Magnesium (Mg) is known to exert diverse actions on cardiometabolic function; suboptimal Mg intake and status may contribute significantly to adverse metabolic and cardiovascular health. While type 2 ...diabetes mellitus (T2DM) is the most common cause of Mg depletion, research gaps exist regarding the potential influence of transient states of impaired glycemia, such as gestational diabetes, on subsequent Mg biomarkers or Mg-glycemic associations in affected mothers or their offspring. Further, whether or not diabetes is an important effect modifier of associations between Mg biomarkers and cardiovascular endpoints, such as arrhythmias, is unknown. It has long been observed, however, that the determination of Mg status is riddled with challenges, and no simple, rapid, and accurate test has emerged in subsequent decades. Plasma (pMg) and serum Mg (sMg) remain the most commonly used biomarkers clinically and in the literature; comparatively little is known about erythrocyte Mg (rMg) and cardiometabolic outcomes. The Canadian Community Health Survey (2004) revealed that 45% of males aged 30–50 years and a similar percentage of women had Mg intakes below the estimated average requirement (EAR); 65% of men over 71 years of age had Mg intake below the EAR. Subpopulations living in Canada report especially low Mg intakes — among aboriginal populations, such as the James Bay Cree from Mistissini, 72.6% of adult men and a similar percentage of women had Mg intakes below the EAR. Canadian Inuit adults experiencing food insecurity also consume Mg below recommended levels. The main objectives of this thesis were to (i) determine if gestational diabetes history prospectively influences Mg concentrations or associations between Mg and glycemic variables in mothers and offspring 15-years post-partum (Montreal cohort); (ii) to examine associations between sMg, rMg, and cardiovascular risk profiles in adults from 2 ethnically distinct, cross-sectional studies (Cree, Inuit) and evaluate the utility of rMg as a cardiovascular risk associate; and (iii) to estimate the risk of an arrhythmia associated with mortality as well as the risk of ventricular premature beats across the sMg concentration gradient, and assess potential effect modification by T2DM status (Cree). Secondary data analysis was conducted on data collected from 3 diverse studies: (i) Diabetic pregnancies: Longitudinal follow-up study of mother-offspring pairs (multiethnic Montreal cohort); (ii) Nituuchischaayihtitaau Aschii: A multi-community environment and health longitudinal study in Iiyiyiu Aschii (Cree survey); (iii) International Polar Year (IPY) Inuit Health Survey (Inuit survey). Associations between Mg biomarkers and endpoints were examined in multivariate linear and logistic regression models. It was found that a gestational diabetes history of 15 years prior was associated with reduced pMg in mothers (p = 0.002) and elevated pMg in teenage offspring (p = 0.002) relative to mother and offspring controls without gestational diabetes history. Associations between Mg status and some glycemic variables (fasting glucose, insulin, and insulin sensitivity) were stronger in mothers and offspring with gestational diabetes history than those without. In Cree adults without T2DM, sMg was inversely associated with fasting glucose (p = 0.001), in addition to cardiovascular variables such as hsCRP (p = 0.038) and carotid-intima media thickness (p = 0.044). rMg was significantly associated with adiposity in both Cree and Inuit (p < 0.001), but no associations between rMg and fasting glucose, insulin, hsCRP, blood pressure, nor carotid intima-media thickness were observed. In Cree, hypomagnesaemia (sMg <0.70 mmol/L) was associated with an increased prevalence of ventricular premature beats (p < 0.05). T2DM was a significant effect modifier of the association between sMg and risk of this arrhythmia (p < 0.05). Transient states of impaired glycemia (gestational diabetes) may be associated with low pMg and its associations with glycemic outcome variables in affected mothers and offspring 15 years post-partum. Unlike sMg or pMg, there is no current evidence that total rMg is significantly associated with a favourable cardiovascular risk profile or adds value to cardiometabolic risk assessment. Prevalence of ventricular premature beats is more common in Cree adults with hypomagnesaemia and T2DM. Further investigations evaluating the potential utility and predictive value of pMg and sMg as markers of cardiometabolic risk are warranted.
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DOBA, FSPLJ, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The metabolic effects of omega-6 polyunsaturated fatty acids (PUFAs) remain contentious, and little evidence is available regarding their potential role in primary prevention of type 2 diabetes. We ...aimed to assess the associations of linoleic acid and arachidonic acid biomarkers with incident type 2 diabetes.
We did a pooled analysis of new, harmonised, individual-level analyses for the biomarkers linoleic acid and its metabolite arachidonic acid and incident type 2 diabetes. We analysed data from 20 prospective cohort studies from ten countries (Iceland, the Netherlands, the USA, Taiwan, the UK, Germany, Finland, Australia, Sweden, and France), with biomarkers sampled between 1970 and 2010. Participants included in the analyses were aged 18 years or older and had data available for linoleic acid and arachidonic acid biomarkers at baseline. We excluded participants with type 2 diabetes at baseline. The main outcome was the association between omega-6 PUFA biomarkers and incident type 2 diabetes. We assessed the relative risk of type 2 diabetes prospectively for each cohort and lipid compartment separately using a prespecified analytic plan for exposures, covariates, effect modifiers, and analysis, and the findings were then pooled using inverse-variance weighted meta-analysis.
Participants were 39 740 adults, aged (range of cohort means) 49-76 years with a BMI (range of cohort means) of 23·3-28·4 kg/m
, who did not have type 2 diabetes at baseline. During a follow-up of 366 073 person-years, we identified 4347 cases of incident type 2 diabetes. In multivariable-adjusted pooled analyses, higher proportions of linoleic acid biomarkers as percentages of total fatty acid were associated with a lower risk of type 2 diabetes overall (risk ratio RR per interquintile range 0·65, 95% CI 0·60-0·72, p<0·0001; I
=53·9%, p
=0·002). The associations between linoleic acid biomarkers and type 2 diabetes were generally similar in different lipid compartments, including phospholipids, plasma, cholesterol esters, and adipose tissue. Levels of arachidonic acid biomarker were not significantly associated with type 2 diabetes risk overall (RR per interquintile range 0·96, 95% CI 0·88-1·05; p=0·38; I
=63·0%, p
<0·0001). The associations between linoleic acid and arachidonic acid biomarkers and the risk of type 2 diabetes were not significantly modified by any prespecified potential sources of heterogeneity (ie, age, BMI, sex, race, aspirin use, omega-3 PUFA levels, or variants of the FADS gene; all p
≥0·13).
Findings suggest that linoleic acid has long-term benefits for the prevention of type 2 diabetes and that arachidonic acid is not harmful.
Funders are shown in the appendix.
IMPORTANCE: The role of ω-3 polyunsaturated fatty acids for primary prevention of coronary heart disease (CHD) remains controversial. Most prior longitudinal studies evaluated self-reported ...consumption rather than biomarkers. OBJECTIVE: To evaluate biomarkers of seafood-derived eicosapentaenoic acid (EPA; 20:5ω-3), docosapentaenoic acid (DPA; 22:5ω-3), and docosahexaenoic acid (DHA; 22:6ω-3) and plant-derived α-linolenic acid (ALA; 18:3ω-3) for incident CHD. DATA SOURCES: A global consortium of 19 studies identified by November 2014. STUDY SELECTION: Available prospective (cohort, nested case-control) or retrospective studies with circulating or tissue ω-3 biomarkers and ascertained CHD. DATA EXTRACTION AND SYNTHESIS: Each study conducted standardized, individual-level analysis using harmonized models, exposures, outcomes, and covariates. Findings were centrally pooled using random-effects meta-analysis. Heterogeneity was examined by age, sex, race, diabetes, statins, aspirin, ω-6 levels, and FADS desaturase genes. MAIN OUTCOMES AND MEASURES: Incident total CHD, fatal CHD, and nonfatal myocardial infarction (MI). RESULTS: The 19 studies comprised 16 countries, 45 637 unique individuals, and 7973 total CHD, 2781 fatal CHD, and 7157 nonfatal MI events, with ω-3 measures in total plasma, phospholipids, cholesterol esters, and adipose tissue. Median age at baseline was 59 years (range, 18-97 years), and 28 660 (62.8%) were male. In continuous (per 1-SD increase) multivariable-adjusted analyses, the ω-3 biomarkers ALA, DPA, and DHA were associated with a lower risk of fatal CHD, with relative risks (RRs) of 0.91 (95% CI, 0.84-0.98) for ALA, 0.90 (95% CI, 0.85-0.96) for DPA, and 0.90 (95% CI, 0.84-0.96) for DHA. Although DPA was associated with a lower risk of total CHD (RR, 0.94; 95% CI, 0.90-0.99), ALA (RR, 1.00; 95% CI, 0.95-1.05), EPA (RR, 0.94; 95% CI, 0.87-1.02), and DHA (RR, 0.95; 95% CI, 0.91-1.00) were not. Significant associations with nonfatal MI were not evident per 1 SD. Across quintiles, lower risk of nonfatal MI was evident with EPA (RR, 0.71; 95% CI, 0.56-0.90) and ALA (RR, 0.87; 95% CI, 0.78-0.97), and lower risk of fatal CHD was evident with DPA (RR, 0.76; 95% CI, 0.65-0.90) and DHA (RR, 0.77; 95% CI, 0.64-0.89). Associations appeared generally stronger in phospholipids and total plasma. Restricted cubic splines did not identify evidence of nonlinearity in dose responses. CONCLUSIONS AND RELEVANCE: On the basis of available studies of free-living populations globally, biomarker concentrations of seafood and plant-derived ω-3 fatty acids are associated with a lower incidence of fatal CHD.
Abstract Objectives The goal of this study was to determine the relative contribution of major lifestyle factors on the development of heart failure (HF) in older adults. Background HF incurs high ...morbidity, mortality, and health care costs among adults ≥65 years of age, which is the most rapidly growing segment of the U.S. population. Methods We prospectively investigated separate and combined associations of lifestyle risk factors with incident HF (1,380 cases) over 21.5 years among 4,490 men and women in the Cardiovascular Health Study, which is a community-based cohort of older adults. Lifestyle factors included 4 dietary patterns (Alternative Healthy Eating Index, Dietary Approaches to Stop Hypertension, an American Heart Association 2020 dietary goals score, and a Biologic pattern, which was constructed using previous knowledge of cardiovascular disease dietary risk factors), 4 physical activity metrics (exercise intensity, walking pace, energy expended in leisure activity, and walking distance), alcohol intake, smoking, and obesity. Results No dietary pattern was associated with developing HF (p > 0.05). Walking pace and leisure activity were associated with a 26% and 22% lower risk of HF, respectively (pace >3 mph vs. <2 mph; hazard ratio HR: 0.74; 95% confidence interval CI: 0.63 to 0.86; leisure activity ≥845 kcal/week vs. <845 kcal/week; HR: 0.78; 95% CI: 0.69 to 0.87). Modest alcohol intake, maintaining a body mass index <30 kg/m2 , and not smoking were also independently associated with a lower risk of HF. Participants with ≥4 healthy lifestyle factors had a 45% (HR: 0.55; 95% CI: 0.42 to 0.74) lower risk of HF. Heterogeneity by age, sex, cardiovascular disease, hypertension medication use, and diabetes was not observed. Conclusions Among older U.S. adults, physical activity, modest alcohol intake, avoiding obesity, and not smoking, but not dietary patterns, were associated with a lower risk of HF.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Epidemiological studies report inverse associations between blood vitamin D, as measured by 25-hydroxyvitamin D 25(OH)D concentrations, and insulin resistance (IR) among predominantly overweight ...individuals. In a cross-sectional survey of 5 Cree communities in Quebec, Canada, we determined if 25(OH)D is associated with IR and β-cell function in a largely obese, ethnic minority at high risk of developing type 2 diabetes. A total of 510 participants (=18 y) without type 1 or type 2 diabetes, assessed for serum 25(OH)D, fasting plasma glucose and insulin, and anthropometric and lifestyle variables, were included in the analyses. Multivariable linear regressions adjusted for covariates were performed for homeostasis model assessment of IR (HOMA-IR) and β-cell function (HOMA-B) in relation to serum 25(OH)D. Serum 25(OH)D (per 10 nmol/L increment) was inversely associated with HOMA-IR (β = -0.005; SE = 0.002; P = 0.004) and HOMA-B (β = -0.004; SE = 0.002;P = 0.006) in models adjusted for age, sex, physical activity, education, alcohol consumption, and smoking. When further adjusted for BMI, associations were no longer significant for either HOMA-IR (β = 0.001, SE = 0.002,P = 0.572) or HOMA-B(β = 0.001, SE = 0.001,P = 0.498). The modest inverse associations between 25(OH)D and IR reported previously were not observed in this population after adjusting for adiposity. Future longitudinal studies investigating the interrelationship among 25(OH)D, adiposity, and the risk of developing metabolic syndrome and type 2 diabetes are warranted.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
. The strongest locus which associated with type 2 diabetes (T2D) by the common variant rs7903146 is the transcription factor 7-like 2 gene (
). We aimed to quantify the interaction of diet/lifestyle ...interventions and the genetic effect of
rs7903146 on glycemic traits, body weight, or waist circumference in overweight or obese adults in several randomized controlled trials (RCTs).
. From October 2016 to May 2018, a large collaborative analysis was performed by pooling individual-participant data from 7 RCTs. These RCTs reported changes in glycemic control and adiposity of the variant rs7903146 after dietary/lifestyle-related interventions in overweight or obese adults. Gene treatment interaction models which used the genetic effect encoded by the allele dose and common covariates were applicable to individual participant data in all studies.
. In the joint analysis, a total of 7 eligible RCTs were included (
). Importantly, we observed a significant effect modification of diet/lifestyle-related interventions on the
variant rs7903146 and changes in fasting glucose. Compared with the control group, diet/lifestyle interventions were related to lower fasting glucose by -3.06 (95% CI, -5.77 to -0.36) mg/dL (test for heterogeneity and overall effect:
,
;
,
) per one copy of the
T risk allele. Furthermore, regardless of genetic risk, diet/lifestyle interventions were associated with lower waist circumference. However, there was no significant change for diet/lifestyle interventions in other glycemic control and adiposity traits per one copy of
risk allele.
. Our findings suggest that carrying the
T risk allele may have a modestly greater benefit for specific diet/lifestyle interventions to improve the control of fasting glucose in overweight or obese adults.
Abstract only Introduction: The role of magnesium (Mg) in blood pressure (BP) is controversial, due to inconsistent results from prior individual trials or systematic reviews and meta-analyses. ...Hypothesis: We aimed to quantify the effect of oral Mg supplementation on systolic and diastolic BP by synthesizing available evidence from randomized double-blinded placebo-controlled trials. We also examined whether changes in BP were related to elevation in serum Mg levels by Mg supplementation. Methods: We searched all trials of oral Mg supplementation among healthy or hypertensive adults published before February 1, 2015 from databases of MEDLINE and EMBASE. A random-effects meta-analysis was performed to estimate weighted mean differences (WMDs) and 95% confidence intervals (CIs) of BP changes. The possible heterogeneity between studies were explored by subgroup analyses. We used restricted cubic spline curves to depict time- and dose-responses of BP in relation to changes of serum Mg levels. Results: In total, 33 eligible trials involving 2,500 participants were included. Mg supplementation at a median dose of 368 mg/day elemental Mg for a median duration of 3 months led to significantly reduced supine BPs by 2.08 mmHg (95% CI: 0.49, 3.68) for systolic BP and 1.83 mmHg (95% CI: 0.77, 2.90) for diastolic BP compared with the placebo. Overall, Mg supplementation significantly increased serum Mg concentrations by 0.05 mmol/L (95% CI: 0.03, 0.07 mmol/L). Our time- and dose-response analyses showed that Mg supplementation with 200 mg/day for 1 month was sufficient to significantly raise serum Mg and lower supine BPs (all P-values < 0.0001). However, higher doses (≥ 300 mg/day) and longer durations (≥ 2 months) were needed to achieve maximal effects. On average, per 0.1 mmol/L increment in serum Mg was associated with a supine DBP reduction of 2.26 mmHg (95% CI: 0.27, 4.26 mmHg), while the linear or curvilinear relationship with supine SBP was non-significant. In addition, there were non-significant changes in standing BPs (all P-values > 0.05). Conclusions: Our meta-analysis showed that Mg supplementation significantly lowered supine BPs which were significantly related with elevated serum Mg levels. Our findings support an antihypertensive effect of Mg, although future large well-designed randomized controlled trials with longer follow-up, selection of participants with low Mg levels, and ambulatory BP monitoring are warranted.
Gestational diabetes mellitus (GDM) and low magnesium (Mg) intake and status are associated with an increased risk of type 2 diabetes. However, Mg homeostasis may be modified by GDM. We sought to ...determine if a history of GDM prospectively modifies associations between Mg and glycemic variables in mothers and their offspring.
Plasma and dietary Mg, anthropometric, lifestyle and glycemic variables were assessed in mothers affected by GDM during 1989-1990, a comparative group of normoglycemic women, pregnant during the same time period, and the 15-year-old, nondiabetic daughters of affected and unaffected pregnancies (n = 332). Multivariate regression analyses evaluated the cross-sectional association between plasma and dietary Mg with glycemic variables in mothers and daughters.
Plasma Mg was lower in mothers with a history of GDM in comparison to control mothers after adjustment for current type 2 diabetes, race and body mass index (0.90 ± 0.01 versus 0.96 ± 0.01 mmol/L; p = 0.002). Plasma Mg was significantly associated with insulin sensitivity and was inversely associated with fasting insulin in GDM mothers only (p<0.05). Plasma and dietary Mg were significantly inversely associated with glycated hemoglobin and fasting glucose, respectively, in nondiabetic teenage daughters. For fasting glucose, plasma Mg was inversely associated in GDM-born daughters only.
Associations between plasma Mg and some glycemic variables may be stronger in mothers and offspring with a history of GDM.
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