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Precision stratification of prognostic risk factors associated with outcomes in gestational diabetes mellitus: a systematic review.
Semnani-Azad, Z, Gaillard, R, Hughes, AE, Boyle, KE, Tobias, DK, , , Perng, W
Communications medicine. 2024;(1):9
Abstract
BACKGROUND The objective of this systematic review is to identify prognostic factors among women and their offspring affected by gestational diabetes mellitus (GDM), focusing on endpoints of cardiovascular disease (CVD) and type 2 diabetes (T2D) for women, and cardiometabolic profile for offspring. METHODS This review included studies published in English language from January 1st, 1990, through September 30th, 2021, that focused on the above outcomes of interest with respect to sociodemographic factors, lifestyle and behavioral characteristics, traditional clinical traits, and 'omics biomarkers in the mothers and offspring during the perinatal/postpartum periods and across the lifecourse. Studies that did not report associations of prognostic factors with outcomes of interest among GDM-exposed women or children were excluded. RESULTS Here, we identified 109 publications comprising 98 observational studies and 11 randomized-controlled trials. Findings indicate that GDM severity, maternal obesity, race/ethnicity, and unhealthy diet and physical activity levels predict T2D and CVD in women, and greater cardiometabolic risk in offspring. However, using the Diabetes Canada 2018 Clinical Practice Guidelines for studies, the level of evidence was low due to potential for confounding, reverse causation, and selection biases. CONCLUSIONS GDM pregnancies with greater severity, as well as those accompanied by maternal obesity, unhealthy diet, and low physical activity, as well as cases that occur among women who identify as racial/ethnic minorities are associated with worse cardiometabolic prognosis in mothers and offspring. However, given the low quality of evidence, prospective studies with detailed covariate data collection and high fidelity of follow-up are warranted.
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Second international consensus report on gaps and opportunities for the clinical translation of precision diabetes medicine.
Tobias, DK, Merino, J, Ahmad, A, Aiken, C, Benham, JL, Bodhini, D, Clark, AL, Colclough, K, Corcoy, R, Cromer, SJ, et al
Nature medicine. 2023;(10):2438-2457
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Abstract
Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine.
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Association of branched chain fatty acids with cardiometabolic disorders in humans: a systematic review.
Yehia, NA, Lai, KZH, Semnani-Azad, Z, Blanco Mejia, S, Bazinet, RP, Beaudry, JL, Hanley, AJ
Nutrition reviews. 2023;(2):180-190
Abstract
CONTEXT Despite advances in treatments for cardiometabolic disorders such as type 2 diabetes mellitus and obesity, the increasing frequency of these conditions is of major clinical and public health concern. Therefore, primary prevention including diet and lifestyle approaches continues to play a key role in risk reduction. Meta-analyses of prospective cohort studies have documented inverse associations of dairy consumption with the incidence of different cardiometabolic disorders. Dairy is the largest dietary contributor of branched chain fatty acids (BCFAs), which have been suggested to not only serve as biomarkers of dairy consumption but may also have bioactive properties contributing to reducing the risk of cardiometabolic outcomes. To date, however, the literature on this topic has not been systematically reviewed. OBJECTIVE The aim here was to report the results of a systematic review of the association of BCFAs with cardiometabolic disorders in humans. DATA SOURCES Search terms were developed and run through the Ovid MEDLINE, Ovid Embase, and the Cochrane Library databases. DATA EXTRACTION Articles were selected on the basis of prespecified inclusion criteria and assessed for risk of bias by independent reviewers. RESULTS Four studies (n = 2 cross sectional; n = 1 randomized feeding trial and n = 1 pre-post study) were identified. Two studies reported significant inverse associations between serum BCFAs and insulin resistance, triglycerides and/or body mass index. One study identified an inverse association between adipose tissue monomethyl BCFAs and skeletal muscle insulin resistance. In contrast, the randomized feeding trial reported no significant differences to stool BCFA concentrations or body mass index in obese participants following assignment to fruit-vegetable or whole-grain diet groups compared with a refined-grain control group. CONCLUSIONS Current evidence suggests beneficial associations of circulating BCFAs with cardiometabolic risk phenotypes, although data in human participants are limited, indicating that additional research is required. PROSPERO REGISTRATION NO CRD42021224975.
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Lifestyle Factors Associated with Circulating Very Long-Chain Saturated Fatty Acids in Humans: A Systematic Review of Observational Studies.
Lai, KZH, Yehia, NA, Semnani-Azad, Z, Mejia, SB, Boucher, BA, Malik, V, Bazinet, RP, Hanley, AJ
Advances in nutrition (Bethesda, Md.). 2023;(1):99-114
Abstract
Recent observational studies have documented inverse associations of circulating very long-chain saturated fatty acids (VLCSFAs), namely arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0), with cardiometabolic outcomes. In addition to their endogenous production, it has been suggested that dietary intake or an overall healthier lifestyle may influence VLCSFA concentrations; however, a systematic review of the modifiable lifestyle contributors to circulating VLCSFAs is lacking. Therefore, this review aimed to systematically assess the effects of diet, physical activity, and smoking on circulating VLCSFAs. Following registration on PROSPERO (International Prospective Register of Systematic Reviews) (ID: CRD42021233550), a systematic search of observational studies was conducted in MEDLINE, EMBASE, and The Cochrane databases up to February 2022. A total of 12 studies consisting of mostly cross-sectional analyses were included in this review. The majority of the studies documented the associations of dietary intake with total plasma or red blood cell VLCSFAs, in which a range of macronutrients and food groups were examined. Two cross-sectional analyses showed a consistent positive association between total fat and peanut intake with 22:0 and 24:0 and an inverse association between alcohol intake and 20:0 and 22:0. Furthermore, a moderate positive association between physical activity and 22:0 and 24:0 was observed. Lastly, there were conflicting results on the effects of smoking on VLCSFA. Although most studies had a low risk of bias; the findings of this review are limited by the bi-variate analyses presented in the majority of the included studies, therefore, the impact of confounding is unclear. In conclusion, although the current observational literature examining lifestyle determinants of VLCSFAs is limited, existing evidence suggests that circulating 22:0 and 24:0 may be influenced by higher total and saturated fat consumption and nut intake.
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ADA/EASD Precision Medicine in Diabetes Initiative: An International Perspective and Future Vision for Precision Medicine in Diabetes.
Nolan, JJ, Kahkoska, AR, Semnani-Azad, Z, Hivert, MF, Ji, L, Mohan, V, Eckel, RH, Philipson, LH, Rich, SS, Gruber, C, et al
Diabetes care. 2022;(2):261-266
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Metabolomic profile of combined healthy lifestyle behaviours in humans: A systematic review.
Kaspy, MS, Semnani-Azad, Z, Malik, VS, Jenkins, DJA, Hanley, AJ
Proteomics. 2022;(18):e2100388
Abstract
A combination of healthy lifestyle behaviours (i.e., regular physical activity, nutritious diet, no smoking, moderate alcohol, and healthy body mass) has been consistently associated with beneficial health outcomes including reduced risk of cardiometabolic diseases. Metabolomic profiles, characterized by distinct sets of biomarkers, have been described for healthy lifestyle behaviours individually and in combination. However, recent literature calls for systematic evaluation of these heterogenous data to identify potential clinical biomarkers relating to a combined healthy lifestyle. The objective was to systematically review existing literature on the metabolomic profile of combined healthy lifestyle behaviours. MEDLINE, EMBASE and Cochrane databases were searched through March 2022. Studies in humans outlining the metabolomic profile of a combination of two or more healthy lifestyle behaviours were included. Collectively, the metabolomic profile following regular adherence to combined healthy lifestyle behaviours points to a positive association with beneficial fatty acids and phosphocreatine, and inverse associations with triglycerides, trimethylamine N-oxide, and acylcarnitines. The findings suggest that a unique metabolomic profile is associated with combined healthy lifestyle behaviours. Additional research is warranted to further describe this metabolomic profile using targeted and untargeted metabolomic approaches along with uniform definitions of combined healthy lifestyle variables across populations.
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The association of soluble CD163, a novel biomarker of macrophage activation, with type 2 diabetes mellitus and its underlying physiological disorders: A systematic review.
Semnani-Azad, Z, Blanco Mejia, S, Connelly, PW, Bazinet, RP, Retnakaran, R, Jenkins, DJA, Harris, SB, Hanley, AJ
Obesity reviews : an official journal of the International Association for the Study of Obesity. 2021;(9):e13257
Abstract
This systematic review investigates the association of sCD163, a novel biomarker of macrophage activation, with type 2 diabetes mellitus (T2DM), insulin resistance, and beta-cell dysfunction. Sixteen studies (seven cross-sectional, two case-control, one nested case-control, three prospective cohort, and three experimental) were identified. Most studies demonstrated that elevated sCD163 concentrations were associated with increased insulin resistance. Cross-sectional, case-control, and nested case-control studies showed higher sCD163 in subjects with T2DM compared with healthy individuals. An 18-year follow-up prospective cohort study showed that elevated baseline sCD163 was a strong predictor of T2DM incidence. Prospective cohort studies demonstrated that baseline measures and longitudinal changes in sCD163 were positively associated with insulin resistance; however, associations with beta-cell function were inconsistent. Two experimental studies evaluated the relationship of sCD163 with T2DM and HOMA-IR after weight-reducing interventions. After very low-calorie diet treatments, sCD163 concentration declined significantly in patients with T2DM but was not associated with insulin resistance. Bariatric surgery did not significantly impact sCD163 levels. In a double-blind randomized controlled trial, resveratrol supplementation significantly reduced circulating sCD163 in T2DM patients. Current studies demonstrate the potential utility of sCD163 as an early biomarker of T2DM risk and highlight a potential mechanism linking obesity with T2DM onset.
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Changes in adiposity mediate the associations of diet quality with insulin sensitivity and beta-cell function.
Lai, KZH, Semnani-Azad, Z, Retnakaran, R, Harris, SB, Hanley, AJ
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2021;(11):3054-3063
Abstract
BACKGROUND AND AIMS To examine the mediating role of adiposity on the associations of diet quality with longitudinal changes in insulin sensitivity and beta-cell function. METHODS AND RESULTS Adults at-risk for type 2 diabetes (T2D) in the PROMISE cohort had 4 assessments over 9 years (n = 442). Alternate Healthy Eating Index (AHEI) scores were used to assess diet quality. Generalized Estimating Equations (GEE) evaluated the associations between the AHEI and longitudinal changes in insulin sensitivity (HOMA2-%S and ISI) and beta-cell function (IGI/HOMA-IR and ISSI-2). The proportion of the mediating effect of waist circumference changes was estimated using the difference method. In the primary longitudinal analysis, AHEI was positively associated with insulin sensitivity and beta-cell function over time (% difference per standard deviation increase of AHEI for HOMA2-%S (β = 11.0, 95%CI 5.43-17.0), ISI (β = 10.4, 95%CI 4.35-16.8), IGI/HOMA-IR (β = 7.12, 95%CI 0.98-13.6) and ISSI-2 (β = 4.38, 95%CI 1.05-7.80), all p < 0.05). There was no significant association between AHEI and dysglycemia incidence (OR = 0.95, 95%CI 0.77-1.17). Adjustments for longitudinal changes in waist circumference substantially attenuated all associations of AHEI with insulin sensitivity and beta-cell function. Mediation analysis indicated that waist circumference mediated 73%, 70%, 83% and 81% of the association between AHEI and HOMA2-%S, ISI, IGI/HOMA-IR, and ISSI-2, respectively (all p < 0.01). CONCLUSION In a Canadian population at-risk for T2D, AHEI score was positively associated with changes in insulin sensitivity and beta-cell function. These associations were substantially mediated by waist circumference, suggesting that changes in adiposity may represent an important pathway linking diet quality with risk phenotypes for T2D.
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The Macrophage Activation Marker Soluble CD163 is Longitudinally Associated With Insulin Sensitivity and β-cell Function.
Semnani-Azad, Z, Connelly, PW, Johnston, LW, Retnakaran, R, Harris, SB, Zinman, B, Hanley, AJ
The Journal of clinical endocrinology and metabolism. 2020;(3):e285-94
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Abstract
CONTEXT Chronic inflammation arising from adipose tissue macrophage (ATM) activation may be central in type 2 diabetes etiology. Our objective was to assess the longitudinal associations of soluble CD163 (sCD163), a novel biomarker of ATM activation, with insulin sensitivity, β-cell function, and dysglycemia in high-risk subjects. METHODS Adults at risk for type 2 diabetes in the Prospective Metabolism and Islet Cell Evaluation (PROMISE) study had 3 assessments over 6 years (n = 408). Levels of sCD163 were measured using fasting serum. Insulin sensitivity was assessed by HOMA2-%S and the Matsuda index (ISI). β-cell function was determined by insulinogenic index (IGI) over HOMA-IR and insulin secretion-sensitivity index-2 (ISSI-2). Incident dysglycemia was defined as the onset of impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes. Generalized estimating equations (GEE) evaluated longitudinal associations of sCD163 with insulin sensitivity, β-cell function, and incident dysglycemia adjusting for demographic and lifestyle covariates. Areas under receiver-operating-characteristic curve (AROC) tested whether sCD163 improved dysglycemia prediction in a clinical model. RESULTS Longitudinal analyses showed significant inverse associations between sCD163 and insulin sensitivity (% difference per standard deviation increase of sCD163 for HOMA2-%S (β = -7.01; 95% CI, -12.26 to -1.44) and ISI (β = -7.60; 95% CI, -11.09 to -3.97) and β-cell function (ISSI-2 (β = -4.67; 95 %CI, -8.59 to -0.58) and IGI/HOMA-IR (β = -8.75; 95% CI, -15.42 to -1.56)). Increased sCD163 was associated with greater risk for incident dysglycemia (odds ratio = 1.04; 95% CI, 1.02-1.06; P < 0.001). Adding sCD163 data to a model with clinical variables improved prediction of incident dysglycemia (AROC=0.6731 vs 0.638; P < 0.05). CONCLUSIONS sCD163 was longitudinally associated with core disorders that precede the onset of type 2 diabetes.
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Association of Major Food Sources of Fructose-Containing Sugars With Incident Metabolic Syndrome: A Systematic Review and Meta-analysis.
Semnani-Azad, Z, Khan, TA, Blanco Mejia, S, de Souza, RJ, Leiter, LA, Kendall, CWC, Hanley, AJ, Sievenpiper, JL
JAMA network open. 2020;3(7):e209993
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Plain language summary
Fructose is a type of sugar that has been implicated as a contributor to the development of metabolic syndrome (MetS), which is a condition where large waist circumference, high blood pressure and elevated blood lipid levels may all coexist. However, it remains unclear as to the role of fructose containing foods in the development of MetS. This systematic review and meta-analysis of 13 prospective cohort studies aimed to determine the association of several fructose containing foods and drinks with MetS. The results showed that sugary drinks containing fructose increased the risk of MetS, whereas no associations were found with mixed fruit juice, 100% fruit juice, honey, ice cream or confectionary. Interestingly fruit and yoghurt containing fructose decreased the risk of developing MetS. It was concluded that fructose containing food and drinks are not all equal in their biological effects. Sugary drinks increased the risk of developing MetS but yoghurt and fruit had a protective effect against development. Reasons for this could be due to a generally unhealthier lifestyle in those who consume sugary drinks or may be due to the increased protective effects associated with the vitamins and minerals in fruit and yoghurt. This study could be used by healthcare professionals to recommend a diet eliminating sugary drinks and containing regular fruit and yoghurt intake.
Abstract
Importance: Sugar-sweetened beverages (SSBs) are associated with increased risk of metabolic syndrome (MetS). However, the role of other important food sources of fructose-containing sugars in the development of MetS remains unclear. Objective: To examine the association of major food sources of fructose-containing sugars with incident MetS. Data Sources: MEDLINE, Embase, and Cochrane Library were searched from database inception to March 24, 2020, in addition to manual searches of reference lists from included studies using the following search terms: sugar-sweetened beverages, fruit drink, yogurt, metabolic syndrome, and prospective study. Study Selection: Inclusion criteria included prospective cohort studies of 1 year or longer that investigated the association of important food sources of fructose-containing sugars with incident MetS in participants free of MetS at the start of the study. Data Extraction and Synthesis: Study quality was assessed using the Newcastle-Ottawa Scale. Extreme quantile risk estimates for each food source with MetS incidence were pooled using a random-effects meta-analysis. Interstudy heterogeneity was assessed (Cochran Q statistic) and quantified (I2 statistic). Dose-response analyses were performed using a 1-stage linear mixed-effects model. The certainty of the evidence was assessed using GRADE (Grading of Recommendations, Assessment, Development, and Evaluation). Results were reported according to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) and Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. Main Outcomes and Measures: Pooled risk ratio (RR) of incident MetS (pairwise and dose response). Results: Thirteen prospective cohort studies (49 591 participants [median age, 51 years; range, 6-90 years]; 14 205 with MetS) that assessed 8 fructose-containing foods and MetS were included. An adverse linear dose-response association for SSBs (RR for 355 mL/d, 1.14; 95% CI, 1.05-1.23) and an L-shaped protective dose-response association for yogurt (RR for 85 g/d, 0.66; 95% CI, 0.58-0.76) and fruit (RR for 80 g/d, 0.82; 95% CI, 0.78-0.86) was found. Fruit juices (mixed and 100%) had a U-shaped dose-response association with protection at moderate doses (mixed fruit juice: RR for 125 mL/d, 0.58; 95% CI, 0.42-0.79; 100% fruit juice: RR for 125 mL/d, 0.77; 95% CI, 0.61-0.97). Honey, ice cream, and confectionary had no association with MetS incidence. The certainty of the evidence was moderate for SSBs, yogurt, fruit, mixed fruit juice, and 100% fruit juice and very low for all other food sources. Conclusions and Relevance: The findings of this meta-analysis suggest that the adverse association of SSBs with MetS does not extend to other food sources of fructose-containing sugars, with a protective association for yogurt and fruit throughout the dose range and for 100% fruit juice and mixed fruit juices at moderate doses. Therefore, current policies and guidelines on the need to limit sources of free sugars may need to be reexamined.