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ObjectiveTrans fatty acids (TFAs) have harmful biologic effects that could increase the risk of type 2 diabetes (T2D), but evidence remains uncertain. We aimed to investigate the prospective associations of TFA biomarkers and T2D by conducting an individual participant-level pooled analysis.Research design and methodsWe included data from an international consortium of 12 prospective cohorts and nested case-control studies from six nations. TFA biomarkers were measured in blood collected between 1990 and 2008 from 25,126 participants aged ≥18 years without prevalent diabetes. Each cohort conducted de novo harmonized analyses using a prespecified protocol, and findings were pooled using inverse-variance weighted meta-analysis. Heterogeneity was explored by prespecified between-study and within-study characteristics.ResultsDuring a mean follow-up of 13.5 years, 2,843 cases of incident T2D were identified. In multivariable-adjusted pooled analyses, no significant associations with T2D were identified for trans/trans-18:2, relative risk (RR) 1.09 (95% CI 0.94-1.25); cis/trans-18:2, 0.89 (0.73-1.07); and trans/cis-18:2, 0.87 (0.73-1.03). Trans-16:1n-9, total trans-18:1, and total trans-18:2 were inversely associated with T2D (RR 0.81 [95% CI 0.67-0.99], 0.86 [0.75-0.99], and 0.84 [0.74-0.96], respectively). Findings were not significantly different according to prespecified sources of potential heterogeneity (each P ≥ 0.1).ConclusionsCirculating individual trans-18:2 TFA biomarkers were not associated with risk of T2D, while trans-16:1n-9, total trans-18:1, and total trans-18:2 were inversely associated. Findings may reflect the influence of mixed TFA sources (industrial vs. natural ruminant), a general decline in TFA exposure due to policy changes during this period, or the relatively limited range of TFA levels.

ObjectiveWe performed a secondary analysis to evaluate the effect of the Women's Health Initiative dietary intervention on incident diabetes and diabetes treatment in postmenopausal women.Research design and methodsA total of 48,835 women were randomized to a comparison group or an intervention group that underwent a behavioral/nutritional modification program to decrease fat and increase vegetable, fruit, and grain intake for an average of 8.1 years. Ninety-three percent of participants completed the intervention, and 71% participated in active follow-up through 30 September 2015 (median 17.3 years). We measured time to development of treated diabetes and progression from oral antihyperglycemic agents to insulin. Serum glucose and insulin were measured in a subsample of women (N = 2,324) at baseline and years 1, 3, and 6.ResultsDuring the trial, intervention group women had lower rates of initiation of insulin therapy (hazard ratio [HR] 0.74 [95% CI 0.59, 0.94]; P = 0.01). Moreover, women with baseline waist circumference ≥88 cm (P interaction = 0.01) and worse metabolic syndrome scores (P interaction = 0.02) had the greatest reduction in risk of initiating insulin therapy. The decreased risk from the intervention was present during the cumulative follow-up (HR 0.88 [95% CI 0.78, 0.99]; P = 0.04). In participants with measured biomarkers (5.8% subsample) who had baseline glucose

ObjectiveIn older women, higher levels of estrogen may exacerbate the increased risk for cognitive impairment conveyed by diabetes. We examined whether the effect of postmenopausal hormone therapy (HT) on cognitive impairment incidence differs depending on type 2 diabetes.Research design and methodsThe Women's Health Initiative (WHI) randomized clinical trials assigned women to HT (0.625 mg/day conjugated equine estrogens with or without [i.e., unopposed] 2.5 mg/day medroxyprogesterone acetate) or matching placebo for an average of 4.7-5.9 years. A total of 7,233 women, aged 65-80 years, were classified according to type 2 diabetes status and followed for probable dementia and cognitive impairment (mild cognitive impairment or dementia).ResultsThrough a maximum of 18 years of follow-up, women with diabetes had increased risk of probable dementia (hazard ratio [HR] 1.54 [95% CI 1.16-2.06]) and cognitive impairment (HR 1.83 [1.50-2.23]). The combination of diabetes and random assignment to HT increased their risk of dementia (HR 2.12 [1.47-3.06]) and cognitive impairment (HR 2.20 [1.70-2.87]) compared with women without these conditions, interaction P = 0.09 and P = 0.08. These interactions appeared to be limited to women assigned to unopposed conjugated equine estrogens.ConclusionsThese analyses provide additional support to a prior report that higher levels of estrogen may exacerbate risks that type 2 diabetes poses for cognitive function in older women. The role estrogen plays in suppressing non-glucose-based energy sources in the brain may explain this interaction.

OBJECTIVE: To prospectively examine the associations of habitual calcium supplementation with cardiovascular disease (CVD) events and mortality in individuals with and without diabetes. RESEARCH DESIGN AND METHODS: The main analysis included 434,374 participants from the UK Biobank. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs. Interactions of calcium supplement use with diabetes status were tested on multiplicative and additive scales. RESULTS: Over a median follow-up of 8.1 and 11.2 years, 26,374 incident CVD events and 20,526 deaths were documented, respectively. After multivariable adjustment, habitual calcium supplementation was significantly associated with higher risks of CVD incidence (HR 1.34; 95% CI 1.14, 1.57), CVD mortality (HR 1.67; 95% CI 1.19, 2.33), and all-cause mortality (HR 1.44; 95% CI 1.20, 1.72) in participants with diabetes, whereas no significant association was observed in participants without diabetes (HR 0.97 [95% CI 0.92, 1.03] for CVD incidence; HR 1.05 [95% CI 0.90, 1.23] for CVD mortality; HR 1.02 [95% CI 0.96, 1.09] for all-cause mortality). Significant multiplicative and additive interactions were found between habitual calcium supplementation and diabetes status on risks of CVD events and mortality (all Pinteraction < 0.05). In contrast, no significant interactions were observed between dietary or serum calcium and diabetes status. CONCLUSIONS: Habitual use of calcium supplements was significantly associated with higher risk of CVD events and mortality in people with diabetes but not in people without diabetes. Further studies are needed to balance potentially adverse effects of calcium supplement against likely benefits, particularly among patients with diabetes. [ABSTRACT FROM AUTHOR]

ObjectiveTo examine determinants of racial/ethnic differences in diabetes incidence among postmenopausal women participating in the Women's Health Initiative.Research design and methodsData on race/ethnicity, baseline diabetes prevalence, and incident diabetes were obtained from 158,833 women recruited from 1993-1998 and followed through August 2009. The relationship between race/ethnicity, other potential risk factors, and the risk of incident diabetes was estimated using Cox proportional hazards models from which hazard ratios (HRs) and 95% CIs were computed.ResultsParticipants were aged 63 years on average at baseline. The racial/ethnic distribution was 84.1% non-Hispanic white, 9.2% non-Hispanic black, 4.1% Hispanic, and 2.6% Asian. After an average of 10.4 years of follow-up, compared with whites and adjusting for potential confounders, the HRs for incident diabetes were 1.55 for blacks (95% CI 1.47-1.63), 1.67 for Hispanics (1.54-1.81), and 1.86 for Asians (1.68-2.06). Whites, blacks, and Hispanics with all factors (i.e., weight, physical activity, dietary quality, and smoking) in the low-risk category had 60, 69, and 63% lower risk for incident diabetes. Although contributions of different risk factors varied slightly by race/ethnicity, most findings were similar across groups, and women who had both a healthy weight and were in the highest tertile of physical activity had less than one-third the risk of diabetes compared with obese and inactive women.ConclusionsDespite large racial/ethnic differences in diabetes incidence, most variability could be attributed to lifestyle factors. Our findings show that the majority of diabetes cases are preventable, and risk reduction strategies can be effectively applied to all racial/ethnic groups.

OBJECTIVE: Evidence is limited regarding the associations between vitamin D status and microvascular complications in individuals with type 2 diabetes (T2D), among whom vitamin D deficiency or insufficiency is particularly common. In this study we aimed to prospectively investigate the associations of serum 25-hydroxyvitamin D [25(OH)D] and vitamin D receptor (VDR) polymorphisms with risk of diabetic microvascular complications. RESEARCH DESIGN AND METHODS: This analysis included 14,709 participants with T2D who were free of microvascular complications from the UK Biobank. Incidence of diabetic microvascular complications was ascertained via electronic health records. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs. RESULTS: Median serum 25(OH)D concentration was 40.7 nmol/L (interquartile range 27.5, 56.4). During a median of 11.2 years of follow-up, 1,370 people developed diabetic microvascular complications. Compared with participants with 25(OH)D <25 nmol/L, individuals with 25(OH)D ≥75 nmol/L had a multivariable-adjusted HR of 0.65 (95% CI 0.51, 0.84) for composite diabetic microvascular complications, 0.62 (0.40, 0.95) for diabetic retinopathy, 0.56 (0.40, 0.79) for diabetic nephropathy, and 0.48 (0.26, 0.89) for diabetic neuropathy. In addition, in comparisons with participants with 25(OH)D <25 nmol/L and minor allele homozygotes (TT of rs1544410 and GG of rs731236), the multivariable-adjusted HRs of composite diabetic microvascular complications were 0.54 (0.38, 0.78) and 0.55 (0.38, 0.80) for participants with serum 25(OH)D ≥50 nmol/L and major allele homozygotes (CC and AA), respectively, although no significant interaction was observed. CONCLUSIONS: Higher serum 25(OH)D concentrations were significantly associated with lower risk of diabetic microvascular complications, including diabetic retinopathy, diabetic nephropathy, and diabetic neuropathy. Our findings suggest a potential beneficial role of maintaining adequate vitamin D status in the prevention of diabetic microvascular complications. [ABSTRACT FROM AUTHOR]

Objective: We examined lifestyle factors with midlife weight change according to history of gestational diabetes mellitus (GDM) in a large longitudinal female cohort.Research Design and Methods: In the Nurses' Health Study II, we categorized changes in lifestyle within 4-year periods and estimated their associations with concurrent changes in body weight (kilograms) among parous women after age 40 years by GDM history status (N = 54,062; 5.3% with a history of GDM) for the following: diet quality (Alternate Healthy Eating Index [AHEI]), leisure-time physical activity (PA), alcohol consumption, and smoking status.Results: Over a median follow-up of 13 years, average 4-year weight gain was 1.10 and 1.33 kg for women with and without prior GDM, respectively. Women with improved diet quality had favorable 4-year weight change, particularly those with a history of GDM (AHEI change [95% CI] from low to high -2.97 kg [-4.34, -1.60] vs. -1.19 kg [-1.41, -0.96] for GDM vs. non-GDM, respectively; P heterogeneity = 0.04). Increasing PA was associated with weight maintenance for GDM women only (PA increase [95% CI] from low to high 0.26 kg [-0.25, 0.77] vs. 0.90 kg [0.80, 1.01] for GDM vs. non-GDM, respectively; P heterogeneity = 0.02). For both GDM and non-GDM women, weight change did not differ significantly with change in alcohol consumption, while women who quit smoking had significant weight gain (4.38 kg for GDM and 3.85 kg for non-GDM).Conclusions: Improvements in diet quality and PA were related to less weight gain in midlife among parous women, and the benefit of such improvements on weight management was particularly pronounced among women with a history of GDM. [ABSTRACT FROM AUTHOR]