Abstract P219: Changes in Dental Health and Coronary Heart Disease Risk: Two Prospective Cohort Studies in Men and Women

Introduction: Dental health problems such as tooth loss are related to inflammation and detrimental dietary changes, and may be linked to elevated risks of future heart disease. Most previous studies only investigated pre-existing tooth loss at baseline; hence, whether incident (more recent and later in life) tooth loss is associated with an increased risk of future coronary heart disease (CHD) remains unclear. Hypothesis: We prospectively investigated how recent tooth loss was associated with subsequent risk of CHD in middle-aged adults. Methods: This prospective study included women from the Nurses’ Health Study (NHS) and men from the Health Professionals Follow-Up Study (HPFS) who were initially free of CHD and cancer. Participants were asked about the number of natural teeth first in 1986 in the HPFS, and in 1992 in the NHS. On follow-up questionnaires, participants reported whether they had any recent tooth loss. We calculated cumulative tooth loss during an 8-year assessment period (1992-2000 in the NHS; 1986-1998 in the HPFS) among participants aged 45-69 y. Hazard ratios (HRs) for the incidence of CHD (fatal CHD or non-fatal MI) were examined across categories of the number of tooth loss (none, 1 loss, and 2 or more loss). Follow-up time was calculated after the assessment of tooth loss until the end of follow-up in 2012. We examined risks of CHD separately among individuals with 25-32 natural teeth at the initial examination (n=41939, among whom 1754 incident cases of CHD accrued during 540,744 person-years of follow-up), as well as among all eligible participants (n=60967, among whom 2440 incident cases of CHD accrued during 760,351 person-years of follow-up). Results: Among participants with 25-32 natural teeth at baseline, men and women who lost 2 or more teeth had a significantly increased risk of CHD (Pooled: HR 1.23; 95% CI: 1.06, 1.42) as compared to those with no tooth loss, after adjustment for hypertension, dyslipidemia, diabetes, dietary habits (including the Alternative Healthy Eating Index (AHEI) score, alcohol, multivitamin supplement use), lifestyle and demographic factors. The association was also independent of concurrent changes (during the same period of tooth loss assessment) in AHEI score, physical activity, body weight, and status of hypertension, dyslipidemia, and diabetes (pooled HR 1.22, 95% CI: 1.06, 1.41). When we examined the risk of CHD among all the eligible participants, greater loss of teeth (2 or more loss vs. no loss: pooled HR: 1.16; 95% CI: 1.04, 1.30) and having fewer natural teeth (less than 17 vs. 25-32 teeth: pooled HR: 1.25; 95% CI: 1.08, 1.46) were independently and significantly associated with increased risk of CHD. Conclusions: Our results suggest that among middle-aged adults, a higher number of teeth lost in the recent past may be associated with subsequent risk of CHD, independent of the baseline number of natural teeth and traditional risk factors.

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Iron intake and body iron stores, anaemia and risk of hyperglycaemia among Chinese adults: the prospective Jiangsu Nutrition Study (JIN)

Public Health Nutrition ◽

10.1017/s1368980009991868 ◽

2009 ◽

Vol 13 (9) ◽

pp. 1319-1327 ◽

Cited By ~ 40

Author(s):

Zumin Shi ◽

Minghao Zhou ◽

Baojun Yuan ◽

Lu Qi ◽

Yue Dai ◽

...

Keyword(s):

Joint Effect ◽

Food Record ◽

Men And Women ◽

Increased Risk ◽

Nutrition Study ◽

And Gender ◽

Increase Diabetes Risk ◽

Incident Cases ◽

Fourth Quartile

AbstractObjectiveFe supplementation has been used to prevent anaemia in China; however, high Fe intake and body Fe stores may increase diabetes risk. The present study aimed to prospectively examine the association between Fe intake/stores and hyperglycaemia, and to assess the joint effects on anaemia.DesignWe followed 1056 healthy adults aged 20 years and older from 2002 to 2007. Body Fe stores were measured. Dietary data were collected using a 3 d food record and FFQ. Hyperglycaemia was defined as fasting plasma glucose >5·6 mmol/l.ResultsOf the participants, 28·8 % were anaemic at baseline. During the 5 years of follow-up, we documented 125 incident cases of hyperglycaemia, among them twenty-three were diabetic. Haem Fe intake was positively associated with the risk of hyperglycaemia in men and women: the OR (95 % CI) across increasing quartiles of haem Fe intake was 1·00 (referent), 1·49 (0·74, 3·01), 2·16 (1·06, 4·42) and 3·48 (1·71, 7·11), respectively (P for trend <0·001). Comparing the fourth quartile of serum ferritin with the others, the age- and gender-adjusted OR (95 % CI) was 1·54 (1·01, 2·34), P for trend = 0·043. The association between total Fe intake and the risk of hyperglycaemia was significant in men (P for trend = 0·002). Anaemia added additional risk of hyperglycaemia on haem Fe intake. Comparing extreme quartiles of haem Fe intake, the OR (95 % CI) was 5·67 (1·43, 22·49) and 3·44 (1·51, 7·85) for hyperglycaemia among anaemic and non-anaemic participants (P for trend = 0·008 and 0·010, respectively).ConclusionsThe present cohort study suggests that high haem Fe intake, anaemia and high ferritin are associated with an increased risk of hyperglycaemia in Chinese men and women. There was a joint effect between anaemia and haem Fe intake on the risk of hyperglycaemia.

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Increased Risk of Valvular Heart Disease in Systemic Sclerosis: An Underrecognized Cardiac Complication

The Journal of Rheumatology ◽

10.3899/jrheum.201005 ◽

2021 ◽

pp. jrheum.201005

Author(s):

Reto D. Kurmann ◽

Edward A. El-Am ◽

Yasser A. Radwan ◽

Avneek S. Sandhu ◽

Cynthia S. Crowson ◽

...

Keyword(s):

Heart Disease ◽

Systemic Sclerosis ◽

Valvular Heart Disease ◽

Cardiac Involvement ◽

Significant Risk ◽

Fold Increase ◽

Significant Risk Factor ◽

Increased Risk ◽

Incident Cases

Objective Cardiac involvement is a poor prognostic marker in systemic sclerosis (SSc). While diastolic dysfunction, myocardial fibrosis, and arrhythmias are traditionally considered features of primary cardiac involvement in SSc, the incidence of valvular heart disease (VHD) is not well reported. Our objective was to examine the prevalence of VHD at time of SSc diagnosis and incidence of VHD during follow up compared to non-SSc subjects. Methods Medical records of patients with suspicion of SSc were reviewed to identify incident cases. SSc subjects were matched 1:2 by age- and sex to non-SSc subjects. Results The study included 78 incident SSc cases and 156 non-SSc comparators [56 years (± 15.7), 91% female]. A nearly 4-fold increase in the prevalence of moderate/severe VHD prior to SSc diagnosis compared to non-SSc subjects (6% vs. 0%; P=0.004) was identified. During follow up, 18 SSc and 12 non-SSc patients developed moderate/severe VHD. The cumulative incidence of VHD at 10 years after SSc incidence/index was 17.9% (95% CI: 10.7-29.9%) in patients with SSc compared with 2.3% (95% CI: 0.7-6.3%) in non-SSc subjects (HR: 4.23; 95% CI: 2.03-8.83). Coronary heart disease was the only significant risk factor for VHD. Conclusion SSc patients have a 4-fold increase in the prevalence of moderate/severe VHD at diagnosis compared to non-SSc patients. They also have a 4-fold increased risk of developing moderate/severe VHD after diagnosis of SSc. Aortic stenosis and mitral regurgitation have a much higher prevalence in SSc patients, besides secondary tricuspid regurgitation. Underlying mechanisms for this association require further elucidation.

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Oral Disease in Relation to Future Risk of Dementia and Cognitive Decline: Prospective Cohort Study Based on the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified-Release Controlled Evaluation (Advance) Trial

European Psychiatry ◽

10.1016/j.eurpsy.2011.07.005 ◽

2011 ◽

Vol 28 (1) ◽

pp. 49-52 ◽

Cited By ~ 63

Author(s):

G.-D. Batty ◽

Q. Li ◽

R. Huxley ◽

S. Zoungas ◽

B.-A. Taylor ◽

...

Keyword(s):

Type 2 Diabetes ◽

Cognitive Decline ◽

Tooth Loss ◽

Oral Disease ◽

Modified Release ◽

Increased Risk ◽

Natural Teeth ◽

Controlled Evaluation

AbstractObjectiveExamine the association of oral disease with future dementia/cognitive decline in a cohort of people with type 2 diabetes.MethodsA total of 11,140 men and women aged 55–88 years at study induction with type 2 diabetes participated in a baseline medical examination when they reported the number of natural teeth and days of bleeding gums. Dementia and cognitive decline were ascertained periodically during a 5-year follow-up.ResultsRelative to the group with the greatest number of teeth (more than or equal to 22), having no teeth was associated with the highest risk of both dementia (hazard ratio; 95% confidence interval: 1.48; 1.24, 1.78) and cognitive decline (1.39; 1.21, 1.59). Number of days of bleeding gums was unrelated to these outcomes.ConclusionsTooth loss was associated with an increased risk of both dementia and cognitive decline.

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Joint association between education and polygenic risk score for incident coronary heart disease events: a longitudinal population-based study of 26 203 men and women

Journal of Epidemiology & Community Health ◽

10.1136/jech-2020-214358 ◽

2021 ◽

pp. jech-2020-214358

Author(s):

Pekka Martikainen ◽

Kaarina Korhonen ◽

Aline Jelenkovic ◽

Hannu Lahtinen ◽

Aki Havulinna ◽

...

Keyword(s):

Coronary Heart Disease ◽

Heart Disease ◽

Risk Score ◽

Density Lipoprotein ◽

Population Based ◽

Polygenic Risk Score ◽

Genome Wide ◽

Increased Risk ◽

Region Of Residence

BackgroundGenetic vulnerability to coronary heart disease (CHD) is well established, but little is known whether these effects are mediated or modified by equally well-established social determinants of CHD. We estimate the joint associations of the polygenetic risk score (PRS) for CHD and education on CHD events.MethodsThe data are from the 1992, 1997, 2002, 2007 and 2012 surveys of the population-based FINRISK Study including measures of social, behavioural and metabolic factors and genome-wide genotypes (N=26 203). Follow-up of fatal and non-fatal incident CHD events (N=2063) was based on nationwide registers.ResultsAllowing for age, sex, study year, region of residence, study batch and principal components, those in the highest quartile of PRS for CHD had strongly increased risk of CHD events compared with the lowest quartile (HR=2.26; 95% CI: 1.97 to 2.59); associations were also observed for low education (HR=1.58; 95% CI: 1.32 to 1.89). These effects were largely independent of each other. Adjustment for baseline smoking, alcohol use, body mass index, igh-density lipoprotein (HDL) and total cholesterol, blood pressure and diabetes attenuated the PRS associations by 10% and the education associations by 50%. We do not find strong evidence of interactions between PRS and education.ConclusionsPRS and education predict CHD events, and these associations are independent of each other. Both can improve CHD prediction beyond behavioural risks. The results imply that observational studies that do not have information on genetic risk factors for CHD do not provide confounded estimates for the association between education and CHD.

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MO491ASSOCIATION BETWEEN SERUM URIC ACID LEVEL AND CHRONIC KIDNEY DISEASE INCIDENCE STRATIFIED BY SEX IN MIDDLE-AGED ADULTS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab087.0011 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Shingo Nakayama ◽

Michihiro Satoh ◽

Takahisa Murakami ◽

Yukako Tatsumi ◽

Tomoko Muroya ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Uric Acid ◽

Kidney Disease ◽

Serum Uric Acid ◽

Health Check ◽

Middle Aged ◽

Men And Women ◽

Increased Risk ◽

The Mean ◽

Middle Aged Adults

Abstract Background and Aims While previous studies have reported the association between serum uric acid (SUA) and chronic kidney disease (CKD) incidence, the sex differences in this association remain controversial. Therefore, we examined the association between SUA levels and CKD incidence in middle-aged adults stratified by sex using data from a large-scale health check-up. Method We analyzed information from the JMDC database, which included the annual health check-up data of Japanese employees and their dependents aged <75 years. Among those individuals, we analyzed data from 138,511 individuals without CKD, kidney disease, or a history of cardiovascular disease at baseline. CKD was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 and/or proteinuria. We divided the participants into 9 and 7 groups according to SUA levels for men and women, respectively. A Cox model was applied to assess the adjusted hazard ratios (HRs) for CKD incidence in each SUA level group using an SUA concentration of 4.0–4.9 mg/dL as the reference after adjusting for age, body mass index, current or ex-smoker, current or ex-drinker, diabetes mellitus, dyslipidemia, systolic blood pressure, use of anti-hyperuricemic drugs, and baseline eGFR. Results The mean participant age was 44.1 years, and 29.6% were women. The mean SUA levels were 5.9 mg/dL and 4.1 mg/dL in men and women, respectively. During the mean follow-up period of 4.68 years, 12,589 participants developed CKD. The age-standardized incidence rates for CKD were 17.88/17.80 per 1000 person-years in men/women with SUA concentrations of 4.0–4.9 mg/dL, 209.76 per 1000 person-years in men with SUA ≥11.0 mg/dL, and 73.38 per 1000 person-years in women with SUA ≥ 9.0 mg/dL. The fully adjusted HRs (95% confidence interval [CI], P value) for CKD incidence in the groups with SUA concentrations of <4.0, 10.0–10.9, and ≥11.0 mg/dL compared with those with SUA of 4.0–4.9 mg/dL among men were 1.13 (1.01–1.26, P=0.030), 1.98 (1.32–2.97, P=0.0010), and 3.74 (1.68–8.35, P=0.0013), respectively. In women, the fully adjusted HRs for CKD incidence in the groups with SUA concentrations of <4.0, 8.0–8.9, and ≥9.0 mg/dL were 1.08 (1.01–1.16, P=0.032), 2.39 (1.07–5.35, P=0.034), and 3.20 (0.80–12.8, P=0.10), respectively. Similar results were observed when we performed the sensitivity analysis excluding 8,411 individuals with hypertensive treatment from the main analysis. The HRs for the outcomes caused by the onset of eGFR <60 mL/min/1.73 m2 or proteinuria separately were similar to those for the main results. Conclusion The results of the present study demonstrated an increased risk of CKD in men with SUA concentrations of <4.0 and ≥10.0 mg/dL and <4.0 and ≥8.0 mg/dL in women compared to those with SUA concentrations of 4.0–4.9 mg/dL after adjusting for various covariates. Both high and low SUA levels were risk factors for CKD in middle-aged men and women. Hyperuricemia was demonstrated to cause renal injury due to the intraluminal deposition of uric acid crystals in the renal collecting duct. Hyperuricemia may also induce endothelial dysfunction, activation of the renin-angiotensin system, and induction of inflammation and stimulation of vascular smooth muscle cell proliferation by the induction of cyclooxygenase-2. However, as uric acid is one of the most important antioxidants in human plasma, low SUA levels may increase the risk of CKD incidence through decreased antioxidant activity. These mechanisms are implicated in the pathogenesis of CKD caused by high and low SUA levels. In addition, the SUA levels and ranges associated with increased risks of CKD incidence differed by sex.

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Abstract P196: Bidirectional Association Between Hypertension and Gout: The Singapore Chinese Health Study

Circulation ◽

10.1161/circ.131.suppl_1.p196 ◽

2015 ◽

Vol 131 (suppl_1) ◽

Author(s):

An Pan ◽

Gim Gee Teng ◽

Jian-Min Yuan ◽

Woon-Puay Koh

Keyword(s):

Smoking Status ◽

Final Analysis ◽

Normal Weight ◽

Cox Proportional Hazards ◽

Health Study ◽

Increased Risk ◽

Bidirectional Association ◽

Singapore Chinese ◽

Incident Cases

Introduction: Although it has been hypothesized that the hypertension-gout relation is bidirectional, few studies have addressed this hypothesis in a prospective setting, particularly in the Asian populations. Methods: We analyzed data from the Singapore Chinese Health Study (SCHS), a cohort of 63,257 Chinese aged 45-74 years at recruitment from 1993-98. The information about self reports of physician-diagnosed hypertension and gout was enquired at follow-ups I (1999-2004) and II (2006-2010). We included participants with complete data for both follow-ups and who were free of heart disease, stroke and cancer at follow-up I. For the analysis of hypertension and risk of incident gout, participants with prevalent gout were further excluded and the final analysis included 31,694 participants. For the analysis of gout and risk of incident hypertension, participants with prevalent hypertension were further excluded and the final analysis included 20,490 participants. Cox proportional hazards models were used to estimate multivariable-adjusted relative risks (RRs) and 95% confidence intervals (CIs) with adjustment for age, sex, years of interview, dialect group, education, smoking status, alcohol intake, physical activity, body mass index (BMI) and history of diabetes. Results: The mean age of the participants at baseline was 60.1 (SD 7.3) years, and the average follow-up year was 6.8 (SD 1.4) years. In the analysis of hypertension and risk of gout, 836 incident cases were identified. Compared to normotensive participants, hypertensive patients had a 93% increased risk of developing gout (RR 1.93; 95% CI 1.66-2.24). The association was slightly stronger in women (RR 2.09; 95% CI 1.69-2.58) compared to men (RR 1.72; 95% CI 1.39-2.14; P for interaction=0.056). The association was also stronger in normal weight adults (BMI <24 kg/m2; RR 2.25; 95% CI 1.82-2.77) compared to overweight/obese individuals (BMI ≥24 kg/m2; RR 1.66; 95% CI 1.34-2.04; P for interaction=0.03). In the parallel analysis of gout and risk of hypertension, 5491 participants reported to have newly diagnosed hypertension during the follow-up. Compared to participants without gout, those with gout had a 17% increased risk of developing hypertension (RR 1.17; 95% CI 1.01-1.35). The association was evident in men (RR 1.29; 95% CI 1.07-1.55) but not in women (RR 0.94; 95% CI 0.73-1.20; P for interaction=0.03). The association was present in normal weight adults (RR 1.34; 95% CI 1.09-1.64) but not among overweight/obese individuals (RR 0.99; 95% CI 0.80-1.23; P for interaction=0.03). Conclusions: Our results provide compelling evidence that the hypertension-gout association is bidirectional in Chinese population. The potential interactions of the bidirectional association with sex and obesity deserve further investigations.

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Abstract 19314: Impact of Body Mass Index on Clinical Outcomes in Complex Adult Congenital Heart Disease

Circulation ◽

10.1161/circ.130.suppl_2.19314 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Norihisa Toh ◽

Ines Uribe Morales ◽

Zakariya Albinmousa ◽

Tariq Saifullah ◽

Rachael Hatton ◽

...

Keyword(s):

Heart Failure ◽

Body Mass Index ◽

Congenital Heart Disease ◽

Heart Disease ◽

Congenital Heart ◽

Adult Congenital Heart Disease ◽

Cardiac Events ◽

Increased Risk ◽

Adult Congenital

Background: Obesity can adversely affect most organ systems and increases the risk of comorbidities likely to be of consequence for patients with complex adult congenital heart disease (ACHD). Conversely, several studies have demonstrated that low body mass index (BMI) is a risk factor for heart failure and adverse outcomes after cardiac surgery. However, there are currently no data regarding the impact of BMI in ACHD. Methods: We examined the charts of 87 randomly selected, complex ACHD patients whose first visit to our institution was at 18-22 years old. Patients were categorized according to BMI at initial visit: underweight (BMI < 18.5 kg/m 2 ), normal (BMI 18.5 - 24.9 kg/m 2 ), overweight/obese (BMI ≥ 25 kg/m 2 ). Events occurring during follow-up were recorded. Data was censured on 1/1/2014. Cardiac events were defined as a composite of cardiac death, heart transplantation or admission for heart failure. Results: The cohort included patients with the following diagnoses: tetralogy of Fallot n=31, Mustard n=28, Fontan n=17, ccTGA n=9 and aortic coarctation n=2. The median (IQR) duration of follow-up was 8.7 (4.2 - 1.8) years. See table for distribution and outcomes by BMI category. Cardiac events occurred in 17/87 patients. After adjustment for age, sex, and underlying disease, the underweight group had increased risk of cardiac events (HR=12.9, 95% CI: 2.8-61.5, p < 0.05). Kaplan-Meier curves demonstrate the poorer prognosis of underweight patients (Figure). Conclusions: Underweight was associated with increased risk of late cardiac events in ACHD patients. We were unable to demonstrate significant overweight/obesity impact.

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Associations of ophthalmic and systemic conditions with incident dementia in the UK Biobank

British Journal of Ophthalmology ◽

10.1136/bjophthalmol-2021-319508 ◽

2021 ◽

pp. bjophthalmol-2021-319508

Author(s):

Xianwen Shang ◽

Zhuoting Zhu ◽

Yu Huang ◽

Xueli Zhang ◽

Wei Wang ◽

...

Keyword(s):

Heart Disease ◽

Age Related Macular Degeneration ◽

Hospital Inpatient ◽

Uk Biobank ◽

Age Related ◽

Incident Dementia ◽

Increased Risk ◽

The Uk ◽

Systemic Condition

AimsTo examine independent and interactive associations of ophthalmic and systemic conditions with incident dementia.MethodsOur analysis included 12 364 adults aged 55–73 years from the UK Biobank cohort. Participants were assessed between 2006 and 2010 at baseline and were followed up until the early of 2021. Incident dementia was ascertained using hospital inpatient, death records and self-reported data.ResultsOver 1 263 513 person-years of follow-up, 2304 cases of incident dementia were documented. The multivariable-adjusted HRs (95% CI) for dementia associated with age-related macular degeneration (AMD), cataract, diabetes-related eye disease (DRED) and glaucoma at baseline were 1.26 (1.05 to 1.52), 1.11 (1.00 to 1.24), 1.61 (1.30 to 2.00) and (1.07 (0.92 to 1.25), respectively. Diabetes, heart disease, stroke and depression at baseline were all associated with an increased risk of dementia. Of the combination of AMD and a systemic condition, AMD-diabetes was associated with the highest risk for incident dementia (HR (95% CI): 2.73 (1.79 to 4.17)). Individuals with cataract and a systemic condition were 1.19–2.29 times more likely to develop dementia compared with those without cataract and systemic conditions. The corresponding number for DRED and a systemic condition was 1.50–3.24. Diabetes, hypertension, heart disease, depression and stroke newly identified during follow-up mediated the association between cataract and incident dementia as well as the association between DRED and incident dementia.ConclusionsAMD, cataract and DRED but not glaucoma are associated with an increased risk of dementia. Individuals with both ophthalmic and systemic conditions are at higher risk of dementia compared with those with an ophthalmic or systemic condition only.

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Pregnancy, pregnancy loss and the risk of diabetes in Chinese women: findings from the China Kadoorie Biobank

European Journal of Epidemiology ◽

10.1007/s10654-019-00582-7 ◽

2019 ◽

Vol 35 (3) ◽

pp. 295-303

Author(s):

Sanne A. E. Peters ◽

◽

Ling Yang ◽

Yu Guo ◽

Yiping Chen ◽

...

Keyword(s):

Pregnancy Loss ◽

Cox Regression ◽

Chinese Women ◽

Later Life ◽

Induced Abortion ◽

Hazard Ratios ◽

Increased Risk ◽

History Of ◽

Incident Cases

AbstractPregnancy and pregnancy loss may be associated with increased risk of diabetes in later life. However, the evidence is inconsistent and sparse, especially among East Asians where reproductive patterns differ importantly from those in the West. We examined the associations of pregnancy and pregnancy loss (miscarriage, induced abortion, and still birth) with the risk of incident diabetes in later life among Chinese women. In 2004–2008, the nationwide China Kadoorie Biobank recruited 302 669 women aged 30–79 years from 10 (5 urban, 5 rural) diverse localities. During 9.2 years of follow-up, 7780 incident cases of diabetes were recorded among 273,383 women without prior diabetes and cardiovascular disease at baseline. Cox regression yielded multiple-adjusted hazard ratios (HRs) for the risk of diabetes associated with pregnancy and pregnancy loss. Overall, 99% of women had been pregnant, of whom 10%, 53%, and 6% reported having a history of miscarriage, induced abortion, and stillbirth, respectively. Among ever pregnant women, each additional pregnancy was associated with an adjusted HR of 1.04 (95% CI 1.03; 1.06) for diabetes. Compared with those without pregnancy loss, women with a history of pregnancy loss had an adjusted HR of 1.07 (1.02; 1.13) and the HRs increased with increasing number of pregnancy losses, irrespective of the number of livebirths; the adjusted HR was 1.03 (1.00; 1.05) for each additional pregnancy loss. The strength of the relationships differed marginally by type of pregnancy loss. Among Chinese women, a higher number of pregnancies and pregnancy losses were associated with a greater risk of diabetes.

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Circulating metabolites and the risk of type 2 diabetes: a prospective study of 11,896 young adults from four Finnish cohorts

Diabetologia ◽

10.1007/s00125-019-05001-w ◽

2019 ◽

Vol 62 (12) ◽

pp. 2298-2309 ◽

Cited By ~ 16

Author(s):

Ari V. Ahola-Olli ◽

Linda Mustelin ◽

Maria Kalimeri ◽

Johannes Kettunen ◽

Jari Jokelainen ◽

...

Keyword(s):

Type 2 Diabetes ◽

Young Adults ◽

Fasting Glucose ◽

Diabetes Risk ◽

Increased Risk ◽

Metabolic Biomarkers ◽

Incident Cases ◽

Future Diabetes

Abstract Aims/hypothesis Metabolomics technologies have identified numerous blood biomarkers for type 2 diabetes risk in case−control studies of middle-aged and older individuals. We aimed to validate existing and identify novel metabolic biomarkers predictive of future diabetes in large cohorts of young adults. Methods NMR metabolomics was used to quantify 229 circulating metabolic measures in 11,896 individuals from four Finnish observational cohorts (baseline age 24–45 years). Associations between baseline metabolites and risk of developing diabetes during 8–15 years of follow-up (392 incident cases) were adjusted for sex, age, BMI and fasting glucose. Prospective metabolite associations were also tested with fasting glucose, 2 h glucose and HOMA-IR at follow-up. Results Out of 229 metabolic measures, 113 were associated with incident type 2 diabetes in meta-analysis of the four cohorts (ORs per 1 SD: 0.59–1.50; p< 0.0009). Among the strongest biomarkers of diabetes risk were branched-chain and aromatic amino acids (OR 1.31–1.33) and triacylglycerol within VLDL particles (OR 1.33–1.50), as well as linoleic n-6 fatty acid (OR 0.75) and non-esterified cholesterol in large HDL particles (OR 0.59). The metabolic biomarkers were more strongly associated with deterioration in post-load glucose and insulin resistance than with future fasting hyperglycaemia. A multi-metabolite score comprised of phenylalanine, non-esterified cholesterol in large HDL and the ratio of cholesteryl ester to total lipid in large VLDL was associated with future diabetes risk (OR 10.1 comparing individuals in upper vs lower fifth of the multi-metabolite score) in one of the cohorts (mean age 31 years). Conclusions/interpretation Metabolic biomarkers across multiple molecular pathways are already predictive of the long-term risk of diabetes in young adults. Comprehensive metabolic profiling may help to target preventive interventions for young asymptomatic individuals at increased risk.

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