Prevention of type 2 diabetes (T2D) is a great challenge worldwide. The aim of this evidence synthesis was to summarize the available evidence in order to update the European Association for the Study of Diabetes (EASD) clinical practice guidelines for nutrition therapy. We conducted a systematic review and, where appropriate, meta-analyses of randomized controlled trials (RCTs) carried out in people with impaired glucose tolerance (IGT) (six studies) or dysmetabolism (one study) to answer the following questions: What is the evidence that T2D is preventable by lifestyle changes? What is the optimal diet (with a particular focus on diet quality) for prevention, and does the prevention of T2D result in a lower risk of late complications of T2D? The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was applied to assess the certainty of the trial evidence. Altogether seven RCTs (N = 4090) fulfilled the eligibility criteria and were included in the meta-analysis. The diagnosis of incident diabetes was based on an oral glucose tolerance test (OGTT). The overall risk reduction of T2D by the lifestyle interventions was 0.53 (95% CI 0.41; 0.67). Most of the trials aimed to reduce weight, increase physical activity, and apply a diet relatively low in saturated fat and high in fiber. The PREDIMED trial that did not meet eligibility criteria for inclusion in the meta-analysis was used in the final assessment of diet quality. We conclude that T2D is preventable by changing lifestyle and the risk reduction is sustained for many years after the active intervention (high certainty of evidence). Healthy dietary changes based on the current recommendations and the Mediterranean dietary pattern can be recommended for the long-term prevention of diabetes. There is limited or insufficient data to show that prevention of T2D by lifestyle changes results in a lower risk of cardiovascular and microvascular complications.

The effects of both the amount and quality of dietary fat have been studied intensively during the past decades. Previously, low-fat diets were recommended without much attention to the quality of fat, whereas there is general emphasis on the quality of fat in current guidelines. The objective of this systematic review (SR) was to assess the evidence of an effect of the amount and type of dietary fat on body weight (BW), risk factors, and risk of non-communicable diseases, that is, type 2 diabetes (T2DM), cardiovascular diseases (CVD), and cancer in healthy subjects or subjects at risk for these diseases. This work was performed in the process of updating the fourth edition of the Nordic Nutrition Recommendations from 2004. The literature search was performed in October 2010 covering articles published since January 2000. A complementary search was done in February 2012 covering literature until December 2011. Two authors independently selected articles for inclusion from a total of about 16,000 abstracts according to predefined criteria. Randomized controlled trials (RCT) and prospective cohort studies (PCS) were included as well as nested case–control studies. A few retrospective case–control studies were also included when limited or no data were available from other study types. Altogether 607 articles were quality graded and the observed effects in these papers were summarized. Convincing evidence was found that partial replacement of saturated fat (SFA) with polyunsaturated fat (PUFA) or monounsaturated fat (MUFA) lowers fasting serum/plasma total and LDL cholesterol concentrations. The evidence was probable for a decreasing effect of fish oil on concentration of serum/plasma total triglycerides as compared with MUFA. Beneficial effect of MUFA both on insulin sensitivity and fasting plasma/serum insulin concentration was considered as probable in comparisons of MUFA and carbohydrates versus SFA, whereas no effect was found on fasting glucose concentration in these comparisons. There was probable evidence for a moderate direct association between total fat intake and BW. Furthermore, there was convincing evidence that partial replacement of SFA with PUFA decreases the risk of CVD, especially in men. This finding was supported by an association with biomarkers of PUFA intake; the evidence of a beneficial effect of dietary total PUFA, n-6 PUFA, and linoleic acid (LA) on CVD mortality was limited suggestive. Evidence for a direct association between total fat intake and risk of T2DM was inconclusive, whereas there was limited-suggestive evidence from biomarker studies that LA is inversely associated with the risk of T2DM. However, there was limited-suggestive evidence in biomarker studies that odd-chain SFA found in milk fat and fish may be inversely related to T2DM, but these associations have not been supported by controlled studies. The evidence for an association between dietary n-3 PUFA and T2DM was inconclusive. Evidence for effects of fat on major types of cancer was inconclusive regarding both the amount and quality of dietary fat, except for prostate cancer where there was limited-suggestive evidence for an inverse association with intake of ALA and for ovarian cancer for which there was limited-suggestive evidence for a positive association with intake of SFA. This SR reviewed a large number of studies focusing on several different health outcomes. The time period covered by the search may not have allowed obtaining the full picture of the evidence in all areas covered by this SR. However, several SRs and meta-analyses that covered studies published before year 2000 were evaluated, which adds confidence to the results. Many of the investigated questions remain unresolved, mainly because of few studies on certain outcomes, conflicting results from studies, and lack of high quality–controlled studies. There is thus an evident need of highly controlled RCT and PCS with sufficient number of subjects and long enough duration, specifically regarding the effects of the amount and quality of dietary fat on insulin sensitivity, T2DM, low-grade inflammation, and blood pressure. New metabolic and other potential risk markers and utilization of new methodology in the area of lipid metabolism may provide new insight.Keywords: body weight; cancer; cardiovascular disease; fat; fatty acid; diet; vegetable oil; stroke; type 2 diabetes(Published: 10 July 2014)Citation: Food & Nutrition Research 2014, 58: 25145 - http://dx.doi.org/10.3402/fnr.v58.25145Special Issue: This paper is part of the Nordic Nutrition Recommendations - The NNR5 project. More papers from this issue can be found at http://www.foodandnutritionresearch.net

Background: With no approved pharmacotherapy to date, the present therapeutic cornerstone for non-alcoholic fatty liver diseases (NAFLD) is a lifestyle intervention. Guidelines endorse weight loss through dietary modifications, physical exercise, or both. However, no consensus exists on the optimal dietary treatment.Objectives: The aim of our systematic review and meta-analysis was to summarize and assess the evidence for applied types of dietary interventions on the liver and metabolic outcomes in patients with NAFLD, aside from any effects of exercise intervention.Methods: This systematic review was conducted according to the Preferred Reporting Items of Systematic Reviews and Meta-analysis (PRISMA) statement guidelines. The search was conducted in PubMed, Scopus, and Cochrane databases in February 2020. Included were only dietary interventions without exercise. This study was registered at PROSPERO: CRD42020203573.Results: Eight randomized controlled trials, seven with endpoint reduction of hepatic steatosis, one with an assessment of endpoint fibrosis, were included in this systematic review, five of which were included in the meta-analysis. Mediterranean dietary interventions without energy restriction (n = 3) showed significant reduction of intrahepatic lipid content (IHL) (SDM: −0.57, 95% CI: −1.04, −0.10), but there was no significant change in alanine transaminase (ALT) (SDM: 0.59, 95% CI: −0.5, −1.68). Hypocaloric dietary interventions with foods high in unsaturated fatty acids (n = 2) led to a significant decrease in ALT (SDM: −1.09, 95% CI: −1.49, −0.69) and aspartate aminotransferase (AST) (SDM: −0.75, 95% CI: −1.27, 0.23); yet effects on steatosis could not be aggregated due to different assessment techniques. Mediterranean diet did not lead to significant changes in concentrations of gamma-glutamyl transpeptidase (γGT), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), fasting glucose or insulin, or homeostatic assessment for insulin resistance.Conclusions: In patients with NAFLD, Mediterranean and hypocaloric dietary interventions favoring unsaturated fatty acids result in improvements in IHL and transaminases. Since many dietary intervention studies are combined with exercise interventions and there is a paucity of ample-sized studies examining dietary interventions on the more advanced and clinically relevant stages of NAFLD, that is active and fibrotic NASH, with multiparametric imaging and liver histology as outcome measures, the optimal dietary invention in NAFLD remains to be defined.

One of the focuses of non-alcoholic fatty liver disease (NAFLD) treatment is exercise. Randomized controlled trials investigating the effects of exercise without dietary changes on NAFLD-related clinical parameters (liver parameters, lipid metabolism, glucose metabolism, gut microbiota, and metabolites) were screened using the PubMed, Scopus, Web of Science, and Cochrane databases on 13 February 2020. Meta-analyses were performed on 10 studies with 316 individuals who had NAFLD across three exercise regimens: aerobic exercise, resistance training, and a combination of both. No studies investigating the role of gut microbiota and exercise in NAFLD were found. A quality assessment via the (RoB)2 tool was conducted and potential publication bias, statistical outliers, and influential cases were identified. Overall, exercise without significant weight loss significantly reduced the intrahepatic lipid (IHL) content (SMD: −0.76, 95% CI: −1.04, −0.48) and concentrations of alanine aminotransaminase (ALT) (SMD: −0.52, 95% CI: −0.90, −0.14), aspartate aminotransaminase (AST) (SMD: −0.68, 95% CI: −1.21, −0.15), low-density lipoprotein cholesterol (SMD: −0.34, 95% CI: −0.66, −0.02), and triglycerides (TG) (SMD: −0.59, 95% CI: −1.16, −0.02). The concentrations of high-density lipoprotein cholesterol, total cholesterol (TC), fasting glucose, fasting insulin, and glycated hemoglobin were non-significantly altered. Aerobic exercise alone significantly reduced IHL, ALT, and AST; resistance training alone significantly reduced TC and TG; a combination of both exercise types significantly reduced IHL. To conclude, exercise overall likely had a beneficial effect on alleviating NAFLD without significant weight loss. The study was registered at PROSPERO: CRD42020221168 and funded by the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement no. 813781.

The mechanisms by which exercise benefits patients with non-alcoholic fatty liver disease (NAFLD), the most common liver disease worldwide, remain poorly understood. A non-targeted liquid chromatography-mass spectrometry (LC–MS)-based metabolomics analysis was used to identify metabolic changes associated with NAFLD in humans upon exercise intervention (without diet change) across four different sample types—adipose tissue (AT), plasma, urine, and stool. Altogether, 46 subjects with NAFLD participated in this randomized controlled intervention study. The intervention group (n = 21) performed high-intensity interval training (HIIT) for 12 weeks while the control group (n = 25) kept their sedentary lifestyle. The participants' clinical parameters and metabolic profiles were compared between baseline and endpoint. HIIT significantly decreased fasting plasma glucose concentration (p = 0.027) and waist circumference (p = 0.028); and increased maximum oxygen consumption rate and maximum achieved workload (p < 0.001). HIIT resulted in sample-type-specific metabolite changes, including accumulation of amino acids and their derivatives in AT and plasma, while decreasing in urine and stool. Moreover, many of the metabolite level changes especially in the AT were correlated with the clinical parameters monitored during the intervention. In addition, certain lipids increased in plasma and decreased in the stool. Glyco-conjugated bile acids decreased in AT and urine. The 12-week HIIT exercise intervention has beneficial ameliorating effects in NAFLD subjects on a whole-body level, even without dietary changes and weight loss. The metabolomics analysis applied to the four different sample matrices provided an overall view on several metabolic pathways that had tissue-type specific changes after HIIT intervention in subjects with NAFLD. The results highlight especially the role of AT in responding to the HIIT challenge, and suggest that altered amino acid metabolism in AT might play a critical role in e.g. improving fasting plasma glucose concentration.Trial registration ClinicalTrials.gov (NCT03995056).

Low-grade inflammation (LGI) has been suggested to be involved in the development of chronic diseases. Healthy dietary patterns, such as the Mediterranean diet (MD), may decrease the markers of LGI. Healthy Nordic diet (HND) has many similarities with MD, but its effects on LGI are less well known. Both of these dietary patterns emphasize the abundant use of fruits and vegetables (and berries in HND), whole grain products, fish, and vegetable oil (canola oil in HND and olive oil in MD), but restrict the use of saturated fat and red and processed meat. The aim of this narrative review is to summarize the results of studies, which have investigated the associations or effects of HND on the markers of LGI. Altogether, only two publications of observational studies and eight publications of intervention trials were found through the literature search. Both observational studies reported an inverse association between the adherence to HND and concentration of high sensitivity C-reactive protein (hsCRP). A significant decrease in the concentration of hsCRP was reported in two out of four intervention studies measuring hsCRP. Single intervention studies reported the beneficial effects on interleukin 1Ra and Cathepsin S. Current evidence suggests the beneficial effects on LGI with HND, but more carefully controlled studies are needed to confirm the anti-inflammatory effects of the HND.