Dissecting Causal Relationships Between Gut Microbiota, Blood Metabolites, and Stroke: A Mendelian Randomization Study / 대한뇌졸중학회지

Background@#and Purpose We investigated the causal relationships between the gut microbiota (GM), stroke, and potential metabolite mediators using Mendelian randomization (MR). @*Methods@#We leveraged the summary statistics of GM (n=18,340 in the MiBioGen consortium), blood metabolites (n=115,078 in the UK Biobank), and stroke (cases n=60,176 and controls n=1,310,725 in the Global Biobank Meta-Analysis Initiative) from the largest genome-wide association studies to date. We performed bidirectional MR analyses to explore the causal relationships between the GM and stroke, and two mediation analyses, two-step MR and multivariable MR, to discover potential mediating metabolites. @*Results@#Ten taxa were causally associated with stroke, and stroke led to changes in 27 taxa. In the two-step MR, Bifidobacteriales order, Bifidobacteriaceae family, Desulfovibrio genus, apolipoprotein A1 (ApoA1), phospholipids in high-density lipoprotein (HDL_PL), and the ratio of apolipoprotein B to ApoA1 (ApoB/ApoA1) were causally associated with stroke (all P<0.044). The causal associations between Bifidobacteriales order, Bifidobacteriaceae family and stroke were validated using the weighted median method in an independent cohort. The three GM taxa were all positively associated with ApoA1 and HDL_PL, whereas Desulfovibrio genus was negatively associated with ApoB/ApoA1 (all P<0.010). Additionally, the causal associations between the three GM taxa and ApoA1 remained significant after correcting for the false discovery rate (all q-values <0.027). Multivariable MR showed that the associations between Bifidobacteriales order, Bifidobacteriaceae family and stroke were mediated by ApoA1 and HDL_PL, each accounting for 6.5% (P=0.028) and 4.6% (P=0.033); the association between Desulfovibrio genus and stroke was mediated by ApoA1, HDL_PL, and ApoB/ApoA1, with mediated proportions of 7.6% (P=0.019), 4.2% (P=0.035), and 9.1% (P=0.013), respectively. @*Conclusion@#The current MR study provides evidence supporting the causal relationships between several specific GM taxa and stroke and potential mediating metabolites.

Relationship between metabolically healthy obesity and atherosclerosis / 中华内分泌代谢杂志

Objective:To investigate the association between metabolically healthy obesity(MHO) and atherosclerosis risk among Chinese community population aged 40 or older.Methods:A total of 9 525 participants without cardiovascular diseases (3 621 men and 5 904 women) from Jiading community in Shanghai were enrolled to complete questionnaires, undergo extensive physical examination including brachial-ankle pulse wave velocity (baPWV) and blood pressure (BP) assessment, and laboratory screening. According to body mass index (BMI) and metabolic status, these participants were categorized into 4 groups including metabolically healthy non-obese (MHNO), metabolically unhealthy non-obese (MUNO), MHO, and metabolically unhealthy obese (MUO). High baPWV was defined as baPWV>1 400 mm/s, and high pulse pressure (PP) was defined as PP above fourth quartile of the population. Multivariate logistic regression model was conducted to explore the relationship between MHO and high baPWV as well as high PP after adjusting for confounders. Results:After multivariable adjustment, such as sex, age, current smoking, current drinking, and education, logistic regression analysis showed that MHO was significantly correlated with high baPWV ( OR=1.18, 95% CI 1.02-1.37) and high PP ( OR=1.72, 95% CI 1.43-2.08) in comparison with MHNO. Otherwise, both MUNO and MUO subjects were at higher risk for suffering from high baPWV (MUNO: OR=3.02, 95% CI 2.60-3.50; MUO: OR=3.26, 95% CI 2.87-3.70) and high PP (MUNO: OR=2.56, 95% CI 2.17-3.02; MUO: OR=3.49, 95% CI 3.01-4.06). Conclusion:On the basis of Chinese community population, there was a pronounced correlation between the MHO phenotype and the increased risk of developing atherosclerosis.

Generalized lipodystrophy type 1 due to compound heterozygous mutation of AGPAT2 gene: One case report and literature review / 中华内分泌代谢杂志

Congenital generalized lipodystrophy type 1 (CGL1) is an autosomal recessive genetic disease caused by mutations in AGPAT2 gene. The main clinical mainifestations include body subcutaneous fat loss, muscle hypertrophy, obvious subcutaneous veins, pseudoacromegaly, hirsutism, and acanthosis nigricans. What′s more, CGL1 is always accompanied by metabolic diseases. Therefore, it is easily misdiagnosed as metabolic syndrome, type 2 diabetes, polycystic ovary syndrome, acromegaly, or Cushing′s syndrome. Meanwhile, it is difficult to distinguish it from partial lipoatrophy syndrome. In this article, we present clinical and molecular characteristics of a patient with CGL1 and review mutations reported in literature to replenish current knowledge about this orphan disease.

Relationship between famine exposure in early life and type 2 diabetes mellitus in adulthood / 中华内分泌代谢杂志

Objective:To investigate the correlation between exposure to famine in early life and later risk of type 2 diabetes in adulthood.Methods:A cluster sampling method was used to include 8 868 residents who were lived in the Jiading community of Shanghai during the Great Famine from 1959 to 1962 in China. Subjects were divided into non-exposed group, fetal exposure group, childhood exposure group, and adolescent exposure group. Logistic regression model was used to analyze the relationship between famine exposure in early life and the risk of type 2 diabetes in adulthood. Results:Famine exposure during childhood and adolescent both increased the risk of developing type 2 diabetes in adulthood in women. No significant correlation was observed in men. In subjects with less physical activity and lower education level, the risk of developing type 2 diabetes mellitus in adulthood was significantly higher in the famine-exposed group than that of non-exposed groupand the interactions were statistically significant.Conclusion:Early life famine exposure increases the risk of developing type 2 diabetes in adults, especially in women.

New insights into the growing diabetes epidemic in China: middle-aged obesity-related insulin resistance becomes the major threat / 中华内分泌代谢杂志

Delineation of the relationship between insulin resistance, β cell dysfunction, and obesity is crucial for the prevention and effective management of diabetes. Previous studies have indicated that, compared with type 2 diabetes in Caucasian, type 2 diabetes in East Asians is characterized primarily by β cell dysfunction rather than insulin resistance. This pathophysiological characterization of diabetes in East Asians is mainly derived from Japanese and Asian-American populations, whereas data from mainland China are scarce. Over the past four decades, China has witnessed a substantial rise in obesity, in parallel with the transitions from principally active lifestyles and calorie-restricted diets to sedentary life styles and energy-dense, western diets. Obesity is an insulin resistance state and the major factor driving the worldwide epidemic of diabetes. It is unknown whether, and if so how, obesity affects the two primary mechanisms, insulin resistance and β cell dysfunction, responsible for the development of diabetes in the Chinese population. Recently, the Lancet Diabetes & Endocrinology published an original research paper from the China Cardiometabolic Disease and Cancer Cohort Study (4C). From a public health perspective, the results of this study reinforce the urgency of tackling obesity as a major preventive strategy for the epidemic of type 2 diabetes in China.

Expert recommendations for diabetes with or without COVID-19 management in communities / 中华内分泌代谢杂志

Since December 2019, the outbreak of coronavirus disease 2019 (COVID-19) has occurred in China. Higher risk of COVID-19 infection and worse prognosis were observed among patients with diabetes. There are rigorous challenges existing in terms of diabetes prevention and glycemic control in primary medical care during period of COVID-19. Here, expert recommendations were presented by Chinese diabetologists, healthcare providers, and public health administrators to improve the ability of primary health facilities and provide standardized basic public health and medical services throughout the country. The main contents include basic requirements for management, workflow of health management, referral, treatment, as well as the long-term follow-up.

Serum uric acid and risk of incident diabetes in middle-aged and elderly Chinese adults: prospective cohort study / 医学前沿

The association between serum uric acid and the risk of incident diabetes in Chinese adults remains unknown. This study aimed to investigate this association in a community-dwelling population aged ≥ 40 years in Shanghai, China. Oral glucose tole3rance test was conducted during baseline and follow-up visits. Relative risk regression was utilized to examine the associations between baseline gender-specific serum uric acid levels and incident diabetes risk. A total of 613 (10.3%) incident diabetes cases were identified during the follow-up visit after 4.5 years. Fasting plasma glucose, postload glucose, and glycated hemoglobin A1c during the follow-up visit progressively increased across the sex-specific quartiles of serum uric acid (all Ps < 0.05). The incidence rate of diabetes increased across the quartiles of serum uric acid (7.43%, 8.77%, 11.47%, and 13.43%). Multivariate adjusted regression analysis revealed that individuals in the highest quartile had 1.36-fold increased risk of diabetes compared with those in the lowest quartile of serum uric acid (odds ratio (95% confidence interval) = 1.36 (1.06-1.73)). Stratified analysis indicated that the association was only observed in women. Accordingly, serum uric acid was associated with the increased risk of incident diabetes among middle-aged and elderly Chinese women.

Expert recommendations for diabetes with or without COVID-19 management in communities / 中华内分泌代谢杂志

Since December 2019, the outbreak of coronavirus disease 2019 (COVID-19) has occurred in China. Higher risk of COVID-19 infection and worse prognosis were observed among patients with diabetes. There are rigorous challenges existing in terms of diabetes prevention and glycemic control in primary medical care during period of COVID-19. Here, expert recommendations were developed by Chinese diabetologists, healthcare providers, and public health administrators to improve the ability of primary health facilities and provide standardized basic public health and medical services throughout country. The main contents include basic requirements for management, workflow of health management, referral, treatment, and long-term follow-up.

Type 2 diabetes is causally associated with depression: a Mendelian randomization analysis / 医学前沿

Type 2 diabetes (T2D) has been associated with a high prevalence of depression.We aimed to determine the causal relation by performing a Mendelian randomization (MR) study using 34 T2D risk genetic variants validated in East Asians as the instrumental variable (IV). An MR analysis was performed involving 11 506 participants from a large longitudinal study. The T2D genetic risk score (GRS) was built using the 34 typical T2D common variants. We used T2D_GRS as the IV estimator and performed inverse-variance weighted (IVW) and Egger MR analysis. The T2D_GRS was found to be associated with depression with an OR of 1.21 (95% CI: 1.07-1.37) after adjustments for age, sex, body mass index, current smoking and drinking, physical activity, education, and marital status. Using T2D_GRS as the IV, we similarly found a causal relationship between genetically determined T2D and depression (OR: 1.84, 95% CI: 1.25-2.70). Though we found no association between the combined effect of the genetic IVs for T2D and depression with EggerMR(OR: 0.95, 95%CI: 0.42-2.14), we found an association for T2D and depression with IVW (OR: 1.75, 95% CI: 1.31-2.46) after excluding pleiotropic SNPs. Overall, the MR analyses provide evidence inferring a potential causal relationship between T2D and depression.

Association of age at menarche with the risks of diabetes mellitus and metabolic syndrome in adulthood in Shanghai Jiading community postmenopausal women / 中华内分泌代谢杂志

Objective To investigate the association of age at menarche with the risks of diabetes and metabolic syndrome ( MS) in adulthood in Shanghai community postmenopausal women. Methods A total of 10375 residents over 40 years in Jiading, Shanghai were identified by a cluster sampling method. After taking standardized questionnaire surveys, physical examinations, and biochemical parameters testing, we gathered their lifestyle and medicine information. A total of 4723 postmenopausal women were enrolled in the study. The population was divided into three groups according to age at menarche, and their risks of MS and diabetes in various groups were compared. Results After multivariate adjustment, postmenopausal women with a menarche age<15 years had a 29％increased risk of diabetes(95％CI 1.03-1.61) and a 45％ increased risk of MS(95％ CI 1.20-1.76) in adulthood, compared with those with menarcheal age at 15-18 years. Among the five components of MS, earlier age of menarche was associated with higher risks of hypertriglyceridemia, low high density lipoprotein-cholesterol, and central obesity. Conclusions In Shanghai Jiading community postmenopausal women, age at menarche is associated with the risk of diabetes and MS, independent of the body mass index in adulthood.

Association of serum alanine aminotransferase with the risk of cardiovascular disease in middle-aged and elderly Chinese / 中华内分泌代谢杂志

Objective To investigate the association between levels of serum alanine aminotransferase (ALT) and the risks of cardiovascular disease in Chinese. Methods A survey of 10 375 subjects aged 40 or older in Jiading District of Shanghai was performed using cluster sampling. All the subjects were recruited to undergo questionnaire interview, anthropometric measurements, and fasting blood sampling. A total of 8 877 participants were included in the final analyses, including 5 664 females and 3 213 males. The mean age of individuals was ( 58.68 ± 9.22)yearsinmenand(57.65±8.93)yearsinwomen(P＜0.01).10-yearriskforafirsthardatherosclerotic cardiovascular diseases (ASCVD) event was calculated. Results Increased ALT levels were associated with more unfavorable cardiovascular risk profiles and 10-year risk for ASCVD. Increased ALT levels were associated with the prevalence of diabetes mellitus in female participants, while in male participants the prevalence of diabetes mellitus appeared as a U-distribution. The prevalence of hypertension and hyperlipidemia were 66.04%, 52.74%and 64.49%, 47.63% respectively. Increased serum ALT was associated with higher prevalence of 10-year risk for ASCVD. As compared with participants in the first ALT quartile, the risks of 10-year risk for ASCVD were increased by 148%(OR＝2.48, 95%CI 1.78-3.45) and 139%(OR＝2.39, 95%CI 1.78-3.19), respectively in male and female participants. As compared with participants in the first ALT quartile, higher prevalence of 10-year risk for ASCVD were increased by 96%(OR＝1.96, 95%CI 1.30-2.95), while there was no significantly statistical difference in men. Conclusion A high-normal serum ALT level was significantly associated with an increased risk of the cardiovascular disease in middle-aged and elderly Chinese.

Association between neck circumference and cardiovascular risk factors in middle-aged and elderly nondiabetic people in Jiading District, Shanghai / 上海交通大学学报（医学版）

Objective· To investigate the association between neck circumference (NC) and cardiovascular risk factors among middle-aged and elderly people without diabetes in Jiading District in Shanghai.Methods· A cross-sectional study was conducted among 4 657 nondiabetic inhabitants aged 40 and above in Jiading District,Shanghai from August 2014 to July 2015.Clinical information collection,anthropometric measurements,and biochemical analyses were performed.The objects were divided into 4 groups according to the quartiles of NC in order to analyze association between NC and cardiovascular risk factors.Results· With increase of NC,the prevalences of abdominal obesity,insulin resistance,hypertension,and dyslipidemia all increased as well as waist circumference,body mass index (BMI),blood pressure,lipid profile,fast blood glucose,and HOMA-IR level (all Ptrend ＜0.01).Multiple Logistic regression analysis showed that individuals in Q2,Q3 and Q4 group had significantly higher risk of abdominal obesity,insulin resistance,hypertension,and dyslipidemia compared with those in Q1 group after age,sex,smoking,drinking,physical activity,BMI,waist circumference,systolic blood pressure,C-reactive protein,fast blood glucose,and lipid profile were corrected (all Ptrend ＜0.01).Conclusion· NC is positively and independently correlated with cardiovascular risk factors in middle-aged and elderly nondiabetic people in Jiading District in Shanghai.

Association between gallstone and non-alcoholic fatty liver disease in middle-aged and elderly Chinese in Shanghai local communities / 中华内分泌代谢杂志

Objective To investigate the association between gallstone and non-alcoholic fatty liver disease (NAFLD)in middle-aged and elderly Chinese. Methods A cross-sectional study was conducted in 8934 Chinese adults from Jiading District, Shanghai. Questionnaire interview, anthropometric measurements, biochemical evaluation, and abdominal ultrasonography were performed in all the participants. Results Compared with participants without gallstone,individuals with gallstone had significantly higher prevalence of NAFLD(28.8% and 42.9%,respectively;P<0.01). Using participants without gallstone as the reference,participants with gallstone were associated with an increased risk of NAFLD after adjustment for multiple covariatesodds ratios(OR)and 95% confidence interval(CI)was 1.39(1.45-1.69). In addition,compared with participants without cholecystectomy, participants with cholecystectomy were associated with an increased risk of NAFLD(OR=1. 44, 95% CI 1. 04-1.99). Conclusion The presence of gallstone and cholecystectomy were positively associated with NAFLD in middle-aged and elderly Chinese.

Non-islet-cell tumor induced hypoglycemia:one case report and literature review / 中华内分泌代谢杂志

A patient with severe hypoglycemia due to insulin-like growth factor ( IGF)-IIsecreted by a giant solitary fibrous tumor of the pleura ( SFTP) was investigated through comprehensively reviewing his medical history and clinical records. The patient had severe hypoglycemia accompanied with significantly decreased serum insulin level. A solitary fibrous tumor of the pleura was found, and right pneumonectomy removed this giant tumor. Two years after the operation, the patient was fit and well with no further hypoglycemia episodes. Non-islet-cell tumor hypoglycemia should be considered in patients who have hypoglycemia episodes accompanied with significantly decreased serum insulin level.

Association of low-grade albuminuria with carotid intima-media thickness / 中华内分泌代谢杂志

Objective To analyze the association of elevated carotid intima-media thickness(CIMT)with low-grade albuminuria in a community-based population. Methods A total of 10 375 participants aged 40 years or older were recruited using cluster sampling from Jiading district, Shanghai. Standardized questionnaires were adopted to collect information on health status and lifestyles. Anthropometric measurements including weight, height, and blood pressure, and biochemical tests for blood and urine were performed. CIMT was detected by B-mode ultrasound examinations. 9 523 subjects were included for final analysis. All these subjects were divided into 4 groups according to sex-specific urinary albumin to creatinine ratio ( UACR ) quartiles. CIMT≥upper decile of the population was defined as elevated CIMT and low-grade albuminuria was defined as UACR≥sex-specific upper quartile. The relationship between UACR and CIMT was investigated by multiple logistic regression analysis. Results The prevalence of elevated CIMT in this population aged 40 years or older with albuminuria in normal range was 21. 44%. Comparing to participants without elevated CIMT, those with elevated CIMT showed higher level of UACR (4. 79 vs 4. 51 mg/g, P<0. 01). The metabolic status was deteriorated with the increment of UACR level. The prevalences of elevated CIMT were 18. 99%, 19. 24%, 20. 20%, and 27. 33% from the lowest to highest UACR quartile, respectively(Ptrend<0. 01). After adjusting for some conventional cardiovascular risk factors, multiple logistic regression revealed that compared with the participants in the lowest quartile of UACR, those in the highest quartile had a 1. 25-fold risk of elevated CIMT. Conclusions This study shows that low-grade albuminuria is positively associated with elevated CIMT, independent of conventional cardiovascular risk factors in middle-aged and elderly adults.

Extremely mild cholesterol side chain cleavage enzyme deficiency with infertility as the only presenting complaint / 中华内分泌代谢杂志

[Summary] All patients with cholesterol side-chain cleavage enzyme ( P450scc) deficiency that have been reported presented with early adrenal failure. Here we described a 35-year-old male presented with infertility as the only initial presenting complaint. He had received two separate surgeries to remove bilateral testicular masses. We reevaluated the resected tumors and found testicular adrenal rest tumor ( TART) pathology in the resected tumor. We profiled steroid hormones and found significantly elevated ACTH. CT scan revealed bilateral adrenal hyperplasia. Mutation screening identified compound heterozygous mutations (R353W and P432L) in the P450scc encoding gene (CYP11A1). The patient was finally diagnosed as congenital adrenal hyperplasia.

Associations between adipose tissue distribution and macro-vascular complications:A cross-sectional study in type 2 diabetic patients / 中华内分泌代谢杂志

Objective This study aimed to investigate the associations between adipose tissue distribution and risks of macro-vascular complications in type 2 diabetic patients. Methods The study included T2DM patients either previously diagnosed by questionnaire or newly diagnosed with fasting plasma glucose(FPG)≥7. 0 mmol/L and/or 2 hour postprandial glucose ( 2h PG )≥11. 1 mmol/L from residents older than 40 years from Jiading Community, Shanghai, China(n=10 375). Each participant had gone through anthropometric measurements, blood tests, vascular function tests including carotid intima-media thickness ( CIMT ) , ankle-brachial index ( ABI ) , branchial-ankle pulse wave velocity( baPWV) as well as carotid plaques. Results WHR quartiles was significantly associated with high risks for ten-year cardiovascular disease risks [ ASCVD high risk: OR:1. 17 ( 1. 05-1. 31 );Framingham high risk:1. 13(1. 00-1. 29)]. However, WHR has no significant relations with risks of increased carotid intima-media thickness( CIMT) , abnormal ankle-brachial index( ABI) , increased brachial ankle pulse wave velocity( baPWV) or carotid plaques. Conclusions In type 2 diabetic patients, abdominal adipose tissue has an independent role in high risk for ten-year cardiovascular diseases. However it has no relations with other vascular functions including increased CIMT, abnormal ABI, increased baPWV, or carotid plaque.

Adrenal Castleman′s disease:A case report and literature review / 中华内分泌代谢杂志

Objective To raise the awareness of adrenal Castleman′s disease by analyzing the clinical features and management of a patient with adrenal Castleman′s disease. Methods A case of adrenal Castleman′s disease of our hospital was retrospectively analyzed, including clinical feature, laboratory findings, pathology, treatment, and follow-up. All the data and pertinent literatures were reviewed and analyzed. Results An incidentaloma measuring 4. 8 cm × 6. 3 cm in the right adrenal gland was observed in a 30-year-old men in a ultrasonography examination performed due to a medical check-up. Laboratory analysis showed that the lesion was not hyperfunctioning. The patient subsequently underwent an exploratory laparotomy. Pathological examination revealed retroperitoneally localized Castleman′s disease of the hyaline vascular type. Conclusion Adrenal Castleman′s disease is a rare cause of lymph node hypertrophy, and it is necessary to keep in mind the possibility of its occurrence and take it into consideration in the differential diagnosis of any solitary, heterogeneous, and hypervascular retroperitoneal mass. The proper cooperation between the clinician and pathologist allows early diagnosis and suitable therapy.

Hypoglycemia associated with the abnormal expression of insulin like growth factor-Ⅱ in a pleural solitary fibroma / 中华内分泌代谢杂志

High expressions of IGF Ⅱ mRNA and protein were demonstrated by RT PCR and IRMA analysis in tumor tissue of a patient with non islet cell tumor induced hypoglycaemia (NICTH). Northern blotting results displayed abundant 6.0, 5.3, 5.0, 4.8 kb IGF Ⅱ transcripts in the tumor. It suggests that autosecretive production of IGF Ⅱ of the tumor plays an important role in the pathogenesis of tumor induced hypoglycemia.

Leptin level and its role in the regulation of reproductive function in females with anorexia nervosa / 中华内分泌代谢杂志

Objective To explore the relationship between serum leptin level and the hypothalamuspituitary-gonad ( HPG) axis in female adolescents with anorexia nervosa ( AN). Methods Sixteen newly diagnosed female adolescents with AN in Shanghai and Zhejiang province were investigated, and their serum leptin, FSH, LH and body composition were measured before and after 18 weeks treatment, and their menorrhea cycles were observed. The rhythm of 24 h serum leptin secretion was studied in 4 patients with AN. Twenty-six, healthy females with normal weight and without contraceptive medication were studied as controls. Results (1) All of 16 patients had amenorrhea, 3 primary amenorrhea and 13 secondary amenorrhea. At admission LH in 14 patients and FSH in 12 patients were below the low limit of the normal reference range (1.5 U/L and 4. 6 U/L respectively), and among them 5 patiend had both 15% weight gain and significantly increased serum leptin level (P