Aims/hypothesis Type 2 diabetes is regarded as inevitably progressive, with irreversible beta cell failure. The hypothesis was tested that both beta cell failure and insulin resistance can be reversed by dietary restriction of energy intake. Methods Eleven people with type 2 diabetes (49.5 ± 2.5 years, BMI 33.6 ± 1.2 kg/m², nine male and two female) were studied before and after 1, 4 and 8 weeks of a 2.5 MJ (600 kcal)/day diet. Basal hepatic glucose output, hepatic and peripheral insulin sensitivity and beta cell function were measured. Pancreas and liver triacylglycerol content was measured using three-point Dixon magnetic resonance imaging. An age-, sex- and weight-matched group of eight non-diabetic participants was studied. Results After 1 week of restricted energy intake, fasting plasma glucose normalised in the diabetic group (from 9.2 ± 0.4 to 5.9 ± 0.4 mmol/l; p = 0.003). Insulin suppression of hepatic glucose output improved from 43 ± 4% to 74 ± 5% (p = 0.003 vs baseline; controls 68 ± 5%). Hepatic triacylglycerol content fell from 12.8 ± 2.4% in the diabetic group to 2.9 ± 0.2% by week 8 (p = 0.003). The first-phase insulin response increased during the study period (0.19 ± 0.02 to 0.46 ± 0.07 nmol min⁻¹ m⁻²; p < 0.001) and approached control values (0.62 ± 0.15 nmol min⁻¹ m⁻²; p = 0.42). Maximal insulin response became supranormal at 8 weeks (1.37 ± 0.27 vs controls 1.15 ± 0.18 nmol min⁻¹ m⁻²). Pancreatic triacylglycerol decreased from 8.0 ± 1.6% to 6.2 ± 1.1% (p = 0.03). Conclusions/interpretation Normalisation of both beta cell function and hepatic insulin sensitivity in type 2 diabetes was achieved by dietary energy restriction alone. This was associated with decreased pancreatic and liver triacylglycerol stores. The abnormalities underlying type 2 diabetes are reversible by reducing dietary energy intake.

Observational studies report reduced colorectal cancer in regular aspirin consumers. Randomised controlled trials have shown reduced risk of adenomas but none have employed prevention of colorectal cancer as a primary endpoint. The CAPP2 trial aimed to investigate the antineoplastic effects of aspirin and a resistant starch in carriers of Lynch syndrome, the major form of hereditary colorectal cancer; we now report long-term follow-up of participants randomly assigned to aspirin or placebo. In the CAPP2 randomised trial, carriers of Lynch syndrome were randomly assigned in a two-by-two factorial design to 600 mg aspirin or aspirin placebo or 30 g resistant starch or starch placebo, for up to 4 years. Randomisation was in blocks of 16 with provision for optional single-agent randomisation and extended postintervention double-blind follow-up; participants and investigators were masked to treatment allocation. The primary endpoint was development of colorectal cancer. Analysis was by intention to treat and per protocol. This trial is registered, ISRCTN59521990. 861 participants were randomly assigned to aspirin or aspirin placebo. At a mean follow-up of 55·7 months, 48 participants had developed 53 primary colorectal cancers (18 of 427 randomly assigned to aspirin, 30 of 434 to aspirin placebo). Intention-to-treat analysis of time to first colorectal cancer showed a hazard ratio (HR) of 0·63 (95% CI 0·35-1·13, p=0·12). Poisson regression taking account of multiple primary events gave an incidence rate ratio (IRR) of 0·56 (95% CI 0·32-0·99, p=0·05). For participants completing 2 years of intervention (258 aspirin, 250 aspirin placebo), per-protocol analysis yielded an HR of 0·41 (0·19-0·86, p=0·02) and an IRR of 0·37 (0·18-0·78, p=0·008). No data for adverse events were available postintervention; during the intervention, adverse events did not differ between aspirin and placebo groups. 600 mg aspirin per day for a mean of 25 months substantially reduced cancer incidence after 55·7 months in carriers of hereditary colorectal cancer. Further studies are needed to establish the optimum dose and duration of aspirin treatment. European Union; Cancer Research UK; Bayer Corporation; National Starch and Chemical Co; UK Medical Research Council; Newcastle Hospitals trustees; Cancer Council of Victoria Australia; THRIPP South Africa; The Finnish Cancer Foundation; SIAK Switzerland; Bayer Pharma.

The Dietary Approach to Stop Hypertension (DASH) is recommended to lower blood pressure (BP), but its effects on cardiometabolic biomarkers are unclear. A systematic review and meta-analysis of randomised controlled trials (RCT) was conducted to determine the effects of the DASH diet on cardiovascular risk factors. Medline, Embase and Scopus databases were searched from inception to December 2013. Inclusion criteria were as follows: (1) DASH diet; (2) RCT; (3) risk factors including systolic and diastolic BP and glucose, HDL, LDL, TAG and total cholesterol concentrations; (4) control group. Random-effects models were used to determine the pooled effect sizes. Meta-regression analyses were carried out to examine the association between effect sizes, baseline values of the risk factors, BMI, age, quality of trials, salt intake and study duration. A total of twenty articles reporting data for 1917 participants were included in the meta-analysis. The duration of interventions ranged from 2 to 24 weeks. The DASH diet was found to result in significant decreases in systolic BP ( − 5·2 mmHg, 95 % CI − 7·0, − 3·4; P< 0·001) and diastolic BP ( − 2·6 mmHg, 95 % CI − 3·5, − 1·7; P< 0·001) and in the concentrations of total cholesterol ( − 0·20 mmol/l, 95 % CI − 0·31, − 0·10; P< 0·001) and LDL ( − 0·10 mmol/l, 95 % CI − 0·20, − 0·01; P= 0·03). Changes in both systolic and diastolic BP were greater in participants with higher baseline BP or BMI. These changes predicted a reduction of approximately 13 % in the 10-year Framingham risk score for CVD. The DASH diet improved cardiovascular risk factors and appeared to have greater beneficial effects in subjects with an increased cardiometabolic risk. The DASH diet is an effective nutritional strategy to prevent CVD.

Physical activity is associated with lower cardiovascular and all-cause mortality. However, the effects of different exercise modalities on arterial stiffness are currently unclear. Our objectives were to investigate the effects of exercise modalities (aerobic, resistance or combined) on pulse wave velocity (PWV) and augmentation index (AIx), and to determine whether the effects on these indices differed according to the participants' or exercise characteristics. We searched the Medline, Embase and Cochrane Library databases from inception until April 2014 for randomized controlled trials lasting ≥4 weeks investigating the effects of exercise modalities on PWV and AIx in adults aged ≥18 years. Forty-two studies (1627 participants) were included in this analysis. Aerobic exercise improved both PWV (WMD: −0.63 m/s, 95% CI: −0.90, −0.35) and AIx (WMD:−2.63%, 95% CI: −5.25 to −0.02) significantly. Aerobic exercise training showed significantly greater reduction in brachial-ankle (WMD: −1.01 m/s, 95% CI: −1.57, −0.44) than in carotid-femoral (WMD: -0.39 m/s, 95% CI: −0.52, −0.27) PWV. Higher aerobic exercise intensity was associated with larger reductions in AIx (β: −1.55%, CI −3.09, 0.0001). In addition, aerobic exercise had a significantly larger effect in reducing PWV (WMD:−1.0 m/s, 95% CI: −1.43, −0.57) in participants with stiffer arteries (PWV ≥8 m/s). Resistance exercise had no effect on PWV and AIx. There was no significant effect of combined exercise on PWV and AIx. We conclude that aerobic exercise improved arterial stiffness significantly and that the effect was enhanced with higher aerobic exercise intensity and in participants with greater arterial stiffness at baseline. Database registration: CRD42014009744,.

In order to establish firm evidence for the health effects of dietary polyphenol consumption, it is essential to have quantitative information regarding their dietary intake. The usefulness of the current methods, which rely mainly on the assessment of polyphenol intake using food records and food composition tables, is limited as they fail to assess total intake accurately. This review highlights the problems associated with such methods with regard to polyphenol-intake predictions. We suggest that the development of biological biomarkers, measured in both blood and urine, are essential for making accurate estimates of polyphenol intake. However, the relationship between dietary intakes and nutritional biomarkers are often highly complex. This review identifies the criteria that must be considered in the development of such biomarkers. In addition, we provide an assessment of the limited number of potential biomarkers of polyphenol intake currently available.