Lenticular and retinal glutathione metabolism and its role in the diabetic complications of the eye.

This study has examined the key sequential changes in glutathione and intermediary metabolism of the diabetic rat lens. An in vivo streptozotocin-induced diabetic model and an in vitro hyperglycaemic incubation model have been used to evaluate the role glutathione maintenance plays in respect to oxidative processes and the ensuing pathological changes that occur in the diabetic lens and retina. In the in vivo model, the glutathione levels fall 3 days after the induction of diabetes, this is followed by a decrease in the NADPH and ATP. Manipulation of the in vivo model by treatment with verapamil, a calcium blocker, vanadate, which mimics insulin action and nicotinamide, a diabetogenic protective agent, have also been studied. The in vitro model, employing a 1 or 24 hour incubation, under normal and hyperglycaemic tissue culture conditions, showed similar changes to diabetes in lenticular glutathione levels and energy state. The effects of oxidative assault (hydrogen peroxide and altering oxygen tension) on these parameters was also studied. The results show that a depletion of glutathione is quickly followed by the fall in ATP and NADPH. These are important indicators of the development of cataracts. These results are discussed in relation to the competition between sorbitol formation and glutathione reduction, for NADPH. How pentose phosphate pathway activity and other metabolic routes of the lens are modulated by changes resulting from elevated glucose and depleted metabolites is discussed. In the in vivo lens, metabolism proceeds under anaerobic conditions, the metabolic profile in the air/CO2 and O2/CO2 incubations are quite different, indicating studies closer to the physiological condition, could provide information on the level of oxidative stress at which normal energy status can be sustained. A fall in glutathione appears to be one of the initial perturbations in cataract formation. Maintenance of the reduced sulphydryl environment is fundamental to lens clarity by maintaining an environment in which lens crystallins can provide the high refractive index necessary to focus light

Sociocognitive factors associated with lifestyle intervention attrition after successful weight loss among participants with prediabetes—The PREVIEW study

Abstract Introduction Major risk factors for type 2 diabetes are lifestyle choices such as lack of physical activity (PA) and poor diet. Many individuals either do not take part or struggle to complete interventions supporting lifestyle changes. Demographic and theory-based sociocognitive factors associated with PREVIEW intervention attrition after successful weight loss were examined. Methods Participants (1,856) who started the weight maintenance phase after completion of low-energy diet were retrospectively divided into three clusters depending on the point they left the trial. Discriminant analysis examined which demographic and theory-based sociocognitive variables were associated with cluster membership. Results Most of the participants were women and well-educated. Two discriminant functions were calculated (?2(24) = 247.0, p ≥ .05, d = 0.78). The demographic variables, such as age and ethnicity, and the social cognitive variable outcome expectancies on the other side were associated with cluster membership. Older age, Caucasian ethnicity, and fewer expected disadvantages of PA were associated with high success. Discussion The discriminant model gave insight into some factors associated with early attrition. For practitioners planning interventions it underlines the necessity to take extra attention to younger participants and to those being afraid that being physically active causes unpleasant ramifications.Peer reviewe

Can a Higher Protein/Low Glycemic Index vs. a Conventional Diet Attenuate Changes in Appetite and Gut Hormones Following Weight Loss? : A 3-Year PREVIEW Sub-study

Background: Previous research showed that weight-reducing diets increase appetite sensations and/or circulating ghrelin concentrations for up to 36 months, with transient or enduring perturbations in circulating concentrations of the satiety hormone peptide YY. Objective: This study assessed whether a diet that is higher in protein and low in glycemic index (GI) may attenuate these changes. Methods: 136 adults with pre-diabetes and a body mass index of >= 25 kg/m(2) underwent a 2-month weight-reducing total meal replacement diet. Participants who lost >= 8% body weight were randomized to one of two 34-month weight-maintenance diets: a higher-protein and moderate-carbohydrate (CHO) diet with low GI, or a moderate-protein and higher-CHO diet with moderate GI. Both arms involved recommendations to increase physical activity. Fasting plasma concentrations of total ghrelin and total peptide YY, and appetite sensations, were measured at 0 months (pre-weight loss), at 2 months (immediately post-weight loss), and at 6, 12, 24, and 36 months. Results: There was a decrease in plasma peptide YY concentrations and an increase in ghrelin after the 2-month weight-reducing diet, and these values approached pre-weight-loss values by 6 and 24 months, respectively (P = 0.32 and P = 0.08, respectively, vs. 0 months). However, there were no differences between the two weight-maintenance diets. Subjective appetite sensations were not affected by the weight-reducing diet nor the weight-maintenance diets. While participants regained an average of similar to 50% of the weight they had lost by 36 months, the changes in ghrelin and peptide YY during the weight-reducing phase did not correlate with weight regain. Conclusion: A higher-protein, low-GI diet for weight maintenance does not attenuate changes in ghrelin or peptide YY compared with a moderate-protein, moderate-GI diet.Peer reviewe

Socio-economic factors, mood, primary care utilization, and quality of life as predictors of intervention cessation and chronic stress in a type 2 diabetes prevention intervention (PREVIEW Study)

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.publishersversionpublishe

Animal-based food choice and associations with long-term weight maintenance and metabolic health after a large and rapid weight loss : The PREVIEW study

Peer reviewe

Perceived stress as a predictor of eating behavior during the 3-year PREVIEW lifestyle intervention

Peer reviewe

Intended and Observed Changes in Intervening Mechanisms

BACKGROUND: Lifestyle interventions can prevent type 2 diabetes (T2D) by successfully inducing behavioral changes (eg, avoiding physical inactivity and sedentariness, increasing physical activity and/or healthy eating) that reduce body weight and normalize metabolic levels (eg, HbA1c). For interventions to be successful, it is important to influence "behavioral mechanisms" such as self-efficacy, which motivate behavioral changes. Theory-based expectations of how self-efficacy, chronic stress, and mood changed over time were investigated through a group-based behavior change intervention (PREMIT). At 8 intervention sites, PREMIT was offered by trained primary care providers in 18 group-sessions over a period of 36 months, divided into 4 intervention phases. Adherence to the intervention protocol was assessed. METHOD: Participants (n = 962) with overweight and prediabetes who had achieved ≥8% weight loss during a diet reduction period and completed the intervention were categorized into 3 groups: infrequent, frequent, or very frequent group sessions attendance. The interactions between participation in the group sessions and changes in self-efficacy, stress, and mood were multivariate tested. Intervention sites were regularly asked where and how they deviated from the intervention protocol. RESULTS: There was no increase in the participants' self-efficacy in any group. However, the level of self-efficacy was maintained among those who attended the group sessions frequently, while it decreased in the other groups. For all participants, chronic stress and the frequency of attending group sessions were inversely related. Significant differences in mood were found for all groups. All intervention centers reported specific activities, additional to intervention protocol, to promote participation in the group sessions. CONCLUSIONS: The results suggest that the behavioral changes sought by trained primary care providers are related to attendance frequency and follow complex trajectories. The findings also suggest that group-based interventions in naturalistic primary care settings aimed at preventing T2D require formats and strategies that encourage participants to attend group sessions regularly.publishersversionpublishe

PREVIEW: Prevention of Diabetes through Lifestyle Intervention and Population Studies in Europe and around the World. Design, Methods, and Baseline Participant Description of an Adult Cohort Enrolled into a Three-Year Randomised Clinical Trial

Type-2 diabetes (T2D) is one of the fastest growing chronic diseases worldwide. The PREVIEW project has been initiated to find the most effective lifestyle (diet and physical activity) for the prevention of T2D, in overweight and obese participants with increased risk for T2D. The study is a three-year multi-centre, 2 × 2 factorial, randomised controlled trial. The impact of a high-protein, low-glycaemic index (GI) vs. moderate protein, moderate-GI diet in combination with moderate or high-intensity physical activity on the incidence of T2D and the related clinical end-points are investigated. The intervention started with a two-month weight reduction using a low-calorie diet, followed by a randomised 34-month weight maintenance phase comprising four treatment arms. Eight intervention centres are participating (Denmark, Finland, United Kingdom, The Netherlands, Spain, Bulgaria, Australia, and New Zealand). Data from blood specimens, urine, faeces, questionnaires, diaries, body composition assessments, and accelerometers are collected at months 0, 2, 6, 12, 18, 24, and 36. In total, 2326 adults were recruited. The mean age was 51.6 (SD 11.6) years, 67% were women. PREVIEW is, to date, the largest multinational trial to address the prevention of T2D in pre-diabetic adults through diet and exercise intervention. Participants will complete the final intervention in March, 2018.Peer reviewe

Compositional analysis of the associations between 24-h movement behaviours and cardio-metabolic risk factors in overweight and obese adults with pre-diabetes from the PREVIEW study : cross-sectional baseline analysis

Background Physical activity, sedentary time and sleep have been shown to be associated with cardio-metabolic health. However, these associations are typically studied in isolation or without accounting for the effect of all movement behaviours and the constrained nature of data that comprise a finite whole such as a 24 h day. The aim of this study was to examine the associations between the composition of daily movement behaviours (including sleep, sedentary time (ST), light intensity physical activity (LIPA) and moderate-to-vigorous activity (MVPA)) and cardio-metabolic health, in a cross-sectional analysis of adults with pre-diabetes. Further, we quantified the predicted differences following reallocation of time between behaviours. Methods Accelerometers were used to quantify daily movement behaviours in 1462 adults from eight countries with a body mass index (BMI) >= 25 kg center dot m(- 2), impaired fasting glucose (IFG; 5.6-6.9 mmol center dot l(- 1)) and/or impaired glucose tolerance (IGT; 7.8-11.0 mmol center dot l(- 1) 2 h following oral glucose tolerance test, OGTT). Compositional isotemporal substitution was used to estimate the association of reallocating time between behaviours. Results Replacing MVPA with any other behaviour around the mean composition was associated with a poorer cardio-metabolic risk profile. Conversely, when MVPA was increased, the relationships with cardiometabolic risk markers was favourable but with smaller predicted changes than when MVPA was replaced. Further, substituting ST with LIPA predicted improvements in cardio-metabolic risk markers, most notably insulin and HOMA-IR. Conclusions This is the first study to use compositional analysis of the 24 h movement composition in adults with overweight/obesity and pre-diabetes. These findings build on previous literature that suggest replacing ST with LIPA may produce metabolic benefits that contribute to the prevention and management of type 2 diabetes. Furthermore, the asymmetry in the predicted change in risk markers following the reallocation of time to/from MVPA highlights the importance of maintaining existing levels of MVPA.Peer reviewe

What Is the Profile of Overweight Individuals Who Are Unsuccessful Responders to a Low-Energy Diet? A PREVIEW Sub-study

This study was performed to evaluate the profile of overweight individuals with pre-diabetes enrolled in PREVIEW who were unable to achieve a body weight loss of >= 8% of the baseline value in response to a 2-month low-energy diet (LED). Their baseline profile reflected potential stress-related vulnerability that predicted a reduced response of body weight to a LED programme. The mean daily energy deficit maintained by unsuccessful weight responders of both sexes was less than the estimated level in successful female (656 vs. 1,299 kcal, p < 0.01) and male (815 vs. 1,659 kcal, p < 0.01) responders. Despite this smaller energy deficit, unsuccessful responders displayed less favorable changes in susceptibility to hunger and appetite sensations. They also did not benefit from the intervention regarding the ability to improve sleep quality. In summary, these results show that some individuals display a behavioral vulnerability which may reduce the ability to lose weight in response to a diet-based weight loss program. They also suggest that this vulnerability may be accentuated by a prolonged diet restriction.Peer reviewe