Nuclear-Targeting Lipid PtIV Prodrug Amphiphile Cooperates with siRNA for Enhanced Cancer Immunochemotherapy by Amplifying Pt-DNA Adducts and Reducing Phosphatidylserine Exposure.

Patients treated with Pt-based anticancer drugs (PtII) often experience severe side effects and are susceptible to cancer recurrence due to the limited bioavailability of PtII and tumor-induced immunosuppression. The exposure of phosphatidylserine on the cell's outer surface induced by PtII results in profound immunosuppression through the binding of phosphatidylserine to its receptors on immune cells. Here, we report a novel approach for enhanced cancer chemoimmunotherapy, where a novel nuclear-targeting lipid PtIV prodrug amphiphile was used to deliver a small interfering RNA (siXkr8) to simultaneously amplify Pt-DNA adducts and reduce the level of exposure of phosphatidylserine. This drug delivery vehicle is engineered by integrating the PtIV prodrug with self-assembly performance and siXkr8 into a lipid nanoparticle, which shows tumor accumulation, cancer cell nucleus targeting, and activatable in a reduced microenvironment. It is demonstrated that nuclear-targeting lipid PtIV prodrug increases the DNA cross-linking, resulting in increased Pt-DNA adduct formation. The synergistic effects of the PtIV prodrug and siXkr8 contribute to the improvement of the tumor immune microenvironment. Consequently, the increased Pt-DNA adducts and immunogenicity effectively inhibit primary tumor growth and prevent tumor recurrence. These results underscore the potential of utilizing the nuclear-targeting lipid PtIV prodrug amphiphile to enhance Pt-DNA adduct formation and employing siXkr8 to alleviate immunosuppression during chemotherapy.

Maintaining healthy sleep patterns and frailty transitions: a prospective Chinese study.

BACKGROUND: Little is known about the effects of maintaining healthy sleep patterns on frailty transitions. METHODS: Based on 23,847 Chinese adults aged 30-79 in a prospective cohort study, we examined the associations between sleep patterns and frailty transitions. Healthy sleep patterns included sleep duration at 7 or 8 h/d, without insomnia disorder, and no snoring. Participants who persisted with a healthy sleep pattern in both surveys were defined as maintaining a healthy sleep pattern and scored one point. We used 27 phenotypes to construct a frailty index and defined three statuses: robust, prefrail, and frail. Frailty transitions were defined as the change of frailty status between the 2 surveys: improved, worsened, and remained. Log-binomial regression was used to calculate the prevalence ratio (PR) to assess the effect of sleep patterns on frailty transitions. RESULTS: During a median follow-up of 8.0 years among 23,847 adults, 45.5% of robust participants, and 10.8% of prefrail participants worsened their frailty status, while 18.6% of prefrail participants improved. Among robust participants at baseline, individuals who maintained sleep duration of 7 or 8 h/ds, without insomnia disorder, and no-snoring were less likely to worsen their frailty status; the corresponding PRs (95% CIs) were 0.92 (0.89-0.96), 0.76 (0.74-0.77), and 0.85 (0.82-0.88), respectively. Similar results were observed among prefrail participants maintaining healthy sleep patterns. Maintaining healthy sleep duration and without snoring, also raised the probability of improving the frailty status; the corresponding PRs were 1.09 (1.00-1.18) and 1.42 (1.31-1.54), respectively. Besides, a dose-response relationship was observed between constantly healthy sleep scores and the risk of frailty transitions (P for trend < 0.001). CONCLUSIONS: Maintaining a comprehensive healthy sleep pattern was positively associated with a lower risk of worsening frailty status and a higher probability of improving frailty status among Chinese adults.

The Association Between Age at Initiation of Alcohol Consumption and Type 2 Diabetes Mellitus: A Cohort Study of 0.5 Million Persons in China.

It is well known that alcohol consumption is associated with type 2 diabetes mellitus. However, the association of age at initiation of alcohol consumption and duration of alcohol drinking with type 2 diabetes mellitus among Chinese adults is not fully understood. This study was based on data from the China Kadoorie Biobank, which included 512,712 participants aged 30-79 years who were living in China in 2004-2008. A Cox proportional hazards model was used to estimate the association of AAI and drinking duration with type 2 diabetes. After adjustment for potential covariates, ages at alcohol initiation (AAIs) of 18.1-29.0 years, 29.1-39.0 years, and >39.0 years were associated with 22% (95% confidence interval (CI): 14, 30), 25% (95% CI: 17, 33), and 32% (95% CI: 24, 39) lower hazards of type 2 diabetes compared with abstaining, respectively. Drinking durations of <10.1 years, 10.1-20.0 years, and 20.1-30.0 years were associated with a lower risk of type 2 diabetes, compared with abstaining. Among current (weekly) drinkers, AAI <18.1 years and drinking duration >30.0 years were associated with 18% (95% CI: 4, 33) and 20% (95% CI: 3, 40) higher hazards of type 2 diabetes, compared with AAI 18.1-29.0 years and drinking duration <10.1 years, respectively. In conclusion, late AAI and a short drinking duration were associated with a lower risk of type 2 diabetes in this large prospective cohort study of Chinese adults, but early AAI and long drinking duration were not.

Body-mass index and long-term risk of sepsis-related mortality: a population-based cohort study of 0.5 million Chinese adults.

BACKGROUND: Sepsis represents a major worldwide healthcare burden. However, how body-mass index (BMI) is related to the long-term risk of sepsis-related mortality in low- and middle-income countries remains uncertain. METHODS: We examined the associations of sepsis-related mortality with both baseline BMI and waist circumference (WC) using data from China Kadoorie Biobank, a prospective cohort recruited during 2004-2008 and followed up to December 2016. After excluding participants with chronic obstructive pulmonary disease, tuberculosis, cancer, heart disease, and stroke, and omitting the first 3 years of follow-up, 440,763 participants remained for analysis. RESULTS: During a median follow-up of 10.0 years, 1957 sepsis-related deaths (3,134,870 person-years) were included for analysis. Compared with reference BMI of 22.5 to < 25.0 kg/m2, the multivariable-adjusted hazard ratios (HRs) for sepsis-related mortality were 2.42 (95% CIs 2.07-2.84) for BMI of < 18.5, 1.59 (1.36-1.85) for 18.5 to < 20.0, 1.21 (1.06-1.38) for 20.0 to < 22.5, 0.97 (0.83-1.13) for 25.0 to < 27.5, 0.98 (0.80-1.21) for 27.5 to < 30.0, and 1.22 (0.93-1.60) for ≥ 30.0 kg/m2. Further adjustment for WC led to slightly augmentation of the effect size for the lower BMI groups and null association in the obese group. In the association analysis between WC and sepsis-related mortality, compared with the middle quintile group, only the highest quintile group showed an increased risk of sepsis-related mortality after adjusted for BMI (HR = 1.54; 95% CI 1.28-1.84). CONCLUSIONS: Underweight, lower normal weight, and abdominal obesity are associated with increased future risk of sepsis-related mortality over 10 years in the Chinese population. The double burden of underweight and obesity indicates a heavy sepsis burden faced by low- and middle-income countries.

Multimorbidity patterns and association with mortality in 0.5 million Chinese adults.

BACKGROUND: Few studies have assessed the relationship between multimorbidity patterns and mortality risk in the Chinese population. We aimed to identify multimorbidity patterns and examined the associations of multimorbidity patterns and the number of chronic diseases with the risk of mortality among Chinese middle-aged and older adults. METHODS: We used data from the China Kadoorie Biobank and included 512,723 participants aged 30 to 79 years. Multimorbidity was defined as the presence of two or more of the 15 chronic diseases collected by self-report or physical examination at baseline. Multimorbidity patterns were identified using hierarchical cluster analysis. Cox regression was used to estimate the associations of multimorbidity patterns and the number of chronic diseases with all-cause and cause-specific mortality. RESULTS: Overall, 15.8% of participants had multimorbidity. The prevalence of multimorbidity increased with age and was higher in urban than rural participants. Four multimorbidity patterns were identified, including cardiometabolic multimorbidity (diabetes, coronary heart disease, stroke, and hypertension), respiratory multimorbidity (tuberculosis, asthma, and chronic obstructive pulmonary disease), gastrointestinal and hepatorenal multimorbidity (gallstone disease, chronic kidney disease, cirrhosis, peptic ulcer, and cancer), and mental and arthritis multimorbidity (neurasthenia, psychiatric disorder, and rheumatoid arthritis). During a median of 10.8 years of follow-up, 49,371 deaths occurred. Compared with participants without multimorbidity, cardiometabolic multimorbidity (hazard ratios [HR] = 2.20, 95% confidence intervals [CI]: 2.14 - 2.26) and respiratory multimorbidity (HR = 2.13, 95% CI:1.97 - 2.31) demonstrated relatively higher risks of mortality, followed by gastrointestinal and hepatorenal multimorbidity (HR = 1.33, 95% CI:1.22 - 1.46). The mortality risk increased by 36% (HR = 1.36, 95% CI: 1.35 - 1.37) with every additional disease. CONCLUSION: Cardiometabolic multimorbidity and respiratory multimorbidity posed the highest threat on mortality risk and deserved particular attention in Chinese adults.

Healthy lifestyle and life expectancy at age 30 years in the Chinese population: an observational study.

BACKGROUND: The improvement of life expectancy is one of the aims of the Healthy China 2030 blueprint. We aimed to investigate the extent to which healthy lifestyles are associated with life expectancy in Chinese adults. METHODS: We used the prospective China Kadoorie Biobank (CKB) study to examine the relative risk of mortality associated with individual and combined lifestyle factors (never smoking or quitting not for illness, no excessive alcohol use, being physically active, healthy eating habits, and healthy body shape). Participants with coronary heart disease, stroke, cancer, or missing values for body-mass index were excluded. For analysis of chronic respiratory diseases, participants with chronic obstructive pulmonary disease or asthma were excluded. We estimated the national prevalence of lifestyle factors using data from the China Nutrition and Health Surveillance (CNHS; 2015) and derived mortality rates from the Global Burden of Diseases, Injuries, and Risk Factors Study (2015). All three data sources were combined to estimate the life expectancy of individuals at age 30 years following different levels of lifestyle factors by using the life table method. The cause-specific decomposition of the life expectancy differences was analysed using Arriaga's method. FINDINGS: After the exclusion of CKB participants with coronary heart disease, stroke, cancer, or missing BMI data at baseline, 487 209 were included in the primary analysis. Participants with COPD or asthma at baseline were additionally excluded for chronic respiratory disease-related analysis, leaving 451 233 participants with data available for analysis. Data from 171 127 adults aged 30-84 years from the CNHS 2015 were used to estimate the sex-specific and age-specific prevalence of lifestyle-related factors. There were 42 496 deaths documented over a median follow-up of 11·1 years (IQR 10·2-12·1) in CKB. The adjusted hazard ratios (aHRs) of participants adopting five versus 0-1 low-risk factors was 0·38 (95% CI 0·34-0·43) for all-cause mortality, aHR 0·37 (0·30-0·46) for cardiovascular disease mortality, aHR 0·47 (0·39-0·56) for cancer mortality, and aHR 0·30 (0·14-0·64) for chronic respiratory disease mortality. The life expectancy at age 30 years for individuals with 0-1 low-risk factors was on average 41·7 years (95% CI 41·5-42·0) for men and 47·3 years (46·6-48·0) for women. For individuals with all five low-risk factors, the life expectancy at age 30 was 50·5 years (95% CI 48·5-52·4) for men and 55·4 years (53·5-57·4) for women; meaning a difference of 8·8 years (95% CI 6·8-10·7) for men and 8·1 years (6·5-9·9) for women. The estimated extended life expectancy for men and women was mainly attributable to reduced death from cardiovascular disease (2·4 years [27% of the total extended life expectancy] for men and 3·7 years [46%] for women), cancer (2·6 years [30%] for men and 0·9 years [11%] for women), and chronic respiratory disease (0·6 years [7%] for men and 1·2 years [15%] for women). INTERPRETATION: Our findings suggest that increasing the adoption of these five healthy lifestyle factors through public health interventions could be associated with substantial gains in life expectancy in the Chinese population. FUNDING: National Natural Science Foundation of China, National Key Research and Development Program of China, Kadoorie Charitable Foundation, UK Wellcome Trust.

Impact of COVID-19 Pandemic on the Clinical Activities in Obstetrics and Gynecology: A National Survey in China.

Objective: Few studies have quantified the influence of coronavirus disease 2019 (COVID-19) pandemic on medical providers. This is the first national study to investigate the impact of the pandemic on physicians practicing obstetrics and gynecology in China. Methods: A two-stage, stratified, cluster sampling method was performed based on the city categories (category 1, fewer than 10,000 beds; category 2, 10,000-30,000; and category 3, more than 30,000) and public hospital levels (primary, secondary, and tertiary). Physicians practicing obstetrics and gynecology reported the relevant changes in their general clinical activities and changes in the management of specific diseases or conditions occurring during the periods that they were most strongly affected. These changes were compared by municipal and hospital characteristics. Results: Questionnaires were collected from a representative sample of 11,806 physicians actively practicing obstetrics and gynecology in 779 hospitals from 157 cities of 31 provinces. Except emergency visits and online consultations, category 3 cities, tertiary hospitals and general hospitals had greater reductions in overall clinical activities than category 1 cities, primary hospitals and specialized hospitals (all adjusted p < 0.05), respectively. The differences also existed in the management of specific diseases and conditions, especially for less urgent conditions, including cervical cancer screening, instructions regarding contraception and miscarriage, and assisted reproduction (all p < 0.05). Conclusions: During the COVID-19 pandemic, the clinical obstetrics and gynecology activities in China markedly decreased, with significant differences across municipal and hospital characteristics. Trial Registration: This study was registered with ClinicalTrials.gov on July 27, 2020 (NCT04491201).

Consumption of Tea, Alcohol, and Fruits and Risk of Kidney Stones: A Prospective Cohort Study in 0.5 Million Chinese Adults.

A few prospective studies have suggested that tea, alcohol, and fruit consumption may reduce the risk of kidney stones. However, little is known whether such associations and their combined effect persist in Chinese adults, for whom the popular tea and alcohol drinks are different from those investigated in the aforementioned studies. The present study included 502,621 participants from the China Kadoorie Biobank (CKB). Information about tea, alcohol, and fruit consumption was self-reported at baseline. The first documented cases of kidney stones during follow-up were collected through linkage with the national health insurance system. Cox regression was used to calculate the hazard ratio (HR) and 95% confidence interval (CI). During a median of 11.1 years of follow-up, we collected 12,407 cases of kidney stones. After multivariable adjustment, tea, alcohol, and fruit consumption were found to be negatively associated with kidney stone risk, but the linear trend was only found in tea and fruit consumption. Compared with non-tea consumers, the HR (95% CI) for participants who drank ≥7 cups of tea per day was 0.73 (0.65-0.83). Compared with non-alcohol consumers, the HR (95% CI) was 0.79 (0.72-0.87) for participants who drank pure alcohol of 30.0-59.9 g per day but had no further decrease with a higher intake of alcohol. Compared with less-than-weekly consumers, the HR (95% CI) for daily fruit consumers was 0.81 (0.75-0.87). Even for those who did not drink alcohol excessively, increasing tea and fruit consumption could also independently reduce the stone risk. Among Chinese adults, tea, alcohol, and fruit consumption was associated with a lower risk of kidney stones.

Adherence to Healthy Lifestyle and Attenuation of Biological Aging in Middle-Aged and Older Chinese Adults.

BACKGROUND: Little is known about the effects of lifestyle modification on biological aging in population-based studies of middle-aged and older adults. METHOD: We examined the individual and joint associations of multiple lifestyle factors with accelerated biological aging measured by change in frailty index (FI) over 8 years in a prospective study of Chinese adults. Data were obtained on 24 813 participants in the China Kadoorie Biobank on lifestyle factors and frailty status at baseline and at 8 years after baseline. Adherence to healthy lifestyle factors included nonsmoking or quitting smoking for reasons other than illness, avoidance of heavy alcohol consumption, daily intake of fruit and vegetables, being physically active, body mass index of 18.5-23.9 kg/m2, and waist-to-hip ratio of <0.90 (men)/0.85 (women). FI was constructed separately at baseline and resurvey using 25 age- and health-related items. RESULTS: Overall, 8 760 (35.3%) individuals had a worsening frailty status. In multivariable-adjusted logistic regression analyses, adherence to healthy lifestyle was associated with a lower risk of worsening frailty status. Compared with robust participants maintaining 0-1 healthy lifestyle factors, the corresponding odds ratios (95% CIs) were 0.93 (0.83-1.03), 0.75 (0.67-0.84), 0.68 (0.60-0.77), and 0.55 (0.46-0.65) for robust participants with 2, 3, 4, and 5-6 healthy lifestyle factors. The decreased risk of frailty status worsening by adherence to healthy lifestyle factors was similar in both middle-aged and older adults, and in both robust and prefrail participants at baseline. CONCLUSIONS: Adherence to a healthy lifestyle may attenuate the rate of change in biological aging in middle-aged and older Chinese adults.

Age-Specific Associations Between Habitual Snoring and Cardiovascular Diseases in China: A 10-Year Cohort Study.

BACKGROUND: Limited convincing evidence is available of the relationship between habitual snoring and cardiovascular diseases (CVDs). RESEARCH QUESTION: Is habitual snoring associated with total CVD and CVD subtypes in different age groups of Chinese adults? STUDY DESIGN AND METHODS: The China Kadoorie Biobank study enrolled more than 0.5 million adults aged 30 to 79 years from 10 regions in China. Snoring status and other baseline characteristics were collected from 2004 to 2008, using an interviewer-administered laptop-based questionnaire. The current analysis included 489,583 participants without stroke or coronary heart disease at baseline. Cox proportional hazards models were used to calculate the adjusted hazard ratios (HRs) and 95% CIs of cardiovascular diseases (CVDs) for habitual snoring vs nonhabitual snoring. RESULTS: During a median follow-up of 9.6 years, 130,935 participants developed CVDs. Associations between habitual snoring and CVDs varied with age. Among participants aged younger than 50 years at baseline, habitual snoring was associated with an increased risk of total CVD (HR, 1.11; 95% CI, 1.07-1.14) after adjustment for known CVD risk factors, including systolic BP. The corresponding HRs (95% CIs) for ischemic heart disease, ischemic stroke, and hemorrhagic stroke were 1.18 (1.12-1.24), 1.12 (1.05-1.19), and 1.05 (0.92-1.19), respectively. However, such associations in adults aged 50 to 64 years were much weaker, and no statistically significant association was observed among individuals aged ≥65 years. Age-specific risk estimates were generally similar across sex and obesity subgroups. INTERPRETATION: Habitual snoring was associated with increased risks of total CVD, ischemic heart disease, ischemic stroke, but not hemorrhagic stroke in Chinese, and these associations were mainly limited to those aged <50 years. Clinicians in China are encouraged to identify snoring, particularly in younger adults.

Diagnostic Strategies for Recurrent Cervical Cancer: A Cohort Study.

OBJECTIVE: The effectiveness of various strategies for the post-treatment monitoring of cervical cancer is unclear. This pilot study was conducted to explore recurrence patterns in and diagnostic strategies for patients with uterine cervical cancer who were meticulously followed using a customized monitoring plan. METHODS: The epidemiological and clinical data of patients with recurrent cervical cancer treated from March 2012 to April 2018 at a tertiary teaching hospital were retrospectively collected. The diagnostic methods and their reliability were compared across patients with various clinicopathological characteristics and were associated with survival outcomes. RESULTS: Two hundred sixty-four patients with recurrent cervical cancer were included in the study, among which recurrence occurred in the first three years after the last primary treatment in 214 patients (81.06%). Half of the recurrence events (50.76%) occurred only within the pelvic cavity, and most lesions (78.41%) were multiple in nature. Among all recurrent cases, approximately half were diagnosed based on clinical manifestations (n=117, 44.32%), followed by imaging examinations (n=76, 28.79%), serum tumor markers (n=34, 12.88%), physical examinations (n=33, 12.50%) and cervical cytology with or without high-risk human papillomavirus (hrHPV) testing (n=4, 1.52%). The reliability of the diagnostic methods was affected by the stage (p<0.001), primary treatment regimen (p=0.001), disease-free survival (p=0.022), recurrence site (p=0.002) and number of recurrence sites (p=0.001). Primary imaging methods (sonography and chest X-ray) were not inferior to secondary imaging methods (computed tomography, magnetic resonance imaging and positron emission tomography-computed tomography) in the detection of recurrence. The chest X-ray examination only detected three cases (1.14%) of recurrence. Patients assessed with various diagnostic strategies had similar progression-free and overall survival outcomes. CONCLUSIONS: A meticulous evaluation of clinical manifestations might allow recurrence to be discovered in a timely manner in most patients with cervical cancer. Specific diagnostic methods for revealing recurrence were not associated with the survival outcomes.

Frailty index and all-cause and cause-specific mortality in Chinese adults: a prospective cohort study.

BACKGROUND: The fraily index is a useful proxy measure of accelerated biological ageing and in estimating all-cause and cause-specific mortality in older individuals in European and US populations. However, the predictive value of the frailty index in other populations outside of Europe and the USA and in adults younger than 50 years is unknown. We aimed to examine the association between the frailty index and mortality in a population of Chinese adults. METHODS: In this prospective cohort study, we used data from the China Kadoorie Biobank. We included adults aged 30-79 years from ten areas (five urban areas and five rural areas) of China who had no missing values for the items that made up the frailty index. We did not exclude participants on the basis of baseline morbidity status. We calculated the follow-up person-years from the baseline date to either the date of death, loss to follow-up, or Dec 31, 2017, whichever came first, through linkage with the registries of China's Disease Surveillance Points system and local residential records. Active follow-up visits to local communities were done annually for participants who were not linked to any established registries. Causes of death from official death certificates were supplemented, if necessary, by reviewing medical records or doing standard verbal autopsy procedures. The frailty index was calculated using 28 baseline variables, all of which were health status deficits measured by use of questionnaires and physical examination. We defined three categories of frailty status: robust (frailty index ≤0·10), prefrail (frailty index >0·10 to <0·25), and frail (frailty index ≥0·25). The primary outcomes were all-cause mortality and cause-specific mortality in Chinese adults aged 30-79 years. We used a Cox proportional hazards model to estimate the associations between the frailty index and all-cause and cause-specific mortality, adjusting for chronological age, education, and lifestyle factors. FINDINGS: 512 723 participants, recruited between June 25, 2004, and July 15, 2008, were followed up for a median of 10·8 years (IQR 10·2-13·1; total follow-up 5 551 974 person-years). 291 954 (56·9%) people were categorised as robust, 205 075 (40·0%) people were categorised as prefrail, and 15 694 (3·1%) people were categorised as frail. Women aged between 45 years and 79 years had a higher mean frailty index and a higher prevalence of frailty than did men. During follow-up, 49 371 deaths were recorded. After adjustment for established and potential risk factors for death, each 0·1 increment in the frailty index was associated with a higher risk of all-cause mortality (hazard ratio [HR] 1·68, 95% CI 1·66-1·71). Such associations were stronger among younger adults than among older adults (pinteraction<0·0001), with HRs per 0·1 increment of the frailty index of 1·95 (95% CI 1·87-2·03) for those younger than 50 years, 1·80 (1·76-1·83) for those aged 50-64 years, and 1·56 (1·53-1·59) for those 65 years and older. After adjustments, there was no difference between the sexes in the association between the frailty index and all-cause mortality (pinteraction=0·75). For each 0·1 increment of the frailty index, the corresponding HRs for risk of death were 1·89 (95% CI 1·83-1·94) from ischaemic heart disease, 1·84 (1·79-1·89) from cerebrovascular disease, 1·19 (1·16-1·22) from cancer, 2·54 (2·45-2·63) from respiratory disease, 1·78 (1·59-2·00) from infection, and 1·78 (1·73-1·83) from all other causes. INTERPRETATION: The frailty index is associated with all-cause and cause-specific mortality independent of chronological age in younger and older Chinese adults. The identification of younger adults with accelerated ageing by use of surrogate measures could be useful for the prevention of premature death and the extension of healthy active life expectancy. FUNDING: The National Natural Science Foundation of China, the National Key R&D Program of China, the Chinese Ministry of Science and Technology, the Kadoorie Charitable Foundation, and the Wellcome Trust.

Habitual snoring, adiposity measures and risk of type 2 diabetes in 0.5 million Chinese adults: a 10-year cohort.

OBJECTIVES: The present study aimed to examine whether habitual snoring was independently associated with risk of type 2 diabetes among Chinese adults, and to assess the role that adiposity measures play in the snoring-diabetes association, as well as to evaluate the joint influence of snoring and adiposity measures on diabetes. RESEARCH DESIGN AND METHODS: The China Kadoorie Biobank study recruited 512 715 adults aged 30-79 years from 10 regions in China during 2004 and 2008. Data from 482 413 participants without baseline diabetes were analyzed in the present study. Autoregressive cross-lagged panel analysis was used to assess the longitudinal relationship between adiposity measures and habitual snoring. Cox proportional hazards models were used to examine the association between habitual snoring and diabetes risk. RESULTS: Both higher body mass index and waist circumference were associated with higher risks of subsequent habitual snoring, whereas no reverse association was detected. A total of 16 479 type 2 diabetes cases were observed during a 10-year follow-up. Habitual snoring was independently associated with 12% (95% CI 6% to 18%) and 14% (95% CI 9% to 19%) higher risks of diabetes among men and women, respectively. Habitual snorers who had general obesity or central obesity were about twice as likely to develop diabetes as non-snorers at the lowest levels of adiposity measures. CONCLUSION: Habitual snoring was independently associated with a higher risk of type 2 diabetes among Chinese adults. It is important to maintain both a healthy weight and a normal waist circumference to prevent or alleviate habitual snoring and ultimately prevent diabetes among Chinese adults.

Genetic risk, adherence to a healthy lifestyle, and type 2 diabetes risk among 550,000 Chinese adults: results from 2 independent Asian cohorts.

BACKGROUND: Whether genetic susceptibility to type 2 diabetes is modified by a healthy lifestyle among Chinese remains unknown. OBJECTIVES: The aim of the study was to determine whether genetic risk and adherence to a healthy lifestyle contribute independently to the risk of developing type 2 diabetes. METHODS: We defined a lifestyle score using BMI, alcohol intake, smoking, physical activities, and diets in 461,030 participants from the China Kadoorie Biobank and 38,434 participants from the Singapore Chinese Health Study. A genetic risk score was constructed based on type 2 diabetes loci among 100,175 and 16,172 participants in each cohort, respectively. A Cox proportional-hazards model was used to estimate the interaction between genetic and lifestyle factors on the risk of type 2 diabetes. RESULTS: In 2 independent Asian cohorts, we consistently found a healthy lifestyle (the bottom quintile of lifestyle score) was associated with a substantially lower risk of type 2 diabetes than an unhealthy lifestyle (the top quintile of lifestyle score) regardless of genetic risk. In those at a high genetic risk, the risk of type 2 diabetes was 57% lower among participants with a healthy lifestyle than among those with an unhealthy lifestyle in the pooled cohorts. Among participants at high genetic risk, the standardized 10-y incidence of type 2 diabetes was 7.11% in those with an unhealthy lifestyle vs. 2.45% in those with a healthy lifestyle. CONCLUSIONS: In 2 independent cohorts involving 558,302 Chinese participants, we did not observe an interaction between genetics and lifestyle with type 2 diabetes risk, but our findings provide replicable evidence to show lifestyle factors and genetic factors were independently associated with the risk of type 2 diabetes. Within any genetic risk category, a healthy lifestyle was associated with a significantly lower risk of type 2 diabetes among the Chinese population.