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Association of omega 3 polyunsaturated fatty acids with incident chronic kidney disease: pooled analysis of 19 cohorts.
Ong, KL, Marklund, M, Huang, L, Rye, KA, Hui, N, Pan, XF, Rebholz, CM, Kim, H, Steffen, LM, van Westing, AC, et al
BMJ (Clinical research ed.). 2023;:e072909
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Abstract
OBJECTIVE To assess the prospective associations of circulating levels of omega 3 polyunsaturated fatty acid (n-3 PUFA) biomarkers (including plant derived α linolenic acid and seafood derived eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid) with incident chronic kidney disease (CKD). DESIGN Pooled analysis. DATA SOURCES A consortium of 19 studies from 12 countries identified up to May 2020. STUDY SELECTION Prospective studies with measured n-3 PUFA biomarker data and incident CKD based on estimated glomerular filtration rate. DATA EXTRACTION AND SYNTHESIS Each participating cohort conducted de novo analysis with prespecified and consistent exposures, outcomes, covariates, and models. The results were pooled across cohorts using inverse variance weighted meta-analysis. MAIN OUTCOME MEASURES Primary outcome of incident CKD was defined as new onset estimated glomerular filtration rate <60 mL/min/1.73 m2. In a sensitivity analysis, incident CKD was defined as new onset estimated glomerular filtration rate <60 mL/min/1.73 m2 and <75% of baseline rate. RESULTS 25 570 participants were included in the primary outcome analysis and 4944 (19.3%) developed incident CKD during follow-up (weighted median 11.3 years). In multivariable adjusted models, higher levels of total seafood n-3 PUFAs were associated with a lower incident CKD risk (relative risk per interquintile range 0.92, 95% confidence interval 0.86 to 0.98; P=0.009, I2=9.9%). In categorical analyses, participants with total seafood n-3 PUFA level in the highest fifth had 13% lower risk of incident CKD compared with those in the lowest fifth (0.87, 0.80 to 0.96; P=0.005, I2=0.0%). Plant derived α linolenic acid levels were not associated with incident CKD (1.00, 0.94 to 1.06; P=0.94, I2=5.8%). Similar results were obtained in the sensitivity analysis. The association appeared consistent across subgroups by age (≥60 v <60 years), estimated glomerular filtration rate (60-89 v ≥90 mL/min/1.73 m2), hypertension, diabetes, and coronary heart disease at baseline. CONCLUSIONS Higher seafood derived n-3 PUFA levels were associated with lower risk of incident CKD, although this association was not found for plant derived n-3 PUFAs. These results support a favourable role for seafood derived n-3 PUFAs in preventing CKD.
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Lifestyle Intervention Guided by Group and Internet-Based Counseling in the T2D-GENE Trial Supports Its Applicability and Feasibility.
Schwab, U, Lankinen, M, Uusitupa, M, Laakso, M
Nutrients. 2023;(7)
Abstract
Type 2 diabetes (T2D) can be prevented or postponed by lifestyle modifications as shown by previous intervention studies. In most of these studies, participants have received resource-demanding individual counseling. In the 3-year T2D-GENE trial with lifestyle intervention, we investigated whether a less resource-demanding form of group and internet-based counseling is feasible and effective in preventing T2D in people with an increased risk for T2D. Altogether, 628 middle-aged to elderly men either with a high number or low number of T2D risk alleles were recruited. Five to seven group sessions were organized during the intervention, in addition to information and activities delivered via the web portal, and weekly monitoring of body weight and physical activity. Four-day food records with personal feedback were documented five times during the study. Of the 549 participants completing the study, over 90% participated in the group sessions and kept the food records. The four self-feedback tasks delivered during the second and the third years of the study were completed by 80-89% of the participants. In conclusion, a group and web portal-based lifestyle intervention is applicable for middle-aged to elderly men as a lifestyle modification aiming to prevent T2D.
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Type 2 Diabetes Prevention Programs-From Proof-of-Concept Trials to National Intervention and Beyond.
Tuomilehto, J, Uusitupa, M, Gregg, EW, Lindström, J
Journal of clinical medicine. 2023;(5)
Abstract
The prevention of type 2 diabetes (T2D) in high-risk people with lifestyle interventions has been demonstrated by several randomized controlled trials. The intervention effect has sustained up to 20 years in post-trial monitoring of T2D incidence. In 2000, Finland launched the national T2D prevention plan. For screening for high T2D risk, the non-laboratory Finnish Diabetes Risk Score was developed and widely used, also in other countries. The incidence of drug-treated T2D has decreased steadily since 2010. The US congress authorized public funding for a national diabetes prevention program (NDPP) in 2010. It was built around a 16-visit program that relies on referral from primary care and self-referral of persons with either prediabetes or by a diabetes risk test. The program uses a train-the-trainer program. In 2015 the program started the inclusion of online programs. There has been limited implementation of nationwide T2D prevention programs in other countries. Despite the convincing results from RCTs in China and India, no translation to the national level was introduced there. T2D prevention efforts in low-and middle-income countries are still limited, but results have been promising. Barriers to efficient interventions are greater in these countries than in high-income countries, where many barriers also exist. Health disparities by socioeconomic status exist for T2D and its risk factors and form a challenge for preventive interventions. It seems that a stronger commitment to T2D prevention is needed, such as the successful WHO Framework Convention on Tobacco Control, which legally binds the countries to act.
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The effect of vitamin D3 supplementation on atrial fibrillation in generally healthy men and women: The Finnish Vitamin D Trial.
Virtanen, JK, Hantunen, S, Lamberg-Allardt, C, Manson, JE, Nurmi, T, Uusitupa, M, Voutilainen, A, Tuomainen, TP
American heart journal. 2023;:177-182
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Abstract
Atrial fibrillation is a common cardiac arrhythmia with high morbidity risk. Observational studies suggest that vitamin D deficiency is associated with higher atrial fibrillation risk but there is limited evidence whether vitamin D supplementation could affect the risk. In these post hoc analyses from the Finnish Vitamin D Trial, we compared the incidence of atrial fibrillation with 5-year supplementation of vitamin D3 (1600 IU/d or 3200 IU/d) vs placebo. CLINICAL TRIAL REGISTRY NUMBER ClinicalTrials.gov: NCT01463813, https://clinicaltrials.gov/ct2/show/NCT01463813.
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Combination of Multiple Low-Risk Lifestyle Behaviors and Incident Type 2 Diabetes: A Systematic Review and Dose-Response Meta-analysis of Prospective Cohort Studies.
Khan, TA, Field, D, Chen, V, Ahmad, S, Mejia, SB, Kahleová, H, Rahelić, D, Salas-Salvadó, J, Leiter, LA, Uusitupa, M, et al
Diabetes care. 2023;(3):643-656
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OBJECTIVE Combined low-risk lifestyle behaviors (LRLBs) have been associated with a reduction in type 2 diabetes risk. This relationship has not been systematically quantified. RESEARCH DESIGN AND METHODS A systematic review and meta-analysis was conducted to assess the association of combined LRLBs with type 2 diabetes. Databases were searched up to September 2022. Prospective cohort studies reporting the association between a minimum of three combined LRLBs (including healthy diet) with incident type 2 diabetes were included. Independent reviewers extracted data and assessed study quality. Risk estimates of extreme comparisons were pooled using a random-effects model. Global dose-response meta-analysis (DRM) for maximum adherence was estimated using a one-stage linear mixed model. The certainty of the evidence was assessed using GRADE (Grading of Recommendations, Assessment, Development and Evaluations). RESULTS Thirty cohort comparisons (n = 1,693,753) involving 75,669 incident type 2 diabetes cases were included. LRLBs, with author-defined ranges, were healthy body weight, healthy diet, regular exercise, smoking abstinence or cessation, and light alcohol consumption. LRLBs were associated with 80% lower risk of type 2 diabetes (relative risk [RR] 0.20; 95% CI 0.17-0.23), comparing the highest with lowest adherence. Global DRM for maximum adherence to all five LRLBs reached 85% protection (RR 0.15; 95% CI 0.12-0.18). The overall certainty of the evidence was graded as high. CONCLUSIONS There is a very good indication that a combination of LRLBs that includes maintaining a healthy bodyweight, healthy diet, regular exercise, smoking abstinence or cessation, and light alcohol consumption is associated with a lower risk of incident type 2 diabetes.
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Not all very-low-carbohydrate diets are created equal. Reply to Conte C, Camajani E, Lai A, Caprio M [letter].
Reynolds, AN, Kahleova, H, Uusitupa, M, Hermansen, K, Aas, AM, Schwab, U, Lean, MEJ, Pfeiffer, A, Salas-Salvadó, J, Mann, JI
Diabetologia. 2023;(9):1754-1755
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Eating behavior dimensions and 9-year weight loss maintenance: a sub-study of the Finnish Diabetes prevention study.
Salmela, J, Konttinen, H, Lappalainen, R, Muotka, J, Antikainen, A, Lindström, J, Tuomilehto, J, Uusitupa, M, Karhunen, L
International journal of obesity (2005). 2023;(7):564-573
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BACKGROUND Behavioral processes through which lifestyle interventions influence risk factors for type 2 diabetes (T2DM), e.g., body weight, are not well-understood. We examined whether changes in psychological dimensions of eating behavior during the first year of lifestyle intervention would mediate the effects of intervention on body weight during a 9-year period. METHODS Middle-aged participants (38 men, 60 women) with overweight and impaired glucose tolerance (IGT) were randomized to an intensive, individualized lifestyle intervention group (n = 51) or a control group (n = 47). At baseline and annually thereafter until nine years body weight was measured and the Three Factor Eating Questionnaire assessing cognitive restraint of eating with flexible and rigid components, disinhibition and susceptibility to hunger was completed. This was a sub-study of the Finnish Diabetes Prevention Study, conducted in Kuopio research center. RESULTS During the first year of the intervention total cognitive (4.6 vs. 1.7 scores; p < 0.001), flexible (1.7 vs. 0.9; p = 0.018) and rigid (1.6 vs. 0.5; p = 0.001) restraint of eating increased, and body weight decreased (-5.2 vs. -1.2 kg; p < 0.001) more in the intervention group compared with the control group. The difference between the groups remained significant up to nine years regarding total (2.6 vs. 0.1 scores; p = 0.002) and rigid restraint (1.0 vs. 0.4; p = 0.004), and weight loss (-3.0 vs. 0.1 kg; p = 0.046). The first-year increases in total, flexible and rigid restraint statistically mediated the impact of intervention on weight loss during the 9-year study period. CONCLUSIONS Lifestyle intervention with intensive and individually tailored, professional counselling had long-lasting effects on cognitive restraint of eating and body weight in middle-aged participants with overweight and IGT. The mediation analyses suggest that early phase increase in cognitive restraint could have a role in long-term weight loss maintenance. This is important because long-term weight loss maintenance has various health benefits, including reduced risk of T2DM.
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Nordic dietary patterns and cardiometabolic outcomes: a systematic review and meta-analysis of prospective cohort studies and randomised controlled trials.
Massara, P, Zurbau, A, Glenn, AJ, Chiavaroli, L, Khan, TA, Viguiliouk, E, Mejia, SB, Comelli, EM, Chen, V, Schwab, U, et al
Diabetologia. 2022;65(12):2011-2031
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Plain language summary
Dietary patterns high in plant foods such as the Mediterranean diet, Dietary Approaches for Stopping Hypertension (DASH), Portfolio and healthy vegetarian are associated with a lower risk of cardio vascular disease (CVD) and certain cardiometabolic risk factors in adults with and without diabetes. In Northern European countries it may be more difficult to apply these dietary principals due to availability and cost of specific foods. Nordic dietary patterns include foods such as rye, oats and barley, berries and temperate fruits like apples and pears, vegetables (especially root and cruciferous vegetables), legumes, fish/shellfish, nuts and canola oil/rapeseed oil and low-fat dairy foods. The benefits of Nordic dietary patterns have been recognised but to update the clinical practice guidelines for the European Association for the Study of Diabetes (EASD), a systematic review and meta-analysis was commissioned. 15 cohort studies and 6 RCTs were included. Adopting Nordic dietary patterns is associated with small important reductions in the risk of major CVD outcomes and diabetes. These are supported by similar reductions in LDL-cholesterol and other cardiometabolic risk factors. The available evidence provides a generally good indication of the likely benefits of Nordic dietary patterns in people with or at risk for diabetes.
Abstract
AIMS/HYPOTHESIS Nordic dietary patterns that are high in healthy traditional Nordic foods may have a role in the prevention and management of diabetes. To inform the update of the EASD clinical practice guidelines for nutrition therapy, we conducted a systematic review and meta-analysis of Nordic dietary patterns and cardiometabolic outcomes. METHODS We searched MEDLINE, EMBASE and The Cochrane Library from inception to 9 March 2021. We included prospective cohort studies and RCTs with a follow-up of ≥1 year and ≥3 weeks, respectively. Two independent reviewers extracted relevant data and assessed the risk of bias (Newcastle-Ottawa Scale and Cochrane risk of bias tool). The primary outcome was total CVD incidence in the prospective cohort studies and LDL-cholesterol in the RCTs. Secondary outcomes in the prospective cohort studies were CVD mortality, CHD incidence and mortality, stroke incidence and mortality, and type 2 diabetes incidence; in the RCTs, secondary outcomes were other established lipid targets (non-HDL-cholesterol, apolipoprotein B, HDL-cholesterol, triglycerides), markers of glycaemic control (HbA1c, fasting glucose, fasting insulin), adiposity (body weight, BMI, waist circumference) and inflammation (C-reactive protein), and blood pressure (systolic and diastolic blood pressure). The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach was used to assess the certainty of the evidence. RESULTS We included 15 unique prospective cohort studies (n=1,057,176, with 41,708 cardiovascular events and 13,121 diabetes cases) of people with diabetes for the assessment of cardiovascular outcomes or people without diabetes for the assessment of diabetes incidence, and six RCTs (n=717) in people with one or more risk factor for diabetes. In the prospective cohort studies, higher adherence to Nordic dietary patterns was associated with 'small important' reductions in the primary outcome, total CVD incidence (RR for highest vs lowest adherence: 0.93 [95% CI 0.88, 0.99], p=0.01; substantial heterogeneity: I2=88%, pQ<0.001), and similar or greater reductions in the secondary outcomes of CVD mortality and incidence of CHD, stroke and type 2 diabetes (p<0.05). Inverse dose-response gradients were seen for total CVD incidence, CVD mortality and incidence of CHD, stroke and type 2 diabetes (p<0.05). No studies assessed CHD or stroke mortality. In the RCTs, there were small important reductions in LDL-cholesterol (mean difference [MD] -0.26 mmol/l [95% CI -0.52, -0.00], pMD=0.05; substantial heterogeneity: I2=89%, pQ<0.01), and 'small important' or greater reductions in the secondary outcomes of non-HDL-cholesterol, apolipoprotein B, insulin, body weight, BMI and systolic blood pressure (p<0.05). For the other outcomes there were 'trivial' reductions or no effect. The certainty of the evidence was low for total CVD incidence and LDL-cholesterol; moderate to high for CVD mortality, established lipid targets, adiposity markers, glycaemic control, blood pressure and inflammation; and low for all other outcomes, with evidence being downgraded mainly because of imprecision and inconsistency. CONCLUSIONS/INTERPRETATION Adherence to Nordic dietary patterns is associated with generally small important reductions in the risk of major CVD outcomes and diabetes, which are supported by similar reductions in LDL-cholesterol and other intermediate cardiometabolic risk factors. The available evidence provides a generally good indication of the likely benefits of Nordic dietary patterns in people with or at risk for diabetes. REGISTRATION ClinicalTrials.gov NCT04094194. FUNDING Diabetes and Nutrition Study Group of the EASD Clinical Practice.
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Vitamin D supplementation and prevention of cardiovascular disease and cancer in the Finnish Vitamin D Trial: a randomized controlled trial.
Virtanen, JK, Nurmi, T, Aro, A, Bertone-Johnson, ER, Hyppönen, E, Kröger, H, Lamberg-Allardt, C, Manson, JE, Mursu, J, Mäntyselkä, P, et al
The American journal of clinical nutrition. 2022;(5):1300-1310
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BACKGROUND Vitamin D insufficiency is associated with risks of cardiovascular diseases (CVD) and cancer in observational studies, but evidence for benefits with vitamin D supplementation is limited. OBJECTIVES To investigate the effects of vitamin D3 supplementation on CVD and cancer incidences. METHODS The study was a 5-year, randomized, placebo-controlled trial among 2495 male participants ≥60 years and post-menopausal female participants ≥65 years from a general Finnish population who were free of prior CVD or cancer. The study had 3 arms: placebo, 1600 IU/day, or 3200 IU/day vitamin D3. Follow-up was by annual study questionnaires and national registry data. A representative subcohort of 551 participants had more detailed in-person investigations. The primary endpoints were incident major CVD and invasive cancer. Secondary endpoints included the individual components of the primary CVD endpoint (myocardial infarction, stroke, and CVD mortality), site-specific cancers, and cancer death. RESULTS During the follow-up, there were 41 (4.9%), 42 (5.0%), and 36 (4.3%) major CVD events in the placebo, 1600 IU/d (compared with placebo: HR: 0.97; 95% CI: 0.63-1.49; P = 0.89), and 3200 IU/d (HR: 0.84; 95% CI: 0.54-1.31; P = 0.44) arms, respectively. Invasive cancer was diagnosed in 41 (4.9%), 48 (5.8%), and 40 (4.8%) participants in the placebo, 1600 IU/d (HR: 1.14; 95% CI: 0.75-1.72; P = 0.55), and 3200 IU/d (HR: 0.95; 95% CI: 0.61-1.47; P = 0.81) arms, respectively. There were no significant differences in the secondary endpoints or total mortality. In the subcohort, the mean baseline serum 25-hydroxyvitamin D concentration was 75 nmol/L (SD, 18 nmol/L). After 12 months, the concentrations were 73 nmol/L (SD, 18 nmol/L), 100 nmol/L (SD, 21 nmol/L), and 120 nmol/L (SD, 22 nmol/L) in the placebo, 1600 IU/d, and 3200 IU/d arms, respectively. CONCLUSIONS Vitamin D3 supplementation did not lower the incidences of major CVD events or invasive cancer among older adults, possibly due to sufficient vitamin D status in most participants at baseline.
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PUFA ω-3 and ω-6 biomarkers and sleep: a pooled analysis of cohort studies on behalf of the Fatty Acids and Outcomes Research Consortium (FORCE).
Murphy, RA, Tintle, N, Harris, WS, Darvishian, M, Marklund, M, Virtanen, JK, Hantunen, S, de Mello, VD, Tuomilehto, J, Lindström, J, et al
The American journal of clinical nutrition. 2022;(3):864-876
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BACKGROUND n-3 and n-6 PUFAs have physiologic roles in sleep processes, but little is known regarding circulating n-3 and n-6 PUFA and sleep parameters. OBJECTIVES We sought to assess associations between biomarkers of n-3 and n-6 PUFA intake with self-reported sleep duration and difficulty falling sleeping in the Fatty Acids and Outcome Research Consortium. METHODS Harmonized, de novo, individual-level analyses were performed and pooled across 12 cohorts. Participants were 35-96 y old and from 5 nations. Circulating measures included α-linolenic acid (ALA), EPA, docosapentaenoic acid (DPA), DHA, EPA + DPA + DHA, linoleic acid, and arachidonic acid. Sleep duration (10 cohorts, n = 18,791) was categorized as short (≤6 h), 7-8 h (reference), or long (≥9 h). Difficulty falling asleep (8 cohorts, n = 12,500) was categorized as yes or no. Associations between PUFAs, sleep duration, and difficulty falling sleeping were assessed by cross-sectional multinomial logistic regression using standardized protocols and covariates. Cohort-specific multivariable-adjusted ORs per quintile of PUFAs were pooled with inverse-variance weighted meta-analysis. RESULTS In pooled analysis adjusted for sociodemographic characteristics and health status, participants with higher very long-chain n-3 PUFAs were less likely to have long sleep duration. In the top compared with the bottom quintiles, the multivariable-adjusted ORs (95% CIs) for long sleep were 0.78 (95% CI: 0.65, 0.95) for DHA and 0.76 (95% CI: 0.63, 0.93) for EPA + DPA + DHA. Significant associations for ALA and n-6 PUFA with short sleep duration or difficulty falling sleeping were not identified. CONCLUSIONS Participants with higher concentrations of very long-chain n-3 PUFAs were less likely to have long sleep duration. While objective biomarkers reduce recall bias and misclassification, the cross-sectional design limits assessment of the temporal nature of this relation. These novel findings across 12 cohorts highlight the need for experimental and biological assessments of very long-chain n-3 PUFAs and sleep duration.