Journal
DIABETES CARE
Volume 36, Issue 11, Pages 3526-3534Publisher
AMER DIABETES ASSOC
DOI: 10.2337/dc13-0446
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Funding
- European Union [LSHM-CT-2006-037197]
- NL Agency [IGE05012]
- Board of the UMC Utrecht
- Swedish Research Council
- Novo Nordisk
- Swedish Diabetes Association
- Swedish Heart-Lung Foundation
- Danish Cancer Society
- German Cancer Aid, German Ministry of Research (BMBF)
- Cancer Research UK
- Medical Research Council UK
- Asturias Regional Government
- Vasterboten County Council
- Dutch Ministry of Public Health, Welfare, and Sports (VWS)
- Netherlands Cancer Registry (NKR)
- LK Research Funds
- Dutch Prevention Funds
- Dutch ZON (Zorg Onderzoek Nederland)
- World Cancer Research Fund (WCRF)
- Statistics Netherlands
- Health Research Fund (FIS) of the Spanish Ministry of Health
- CIBER en Epidemiologia y Salud Publica (CIBERESP) Spain
- Murcia Regional Government (6236)
- AIRE-ONLUS Ragusa
- AVIS-Ragusa
- Sicilian Regional Government
- VWS
- NKR
- WCRF
- Imperial College Biomedical Research Centre
- MRC [MC_U106179472, MC_UU_12015/5, MC_UU_12015/1, MC_UP_A100_1003, MC_UU_12015/2] Funding Source: UKRI
- Medical Research Council [MC_UU_12015/1, MC_UU_12015/2, G1000143, MC_U106179472, MC_U106179471, MC_UU_12015/5, G0401527, MC_UP_A100_1003] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0512-10135, NF-SI-0512-10114] Funding Source: researchfish
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OBJECTIVEYounger age at menarche, a marker of pubertal timing in girls, is associated with higher risk of later type 2 diabetes. We aimed to confirm this association and to examine whether it is explained by adiposity.RESEARCH DESIGN AND METHODSThe prospective European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study consists of 12,403 incident type 2 diabetes cases and a stratified subcohort of 16,154 individuals from 26 research centers across eight European countries. We tested the association between age at menarche and incident type 2 diabetes using Prentice-weighted Cox regression in 15,168 women (n = 5,995 cases). Models were adjusted in a sequential manner for potential confounding and mediating factors, including adult BMI.RESULTSMean menarcheal age ranged from 12.6 to 13.6 years across InterAct countries. Each year later menarche was associated with 0.32 kg/m(2) lower adult BMI. Women in the earliest menarche quintile (8-11 years, n = 2,418) had 70% higher incidence of type 2 diabetes compared with those in the middle quintile (13 years, n = 3,634), adjusting for age at recruitment, research center, and a range of lifestyle and reproductive factors (hazard ratio [HR], 1.70; 95% CI, 1.49-1.94; P < 0.001). Adjustment for BMI partially attenuated this association (HR, 1.42; 95% CI, 1.18-1.71; P < 0.001). Later menarche beyond the median age was not protective against type 2 diabetes.CONCLUSIONSWomen with history of early menarche have higher risk of type 2 diabetes in adulthood. Less than half of this association appears to be mediated by higher adult BMI, suggesting that early pubertal development also may directly increase type 2 diabetes risk.
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