Dataset Information

Age at menopause, reproductive life span, and type 2 diabetes risk: results from the EPIC-InterAct study.

ABSTRACT:

Objective

Age at menopause is an important determinant of future health outcomes, but little is known about its relationship with type 2 diabetes. We examined the associations of menopausal age and reproductive life span (menopausal age minus menarcheal age) with diabetes risk.

Research design and methods

Data were obtained from the InterAct study, a prospective case-cohort study nested within the European Prospective Investigation into Cancer and Nutrition. A total of 3,691 postmenopausal type 2 diabetic case subjects and 4,408 subcohort members were included in the analysis, with a median follow-up of 11 years. Prentice weighted Cox proportional hazards models were adjusted for age, known risk factors for diabetes, and reproductive factors, and effect modification by BMI, waist circumference, and smoking was studied.

Results

Mean (SD) age of the subcohort was 59.2 (5.8) years. After multivariable adjustment, hazard ratios (HRs) of type 2 diabetes were 1.32 (95% CI 1.04-1.69), 1.09 (0.90-1.31), 0.97 (0.86-1.10), and 0.85 (0.70-1.03) for women with menopause at ages <40, 40-44, 45-49, and ?55 years, respectively, relative to those with menopause at age 50-54 years. The HR per SD younger age at menopause was 1.08 (1.02-1.14). Similarly, a shorter reproductive life span was associated with a higher diabetes risk (HR per SD lower reproductive life span 1.06 [1.01-1.12]). No effect modification by BMI, waist circumference, or smoking was observed (P interaction all > 0.05).

Conclusions

Early menopause is associated with a greater risk of type 2 diabetes.

SUBMITTER: Brand JS

PROVIDER: S-EPMC3609516 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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Publications

Age at menopause, reproductive life span, and type 2 diabetes risk: results from the EPIC-InterAct study.

Brand Judith S JS van der Schouw Yvonne T YT Onland-Moret N Charlotte NC Sharp Stephen J SJ Ong Ken K KK Khaw Kay-Tee KT Ardanaz Eva E Amiano Pilar P Boeing Heiner H Chirlaque Maria-Dolores MD Clavel-Chapelon Françoise F Crowe Francesca L FL de Lauzon-Guillain Blandine B Duell Eric J EJ Fagherazzi Guy G Franks Paul W PW Grioni Sara S Groop Leif C LC Kaaks Rudolf R Key Timothy J TJ Nilsson Peter M PM Overvad Kim K Palli Domenico D Panico Salvatore S Quirós J Ramón JR Rolandsson Olov O Sacerdote Carlotta C Sánchez María-José MJ Slimani Nadia N Teucher Birgit B Tjonneland Anne A Tumino Rosario R van der A Daphne L DL Feskens Edith J M EJ Langenberg Claudia C Forouhi Nita G NG Riboli Elio E Wareham Nicholas J NJ

Diabetes care 20121210 4

<h4>Objective</h4>Age at menopause is an important determinant of future health outcomes, but little is known about its relationship with type 2 diabetes. We examined the associations of menopausal age and reproductive life span (menopausal age minus menarcheal age) with diabetes risk.<h4>Research design and methods</h4>Data were obtained from the InterAct study, a prospective case-cohort study nested within the European Prospective Investigation into Cancer and Nutrition. A total of 3,691 postm ...[more]

PMID: 23230098

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Project description:BackgroundUnderstanding of the genetic basis of type 2 diabetes (T2D) has progressed rapidly, but the interactions between common genetic variants and lifestyle risk factors have not been systematically investigated in studies with adequate statistical power. Therefore, we aimed to quantify the combined effects of genetic and lifestyle factors on risk of T2D in order to inform strategies for prevention.Methods and findingsThe InterAct study includes 12,403 incident T2D cases and a representative sub-cohort of 16,154 individuals from a cohort of 340,234 European participants with 3.99 million person-years of follow-up. We studied the combined effects of an additive genetic T2D risk score and modifiable and non-modifiable risk factors using Prentice-weighted Cox regression and random effects meta-analysis methods. The effect of the genetic score was significantly greater in younger individuals (p for interaction ?=?1.20×10-4). Relative genetic risk (per standard deviation [4.4 risk alleles]) was also larger in participants who were leaner, both in terms of body mass index (p for interaction ?=?1.50×10-3) and waist circumference (p for interaction ?=?7.49×10-9). Examination of absolute risks by strata showed the importance of obesity for T2D risk. The 10-y cumulative incidence of T2D rose from 0.25% to 0.89% across extreme quartiles of the genetic score in normal weight individuals, compared to 4.22% to 7.99% in obese individuals. We detected no significant interactions between the genetic score and sex, diabetes family history, physical activity, or dietary habits assessed by a Mediterranean diet score.ConclusionsThe relative effect of a T2D genetic risk score is greater in younger and leaner participants. However, this sub-group is at low absolute risk and would not be a logical target for preventive interventions. The high absolute risk associated with obesity at any level of genetic risk highlights the importance of universal rather than targeted approaches to lifestyle intervention.

Project description:ImportanceMenstrual cycle dysfunction is associated with insulin resistance, a key feature early in the pathogenesis of type 2 diabetes. However, the evidence linking irregular and long menstrual cycles with type 2 diabetes is scarce and inconsistent.ObjectivesTo evaluate the associations between menstrual cycle characteristics at different points throughout a woman's reproductive life span and risk of type 2 diabetes and the extent to which this association is modified by lifestyle factors.Design, setting, and participantsThis prospective cohort study included 75 546 premenopausal US female nurses participating in the Nurses' Health Study II from 1993 to June 30, 2017. Data analysis was performed from February 1 to December 30, 2019.ExposuresSelf-reported usual length and regularity of menstrual cycles at the age ranges of 14 to 17 years, 18 to 22 years, and 29 to 46 years.Main outcomes and measuresIncident type 2 diabetes identified through self-report and confirmed by validated supplemental questionnaires.ResultsAmong the 75 546 women in the study at baseline, the mean (SD) age was 37.9 (4.6) years (range, 29.0-46.0 years). A total of 5608 participants (7.4%) had documented new cases of type 2 diabetes during 1 639 485 person-years of follow-up. After adjustment for potential confounders, women reporting always having irregular menstrual cycles between the age ranges of 14 to 17 years, 18 to 22 years, and 29 to 46 years were, respectively, 32% (95% CI, 22%-44%), 41% (95% CI, 23%-62%), and 66% (95% CI, 49%-84%) more likely to develop type 2 diabetes than women reporting very regular cycles (within 3-4 days of expected period) in the same age range. Similarly, women reporting a usual cycle length of 40 days or more between the age ranges of 18 to 22 years and 29 to 46 years were, respectively, 37% (95% CI, 19%-57%) and 50% (95% CI, 36%-65%) more likely to develop type 2 diabetes during follow-up compared with women reporting a usual cycle length of 26 to 31 days in the same age ranges. These associations appeared to be stronger among women with overweight or obesity, a low-quality diet, and low levels of physical activity. The relative excess risk of type 2 diabetes due to the interaction between irregular and long menstrual cycles and the overall unhealthy lifestyle score was 0.73 (95% CI, 0.57-0.89) and 0.68 (95% CI, 0.54-0.83), respectively.Conclusions and relevanceIn this cohort study of US female nurses participating in the Nurses' Health Study II, irregular and long menstrual cycles throughout life were associated with a greater risk of type 2 diabetes, particularly among women with overweight or obesity, a low-quality diet, and low levels of physical activity.

Dataset Information

Age at menopause, reproductive life span, and type 2 diabetes risk: results from the EPIC-InterAct study.

Objective

Research design and methods

Results

Conclusions

Publications

Age at menopause, reproductive life span, and type 2 diabetes risk: results from the EPIC-InterAct study.

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