutations in the CYP17A1 gene account for this disease. We aim to investigate the CYP17A1 mutation and analyze its possible influence on phenotype in a Chinese patient with 17OHD. Steroid hormones were assayed. The 8 exons of the CYP17A1 gene were amplified and directly sequenced. Wild-type and mutant CYP17A1 cDNA were cloned into pcDNA3.1 expression vectors and transfected into 293T cells. Finally, 17-hydroxylase and 17,20-lyase activity were detected by using progesterone and 17-hydroxypregnenolone as the substrates. A novel missense mutation c.716 G>A located in exon 4 that changed the amino acid from arginine to glutamine (R239Q) was discovered in the patient. Steric model analysis of CYP17A1 showed that R239Q changed the local structure and the electrostatic potential. Functional study indicated that the R239Q mutant caused the complete loss of both 17α-hydroxylase and 17,20-lyase activities. Our study expanded the CYP17A1 mutation spectrum. With a functional study, we confirmed that the novel mutation caused the complete loss of both 17α-hydroxylase and 17,20-lyase activities.

Decreased hepatic glucose production in obese rats by dipeptidyl peptidase-IV inhibitor sitagliptin.

BACKGROUND: Dipeptidyl peptidase-IV (DPP-4) inhibitors are now used to improve postprandial glycemic control in type 2 diabetes. However, their effects on hepatic glucose production (HGP) in obesity are not clear. This study was designed to test the hypothesis that gluconeogenesis and HGP can be modulated by DPP-4 inhibitors in obesity. METHODS: Sprague Dawley male rats were divided into four groups, each on a different diet: general rat chow, n = 10 (G); G + sitagliptin, n = 10; high fat chow (obesity), n = 10 (55% fat calories, HFO); HFO + sitagliptin, n = 10. After 10 weeks, the rats were fasted overnight and glucose metabolism was determined using 3-(3)H-glucose and (14)C-glycerol as tracers. RESULTS: Glycerol rate of appearance (P < 0.00001), plasma glycerol (P < 0.05) and free fatty acid (FFA) (P < 0.05) concentrations, and HGP (P < 0.05) were decreased in HFO + sitagliptin group compared with HFO group, but there was no significant difference between G and G + sitagliptin groups (P > 0.05). Gluconeogenesis in HFO group was five times of that in G rats (P < 0.01), but was significantly declined in HFO + sitagliptin group (P < 0.0001). CONCLUSIONS: Gluconeogenesis and HGP were inhibited by sitagliptin in high fat-induced obese rats due to decreased glycerol availability, which was a result of reduced glycerol release from adipose tissues. The finding suggests that sitagliptin is potentially useful for controlling fasting glucose in obesity, thereby delaying or preventing the development of diabetes.

Transdifferentiation of hepatic oval cells into pancreatic islet beta-cells.

Insulin production by beta-cells derived from hepatic oval cells is a promising new approach for the treatment of diabetes. Hepatic oval cells can be redirected to the beta-cell linage by an appropriate combination of high extracellular glucose, specific extracellular matrix proteins (laminin and fibronectin), cytokines (activin A), and the expression of several differentiation-related transcription factors (Pdx-1, Ngn-3, MafA). We explore the process of hepatic oval cell transdifferentiation into pancreatic islet beta-cells and the cellular signaling pathways involved.