Ian Andrew Macdonald

Aims/hypothesis: Recent studies advocate prediabetes remission as a goal in diabetes prevention, but the optimal dietary composition for prediabetes remission over the long term is unknown. We aimed to examine the long-term effects on prediabetes remission of a prudent diet with moderate protein and a moderate glycaemic index (GI) (akin to general dietary guidelines) vs a high-protein, low-GI diet. Methods: This study is a secondary analysis of PREVIEW, which is a 3 year, multicentre, parallel, randomised trial. Adults with overweight/obesity (BMI ≥ 25 and 2 or BMI ≥ 30 kg/m ² , respectively) and prediabetes (fasting glucose 5.6–6.9 mmol/l and/or 2 h glucose 7.8–11.0 mmol/l determined using an OGTT) were recruited. Eligible participants underwent an 8-week rapid weight loss programme comprising a low-energy diet, followed by a 3 year weight maintenance phase comprising lifestyle intervention. At baseline, participants were randomly assigned to a high-protein (25% of energy from protein), low-GI (GI56). The primary outcome of the current analysis was the number of participants who achieved prediabetes remission (i.e. a return to normal fasting glucose and normal glucose tolerance) at 1 year or 3 years. Secondary outcomes were changes in body weight and composition over 3 years (continuous variables) and maintenance of a ≥8% weight loss target (binary variable). Modified intention-to-treat analyses were performed on all participants who received the dietary intervention ( n =1856). Risk ratios and 95% CI for prediabetes remission and maintaining the weight loss target in each diet group were estimated using multilevel modified Poisson regression adjusted for age and sex. Linear mixed models were used to estimate the dietary effects on changes in body weight and composition. Results: The moderate-protein, moderate-GI group ( n =923) had a higher rate of remission than the high-protein, low-GI group ( n =933) at both 1 year (rate of remission 26.3% vs 20.7%; RR 1.26; 95% CI 1.04, 1.53; p =0.025) and 3 years (20.6% vs 15.5%; RR 1.26; 95% CI 1.06, 1.50; p =0.015). However, body weight and composition changes were similar for participants on the moderate-protein, moderate-GI vs high-protein, low-GI diet at 1 year (54.0% vs 57.3% of participants met the weight loss maintenance target [≥8% of initial body weight]; p =0.215) and 3 years (31.4% vs 30.4%, respectively; p =0.793). The differences in remission rates of the two dietary patterns were independent of body weight and composition changes. Conclusions/interpretation: Following rapid weight loss, a prudent diet with moderate protein and moderate GI was more effective for long-term prediabetes remission than a high-protein, low-GI diet, irrespective of weight change. Trial registration: ClinicalTrials.gov NCT01777893 Graphical

Introduction: Glucose homeostasis may be dependent on liver conditions and influence health-related markers and quality of life (QoL) objective measurements. This study aimed to analyze the interactions of glycemia with liver and health status in a prediabetic population. Subjects and methods: This study included 2220 overweight/obese prediabetics from the multinational PREVIEW project. Anthropometrics; clinical, metabolic and other health-related markers; and QoL variables were analyzed. Univariate and multilinear-adjusted regression models were run to explain the interrelationships and effect modification between glycemia, health-related QoL (applying SF-12) and metabolic/liver health (using the HSI, a putative marker of fatty liver). Results: Relevant age/sex interactions were found concerning the levels of insulin, HOMA-IR, C peptide and transaminases in this prediabetic population. Multivariate models identified age, sex, glucose, WC and QoL as important predictors of HSI variability (adj. R value = 0.1393, p < 0.001), whereas the QoL status was statistically related to age, sex, HOMA-IR and HSI (adj. R value = 0.1130, p < 0.001) in this glycemia-impaired group. Furthermore, the QoL values declined with increased HSI scores, where a significant interaction was found (p = 0.011) when the data were analyzed when comparing lower glycemia vs. higher glycemia in prediabetics. Indeed, an effect modification was featured depending on the glycemia levels concerning the QoL and HSI worsening. Conclusion: Glycemia associations with the QoL status and liver metabolism markers were evidenced, with clinical implications for diabetes and liver disease precision management given the modification of the QoL outcomes depending on the liver status and glycemia concentrations. Notably, independent associations of circulating glucose with age, sex, adiposity, inflammation and C peptide levels were found.

Background: Sedentary lifestyle and unhealthy diet combined with overweight are risk factors for type 2 diabetes (T2D). Lifestyle interventions with weight-loss are effective in T2D-prevention, but unsuccessful completion and chronic stress may hinder efficacy. Determinants of chronic stress and premature cessation at the start of the 3-year PREVIEW study were examined. Methods: Baseline Quality of Life (QoL), social support, primary care utilization, and mood were examined as predictors of intervention cessation and chronic stress for participants aged 25 to 70 with prediabetes (n = 2,220). Moderating effects of sex and socio-economic status (SES) and independence of predictor variables of BMI were tested. Results: Participants with children, women, and higher SES quitted intervention earlier than those without children, lower SES, and men. Lower QoL, lack of family support, and primary care utilization were associated with cessation. Lower QoL and higher mood disturbances were associated with chronic stress. Predictor variables were independent (p ≤ .001) from BMI, but moderated by sex and SES. Conclusions: Policy-based strategy in public health should consider how preventive interventions may better accommodate different individual states and life situations, which could influence intervention completion. Intervention designs should enable in-built flexibility in delivery enabling response to individual needs. Trial registration: ClinicalTrials.gov Identifier: NCT01777893.

Hormones released in response to nutrients in the gastrointestinal (GI) tract, act as physiological signals to regulate appetite and play a role in feeding behaviours. Altered secretion of these ‘appetite’ hormones after feeding in those with obesity (‘Obese’), compared to those with healthy weight (‘Lean’), may drive over-consumption of energy. This study assessed whether gastric emptying rate was implicated in this altered response. Twenty healthy males attended the laboratory once in the morning after an overnight fast. Volume of gastric contents (GCV) and small bowel water (SBW) were assessed using MRI (Philips 3T Ingenia and dStream Anterior Coil) pre, immediately post and every 30-minutes for 4-hours after a standard meal (2.5MJ, 78g Carbohydrate, 24g Protein, 21g Fat). Concurrently, arterialised-venous blood was taken for insulin, ghrelin, GLP-1 and PYY evaluation. Gastric emptying (T₅₀) was derived from GCV. Data are presented as the mean (SD) or standardised effect size (η_p²). 10 Lean [38(14)y, 24(2) kg/m²] and 10 Obese [38(13)y, 34(3)kg/m²] were studied. Fasting insulin [12.5(5.8) vs. 17.6(11.3) mIU/l], Ghrelin [3.2(2.1) vs. 2.9(0.9) ng/ml], GLP-1 [7.2(11.5) vs. 13.3(2.5) pmol/l], PYY [102.3(46.7) vs. 88.4(32.4)pg/ml], SBW [121(96) vs. 168(125)ml] and GCV [59(33) vs. 59(30)ml] did not differ between ‘Lean’ and ‘Obese’. Response of Ghrelin (η_p²=0.005), GLP-1 (η_p²=0.103), PYY (η_p²=0.050) and SBWC (η_p²=0.145) to eating, and T₅₀ [148(51) vs. 170(49) min] did not differ between groups. However, postprandial insulin secretion was greater in obese (η_p²=0.286; P<0.05). Gastric emptying and incretin hormone secretion were not altered in participants with obesity. However, postprandial hyperinsulinemia, associated with insulin resistance, was observed.

Background: Dietary sugars are often linked to the development of overweight and type 2 diabetes (T2D) but inconsistencies remain. Objective: We investigated associations of added, free, and total sugars, and glycaemic index (GI) with indices of glucose metabolism (IGM) and indices of body fatness (IBF) during a 3-year weight loss maintenance intervention. Design: The PREVIEW (PREVention of diabetes through lifestyle Intervention and population studies in Europe and around the World) study was a randomised controlled trial designed to test the effects of four diet and physical activity interventions, after an 8-week weight-loss period, on the incidence of T2D. This secondary observational analysis included pooled data assessed at baseline (8), 26, 52, 104 and 156 weeks from 514 participants with overweight/obesity (age 25–70 year; BMI ≥ 25 kg⋅m⁻²) and with/without prediabetes in centres that provided data on added sugars (Sydney and Helsinki) or free sugars (Nottingham). Linear mixed models with repeated measures were applied for IBF (total body fat, BMI, waist circumference) and for IGM (fasting insulin, HbA1c, fasting glucose, C-peptide). Model A was adjusted for age and intervention centre and Model B additionally adjusted for energy, protein, fibre, and saturated fat. Results: Total sugars were inversely associated with fasting insulin and C-peptide in all centres, and free sugars were inversely associated with fasting glucose and HbA1c (Model B: all p < 0.05). Positive associations were observed between GI and IGM (Model B: fasting insulin, HbA1c, and C-peptide: (all p < 0.01), but not for added sugars. Added sugar was positively associated with body fat percentage and BMI, and GI was associated with waist circumference (Model B: all p < 0.01), while free sugars showed no associations (Model B: p > 0.05). Conclusions: Our findings suggest that added sugars and GI were independently associated with 3-y weight regain, but only GI was associated with 3-y changes in glucose metabolism in individuals at high risk of T2D.

Overnutrition, expressed as overweight and obesity, sometimes combined with inadequate micronutrient intake, coexists together with undernutrition as the major threats of malnutrition in children. Appropriate growth and metabolism of children have been extensively studied as to their association with future metabolic diseases. It is appreciated that early growth is controlled via the biochemical pathways that support organ and tissue growth and development, energy release from dietary intake, and production and release of hormones and growth factors regulating the biochemical processes. Anthropometric measurements, body composition, and their trajectories have been the metrics to evaluate both age-appropriate growth and link to future metabolic disease risk. As factors associated with risk of metabolic disease like childhood obesity are fairly well known, a strategic framework that includes appropriate nutrition and healthy dietary habits, adoption of the right behavior, and healthy food choices from early infancy to childhood is necessary to decrease this risk. The role of industry in this is to provide foods rich in nutrients developmentally appropriate and to promote responsible consumption and age-adapted portion sizes.

There is interest in the impact that dietary interventions can have on preventing the transition from insulin resistance to type 2 diabetes, including a suggestion that the bioactive components of cocoa may enhance fasting insulin sensitivity. However, a role for cocoa flavanols (CF) in reducing insulin resistance in the insulin-stimulated state, an important risk factor for cardiovascular disease, is unresolved. This study investigated whether CF consumption improved whole-body insulin-mediated glucose uptake (‘M’) in females with overweight/obesity, using a randomized, double-blinded, placebo-controlled, parallel-group design. Thirty-two premenopausal females (19–49 years; 27–35 kg·m⁻²) with elevated HOMA-IR (HOMA-IR >1.5) supplemented their habitual diet with two servings/day of a high-flavanol cocoa drink (HFC; 609 mg CF/serving; n = 16) or low-flavanol cocoa drink (LFC; 13 mg CF/serving; n = 16) for 4 weeks. Assessment of HOMA-IR and ‘M’ during a 3-h, 60 mIU insulin·m⁻²·min⁻¹ euglycemic clamp was performed before and after the intervention. Data are the mean (SD). Changes to HOMA-IR (HFC −0.003 (0.57); LFC −0.0402 (0.86)) and ‘M’ (HFC 0.99 (7.62); LFC –1.32 (4.88) µmol·kg⁻¹·min⁻¹) after the intervention were not different between groups. Four weeks’ consumption of ~1.2 g CF/day did not improve indices of fasting insulin sensitivity or insulin-mediated glucose uptake. A recommendation for dietary supplementation with cocoa flavanols to improve glycemic control is therefore not established.