Cigarette Smoking Increases Risk for Incident Metabolic Syndrome in Chinese Men—Shanghai Diabetes Study

Objective To determine whether smoking increases the risk for developing metabolic syndrome （MetS） in Chinese men.Methods A total of 693 men with no MetS at baseline were followed for 2.9‐5.5 years.Subjects were divided into nonsmokers,ex‐smokers,and current smokers according to baseline smoking status.Results After adjusting for age,education level,alcohol intake,fasting plasma insulin,HOMA‐IR index,and BMI at baseline and weight change,current smokers were dose‐dependently associated with increased risk for developing new MetS compared with nonsmokers.The odds ratio （OR） was 2.131 （95% CI,1.264,3.592;P0.01） for the NCEPIII definition or 3.083 （95% CI,1.807,5.295;P0.01） for the JCDCG definition of MetS.Ex‐smokers who had quit for ≥13 years significantly decreased the risk for developing new MetS defined by the JCDCG definition.Compared with nonsmokers,current smokers were significantly associated with increased incidence of hypertriglyceridemia and low HDL‐C.Conclusion Smoking is a risk factor for developing MetS in Chinese men after adjusting for age,education level,alcohol intake,fasting plasma insulin,HOMA‐IR,BMI,and weight change.This could be due to an increased incidence of dyslipidemia.Smoking cessation for 13 years decreased the risk for developing MetS defined by the JCDCG definition.

Liver Enzymes Concentrations Are Closely Related to Pre-diabetes:Findings of the Shanghai Diabetes Study Ⅱ (SHDS Ⅱ)

Objective To investigate the relationship of liver enzymes with hyperglycemia in a large population in Shanghai and identify the association between liver enzymes and insulin resistance. Methods A total of 3 756 participants were enrolled. Each participant underwent an oral glucose tolerance test and completed a questionnaire. Anthropometric indices were recorded and serum samples were collected for measurement. Results Liver enzymes concentrations were independently associated with i-IGT, iFG＋IGT, and diabetes. With the increase of ALT and GGT concentrations, ORs for i-IGT, IFG＋tGT, and diabetes increased gradually. By comparing patients in the highest quartile of GGT concentrations or ALT concentrations with those in the lowest quartile （Q1）, ORs for iqGT, IFG＋IGT, or diabetes was significant after adjustment. Both ALT and GGT concentrations were linearly correlated with HOMA-IR and independently associated with HOMA-IR [ALT OR （95% Cl）： 2.56 （1.51-4.34） P=0.00; GGT OR （95% CI）： 2.66 （1.53-4.65） P=0.00]. Conclusion Serum ALT and GGT concentrations were closely related to pre-diabetes and diabetes in the Shanghai population and positively associated with insulin resistance.

Association of a SLC30A8 Genetic Variant with Monotherapy of Repaglinide and Rosiglitazone Effect in Newly Diagnosed Type 2 Diabetes Patients in China

Objective To investigate a potential relationship between Solute carrier family 30 （zinc transporter） member 8 （SLC3OAS） rs13266634 variant and efficacy of rosiglitazone or repaglinide in treating newly diagnosed Chinese type 2 diabetes patients. Methods A total of 209 diabetic patients without any antihyperglycemic history were recruited and treated with repaglinide or rosiglitazone randomly for 48 weeks （104 and 105 patients, respectively）. Anthropometric measurements and clinical laboratory tests were carried out before and after the treatment. An non-synonymous variant rs13266634 was genotyped by matrix-assisted laser desorption ionization-time of flight mass spectroscopy. Results Ninety-one patients in repaglinide group and ninety-three patients in rosiglitazone group completed the study. 6 value of homeostasis model assessment of beta cell function （HOMA-B） and 6 value of fasting proinsulin levels were statistically significant between three genotype groups （P=0.0149 and 0.0246, respectively） after rosiglitazone treatment. However, no genotype association was observed in the repaglinide or rosiglitazone group with other parameters. Conclusion The SLC3OA8 variant was associated with the efficacy of insulin sensitizer monotherapy on insulin secretion in patients with newly diagnosed type 2 diabetes mellitus in Shanghai, China.

Correlation between Waist Circumference and Carotid Intima-Media Thickness in Women from Shanghai, China

Objective To evaluate whether waist circumference （WC） 〉85 cm is related to asymptomatic preclinical atherosclerosis in women from Shanghai, China. Methods A total of 2365 females aged 〉20 years recruited from 4 communities underwent physical examination and carotid artery scanning. Their carotid intima-media thickness （C-iMT） was measured. Results The C-IMT was significantly higher in overweight or obese women with their BMI 〉25.0 kg/m2 {P〈O.01） and in those with their WC _〉85 cm than in those with their WC 〈85 cm （P〈O.01）. Spearman and partial correlation analysis showed that the C-IMT was significantly correlated with WC which was independent of menopausal status. The C-IMT significantly increased with the increasing WC and reached to a platform in about 85 cm. An increment tendency was found in the subgroup with its WC 〈 85 cm （P〈O.01） while no significant tendency was found in the subgroup with its WC_〉85 cm （P=0.07）. Multiple stepwise regression analysis showed that the WC was an independent risk factor for C-IMT. In logistic regression model, the odd ratio of WC _〉80 cm, _〉80 cm and 〈85 cm and 〉85 cm for evaluating the risk of C-IMT elevation was 2.632, 2.501, and 1.878, respectively. Conclusion WC is significantly correlated with C-IMT in women from Shanghai, China, and WC_〉85 cm may be used in identifying the risk of subclinical carotid atherosclerosis.

Screening for Melanocortin 4 Receptor Mutations in Chinese Extremely Obese Individuals

Accumulating evidence indicates that overweight and obesity are the major international public health concern. Obesity is a major independent risk factor for chronic diseases, such as hypertension, type 2 diabetes, cardiovascular disease, stroke, and certain cancer. Disease burden due to obesity has been dramatically increasing in many countries including China in the past years. According to the Nationwide Health and Nutrition Survey （CHNS）, the prevalence of overweight and obesity among men and women in China increased by 27.6% and 8.8%, respectively, from 1993 to 2009.

Efficacy and safety of metformin and sitagliptin based triple antihyperglycemic therapy(STRATEGY):a multicenter,randomized,controlled,non-inferiority clinical trial

Despite the current guideline's recommendation of a timely stepwise intensification therapy,the "clinical inertia",termed as the delayed treatment intensification,commonly exists in the real world,which may be partly due to the relatively little substantial evidence and no clear consensus regarding the efficacy and safety of triple oral agents in patients inadequately controlled with dual therapy.In this clinical trial performed in 237 centers in China,5,535 type 2 diabetic patients inadequately controlled by previous therapies were treated with a stable metformin/sitagliptin dual therapy for 20 weeks.The patients who did not reach the glycated hemoglobin A1c(HbA1c) goal were then further randomized into glimepiride,gliclazide,repaglinide,or acarbose group for an additional 24-week triple therapy.A mean HbAlc reduction of 0.85%was observed when sitagliptin was added to the patients inadequately controlled with metformin in 16 weeks.Further HbAlc reductions in the 24-week triple therapy stage were 0.65%in glimepiride group,0.70%in gliclazide group,0.61%in repaglinide group,and 0.45%in acarbose group.The non-inferiority criterion for primary hypotheses was met for gliclazide and repaglinide,but not for acarbose,compared with glimepiride,when added to metformin/sitagliptin dual therapy.The incidences of adverse events(AEs) were 29.2%in the dual therapy stage and30.3%in the triple therapy stage.Metformin/sitagliptin as baseline therapy,with the addition of a third oral antihyperglycemic agent,including glimepiride,gliclazide,repaglinide,or acarbose,was effective,safe and well-tolerated for achieving an HbAlc<7.0%goal in type 2 diabetic patients inadequately controlled with previous therapies.The timely augmentation of up to three oral antihyperglycemic agents is valid and of important clinical benefit to prevent patients from exposure to unnecessarily prolonged hyperglycemia.

Targeted gene panel provides advantages over whole-exome sequencing for diagnosing obesity and diabetes mellitus

A small fraction of patients diagnosed with obesity or diabetes mellitus has an underlying monogenic cause.Here,we constructed a targeted gene panel consisting of 83 genes reported to be causative for monogenic obesity or diabetes.We performed this panel in 481 patients to detect causative variants and compared these results with whole-exome sequencing(WES)data available for 146 of these patients.The coverage of targeted gene panel sequencing was significantly higher than that of WES.The diagnostic yield in patients sequenced by the panel was 32.9%with subsequent WES leading to three additional diagnoses with two novel genes.In total,178 variants in 83 genes were detected in 146 patients by targeted sequencing.Three of the 178 variants were missed by WES,although the WES-only approach had a similar diagnostic yield.For the 335 samples only receiving targeted sequencing,the diagnostic yield was 32.2%.In conclusion,taking into account the lower costs,shorter turnaround time,and higher quality of data,targeted sequencing is a more effective screening method for monogenic obesity and diabetes compared to WES.Therefore,this approach could be routinely established and used as a first-tier test in clinical practice for specific patients.

Effectiveness of quality of care for patients with type 2 diabetes in China:findings from the Shanghai Integration Model(SIM)

This cross-sectional study aimed to investigate the quality of care of diabetes in Shanghai,China.A total of 173235 patients with type 2 diabetes in 2017 were included in the analysis.Profiles of risk factors and intermediate outcomes were determined.The patients had a mean age of 66.43±8.12(standard deviation(SD))years and a mean diabetes duration of 7.95±5.53(SD)years.The percentage of patients who achieved the target level for HbA_(1c)(<7.0%)was 48.6%.Patients who achieved the target levels for blood pressure(BP)<130/80 mmHg and low-density lipoprotein-cholesterol(LDL-c)<2.6 mmol/L reached 17.5%and 34.0%,respectively.A total of 3.8%achieved all three target levels,and the value increased to 6.8%with an adaptation of the BP target level(<140/90 mmHg)for those over 65 years.Multivariable analysis identified the factors associated with a great likelihood of achieving all three target levels:male,young age,short diabetes duration,low body mass index,macrovascular complications,no microvascular complications,prescribed with lipid-lowering medication,and no prescription of antihypertensive medication.In conclusion,nearly 50%and one-third of the patients with diabetes met the target levels for HbA_(1c)and LDL-c,respectively,with a low percentage achieving the BP target level.The percentage of patients who achieved all three target levels needs significant improvement.

Effect of Dietary Resistant Starch on Prevention and Treatment of Obesity-related Diseases and Its Possible Mechanisms

Overweight or obesity has become a serious public health problem in the world, scientists are concentrating their efforts on exploring novel ways to treat obesity. Nowadays, the availabilities of bariatric surgery and pharmacotherapy have enhanced obesity treatment, but it should has support from diet, physical exercise and lifestyle modification, especially the functional food. Resistant starch, an indigestible starch, has been studied for years for its beneficial effects on regulating blood glucose level and lipid metabolism. The aim of this review is to summarize the effect of resistant starch on weight loss and the possible mechanisms. According to numerous previous studies it could be concluded that resistant starch can reduce fat accumulation, enhance insulin sensitivity, regulate blood glucose level and lipid metabolism. Recent investigations have focused on the possible associations between resistant starch and incretins as well as gut microbiota. Resistant starch seems to be a promising dietary fiber for the prevention or treatment of obesity and its related diseases.

Comparison of Body Mass Index with Body Fat Percentage in the Evaluation of Obesity in Chinese

Objective To evaluate the present Chinese body mass index （BMI） criteria with body fat percentage （BF%） in determining obesity in Chinese population. Methods A total of 4 907 subjects （age： 20-90 yrs） were enrolled in the baselirie survey of a longitudinal epidemiological study, and 2 638 of them were reevaluated in 5.5 years later. The Chinese BMI and WHO BF% were used to define obesity, respectively. Results The diagnostic agreement between the Chinese BMI and WHO BF% definitions for obesity was poor for both men （kappa： 0.210, 95% CI： 0.179-0.241） and women （kappa： 0.327, 95% CI： 0.296-0.358）. However, BMI had a good correlation with BF% both in men （r： 0.785, P〈0.01） and women （r： 0.864, P〈0.01）. The age and sex-adjusted relative risks （RR） for incidence of type 2 diabetes （T2DM） were significantly higher in subjects with intermediate BF% （BF%：20.1%-25% for men, 30.1%-35% for women） （RR： 2.35, 95% CI： 1.23-4.48） and high BF%（BF%〉25% for men and 〉35% for women）（RR： 2.89, 95% CI： 1.43-5.81）, or in subjects with high BMI （BMI≥ 28 kg/m2） （RR： 2.46, 95% CI： 1.31-4.63） when compared to those with low BF% （BF%≤20% for men ands〈30% for women） or low BMI （BMI〈24 kg/m^2） respectively. No difference in risk could be found in those with intermediate BMI （BMI： 24-27.9 kg/m^2） （RR： 1.44, 95% CI： 0.86-2.40）, as compared to those with low BMI （BMI〈24 kg/m^2）, whose BF% ranged widely from 7.8 to 50.3%. Conclusion BMI was correlated with BF%. Both BMI and BF% were associated with high risk for T2DM. However, BMI had its limitations in the interpretation of subjects with BMI between 24 and 27.9 kg/m^2.

Precise Microdeletion Detection of Prader-Willi Syndrome with Array Comparative Genome Hybridization

Objective Prader-Willi Sydrome （PWS） is a human disorder related to genomic imprinting defect on 15ql 1-13. It is characterized by a series of classic features such as hypotonia, hyperphagia, obesity, osteoporosis, typical facial and body dysmorphosis, hypogonadism, mental and behaviour disorders. Our study was designed to precisely detect the microdeletions, which accounts for 65%-70% of the PWS. Methods Physical and laboratory examinations were firstly performed to diagnose PWS clinically, and to discover novel clinical features. Then the patient was screened with bisulfite-specific sequencing and precisely delineated through high-density array CGH. Results With the bisulfite-specific sequencing, the detected CpG island in the PWS critical region was found homozygously hypermethylated. Then with array CGH, a 2.22 Mb type II microdeletion was detected, covering a region from MKRN3, MAGEL2, NDN, PWRN2, PWRN1, Cl2orf2, SNURF-SNRPN, C/D snoRNAs, to distal of UBE3A. Conclusions Array CGH, after the fast screening of Bisulfite-specific sequencing, is a feasible and precise method to detect microdeletions in PWS patients. A novel feature of metacarpophalangeal joint rigidity was also presented, which is the first time reported in PWS.

Role of Fibroblast Growth Factor 19 in Maintaining Nutrient Homeostasis and Disease

Fibroblast growth factor 19 （FGF19） is a kind of gut-derived postprandial hormone. As an atypical member of the FGF family, FGF19 functions as an endocrine hormone except regulating cell growth and differentiation. FGF19 plays a key role in coordination of liver bile acid biosynthesis and gallbladder motility, and acts as a regulator of metabolic homeostasis, including strengthening insulin sensitivity, decreasing triglyceride concentration and reducing body weight.

Relationship between Waist Circumference and Elevation of Carotid Intima-media Thickness in Newly-diagnosed Diabetic Patients

Objective Waist circumference, as a brief indicator of visceral obesity, is associated with multi-metabolic disorders and cardiovascular diseases. The present study was aimed to find out the relationship between waist circumference and carotid intima media thickness （C-IMT）, as well as the best waist circumference cutoff for identifying C-IMT elevation in Chinese male patients with newly-diagnosed diabetes. Methods Five hundred and seventy-eight patients from Department of Endocrinology and Metabolism in Shanghai Sixth People＇s Hospital affiliated to Shanghai Jiao Tong University were enrolled. Both physical examination （for measurement of waist circumference） and carotid ultrasonography （for measurement of C-IMT） were performed. Results After grouping according to the quartiles of C-IMT, the waist circumference increased across all its quartiles. The waist circumference in 3rd and 4th quartiles （90.7_＋9.8 cm and 90.8＋9.6 cm） was significant higher than in 1st and 2nd quartiles （P〈0.05）. When subjects were divided into 4 groups according to waist circumference, the C-IMT of subjects with waist circumference 90-95 cm was significant higher than that of subjects with waist circumference 85-90 cm and less than 85 cm respectively （P〈0.05）. Both spearman and partial correlation analysis showed that C-IMT was positively correlated with waist circumference （P〈0.01）. C-IMT was found significantly elevated with the increase of waist circumference. Multiple stepwise regression analysis showed that waist circumference was one of the independent risk factors of C-IMT. After an average of 2.23_＋0.85 years follow up, there was a significant elevation of C-IMT in the group with baseline waist circumference over 90 cm P〈0.05）, while no significant difference was detected in the group with baseline waist circumference less than 90 cm （P=0.27）. Logistic regression showed that baseline waist circumference over 90 cm was associated with a relative risk to C-IMT elevation of 1.132 （95% CI 1.043-1.431, P〈0.05）. Conclusion Among newly-diagnosed diabetic male patients, waist circumference over 90 cm not only reflects sub-clinical atherosclerosis in early stage, but also predicts the progression of atherosclerosis.

Data Resource Profile:A Protocol of China National Diabetic Chronic Complications Study

Diabetes affects approximately 10.5%of adults worldwide,and its chronic complications lead to severely disabling sequelae and premature death,thus placing a heavy healthcare burden on both patients affected and society[1].China has experienced a dramatic increase in diabetes prevalence from 0.67%in 1980[2]to 12.8%in 2018[3]and has approximately one-quarter of people with diabetes worldwide[1].It is therefore essential to understand the epidemiologic characteristics of the chronic complications and co-morbidities of diabetes,and the current status of diabetes management to guide planning for appropriate diabetes care and intervention for these complications and co-morbidities at the national level[4-7].

The Impact of Cigarette Smoking on Metabolic Syndrome

Metabolic syndrome （MetS） is a constellation of interconnected cardiometabolic disorders, including obesity, hyperglycemia, dyslipidemia, and elevated blood pressure. MetS is a precursor to type 2 diabetes mellitus （T2DM） and cardiovascular disease （CVD）; it increases the risk of T2DM by 3-4 times[11 and the risk of CVD by 1.4-fold[21, and is more prevalent in obese individuals. As the obesity rates increase, the prevalence of MetS in the population is increased. In 2006, the global prevalence of MetS in adults was estimated to be 20%-25%TM, and in China, in 2007-2008, using the criteria of the Chinese Joint Committee for Developing Chinese Guidelines on Prevention and Treatment of Dyslipidemia in Adults （JCDCG）, it reached 21.9% among the adult population aged 〉20 vears old[4].

Effect of the Gut Microbiota on Obesity and Its Underlying Mechanisms: an Update

Obesity has become one of the most prevalent health issues of our time. According to a 2012 WHO report, around 3.4 million adults die each year as a result of being overweight or obese. Humans are in fact superorganisms composed of both human and microbial cells with 2 sets of genes, those encoded in our own genome and those encoded in our microbiota. All these cells and genes have the potential to influence our health.

BRSK2 in pancreatic β cells promotes hyperinsulinemia-coupled insulin resistance and its genetic variants are associated with human type 2 diabetes

Brain-specific serine/threonine-protein kinase 2(BRSK2)plays critical roles in insulin secretion andβ-cell biology.However,whether BRSK2 is associated with human type 2 diabetes mellitus(T2DM)has not been determined.Here,we report that BRSK2 genetic variants are closely related to worsening glucose metabolism due to hyperinsulinemia and insulin resistance in the Chinese population.BRSK2 protein levels are significantly elevated inβcells from T2DM patients and high-fat diet(HFD)-fed mice due to enhanced protein stability.Mice with inducibleβ-cell-specific Brsk2 knockout(βKO)exhibit normal metabolism with a high potential for insulin secretion under chow-diet conditions.Moreover,βKO mice are protected from HFD-induced hyperinsulinemia,obesity,insulin resistance,and glucose intolerance.Conversely,gain-of-function BRSK2 in matureβcells reversibly triggers hyperglycemia due toβ-cell hypersecretion-coupled insulin resistance.Mechanistically,BRSK2 senses lipid signals and induces basal insulin secretion in a kinase-dependent manner.The enhanced basal insulin secretion drives insulin resistance andβ-cell exhaustion and thus the onset of T2DM in mice fed an HFD or with gain-of-function BRSK2 inβcells.These findings reveal that BRSK2 links hyperinsulinemia to systematic insulin resistance via interplay betweenβcells and insulin-sensitive tissues in the populations carrying human genetic variants or under nutrient-overload conditions.

Application and prospect of artificial intellingence in diabetes care

Diabetes is one of the fastest-growing non-communicable diseases,becoming an important public health concern worldwide as well as in China.Currently,China has the largest population living with diabetes.Artificial intelligence(AI)is a fast-growingfield and its applications to diabetes could enable the delivery of better management services for people with diabetes.This perspective summarized the latestfindings of digital tech-nologies and AI use in the following areas of diabetes care,mainly including screening and risk predictions of diabetes and diabetic complications,precise monitoring and inter-vention combined with new technologies,and mobile health application in self-management support for people with diabetes.Challenges to promote further use of AI in diabetes care included data standardization and integra-tion,performance of AI-based medical devices,motivation of patients,and sensitivity to privacy.In summary,although the AI applications in clinical practice is still at an early stage,we are moving toward a new paradigm for diabetes care with the rapid development and emerging application of AI.

基于大语言模型的糖尿病管理:潜力与展望

The increasing prevalence of diabetes has become a global public health concern in the 21st century.In 2021,it was estimated that 537 million people had diabetes,and this number is projected to reach 643 million by 2030,and 783 million by 2045[1].Such a huge burden of diabetes brings great challenges in its prevention and management,including early diagnosis,timely interventions,and regular monitoring of risk factor control and complications screening.Continuous self-care support and patient empowerment can enhance clinical and psychobehavioural outcomes[2],although these require additional resources including manpower,infrastructure(hard and technology),and finances.The emergence of digital health technologies(DHTs),especially artificial intelligence(AI),may help address these obstacles and alleviate the burden of diabetes[3].Large language models(LLMs),a generative AI that can accept image and text inputs and produce text outputs,have shown promise in various aspects of medical care.

Serum vaspin level in relation to postprandial plasma glucose concentration in subjects with diabetes

Background Vaspin is a newly-identified adipocytokine related to obesity and insulin sensitivity. However, its pathophysiologic role in humans remains largely unknown. The aim of our study was to investigate the relationship between serum vaspin level and glucose metabolism or obesity in Chinese adults. Methods A total of 123 subjects, including 84 subjects with normal glucose tolerance （NGT） and 39 subjects with diabetes, were enrolled in this study. Anthropometric parameters, abdominal fat areas, plasma glucose concentration, serum insulin, lipids, and vaspin level were measured in each participant. Results Serum vaspin concentration was significantly higher in diabetic patients than that in NGT subjects （592 （438-695） pg/ml vs 380 （294-517） pg/ml, P=0.020） in women. In all participants, age, fasting plasma glucose concentration （FPG）, 2-hour post-load plasma glucose （PG2h）, hemoglobin Alc （HbAlc） and high-density lipoprotein cholesterol （HDL-c） significantly increased from the lower tertile to the higher tertile of vaspin. Univariate linear regression analyses revealed that vaspin level was only positively correlated with age （β=0.340, P=0.002） in NGT subjects. And vaspin was positively associated with FPG （β=0.365, P=0.023）, PG2h （β=0.526, P=0.001）, HbAlc （β=0.388, P=0.016）, and HDL-c （β=0.353, P=0.027）, while negatively with homeostasis model assessment of beta cell function （HOMA-β） （β=-0.361, P=-0.024） in diabetic patients. In stepwise multivariate regression analyses, age was independently associated with circulating vaspin in NGT subjects, whereas PG2h was an independent predictor of vaspin in diabetic patients. In addition, there was no significant difference of serum vaspin level between men and women. And no significant correlations between vaspin and body fat indexes were detected. Conclusions Serum vaspin level is higher in diabetic patients than that in NGT subjects in women. Age predicts serum vaspin level in NGT subjects, while PG2h is independently associated with vaspin in diabetic patients.