Functional status associated with postural dizziness, but not postural hypotension, in older adults: a community-based study.

BACKGROUND: Functional status, postural dizziness (PD), and postural hypotension (PH) were important issues in older adults. Only one study on the relationship for the three of them in female was without adjusting some important associated factors. This study was intended to investigate the association of PD and PH with functional status in older people of both genders. METHODS: Based on a stratified randomized cluster sampling, 1361 subjects ≥ 65 years in the community were recruited from Tainan City, Taiwan, from 2000 to 2001. PH was defined as a decrease in systolic/diastolic blood pressure of ≥ 20/10 mm Hg after 1 or 2 min of standing. PD was defined by a positive response to dizziness-like symptoms after standing up from a supine position. Functional status included the activities of daily living (ADLs) and instrumental activities of daily living (IADLs). RESULTS: After adjusting other variables, ADL disability (OR: 1.84, 95% CI: 1.35-2.51) and IADL disability (OR: 1.62, 95% CI: 1.21-2.17) were associated with PD, but not PH. In male and female subgroups, ADL disability (male OR: 1.70, 95% CI: 1.08-2.67; female OR 1.96, 95% CI: 1.26-3.07) was associated with PD. In male, IADL disability was associated with PD (OR: 2.32, 95% CI: 1.36-3.95). CONCLUSIONS: Impaired functional status, shown using ADLs or IADLs, was positively associated with PD, but not PH in older adults ≥ 65 years. Clinically, it may be important to evaluate PD in older adults with ADL or IADL disability.

Targeting fibrinogen-like protein 1 is a novel therapeutic strategy to combat obesity.

Fibrinogen-like-protein 1 (FGL1) is a novel hepatokine that plays an important role in hepatic steatosis and insulin resistance. Although FGL1 expression can be detected in adipose tissues, the functions of FGL1 in adipose tissues are still unknown. In this study, 356 participants with (body mass index (BMI) ≥25 kg/m2 ; n = 134) or without obesity (BMI <25 kg/m2 ; n = 222) were recruited, and we found that the plasma FGL1 concentrations were significantly higher in obese group than those of in the normal weight group, and were positively correlated with age, BMI, waist circumference, fat content, plasma glucose at 2 hours during an oral glucose tolerance test, and the insulin sensitivity index. In univariate analyses, BMI, waist circumference, total fat, visceral fat, and subcutaneous fat areas were positively correlated with FGL1 levels. After adjusting for age and gender, obesity indices, including the BMI and different fat areas, remained significantly associated with FGL1 levels. In order to investigate the causal relationship between FGL1 and obesity, animal and cell models were used. Overexpression of FGL1 in epididymal adipose tissue by lentiviral vector encoding FGL1 increased the fat pad size, whereas FGL1-knockdown by lentiviral vector encoding short-hairpin RNA targeted to FGL1 decreased high-fat diet-induced adiposity. In addition, 3T3-L1 adipocytes were used to clarify the possible mechanism of FGL1-induced adipogenesis. FGL1 induced adipogenesis through an ERK1/2-C/EBPß-dependent pathway in 3T3-L1 adipocytes. These findings highlight the pathophysiological role of FGL1 in obesity, and FGL1 might be a novel therapeutic target to combat obesity.

Metabolic abnormalities, but not obesity per se, associated with chronic kidney disease in a Taiwanese population.

BACKGROUND AND AIMS: It is inconclusive whether obesity itself or metabolic abnormalities are linked to chronic kidney disease (CKD). The aim of this study was to examine the association between different subtypes of obesity and metabolic abnormalities with CKD in adults. METHODS AND RESULTS: This study enrolled 14,983 eligible subjects stratified into metabolically healthy normal weight (MHNW), metabolically healthy overweight (MHOW), metabolically healthy obesity (MHO), metabolically unhealthy normal weight (MUNW), metabolically unhealthy overweight (MUOW), and metabolically unhealthy obesity (MUO) according to body mass index and metabolic syndrome status (ATP-III criteria). The metabolic healthy phenotype was defined as the absence of both metabolic syndrome and any known diabetes, coronary artery disease, stroke, hypertension or dyslipidemia. Early and advanced CKD were defined as eGFR<60, proteinuria, or structural abnormalities as detected by renal sonography. The prevalence of CKD was 2.5, 3.0, 4.0, 10.6, 9.5, and 10.5% in subjects with MHNW, MHOW, MHO, MUNW, MUOW, and MUO, respectively. In the multivariate analysis, the MUNW (OR:2.22, P < 0.001), MUOW (OR:2.22, P < 0.001), and MUO (OR:2.45, P < 0.001) groups were associated with early CKD. For advanced CKD, the OR was 2.56 (P < 0.001), 2.31 (P < 0.001), and 3.49 (P < 0.001) in the MUNW, MUOW, and MUO groups, respectively. The associated risks of early and advanced CKD were not significant in the MHOW and MHO group. MUOW and MUO were associated with higher risk of CKD compared with MHOW and MHO after adjusting other variables. CONCLUSIONS: Metabolic abnormalities, but neither overweight nor obesity, were associated with a higher risk of CKD in adults.

Increased amount and duration of tea consumption may be associated with decreased risk of renal stone disease.

PURPOSE: Previous studies have looked into the association between tea consumption and renal stone disease, but the impact of tea consumption over time has not yet been fully clarified. Our study aimed to examine the amount and duration of tea consumption concomitantly in relation to the risk of renal stone disease. METHODS: A total of 13,842 subjects who underwent health check-ups were recruited. Average tea consumption per day was defined as the amount of tea consumption per day multiplied by the frequency per week divided by seven. A "cup" was defined as 120 mL for each Chinese traditional teapot," and "cup-year" was calculated by multiplying the number of daily cups and the years of tea consumption to express the cumulative dose of tea consumption over time. The diagnosis of renal stone disease was established based on the results of abdominal sonography. RESULTS: The amount of daily tea consumption was 119.2 ± 306.8 and 131.7 ± 347.3 mL in groups with and without renal stone disease. After adjusting for other clinical variables, daily tea consumption ≥ 240 mL vs. none was related to lower risk of renal stone disease (OR = 0.84, CI 0.71-0.99, p = 0.037). In another model, the associated risk of renal stone disease decreased significantly with tea consumption ≥ 20 cup-year (OR = 0.79, CI 0.66-0.94, p = 0.008), but not < 20 cup-year (OR = 0.92, CI 0.78-1.09, p = 0.34). CONCLUSIONS: Daily tea consumption ≥ 240 mL (two cups) was associated with a lower risk of renal stone disease. Tea consumption ≥ 20 cup-year also had a decreased associated risk of renal stone disease.

Gallbladder stones and gallbladder polyps associated with increased risk of colorectal adenoma in men.

BACKGROUND AND AIMS: Most cases of colorectal cancer develop via an adenoma to carcinoma sequence. Gallbladder polyps share some risk factors with colorectal polyps. Little is known about the relationship between gallbladder diseases and different status of colorectal polyps by gender. This study was to investigate the association of gallbladder stones and polyps with colorectal adenomas by gender in a Taiwanese population. METHODS: A total of 7066 eligible subjects who underwent a total colonoscopy as a part of health check-up between January 2001 and August 2009 were recruited. Colonoscopic findings were classified into polyp-free, non-neoplastic polyps and colorectal adenomas. Gallbladder stones and gallbladder polyps were diagnosed based on ultrasonographic findings. RESULTS: There was a significant difference in the status of colon polyps between subjects with and without gallbladder polyps. However, the status of colon polyps was not significantly different between subjects with or without gallbladder stones. After adjusting obesity, fasting plasma glucose, and other variables, there was a positive relationship between gallbladder polyps and colorectal adenomas (odds ratio [OR]: 1.396, 95% confidence interval [CI]: 1.115-1.747) but not non-neoplastic polyps in all subjects. In men, gallbladder polyps (OR: 1.560, 95% CI: 1.204-2.019) and gallbladder stones (OR: 1.465, 95% CI 1.081-1.984) were positively associated with colorectal adenomas. In women, neither gallbladder polyps nor gallbladder stones were significantly related to colon polyps. CONCLUSIONS: Both gallbladder polyps and gallbladder stones were associated with an increased risk of colorectal adenomas in men but not in women. Gender difference was significant for the association between gallbladder lesions and colorectal polyps.

Evodiamine Exerts an Anti-Hepatocellular Carcinoma Activity through a WWOX-Dependent Pathway.

Evodiamine is one of the main components isolated from Evodia rutaecarpa, and it has been reported to exert inhibitory effects on cancers by anti-proliferative and apoptosis-inducing activities. Although the anti-cancer activity of evodiamine has been identified, the precise mechanisms of this action remain obscure. While previous studies indicated that evodiamine exerts anti-tumor effects through inhibiting ß-catenin activity, and WW domain-containing oxidoreductase (WWOX) regulates ß-catenin accumulation in cytoplasm, the effects of evodiamine on the expression of WWOX are still unknown. In this study, we provide evidence that evodiamine dose- and time-dependently inhibits both Mus musculus and Homo sapiens hepatocellular carcinoma (HCC) cells, as well as Hepa1-6 and HepG2 cell proliferation. We further tested the therapeutic effects of evodiamine in Hepa1-6 hepatoma-bearing mice, and we found that treatment of evodiamine by oral gavage significantly decreased the tumor size of the mice. Moreover, the expressions of WWOX were dose-dependently increased in HCC cell lines as well as in Hepa1-6 hepatoma-bearing mice after the treatment with evodiamine. Knockdown of WWOX in HepG2 and Hepa1-6 cells diminished the effects of evodiamine on the inhibitory effect of cancer cell growth, indicating that evodiamine induced anti-cancer activity through a WWOX-dependent pathway. As such, evodiamine activated WWOX to exert an anti-HCC activity, and might be a potential therapeutic or preventive candidate for HCC treatment.

A novel hepatokine, HFREP1, plays a crucial role in the development of insulin resistance and type 2 diabetes.

AIMS/HYPOTHESIS: Type 2 diabetes is highly correlated with nonalcoholic fatty liver disease (NAFLD). Hepatocyte-derived fibrinogen-related protein 1 (HFREP1) is a hepatokine that mediates NAFLD development; however, the role of HFREP1 in the development of insulin resistance and diabetes remains obscure. METHODS: A total of 193 age- and sex-matched participants with normal glucose tolerance, impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and newly diagnosed diabetes (NDD) were recruited for a cross-sectional study. Plasma HFREP1 levels were measured and multivariate linear regression analysis was used to evaluate the relationship between HFREP1, IFG, IGT and NDD. The causal relationship between HFREP1 and insulin resistance was then investigated in animal and cell models. Glucose and insulin tolerance tests, and euglycaemic-hyperinsulinaemic clamp, were used to evaluate insulin sensitivity in animals with Hfrep1 overexpression or knockdown in liver by lentiviral vectors. HepG2 cells were used to clarify the possible mechanism of HFREP1-induced insulin resistance. RESULTS: Plasma HFREP1 concentrations were significantly increased in participants with IFG, IGT and NDD. HFREP1 concentrations were independently associated with fasting plasma glucose levels, insulin resistance, IFG, IGT and NDD. Injection of recombinant HFREP1 or Hfrep1 overexpression induced insulin resistance in mice, and HFREP1 disrupted insulin signalling to induce insulin resistance through an extracellular signal-regulated kinase (ERK)1/2-dependent pathway. Moreover, hepatic knockdown of HFREP1 improved insulin resistance in both mice fed a high-fat diet and ob/ob mice. CONCLUSIONS/INTERPRETATION: These findings highlight the crucial role of HFREP1 in insulin resistance and diabetes, and provide a potential strategy and biomarker for developing therapeutic approaches to combat these diseases.

Increased risk of glomerular hyperfiltration in subjects with impaired glucose tolerance and newly diagnosed diabetes.

BACKGROUND: Glomerular hyperfiltration is closely related to diabetes and may lead to subsequent nephropathy, but the association between glomerular hyperfiltration and prediabetic state is unclear. We examined the relationship of different glycemic statuses, including normal glucose tolerance (NGT), isolated impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and newly diagnosed diabetes (NDD), with glomerular hyperfiltration. METHODS: This study included 12 833 subjects ≥20 years of age without a history of renal disease, cancer, moderate/severe anemia or diabetes and taking medications for hypertension, diabetes, hyperlipidemia or cardiovascular disease from National Cheng Kung University Hospital between January 2000 and August 2009. Hyperfiltration was defined as an estimated GFR (eGFR) above the age- and gender-specific 95th percentile for apparently healthy subjects, while hypofiltration was defined as an eGFR below the 5th percentile. eGFR was assessed using the Chronic Kidney Disease Epidemiology Collaboration equation. RESULTS: After further excluding hypofiltration and adjusting for available confounders, fasting plasma glucose (FPG), 2-hour postload glucose (2hPG), 2hPG-FPG (fluctuating blood glucose), HbA1c (average blood glucose), NDD and IGT but not isolated IFG were significantly associated with increased eGFR and a higher risk of hyperfiltration {NDD: odds ratio [OR] 1.97 [95% confidence interval (CI), 1.48-2.64], P < 0.001; IGT: OR 1.34 (95% CI 1.07-1.66), P = 0.009}. CONCLUSIONS: High glucose states increase hyperfiltration risk. In addition to newly diagnosed diabetes, excessively high GFR also deserves attention in subjects with IGT.

Nonalcoholic fatty liver disease vs. obesity on the risk of erosive oesophagitis.

BACKGROUND: Erosive oesophagitis (EE) may be complicated by oesophageal ulcers, peptic stricture, Barrett's oesophagus and oesophageal adenocarcinoma. There have been few studies examining the influence of nonalcoholic fatty liver disease (NAFLD) on EE, and even fewer exploring the simultaneous effects of NAFLD, general and central obesity on EE. We thus aim to clarify the relationship between NAFLD and EE when general and/or central obesity are considered simultaneously. MATERIALS AND METHODS: In this cross-sectional study, we enrolled 12 090 subjects who underwent a health check-up at the Health Examination Center of a university hospital between January 2000 and August 2009 for analysis. NAFLD was diagnosed using liver ultrasound and EE was defined according to the Los Angeles classification by oesophagogastroduodenoscopy. RESULTS: Subjects with EE (1922; 15·9%) had a higher proportion of NAFLD, general and central obesity. With adjustment for age, gender, hypertension, diabetes mellitus, hiatal hernia, hypertriglyceridemia, high-density lipoprotein cholesterol, alcohol consumption, tea drinking, smoking and habitual exercise, the results of the multivariate analyses showed that general obesity, central obesity and NAFLD were all significantly associated with EE in their separate models. When considering general obesity, central obesity and NAFLD simultaneously, NAFLD, but neither general nor central obesity, remained positively correlated to EE. In addition, male gender, hiatal hernia and hypertriglyceridemia were all significantly associated with EE. CONCLUSION: In addition to general and central obesity, NAFLD is independently associated with increased risk of EE, and the detrimental effect of NAFLD on EE might be greater than those of general and central obesity.

Moderate to severe, but not mild, nonalcoholic fatty liver disease associated with increased risk of gallstone disease.

OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) and gallstone disease (GSD) share some of the same risk factors. The association between NAFLD and GSD was inconsistent. Moreover, there are no studies on the association between GSD and the severity of NAFLD in the literature. The aim of this study was to determine the relationship between the severity of NAFLD and GSD in a Taiwanese population. MATERIALS AND METHODS: A total of 12,033 subjects were enrolled. The diagnoses of GSD and NAFLD were based on the finding of abdominal ultrasonography. The severity of NAFLD was divided into mild, moderate, and severe. RESULTS: Compared with the non-GSD group, the GSD one was older and had a higher BMI, blood pressure, fasting plasma glucose, cholesterol, triglyceride, and higher prevalence of diabetes and hypertension, but they had a lower eGFR and HDL-C level and less prevalence of current smoking and alcohol drinking. There was a significant difference in the severity of NAFLD between subjects with and without GSD. Based on logistic regression, age ≥65 versus <40 years, 40-64.9 versus <40 years, female, current alcohol drinking, diabetes, hypertension, HDL-C level and moderate to severe NAFLD, but not mild NAFLD, were the independently associated risk factors of GSD. CONCLUSION: Moderate to severe, but not mild, NAFLD was associated with an increased risk of GSD, independent of the traditional cardio-metabolic risk factor. Age, female, diabetes, and hypertension were also related to a higher risk of GSD, but HDL-C level and moderate alcohol drinking showed a lower risk.

Gastric Helicobacter pylori infection associated with risk of diabetes mellitus, but not prediabetes.

BACKGROUNDS AND AIM: The association between Helicobacter pylori infection and diabetes was inconsistent in previous studies. Moreover, there are no studies on the relationship between H. pylori infection and prediabetes in the literature. The aim of this study is thus to assess the association of Helicobacter infection, diagnosed by pathology from gastric biopsy, with diabetes and prediabetes. METHODS: This cross-sectional study included 1285 subjects aged 19-85 who underwent esophagogastroduodenoscopy and gastric biopsy during health examinations at National Cheng Kung University Hospital from 2000 to 2009. Subjects were divided into three groups, including normal glucose tolerance, prediabetes, and diabetes. Diabetes and prediabetes were assessed according to the American Diabetes Association diagnostic criteria. Gastric Helicobacter infection was an independent variable. Chi-square tests, analysis of variance, and multinomial logistic regression models were used to analyze the effects of Helicobacter infection on the risk of diabetes and prediabetes while controlling for age, lifestyle, pathological conditions, and laboratory variables. RESULTS: There were significant differences in the prevalence of gastric Helicobacter infection among the three groups. The results of multivariate analysis showed that age, obesity, family history of diabetes, hypertension, and hypertriglyceridemia were significantly related to both prediabetes and diabetes. Helicobacter pylori infection was positively associated with diabetes (odds ratio [OR] 1.42, 95% confidence interval [CI] 1.01-2.01), but not prediabetes (OR 1.02, 95% CI 0.77-1.36), in addition to male gender, education level (≤ 9 vs > 12 years), pre-hypertension, and low high-density lipoprotein cholesterol. CONCLUSIONS: Gastric H. pylori infection is associated with diabetes, but not prediabetes.

In vivo and in vitro anti-tumor effects of fungal extracts.

Fungal extracts are extensively used as nutritional supplements in Far-Eastern Asia. In this study, we aimed to evaluate the anti-cancer activities of some different fungal species against different cancer cell lines. The water or ethanol extracts of Fomitopsis pinicola (F. pinicola), Ganoderma sinense, Fomitopsis officinalis, Polyporus melanopus, and Taiwanofungus camphorates were used to evaluate the anti-cancer activities in various cancer cells. We found that all of the fungi ethanol extracts used in this study exert anti-cancer activities in vitro, whereas water extracts show lower inhibitory activities as determined by 3-(4,5-methylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. Among the tested fungi species, F. pinicola ethanol extract exerts the most significant anti-cancer activity (growth inhibitory ratio 82.8%, p < 0.001) by increasing cell apoptosis. Moreover, F. pinicola ethanol extract significantly decreased tumor size (tumor growth inhibitory ratio 54%, p < 0.05) and increased the lifespan in mice bearing sarcoma-180 tumors. Taken together, this is the first study indicating the anti-tumor effect of F. pinicola in vivo and in vitro. F. pinicola ethanol extract induces cell apoptosis to exert a significant anti-tumor activity, with potential to be a new alternative anti-tumor medicine.

Multiple mechanisms of GW-9508, a selective G protein-coupled receptor 40 agonist, in the regulation of glucose homeostasis and insulin sensitivity.

Activation of G protein-coupled receptor 40 (GPR40) by agonists increases insulin release in isolated islets, whereas it is inconclusive whether GPR40 antagonists decrease blood glucose and increase insulin sensitivity. Although some clinical trials indicated that administration of a GPR40 agonist shows benefits in the regulation of blood glucose homeostasis, the pharmacological mechanisms of this receptor in the improvement of glycemic control remain unclear. Therefore, we used a selective GPR40 agonist, GW-9508, to clarify the role of GPR40 in the regulation of blood glucose. Bolus intraperitoneal injection of GW-9508 in mice showed a slight decrease in blood glucose, with an increase in plasma insulin levels under glucose stimuli. However, long-term treatment with low doses of GW-9508 in high-fat diet-induced (HFD) diabetic mice decreased blood glucose with decreased plasma insulin significantly and improved glucose intolerance and insulin resistance. Using small interfering ribonucleic acid to delete GPR40 in HepG2 cells, we demonstrated that GW-9508 reversed palmitate-induced insulin signaling impairment through a GPR40-dependent pathway. We also found that GW-9508 activates the Akt/GSK-3ß pathway to increase glycogen levels in HepG2 cells. Furthermore, administration of GW-9508 decreased the hepatic expression of fetuin-A in HFD mice significantly and regulated high-glucose- or palmitate-induced fetuin-A expression to increase insulin sensitivity through a GPR40/PLC/PKC pathway in HepG2 cells. Taken together, GW-9508 exerts a partial agonist effect to regulate blood glucose through multiple mechanisms. Investigation of chemicals that act on GPR40 might be a new strategy for the treatment of diabetes.

Multiple and large simple renal cysts are associated with prehypertension and hypertension.

Although simple renal cysts are thought to be related to hypertension, no reports have examined the relationship between simple renal cysts and prehypertension. Here, we evaluated the effects of simple renal cysts on prehypertension and hypertension and the role of serum renin levels in the cyst-related prehypertension/hypertension in adults. A total of 14,995 patients were enrolled and divided into normotension, prehypertension, and hypertension groups. Simple renal cysts were classified into different categories based on number (1 vs. ≥ 2 cm) and size (<2 vs. ≥ 2 cm). In multivariate analysis, simple renal cysts were independently related to prehypertension/hypertension. Two or more simple renal cysts or cyst of ≥ 2 cm were independently associated with prehypertension/hypertension. However, the association between cyst of ≥ 2 cm and prehypertension/hypertension disappeared after further adjusting for serum renin level in an exposure-matched subgroup analysis. Thus, the presence of two or more simple renal cysts and cyst of ≥ 2 cm were the important determinants of prehypertension and hypertension in adults. One possible mechanism of cyst-related prehypertension/hypertension may be related to an increased serum renin level. We recommend close monitoring of blood pressure routinely among patients with two or more simple renal cysts.

The role of hepassocin in the development of non-alcoholic fatty liver disease.

BACKGROUND & AIMS: While non-alcoholic fatty liver disease (NAFLD) is the most common risk factor of chronic liver disease, the mechanisms that initiate its development are obscure. Hepassocin (HPS) is a hepatokine that has been reported to be involved in liver regeneration. In addition to the mitogenic activity of HPS, HPS expression is decreased in patients with hepatoma. However, the role of HPS in NAFLD is still unknown. METHODS: A total of 393 subjects with (n=194) or without (n=199) NAFLD were enrolled to evaluate the serum HPS concentration. In order to clarify the causal inference between HPS and NAFLD, we used experimental animal and cell models. Hepatic overexpression or silencing of HPS was achieved by lentiviral vector delivery in mice and lipofectamine transfection in HepG2 cells. Lipogenesis related proteins were detected by Western blots. The expression of inflammatory factors was determined by real-time polymerase chain reaction. RESULTS: Subjects with NAFLD had a higher serum HPS concentration than those without it. Overexpression of HPS increased hepatic lipid accumulation and NAFLD activity scores (NAS), whereas deletion of HPS improved high fat diet-induced hepatic steatosis and decreased NAS in mice. Additionally, oleic acid, a steatogenic reagent, increased HPS expression in hepatocytes. Furthermore, overexpression of HPS in HepG2 cells induced lipid accumulation through an extracellular signal-regulated kinase 1/2 (ERK1/2)-dependent pathway, whereas deletion of HPS decreased oleic acid-induced lipid accumulation. CONCLUSIONS: The present study provides evidence that HPS plays an important role in NAFLD and induces hepatic lipid accumulation through an ERK1/2-dependent pathway.

The relationship between impaired fasting glucose and self-reported sleep quality in a Chinese population.

OBJECTIVE: Decreased sleep quality and duration predicts the development of type 2 diabetes. Prediabetes is an established risk factor for type 2 diabetes and cardiovascular disease. However, there is limited research on the association between prediabetes and sleep quality. The aim of this study is to investigate this relationship in a Chinese population. METHODS: Subjects were recruited from the Prevention Health Center of National Cheng Kung University Hospital. Anthropometric data and metabolic parameters were measured. The diagnoses of impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and diabetes followed the recommendations of the American Diabetes Association. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). RESULTS: A total of 1805 subjects with normal glucose tolerance (NGT, n = 1217), IFG (n = 118), IGT (n = 287), IFG+IGT (n = 80) and newly diagnosed diabetes (NDD, n = 103) were recruited. The global PSQI scores were 6·07 ± 2·44, 6·74 ± 3·23, 6·91 ± 3·51, 6·74 ± 2·26 and 7·16 ± 3·49 in subjects with NGT, IFG, IGT, IFG+IGT and NDD, respectively. Multivariate linear regression analysis showed that female gender, smoking, IGT, IFG+IGT and NDD, but not IFG, were independent determinants of global PSQI score. Multivariate logistic regression analysis showed that female gender, IGT, IFG+IGT and NDD, but not IFG, were predictors of poor sleepers. CONCLUSIONS: Subjects with prediabetes and NDD had a significantly higher global PSQI score than those with NGT. Furthermore, female gender, smoking, IGT, IFG+IGT and NDD, but not IFG, were significantly associated with poor sleep quality independent of cardiometabolic risk factors in a Chinese population.

Long-Term Consumption of Sucralose Induces Hepatic Insulin Resistance through an Extracellular Signal-Regulated Kinase 1/2-Dependent Pathway.

Sugar substitutes have been recommended to be used for weight and glycemic control. However, numerous studies indicate that consumption of artificial sweeteners exerts adverse effects on glycemic homeostasis. Although sucralose is among the most extensively utilized sweeteners in food products, the effects and detailed mechanisms of sucralose on insulin sensitivity remain ambiguous. In this study, we found that bolus administration of sucralose by oral gavage enhanced insulin secretion to decrease plasma glucose levels in mice. In addition, mice were randomly allocated into three groups, chow diet, high-fat diet (HFD), and HFD supplemented with sucralose (HFSUC), to investigate the effects of long-term consumption of sucralose on glucose homeostasis. In contrast to the effects of sucralose with bolus administration, the supplement of sucralose augmented HFD-induced insulin resistance and glucose intolerance, determined by glucose and insulin tolerance tests. In addition, we found that administration of extracellular signal-regulated kinase (ERK)-1/2 inhibitor reversed the effects of sucralose on glucose intolerance and insulin resistance in mice. Moreover, blockade of taste receptor type 1 member 3 (T1R3) by lactisole or pretreatment of endoplasmic reticulum stress inhibitors diminished sucralose-induced insulin resistance in HepG2 cells. Taken together, sucralose augmented HFD-induced insulin resistance in mice, and interrupted insulin signals through a T1R3-ERK1/2-dependent pathway in the liver.

Renal Stones and Gallstones Correlated with the Ten-Year Risk Estimation of Atherosclerotic Cardiovascular Disease Based on the Pooled Cohort Risk Assessment of Males Aged 40-79.

BACKGROUND: The risk of developing atherosclerotic cardiovascular disease (ASCVD) is unknown for subjects with both gallstones and renal stones, nor is it known whether there is a difference in the risk between gallstones and renal stones. This study aimed to determine the risk relationship between gallstones and renal stones and the risk of ASCVD in a male population. METHODS: We recruited 6371 eligible males aged 40 to 79 years old who did not have a documented ASCVD history. The ten-year ASCVD risk was calculated using the pooled cohort equations developed by the American College of Cardiology (ACC) and the American Heart Association (AHA). The ASCVD risk score was classified as a low risk (<7.5%), an intermediate risk (7.5% to 19.9%), or a high risk (≥20%). The diagnosis of gallstones and renal stones was established based on the results of abdominal sonography. RESULTS: Both gallstones and renal stones were associated with a high level of intermediate risk (OR = 3.21, 95% CI = 1.89-5.49, p < 0.001) and high risk (OR = 3.01, 95% CI = 1.48-6.12, p < 0.001), compared to individuals with no stones at all, after adjusting for the effects of other clinical variables. The possession of gallstones was associated with a higher level of high ASCVD risk (OR = 1.84, 95% CI = 1.31-2.59, p < 0.05) than that of renal stones. CONCLUSIONS: The ASCVD risk was higher for males with gallstones than for those with renal stones. Men with both types of stones faced a risk of ASCVD that was three times higher than that of men without stones.

Different Factors Associated with Morning Blood Pressure Surge in Antihypertensive-Naïve Dipper and Non-Dipper Subjects.

The relationship between the morning blood pressure surge (MBPS) and cardiovascular risk is inconclusive. Previous studies have not taken into consideration dipping status in examining the MBPS and its associated factors. The aim was to examine factors associated with the MBPS in dippers and non-dippers. The MBPS was calculated by data obtained from ambulatory blood pressure monitoring, using the definition of sleep-trough morning surge. Dipping systolic blood pressure (DipSBP) was defined as [1 - (SBPsleeping/SBPawake)] × 100%. The value in milliseconds of standard deviation of normal-to-normal RR interval after waking up (SDNNaw) was calculated during the 2 h period after waking up. A total of 140 eligible subjects were divided into dippers (n = 62) and non-dippers (n = 78). Multiple regression analysis on data for all subjects revealed different correlations with the MBPS: positive in age, body mass index (BMI), and DipSBP, and inverse in cholesterol/high density lipoprotein-cholesterol (HDL-C) ratio, fasting blood glucose, and 2 h SDNNaw. When dippers were examined separately, age, female gender, and BMI correlated positively with MBPS, while cholesterol/HDL-C ratio and 2 h SDNNaw correlated negatively. For non-dippers, only age was associated with the MBPS. The factors associated with the MBPS were different for dippers and non-dippers. The MBPS seems to be a physiological response in this dipper group because age and BMI correlated positively with the MBPS, while parasympathetic neural activity after waking up and cholesterol/HDL-C ratio showed inverse correlations.

Secretory autophagy promotes RAB37-mediated insulin secretion under glucose stimulation both in vitro and in vivo.

High blood glucose is one of the risk factors for metabolic disease and INS (insulin) is the key regulatory hormone for glucose homeostasis. Hypoinsulinemia accompanied with hyperglycemia was diagnosed in mice with pancreatic ß-cells exhibiting autophagy deficiency; however, the underlying mechanism remains elusive. The role of secretory autophagy in the regulation of metabolic syndrome is gaining more attention. Our data demonstrated that increased macroautophagic/autophagic activity leads to induction of insulin secretion in ß-cells both in vivo and in vitro under high-glucose conditions. Moreover, proteomic analysis of purified autophagosomes from ß-cells identified a group of vesicular transport proteins participating in insulin secretion, implying that secretory autophagy regulates insulin exocytosis. RAB37, a small GTPase, regulates vesicle biogenesis, trafficking, and cargo release. We demonstrated that the active form of RAB37 increased MAP1LC3/LC3 lipidation (LC3-II) and is essential for the promotion of insulin secretion by autophagy, but these phenomena were not observed in rab37 knockout (rab37-/-) cells and mice. Unbalanced insulin and glucose concentration in the blood was improved by manipulating autophagic activity using a novel autophagy inducer niclosamide (an antihelminthic drug) in a high-fat diet (HFD)-obesity mouse model. In summary, we reveal that secretory autophagy promotes RAB37-mediated insulin secretion to maintain the homeostasis of insulin and glucose both in vitro and in vivo.