Modification effect of changes in cardiometabolic traits in association between kidney stones and cardiovascular events

BackgroundsWhether longitudinal changes in metabolic status influence the effect of kidney stones on cardiovascular disease (CVD) remains unclarified. We investigated the modification effect of status changes in metabolic syndrome (MetS) in the association of kidney stones with risk of incident CVD events.MethodsWe performed a prospective association and interaction study in a nationwide cohort including 129,172 participants aged ≥ 40 years without CVDs at baseline and followed up for an average of 3.8 years. Kidney stones information was collected by using a questionnaire and validated by medical records. The repeated biochemical measurements were performed to ascertain the metabolic status at both baseline and follow-up.Results4,017 incident total CVDs, 1,413 coronary heart diseases (CHDs) and 2,682 strokes were documented and ascertained during follow-up. Kidney stones presence was significantly associated with 44%, 70% and 31% higher risk of CVDs, CHDs and stroke, respectively. The stratified analysis showed significant associations were found in the incident and sustained MetS patients, while no significant associations were found in the non-MetS at both baseline and follow-up subjects or the MetS remission ones, especially in women. For the change status of each single component of the MetS, though the trends were not always the same, the associations with CVD were consistently significant in those with sustained metabolic disorders, except for the sustained high blood glucose group, while the associations were consistently significant in those with incident metabolic disorders except for the incident blood pressure group. We also found a significant association of kidney stone and CVD or CHD risk in the remain normal glucose or triglycerides groups; while the associations were consistently significant in those with incident metabolic disorders except for the incident blood pressure group. We also found a significant association of kidney stone and CVD or CHD risk in the remain normal glucose or triglycerides groups.ConclusionsA history of kidney stones in women with newly developed MetS or long-standing MetS associated with increased risk of CVD. The mechanisms link kidney stones and CVD risk in the metabolic and non-metabolic pathways were warranted for further studies

The Relative Body Weight Gain From Early to Middle Life Adulthood Associated With Later Life Risk of Diabetes: A Nationwide Cohort Study

AimTo determine the effect of decade-based body weight gain from 20 to 50 years of age on later life diabetes risk.Methods35,611 non-diabetic participants aged ≥ 50 years from a well-defined nationwide cohort were followed up for average of 3.6 years, with cardiovascular diseases and cancers at baseline were excluded. Body weight at 20, 30, 40, and 50 years was reported. The overall 30 years and each 10-year weight gain were calculated from the early and middle life. Cox regression models were used to estimate risks of incident diabetes.ResultsAfter 127,745.26 person-years of follow-up, 2,789 incident diabetes were identified (incidence rate, 2.18%) in 25,289 women (mean weight gain 20-50 years, 7.60 kg) and 10,322 men (7.93 kg). Each 10-kg weight gain over the 30 years was significantly associated with a 39.7% increased risk of incident diabetes (95% confidence interval [CI], 1.33-1.47); weight gain from 20-30 years showed a more prominent effect on the risk of developing diabetes before 60 years than that of after 60 years (Hazard ratio, HR = 1.084, 95% CI [1.049-1.121], P <0.0001 vs. 1.015 [0.975-1.056], P = 0.4643; PInteraction=0.0293). It showed a stable effect of the three 10-year intervals weight gain on risk of diabetes after 60 years (HR=1.055, 1.038, 1.043, respectively, all P < 0.0036).ConclusionsThe early life weight gain showed a more prominent effect on developing diabetes before 60 years than after 60 years; however, each-decade weight gain from 20 to 50 years showed a similar effect on risk developing diabetes after 60 years

Associations between longer habitual day napping and non-alcoholic fatty liver disease in an elderly Chinese population.

Both longer habitual day napping and Non-Alcoholic Fatty Liver Disease (NAFLD) are associated with diabetes and inflammation, but the association between day napping and NAFLD remains unexplored.To investigate the association between the duration of habitual day napping and NAFLD in an elderly Chinese population and to gain insight into the role of inflammatory cytokines in this association.We conducted a series of cross-sectional studies of the community population in Chongqing, China, from 2011 to 2012.Among 6998 participants aged 40 to 75 years, 6438 eligible participants were included in the first study and analyzed to observe the association between day napping duration and NAFLD. In a separate study, 80 non-nappers and 90 nappers were selected to identify the role of inflammatory cytokines in this association. Logistic regression models were used to examine the odds ratios (ORs) of day nap duration with NAFLD.Day nappers had a significantly higher prevalence of NAFLD (P<0.001). Longer day napping duration was associated in a dose-dependent manner with NAFLD (P trend <0.001). After adjustment for potential confounders, the ORs were 1.67 (95% CI 1.13-2.46) for those reporting 0.5-1 h and 1.49 (95% CI 1.01-2.19) for those reporting >1 h of day napping compared with individuals who did not take day naps (all P<0.05). Longer-duration day nappers had higher levels of IL-6 and progranulin (PGRN) but lower levels of Secreted frizzled-related protein-5 (SFRP5, all P trend <0.001). After adjusting for IL-6, PGRN, and SFRP5, the association between day napping duration and NAFLD disappeared (all P>0.05).Longer day napping duration is associated with a higher prevalence of NAFLD, and inflammatory cytokines may be an essential link between day napping and NAFLD

Plasma C1q/TNF-Related Protein-3 (CTRP-3) and High-Mobility Group Box-1 (HMGB-1) Concentrations in Subjects with Prediabetes and Type 2 Diabetes

Aims. To detect the association of C1q/TNF-related protein-3 (CTRP-3) and high-mobility group box-1 (HMGB-1) in subjects with prediabetes (pre-DM) and newly diagnosed type 2 diabetes (nT2DM). Methods. 224 eligible participants were included. The 75 g oral glucose tolerance test (OGTT) and several clinical parameters of metabolic disorders and cytokines were measured. All participants were divided into three groups: normal glucose tolerance (NGT, n=62), pre-DM (n=111), and nT2DM group (n=56). Results. Plasma CTRP-3 concentrations were significantly lower in subjects with pre-DM and nT2DM than that of the NGT group, while plasma HMGB-1 levels were higher in pre-DM and nT2DM group compared with the NGT group (P<0.05). A multiple linear regression analysis showed both plasma CTRP-3 and HMGB-1 concentrations were independently associated with homeostasis model assessment for insulin resistance (HOMA-IR) and interleukin-6 (IL-6) (P<0.05 for all). Further multiple logistical regression analyses revealed that both plasma CTRP-3 and HMGB-1 levels were significantly associated with pre-DM and nT2DM after adjusting for several confounders (P<0.001 for all). Conclusions. Circulating CTRP-3 and HMGB-1 concentrations might be promising biomarkers to predict prediabetes and type 2 diabetes

Maternal hypothyroidism during pregnancy alters the function of the retinol-binding protein 4-mediated mitochondrial permeability conversion pore in the kidneys of offspring rats

OBJECTIVES: To determine the role of the RBP4/PiC/SIRT3 signaling pathway in the opening of the mitochondria permeability transition pore (mPTP) in offspring rats with hypothyroidism during pregnancy. METHODS: Sixty Sprague-Dawley (SD) rats were employed in this study. Pregnancy was deemed successful when a sperm was found in the uterus. After one week of pregnancy, offspring rats were divided into the following groups: overall hypothyroidism group (OH group), subclinical hypothyroidism group (SCH group), and normal control group (CON group). The establishment of the hypothyroidism model was confirmed when the serum thyroid stimulating hormone (TSH) levels were higher than normal value and TT4 level was within the normal range. The renal mitochondria of offspring rats were extracted on the 14th postnatal day (P14) and 35th postnatal day (P35). RESULTS: At P14, no significant differences in the degree of mPTP opening and expression of phosphoric acid carrier vector (PiC) were detected between the rats in the OH group and the SCH group. However, the expression level of silent mating-type information regulation 3 homolog (SIRT3) was markedly reduced. Retinol-binding protein 4 (RBP4) expression increased in the rats from the OH group, relative to that in those from the SCH group. At P35, the degree of mPTP opening and the expression levels of PiC and RBP4 in the OH group were higher than those in the SCH group. However, SIRT3 expression in the OH group was lower than that observed in the SCH group. CONCLUSION: RBP4 plays an important role in early renal mitochondrial damage and renal impairment in rats suffering from hypothyroidism during pregnancy. The RBP4/PiC/SIRT3 pathway is thus involved in the opening of the renal mPTP in offspring rats with hyperthyroidism

Plasma HMGB-1 Levels in Subjects with Obesity and Type 2 Diabetes: A Cross-Sectional Study in China

<div><p>Object</p><p>To detect the levels of plasma High-Mobility Group Box-1(HMGB1) in Chinese subject with obesity and type 2 diabetes mellitus (T2DM), and to investigate the correlations between plasma HMGB1 concentration and parameters of body fat, insulin resistance (IR) metabolism and inflammation.</p><p>Methods</p><p>This study recruited 79 normal glucose tolerance (NGT) subjects and 76 newly diagnosed T2DM patients. NGT and T2DM groups were divided into normal weight (NW) and obese (OB)subgroups respectively. Anthropometric parameters such as height, weight, waist circumference, hip circumference and blood pressure were measured. Plasma concentrations of HMGB1, IL-6, fasting plasma glucose (FPG), 2 hours post challenge plasma glucose (2hPG), serum lipid, glycated hemoglobin (HbA_1C) and fasting insulin (FINS) were examined. The homeostasis model assessment (HOMA) was performed to assess IR status.</p><p>Results</p><p>Plasma HMGB1 levels were higher in T2DM group than that in NGT group. The concentrations of serum HMGB1 were also higher in subjects with OB than those in subjects with NW both in NGT and T2DM groups. Plasma levels of HMGB1 were positively correlated with waist hip ratio (WHR), blood pressure, FPG, FINS, HOMA-IR, TG, IL-6 and negatively correlated with HOMA-βand high-density lipoprotein-cholesterol (HDL-c) independent of age, gender and BMI. Plasma levels of HMGB1 were significantly correlated with diabetes in fully adjusted models.</p><p>Conclusion</p><p>Plasma HMGB1 levels were increased in Chinese subjects with pure T2DM, which might be caused by IR. Serum HMGB1 participated in the pathological process of obesity and T2DM via its proinflammatory effect.</p></div

Partial correlations analysis of variables associated with circulating HMGB1 concentration in study population.

<p>BMI, body mass index; Wc, waist circumference; WHR, waist hip ratio; SBP, systolic blood pressure; DBP, diastolic blood pressure; FPG, fasting plasma glucose; 2hPG, 2h postchallenge plasma glucose; HbA_1C, glycated hemoglobin; FINS, fasting serum insulin; HOMA-IR, Homeostasis Model Assessment for insulin resistance; HOMA-β, Homeostasis Model Assessment for beta-cell function; TC, total cholesterol; TG, triglyceride; HDL-c, high-density lipoprotein-cholesterol; LDL-c, low-density lipoprotein-cholesterol; IL-6, interleukin- 6.</p><p>Partial correlations analysis of variables associated with circulating HMGB1 concentration in study population.</p

Clinical and laboratory characteristics of the study subjects.

<p>Data are presented as means±SD. NGT, normal glucose tolerance; T2DM, type 2 diabetes mellitus; NW, normal weight; OB, obesity; BMI, body mass index; Wc, waist circumference; WHR, waist hip ratio; SBP, systolic blood pressure; DBP, diastolic blood pressure; FPG, fasting plasma glucose; 2hPG, 2 hours postchallenge plasma glucose; HbA_1C, glycated hemoglobin; FINS, fasting serum insulin; HOMA-IR, Homeostasis Model Assessment for insulin resistance; HOMA-β, Homeostasis Model Assessment for beta-cell function; TC, total cholesterol; TG, triglyceride; HDL-c, high-density lipoprotein-cholesterol; LDL-c, low-density lipoprotein-cholesterol; IL-6, interleukin- 6.</p><p>^aP<0.05 compared with NGT-NW,</p><p>^bP<0.05 compared with T2DM-NW,</p><p>^cP<0.05 compared with NGT-OB,</p><p>^dP<0.01 compared with NGT-NW,</p><p>^eP<0.01 compared with T2DM-NW,</p><p>^fP<0.01 compared with NGT-OB.</p><p>Clinical and laboratory characteristics of the study subjects.</p