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Comparative effects of vitamin and mineral supplements in the management of type 2 diabetes in primary care: A systematic review and network meta-analysis of randomized controlled trials.
Xia, J, Yu, J, Xu, H, Zhou, Y, Li, H, Yin, S, Xu, D, Wang, Y, Xia, H, Liao, W, et al
Pharmacological research. 2023;188:106647
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Type 2 diabetes mellitus (T2DM), characterised by sustained hyperglycaemia and insulin resistance, remains a severe driver of chronic metabolic diseases such as cardiovascular diseases. The aim of this study was to investigate and compare the efficacy of vitamin and mineral supplements in the management of glycaemic control and lipid metabolism for type 2 diabetic patients to inform clinical practice. This study is a systematic review and meta-analysis of one hundred and seventy articles with a total of 4223 adults with T2DM. Participants were randomised to either the placebo/no treatment group (n= 6345) or to the treatment group (n= 7878). Results show that: - chromium was the most effective micronutrient for decreasing fasting blood glucose and insulin resistance. - vitamin K was the top-ranked micronutrient in reducing haemoglobin A1C and fasting insulin levels. - vanadium was the top-ranked micronutrient in total cholesterol reductions. - niacin was ranked as the most effective in triglycerides reductions and increasing high-density lipoprotein cholesterol levels. - vitamin E was the top-ranked micronutrient in low-density lipoprotein cholesterol reductions. Authors conclude that micronutrient supplements especially chromium, vitamin E, vitamin K, vanadium, and niacin supplements, may be more effective in the management of T2DM compared with other micronutrients.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Clinicians could consider the adjunctive effect of micronutrients supplements, such as chromium, vitamin E, vitamin K, vanadium, and niacin supplements in a nutrition protocol to manage T2DM and slow or prevent its complications.
- The study authors state that the vitamin and mineral supplements under review had a statistically significant improvement, however they did not reach the study threshold for clinical significance. Therefore they advise caution in utilising micronutrient supplements in the management of glucose and lipid metabolism for T2DM.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Objectives
The aim of this systematic review was to evaluate the comparative effects of vitamin and mineral supplements on managing glycemic control and lipid metabolism for type 2 diabetes mellitus (T2DM).
Methodology
This systematic review is registered with PROSPERO and adhered to PRISMA-2020 guidelines for network meta-analysis
The Cochrane Collaboration’s risk-of-bias tool was used to assess eligible randomised trials
8 prespecified markers identified and assessed in this study : 1) HbA1c (%), 2) fasting blood glucose (mmol/L), 3) total cholesterol (mmol/L), 4) triglycerides (mmol/L), 5) fasting insulin (μIU/mL), 6) HOMA-IR, 7) LDL-c (mmol/L), and 8) HDL-c (mmol/L).
Results
- 170 RCT trials of 14223 participants with T2DM treated with vitamin supplements, mineral supplements, or placebo/no treatment were included
- Low to very low certainty evidence established chromium supplements as the most effective in reducing fasting blood glucose levels and homeostasis model assessment of insulin resistance (SUCRAs: 90.4% and 78.3%, respectively)
- Vitamin K supplements ranked best in reducing glycated haemoglobin A1c and fasting insulin levels (SUCRAs: 97.0% and 82.3%, respectively), with moderate to very low certainty evidence
- Vanadium supplements ranked best in lowering total cholesterol levels with very low evidence certainty (SUCRAs:100%)
- Niacin supplements ranked best in triglyceride reductions and increasing high-density lipo-protein cholesterol levels with low to very low evidence certainty (SUCRAs:93.7% and 94.6%, respectively)
- Vitamin E supplements ranked best in reducing low-density lipoprotein cholesterol levels with very low evidence certainty (SUCRAs:80.0%).
Conclusion
- Micronutrient supplements, such as chromium, vitamin E, vitamin K, vanadium, and niacin supplements, may be efficacious in managing T2DM
- It should be noted that the evidence certainty for all was low.
Clinical practice applications:
- Chromium plays an important role in carbohydrate and lipid metabolism and was the most effective micronutrient for decreasing fasting blood glucose, HbA1c, fasting insulin, and HOMA-IR reductions. More pronounced effects were seen for chromium than vitamin E, vitamin C, niacin, selenium, and magnesium supplements
- Vitamin K was the top-ranked micronutrient in reducing HbA1c and fasting insulin levels. The mechanism through which Vitamin K affects glucose metabolism is proposed as activation of the AMP-activated protein kinase/sirtuin 1, that in turn increases phosphocreatine 3-kinase and glucose transporter 2 to decrease insulin resistance and fasting glucose.
- Vanadium was the top-ranked micronutrient in total cholesterol (TC) reductions, where supplementation dosage should be carefully considered, as vanadium compounds can be moderately or highly toxic. Vanadium supplementation is only recommended in cases of vanadium deficiency or diabetes, hyperlipidemia, and hypertension, where the intake of vanadium from food should be enhanced in preference to supplementation
- Niacin was ranked as the most effective in triglyceride (TG) reductions and increasing HDL cholesterol levels. The dose of niacin could not be determined
- Vitamin E was the top-ranked micronutrient in low-density lipo- protein (LDL) cholesterol reductions.
Considerations for future research:
- Considering the clinical importance of these findings, new research is needed to get better insight into the efficacy of micronutrient supplements in managing T2DM
- Selenium homeostasis, selenoprotein, insulin signaling/secretion, and carbohydrate/lipid metabolism are linked in multiple and complex ways but the authors could not explain why chromium supplementation would lower blood glucose more effectively than selenium supplementation, and suggest more research is needed to clarify this
- While vitamin K status could be an emerging treatment target in T2DM prevention and management, it remains to be determined whether vitamin K supplementation has an advantage over other nutrients in terms of hypoglycemic effect, and further research is necessary
- The beneficial effect of vitamin E and niacin supplements regarding lipid metabolism warrant investigation through more rigorous comparative studies.
Abstract
Medical nutrition treatment can manage diabetes and slow or prevent its complications. The comparative effects of micronutrient supplements, however, have not yet been well established. We aimed at evaluating the comparative effects of vitamin and mineral supplements on managing glycemic control and lipid metabolism for type 2 diabetes mellitus (T2DM) to inform clinical practice. Electronic and hand searches for randomized controlled trials (RCTs) were performed until June 1, 2022. We selected RCTs enrolling patients with T2DM who were treated with vitamin supplements, mineral supplements, or placebo/no treatment. Data were pooled via frequentist random-effects network meta-analyses. A total of 170 eligible trials and 14223 participants were included. Low to very low certainty evidence established chromium supplements as the most effective in reducing fasting blood glucose levels and homeostasis model assessment of insulin resistance (SUCRAs: 90.4% and 78.3%, respectively). Vitamin K supplements ranked best in reducing glycated hemoglobin A1c and fasting insulin levels (SUCRAs: 97.0% and 82.3%, respectively), with moderate to very low certainty evidence. Vanadium supplements ranked best in lowering total cholesterol levels with very low evidence certainty (SUCRAs:100%). Niacin supplements ranked best in triglyceride reductions and increasing high-density lipoprotein cholesterol levels with low to very low evidence certainty (SUCRAs:93.7% and 94.6%, respectively). Vitamin E supplements ranked best in reducing low-density lipoprotein cholesterol levels with very low evidence certainty (SUCRAs:80.0%). Our analyses indicated that micronutrient supplements, especially chromium, vitamin E, vitamin K, vanadium, and niacin supplements, may be more efficacious in managing T2DM than other micronutrients. Considering the clinical importance of these findings, new research is needed to get better insight into this issue.
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Effects of Diet on 10-Year Atherosclerotic Cardiovascular Disease Risk (from the DASH Trial).
Jeong, SY, Wee, CC, Kovell, LC, Plante, TB, Miller, ER, Appel, LJ, Mukamal, KJ, Juraschek, SP
The American journal of cardiology. 2023;187:10-17
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Determining the 10-year risk of heart disease can be used as tool to determine appropriate treatment plans. This study of 459 adults aged 22-75 years with obesity aimed to compare the effects on the 10-year risk for the development heart disease of an 8-week dietary approaches to stop hypertension (DASH) diet, with the standard American diet (AD) and a diet high in fruits and vegetables (F/V). The results showed that the DASH diet significantly improved risk factors such as systolic blood pressure and total cholesterol. However, the F/V diet had an improvement in good cholesterol, which the DASH diet did not. This equated to a similar 10% reduction in the 10-year heart disease risk compared to the AD. It was concluded that compared to a typical AD, DASH and F/V diets reduced the risk for heart disease over a 10-year period. However, the actual risk reduction was only small and individuals with obesity may need to reduce their risk further with other therapies. This study could be used by healthcare professionals to recommend a DASH diet or a diet high in fruits and vegetables to reduce the long-term risk for heart disease alongside other proven therapies or methods to reduce risk.
Expert Review
Conflicts of interest:
None
Take Home Message:
- DASH and F/V diets may be of benefit to obese individuals to decrease their risk for ASCVD
- The DASH diet did reduce HDL cholesterol and recommendations should be made to limit this effect (e.g. exercise and more fruit and vegetables in the diet).
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
This study aimed to determine the effect of the Dietary Approaches to Stop Hypertension (DASH) diet compared to a standard American diet (AD) and a diet emphasising fruits and vegetables (F/V) on the 10-year risk of atherosclerotic cardiovascular disease (ASCVD) and how adopting these diets affect specific risk factors (e.g systolic blood pressure (SBP), diastolic blood pressure (DBP) and blood lipids).
Methods
- Secondary analysis from the DASH trial which ran for 8 weeks in 459 adults aged 22-75 years with obesity
- All meals were provided and dietary intake was adjusted to prevent weight loss
- The primary outcome was an absolute and relative difference in 10-year ASCVD risk from baseline.
Participants were randomised to one of three diets:
1) DASH diet
2) F/V diet, similar to AD but with more fruits and vegetables and higher potassium and magnesium
3) Standard AD.
Results
- DASH significantly lowered SBP, total cholesterol, and HDL cholesterol compared to F/V (absolute difference SBP: -2.8, (95% confidence interval [CI]-4.5, -1.2), total cholesterol: 9.3 (-14.7, 3.9), and HDL cholesterol: -3.5 (-5.0, -2.1) P=<0.05 for all)
- DASH significantly lowered SBP, total cholesterol, and HDL cholesterol compared to AD (absolute difference SBP: -5.3 (-7.0, -3.7), total cholesterol: -13.1 (-18.5, -7.7), and HDL cholesterol: -3.8 (-5.2, -2.4) P=<0.05 for all)
- Compared to AD, DASH and F/V diets reduced 10-year ASCVD relative risk by -10.3%
( −14.4 to −5.9) and −9.9% ( −14.0 to −5.5) respectively
- This translated into low actual risk reductions of -0.21% for the F/V diet and -0.17% for the DASH diet
- Although DASH improved SBP, and total cholesterol compared to F/V, no differences in ASCVD risk between DASH and F/V were apparent. This was attributable to the detrimental effect of the DASH diet on HDL cholesterol, which was not seen in the F/V diet
- The effects of the DASH diet were more pronounced in black participants and in women.
Conclusion
Compared to the AD, DASH and F/V reduced 10-year ASCVD risk by approximately 10% over 8-weeks. The DASH diet was more effective for women and black adults.
Clinical practice applications:
- DASH and F/V diets decrease risk factors and an individual’s risk of ASCVD, and should be encouraged in individuals with obesity, especially women and black adults
- However, these diets do still leave obese individuals at risk for ASCVD.
Considerations for future research:
- Research on these diets in combination with weight loss regimes may give more pronounced results
- It may also be interesting to understand the mechanisms behind why the DASH diet reduces HDL cholesterol.
Abstract
Although modern risk estimators, such as the American College of Cardiology/American Heart Association Pooled Cohort Equation, play a central role in the decisions of patients to start pharmacologic therapy to prevent atherosclerotic cardiovascular disease (ASCVD), there is limited evidence to inform expectations for 10-year ASCVD risk reduction from established lifestyle interventions. Using data from the original DASH (Dietary Approaches to Stop Hypertension) trial, we determined the effects of adopting the DASH diet on 10-year ASCVD risk compared with adopting a control or a fruits and vegetables (F/V) diet. The DASH trial included 459 adults aged 22 to 75 years without CVD and not taking antihypertensive or diabetes mellitus medications, who were randomized to controlled feeding of a control diet, an F/V diet, or the DASH diet for 8 weeks. We determined 10-year ASCVD risk with the American College of Cardiology/American Heart Association Pooled Cohort Equation based on blood pressure and lipids measured before and after the 8-week intervention. Compared with the control diet, the DASH and F/V diets changed 10-year ASCVD risk by -10.3% (95% confidence interval [CI] -14.4 to -5.9) and -9.9% (95% CI -14.0 to -5.5) respectively; these effects were more pronounced in women and Black adults. There was no difference between the DASH and F/V diets (-0.4%, 95% CI -6.9 to 6.5). ASCVD reductions attributable to the difference in systolic blood pressure alone were -14.6% (-17.3 to -11.7) with the DASH diet and -7.9% (-10.9 to -4.8) with the F/V diet, a net relative advantage of 7.2% greater relative reduction from DASH compared with F/V. This was offset by the effects on high-density lipoprotein of the DASH diet, which increased 10-year ASCVD by 8.8% (5.5 to 12.3) compared with the more neutral effect of the F/V diet of -1.9% (-5.0 to 1.2). In conclusion, compared with a typical American diet, the DASH and F/V diets reduced 10-year ASCVD risk scores by about 10% over 8 weeks. These findings are informative for counseling patients on both choices of diet and expectations for 10-year ASCVD risk reduction.
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Impact of α-Linolenic Acid, the Vegetable ω-3 Fatty Acid, on Cardiovascular Disease and Cognition.
Sala-Vila, A, Fleming, J, Kris-Etherton, P, Ros, E
Advances in nutrition (Bethesda, Md.). 2022;13(5):1584-1602
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α-Linolenic acid (ALA) is an omega-3 fatty acid found in seeds and nuts such as flaxseeds, chia seeds, and walnuts and in oils such as canola oil, soybean oil, flaxseed oil and walnut oil. It has been shown to reduce the risk of coronary heart disease and cardiovascular disease. This meta-analysis examined the results of various studies, including epidemiologic studies, randomized controlled trials, and systematic reviews, to evaluate the beneficial effects of ALA in improving cognitive function and reducing the risk of cardiovascular disease and coronary heart disease. The included studies showed a correlation between ALA intake and a decreased risk of cardiovascular disease and coronary heart disease, possibly due to ALA's anti-inflammatory properties, as well as its ability to reduce total cholesterol, LDL cholesterol, triglycerides, and blood pressure. The analysis also found that ALA intake may reduce the risk of type 2 diabetes and cognitive impairment. Healthcare professionals can leverage the findings of this analysis to educate individuals about the benefits of dietary ALA in improving cardiovascular and cognitive outcomes. However, further studies are necessary to establish definitive conclusions and determine therapeutic dosage.
Abstract
Given the evidence of the health benefits of plant-based diets and long-chain n-3 (ω-3) fatty acids, there is keen interest in better understanding the role of α-linolenic acid (ALA), a plant-derived n-3 fatty acid, on cardiometabolic diseases and cognition. There is increasing evidence for ALA largely based on its major food sources (i.e., walnuts and flaxseed); however, this lags behind our understanding of long-chain n-3 fatty acids. Meta-analyses of observational studies have shown that increasing dietary ALA is associated with a 10% lower risk of total cardiovascular disease and a 20% reduced risk of fatal coronary heart disease. Three randomized controlled trials (RCTs) [AlphaOmega trial, Prevención con Dieta Mediterránea (PREDIMED) trial, and Lyon Diet Heart Study] all showed benefits of diets high in ALA on cardiovascular-related outcomes, but the AlphaOmega trial, designed to specifically evaluate ALA effects, only showed a trend for benefit. RCTs have shown that dietary ALA reduced total cholesterol, LDL cholesterol, triglycerides, and blood pressure, and epidemiologic studies and some trials also have shown an anti-inflammatory effect of ALA, which collectively account for, in part, the cardiovascular benefits of ALA. A meta-analysis reported a trend toward diabetes risk reduction with both dietary and biomarker ALA. For metabolic syndrome and obesity, the evidence for ALA benefits is inconclusive. The role of ALA in cognition is in the early stages but shows promising evidence of counteracting cognitive impairment. Much has been learned about the health benefits of ALA and with additional research we will be better positioned to make strong evidence-based dietary recommendations for the reduction of many chronic diseases.
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Small Interfering RNA to Reduce Lipoprotein(a) in Cardiovascular Disease.
O'Donoghue, ML, Rosenson, RS, Gencer, B, López, JAG, Lepor, NE, Baum, SJ, Stout, E, Gaudet, D, Knusel, B, Kuder, JF, et al
The New England journal of medicine. 2022;387(20):1855-1864
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Numerous epidemiologic studies over the past three decades have shown an association between higher circulating lipoprotein(a) concentrations and an increased risk of atherosclerotic cardiovascular disease. The aim of this study was to evaluate the efficacy and safety of repeated administration of a small interfering RNA designed to lower the body's production of apolipoprotein(a). This study is a multicentre, randomised, double-blind, placebo-controlled, dose-finding trial. Patients were randomly assigned in a 1:1:1:1:1 ratio to receive one of four doses of small interfering RNA (n= 281) (10 mg every 12 weeks, 75 mg every 12 weeks, 225 mg every 12 weeks, or 225 mg every 24 weeks) or matching placebo, administered subcutaneously. Results show that treatment with small interfering RNA markedly reduced the concentration of lipoprotein(a) in a dose-dependent manner and appeared to be safe. At higher doses, the treatment reduced the lipoprotein(a) concentration by more than 95%, as compared with placebo, with nearly all patients who received the treatment with small interfering RNA having a lipoprotein(a) concentration of less than 125 nmol per litre. Authors conclude that further large-scale interventions are needed to confirm a causal role for lipoprotein(a) in atherosclerotic cardiovascular disease.
Abstract
BACKGROUND Lipoprotein(a) is a presumed risk factor for atherosclerotic cardiovascular disease. Olpasiran is a small interfering RNA that reduces lipoprotein(a) synthesis in the liver. METHODS We conducted a randomized, double-blind, placebo-controlled, dose-finding trial involving patients with established atherosclerotic cardiovascular disease and a lipoprotein(a) concentration of more than 150 nmol per liter. Patients were randomly assigned to receive one of four doses of olpasiran (10 mg every 12 weeks, 75 mg every 12 weeks, 225 mg every 12 weeks, or 225 mg every 24 weeks) or matching placebo, administered subcutaneously. The primary end point was the percent change in the lipoprotein(a) concentration from baseline to week 36 (reported as the placebo-adjusted mean percent change). Safety was also assessed. RESULTS Among the 281 enrolled patients, the median concentration of lipoprotein(a) at baseline was 260.3 nmol per liter, and the median concentration of low-density lipoprotein cholesterol was 67.5 mg per deciliter. At baseline, 88% of the patients were taking statin therapy, 52% were taking ezetimibe, and 23% were taking a proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor. At 36 weeks, the lipoprotein(a) concentration had increased by a mean of 3.6% in the placebo group, whereas olpasiran therapy had significantly and substantially reduced the lipoprotein(a) concentration in a dose-dependent manner, resulting in placebo-adjusted mean percent changes of -70.5% with the 10-mg dose, -97.4% with the 75-mg dose, -101.1% with the 225-mg dose administered every 12 weeks, and -100.5% with the 225-mg dose administered every 24 weeks (P<0.001 for all comparisons with baseline). The overall incidence of adverse events was similar across the trial groups. The most common olpasiran-related adverse events were injection-site reactions, primarily pain. CONCLUSIONS Olpasiran therapy significantly reduced lipoprotein(a) concentrations in patients with established atherosclerotic cardiovascular disease. Longer and larger trials will be necessary to determine the effect of olpasiran therapy on cardiovascular disease. (Funded by Amgen; OCEAN[a]-DOSE ClinicalTrials.gov number, NCT04270760.).
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Metabolic dysfunction-associated fatty liver disease and cardiovascular disease: A meta-analysis.
Wen, W, Li, H, Wang, C, Chen, C, Tang, J, Zhou, M, Hong, X, Cheng, Y, Wu, Q, Zhang, X, et al
Frontiers in endocrinology. 2022;13:934225
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Non-alcoholic fatty liver disease (NAFLD) is a multi-system disease that not only affects the structure and function of the liver but also increases the incidence of type 2 diabetes, cardiovascular disease (CVD), cerebrovascular disease, and chronic kidney disease. In 2020, experts reached a consensus to recommend a more appropriate term to more accurately and positively define fatty liver disease associated with metabolic disorders, namely, metabolic dysfunction-associated fatty liver disease (MAFLD). The aim of this study was to investigate the risk of CVD incidence or CVD mortality in patients diagnosed with MAFLD. This study is a meta-analysis of ten cohort studies. Results show that patients in the MAFLD group had a significantly increased relative risk of CVD or death from CVD during the follow-up compared with the control group. Authors conclude that even though there is a positive association between MAFLD and the risk of CVD or death from CVD, further studies are needed to demonstrate different effects of the newly defined MAFLD on CVD compared with previous NAFLD.
Abstract
BACKGROUND Metabolic dysfunction-associated fatty liver disease [MAFLD, formerly known as nonalcoholic fatty liver disease (NAFLD)] is one of the most important causes of liver disease worldwide, while cardiovascular disease (CVD) is still one of the main causes of morbidity and mortality worldwide, and the two are closely related. This study aimed to investigate the risk of CVD incidence or CVD-related mortality (CVD mortality) in patients diagnosed with MAFLD under new concepts and new diagnostic criteria. METHODS We searched English databases PubMed, Web of Science, Embase, and Cochrane Library for relevant literature. The language was restricted to English. RESULTS By 22 January 2022, 556 published studies were obtained through preliminary retrieval, and 10 cohort studies were included in this study. All statistical analyses were performed using Review Manager 5.2 software. Compared with the control group, patients in the MAFLD group had a significantly higher relative risk of CVD incidence or CVD mortality during the follow-up, with an RR rate of 1.95 (95% CI 1.76-2.17, p < 0.01). The incidence of CVD in the MAFLD group was more than twice that in the control group (RR 2.26, 95% CI 2.00-2.54, p < 0.01). The mortality rate of CVD was 1.57 times higher than that in the control group (RR 1.57, 95% CI 1.42-1.72, p < 0.01). CONCLUSIONS Patients diagnosed with MAFLD alone had higher cardiovascular mortality than those diagnosed with NAFLD alone based on the available data.
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Efficacy of telemedicine for the management of cardiovascular disease: a systematic review and meta-analysis.
Kuan, PX, Chan, WK, Fern Ying, DK, Rahman, MAA, Peariasamy, KM, Lai, NM, Mills, NL, Anand, A
The Lancet. Digital health. 2022;4(9):e676-e691
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Digital health interventions (DHIs) have the potential to transform the diagnosis, monitoring, and management of chronic cardiovascular conditions. Many DHIs are widely deployed in health systems across the world, with adoption rapidly increasing in response to the coronavirus disease 2019 pandemic. The aim of this study was to provide an updated synthesis of evidence on the effectiveness of telemedicine in the management of cardiovascular diseases. This study is a systematic review and meta-analysis of seventy-two studies with a total of 127,869 participants, of whom 82,818 (65%) were males and 45051 (35%) were females. Results showed reduced cardiovascular-related mortality and hospitalisation for patients with heart failure who received combined remote telemedicine monitoring and consultation compared with usual care. Authors conclude that the findings of their study suggest a definite role for telemedicine in the management of heart failure, particularly in early treatment optimisation, but the value is less clear for long-term management strategy and other cardiovascular diseases. Thus, future research should focus to address the application of these technologies to unselected populations and longer-term effectiveness.
Abstract
BACKGROUND Telemedicine has been increasingly integrated into chronic disease management through remote patient monitoring and consultation, particularly during the COVID-19 pandemic. We did a systematic review and meta-analysis of studies reporting effectiveness of telemedicine interventions for the management of patients with cardiovascular conditions. METHODS In this systematic review and meta-analysis, we searched PubMed, Scopus, and Cochrane Library from database inception to Jan 18, 2021. We included randomised controlled trials and observational or cohort studies that evaluated the effects of a telemedicine intervention on cardiovascular outcomes for people either at risk (primary prevention) of cardiovascular disease or with established (secondary prevention) cardiovascular disease, and, for the meta-analysis, we included studies that evaluated the effects of a telemedicine intervention on cardiovascular outcomes and risk factors. We excluded studies if there was no clear telemedicine intervention described or if cardiovascular or risk factor outcomes were not clearly reported in relation to the intervention. Two reviewers independently assessed and extracted data from trials and observational and cohort studies using a standardised template. Our primary outcome was cardiovascular-related mortality. We evaluated study quality using Cochrane risk-of-bias and Newcastle-Ottawa scales. The systematic review and the meta-analysis protocol was registered with PROSPERO (CRD42021221010) and the Malaysian National Medical Research Register (NMRR-20-2471-57236). FINDINGS 72 studies, including 127 869 participants, met eligibility criteria, with 34 studies included in meta-analysis (n=13 269 with 6620 [50%] receiving telemedicine). Combined remote monitoring and consultation for patients with heart failure was associated with a reduced risk of cardiovascular-related mortality (risk ratio [RR] 0·83 [95% CI 0·70 to 0·99]; p=0·036) and hospitalisation for a cardiovascular cause (0·71 [0·58 to 0·87]; p=0·0002), mostly in studies with short-term follow-up. There was no effect of telemedicine on all-cause hospitalisation (1·02 [0·94 to 1·10]; p=0·71) or mortality (0·90 [0·77 to 1·06]; p=0·23) in these groups, and no benefits were observed with remote consultation in isolation. Small reductions were observed for systolic blood pressure (mean difference -3·59 [95% CI -5·35 to -1·83] mm Hg; p<0·0001) by remote monitoring and consultation in secondary prevention populations. Small reductions were also observed in body-mass index (mean difference -0·38 [-0·66 to -0·11] kg/m2; p=0·0064) by remote consultation in primary prevention settings. INTERPRETATION Telemedicine including both remote disease monitoring and consultation might reduce short-term cardiovascular-related hospitalisation and mortality risk among patients with heart failure. Future research should evaluate the sustained effects of telemedicine interventions. FUNDING The British Heart Foundation.
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Cardiometabolic Risk Factors and Incident Cardiovascular Disease Events in Women vs Men With Type 1 Diabetes.
Braffett, BH, Bebu, I, El Ghormli, L, Cowie, CC, Sivitz, WI, Pop-Busui, R, Larkin, ME, Gubitosi-Klug, RA, Nathan, DM, Lachin, JM, et al
JAMA network open. 2022;5(9):e2230710
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In the general population, women have a lower absolute risk of cardiovascular disease (CVD) compared with men. However, among individuals with type 1 or type 2 diabetes, the relative risk of CVD is similar or higher in women compared with men. The aim of this study was to assess sex differences in achieving recommended CVD risk management targets and associations with CVD events. This is a cohort study which included a total of 1441 (men n= 736) participants with type 1 diabetes. Results show that the prevalence and mean levels of most cardiometabolic risk factors (except for pulse rate and haemoglobin A1c) were consistent with a less atherogenic profile among women compared with men. Furthermore, achieving treatment targets for blood pressure, lipids, and glucose was associated with significantly decreased risk of CVD in both women and men. Authors conclude that their findings argue for a recalibration of CVD risk factor stratification in revised clinical care guidelines and therapeutic recommendations by sex for individuals with type 1 diabetes.
Abstract
IMPORTANCE The lower risk of cardiovascular disease (CVD) among women compared with men in the general population may be diminished among those with diabetes. OBJECTIVE To evaluate cardiometabolic risk factors and their management in association with CVD events in women vs men with type 1 diabetes enrolled in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study. DESIGN, SETTING, AND PARTICIPANTS This cohort study used data obtained during the combined DCCT (randomized clinical trial, conducted 1983-1993) and EDIC (observational study, conducted 1994 to present) studies through April 30, 2018 (mean [SD] follow-up, 28.8 [5.8] years), at 27 clinical centers in the US and Canada. Data analyses were performed between July 2021 and April 2022. EXPOSURE During the DCCT phase, patients were randomized to intensive vs conventional diabetes therapy. MAIN OUTCOMES AND MEASURES Cardiometabolic risk factors and CVD events were assessed via detailed medical history and focused physical examinations. Blood and urine samples were assayed centrally. CVD events were adjudicated by a review committee. Linear mixed models and Cox proportional hazards models evaluated sex differences in cardiometabolic risk factors and CVD risk over follow-up. RESULTS A total of 1441 participants with type 1 diabetes (mean [SD] age at DCCT baseline, 26.8 [7.1] years; 761 [52.8%] men; 1390 [96.5%] non-Hispanic White) were included. Over the duration of the study, compared with men, women had significantly lower body mass index (BMI, calculated as weight in kilograms divided by height in meters squared; β = -0.43 [SE, 0.16]; P = .006), waist circumference (β = -10.56 cm [SE, 0.52 cm]; P < .001), blood pressure (systolic: β = -5.77 mm Hg [SE, 0.35 mm Hg]; P < .001; diastolic: β = -3.23 mm Hg [SE, 0.26 mm Hg]; P < .001), and triglyceride levels (β = -10.10 mg/dL [SE, 1.98 mg/dL]; P < .001); higher HDL cholesterol levels (β = 9.36 mg/dL [SE, 0.57 mg/dL]; P < .001); and similar LDL cholesterol levels (β = -0.76 mg/dL [SE, 1.22 mg/dL]; P = .53). Women, compared with men, achieved recommended targets more frequently for blood pressure (ie, <130/80 mm Hg: 90.0% vs 77.4%; P < .001) and triglycerides (ie, <150 mg/dL: 97.3% vs 90.5%; P < .001). However, sex-specific HDL cholesterol targets (ie, ≥50 mg/dL for women, ≥40 mg/dL for men) were achieved less often (74.3% vs 86.6%; P < .001) and cardioprotective medications were used less frequently in women than men (ie, angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker: 29.6% [95% CI, 25.7%-33.9%] vs 40.0% [95% CI, 36.1%-44.0%]; P = .001; lipid-lowering medication: 25.3% [95% CI, 22.1%-28.7%] vs 39.6% [95% CI, 36.1%-43.2%]; P < .001). Women also had significantly higher pulse rates (mean [SD], 75.2 [6.8] beats per minute vs 71.8 [6.9] beats per minute; P < .001) and hemoglobin A1c levels (mean [SD], 8.3% [1.0%] vs 8.1% [1.0%]; P = .01) and achieved targets for tighter glycemic control less often than men (ie, hemoglobin A1c <7%: 11.2% [95% CI, 9.3%-13.3%] vs 14.0% [95% CI, 12.0%-16.3%]; P = .03). CONCLUSIONS AND RELEVANCE These findings suggest that despite a more favorable cardiometabolic risk factor profile, women with type 1 diabetes did not have a significantly lower CVD event burden than men, suggesting a greater clinical impact of cardiometabolic risk factors in women vs men with diabetes. These findings call for conscientious optimization of the control of CVD risk factors in women with type 1 diabetes.
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Effects of regular sauna bathing in conjunction with exercise on cardiovascular function: a multi-arm, randomized controlled trial.
Lee, E, Kolunsarka, I, Kostensalo, J, Ahtiainen, JP, Haapala, EA, Willeit, P, Kunutsor, SK, Laukkanen, JA
American journal of physiology. Regulatory, integrative and comparative physiology. 2022;323(3):R289-R299
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Physical activity and exercise training are well-documented strategies to prevent ailments and various diseases. However, unlike exercise, heat therapy and the health benefits of Finnish sauna bathing are still not well understood, despite its increasing use throughout the world. The aim of this study was to compare the cardiovascular adaptations of regular exercise alone (EXE) to regular exercise and sauna bathing (EXS), with a sedentary control (CON) group. This study is an 8-week multi-arm randomised controlled trial. Forty-eight participants (females n= 42) were randomly assigned into the EXS, EXE, or the CON group. Results show that regular exercise using the recommended guidelines three times a week, for 50 minutes each time, can effectively improve cardiorespiratory fitness (CRF) and body composition. The addition of a regular 15-minute typical Finnish sauna after exercise supplemented the gains in CRF, reductions in systolic blood pressure, and lowered total cholesterol levels considerably. Authors conclude that sauna bathing is a safe and simple lifestyle modification and steps should be taken to make it more accessible worldwide. Thus, future studies should seek to understand the optimal exposure durations, frequencies, modalities, and temperatures for various beneficial adaptations.
Abstract
Regular exercise and sauna bathing have each been shown to improve cardiovascular function in clinical populations. However, experimental data on the cardiovascular adaptations to regular exercise in conjunction with sauna bathing in the general population are lacking. Therefore, we compared the effects of exercise and sauna bathing to regular exercise using a multi-arm randomized controlled trial. Participants (n = 47) aged 49 ± 9 with low physical activity levels and at least one traditional cardiovascular disease (CVD) risk factor were randomly assigned (1:1:1) to guideline-based regular exercise and 15-min postexercise sauna (EXS), guideline-based regular exercise (EXE), or control (CON) for 8 wk. The primary outcomes were blood pressure (BP) and cardiorespiratory fitness (CRF). Secondary outcomes included fat mass, total cholesterol levels, and arterial stiffness. EXE had a greater change in CRF (+6.2 mL/kg/min; 95% CI, +4.2 to +8.3 mL/kg/min) and fat mass but no differences in BP when compared with CON. EXS displayed greater change in CRF (+2.7 mL/kg/min; 95% CI, +0.2 to +5.3 mL/kg/min), lower systolic BP (-8.0 mmHg; 95% CI, -14.6 to -1.4 mmHg), and lower total cholesterol levels compared with EXE. Regular exercise improved CRF and body composition in sedentary adults with CVD risk factors. However, when combined with exercise, sauna bathing demonstrated a substantially supplementary effect on CRF, systolic BP, and total cholesterol levels. Sauna bathing is a valuable lifestyle tool that complements exercise for improving CRF and decreasing systolic BP. Future research should focus on the duration and frequency of exposure to ascertain the dose-response relationship.
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Effects of curcumin and/or coenzyme Q10 supplementation on metabolic control in subjects with metabolic syndrome: a randomized clinical trial.
Sangouni, AA, Taghdir, M, Mirahmadi, J, Sepandi, M, Parastouei, K
Nutrition journal. 2022;21(1):62
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Metabolic syndrome (MetS) is a cluster of metabolic disorders such as hyperlipidaemia, hypertension, hyperglycaemia, insulin resistance, and abdominal obesity. MetS is associated with cardiovascular disease (CVD), type 2 diabetes mellitus and non-alcoholic fatty liver disease. The aim of this study was to investigate the effects of curcumin and/or coenzyme Q10 supplementation on metabolic syndrome components in subjects with MetS. This study is a 2×2 factorial, randomised, double-blinded, placebo-controlled study which was conducted for 12 weeks. Eighty-eight subjects were randomly assigned into four groups. All subjects completed the trial. Results show that curcumin supplementation improves lipid profile, but it does not have any effect on body composition, hypertension and fasting plasma glucose. However, supplementation with coenzyme Q10 as well as curcumin plus coenzyme Q10 did not show any significant effects on lipid profile, body composition, hypertension and fasting plasma glucose. Authors conclude that curcumin supplementation (especially by its effects on dyslipidaemia) is more effective than coenzyme Q10 as well as the combination of curcumin and coenzyme Q10 in the management of MetS. However, curcumin, coenzyme Q10 and their combination have no effect on body composition, hypertension and glycaemic control.
Abstract
BACKGROUND Metabolic syndrome (MetS) as a cluster of conditions including hyperlipidemia, hypertension, hyperglycemia, insulin resistance, and abdominal obesity is linked to cardiovascular diseases and type 2 diabetes. Evidence suggested that intake of curcumin and coenzyme Q10 may have therapeutic effects in the management of MetS. AIMS We investigated the effects of curcumin and/or coenzyme Q10 supplementation on metabolic syndrome components including systolic blood pressure (SBP), diastolic blood pressure (DBP), waist circumference (WC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-c) and fasting plasma glucose (FPG) as primary outcomes, and total cholesterol (TC), low density lipoprotein-cholesterol (LDL-c) and body mass index (BMI) as secondary outcomes in subjects with MetS. METHODS In this 2 × 2 factorial, randomized, double-blinded, placebo-controlled study, 88 subjects with MetS were randomly assigned into four groups including curcumin plus placebo (CP), or coenzyme Q10 plus placebo (QP), or curcumin plus coenzyme Q10 (CQ), or double placebo (DP) for 12 weeks. RESULTS The CP group compared with the three other groups showed a significant reduction in HDL-c (P = 0.001), TG (P < 0.001), TC (P < 0.001), and LDL-c (P < 0.001). No significant differences were seen between the four groups in terms of SBP, DBP, FPG, WC, BMI and weight. CONCLUSION Curcumin improved dyslipidemia, but had no effect on body composition, hypertension and glycemic control. Furthermore, coenzyme Q10 as well as the combination of curcumin and coenzyme Q10 showed no therapeutic effects in subjects with MetS. The trial was registered on 09/21/2018 at the Iranian clinical trials website (IRCT20180201038585N2), URL: https://www.irct.ir/trial/32518 .
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Impact of Replacement of Individual Dietary SFAs on Circulating Lipids and Other Biomarkers of Cardiometabolic Health: A Systematic Review and Meta-Analysis of Randomized Controlled Trials in Humans.
Sellem, L, Flourakis, M, Jackson, KG, Joris, PJ, Lumley, J, Lohner, S, Mensink, RP, Soedamah-Muthu, SS, Lovegrove, JA
Advances in nutrition (Bethesda, Md.). 2022;13(4):1200-1225
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Cardiovascular disease is one of the leading causes of mortality worldwide, and metabolic disorders such as diabetes, hyperlipidaemia, and hypertension contribute to this risk. Cardiometabolic disease (CMD) can be reduced by reducing saturated fatty acids (SFAs) and replacing them with unsaturated fatty acids (UFAs). Dietary SFA's are classified as a whole group in general dietary guidelines. However, blood lipid levels and other biomarkers of CMD may be affected differently by individual dietary SFAs. In this systematic review and meta-analysis, 44 randomised controlled trials were included that investigated the effects of replacing SFAs with individual dietary SFAs or UFAs on markers of CMD. CMD markers like Total cholesterol (TC), LDL cholesterol, and apoB concentrations were significantly reduced by replacing 1.5%TE of palmitic acid with oleic acid or UFAs for 14 days. The research also showed associations between apoB and LDL-cholesterol and apoA-I and HDL-cholesterol concentrations. Dietary palmitic acid substituted with UFAs significantly reduced fasting LDL-cholesterol and total cholesterol. The majority of studies included in this study focused on dietary palmitic acid and not much on stearic acid, myristic acid, or lauric acid. Therefore, further robust studies are required to assess the effect of individual dietary SFAs on the markers of CMD, including markers of inflammation, hemostasis, glycemic control, or metabolic hormones. Healthcare professionals can use this study to understand the benefits of substituting SFAs with UFAs on CMD markers.
Abstract
Little is known of the impact of individual SFAs and their isoenergetic substitution with other SFAs or unsaturated fatty acids (UFAs) on the prevention of cardiometabolic disease (CMD). This systematic literature review assessed the impact of such dietary substitutions on a range of fasting CMD risk markers, including lipid profile, markers of glycemic control and inflammation, and metabolic hormone concentrations. Eligible randomized controlled trials (RCTs) investigated the effect of isoenergetic replacements of individual dietary SFAs for ≥14 d on ≥1 CMD risk markers in humans. Searches of the PubMed, Embase, Scopus, and Cochrane CENTRAL databases on 14 February, 2021 identified 44 RCTs conducted in participants with a mean ± SD age of 39.9 ± 15.2 y. Studies' risk of bias was assessed using the Cochrane Risk of Bias tool 2.0 for RCTs. Random-effect meta-analyses assessed the effect of ≥3 similar dietary substitutions on the same CMD risk marker. Other dietary interventions were described in qualitative syntheses. We observed reductions in LDL-cholesterol concentrations after the replacement of palmitic acid (16:0) with UFAs (-0.36 mmol/L; 95% CI: -0.50, -0.21 mmol/L; I2 = 96.0%, n = 18 RCTs) or oleic acid (18:1n-9) (-0.16 mmol/L; 95% CI: -0.28, -0.03 mmol/L; I2 = 89.6%, n = 9 RCTs), with a similar impact on total cholesterol and apoB concentrations. No effects on other CMD risk markers, including HDL-cholesterol, triacylglycerol, glucose, insulin, or C-reactive protein concentrations, were evident. Similarly, we found no evidence of a benefit from replacing dietary stearic acid (18:0) with UFAs on CMD risk markers (n = 4 RCTs). In conclusion, the impact of replacing dietary palmitic acid with UFAs on lipid biomarkers is aligned with current public health recommendations. However, owing to the high heterogeneity and limited studies, relations between all individual SFAs and biomarkers of cardiometabolic health need further confirmation from RCTs. This systematic review was registered at www.crd.york.ac.uk/prospero/ as CRD42020084241.