Evaluation of Triglyceride Glucose Index and Homeostasis Model of Insulin Resistance in Patients with Polycystic Ovary Syndrome.

Purpose: To use the triglyceride glucose (TyG) index to evaluate insulin resistance (IR) in patients with polycystic ovary syndrome (PCOS) and to explore alternative indicators for early identification of IR. Patients and Methods: This study included 114 patients with PCOS and 61 healthy volunteers. Pearson or Spearman correlations were calculated to compare the association between the TyG index and triglyceride glucose body mass index (TyG-BMI) with homeostatic model assessment for IR (HOMA-IR), homeostasis model assessment for ß-cell function (HOMA-ß), quantitative insulin sensitivity check index (QUICKI), and fasting glucose-to-insulin ratio (FG-IR). The receiver operating characteristic (ROC) curve was used to evaluate the sensitivity and specificity of the TyG index and TyG-BMI in identifying IR (defined as HOMA-IR ≥2.5) in patients with PCOS. Results: Correlation analyses revealed that the TyG index of the PCOS group was positively correlated with HOMA-IR (r=0.515, P<0.01) and HOMA-ß (r=0.348, P<0.01), but negatively correlated with QUICKI (r=-0.532, P<0.01) and FG-IR (r=-0.394, P<0.01). The ROC curve of IR defined by HOMA-IR showed that the AUC value of TyG-BMI was the highest, at 0.796 (95% confidence interval (CI): 0.710-0.866, P<0.001) when the cut-off point was 191.53, with 85.3% sensitivity and 73.9% specificity values. For the TyG index, the AUC was 0.781 (95% CI: 0.693-0.853, P<0.001) when 8.51 was the cut-off point, with a sensitivity of 63.2% and specificity of 87.0%. Conclusion: This study found that the TyG index and TyG-BMI performed better than traditional lipid ratios, such as triglycerides/high density lipoprotein cholesterol (TG/HDL-C), in predicting IR and may be used as markers of IR in Chinese patients with PCOS.

Alterations of bacteriome, mycobiome and metabolome characteristics in PCOS patients with normal/overweight individuals.

To characterize the gut bacteriome, mycobiome and serum metabolome profiles in polycystic ovary syndrome (PCOS) patients with normal/overweight individuals and evaluate a potential microbiota-related diagnostic method development for PCOS, 16S rRNA and ITS2 gene sequencing using 88 fecal samples and 87 metabolome analysis from serum samples are conducted and PCOS classifiers based on multiomics markers are constructed. There are significant bacterial, fungal community and metabolite differences among PCOS patients and healthy volunteers with normal/overweight individuals. Healthy individuals with overweight/obesity display less abnormal metabolism than PCOS patients and uniquely higher abundance of the fungal genus Mortierella. Nine bacterial genera, 4 predicted pathways, 11 fungal genera and top 30 metabolites are screened out which distinguish PCOS from healthy controls, with AUCs of 0.84, 0.64, 0.85 and 1, respectively. The metabolite-derived model is more accurate than the microbe-based model in discriminating normal BMI PCOS (PCOS-LB) from normal BMI healthy (Healthy-LB), PCOS-HB from Healthy-HB. Featured bacteria, fungi, predicted pathways and serum metabolites display higher associations with free androgen index (FAI) in the cooccurrence network. In conclusion, our data reveal that hyperandrogenemia plays a central role in the dysbiosis of intestinal microecology and the change in metabolic status in patients with PCOS and that its effect exceeds the role of BMI. Healthy women with high BMI showed unique microbiota and metabolic features.The priority of predictive models in discriminating PCOS from healthy status in this study were serum metabolites, fungal taxa and bacterial taxa.

Effectiveness of clinical pharmacist-led smartphone application on medication adherence, insulin injection technique and glycemic control for women with gestational diabetes receiving multiple daily insulin injection: A randomized clinical trial.

AIM: To investigate the efficacy of a clinical pharmacist-led smartphone application (app) on medication adherence, insulin injection technique (IIT) and diabetes-related outcomes among women with gestational diabetes mellitus (GDM) receiving insulin therapy. METHOD: In all, 124 women were randomly (1:1 ratio) assigned to receive app intervention plus usual care (intervention) or usual care (control), and were followed up till 12 weeks postpartum. Interventions centralized on medication adherence and IIT. Primary outcome was medication adherence assessed by the 5-item Medication Adherence Report Scale. Secondary outcomes included IIT, insulin requirement, prepartal and puerperal glycemic control, hypoglycemia, and pregnancy and neonatal outcomes. RESULTS: A total of 119 patients completed the follow-up evaluation (58 intervention, 61 control). Significant more women with high medication adherence in the intervention group was observed (69.0% vs. 34.4%, p = 0.000). The other notable benefits (all p < 0.05) included patient percentage with appropriate IIT, lesser preprandial insulin dose, patient proportion with both qualified prepartal FPG and 2 hPG, and puerperal FPG or HbA1c, fewer hypoglycemia, and lower neonatal intensive care unit (NICU) admission rate. Cesarean delivery rate was higher among intervention cases (p < 0.05). Qualified prepartal glycemic control was related to high medication adherence and proper IIT. NICU admission was associated with complicated with gestational hypertension, deficient medication adherence and premature rupture of fetal membrane. CONCLUSION: Combined with usual care, clinical pharmacist-led smartphone app might be a valid tool for GDM management.

Reduced stress-associated FKBP5 DNA methylation together with gut microbiota dysbiosis is linked with the progression of obese PCOS patients.

Polycystic ovary syndrome (PCOS) is a common endocrine disease in females that is characterized by hyperandrogenemia, chronic anovulation, and polycystic ovaries. However, the exact etiology and pathogenesis of PCOS are still unknown. The aim of this study was to clarify the bacterial, stress status, and metabolic differences in the gut microbiomes of healthy individuals and patients with high body mass index (BMI) PCOS (PCOS-HB) and normal BMI PCOS (PCOS-LB), respectively. Here, we compared the gut microbiota characteristics of PCOS-HB, PCOS-LB, and healthy controls by 16S rRNA gene sequencing, FK506-binding protein 5 (FKBP5) DNA methylation and plasma metabolite determination. Clinical parameter comparisons indicated that PCOS patients had higher concentrations of total testosterone, androstenedione, dehydroepiandrosterone sulfate, luteinizing hormone, and HOMA-IR while lower FKBP5 DNA methylation. Significant differences in bacterial diversity and community were observed between the PCOS and healthy groups but not between the PCOS-HB and PCOS-LB groups. Bacterial species number was negatively correlated with insulin concentrations (both under fasting status and 120 min after glucose load) and HOMA-IR but positively related to FKBP5 DNA methylation. Compared to the healthy group, both PCOS groups had significant changes in bacterial genera, including Prevotella_9, Dorea, Maihella, and Slackia, and plasma metabolites, including estrone sulfate, lysophosphatidyl choline 18:2, and phosphatidylcholine (22:6e/19:1). The correlation network revealed the complicated interaction of the clinical index, bacterial genus, stress indices, and metabolites. Our work links the stress responses and gut microbiota characteristics of PCOS disease, which might afford perspectives to understand the progression of PCOS.

Evaluation of the Efficacy of Sex Hormone-Binding Globulin in Insulin Resistance Assessment Based on HOMA-IR in Patients with PCOS.

This study aimed to evaluate the efficacy of SHBG in predicting insulin resistance (IR) in newly diagnosed, untreated patients with polycystic ovary syndrome (PCOS). Hundred newly diagnosed, untreated patients with PCOS and 61 subjects without PCOS (41 healthy volunteers with normal BMI and 20 subjects with overweight/obese) were included in the study. Receiver-operating characteristic (ROC) analysis was used to assess the effectiveness of SHBG in predicting IR in overweight/obese and non-overweight PCOS patients and the optimal cut-off values of SHBG. The results showed negative correlations between log-SHBG and log-I0 (r = - 0.372, P < 0.001) and log-SHBG and log-Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) (r = - 0.393, P < 0.001) after adjusting for blood pressure, serum lipid, age, and body mass index (BMI) in all of the PCOS patients. In patients with IR (defined as HOMA-IR ≥2.29), the area under the ROC curves (AUCs) of the SHBG for ROC analysis in the non-overweight group, overweight/obese group, and all PCOS patients were 0.774 (P = 0.0001), 0.922 (P = 0.0001), and 0.885 (P = 0.0001), respectively. The optimal cut-off value of SHBG was 37 nmol/L with a sensitivity of 97.62% and specificity of 80.85% in the overweight group. In patients with IR (HOMA-IR ≥2.5), the AUCs of SHBG for ROC analysis in the non-overweight group, overweight/obese group, and all PCOS patients were 0.741 (P = 0.0003), 0.928 (P = 0.0001), and 0.880 (P = 0.0001), respectively. The optimal cut-off value of SHBG was 30.2 nmol/L with a sensitivity of 97.44% and specificity of 82.69% in the overweight/obese group. In conclusion, this study observed a negative correlation between SHBG and HOMA-IR in PCOS patients after adjustment of confounding factors. SHBG was an independent influential factor of HOMA-IR and can be used as a positive predictive marker for IR in PCOS patients, especially in those who are overweight/obese.

Obesity and Overweight Are Independently Associated with Greater Survival in Critically Ill Diabetic Patients: A Retrospective Cohort Study.

BACKGROUND: The relationship between obesity and the outcomes of critically ill diabetic patients is not completely clear. We aimed to assess the effects of obesity and overweight on the outcomes among diabetic patients in the intensive care unit (ICU). METHODS: Critically ill diabetic patients in the ICU were classified into three groups according to their body mass index. The primary outcomes were 30-day and 90-day mortality. ICU and hospital length of stay (LOS) and incidence and duration of mechanical ventilation were also assessed. Cox regression models were developed to evaluate the relationship between obesity and overweight and mortality. RESULTS: A total of 6108 eligible patients were included. The 30-day and 90-day mortality in the normal weight group were approximately 1.8 times and 1.5 times higher than in the obesity group and overweight group, respectively (P < 0.001, respectively). Meanwhile, the ICU (median (IQ): 2.9 (1.7, 5.3) vs. 2.7 (1.6, 4.8) vs. 2.8 (1.8, 5.0)) and hospital (median (IQ): 8.3 (5.4, 14.0) vs. 7.9 (5.1, 13.0) vs. 8.3 (5.3, 13.6)) LOS in the obesity group and overweight group were not longer than in the normal weight group. Compared with normal weight patients, obese patients had significantly higher incidence of mechanical ventilation (58.8% vs. 64.7%, P < 0.001) but no longer ventilation duration (median (IQ): 19.3 (7.0, 73.1) vs. 19.0 (6.0, 93.7), P = 1). Multivariate Cox regression showed that obese and overweight patients had lower 30-day (HR (95% CI): 0.62 (0.51, 0.75); 0.76 (0.62, 0.92), respectively) and 90-day (HR (95% CI): 0.60 (0.51, 0.70); 0.79 (0.67, 0.93), respectively) mortality risks than normal weight patients. CONCLUSIONS: Obesity and overweight were independently associated with greater survival in critically ill diabetic patients, without increasing the ICU and hospital LOS. Large multicenter prospective studies are needed to confirm our findings and the underlying mechanisms warrant further investigation.

Comparison of the efficacy of different androgens measured by LC-MS/MS in representing hyperandrogenemia and an evaluation of adrenal-origin androgens with a dexamethasone suppression test in patients with PCOS.

BACKGROUND: The aims of this study were to compare the efficacy of different androgens measured by liquid chromatography-mass spectrometry (LC-MS/MS) in representing hyperandrogenemia and to evaluate adrenal-origin androgens with a dexamethasone suppression test in patients with polycystic ovary syndrome (PCOS). METHODS: One hundred and two patients with PCOS and 41 healthy volunteers were recruited and total serum testosterone (TT), androstenedione (AD), dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) were measured by LC-MS/MS. ROC analysis was performed to compare the efficacy of different androgens in representing hyperandrogenemia. Dexamethasone suppression test was performed in 51 patients with PCOS and above indicators were measured after dexamethasone administration. The prediction efficacy of DHEA and DHEA-S at baseline in the dexamethasone suppression test was evaluated with ROC analysis. RESULTS: The AUCs of TT, AD, free androgen index (FAI) and DHEA-S in ROC analysis for representing hyperandrogenemia were 0.816, 0.842, 0.937 and 0.678, respectively. The optimal cutoff value of TT was 0.337 ng/ml, with a sensitivity of 72.0% and specificity of 82.93%. The optimal cutoff value for AD was 1.309 ng/ml, with a sensitivity of 81.0% and specificity of 73.17%. The optimal cutoff value of the FAI was 2.50, with a sensitivity of 87.0% and specificity of 92.68%. Alternatively, AD or FAI more than the optimal cutoff values as evidence of hyperandrogenemia had the highest sensitivity of 91.18%. The levels of cortisol, DHEA and DHEA-S were all suppressed to narrow ranges after dexamethasone administration. Nine and 8 of 51 patients with PCOS had significant decreases in TT and AD, respectively. DHEA can be used as a indicator for predicting significant decrease of TT in dexamethasone suppression test with cutoff value of 13.28 ng/ml. A total of 27.5% (14/51) of patients had DHEA-S excess, but only 1 of 9 patients who had a significant decrease in TT had elevated level of DHEA-S at baseline. CONCLUSIONS: AD measured by LC-MS/MS can represent hyperandrogenemia in PCOS patients and, combined with TT or FAI, can improve the screening efficiency of hyperandrogenemia. Seventeen percent of PCOS patients had adrenal-origin androgen dominance, with TT significantly decreasing after 2 days of dexamethasone administration. Adrenal-origin androgen dominance was not parallel with DHEA-S excess in patients with PCOS.

Effects of different diet-induced postnatal catch-up growth on glycolipid metabolism in intrauterine growth retardation male rats.

A number of studies have reported the occurrence of long-term metabolic disorders in mammals following intrauterine growth retardation (IUGR). However, the effects of dietary patterns during IUGR have not been fully elucidated. The present study aimed to evaluate the effects of different dietary patterns during critical growth windows on metabolic outcomes in the offspring of rats with IUGR. Male offspring rats from mothers fed either a normal or low-protein diet were randomly assigned to one of the following groups: Normal diet throughout pregnancy, lactation and after weaning (CON); normal diet throughout pregnancy and high-fat diet throughout lactation and after weaning (N + H + H); low-protein diet throughout pregnancy and high-fat diet throughout lactation and after weaning (IUGR + H + H); low-protein diet throughout pregnancy and lactation and high-fat diet after weaning (IUGR + L + H); and low-protein diet throughout pregnancy and normal diet throughout lactation and after weaning. During lactation, the male offspring in the N + H + H group exhibited the fastest growth rate, whereas the slowest rate was in the IUGR + L + H group. Following weaning, all IUGR groups demonstrated significant catch-up growth. Abnormal insulin tolerance were observed in the N + H + H, IUGR + H + H and IUGR + L + H groups and insulin sensitivity was decreased in IUGR + L + H group. The triglycerides/high-density lipoprotein ratio in the IUGR + L + H group was significantly higher compared with in the other groups. The abdominal circumference, Lee's index and adipocyte diameter of IUGR groups were significantly increased compared with the CON group. High levels of leptin and interleukin-6 in adipose tissues, and low adiponectin were observed in the IUGR + L + H group. Different dietary patterns during specific growth windows showed numerous impacts on glycolipid metabolism in IUGR offspring. The present study elucidated the mechanisms and potential options for IUGR treatment and prevention.

Effectiveness and safety of human amnion/chorion membrane therapy for diabetic foot ulcers: An updated meta-analysis of randomized clinical trials.

Human amnion/chorion membrane therapy has shown advantages in the management of diabetic foot ulcers and its effectiveness has been evaluated in the systematic reviews and meta-analyses. However, the number of patients included in the previous literatures was small and the safety profile of human amnion/chorion membrane therapy was not concerned. Therefore, we conducted an updated meta-analysis to better understand the effectiveness and safety of human amnion/chorion membrane therapy for diabetic foot ulcers. The PubMed, Embase, Cochrane Library, and ClinicalTrial.gov databases were searched for any randomized clinical trials comparing human amnion/chorion membrane therapy and standard therapy in the treatment of diabetic foot ulcers. Ulcer healing rate was considered as the primary outcome and the secondary outcomes mainly included mean time to ulcer healing and adverse events. Nine RCTs with 541 patients were included. Compared with merely standard therapy, human amnion/chorion membrane therapy plus standard therapy improved the ulcer healing rates at 6 weeks (RR = 3.50, 95% CI: 2.35-5.21), 12 weeks (RR = 2.09, 95% CI: 1.53-2.85) and 16 weeks (RR = 1.70, 95% CI: 1.25-2.30), and also shortened the healing time (MD = -4.58, 95% CI: -5.70 to -3.46). Meanwhile, no significant difference was observed in the number of patients with adverse events (RR = 0.56, 95% CI: 0.31-1.03) between two groups. This meta-analysis suggests that human amnion/chorion membrane therapy as an adjuvant treatment could promote the healing of diabetic foot ulcers and has a safety profile. More evidence from large high-quality randomized clinical trials with long follow-up duration are in urgent need to further confirm our findings.

The amputation and survival of patients with diabetic foot based on establishment of prediction model.

OBJECTIVE: The objective of this paper is to study the establishment of predictive models and the amputation and survival of patients with diabetic foot. METHODS: A total of 200 inpatients with diabetic foot were selected as the research subject in this study. The amputation and survival status of diabetic foot patients were followed up by telephone. The relevant indicators were screened by cluster analysis. The predictive model was established respectively based on proportional hazard regression analysis, back propagation neural network (BPNN) and BPNN based on genetic algorithm optimization, and the reliability of the three prediction models (PM) was evaluated and compared. RESULTS: The risk factors for amputation were severe ulcer disease, glycosylated hemoglobin and low-density lipoprotein cholesterol. The risk factors for death were cerebrovascular disease, severe ulcer disease and peripheral arterial disease. In case that the outcome was amputation, the PM of BPNN and the PM of BPNN based on genetic algorithm optimization have obviously higher AUC (area under the receiver operating characteristic curve) than the PM of proportional hazard regression analysis, and the difference was statistically significant (P < 0.05). Among the three PMs, the PM based on BPNN had the highest AUC, sensitivity and specificity (SAS). In case that the outcome was death, the PM of BPNN and the PM of BPNN based on genetic algorithm optimization had almost the same AUC, and were obviously higher than the PM based on proportional hazard regression analysis. The difference was statistically significant (P < 0.05). The PM based on BPNN and the BPNN based on genetic algorithm optimization had higher SAS than the PM based on COX regression analysis. CONCLUSION: The PM of BPNN and BPNN based on genetic algorithm optimization have better prediction effect than the PM based on proportional hazard regression analysis. It can be used for amputation and survival analysis of diabetic foot patients.

The Efficacy and Safety of Acellular Matrix Therapy for Diabetic Foot Ulcers: A Meta-Analysis of Randomized Clinical Trials.

BACKGROUND: Acellular matrix (AM) therapy has shown promise in the treatment of diabetic foot ulcers (DFUs) in several studies. The clinical effects of AM therapy were not well established. Therefore, we conducted a meta-analysis of randomized clinical trials (RCTs) to examine the efficacy and safety of AM therapy for patients with DFUs. METHODS: A literature search of 5 databases was performed to identify RCTs comparing AM therapy to standard therapy (ST) in patients with DFUs. The primary outcome was the complete healing rate and the secondary outcomes mainly included time to complete healing and adverse events. RESULTS: Nine RCTs involving 897 patients were included. Compared with ST group, patients allocated to AM group had a higher complete healing rate both at 12 weeks (risk ratio (RR) = 1.73, 95% confidence interval (CI): 1.31 to 2.30) and 16 weeks (RR = 1.56, 95% CI: 1.28 to 1.91), a shorter time to complete healing (mean difference (MD) = -2.41; 95% CI: -3.49 to -1.32), and fewer adverse events (RR = 0.64, 95% CI: 0.44 to 0.93). CONCLUSION: The present study suggests that AM therapy as an adjuvant treatment could further promote the healing of full-thickness, noninfected, and nonischemia DFUs. AM therapy also has a safety profile. More large well-designed randomized clinical trials with long follow-up duration are needed to further explore the efficacy and safety of AM therapy for DFUs.

Inhibition of Slug effectively targets leukemia stem cells via the Slc13a3/ROS signaling pathway.

Leukemia stem cells (LSCs) are the rare populations of acute myeloid leukemia (AML) cells that are able to initiate, maintain, and propagate AML. Targeting LSCs is a promising approach for preventing AML relapse and improving long-term outcomes. While Slug, a zinc-finger transcription repressor, negatively regulates the self-renewal of normal hematopoietic stem cells, its functions in AML are still unknown. We report here that Slug promotes leukemogenesis and its loss impairs LSC self-renewal and delays leukemia progression. Mechanistically, Slc13a3, a direct target of Slug in LSCs, restricts the self-renewal of LSCs and markedly prolongs recipient survival. Genetic or pharmacological inhibition of SLUG or forced expression of Slc13a3 suppresses the growth of human AML cells. In conclusion, our studies demonstrate that Slug differentially regulates self-renewal of LSCs and normal HSCs, and both Slug and Slc13a3 are potential therapeutic targets of LSCs.

Impact of disease-management programs on metabolic control in patients with type 1 diabetes mellitus: A cohort study in Shantou, China.

The aim of this study is to evaluate the effect of diabetes disease management program (DMP) on glycemic control in type 1 diabetes mellitus (T1DM) patients in Shantou China.A sample of 240 participants recruited from 3C study Shantou subgroup was followed up in DMP for 3 years. The DMP provided self-management education, individualized therapy plan, diabetes complications screening, and laboratory examination periodical according to clinical practice guidelines. Primary outcomes were changes in hemoglobin A1C (HbA1c).Two hundred one of the participants completed the follow-up. There was a significant decrease in the HbA1c levels after DMP implemented. The mean (± SD) pre- and post-intervention HbA1c levels were 10.26% ±â€Š3.30% and 8.57% ±â€Š1.57% respectively with a P value <0.001. General linear mixed model analyse demonstrated that changes in glycemic control were associated with insulin treatment regimen, frequency of Self-Monitoring of Blood Glucose (SMBG), diabetes diet adherence, physical activity, and duration of diabetes.DMP helped to improve glycemic control and should be general implemented in China's T1DM. Individuals with basal-bolus regimen (multiple daily injections or pump therapy), more frequency of SMBG, following a diabetes diet, more physical activity, shorter diabetes duration may derive greater benefits from DMP.

Diabetes Self-Care Activities and Health-Related Quality-of-Life of individuals with Type 1 Diabetes Mellitus in Shantou, China.

OBJECTIVE: To assess diabetes self-care behaviours and health-related quality-of-life (HRQoL) in people with type 1 diabetes mellitus (T1DM), in China. METHODS: Individuals with T1DM underwent face-to-face interviews over a 7-day questionnaire period. The Summary of Diabetes Self-Care Activities (SDSCA) was used to assess self-care behaviours. EQ-5D-3L was used to quantify HRQoL. RESULTS: Of self-care activities, individuals (n = 322) were most likely to adhere to treatment and least likely to perform foot care. A total of 78.9% of participants did not examine their feet and 33.9% of participants did not monitor blood glucose during the questionnaire period. Moderate/severe anxiety or depression was reported by 28.6% of participants; 23.9% reported moderate/severe pain or discomfort. The individual's level of diabetes education, insulin injection regimen and HbA1c were independently associated with total SDSCA score. Household income and age were independently associated with EQ-5D index. CONCLUSIONS: Enhancing diabetes education in individuals and implementing strict insulin regimens could improve self-care behaviours in people with T1DM in China.

GPR109A Expression in the Murine Min6 Pancreatic Beta Cell Line, and Its Relation with Glucose Metabolism and Inflammation.

BACKGROUND: Nicotinic acid has been used clinically to manage dyslipidemia for many years, and its receptor, GPR109A, is expressed in various tissues or cells. It is not known if GPR109A is also expressed in pancreatic beta cells or if it takes part in maintaining homeostasis of glucose metabolism. AIMS: In this study, the expression of GPR109A was investigated in the murine Min6 pancreatic beta cell line. The anti-inflammatory role of GPR109A in MIN6 cells was also explored. METHODS: RT-PCR, western blotting, and immunocytochemical staining were used to detect the expression of GPR109A in MIN6 cells. Real-Time RT-PCR was used to investigate GPR109A mRNA levels influenced by IFN-γ and glucose. Cell viability and cytoplasmic nitrite levels were measured colorimetrically. RESULTS: We have identified that MIN6 cell, a mouse pancreatic beta cell line, expresses GPR109A transcripts and protein. GPR109A protein is mainly located in the cell membrane and cytoplasm. GPR109A mRNA increased more than 9-fold in MIN6 cells incubated with IFN-γ. High glucose inhibited GPR109A mRNA expression. Nitric oxide accumulation, induced by IFN-γ/TNF-α, was inhibited by nicotinic acid and 3-hydroxy-butyrate. CONCLUSIONS: Our results suggest that the expression of GPR109A in pancreatic beta cells is not only influenced by inflammation and glucose, but also plays a protective role under inflammatory conditions. Moreover, the MIN6 cell line may serve as a cellular model for further investigation of GPR109A-mediated signal transduction in modulating metabolism and diabetes.

Different effect of handle region peptide on ß-cell function in different sexes of rats neonatally treated with sodium L-glutamate.

BACKGROUND The (pro)renin receptor ((P)RR) was reported to be expressed in various tissues including the pancreas, and handle region peptide (HRP) is believed to block the function of (P)RR. This study aimed to investigate the effect of HRP on the glucose tolerance status and ß-cell function of female rats, neonatally treated with sodium L-glutamate (MSG) and to compare with the previously reported HRP effect on male rats. MATERIAL AND METHODS Female MSG rats aged 8 weeks were divided into MSG control group and HRP treated group and the normal SD rats served as control. The MSG rats were treated with HRP by osmotic minipumps with dose of 1 mg/kg per day for total 28 days. Glucose tolerance status was evaluated at the end of the study. Islets α-cell and ß-cell were marked with insulin antibody and glucagon antibody respectively. The proliferation of islet cells and expression of subunit of NADPH oxidase P22phox were marked by PCNA and P22phox antibody. Picrosirius red staining was performed for evaluating fibrosis of islets. RESULTS HRP improved the glucose status tolerance with decreasing α-cell mass, islets PCNA-positive cells, expression of P22phox and picrosirius red stained areas, and increasing ß-cell mass in female MSG rats. The indexes with obviously interacted effect of sexes and HRP for the MSG rats were the AUC of blood glucose concentration (P<0.01), α-cell mass (P<0.05), proliferation of islet cells (P<0.01) and area of picrosirius red staining (P<0.01). CONCLUSIONS HRP improved the glucose tolerance status in the females although it was previously reported to worsen the glucose tolerance in male MSG rats. Different levels of sex hormones may partly account for the disparate effects observed for HRP in different sexes.

Handle Region Peptide Ameliorating Insulin Resistance but Not ß Cell Functions in Male Rats Neonatally Treated with Sodium L-Glutamate.

Handle region peptide (HRP), which was recognized as a blocker of (pro)renin receptor ((P)RR), may block the function of (P)RR. The aim of this study was to investigate the effect of HRP with a large dose of 1 mg/kg/d on glucose status in the rats treated neonatally with monosodium L-glutamate (MSG). At the age of 8 weeks, the MSG rats were randomly divided into MSG control group, HRP treated group with minipump (MSG-HRP group), losartan treated group (MSG-L group), and HRP and losartan cotreated group (MSG-HRP-L group) and fed with high-fat diet for 4 weeks. Losartan but not HRP increased the levels of insulin releasing and ameliorate glucose status although both losartan and HRP improved insulin sensitivity. On the one hand, both losartan and HRP decreased levels of pancreatic local Ang-II and NADPH oxidase activity as well as its subunits P(22phox). On the other hand, losartan but not HRP decreased α -cell mass and number of PCNA-positive cells located periphery of the islets and decreased picrosirius red stained area in islets. HRP ameliorating insulin resistance but not ß -cell functions leads to hyperglycemia in the end in male MSG rats, and the dual characters of HRP may partly account for the phenomenon.

[Biomarkers of endothelial dysfunction and risk of early organ damage: a comparison between patients with primary aldosteronism and essential hypertension].

OBJECTIVE: To compare plasma concentrations of biomarkers of endothelial dysfunction between patients with primary aldosteronism (PA) and essential hypertension (EH), and to determine whether elevated levels of these biomarkers could predict development of early organ damage. METHODS: Thirty-six PA patients and 39 EH patients matched for age, sex, blood pressure and duration of hypertension were included in this study. Plasma levels of biomarkers reflecting endothelial dysfunction (von Willebrand factor, vWF; soluble intercellular adhesion molecule 1, sICAM-1; and oxidized low density lipoprotein, ox-LDL) were detected and compared between PA and EH patients. Left ventricular mass index (LVMI) determined by echocardiography, 24-hour urinary protein quantitative determination and urinary albumin excretion rate (UAER) were analyzed to evaluate early organ damage. Left ventricular hypertrophy was defined as LVMI > 125 g/m(2) in men and > 120 g/m(2) in women, and UAER between 20 µg/min and 200 µg/min was defined as microalbuminuria. RESULTS: vWF [(122.3 ± 53.8)% vs. (113.1 ± 68.3)%], sICAM-1 [(401.0 ± 74.1) µg/L vs. (300.9 ± 87.0) µg/L], ox-LDL [(13.6 ± 10.0) U/L vs. (8.1 ± 5.9) U/L], LVMI [(124.7 ± 33.6) g/m(2) vs. (109.1 ± 25.7) g/m(2)], 24-hour urinary protein quantitation [24 h UPQ, (0.17 ± 0.10) g vs. (0.09 ± 0.04) g] and UAER [(25.9 ± 7.7) µg/min vs. (9.7 ± 5.9) µg/min] were significantly higher in PA group than in EH group (all P < 0.05). Elevated plasma vWF, sICAM-1 levels and plasma aldosterone concentration independently predicted microalbuminuria. Whereas, elevated plasma vWF and ox-LDL levels, plasma aldosterone concentration and systolic blood pressure independently predicted left ventricular hypertrophy. CONCLUSION: Patients with PA have severer endothelial dysfunction reflected by multiple biomarkers and earlier organ damage than patients with EH, and plasma aldosterone concentration and multiple endothelial dysfunction biomarkers could independently predict early organ damage.

Effect of age on aldosterone/renin ratio (ARR) and comparison of screening accuracy of ARR plus elevated serum aldosterone concentration for primary aldosteronism screening in different age groups.

The serum aldosterone concentration (SAC)/plasma renin activity (PRA) ratio (ARR) is considered a useful screening test in the differential diagnosis of essential hypertension (EH) and primary aldosteronism (PA). The purpose of this study is to investigate the effect of age on ARR and compare the screening accuracy of ARR plus elevated SAC for PA screening in different age groups. Thirty-nine patients with PA, 274 patients with EH, and 153 healthy volunteers were recruited. Blood was sampled for SAC and PRA measuring under keeping upright posture for 1 h. Levels of SAC, PRA, and ARR were compared at different ages range for the respective three groups of subjects. The screening accuracy of ARR plus elevated SAC was compared in different age groups and PA patients served as the same positive subjects. In the EH group, logarithmically transformed ARR (Log-ARR) increased with advancing age and reached its peak in the ≥ 60 years group; in the normotensives group, Log-ARR reached its peak in the 40-49 years group and slightly declined with advancing age. In the PA group, Log-ARR was not age dependent. Screening accuracy increased when combined index of ARR and SAC was used in the ≥ 40 years group but not in the <40 years group. Although the number of EH patients with elevated ARR increased with advancing age, but the screening accuracy and cutoff values of ARR were not affected by age. Using the combined index of ARR and SAC increased the screening accuracy for the patients older than 40 years, but not necessary for the patients younger than 40 years.

[New index of using serum sodium and potassium and urine sodium and potassium jointly in screening primary aldosteronism in hypertensive patients].

OBJECTIVE: Although the aldosterone-to-renin ratio (ARR) is valuable in the screening for primary aldosteronism (PA). However, the hormonal determinations are both time-consuming and expensive. So we tried to use new indexes of serum sodium to urinary sodium to serum potassium to urinary potassium (SUSPUP) and serum sodium to urinary sodium to (serum potassium)2 to urinary potassium (SUSPPUP) in screening of PA. METHODS: The present study included 39 patients with PA, 296 patients with essential hypertension and 158 normosensitive subjects. Serum potassium and sodium, urine potassium and sodium were measured by ion-selective electrodes. In addition, serum aldosterone concentration and plasma rennin activity after staying upright for one hour were measured by radioimmunoassay. The serum potassium and sodium, urine potassium and sodium in these groups were evaluated in the screening of SUSPPUP for differentiating PA from hypertensive patients. RESULTS: (1) Compared with healthy volunteers, the essential hypertension patients had lower levels of both serum potassium and urine sodium, higher levels of serum sodium. Compared with healthy volunteers and primary hypertension patients, the PA patients had the lowest serum potassium and highest serum sodium, urine potassium resulting in the highest SUSPUP and SUSPPUP ratio. (2) The AUCs of SUSPUP and SUSPPUP were 0.824 and 0.840 respectively according to the ROC curve. The optimal cutoffs of SUSPUP and SUSPPUP were 14.44 and 4.08 respectively. CONCLUSION: The SUSPUP and SUSPPUP ratios are rapid and inexpensive indices to assess the extent of mineralocorticoid excess. Therefore they may be employed to screen PA in hypertensive patients.