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Diabetes-specific formulas high in monounsaturated fatty acids and metabolic outcomes in patients with diabetes or hyperglycaemia. A systematic review and meta-analysis.
Sanz-París, A, Matía-Martín, P, Martín-Palmero, Á, Gómez-Candela, C, Camprubi Robles, M
Clinical nutrition (Edinburgh, Scotland). 2020;(11):3273-3282
Abstract
OBJECTIVE The aim of this study was to compare the metabolic benefits of diabetes-specific formulas (DSF) high in monounsaturated fatty acids (MUFA) with standard formulas (STDF) in adult patients with type 1, type 2 diabetes or stress-induced hyperglycaemia. RESEARCH DESIGN AND METHODS A systematic review and meta-analysis were conducted through a literature search using different electronic databases from the index date to December 2018. We included randomised controlled trials that assessed the health benefits of high MUFA DSF vs STDF. Included outcomes were glycaemic control, lipid metabolism and tolerance. Effect sizes were calculated as standardised mean differences (SMDs) (<0.4 were considered small, 0.4-0.7 moderate and >0.7 large). This systematic review was registered as CRD42018108931 on Prospero. RESULTS Of 385 references reviewed, 18 studies involving 845 adults met our inclusion criteria and contributed to the meta-analysis. Use of a high MUFA DSF compared with a STDF was associated with a statistically significant decrease in peak of postprandial glucose [SMD -1.53, 95% confidence interval (CI) -2.44 to -0.61], incremental glucose response (SMD -1.19, 95% CI -1.71 to -0.68), area under the curve of plasma insulin (SMD -0.65, 95% CI -1.03 to -0.26), mean blood glucose level (SMD -0.41, 95% CI -0.63 to -0.19), glycosylated haemoglobin (HbA1c) change (SMD -0.63, 95% CI -1.21 to -0.05), glucose variability (SMD -0.93, -1.55 to -0.31), mean administered insulin dose (SMD -0.49, 95% CI -0.85 to -0.14), mean blood triglycerides (SMD -0.34, 95% CI -0.65 to -0.03) and increase of mean blood high-density lipoproteins (SMD +0.42, 95% CI 0.08 to 0.76). Non-significant differences were found for tolerance [odds ratio (OR) 0.95, 95% CI 0.87 to 1.05]. CONCLUSIONS This meta-analysis shows that a DSF (oral supplements and tube feeds) high in MUFAs can improve glucose control and metabolic risk factors among patients with diabetes or stress-induced hyperglycaemia compared with a STDF.
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Effect of high-carbohydrate or high-monounsaturated fatty acid diets on blood pressure: a systematic review and meta-analysis of randomized controlled trials.
Jovanovski, E, de Castro Ruiz Marques, A, Li, D, Ho, HVT, Blanco Mejia, S, Sievenpiper, JL, Zurbau, A, Komishon, A, Duvnjak, L, Bazotte, RB, et al
Nutrition reviews. 2019;(1):19-31
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CONTEXT Current dietary guidelines for cardiovascular disease risk management recommend restricting intake of saturated fatty acids (SFAs). However, the optimal macronutrient profile, in the context of a low-SFA diet, remains controversial. The blood-pressure effect of replacing SFAs in diets with monounsaturated fatty acids (MUFAs) compared with carbohydrate has not been quantified to date. OBJECTIVE To synthesize the evidence for the effect of substituting a high-carbohydrate (high-CHO) diet for a high-monounsaturated fatty acid (high-MUFA) diet on blood pressure, a systematic review and meta-analysis of randomized clinical trials in a population without health restrictions was conducted. DATA SOURCES MEDLINE, EMBASE, and Cochrane Central Register of Controlled Clinical Trials were searched through June 7, 2017. Randomized controlled trials of > 3 weeks duration that assessed the effect of high-MUFA diets in isocaloric substitution for high-CHO diets on systolic blood pressure (SBP) and diastolic blood pressure (DBP) were included. DATA EXTRACTION Data were pooled using the generic-inverse variance method with random effects models and expressed as mean differences (MDs) with 95% confidence intervals (CIs). Heterogeneity was assessed by Cochran Q statistic and quantified by the I2 statistic. The quality of the evidence was assessed with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. RESULTS Fourteen trials (n = 980 participants) were included in the analysis. Comparatively, the high-MUFA diets in isocaloric substitution for high-CHO diets did not demonstrate a greater reduction in blood pressure (SBP: MD, -0.08 mmHg [95%CI, -1.01 to 0.84], P = 0.86; DBP: MD = 0.01 mmHg [95%CI, -0.73 to 0.75], P = 0.98). The overall quality of the evidence was assessed as moderate. CONCLUSIONS In the context of low SFAs, high-MUFA diets in isocaloric substitution for high-CHO diets did not affect blood pressure in individuals with and without hypertension. Large-scale trials achieving higher MUFA targets are required to support these findings. CLINICALTRIALS.GOV ID NCT02626325.
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Fluvastatin for lowering lipids.
Adams, SP, Sekhon, SS, Tsang, M, Wright, JM
The Cochrane database of systematic reviews. 2018;(3):CD012282
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BACKGROUND Fluvastatin is thought to be the least potent statin on the market, however, the dose-related magnitude of effect of fluvastatin on blood lipids is not known. OBJECTIVES Primary objectiveTo quantify the effects of various doses of fluvastatin on blood total cholesterol, low-density lipoprotein (LDL cholesterol), high-density lipoprotein (HDL cholesterol), and triglycerides in participants with and without evidence of cardiovascular disease.Secondary objectivesTo quantify the variability of the effect of various doses of fluvastatin.To quantify withdrawals due to adverse effects (WDAEs) in randomised placebo-controlled trials. SEARCH METHODS The Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials up to February 2017: the Cochrane Central Register of Controlled Trials (CENTRAL) (2017, Issue 1), MEDLINE (1946 to February Week 2 2017), MEDLINE In-Process, MEDLINE Epub Ahead of Print, Embase (1974 to February Week 2 2017), the World Health Organization International Clinical Trials Registry Platform, CDSR, DARE, Epistemonikos and ClinicalTrials.gov. We also contacted authors of relevant papers regarding further published and unpublished work. No language restrictions were applied. SELECTION CRITERIA Randomised placebo-controlled and uncontrolled before and after trials evaluating the dose response of different fixed doses of fluvastatin on blood lipids over a duration of three to 12 weeks in participants of any age with and without evidence of cardiovascular disease. DATA COLLECTION AND ANALYSIS Two review authors independently assessed eligibility criteria for studies to be included, and extracted data. We entered data from placebo-controlled and uncontrolled before and after trials into Review Manager 5 as continuous and generic inverse variance data, respectively. WDAEs information was collected from the placebo-controlled trials. We assessed all trials using the 'Risk of bias' tool under the categories of sequence generation, allocation concealment, blinding, incomplete outcome data, selective reporting, and other potential biases. MAIN RESULTS One-hundred and forty-five trials (36 placebo controlled and 109 before and after) evaluated the dose-related efficacy of fluvastatin in 18,846 participants. The participants were of any age with and without evidence of cardiovascular disease, and fluvastatin effects were studied within a treatment period of three to 12 weeks. Log dose-response data over doses of 2.5 mg to 80 mg revealed strong linear dose-related effects on blood total cholesterol and LDL cholesterol and a weak linear dose-related effect on blood triglycerides. There was no dose-related effect of fluvastatin on blood HDL cholesterol. Fluvastatin 10 mg/day to 80 mg/day reduced LDL cholesterol by 15% to 33%, total cholesterol by 11% to 25% and triglycerides by 3% to 17.5%. For every two-fold dose increase there was a 6.0% (95% CI 5.4 to 6.6) decrease in blood LDL cholesterol, a 4.2% (95% CI 3.7 to 4.8) decrease in blood total cholesterol and a 4.2% (95% CI 2.0 to 6.3) decrease in blood triglycerides. The quality of evidence for these effects was judged to be high. When compared to atorvastatin and rosuvastatin, fluvastatin was about 12-fold less potent than atorvastatin and 46-fold less potent than rosuvastatin at reducing LDL cholesterol. Very low quality of evidence showed no difference in WDAEs between fluvastatin and placebo in 16 of 36 of these short-term trials (risk ratio 1.52 (95% CI 0.94 to 2.45). AUTHORS' CONCLUSIONS Fluvastatin lowers blood total cholesterol, LDL cholesterol and triglyceride in a dose-dependent linear fashion. Based on the effect on LDL cholesterol, fluvastatin is 12-fold less potent than atorvastatin and 46-fold less potent than rosuvastatin. This review did not provide a good estimate of the incidence of harms associated with fluvastatin because of the short duration of the trials and the lack of reporting of adverse effects in 56% of the placebo-controlled trials.
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Discovery and fine-mapping of loci associated with MUFAs through trans-ethnic meta-analysis in Chinese and European populations.
Hu, Y, Tanaka, T, Zhu, J, Guan, W, Wu, JHY, Psaty, BM, McKnight, B, King, IB, Sun, Q, Richard, M, et al
Journal of lipid research. 2017;(5):974-981
Abstract
MUFAs are unsaturated FAs with one double bond and are derived from endogenous synthesis and dietary intake. Accumulating evidence has suggested that plasma and erythrocyte MUFA levels are associated with cardiometabolic disorders, including CVD, T2D, and metabolic syndrome (MS). Previous genome-wide association studies (GWASs) have identified seven loci for plasma and erythrocyte palmitoleic and oleic acid levels in populations of European origin. To identify additional MUFA-associated loci and the potential functional variant at each locus, we performed ethnic-specific GWAS meta-analyses and trans-ethnic meta-analyses in more than 15,000 participants of Chinese and European ancestry. We identified novel genome-wide significant associations for vaccenic acid at FADS1/2 and PKD2L1 [log10(Bayes factor) ≥ 8.07] and for gondoic acid at FADS1/2 and GCKR [log10(Bayes factor) ≥ 6.22], and also observed improved fine-mapping resolutions at FADS1/2 and GCKR loci. The greatest improvement was observed at GCKR, where the number of variants in the 99% credible set was reduced from 16 (covering 94.8 kb) to 5 (covering 19.6 kb, including a missense variant rs1260326) after trans-ethnic meta-analysis. We also confirmed the previously reported associations of PKD2L1, FADS1/2, GCKR, and HIF1AN with palmitoleic acid and of FADS1/2 and LPCAT3 with oleic acid in the Chinese-specific GWAS and the trans-ethnic meta-analyses. Pathway-based analyses suggested that the identified loci were in unsaturated FA metabolism and signaling pathways. Our findings provide novel insight into the genetic basis relevant to MUFA metabolism and biology.
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Metabolic Effects of Monounsaturated Fatty Acid-Enriched Diets Compared With Carbohydrate or Polyunsaturated Fatty Acid-Enriched Diets in Patients With Type 2 Diabetes: A Systematic Review and Meta-analysis of Randomized Controlled Trials.
Qian, F, Korat, AA, Malik, V, Hu, FB
Diabetes care. 2016;(8):1448-57
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OBJECTIVE Dietary interventions in patients with type 2 diabetes (T2D) are important for preventing long-term complications. Although a healthy diet is crucial, there is still uncertainty about the optimal macronutrient composition. We performed a meta-analysis comparing diets high in cis-monounsaturated fatty acids (MUFA) to diets high in carbohydrates (CHO) or in polyunsaturated fatty acids (PUFA) on metabolic risk factors in patients with T2D. RESEARCH DESIGN AND METHODS We systematically reviewed PubMed, MEDLINE, and Cochrane databases and prior systematic reviews and meta-analyses to identify interventions assessing HbA1c, fasting plasma glucose and insulin, LDL and HDL cholesterol, triglycerides, body weight, or systolic/diastolic blood pressure. Meta-analyses were conducted using both fixed- and random-effects models to calculate the weighted mean difference (WMD) and 95% CI. RESULTS We identified 24 studies totaling 1,460 participants comparing high-MUFA to high-CHO diets and 4 studies totaling 44 participants comparing high-MUFA to high-PUFA diets. When comparing high-MUFA to high-CHO diets, there were significant reductions in fasting plasma glucose (WMD -0.57 mmol/L [95% CI -0.76, -0.39]), triglycerides (-0.31 mmol/L [-0.44, -0.18]), body weight (-1.56 kg [-2.89, -0.23]), and systolic blood pressure (-2.31 mmHg [-4.13, -0.49]) along with significant increases in HDL cholesterol (0.06 mmol/L [0.02, 0.10]). When high-MUFA diets were compared with high-PUFA diets, there was a significant reduction in fasting plasma glucose (-0.87 mmol/L [-1.67, -0.07]). All of the outcomes had low to medium levels of heterogeneity, ranging from 0.0 to 69.5% for diastolic blood pressure (Phet = 0.011). CONCLUSIONS Our meta-analysis provides evidence that consuming diets high in MUFA can improve metabolic risk factors among patients with T2D.
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Effects of Saturated Fat, Polyunsaturated Fat, Monounsaturated Fat, and Carbohydrate on Glucose-Insulin Homeostasis: A Systematic Review and Meta-analysis of Randomised Controlled Feeding Trials.
Imamura, F, Micha, R, Wu, JH, de Oliveira Otto, MC, Otite, FO, Abioye, AI, Mozaffarian, D
PLoS medicine. 2016;(7):e1002087
Abstract
BACKGROUND Effects of major dietary macronutrients on glucose-insulin homeostasis remain controversial and may vary by the clinical measures examined. We aimed to assess how saturated fat (SFA), monounsaturated fat (MUFA), polyunsaturated fat (PUFA), and carbohydrate affect key metrics of glucose-insulin homeostasis. METHODS AND FINDINGS We systematically searched multiple databases (PubMed, EMBASE, OVID, BIOSIS, Web-of-Knowledge, CAB, CINAHL, Cochrane Library, SIGLE, Faculty1000) for randomised controlled feeding trials published by 26 Nov 2015 that tested effects of macronutrient intake on blood glucose, insulin, HbA1c, insulin sensitivity, and insulin secretion in adults aged ≥18 years. We excluded trials with non-isocaloric comparisons and trials providing dietary advice or supplements rather than meals. Studies were reviewed and data extracted independently in duplicate. Among 6,124 abstracts, 102 trials, including 239 diet arms and 4,220 adults, met eligibility requirements. Using multiple-treatment meta-regression, we estimated dose-response effects of isocaloric replacements between SFA, MUFA, PUFA, and carbohydrate, adjusted for protein, trans fat, and dietary fibre. Replacing 5% energy from carbohydrate with SFA had no significant effect on fasting glucose (+0.02 mmol/L, 95% CI = -0.01, +0.04; n trials = 99), but lowered fasting insulin (-1.1 pmol/L; -1.7, -0.5; n = 90). Replacing carbohydrate with MUFA lowered HbA1c (-0.09%; -0.12, -0.05; n = 23), 2 h post-challenge insulin (-20.3 pmol/L; -32.2, -8.4; n = 11), and homeostasis model assessment for insulin resistance (HOMA-IR) (-2.4%; -4.6, -0.3; n = 30). Replacing carbohydrate with PUFA significantly lowered HbA1c (-0.11%; -0.17, -0.05) and fasting insulin (-1.6 pmol/L; -2.8, -0.4). Replacing SFA with PUFA significantly lowered glucose, HbA1c, C-peptide, and HOMA. Based on gold-standard acute insulin response in ten trials, PUFA significantly improved insulin secretion capacity (+0.5 pmol/L/min; 0.2, 0.8) whether replacing carbohydrate, SFA, or even MUFA. No significant effects of any macronutrient replacements were observed for 2 h post-challenge glucose or insulin sensitivity (minimal-model index). Limitations included a small number of trials for some outcomes and potential issues of blinding, compliance, generalisability, heterogeneity due to unmeasured factors, and publication bias. CONCLUSIONS This meta-analysis of randomised controlled feeding trials provides evidence that dietary macronutrients have diverse effects on glucose-insulin homeostasis. In comparison to carbohydrate, SFA, or MUFA, most consistent favourable effects were seen with PUFA, which was linked to improved glycaemia, insulin resistance, and insulin secretion capacity.
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Effect of Insulin Resistance on Monounsaturated Fatty Acid Levels: A Multi-cohort Non-targeted Metabolomics and Mendelian Randomization Study.
Nowak, C, Salihovic, S, Ganna, A, Brandmaier, S, Tukiainen, T, Broeckling, CD, Magnusson, PK, Prenni, JE, Wang-Sattler, R, Peters, A, et al
PLoS genetics. 2016;(10):e1006379
Abstract
Insulin resistance (IR) and impaired insulin secretion contribute to type 2 diabetes and cardiovascular disease. Both are associated with changes in the circulating metabolome, but causal directions have been difficult to disentangle. We combined untargeted plasma metabolomics by liquid chromatography/mass spectrometry in three non-diabetic cohorts with Mendelian Randomization (MR) analysis to obtain new insights into early metabolic alterations in IR and impaired insulin secretion. In up to 910 elderly men we found associations of 52 metabolites with hyperinsulinemic-euglycemic clamp-measured IR and/or β-cell responsiveness (disposition index) during an oral glucose tolerance test. These implicated bile acid, glycerophospholipid and caffeine metabolism for IR and fatty acid biosynthesis for impaired insulin secretion. In MR analysis in two separate cohorts (n = 2,613) followed by replication in three independent studies profiled on different metabolomics platforms (n = 7,824 / 8,961 / 8,330), we discovered and replicated causal effects of IR on lower levels of palmitoleic acid and oleic acid. A trend for a causal effect of IR on higher levels of tyrosine reached significance only in meta-analysis. In one of the largest studies combining "gold standard" measures for insulin responsiveness with non-targeted metabolomics, we found distinct metabolic profiles related to IR or impaired insulin secretion. We speculate that the causal effects on monounsaturated fatty acid levels could explain parts of the raised cardiovascular disease risk in IR that is independent of diabetes development.
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Dietary fat intake and endometrial cancer risk: A dose response meta-analysis.
Zhao, J, Lyu, C, Gao, J, Du, L, Shan, B, Zhang, H, Wang, HY, Gao, Y
Medicine. 2016;(27):e4121
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Since body fatness is a convincing risk factor for endometrial cancer, dietary fat intake was speculated to be associated with endometrial cancer risk. However, epidemiological studies are inconclusive. We aimed to conduct a meta-analysis to assess the associations between dietary fat intake and endometrial cancer risk. We searched the PubMed, Embase, and Web of science databases updated to September 2015. In total, 7 cohort and 14 case-control studies were included. Pooled analysis of case-control studies suggested that endometrial cancer risk was significantly increased by 5% per 10% kilocalories from total fat intake (P=0.02) and by 17% per 10 g/1000 kcal of saturated fat intake (P < 0.001). Summary of 3 cohort studies showed significant inverse association between monounsaturated fatty acids and endometrial cancer risk (odds ratio = 0.84, 95% confidence interval = 0.73-0.98) with a total of 524583 participants and 3503 incident cases. No significant associations were found for polyunsaturated fatty acids and linoleic acid. In conclusion, positive associations with endometrial cancer risk were observed for total fat and saturated fat intake in the case-control studies. Results from the cohort studies suggested higher monounsaturated fatty acids intake was significantly associated with lower endometrial cancer risk.
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Effects of monounsaturated fatty acids on glycaemic control in patients with abnormal glucose metabolism: a systematic review and meta-analysis.
Schwingshackl, L, Strasser, B, Hoffmann, G
Annals of nutrition & metabolism. 2011;(4):290-6
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BACKGROUND/AIMS: In 2008, the American Diabetes Association recommended low-carbohydrate or low-fat diets for weight management in patients with established type 2 diabetes (T2D), while the amount of monounsaturated fatty acids (MUFA) was not specified. This systematic review focused on the effects of diets high in MUFA versus diets low in MUFA on important risk factors of T2D (i.e. plasma glucose, insulin, homeostasis model assessment of insulin resistance and glycosylated haemoglobin, HbA1c). METHODS Nine randomized controlled intervention trials with a total of 1,547 participants and a running time of at least 6 months, comparing diets high versus low in MUFA among adults with abnormal glucose metabolism (T2D, impaired glucose tolerance and insulin resistant), being overweight or obese, have been included in the meta-analysis. We performed a random effects meta-analysis to determine the weighted mean differences with 95% confidence intervals using the software package Review Manager 5.0.25 of the Cochrane Collaboration. RESULTS Significant differences in HbA1c were found (weighted mean difference -0.21%, 95% CI -0.40 to -0.02; p = 0.03), favouring the high MUFA groups. In contrast, fasting plasma glucose, fasting plasma insulin as well as the homeostasis model assessment of insulin resistance were not affected by the amounts of MUFA in the dietary protocols. CONCLUSIONS In summary, this systematic review found that high MUFA diets appear to be effective in reducing HbA1c, and therefore, should be recommended in the dietary regimes of T2D.
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Effects of monounsaturated fatty acids on cardiovascular risk factors: a systematic review and meta-analysis.
Schwingshackl, L, Strasser, B, Hoffmann, G
Annals of nutrition & metabolism. 2011;(2-4):176-86
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The appropriate pattern of macronutrient distribution for dietary protocols aimed at treating or preventing obesity and its associated cardiovascular diseases is still a controversial topic of discussion. Recommendations considering a specific percentage or range for monounsaturated fatty acids (MUFA) are rare. It was the aim of this study to analyze long-term, randomized, controlled dietary intervention trials and to investigate the effects of MUFA on the biomarkers of obesity and cardiovascular risk factors. Dietary regimens with a high amount of MUFA (>12%) were compared to those with ≤12%. The biomarkers taken into account were weight, waist circumference, fat mass, total cholesterol, LDL cholesterol, HDL cholesterol, triacylglycerols, systolic and diastolic blood pressure, as well as C-reactive protein. A total of 12 studies met the inclusion criteria. Data analysis was performed using the Review Manager 5.0.25 software. Significant differences between high- and low-MUFA protocols could be observed with respect to fat mass [-1.94 kg (confidence interval -3.72, -0.17), p = 0.03], systolic blood pressure [-2.26 mm Hg (confidence interval -4.28, -0.25), p = 0.03] and diastolic blood pressure [-1.15 mm Hg (confidence interval -1.96, -0.34), p = 0.005] favoring the dietary protocols with >12% MUFA. Therefore, MUFA might represent a useful tool in the design of dietary regimens for obesity and cardiovascular disease.