Background: Globally, 1 in 11 adults has diabetes mellitus, and most of these cases are type 2 diabetes (T2D). The risk of T2D is influenced by many factors, including diet. The synthesis of long-chain n-6 polyunsaturated fatty acids (LC n-6 PUFA) has been posited as a risk factor for T2D; however, its causal role is uncertain. Aim: To test the causal effect of LC n-6 PUFA synthesis on insulin resistance and transgenerational T2D risk in a large cohort of men and women. Methods: Two-sample mendelian randomization (MR) was conducted to evaluate the effect of low or high levels of LC n-6 PUFA synthesis on glycemia and development of T2D in the UK Biobank (n = 463,010) and Meta-Analysis of Glucose-and Insulin-Related Traits Consortium (MAGIC; n = 5,130) cohorts. The increased likelihood of a predisposition to low or high LC n-6 PUFA synthesis and the risk of T2D was also investigated using the participants' siblings and parents. In MR-Base, 4 genetic variants associated with LC n-6 PUFA synthesis were found (p < 10-8). After pruning, 1 variant (rs174547) on the FADS1 gene was retained. Results: Lower LC n-6 PUFA synthesis and abundance (per % unit decrease) are associated with small reductions in the insulin disposition index (-0.038 ± 0.012 mM-1 ; p = 0.002) within MAGIC. In the UK Biobank, we report negligible effects of low n-6 PUFA synthesis on the odds of T2D (OR < 1%; p < 0.05). Additionally, reduced LC n-6 PUFA synthesis does not appear to be a contributor to familial T2D risk. No significant association was observed between LC n-6 PUFA synthesis and BMI. Conclusion: In a primarily white European population, LC n-6 PUFA synthesis is not a major contributor to T2D risk.
Background Gestational Diabetes Mellitus (GDM) is the most common global pregnancy complication; however, prevalence varies substantially between ethnicities with South Asians (SA) experiencing up to 3-times the risk of the disease compared to white Europeans (WEs). Factors driving this discrepancy are unclear, although the metabolome is of great interest as GDM is known to be characterised by metabolic dysregulation. Objectives This primary aim was to characterise and compare the metabolic profiles of GDM in SA and WE women (at < 28 weeks’ gestation) from the Born in Bradford (BIB) prospective birth cohort in the UK. Methods 146 fasting serum metabolites, from 2668 pregnant WE and 2671 pregnant South Asian (SA) women (average BMI 26.2 kg/m2, average age 27.3 years) were analysed using partial least squares discriminatory analyses to characterise GDM status. Linear associations between metabolite values and post-oral glucose tolerance test measures of dysglycemia (fasting glucose and 2-hour post glucose) were also examined. Results Seven metabolites associated with GDM status in both ethnicities (variable importance in projection (VIP) ≥1), while 6 additional metabolites associated with GDM only in WE women. Unique metabolic profiles were observed in healthy weight women who later developed GDM, with distinct metabolite patterns identified by ethnicity and BMI status. Of the metabolite values analysed in relation to dysglycemia, lactate, histidine, apolipoprotein A1, HDL cholesterol, HDL2 cholesterol associated with decreased glucose concentration, while DHA and the diameter of very low-density lipoprotein particles (nm) associated with increased glucose concertation in WE women; while in SAs albumin alone associated with decreased glucose concentration. Conclusions This study shows that the metabolic risk profile for GDM differs between WE and SA women enrolled in BiB the UK. This suggests that aetiology of the disease differs between ethnic groups and that ethnic-appropriate prevention strategies may be beneficial.
Globally, one in seven pregnant women are diagnosed with gestational diabetes mellitus (GDM), conferring short- and long-term health risks to both mother and child. While dietary prevention strategies are common in clinical practice, their effectiveness in different ethnicities is uncertain. To better inform prevention strategies, here the effects of unhealthy and healthy diets on GDM risk within distinct ethnic or cultural populations and geographic regions were evaluated and summarised. Pubmed, Scopus, Cochrane and OVID were systematically searched to identify randomised controlled trials (RCTs) and observational studies that investigated diet and GDM. A grouped analysis of common ‘healthy’ and ‘unhealthy’ diets was performed first, before analysing individual dietary patterns (e.g., prudent, Mediterranean). Random effect models and dose response analyses were performed where possible. PROSPERO (CRD42019140873). Thirty-eight publications provided information on 5 population groups: white European (WE), Asian, Iranian, Mediterranean and Australian. No associations were identified between healthy diets and GDM incidence in RCTs in any population. However, when synthesizing observational studies, healthy diets reduced odds of GDM by 23% (95% CI: 0.70–0.89, p<0.001, I2 = 75%), while unhealthy diets increased odds of GDM by 61% (95% CI: 1.41–1.81, p<0.0001, I2 = 0%) in WE women. No evidence of consistent effects in other populations were observed, even when adequately powered. Diet consistently associated with GDM risk in WEs but not in other populations. Heterogenous use and reporting of ethnically and culturally appropriate diets and dietary assessment tools, particularly in RCTs, raises uncertainty regarding the lack of association found in non-WE populations. Future studies require the use of culturally appropriate tools to confidently evaluate dietary and metabolic mediators of GDM and inform culturally-specific dietary prevention strategies.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.