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Cardiovascular disease (CVD) results in more than half of the mortality and the majority of morbidity in patients with type 2 diabetes. We aim to evaluate the associations of urinary concentrations of phthalate metabolites with CVD in diabetic patients and explore whether CVD risk factors mediate or interact with these associations. A total of 675 type 2 diabetic participants were enrolled from Shanghai, China, in 2018. CVD was defined as a self-reported diagnosis by a physician including coronary heart disease, myocardial infarction, or stroke; it was further reconfirmed in the records from the registration platform. Ten phthalate metabolites were measured in urine. We found positive associations were found among the level of monoethyl phthalate and monoisobutyl phthalate and CVD (OR 1.138, 95% CI 1.032, 1.254; OR 1.369, 95% CI 1.049, 1.786, respectively). Monoisobutyl phthalate and monobenzyl phthalate were marginally and positively associated with carotid intima-media thickness and common carotid artery diameter, respectively. None of the CVD risk factors, including HOMA-IR, body mass index, lipid profile, or blood pressure, significantly mediated the association between the metabolites and CVD. The conditional indirect effect on CVD was significantly stronger for current smoking and dyslipidemia for monoethyl phthalate and for no statin usage and men for monoisobutyl phthalate. In conclusion, phthalate exposure was positively associated with CVD in Chinese with type 2 diabetes. Type 2 diabetic men who are currently smoking, have an uncontrolled lipid profile, and are not using statins might be more susceptible to CVD when exposed to phthalates.

Early famine exposure has been related to the development of type 2 diabetes; however, little is known about whether the genetic background modifies this association. We aimed to investigate the joint effects of famine exposure at different stages of early life and genetic susceptibility on diabetes risk in adulthood. The study included 8350 participants from the Survey on Prevalence in East China for Metabolic Diseases and Risk Factors (SPECT-China) who were born around the time of the Chinese Great Famine. We determined famine exposure subgroups according to the birth year as nonexposed (1963–1974), fetal-exposed (1959–1962), childhood-exposed (1949–1958), and adolescence-exposed (1941–1948). We developed a genetic risk score of 21 variants previously associated with type 2 diabetes in East Asians. Hierarchical logistic models were used to examine the association of famine exposure and genetic risk with diabetes. The age-standardised prevalence of diabetes in nonexposed, fetal-exposed, childhood-exposed and adolescence-exposed subgroups was 13.0%, 18.2%, 15.1% and 13.2%, respectively. Compared with nonexposed participants, fetal-exposed participants showed an increased risk of diabetes in adulthood (OR 1.47; 95% CI 1.13, 1.93). A higher genetic risk score was associated with an increased risk of diabetes (OR 1.23; 95% CI 1.15, 1.31 per SD increment). The association between famine exposure and diabetes was consistent across genetic risk strata (all p for interaction >0.05). When considered jointly, fetal- or childhood-exposed participants at high genetic risk (highest tertile of genetic risk score) had 2.60-fold (95% CI 1.71, 3.93) and 1.95-fold (95% CI 1.24, 3.05) higher risks of diabetes, respectively, compared with nonexposed participants at low genetic risk (lowest tertile). Prenatal exposure to famine was associated with an increased risk of type 2 diabetes in Chinese adults independent of genetic risk score using 21 variants common in the East Asian population. Famine exposure and genetic susceptibility may exhibit an additive effect on diabetes development.

Background Bone is thought to be the reservoir of the human lead burden, and vitamin D is associated with bone turnover. We aimed to explore whether exposure to lower 25-hydroxy vitamin D (25(OH)D) levels was associated with higher blood lead levels (BLLs) by increasing the bone turnover rate in individuals with type 2 diabetes. Methods A total of 4103 type 2 diabetic men and postmenopausal women in Shanghai, China, were enrolled in 2018. Their 25(OH)D, β-C-terminal telopeptide (β-CTX), N-MID osteocalcin and procollagen type 1 N-peptide (P1NP) levels were detected. Their BLLs were determined by atomic absorption spectrometry. Mediation analyses were performed to identify the possible role that bone turnover played in the underlying mechanisms. Results In both the men and postmenopausal women, all three bone turnover markers were inversely associated with 25(OH)D and positively associated with the BLL (all P < 0.01) after adjusting for age, current smoking habits, metabolic parameters, duration of diabetes, vitamin D intake, and use of anti-osteoporosis medication. In the mediation analyses, none of the direct associations between 25(OH)D and BLL was significant for the three bone turnover markers, but all three bone turnover markers were found to be significant mediators of the indirect associations between 25(OH)D and BLL. Conclusion The association between vitamin D and BLL was fully mediated by bone turnover markers in type 2 diabetic patients (mediation effect). This finding suggested that vitamin D may protect against blood lead exposure from the bone reservoir by decreasing bone turnover in individuals with type 2 diabetes.

Context The double burden of malnutrition (DBM), undernutrition in early life and an obesogenic environment later on, influences later risk of chronic disorders. The Great Famine in China from 1959 to1962 and remarkable economic development from the 1980s provided such a burden for a large number of people in their 60s. Objective We aimed to analyze the effect of economic status on the association between famine exposure in early life and hyperuricemia in adulthood. Design and Setting Participants numbering 12 666 were enrolled in China based on the Survey on Prevalence in East China for Metabolic Diseases and Risk Factors (SPECT-China) Study from 2014 to 2016. Participants Participants with fetal or childhood famine exposure (birth year 1949-1962) formed the exposure group. Main Outcome Measure Hyperuricemia was defined as uric acid (UA) > 420 μmol/L for men and > 360 μmol/L for women. The association of famine with hyperuricemia was assessed via regression analyses. Results Early-life famine exposure was negatively associated with UA levels (P = .045) but was not associated with hyperuricemia (P = .226) in the whole study population. Economic status could moderate the association of famine exposure with UA and hyperuricemia (P ≤ .001). In participants with high economic status, early-life famine exposure was positively associated with UA levels (unstandardized coefficients 7.61, 95% CI 3.63-11.59, P < .001), and with hyperuricemia (odds ratio 1.47, 95% CI 1.19-1.81, P < .001). Conclusions Economic status could moderate the association between exposure to famine in early life and hyperuricemia in adulthood, indicating that the DBM might affect hyperuricemia in an opposite direction of the effects of undernutrition in early life alone.

Background The principal function of iodine acts on thyroid function, but in recent years, the role of iodine deficiency in metabolism has also been gradually revealed. We aimed to investigate the current status of iodized salt consumption and urinary iodine concentration (UIC) in an urban Chinese population with type 2 diabetes, and to further explore whether UIC was associated with diabetic microvascular complications. Methods Four thousand five hundred fifty-nine subjects with diabetes from 7 communities in downtown Shanghai were enrolled in the cross-sectional Metal Study in 2018. UIC was detected using an inductively coupled plasma-mass spectrometer. Diabetic kidney disease (DKD) was defined as urinary albumin-to-creatinine ratio (UACR) > 30 mg/g or estimated glomerular filtration rate 2. Diabetic retinopathy (DR) was evaluated by high-quality fundus photographs and was remotely read by ophthalmologist. Results The median UIC of subjects with diabetes was 115.4 μg/L (78.9–170.8) in downtown Shanghai. Among all the subjects, 52.7% consumed non-iodized salt and 40.4% were iodine deficient. Iodine deficiency (UIC Conclusions A concerning number of subjects with diabetes consumed non-iodized salt and suffered from iodine deficiency in coastal regions of China. Low UIC might be a risk factor for DKD, which should be further confirmed by longitudinal prospective studies.

Background and aims Obesity, especially abdominal obesity, has been considered a risk factor for diabetic complications. Many abdominal obesity indices have been established, including neck circumference (NC), waist-to-hip ratio (WHR), lipid accumulation product (LAP), visceral adiposity index (VAI) and the Chinese visceral adiposity index (CVAI). However, studies investigating the associations between these indices and diabetic complications are limited. The objective of this study was to investigate the associations of the abdominal obesity indices with cardiovascular and cerebrovascular disease (CVD), diabetic kidney disease (DKD) and diabetic retinopathy (DR). Methods A total of 4658 diabetic participants were enrolled from seven communities in Shanghai, China, in 2018. Participants completed questionnaires and underwent blood pressure, glucose, lipid profile, and urine albumin/creatinine ratio measurements; fundus photographs; and anthropometric parameters, including height, weight, waist circumference (WC), NC and hip circumference (HC). Results In men, a one standard deviation (SD) increase in CVAI level was significantly associated with a greater prevalence of CVD (OR 1.35; 95% CI 1.13, 1.62) and DKD (OR 1.38; 95% CI 1.12, 1.70) (both P P Conclusions CVAI was most strongly associated with the prevalence of CVD and DKD among the abdominal obesity indices, and NC was unique associated with the prevalence of CCA plaque in Chinese adults with diabetes. Trial registration ChiCTR1800017573, www.chictr.org.cn. Registered 04 August 2018.

Objectives Famine exposure in early life was associated with type 2 diabetes, non-alcoholic fatty liver disease and metabolic syndrome, etc. But evidence in early famine exposure and insulin resistance and beta cell dysfunction were limited. We aimed to investigate whether the association existed between famine exposure in early life and beta cell dysfunction and insulin resistance in adulthood. Methods In all, 7912 non-diabetic participants were included in this study, based on SPECT-China study. Participants with fetal or childhood famine exposure (birth year 1949–1962) were exposure group. Insulin resistance was estimated by the homeostasis model assessment index of insulin resistance (HOMA-IR). Beta cell function, represented by insulin secretion, was estimated by the disposition index. The associations of famine exposure with HOMA-IR and disposition index were assessed via linear regression. Results In men, we did not observe a significant association between early life famine exposure and ln(HOMA-IR) in all three models (P > 0.05 for all). However, in women, early life famine exposure were found to have significant association with ln(HOMA-IR) after adjustments for urbanization, severity of famine exposure, current smoker, waist circumference, hypertension, and dyslipidemia (unstandardized coefficients 0.055, 95% confidence interval 0.021, 0.088, P = 0.001). Early life famine exposure was observed to be negatively associated with ln(disposition index) after adjustments for the above potential confounders, both in men (model 3: unstandardized coefficients −0.042, 95% confidence interval −0.072,−0.012, P = 0.006) and women (model 3: unstandardized coefficients −0.033, 95% confidence interval −0.058,−0.009, P = 0.008). Conclusions In conclusion, exposure to famine in fetal- and childhood- life period is associated with beta cell dysfunction in males and females without diabetes, but early life famine exposure was only associated with insulin resistance in non-diabetic females. These results indicate that malnutrition in early life period may offer a modifiable factor for type 2 diabetes development.

BACKGROUND & AIMS The double burden of malnutrition (DBM) in China resulted in high prevalence of diet-related non-communicable diseases. The aim of this study was to analyse the moderation of economic status in the association between early famine exposure and metabolic dysfunction associated with fatty liver disease (MAFLD) in adulthood. METHODS 10 190 participants in the SPECT-China study enrolled from 2014 to 2016 were included in this study. Participants with fetal famine exposure (birth year 1959-1962) or early-childhood famine exposure (birth year 1955-1958) formed the exposure group. The associations with MAFLD were assessed via regression analyses. RESULTS In men, economic status could not moderate the association between early life famine and MAFLD after adjusting for age, excess alcohol drinking, current smokers, famine severity, waist circumference, diabetes, hypertension, and dyslipidemia (P for interaction = .52). However, in women and in the total population, economic status could moderate the association between early life famine and MAFLD after adjusting for the above confounders (P for interaction = .01). In the total population and in women, early life famine exposure was associated with MAFLD in both low economic status and high economic status. However, in men, early life famine exposure was not associated with MAFLD in low economic status, while in high economic status, early-childhood famine exposure was associated with MAFLD. CONCLUSIONS Economic status could moderate the association between early life famine exposure and MAFLD in total population and in women.

IntroductionExposure to malnutrition in early life has been found to significantly elevate type 2 diabetes risk in adulthood. However, the changes in metabolites resulting from malnutrition in early life have not been studied. The aim of this study was to identify metabolites with levels associated with type 2 diabetes resulting from exposure to China’s Great Famine (1959–1962).Research design and methodsParticipants were from SPECT-China 2014 and SPECT-China2 2019, two cross-sectional studies performed at the same site. In total, 2171 subjects participated in SPECT-China and SPECT-China2 simultaneously. The sample size of fetal-exposed (1959–1962) versus non-exposed (1963–1974) individuals was 82 vs 79 in 2014 and 97 vs 94 in 2019. Metabolomic profiling was performed between famine-exposed and non-exposed groups.ResultsAmong the different famine exposure groups, the fetal-exposed group (1959–1962) had the greatest incidence rate (12.5%), with an OR of 2.11 (95% CI 1.01 to 4.44), compared with the non-exposed group (1963–1974). Moreover, compared with those in the non-exposed group (1963–1974), four metabolites (indole-3-carbinol (I3C), phosphatidylcholine (PC) (22:6(4Z,7Z,10Z,13Z,16Z,19Z)/16:1(9Z)), pyrimidine, and PC(16:1(9Z)/22:5(4Z,7Z,10Z,13Z,16Z))) showed significantly lower relative intensities in the famine and diabetes groups both in 2014 and 2019. Pyrimidine significantly mediated the association of famine exposure with diabetes, and I3C marginally mediated this association.ConclusionsFamine exposure in the fetal period could increase type 2 diabetes risk in adults, even those in their 60s. I3C and pyrimidine are potential mediators of the effects of famine exposure on diabetes development.

Purpose Cardiovascular disease (CVD) results in more than half of the mortality and the majority of morbidity in patients with type 2 diabetes. We aim to evaluate the associations of urinary concentrations of phthalate metabolites with CVD in diabetic patients and explore whether CVD risk factors mediate or interact with these associations.Methods A total of 675 type 2 diabetic participants were enrolled from one community in Shanghai, China in 2018. CVD was defined as a self-reported diagnosis by a physician and included coronary heart disease, myocardial infarction or stroke; it was further reconfirmed in the records from the registration platform. Ten phthalate metabolites were measured in urine.Results Positive associations were found among the level of monoethyl phthalate and monoisobutyl phthalate and CVD (OR 1.138, 95% CI 1.032, 1.254; OR 1.369, 95% CI 1.049, 1.786, respectively). Monoisobutyl phthalate and monobenzyl phthalate were marginally and positively associated with carotid intima-media thickness and common carotid artery diameter, respectively. None of the CVD risk factors, including HOMA-IR, body mass index, lipid profile or blood pressure, significantly mediated the association between the metabolites and CVD. The conditional indirect effect on CVD was significantly stronger for current smoking and dyslipidemia for monoethyl phthalate and for no statin usage and men for monoisobutyl phthalate.Conclusion Phthalate exposure was positively associated with CVD in type 2 diabetes. Type 2 diabetic men who are currently smoking, have an uncontrolled lipid profile and are not using statins may be more susceptible to CVD when exposed to phthalates.

Aims: Some studies have reported associations between bilirubin and diabetic microvascular complications. However, these studies focused only on total bilirubin (TBIL) without distinguishing different bilirubin subtypes. In this study, we aimed to investigate the associations of TBIL, direct bilirubin (DBIL) and indirect bilirubin (IBIL) levels with albuminuria/creatinine ratio (ACR) and the prevalence of diabetic retinopathy (DR) among diabetic adults. Methods: We analyzed 4368 individuals out of 4813 diabetic participants enrolled from seven communities in 2018 in a cross-sectional study. Participants underwent several checkups, including the measurement of anthropometric parameters, blood pressure, glucose, lipid profile, TBIL, DBIL, IBIL and ACR. DR was detected by high-quality fundus photographs and was remotely read by ophthalmologists. Results: Compared with the first quartile of DBIL, participants in the fourth quartile had a lower prevalence of high ACR (odds ratio (OR) 0.76; 95% confidence interval (CI) 0.59, 0.99) ( p for trend Conclusion: DBIL had a stronger association with high ACR and DR than TBIL or IBIL did in diabetic adults. The effect of DBIL on diabetic complications should be noted and investigated in further studies.

Previous studies have suggested that a high blood lead level (BLL) is associated with cardiovascular outcomes and impaired renal function in the general population; however, studies investigating the effect of a high BLL on diabetic vascular complications have been limited. We aimed to investigate whether a higher BLL is associated with cardiovascular disease (CVD) and diabetic kidney disease (DKD).We analyzed 4234 individuals out of 4813 diabetic participants enrolled from seven communities in China in 2018 in this cross-sectional study. Macrovascular measurements, including assessment of common carotid artery (CCA) plaques and their diameters, were performed with ultrasound. CVD was defined as a composite measure including a previous diagnosis of coronary heart disease, myocardial infarction, or stroke. The definition of DKD was an albumin to creatinine ratio (ACR) ≥30 mg/g or an estimated glomerular filtration rate (eGFR) 60 ml/min per 1.73 mThe median age and BLL of the participants were 67 years (interquartile range, 62-72 years) and 26 μg/L (interquartile range, 18-36 μg/L). Compared with the first quartile, the odds ratio (OR) (95% CI) of CCA plaques ranging from none to bilateral in the ordinal logistic regression analysis associated with BLL was 1.53 (1.29, 1.82) in the fourth BLL quartile (P for trend0.01), and the odds of having CVD was significantly increased by 44% for participants in the fourth quartile (1.44 (1.17, 1.76)) (P for trend0.01). The odds of DKD in the fourth BLL quartile increased by 36% (1.36 (1.06, 1.74)) compared with that in the first quartile (P for trend0.05). These associations were adjusted for potential confounders.A high BLL may be a potential risk factor for CVD and DKD in middle-aged and elderly diabetic adults.

Objective The attraction and influx of monocytes into the retina has been considered a critical step in the development of diabetic retinopathy (DR). However, large population studies about the association between peripheral blood monocyte levels, an inexpensive and easily measurable laboratory index, and DR are limited. Thus, we aimed to investigate the association between peripheral blood monocyte levels and DR. Methods A total of 3223 participants out of 3277 adults with diabetes were enrolled from seven communities in China in this cross-sectional survey. Participants underwent several medical examinations, including the measurement of anthropometric factors, blood pressure, routinely analyzed leukocyte characteristics, glucose, lipid profiles, urine albumin/creatinine ratio and fundus photographs. Results The prevalence of DR among the participants in the highest quartile of peripheral blood monocyte levels significantly decreased by 41% (OR 0.59; 95% CI 0.43, 0.81) compared with the participants in the first quartile (P for trend P for trend > 0.05). Associations between leukocyte, neutrophil and lymphocyte levels and DR were also not found (all P for trend > 0.05). These associations were all fully adjusted for age, sex, education status, duration of diabetes history, current smoking, BMI, HbA1c, dyslipidemia, systolic blood pressure and insulin therapy. Conclusion Decreased peripheral blood monocyte levels were associated with increased odds of DR after adjusting for potential confounders in diabetic adults. However, causation remains to be demonstrated.

Phthalates are ubiquitous in different environmental exposure media around the world. Recent years, issues on the relationships of phthalates and endocrine disorders raise attention. Evidence of thyroid disruption as a result of phthalates expose among euthyroid participants with diabetes is very limited. We aimed to evaluate the association between phthalate and thyroid function, and to explore whether thyroid autoimmunity mediated this association. Concurrent urine and blood samples were collected from 538 participant in METAL study. We measured urinary concentrations of ten phthalate metabolites (urinary creatinine adjusted), along with serum levels of thyroid-stimulating hormone (TSH), free thyroxin (FT4), free triiodothyronine (FT3), thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb). Euthyroidism was defined as TSH within normal range. After adjusting for age, sex (only with the entire sample), BMI and smoking status, linear regression analyses showed exactly opposite directional results among men and women. TSH levels were negatively associated with mono-2-ethyl-5-carboxypentylphthalate (MECPP), mono-2-ethyl-5-hydroxyhexylphthalate (MEHHP), mono-2-ethyl-5-oxohexylphthalate (MEOHP), mono-2-carboxymethyl-hexyl phthalate (MCMHP) and sum of di (2-ethylhexyl) phthalate metabolites (ΣDEHPm) in men, but positively associated with monoisobutylphthalate (MiBP) and mono-n-butylphthalate (MnBP) in women. Meanwhile, FT4 was positively associated with mono-2-ethylhexylphthalate percentage (%MEHP) in men, but negatively associated with MnBP, MEOHP and MCMHP in women. Further, in women, TPOAb was increasing along with the increased level of MEHP and %MEHP. In the mediation analysis, TPOAb demonstrated a mediating effect whereby MEHP or %MEHP had a positive effect on TSH and a negative effect on FT4 only in women (all P

Introduction: In assessing the development of hyperuricemia in diabetic adults, the role of the sex steroid axis is underappreciated. Furthermore, dehydroepiandrosterone (DHEA) has been recommended as a nutritional supplement. However, is DHEA suitable for diabetic adults with hyperuricemia? This issue has received little attention.Aim: The objective of this study was to investigate the associations between gonadal hormones and uric acid (UA) levels in diabetic adults, paying particular attention to the association between DHEA and UA levels.Methods: We analyzed 4,426 participants out of 4,813 diabetic adults enrolled from seven communities in a cross-sectional survey conducted in 2018. Participants underwent several examinations, including assessments of anthropometric parameters, blood pressure, glucose, lipid profiles, UA, total testosterone (TT), estradiol (E2), the follicle-stimulating hormone (FSH), the luteinizing hormone (LH), and dehydroepiandrosterone (DHEA).Results: Among men and compared with individuals in the first quartile, participants in the fourth quartile of TT and FSH had odds of hyperuricemia that were significantly decreased by so much as 48 and 34%, respectively (both P < 0.05). However, participants in the fourth quartile of DHEA had 79% increased odds of hyperuricemia (P < 0.05). Among postmenopausal women, participants in the fourth quartile of DHEA, TT, and LH had odds of hyperuricemia that were significantly increased by 155, 99, and 76%, respectively (all P < 0.05). These associations were adjusted for potential confounding factors.Conclusions: Sex differences were found in the associations between gonadal hormones and UA levels in diabetic men and postmenopausal women, which should be monitored to prevent hyperuricemia when sex hormone treatment, especially DHEA, is administered. Further studies are needed.

Objective. The neutrophil-to-lymphocyte ratio (NLR) is an inexpensive and easily measurable laboratory index indicating systemic inflammation, while the application of many other inflammatory markers has been limited in daily clinical practice. However, large population studies about investigating the associations of the NLR level with diabetic complications including cardiovascular and cerebrovascular diseases (CVD), diabetic kidney disease (DKD), and diabetic retinopathy (DR) in the same population were limited. The aim of our study is to evaluate the associations between the NLR level and the prevalence of CVD, DKD, and DR in adults with diabetes simultaneously. Methods. A cross-sectional survey of 4,813 diabetic adults was conducted in seven communities in China. Persons underwent several medical examinations, including the measurement of anthropometric factors, blood pressure, routinely analyzed leukocyte characteristics, glucose, lipid profiles, urine albumin/creatinine ratio, and fundus photographs. Results. Compared with the first quartile of the NLR level, the odds of having CVD was significantly increased by 21% for participants in the highest quartile (OR 1.21; 95% CI 1.00, 1.47) (P for trend<0.05). Similarly, the prevalence of DKD among participants in the highest quartile of the NLR level was significantly increased by 150% (OR 2.50; 95% CI 1.95, 3.19) (P for trend<0.05). However, no association was found between the NLR level and the prevalence of DR (P for trend>0.05). These associations were all fully adjusted. Conclusions. A higher NLR level was associated with an increased prevalence of CVD and DKD, other than DR, in diabetic adults.

Objective. Diabetic kidney disease is one of the most common microvascular complications of diabetes mellitus. We aimed to analyze the association of thyroid parameters with kidney disorders, especially in euthyroid participants. Methods. The data were obtained from a cross-sectional study, the METAL study. Thyroid parameters, including thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), triiodothyronine (T3), thyroxin (T4), thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb), of 4136 participants with type 2 diabetes were measured. Two structure parameters of thyroid homeostasis, including the sum activity of step-up deiodinases (SPINA-GD) and thyroid secretory capacity (SPINA-GT), and two pituitary thyrotropic function indices, including Jostel’s TSH index (TSHI) and the thyrotroph thyroid hormone resistance index (TTSI), were also calculated. Kidney disorders were described according to the presence of reduced estimated glomerular filtration rate (eGFR) and/or higher urinary albumin to creatinine ratio (UACR). Results. The prevalence of kidney disorders increased with decreasing FT3 or T3 and increasing FT4 or T4 quartile levels (all P<0.05). After full adjustment, linear regression showed that UACR levels were negatively associated with FT3 and T3 (P<0.001). In addition, eGFR was positively associated with FT3 and T3 and was negatively associated with TSH and FT4 levels and TgAb positivity (all P<0.05). By using binary logistic regression, higher TSH and FT4 and lower FT3 and T3 were associated with kidney disorders (all P<0.05). Similar results were seen in sensitivity analyses, which were performed in 3035 euthyroid diabetic participants; however, TSH was no longer related to them. The area under the receiver operating characteristic curve (AUROC) of lower FT3 for existing kidney disorder was greater than that for any other thyroid hormones (all P<0.001). The cutoff value of FT3 for reduced eGFR was 4.39 pmol/L. Regarding thyroid homeostasis parameters, SPINA-GD was negatively associated with three statuses of kidney disorders, and TSHI and TTSI were positively associated with reduced eGFR (all P<0.05). Conclusions. Among patients with type 2 diabetes, elevated TSH and FT4 (or T4), lower FT3 (or T3), TgAb positivity, lower SPINA-GD, and higher TSHI and TTSI were associated with kidney disorders. The lower FT3, even within the normal range (

Environmental lead exposure has been linked with reduced kidney function. However, evidence about its role in diabetic kidney damage, especially when considering the nutritional status of vitamin D, is sparse. In this observational study, we investigated the association between low-level lead exposure and urinary albumin-to-creatinine ratio (UACR) and assessed potential impact of vitamin D among 4033 diabetic patients in Shanghai, China. Whole blood lead was measured by graphite furnace atomic absorption spectrometry. Serum 25-hydroxyvitamin D [25(OH)D] was tested using a chemiluminescence immunoassay. The associations of blood lead with UACR and albuminuria, defined as UACR ≥30 mg/g, according to 25(OH)D levels were analyzed using linear and Poisson regression models. A doubling of blood lead level was associated with a 10.7% higher UACR (95% CI, 6.19%-15.5%) in diabetic patients with 25(OH)D 50 nmol/L, whereas the association was attenuated toward null (2.03%; 95% CI, -5.18% to 9.78%) in those with 25(OH)D ≥ 50 nmol/L. Similarly, the risk ratios of prevalent albuminuria per doubling of blood lead level between the two groups were 1.09 (95% CI, 1.03-1.15) and 0.99 (95% CI, 0.86-1.14), respectively. Joint analysis demonstrated that a combination of high blood lead and low 25(OH)D corresponded to significantly higher UACR. Among diabetic patients with 25(OH)D 50 nmol/L, the increment of UACR relative to blood lead was more remarkable in those with reduced estimated glomerular filtration rate (60 mL/min/1.73 m

BACKGROUND Kidney dysfunction is linked to nonalcoholic fatty liver disease (NAFLD) progression including fibrosis, steatosis, or inflammation. We aimed to explore whether lower levels of estimated glomerular filtration rate (eGFR) was associated with increased probability of liver fibrosis. METHODS Two thousand six hundred eighty-nine subjects enrolled from Shanghai, China, were included in this study. NAFLD fibrosis score (NFS) was used to risk stratify NAFLD patients for fibrosis. eGFR was used to assess kidney function. The association of eGFR level with elevated NFS, and thus high risk of fibrosis, was analysed by linear regression and multinomial logistic regression. The predictive power of eGFR was evaluated via receiver operating characteristic (ROC) curve. RESULTS A negative association was found between eGFR and NFS (B = -0.21, 95% CI, -0.37 to -0.04, P = .016). As eGFR quartiles decreased, the prevalence of probable fibrosis increased after adjusting for age, sex, current smoking, waist circumference, duration of diabetes, HbA1c , hypertension, dyslipidaemia, and homeostasis model assessment index of insulin resistance (HOMA-IR) (Q4: reference; Q3: 1.49, 95% CI, 0.82-2.71; Q2: 1.88, 95% CI, 0.97-3.67; Q1: 2.70, 95% CI, 1.36-5.37, Pfor trend = .002, 1SD increment: 0.73, 95% CI, 0.58-0.92). The eGFR level can be an effective indicator in differentiating patients with probable presence of fibrosis from those without (AUROC: 0.71, cut-off point: 92.78 mL/min/1.73 m2 , P

Background Associations between sex hormones and vascular remodeling have been extensively studied, but the results vary widely among different races and sex. We aimed to investigate whether total testosterone (TT), estrogen (E2), and dehydroepiandrosterone (DHEA) associate with macrovascular complications and diabetic kidney disease (DKD) among community-dwelling patients with diabetes. Methods A total of 4720 participants with type 2 diabetes were recruited from Shanghai, China. Common carotid artery (CCA) plaques and diameter were assessed by ultrasound. Cardiovascular disease (CVD) was defined by prior diagnosis of coronary heart disease, myocardial infarction or stroke. DKD was defined according to the ADA Guidelines. Results (1) In men, TT was negatively associated with CCA diameter (regression coefficient (β) − 0.044, 95% CI − 0.087, 0). E2 levels were positively associated with CVD and CCA plaque prevalence (OR 1.151, 95% CI 1.038, 1.277 and OR 1.13, 95% CI 1.017, 1.255, respectively). DHEA was negatively associated with CVD (OR 0.809, 95% CI 0.734, 0.893). In postmenopausal women, TT levels were negatively associated with CCA diameter (β − 0.046, 95% CI − 0.083, − 0.010) and positively associated with CVD (OR 1.154, 95% CI 1.038, 1.284). (2) In both men and postmenopausal women, TT levels were negatively associated with the albumin/creatinine ratio and DKD (β − 0.098, 95% CI − 0.154, − 0.043 and OR 0.887, 95% CI 0.790, 0.997 vs. β − 0.084, 95% CI − 0.137, − 0.031 and OR 0.822, 95% CI 0.731, 0.924, respectively) and DHEA levels were positively associated with DKD (OR 1.167, 95% CI 1.038, 1.313 vs. OR 1.251, 95% CI 1.104, 1.418, respectively). Conclusions Our study indicates that macrovascular complications were associated with low TT, DHEA and high E2 in men and with high TT in postmenopausal women. DKD was associated with low TT and high DHEA levels in both genders. Sex hormone replacement therapy requires careful and comprehensive consideration. Trial registration ChiCTR1800017573, http://www.chictr.org.cn. Registered 04 August 2018

Background and Aims: Hyperuricemia is a pathological condition associated with hypertension, metabolic dysfunctions, renal, and cardiovascular diseases. Epidemiologic studies indicated that early life famine exposure influences later risk of chronic disorders. But evidence in the association between famine exposure and hyperuricemia were limited. We aimed to investigate whether the association existed between famine exposure in early life and hyperuricemia in adulthood. Methods: 12666 participants were enrolled in China based on SPECT-China study (ChiCTR-ECS-14005052, www.chictr.org.cn). Hyperuricemia was defined as UA >420 μmol/L for men and >360 μmol/L for women. The associations of famine exposure with hyperuricemia were assessed via logistic regression. Results: For famine exposed women, fetal famine exposure was significantly associated with hyperuricemia (1.63 (95% CI 1.04-2.54), P=0.031). Early life famine exposure was only associated with hyperuricemia in lean women (fetal exposed: 1.9 (95% CI 1.11-3.24); childhood exposed: 1.91 (95% CI 1.05-3.47), P Conclusions: Exposure to famine in early life period may lead to hyperuricemia in female, which indicates malnutrition in early life period may offer a modifiable factor for hyperuricemia development. Disclosure Y. Wang: None. W. Zhang: None. H. Wan: None. C. Chen: None. Y. Chen: None. F. Xia: None. B. Han: None. Q. Li: None. N. Wang: None. Y. Lu: None. Funding National Natural Science Foundation of China (91857117, 81570726, 81600609, 81600614, 81800694]; Science and Technology Commission of Shanghai Municipality (18410722300, 16411971200, 16410723200); Commission of Health and Family Planning of Pudong District (PWZxq2017-17, PW2015D-5); Shanghai Municipal Commission of Health and Family Planning (15GWZK0202, 20164Y0079); Municipal Human Resources Development Program for Outstanding Young Talents in Medical and Health Sciences in Shanghai (2017YQ053); Clinical Research Plan of SHDC (16CR3076B)

Aim: The objective of the study was to investigate whether higher serum urate (SUA) level has consistent association with cardiovascular disease (CVD), diabetic kidney disease (DKD) and diabetic retinopathy (DR) in Chinese adults with type 2 diabetes mellitus (T2DM). Methods: 4,767 diabetic participants were enrolled from seven communities in Huangpu and Pudong District, Shanghai, China in 2018. Participants underwent several checkups, which included the measurement of anthropometric parameters, blood pressure, glucose, lipid profiles, SUA and urine albumin/creatinine ratio (ACR). Results: Compared with the first SUA group, the third group increased the prevalence of CVD by 27% (OR 1.27; 95% CI 1.04, 1.55) (P for trend Conclusions: Higher SUA level was associated with increased odds of CVD, DKD and variety of the diabetic complications, not DR, in middle-aged and elderly diabetic Chinese adults, which means lowering SUA level may be critical for prevention and intervention of diabetic complications. Disclosure H. Wan: None. Y. Wang: None. Y. Chen: None. C. Wang: None. W. Zhang: None. F. Xia: None. N. Wang: None. Y. Lu: None.

Context Hyperuricemia has been considered to increase the risk of stroke, cardiovascular disease and all-cause mortality in type 2 diabetic patients. However, in assessing clinical and pathophysiological development of hyperuricemia, the critical role of the sex steroids axis is underappreciated, particularly concerning the sex specific relations. Objective We aimed to investigate the association between sex hormones and uric acid (UA) concerning the sex specific relations in diabetic adults. Methods 4,460 diabetic participants were enrolled from seven communities in Huangpu and Pudong District, Shanghai, China in 2018 based on METAL study. Participants underwent several checkups, which included the measurement of anthropometric parameters, blood pressure, glucose, lipid profiles, UA and sex hormones including total testosterone (TT), estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH) and dehydroepiandrosterone (DHEA). Results In men, TT and FSH were negatively associated with UA but DHEA was positively associated with UA. E2 and LH were not associated with UA significantly. In postmenopausal women, T, LH and DHEA were all positively associated with UA. E2 and FSH were not significantly associated with UA. These associations were all adjusted for drinking status, smoking status, duration of diabetes, hypertension, dyslipidemia, BMI, HbA1C, HOMA-IR, GFR, aspirin taking and ARBs taking. Conclusions The gender differences were found in the association between sex hormones and UA in diabetic adults. Testosterone might be a biomarker of hyperuricemia in patients with T2DM and the level of UA is suggested to be monitored to prevent hyperuricemia when sex hormone treatment, especially DHEA, is administered.

Context Insulin resistance and beta cell dysfunction are pivotal to the progression of metabolic diseases. Previous studies suggested famine exposure in early life was associated with type 2 diabetes, non-alcoholic fatty liver disease and metabolic syndrome, etc. But evidence in early famine exposure and insulin resistance and β-cell dysfunction were limited. Objective We aimed to investigate whether the association existed between famine exposure in early life and β cell dysfunction and insulin resistance in adulthood. Design and setting 10772 non-diabetic participants were enrolled in China based on SPECT-China study (ChiCTR-ECS-14005052, www.chictr.org.cn). Main outcome measure Insulin resistance was estimated by the homeostasis model assessment index of insulin resistance (HOMA-IR). Beta cell function, represented by insulin secretion, was estimated by the disposition index. The associations of famine exposure with HOMA-IR and disposition index were assessed via linear regression. Results In both men and women, the disposition indices were lower in fetal- and childhood- exposed subjects than non-exposed subjects. In women, the HOMA-IR levels were higher in fetal- and childhood- exposed subjects than non-exposed subjects. In men, we did not observe a significant association between the fetal- and childhood- exposed subjects and ln(HOMA-IR). However, in women, fetal- and childhood- exposed subjects were found to have significant association between famine exposure and ln(HOMA-IR). In both genders, the ln(disposition index) was observed to be significantly associated with fetal exposure to famine. Conclusions Exposure to famine in fetal- and childhood life period may lead to beta cell dysfunction and insulin resistance in non-diabetic male or/and females, which indicates malnutrition in early life period may offer a modifiable factor for type 2 diabetes development.

Background: Strong associations of obesity and diabetes with nonalcoholic fatty liver disease (NAFLD) have been discovered, but their causal relationships and interplay of genetic background was not fully determined. We aimed to assess the causal association of type 2 diabetes and BMI with NAFLD by Mendelian randomization (MR) analysis, and whether these associations were modulated by different levels of type 2 diabetes and body mass index (BMI) genetic risk scores (GRS). Methods: 8,944 participants were enrolled from a large cohort study. Subjects with a history of excessive consumption (male ≥20 g/d, female ≥10 g/d) of pure alcohol, viral hepatitis (including hepatitis B and hepatitis C virus), using medications associated with secondary NAFLD were excluded. We calculated the weighted diabetes and BMI GRS based on 18 and 14 variants that identified and validated in East Asians. Liver steatosis was determined by ultrasound. Results: MR analysis is regarded as independent of confounders affecting the exposure-outcome relationship and guiding definite causal direction. Using MR analysis, in total subjects the causal odds ratio (ORMR) of genetically determined BMI for NAFLD were 1.434 (95% CI 1.234, 1.665), and for genetically determined diabetes, the association was insignificant (OR 1.098, 95%CI 0.890, 1.354). Then, we found DM_GRS and BMI_GRS significantly interacted (P for interaction 0.018). In stratification analyses, in the lowest BMI_GRS quartile, ORMR of diabetes for NAFLD were 1.581 (95%CI 1.071, 2.233) and the association was insignificant in three higher BMI_GRS quartiles. Conversely, in subjects within DM_GRS from quartile one to three, the ORMRs of BMI for NAFLD were 1.769 (95%CI 1.203, 2.601), 1.325 (95%CI 1.025, 1,711) and 1.822 (95%CI 1.025, 2.933) but the association was insignificant in highest DM_GRS. Conclusions: The causal associations of type 2 diabetes and BMI with NAFLD were significantly modulated by the diabetes and adiposity genetic risk showing a wax-and-wane pattern. Individuals with obesity and diabetic patients with low adiposity genetic risk may need screening for NAFLD.

Background: Strong associations between obesity and type 2 diabetes with nonalcoholic fatty liver disease (NAFLD) have been discovered, but their causal relationships and interplay with genetic backgrounds have not been enough determined. We aimed to assess the causal association of type 2 diabetes and body mass index (BMI) with NAFLD using Mendelian randomization (MR) analysis and then whether type 2 diabetes and BMI genetic risk scores (GRSs) moderated these associations. Methods: A total of 8,944 participants were enrolled from 16 sites in East China from 2014-2016 from the SPECT-China study. We calculated the weighted diabetes and BMI GRSs based on 18 and 14 variants, respectively. Liver steatosis was determined by ultrasound. Results: Using MR analysis, the causal odds ratio (ORMR) of genetically determined BMI for NAFLD in all subjects was 1.434 (95% CI 1.234, 1.665), and for genetically determined diabetes, the association was insignificant (OR 1.098, 95% CI 0.890, 1.354). A significant interaction was found between DM_GRS and BMI_GRS (P for interaction = 0.018). Using stratification analyses, the ORMR of diabetes for NAFLD was 1.581 (95% CI 1.071, 2.233), which was in the lowest BMI_GRS quartile. However, the association was insignificant for the three higher BMI_GRS quartiles. Conversely, for subjects in DM_GRS quartiles one to three, the ORMRs of BMI for NAFLD were 1.769 (95% CI 1.203, 2.601), 1.325 (95% CI 1.025, 1,711) and 1.822 (95% CI 1.025, 2.933), although the association was insignificant in the highest DM_GRS. Conclusions: The causal associations of type 2 diabetes and BMI with NAFLD were significantly modulated by the diabetes and adiposity genetic risk showing a model of competing risks. Funding: This study was supported by National Natural Science Foundation of China (91857117, 81570726, 81600609); Science and Technology Commission of Shanghai Municipality (19140902400, 18410722300, 16411971200, 16410723200); the Major Science and Technology Innovation Program of Shanghai Municipal Education Commission (2018YFC1705103); Commission of Health and Family Planning of Pudong District (PWZxq2017-17, PW2015D-5); the Shanghai Municipal Commission of Health and Family Planning (20164Y0079); Municipal Human Resources Development Program for Outstanding Young Talents in Medical and Health Sciences in Shanghai (2017YQ053); Clinical Research Plan of SHDC (16CR3076B); Shanghai JiaoTong University School of Medicine (19XJ11007). Declaration of Interest: The authors declare no conflicts of interest. Ethical Approval: The study protocol was approved by the Ethics Committee of Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine. The study protocol followed the ethical guidelines of the 1975 Declaration of Helsinki as reflected in a priori approval by the appropriate institutional review committee. Informed consent was obtained from all participants included in the study.

Aim Fasting serum C-peptide is a biomarker of insulin production and insulin resistance, but its association with vascular complications in type 2 diabetes mellitus (T2DM) has never been fully elucidated. This study aimed to investigate whether C-peptide is associated with cardiovascular disease (CVD) and diabetic retinopathy (DR). Methods A total of 4793 diabetes patients were enrolled from seven communities in Shanghai, China, in 2018. CVD was defined as a self-reported combination of previous diagnoses, including coronary heart disease, myocardial infarction and stroke. DR was examined using fundus photographs. Logistic regression analyses were performed, and multiple imputed data were used to obtain stabilized estimates. Results Prevalence of CVD increased with increasing C-peptide levels (Q1, Q2, Q3 and Q4: 33%, 34%, 37% and 44%, respectively; Pfor trend Conclusion C-peptide was positively associated with CVD, but inversely associated with DR progression. The association between C-peptide and CVD could be due to associated metabolic risk factors.

Vitamin D deficiency is associated with glycemic dysregulation in many observational studies. However, the causality between them has not been fully established, especially in Asian origin. We used bidirectional Mendelian randomization (MR) analysis to explore the causal relationship between 25-hydroxyvitamin D [25(OH)D] and glycemic status and indices. Participants were included from a survey in East China from 2014 to 2016 (10,338 and 10,655 participants having diabetes and vitamin D-related genotyping information). We calculated weighted genetic risk scores (GRS) as the instrumental variables for 25(OH)D concentration and diabetes based on related single nucleotide polymorphisms. Diagnosis of type 2 diabetes and prediabetes was based on American Diabetes Association criteria. The MR-derived odds ratios of genetically determined 25(OH)D for risk of type 2 diabetes (1565/10655) and prediabetes (3915/10655) was 0.985 (95% CI 0.940, 1.032) and 0.982 (95% CI 0.948, 1.016), respectively. The MR-derived estimates for fasting plasma glucose and HbA1c were also not significant. Moreover, the MR-derived regression coefficients of genetically determined diabetes and prediabetes for 25(OH)D was 0.448 (95% CI − 0.395, 1.291) and 1.303 (95% CI − 1.210, 3.816). Our results support the conclusion that there is no causal association between vitamin D and type 2 diabetes and prediabetes using a bidirectional MR approach in a Chinese population.

Personal care and consumer products are extensively used and contain various chemicals that are recognized as endocrine disrupting chemicals. Few epidemiological studies measured the associations of these chemicals and metabolites, especially phenols, with bone health. We measured the associations between nine urinary phenol biomarkers and BMD and the subsequent prevalence of osteopenia/osteoporosis. National representative data from US adults aged over 20 years who participated in the National Health and Nutrition Examination Survey from 2005 to 2010 were used. 2,267 men, 1,145 premenopausal women and 1,033 postmenopausal women were included in the final analyses. Bisphenol A, benzophenone-3, triclosan, butylparaben, ethylparaben, methylparaben, propylparaben, 2,5-dichlorophenol and 2,4-dichlorophenol were measured by high-performance liquid chromatography-isotope dilution tandem mass spectrometry. Paraben concentrations, especially ethyl-, methyl- and propylparabens, were related to greater BMD in the femoral neck and intertrochanter and lumbar spine in men and premenopausal women. 2,4-dichlorophenol concentrations was associated with lower BMD and a higher prevalence of osteopenia + osteoporosis in men. Bisphenol A was associated with a higher prevalence of osteopenia + osteoporosis in the lumbar spine in postmenopausal women. Benzophenone-3 tended to be associated with a higher BMD of femur in men and premenopausal women. In conclusion, certain urinary personal care and consumer product chemicals and metabolites were significantly associated with BMD or osteopenia + osteoporosis. These results further indicate that, in future research, determination of the causal relationships and detection of undelying mechanism could be next important directions.

The objective of this study was to investigate the different associations of the serum urate (SUA) level with cardiovascular and cerebrovascular diseases (CVD), diabetic kidney disease (DKD) and diabetic retinopathy (DR) in Chinese adults.We analyzed 4767 participants out of 4813 adults with diabetes enrolled from seven communities in a cross-sectional survey. Participants underwent several medical examinations, including the measurement of anthropometric factors, blood pressure, SUA, glucose, lipid profiles, urine albumin/creatinine ratio (ACR) and fundus photographs.Compared with the first SUA tertile, the third tertile increased the prevalence of CVD by 22% (OR 1.22; 95% CI 1.01, 1.46) (P for trend0.05) and increased the prevalence of DKD by 59% (OR 1.59; 95% CI 1.28, 1.97) for KDOQI definition. Compared with the first tertile, the OR (95% CI) of the number of diabetic complications, ranging from 0 to 2, associated with SUA level in ordinal logistic regression was 1.75 (1.44, 2.12) for the third tertile (P for trend0.01). These associations were all fully adjusted. No association was found between the prevalence of DR and the SUA level.A higher SUA level was associated with an increased prevalence of CVD and DKD and a variety of diabetic complications, other than DR, in men and postmenopausal women with T2DM. However, the causation remains to be demonstrated.

This case report describes a 53-year-old male patient with persistent hypertension and hypokalaemia. Laboratory tests showed that the patient had hypokalaemia, hypocalcaemia and reduced urine calcium/creatinine. Levels of aldosterone and renin activity were increased significantly. Serum levels of adrenocorticotropic hormone, plasma total cortisol level, 24-h urinary-free cortisol, catecholamines, thyroid stimulating hormone and free tetraiodothyronine were normal. A novel single heterozygous mutation (c.836T> G [E6]) was found after full sequencing of the solute carrier family 12 member 3 ( SLC12A3) gene exons. The patient was diagnosed as having primary hypertension with Gitelman syndrome (GS). These findings triggered the careful consideration of whether a monistic or dualist approach to the diagnosis of this patient was the most appropriate. Monism may not always be the most appropriate approach for the diagnosis of coexistent hypertension and hypokalaemia. Consideration should be given to the possibility of the independent existence of distinct diseases (i.e. dualism) when secondary hypertension cannot be confirmed by conventional examinations and when a genetic diagnosis is crucial. As a common cause of hypokalaemia with a high level of clinical phenotypic variation, GS does not conform to the usual diagnostic criteria. It should also be noted that single heterozygous SLC12A3 gene mutations can cause disease symptoms and other genetic mutations might be involved in the pathogenesis of GS.

Background Reported studies have showed that Thrombin Activatable Fibrinolysis Inhibitor (TAFI) may be associated with an increased risk of venous thromboembolism. But the relation of VT with TAFI gene SNPs could not be clearly demonstrated. Thus, we conducted a meta-analysis to analyze the associations between three TAFI variants − 438G/A, 505G/A and 1040C/T and the risk of venous thrombosis. Methods We carried out a systematic search to obtain all the eligible studies published before 30th October 2014. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were computed to assess the association. Results 13 eligible studies were enrolled including 2321 patients and 2464 controls. There was a significant association between 505G/A and the risk of VTD under all models except recessive model (G vs. A: OR = 1.13, 95% CI: 1.02, 1.26; GG vs. AA:OR = 1.47, 95% CI: 1.14, 1.88; GA vs. AA: OR = 1.36, 95% CI: 1.06, 1.73; GG + GA vs. AA: OR = 1.41, 95% CI: 1.12, 1.77). Similarly, obvious relationship was observed in subgroup analyses in light of type of disease and ethnicity. Likewise, for 1040C/T variant, significant associations were identified under homozygote, heterozygote and dominant models (CC vs. TT: OR = 1.65, 95% CI: 1.06, 2.59; CT vs. TT: OR = 1.55, 95% CI: 1.19, 2.03; CC + CT vs. TT: OR = 1.55, 95% CI: 1.20, 2.00). Sub-analysis presented significant associations in non-CVT and non-Asian group under homozygote, heterozygote, and dominant models and CVT group in recessive model. Conclusion This meta-analysis showed that − 438G/A variant was not associated with the incidence of venous thrombosis. But in non-Asian populations, G allele and GG genotype of 505G/A may increase the risk of venous thrombosis diseases. GG genotype of 505G/A and one C carrier (CC and CT) of 1040C/T gave rise to the development of venous thrombosis diseases except CVT. Additionally, the heterozygote CT may be a potential contributing factor of gene effect in venous thrombosis.

The authors report three rare cases of neuroschistosomiasis lacking extracranial involvement. No parasitic eggs were detected in the stool with the Kato-Katz thick smear methods. Computed tomography of the brains showed hypodense signals, and magnetic resonance imaging showed isointense signals on T1-weighted images, hyperintense signals on T2-weighted images, and intensely enhancing nodules in the brain after intravenous administration of gadolinium. High-grade gliomas were suspected, and operations or radiosurgery was performed. Cerebral schistosomiasis was confirmed in all cases by biopsy of the brain lesions, revealing granulomas containing embedded Schistosoma japonicum eggs. All cases were definitively diagnosed as brain schistosomiasis japonica. Praziquantel and corticosteroids were administered, and the prognoses were good for all case patients. Although the aforementioned pattern of imaging examinations is not present in all cases of neuroschistosomiasis, a diagnosis of neuroschistosomiasis should be considered when this pattern of imaging is observed; cerebrospinal fluid serological exams are also recommended.

To identify a new regimen to optimize treatment for patients with newly diagnosed type 2 diabetes (T2DM) by short-term continuous subcutaneous insulin infusion (CSII) alone.Methods.60 patients with newly diagnosed T2DM were randomized into two groups (n=30each) and treated for 2 weeks with CSII alone (CSII group) or with CSII plus sitagliptin (CSII + Sig group). The glycemic variability of the patients was measured using a continuous glucose monitoring system (CGMS) for the last 72 hours. A standard meal test was performed before and after the interventions, and the levels of glycated albumin, fasting glucose, fasting C-peptide, postprandial 2 h blood glucose, and postprandial 2 h C-peptide were examined.Results.Compared with the CSII group, the indicators of glycemic variability, such as the mean amplitude of glycemic excursion (MAGE) and the standard deviation of blood glucose (SDBG), were decreased significantly in the CSII + Sig group. The changes before and after treatment in the C-peptide reactivity index (ΔCPI) and the secretory unit of islet in transplantation index (ΔSUIT) indicated a significant improvement in the CSII + Sig group.Conclusions.Add-on therapy with sitagliptin may be an optimized treatment for patients with newly diagnosed T2DM compared with short-term CSII alone.

PURPOSE: To examine the relationship between smoking, quitting, and mortality in older Chinese men. DESIGN AND METHODS: A cohort analytic study was carried out in Xi'an, China. A total of 1268 retired male military cadres aged 60 or older were examined in 1987 and followed for 12 years. RESULTS: At baseline, 388 men were never-smokers, 461 were former smokers, and 419 were current smokers. Through May 1999, a total of 299 had died. The relative risks [95% confidence intervals (CI)] for ever-smoking, after adjusting for age, blood pressure, body mass index, total cholesterol, triglycerides, alcohol drinking, exercise and existing diseases, for deaths resulting from all causes, chronic obstructive pulmonary disease (COPD), lung cancer, and coronary heart disease (CHD) were, respectively, 1.34 (1.02–1.76), 3.23 (0.95–10.91), 2.31 (0.95–5.61), and 1.60 (0.81–3.19). The risks increased significantly with increasing amount and duration of smoking. Compared with current smokers, former smokers had lower risks of total mortality (excess risk reduction of 56%) and from CHD death, but had higher risks for COPD death. CONCLUSIONS: Smoking is a major cause of death in older Chinese and quitting can save lives. Early recognition of the significance of COPD symptoms followed by prompt quitting should be emphasized in the control of the growing tobacco epidemic.

Objective: The aim of this research was to develop a mechanism-based pharmacokinetic-pharmacodynamic(PK-PD) model that could quantitatively characterize the time-dependent relationship between the PK and PD of Resveratrol(Res) in melanoma tumor-bearing mice for elucidation of its functional mechanisms and molecular targets. Methods: The plasma concentration and AUC of Res and its main metabolites (Res-glucuronide,Rse-G; Res-sulfate,Res-S) were respectively fitted to the activities, mRNA and protein levels of tyrosinase and COX-2 for screening of PK input and PD endpoint. Results: The administration of Res could reduce the growth speed of tumor, inhibit the activities of tyrosinase and COX-2, and down regulate the mRNA and protein expression of COX-2 in tumor-bearing mice. Sigmoid Emax model combined with exponential equation was fitted to the PK-PD modeling for the effects of Res treatment on tumor volume, simple Emax model was fitted to the PK-PD modeling for the effects on enzyme activity, mRNA and prot...

While many previous studies have reported an association between the p.R229Q variant of the NPHS2 gene and focal segmental glomerulosclerosis (FSGS) or steroid-resistant nephrotic syndrome (SRNS), a conclusive relationship has not been defined. In this study, we performed a meta-analysis of the published data to investigate the impact of the p.R229Q polymorphism on FSGS and SRNS patients. Despite significant heterogeneity within some of the comparisons, the results revealed significantly higher risks of SRNS in individuals homozygous for the variant allele (OR 7.411, 95% confidence interval 1.876-29.436, p = 0.004) compared to homozygous non-variant individuals. However, the carrier rate of the p.R229Q variant was not significantly different between SRNS patients and steroid-sensitive nephrotic syndrome patients. No statistically significant differences in the p.R229Q carrier rate were observed between FSGS patients and controls or FSGS patients and patients with different pathology classifications. No notable differences in the p.R229Q carrier rate were found between patients and controls in any group with early-onset disease (onset age18). In conclusion, our meta-analysis suggests that for adult-onset disease (onset age18), the homozygous variant could be a potential predictor of hereditary nephrotic syndrome and that the p.R229Q allele cannot currently be considered a risk factor for predicting FSGS.

Astragalus polysaccharide (APS) is an important bioactive component of Astragalus membranaceus Bunge (Leguminosae) that has been used in traditional Chinese medicine for treating muscle wasting, a serious complication with complex mechanism manifested as myofibers atrophy and satellite cells apoptosis. In this study, the anti-atrophy and anti-apoptotic activity of Astragalus polysaccharide (APS) was characterized in C2C12 skeletal muscle myotubes and myoblasts. APS inhibited dexamethasone-induced atrophy by restoring phosphorylation of Akt, m-TOR, P70s6k, rpS6 and FoxO3A/FoxO1. The targets that protected C2C12 myoblasts from damage by H2O2 were promoting cells proliferation and inhibiting cells apoptosis. The protective mechanisms involved mitochondrial pathway and death receptor pathway. Moreover, Antioxidant effect of APS was also detected in this work. Our findings suggested that APS could be explored as a protective and perhaps as a therapeutic agent in the management of muscle wasting.

Background Secretory pituitary adenomas are very common brain tumors. Historically, the treatment armamentarium for secretory pituitary adenomas included neurosurgery, medical management, and fractionated radiotherapy. In recent years, MASEP gamma knife radiosurgery (MASEP GKRS) has emerged as an important treatment modality in the management of secretory pituitary adenomas. The goal of this research is to define accurately the efficacy, safety, complications, and role of MASEP GKRS for treatment of secretory pituitary adenomas. Methods Between 1997 and 2007 a total of 347 patients with secretory pituitary adenomas treated with MASEP GKRS and with at least 60 months of follow-up data were identified. In 47 of these patients some form of prior treatment such as transsphenoidal resection, or craniotomy and resection had been conducted. The others were deemed ineligible for microsurgery because of body health or private choice, and MASEP GKRS served as the primary treatment modality. Endocrinological, ophthalmological, and neuroradiological responses were evaluated. Results MASEP GKRS was tolerated well in these patients under the follow-up period ranged from 60 to 90 months; acute radioreaction was rare and 17 patients had transient headaches with no clinical significance. Late radioreaction was noted in 1 patient and consisted of consistent headache. Of the 68 patients with adrenocorticotropic hormone-secreting(ACTH) adenomas, 89.7% showed tumor volume decrease or remain unchanged and 27.9% experienced normalization of hormone level. Of the 176 patients with prolactinomas, 23.3% had normalization of hormone level and 90.3% showed tumor volume decrease or remain unchanged. Of the 103 patients with growth hormone-secreting(GH) adenomas, 95.1% experienced tumor volume decrease or remain unchanged and 36.9% showed normalization of hormone level. Conclusion MASEP GKRS is safe and effective in treating secretory pituitary adenomas. None of the patients in our study experienced injury to the optic apparatus or had other neuropathies related with gamma knife. MASEP GKRS may serve as a primary treatment method in some or as a salvage treatment in the others. However, treatment must be tailored to meet the patient's symptoms, tumor location, tumor morphometry, and overall health. Longer follow-up is required for a more complete assessment of late radioreaction and treatment efficacy.

We analysed the magnetic resonance imaging (MRI) clinical characteristics as well as serum and cerebrospinal fluid (CSF) immunoassay results in 41 patients with cerebral schistosomiasis. Thirty-five cerebral schistosomiasis patients were diagnosed by imaging and immunoassay, five by post-operative pathological examination and one by diagnostic treatment with praziquantel. We found that MRI showed specific enhancement, forming the 'Buddha's hand' appearance. Although this pattern of MRI enhancement may not be present in all cases of cerebral schistosomiasis, when it is observed a diagnosis of cerebral schistosomiasis should be considered. Meanwhile, CSF immunoassay may also play an important role in the differential diagnosis of cerebral schistosomiasis.

The authors report here a rare case of cerebellar schistosomiasis identified by pathological diagnosis, lacking extracranial involvement. The clinical symptoms included headache, dizziness, and nausea. Studies in blood were normal and no parasite eggs were detected in stool. Computed tomography of brains showed hypodense signal, and magnetic resonance imaging showed isointense signal on T1-weighted images, hyperintense signal on T2-weighted images, and intensely enhancing nodules in the right cerebellum after intravenous administration of gadolinium. A high-grade glioma was suspected, and an operation was performed. The pathologic examination of the biopsy specimen revealed schistosomal granulomas scattered within the parenchyma of the cerebellum. The definitive diagnosis was cerebellar schistosomiasis japonica. A standard use of praziquantel and corticosteroid drugs was applied, and the prognosis was good. When the pattern of imaging examinations is present as mentioned above, a diagnosis of brain schistosomiasis should be considered.

Objective Bone mass content of motion organs i s associated with external force This study involved the effect of gravity and, m uscular strength on bone mass Methods 111 subjects (56 males , 55 females) with exclusion of secondary osteoporosis and bone diseases were ran d omly recraited during physical examination Their general bone mass were measur e d by DEXA and general and local BMD and BMD, lean body mass, and gripping streng th were recorded Results General body weight and lean body m a ss were closely correlated with BMD, but weakly with BMD The correlaion coeffi c ients in females were higher than those in males BMC, lean body mass and grip s trength in males were 3 5%, 27 8% and 44% higher than these in females respect iv ely This may be the important reason that bone mechanical property of males is better than that of females With every 1 kg body weight in males over that in females, the BMC in male was 0 020 kg over that in females With every 1 kg le an body mass in males over that in females, the BMC in males was 0 008 kg over t h at in females So we inferred that weight might be the important external force to determine BMC Conclusions Both weight and muscular strengt h are important factors for determining bone mineral content Application of bon e mechanical measurment to diagnosis of osteoporosis should be further studied