Relation of total sugars, fructose and sucrose with incident type 2 diabetes: a systematic review and meta-analysis of prospective cohort studies.

BACKGROUND: Sugar-sweetened beverages are associated with type 2 diabetes. To assess whether this association holds for the fructose-containing sugars they contain, we conducted a systematic review and meta-analysis of prospective cohort studies. METHODS: We searched MEDLINE, Embase, CINAHL and the Cochrane Library (through June 2016). We included prospective cohort studies that assessed the relation of fructose-containing sugars with incident type 2 diabetes. Two independent reviewers extracted relevant data and assessed risk of bias. We pooled risk ratios (RRs) using random effects meta-analyses. The overall quality of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. RESULTS: Fiffeen prospective cohort studies (251 261 unique participants, 16 416 cases) met the eligibility criteria, comparing the highest intake (median 137, 35.2 and 78 g/d) with the lowest intake (median 65, 9.7 and 25.8 g/d) of total sugars, fructose and sucrose, respectively. Although there was no association of total sugars (RR 0.91, 95% confidence interval [CI] 0.76-1.09) or fructose (RR 1.04, 95% CI 0.84-1.29) with type 2 diabetes, sucrose was associated with a decreased risk of type 2 diabetes (RR 0.89, 95% CI 0.80-0.98). Our confidence in the estimates was limited by evidence of serious inconsistency between studies for total sugars and fructose, and serious imprecision in the pooled estimates for all 3 sugar categories. INTERPRETATION: Current evidence does not allow us to conclude that fructose-containing sugars independent of food form are associated with increased risk of type 2 diabetes. Further research is likely to affect our estimates. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT01608620.

Pregnant women's preferences for and concerns about preterm birth prevention: a cross-sectional survey.

BACKGROUND: Although there is a call for patient-centred prenatal care, women's preferences for and concerns about preterm birth (PTB) prevention have not been well-studied. Therefore, we conducted a cross-sectional survey to determine women's preferences for PTB prevention and their likelihood of following their healthcare provider's recommendations for PTB prevention, as well as factors associated with these responses. METHODS: A piloted self-administered questionnaire was completed by pregnant women who could read English. Data were collected about their preferences for and concerns about PTB prevention, and the likelihood of following their healthcare provider's recommendations, using multivariable logistic regression to control for other factors. RESULTS: Three hundred and eleven women at a median of 32-weeks of gestation completed the survey, a response rate of 85.2%. Most women reported that if they were told they were at increased risk for PTB, they preferred not to use PTB prevention (65.8%), of whom almost all (93.4%) reported they preferred close-monitoring and 6.6% preferred neither monitoring nor prevention. A much smaller proportion of women reported that they would not follow their healthcare provider's recommendation for progesterone (10.9%) compared to pessary (28.7%) or cerclage (50.2%). Women who were neither married nor in a common-law relationship were more likely to report that they would not follow recommendations for progesterone (aOR = 5.88 [95% CI: 1.72, 20.00]). Most women (84.5%) reported they would use other sources of information other than their main healthcare provider to learn more about PTB prevention, with the most popular source being the internet. CONCLUSIONS: Most women reported that if they were told they were at increased risk of PTB, they preferred close-monitoring over using PTB prevention. Their reported likelihood of not following their healthcare provider's recommendations for PTB prevention varied from 10.9% for progesterone to 50.2% for cerclage. These findings suggest that more education about the risk of PTB, PTB preventions, as well as compliance with progesterone is needed and that the internet would be an important source of information. However as our study was completed by women at a median of 32 weeks of gestation, future surveys targeted at women earlier in their pregnancy are needed.

Fructose vs. glucose and metabolism: do the metabolic differences matter?

PURPOSE OF REVIEW: Fructose is seen as uniquely contributing to the pandemics of obesity and its cardiometabolic complications. Much of the evidence for this view derives from the unique biochemical, metabolic, and endocrine responses that differentiate fructose from glucose. To understand whether these proposed mechanisms result in clinically meaningful modification of cardiovascular risk in humans, we update a series of systematic reviews and meta-analyses of controlled feeding trials to assess the cardiometabolic effects of fructose in isocaloric replacement for glucose. RECENT FINDINGS: A total of 20 controlled feeding trials (n = 344) have investigated the effect of fructose in/on cardiometabolic endpoints. Pooled analyses show that although fructose may increase total cholesterol, uric acid, and postprandial triglycerides in isocaloric replacement for glucose, it does not appear to be any worse than glucose in its effects on other aspects of the lipid profile, insulin, or markers of nonalcoholic fatty liver disease. It may also have important advantages over glucose for body weight, glycemic control, and blood pressure. SUMMARY: Depending on the cardiometabolic endpoint in question, fructose has variable effects when replacing glucose. In the absence of clear evidence of net harm, there is no justification to replace fructose with glucose in the diet.

Total fructose intake and risk of hypertension: a systematic review and meta-analysis of prospective cohorts.

OBJECTIVES: Although most controlled feeding trials have failed to show an adverse effect of fructose on blood pressure, concerns continue to be raised regarding the role of fructose in hypertension. To quantify the association between fructose-containing sugar (high-fructose corn syrup, sucrose, and fructose) intake and incident hypertension, a systematic review and meta-analysis of prospective cohort studies was undertaken. METHODS: MEDLINE, EMBASE, CINAHL and the Cochrane Library (through February 5, 2014) were searched for relevant studies. Two independent reviewers reviewed and extracted relevant data. Risk estimates were aggregated comparing the lowest (reference) quintile with highest quintile of intake using inverse variance random effect models and expressed as risk ratios (RR) with 95% confidence intervals (CIs). Interstudy heterogeneity was assessed (Cochran Q statistic) and quantified (I(2) statistic). The Newcastle-Ottawa Scale assessed study quality. Clinicaltrials.gov NCT01608620. RESULTS: Eligibility criteria were met by 3 prospective cohorts (n = 37,375 men and 185,855 women) with 58,162 cases of hypertension observed over 2,502,357 person-years of follow-up. Median fructose intake was 5.7-6.0% total energy in the lowest quintile and 13.9-14.3% total energy in the highest quintile. Fructose intake was not associated with incident hypertension (RR = 1.02, 95% CI, 0.99-1.04), with no evidence of heterogeneity (I(2) = 0%, p = 0.59). Spline curve modeling showed a U-shaped relationship with a negative association at intakes ≤50th percentile (∼10% total energy) and a positive association at higher intakes. CONCLUSIONS: Total fructose intake was not associated with an increased risk of hypertension in 3 large prospective cohorts of U.S. men and women.

Effect of dietary pulse intake on established therapeutic lipid targets for cardiovascular risk reduction: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Evidence from controlled trials encourages the intake of dietary pulses (beans, chickpeas, lentils and peas) as a method of improving dyslipidemia, but heart health guidelines have stopped short of ascribing specific benefits to this type of intervention or have graded the beneficial evidence as low. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the effect of dietary pulse intake on established therapeutic lipid targets for cardiovascular risk reduction. METHODS: We searched electronic databases and bibliographies of selected trials for relevant articles published through Feb. 5, 2014. We included RCTs of at least 3 weeks' duration that compared a diet emphasizing dietary pulse intake with an isocaloric diet that did not include dietary pulses. The lipid targets investigated were low-density lipoprotein (LDL) cholesterol, apolipoprotein B and non-high-density lipoprotein (non-HDL) cholesterol. We pooled data using a random-effects model. RESULTS: We identified 26 RCTs (n = 1037) that satisfied the inclusion criteria. Diets emphasizing dietary pulse intake at a median dose of 130 g/d (about 1 serving daily) significantly lowered LDL cholesterol levels compared with the control diets (mean difference -0.17 mmol/L, 95% confidence interval -0.25 to -0.09 mmol/L). Treatment effects on apolipoprotein B and non-HDL cholesterol were not observed. INTERPRETATION: Our findings suggest that dietary pulse intake significantly reduces LDL cholesterol levels. Trials of longer duration and higher quality are needed to verify these results. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT01594567.

Fructose in obesity and cognitive decline: is it the fructose or the excess energy?

We read with interest the review by Lakhan and Kirchgessner, proposing that high fructose intake promotes obesity, metabolic syndrome, diabetes, and cognitive decline. Their focus on the role of fructose seems premature due to confounding from energy and the heavy reliance on low quality evidence from animal models. There is a lack of high quality evidence directly assessing the role of fructose in cognitive decline. Although one cannot exclude the possibility of a link, it remains an unconfirmed hypothesis.

The effects of inulin-type fructans on cardiovascular disease risk factors: systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Inulin-type fructans (ITF) are the leading prebiotics in the market. Available evidence provides conflicting results regarding the beneficial effects of ITF on cardiovascular disease risk factors. OBJECTIVES: This study aimed to evaluate the effects of ITF supplementation on cardiovascular disease risk factors in adults. METHODS: We searched MEDLINE, EMBASE, Emcare, AMED, CINAHL, and the Cochrane Library databases from inception through May 15, 2022. Eligible randomized controlled trials (RCTs) administered ITF or placebo (for example, control, foods, diets) to adults for ≥2 weeks and reported one or more of the following: low, very-low, or high-density lipoprotein cholesterol (LDL-C, VLDL-C, HDL-C); total cholesterol; apolipoprotein A1 or B; triglycerides; fasting blood glucose; body mass index; body weight; waist circumference; waist-to-hip ratio; systolic or diastolic blood pressure; or hemoglobin A1c. Two reviewers independently and in duplicate screened studies, extracted data, and assessed risk of bias. We pooled data using random-effects model, and assessed the certainty of evidence (CoE) using the Grading of Recommendations, Assessment, Development and Evaluation approach. RESULTS: We identified 1767 studies and included 55 RCTs with 2518 participants in meta-analyses. The pooled estimate showed that ITF supplementation reduced LDL-C [mean difference (MD) -0.14 mmol/L, 95% confidence interval (95% CI: -0.24, -0.05), 38 RCTs, 1879 participants, very low CoE], triglycerides (MD -0.06 mmol/L, 95% CI: -0.12, -0.01, 40 RCTs, 1732 participants, low CoE), and body weight (MD -0.97 kg, 95% CI: -1.28, -0.66, 36 RCTs, 1672 participants, low CoE) but little to no significant effect on other cardiovascular disease risk factors. The effects were larger when study duration was ≥6 weeks and in pre-obese and obese participants. CONCLUSION: ITF may reduce low-density lipoprotein, triglycerides, and body weight. However, due to low to very low CoE, further well-designed and executed trials are needed to confirm these effects. PROSPERO REGISTRATION NUMBER: CRD42019136745.

Fructose-containing sugars, blood pressure, and cardiometabolic risk: a critical review.

Excessive fructose intake from high-fructose corn syrup (HFCS) and sucrose has been implicated as a driving force behind the increasing prevalence of obesity and its downstream cardiometabolic complications including hypertension, gout, dyslidpidemia, metabolic syndrome, diabetes, and non-alcoholic fatty liver disease (NAFLD). Most of the evidence to support these relationships draws heavily on ecological studies, animal models, and select human trials of fructose overfeeding. There are a number of biological mechanisms derived from animal models to explain these relationships, including increases in de novo lipogenesis and uric acid-mediated hypertension. Differences between animal and human physiology, along with the supraphysiologic level at which fructose is fed in these models, limit their translation to humans. Although higher level evidence from large prospective cohorts studies has shown significant positive associations comparing the highest with the lowest levels of intake of sugar-sweetened beverages (SSBs), these associations do not hold true at moderate levels of intake or when modeling total sugars and are subject to collinearity effects from related dietary and lifestyle factors. The highest level of evidence from controlled feeding trials has shown a lack of cardiometabolic harm of fructose and SSBs under energy-matched conditions at moderate levels of intake. It is only when fructose-containing sugars or SSBs are consumed at high doses or supplement diets with excess energy that a consistent signal for harm is seen. The available evidence suggests that confounding by excess energy is an important consideration in assessing the role of fructose-containing sugars and SSBs in the epidemics of hypertension and other cardiometabolic diseases.

Self-withdrawal from scheduled bariatric surgery: Qualitative study exploring patient and healthcare provider perspectives.

The objective of the study was to explore the experience of patients who self-withdrew from their scheduled bariatric surgery (BS) after completing the lengthy multidisciplinary assessment and optimization process, and to examine how these withdrawals affect healthcare providers (HCPs) in a Bariatric Centre of Excellence (BCoE). Interviews were conducted with patients who self-withdrew, within 1 month, from scheduled BS. Additionally, a focus group with HCPs from the same BCoE was completed. The data were analysed using an inductive, emergent thematic approach with open coding in NVivo 12, with comparative analysis to identify common themes between groups. Eleven patients and 14 HCPs participated. HCPs identified several behavioural and logistical red flags among patients who self-withdrew from scheduled BS. Patients and HCPs felt the decision was appropriate, owing to a patient's lack of mental preparedness for change, social supports, or fears of postoperative complications. HCPs reported frustration and described negative impacts on clinic efficiency. Additional mental health resources for patients contemplating self-withdrawal, such as peer support, were suggested. In conclusion, a patient's decision to self-withdraw from a scheduled BS is often sudden, definite, and associated with anxiety, fear of surgical risks and post-operative complications. Additional mental health resources at a BCoE may be beneficial to support patients at risk of self-withdrawal from scheduled BS.

Important food sources of fructose-containing sugars and adiposity: A systematic review and meta-analysis of controlled feeding trials.

BACKGROUND: Sugar-sweetened beverages (SSBs) providing excess energy increase adiposity. The effect of other food sources of sugars at different energy control levels is unclear. OBJECTIVES: To determine the effect of food sources of fructose-containing sugars by energy control on adiposity. METHODS: In this systematic review and meta-analysis, MEDLINE, Embase, and Cochrane Library were searched through April 2022 for controlled trials ≥2 wk. We prespecified 4 trial designs by energy control: substitution (energy-matched replacement of sugars), addition (energy from sugars added), subtraction (energy from sugars subtracted), and ad libitum (energy from sugars freely replaced). Independent authors extracted data. The primary outcome was body weight. Secondary outcomes included other adiposity measures. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to assess the certainty of evidence. RESULTS: We included 169 trials (255 trial comparisons, n = 10,357) assessing 14 food sources at 4 energy control levels over a median 12 wk. Total fructose-containing sugars increased body weight (MD: 0.28 kg; 95% CI: 0.06, 0.50 kg; PMD = 0.011) in addition trials and decreased body weight (MD: -0.96 kg; 95% CI: -1.78, -0.14 kg; PMD = 0.022) in subtraction trials with no effect in substitution or ad libitum trials. There was interaction/influence by food sources on body weight: substitution trials [fruits decreased; added nutritive sweeteners and mixed sources (with SSBs) increased]; addition trials [dried fruits, honey, fruits (≤10%E), and 100% fruit juice (≤10%E) decreased; SSBs, fruit drink, and mixed sources (with SSBs) increased]; subtraction trials [removal of mixed sources (with SSBs) decreased]; and ad libitum trials [mixed sources (with/without SSBs) increased]. GRADE scores were generally moderate. Results were similar across secondary outcomes. CONCLUSIONS: Energy control and food sources mediate the effect of fructose-containing sugars on adiposity. The evidence provides a good indication that excess energy from sugars (particularly SSBs at high doses ≥20%E or 100 g/d) increase adiposity, whereas their removal decrease adiposity. Most other food sources had no effect, with some showing decreases (particularly fruits at lower doses ≤10%E or 50 g/d). This trial was registered at clinicaltrials.gov as NCT02558920 (https://clinicaltrials.gov/ct2/show/NCT02558920).

The effects of fructose intake on serum uric acid vary among controlled dietary trials.

Hyperuricemia is linked to gout and features of metabolic syndrome. There is concern that dietary fructose may increase uric acid concentrations. To assess the effects of fructose on serum uric acid concentrations in people with and without diabetes, we conducted a systematic review and meta-analysis of controlled feeding trials. We searched MEDLINE, EMBASE, and the Cochrane Library for relevant trials (through August 19, 2011). Analyses included all controlled feeding trials ≥ 7 d investigating the effect of fructose feeding on uric acid under isocaloric conditions, where fructose was isocalorically exchanged with other carbohydrate, or hypercaloric conditions, and where a control diet was supplemented with excess energy from fructose. Data were aggregated by the generic inverse variance method using random effects models and expressed as mean difference (MD) with 95% CI. Heterogeneity was assessed by the Q statistic and quantified by I(2). A total of 21 trials in 425 participants met the eligibility criteria. Isocaloric exchange of fructose for other carbohydrate did not affect serum uric acid in diabetic and nondiabetic participants [MD = 0.56 µmol/L (95% CI: -6.62, 7.74)], with no evidence of inter-study heterogeneity. Hypercaloric supplementation of control diets with fructose (+35% excess energy) at extreme doses (213-219 g/d) significantly increased serum uric acid compared with the control diets alone in nondiabetic participants [MD = 31.0 mmol/L (95% CI: 15.4, 46.5)] with no evidence of heterogeneity. Confounding from excess energy cannot be ruled out in the hypercaloric trials. These analyses do not support a uric acid-increasing effect of isocaloric fructose intake in nondiabetic and diabetic participants. Hypercaloric fructose intake may, however, increase uric acid concentrations. The effect of the interaction of energy and fructose remains unclear. Larger, well-designed trials of fructose feeding at "real world" doses are needed.

'Catalytic' doses of fructose may benefit glycaemic control without harming cardiometabolic risk factors: a small meta-analysis of randomised controlled feeding trials.

Contrary to concerns that fructose may have adverse metabolic effects, there is evidence that small, 'catalytic' doses ( ≤ 10 g/meal) of fructose decrease the glycaemic response to high-glycaemic index meals in human subjects. To assess the longer-term effects of 'catalytic' doses of fructose, we undertook a meta-analysis of controlled feeding trials. We searched MEDLINE, EMBASE, CINAHL and the Cochrane Library. Analyses included all controlled feeding trials ≥ 7 d featuring 'catalytic' fructose doses ( ≤ 36 g/d) in isoenergetic exchange for other carbohydrates. Data were pooled by the generic inverse variance method using random-effects models and expressed as mean differences (MD) with 95 % CI. Heterogeneity was assessed by the Q statistic and quantified by I 2. The Heyland Methodological Quality Score assessed study quality. A total of six feeding trials (n 118) met the eligibility criteria. 'Catalytic' doses of fructose significantly reduced HbA1c (MD - 0·40, 95 % CI - 0·72, - 0·08) and fasting glucose (MD - 0·25, 95 % CI - 0·44, - 0·07). This benefit was seen in the absence of adverse effects on fasting insulin, body weight, TAG or uric acid. Subgroup and sensitivity analyses showed evidence of effect modification under certain conditions. The small number of trials and their relatively short duration limit the strength of the conclusions. In conclusion, this small meta-analysis shows that 'catalytic' fructose doses ( ≤ 36 g/d) may improve glycaemic control without adverse effects on body weight, TAG, insulin and uric acid. There is a need for larger, longer ( ≥ 6 months) trials using 'catalytic' fructose to confirm these results.

Dairy Product Consumption and Cardiovascular Health: A Systematic Review and Meta-analysis of Prospective Cohort Studies.

The association between dairy product consumption and cardiovascular health remains highly debated. We quantitatively synthesized prospective cohort evidence on the associations between dairy consumption and risk of hypertension (HTN), coronary heart disease (CHD), and stroke. We systematically searched PubMed, Embase, and Web of Science through August 1, 2020, to retrieve prospective cohort studies that reported on dairy consumption and risk of HTN, CHD, or stroke. We used random-effects models to calculate the pooled RR and 95% CI for the highest compared with the lowest category of intake and for a 1-serving/d increase in consumption. We rated the quality of evidence using NutriGrade. Fifty-five studies were included. Total dairy consumption was associated with a lower risk of HTN (RR for highest compared with lowest level of intake: 0.91, 95% CI: 0.86, 0.95, I2 = 73.5%; RR for 1-serving/d increase: 0.96, 95% CI: 0.94, 0.97, I2 = 66.5%), CHD (highest compared with lowest level of intake: 0.96, 95% CI: 0.92, 1.00, I2 = 46.6%; 1-serving/d increase: 0.98, 95% CI: 0.95, 1.00, I2 = 56.7%), and stroke (highest compared with lowest level of intake: 0.90, 95% CI: 0.85, 0.96, I2 = 60.8%; 1-serving/d increase: 0.96, 95% CI: 0.93, 0.99, I2 = 74.7%). Despite moderate to considerable heterogeneity, these associations remained consistent across multiple subgroups. Evidence on the relation between total dairy and risk of HTN and CHD was of moderate quality and of low quality for stroke. Low-fat dairy consumption was associated with lower risk of HTN and stroke and high-fat dairy with a lower risk of stroke. Milk, cheese, or yogurt consumption showed inconsistent associations with the cardiovascular outcomes in high compared with low intake and dose-response meta-analyses. Total dairy consumption was associated with a modestly lower risk of hypertension, CHD, and stroke. Moderate to considerable heterogeneity was observed in the estimates, and the overall quality of the evidence was low to moderate.

Effects of inulin-type fructans supplementation on cardiovascular disease risk factors: a protocol for a systematic review and meta-analysis of randomised controlled trials.

INTRODUCTION: This review aims to assess the effects of dietary supplementation with inulin-type fructans (ITF) compared with no supplementation on cardiovascular disease risk factors in adults and assess the quality of trial reporting using the Consolidated Standards of Reporting Trials (CONSORT) and CONSORT for abstract (CONSORT-A) checklists. METHODS AND ANALYSIS: We will search randomised controlled trials (RCTs) in MEDLINE, EMBASE, CINAHL, Emcare, AMED and the Cochrane Database of Systematic Reviews from inception to 31 March 2022, without any language restrictions. The RCTs need to administer ITF in adults for at least 2 weeks and assess effects on at least one cardiovascular risk factor. We will exclude RCTs that (1) assessed the postprandial effects of ITF; (2) included pregnant or lactating participants; (3) enrolled participants undergoing treatment that might affect the response to ITF. We will assess the study risk of bias (RoB) using V.2 of the Cochrane RoB tool for RCTs (RoB 2) and the certainty of the evidence using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. We will pool data using a random-effects model. We will use the χ2 test to compare compliance of CONSORT and CONSORT-A checklists and Poisson regression to identify factors associated with better reporting. ETHICS AND DISSEMINATION: Ethics approval is not required for secondary analysis of already published data. We will publish the reviews in a peer-review journal. PROSPERO REGISTRATION NUMBER: CRD42019136745.

Characteristics and quality of systematic reviews and meta-analyses of observational nutritional epidemiology: a cross-sectional study.

BACKGROUND: Dietary recommendations and policies should be guided by rigorous systematic reviews. Reviews that are of poor methodological quality may be ineffective or misleading. Most of the evidence in nutrition comes from nonrandomized studies of nutritional exposures (usually referred to as nutritional epidemiology studies), but to date methodological evaluations of the quality of systematic reviews of such studies have been sparse and inconsistent. OBJECTIVES: We aimed to investigate the quality of recently published systematic reviews and meta-analyses of nutritional epidemiology studies and to propose guidance addressing major limitations. METHODS: We searched MEDLINE (January 2018-August 2019), EMBASE (January 2018-August 2019), and the Cochrane Database of Systematic Reviews (January 2018-February 2019) for systematic reviews of nutritional epidemiology studies. We included a random sample of 150 reviews. RESULTS: Most reviews were published by authors from Asia (n = 49; 32.7%) or Europe (n = 43; 28.7%) and investigated foods or beverages (n = 60; 40.0%) and cancer morbidity and mortality (n = 54; 36%). Reviews often had important limitations: less than one-quarter (n = 30; 20.0%) reported preregistration of a protocol and almost one-third (n = 42; 28.0%) did not report a replicable search strategy. Suboptimal practices and errors in the synthesis of results were common: one-quarter of meta-analyses (n = 30; 26.1%) selected the meta-analytic model based on statistical indicators of heterogeneity and almost half of meta-analyses (n = 50; 43.5%) did not consider dose-response associations even when it was appropriate to do so. Only 16 (10.7%) reviews used an established system to evaluate the certainty of evidence. CONCLUSIONS: Systematic reviews of nutritional epidemiology studies often have serious limitations. Authors can improve future reviews by involving statisticians, methodologists, and researchers with substantive knowledge in the specific area of nutrition being studied and using a rigorous and transparent system to evaluate the certainty of evidence.

Food sources of fructose-containing sugars and glycaemic control: systematic review and meta-analysis of controlled intervention studies.

OBJECTIVE: To assess the effect of different food sources of fructose-containing sugars on glycaemic control at different levels of energy control. DESIGN: Systematic review and meta-analysis of controlled intervention studies. DATA SOURCES: Medine, Embase, and the Cochrane Library up to 25 April 2018. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Controlled intervention studies of at least seven days' duration and assessing the effect of different food sources of fructose-containing sugars on glycaemic control in people with and without diabetes were included. Four study designs were prespecified on the basis of energy control: substitution studies (sugars in energy matched comparisons with other macronutrients), addition studies (excess energy from sugars added to diets), subtraction studies (energy from sugars subtracted from diets), and ad libitum studies (sugars freely replaced by other macronutrients without control for energy). Outcomes were glycated haemoglobin (HbA1c), fasting blood glucose, and fasting blood glucose insulin. DATA EXTRACTION AND SYNTHESIS: Four independent reviewers extracted relevant data and assessed risk of bias. Data were pooled by random effects models and overall certainty of the evidence assessed by the GRADE approach (grading of recommendations assessment, development, and evaluation). RESULTS: 155 study comparisons (n=5086) were included. Total fructose-containing sugars had no harmful effect on any outcome in substitution or subtraction studies, with a decrease seen in HbA1c in substitution studies (mean difference -0.22% (95% confidence interval to -0.35% to -0.08%), -25.9 mmol/mol (-27.3 to -24.4)), but a harmful effect was seen on fasting insulin in addition studies (4.68 pmol/L (1.40 to 7.96)) and ad libitum studies (7.24 pmol/L (0.47 to 14.00)). There was interaction by food source, with specific food sources showing beneficial effects (fruit and fruit juice) or harmful effects (sweetened milk and mixed sources) in substitution studies and harmful effects (sugars-sweetened beverages and fruit juice) in addition studies on at least one outcome. Most of the evidence was low quality. CONCLUSIONS: Energy control and food source appear to mediate the effect of fructose-containing sugars on glycaemic control. Although most food sources of these sugars (especially fruit) do not have a harmful effect in energy matched substitutions with other macronutrients, several food sources of fructose-containing sugars (especially sugars-sweetened beverages) adding excess energy to diets have harmful effects. However, certainty in these estimates is low, and more high quality randomised controlled trials are needed. STUDY REGISTRATION: Clinicaltrials.gov (NCT02716870).

The effects of various diets on glycemic outcomes during pregnancy: A systematic review and network meta-analysis.

AIMS: Evidence to support dietary modifications to improve glycemia during pregnancy is limited, and the benefits of diet beyond limiting gestational weight gain is unclear. Therefore, a systematic review and network meta-analysis of randomized trials was conducted to compare the effects of various common diets, stratified by the addition of gestational weight gain advice, on fasting glucose and insulin, hemoglobin A1c (HbA1c), and homeostatic model assessment for insulin resistance (HOMA-IR) in pregnant women. METHODS: MEDLINE, EMBASE, Cochrane database, and reference lists of published studies were searched through April 2017. Randomized trials directly comparing two or more diets for ≥2-weeks were eligible. Bayesian network meta-analysis was performed for fasting glucose. Owing to a lack of similar dietary comparisons, a standard pairwise meta-analysis for the other glycemic outcomes was performed. The certainty of the pooled effect estimates was assessed using the GRADE tool. RESULTS: Twenty-one trials (1,865 participants) were included. In general, when given alongside gestational weight gain advice, fasting glucose improved in most diets compared to diets that gave gestational weight gain advice only. However, fasting glucose increased in high unsaturated or monounsaturated fatty acids diets. In the absence of gestational weight gain advice, fasting glucose improved in DASH-style diets compared to standard of care. Although most were non-significant, similar trends were observed for these same diets for the other glycemic outcomes. Dietary comparisons ranged from moderate to very low in quality of evidence. CONCLUSION/INTERPRETATION: Alongside with gestational weight gain advice, most diets, with the exception of a high unsaturated or a high monounsaturated fatty acid diet, demonstrated a fasting glucose improvement compared with gestational weight gain advice only. When gestational weight gain advice was not given, the DASH-style diet appeared optimal on fasting glucose. However, a small number of trials were identified and most dietary comparisons were underpowered to detect differences in glycemic outcomes. Further studies that are high in quality and adequately powered are needed to confirm these findings. REGISTRATION: PROSPERO CRD42015026008.