Background/Objectives: The STRIVE study was a multicentre, open-label, real-world clinical trial evaluating the effectiveness of a targeted prescribing pathway for liraglutide 3.0 mg as an adjunct to standard care versus standard care alone in people with obesity attending Specialist Weight Management Services (SWMS) in the UK and Ireland. This post hoc analysis focuses on the standard care arm to explore differences in outcomes between sites, particularly the potential impact of offering meal replacements as part of usual care. Methods: Participants included individuals with a BMI ≥ 35 kg/m² and at least one obesity-related complication who received standard care at five SWMS sites. All sites provided specialist nutrition and exercise counselling; however, only the Dublin site (n = 40) included meal replacements as part of routine care. Baseline characteristics and weight change data were compared between the Dublin and UK cohorts (n = 92) at 52 and 104 weeks. Statistical comparisons were made using appropriate parametric and non-parametric tests. Results: At baseline, the Dublin cohort was significantly older (p < 0.01), had a higher prevalence of hypertension (p < 0.05), and a lower reported incidence of depression/anxiety (p < 0.05) than the UK cohort. At week 52, the Dublin group achieved greater mean weight loss (-6.1%, SD ± 5.7%) compared to the UK cohort (-1.3%, SD ± 6.7%, n = 27, p < 0.01). By week 104, Dublin participants maintained a mean weight loss of -4.4% (SD ± 5.7%) while UK participants had a mean weight gain of 0.37% (SD ± 7.6%) (p < 0.05). Conclusions: The integration of meal replacements as part of usual care may have contributed to the greater and sustained weight loss observed in the Dublin cohort compared to other SWMS in the UK.

BACKGROUND AND AIM:Formula low-energy diets (LED), used intermittently, may assist long-term weight-loss maintenance (WLM). This study compared total diet replacement 2 days/week (5:2TDR) and once-daily meal-replacements (DMR), delivered within a structured WLM programme. METHODS:A 78-week randomised trial was conducted in 63 individuals (75 % female, BMI 23-61 kg/m2), recruited between 12/04/2016 to 05/06/2018, after documented mean (SD) intentional weight-loss >8 kg, achieved using LED, behavioural programmes, or pharmacotherapy. Participants who had received anti-obesity medications were either weight stable or regaining after drug withdrawal. The primary outcome was weight change at 26-weeks following randomisation. Six dietitians and 25/63 (40 %) participants completed qualitative interviews at 26-weeks. Between-group differences were assessed using repeated ANCOVA adjusting for baseline values applying Intention-to-Treat, Per-Protocol, and As-Treated methods. RESULTS:At 26-weeks, 32/33 (97 %) randomised to 5:2TDR, and 29/30 (97 %) randomised to DMR, provided data. Four participants took pre-existing pharmacotherapy (n = 3 orlistat up to 78-weeks and n = 1 liraglutide up to 52-weeks). Mean (SD) pre-study weight-losses were similar between groups: 5:2TDR -15·0 (6·9) kg, DMR -18·8 (9·3) kg, p = 0.056. After 26-weeks WLM, intention-to-treat analysis found further weight-loss -0·9 kg (95 %CI -2·9, 1·5 kg) with 5:2TDR and regain with DMR 3·5 kg (95 %CI 1·3,5·5 kg); between-group difference -4·4 kg (95 %CI -7·3,-1·6 kg), p = 0·005. Maintained weight-losses at 26-weeks from pre-study start of weight loss were -15·8 (9·5) kg with 5:2TDR, -15·2 (10·5) kg with DMR, p = 0·977. Similar results were observed in the per protocol and as treated analyses. Both groups maintained weight losses >15 kg below baseline at 26, 52 and 78-weeks. Results were similar excluding those taking weight loss medications. Both interventions were well accepted. Dietitians successfully adapted LED interventions to overcome social/environmental challenges experienced by participants. CONCLUSIONS:Structured dietary WLM is well accepted and can prevent weight regain after substantial loss, including after glucagon-like peptide-1 agonist withdrawal, and can maintain >15 kg loss up to 78-weeks TRIAL REGISTRATION: Clinicaltrials.gov: identifier NCT02683798.

Intentional weight loss improves cardiometabolic risk factors, which by associated neuroprotective effects may reduce dementia risk. However, assessing change in dementia risk directly demands long-term follow-up. In this study, we assessed whether a recently validated 25-protein signature for dementia risk could detect changes in dementia risk in response to an intentional weight loss program in people with type 2 diabetes (T2D) and associated cardiometabolic features. A potential impact of intentional weight loss on dementia risk was explored in two randomized controlled clinical trials in patients with obesity and T2D, DiRECT and DIADEM-I; both demonstrated that a diet program to induce and maintain weight loss led to diabetes remissions of 46% and 61% at 1 year. The proteomic dementia risk test (derived from the SomaScan™ assay, predicting the probability of incident dementia diagnosis within 20-years of blood draw) was applied to plasma samples at baseline and 1-year in intervention (DiRECT n=118; DIADEM-I n=56) and control (DiRECT n=144; DIADEM-I n=66) participants. This model includes measurements of 25 plasma proteins, but not HbA1c, which might otherwise dominate a prediction of dementia risk in people with T2D. Dementia risk scores were compared within and between trial arms and the association between weight loss amount and the magnitude of dementia risk score change was explored. In both DiRECT and DIADEM-I a significant difference in the change in dementia risk score from baseline to 1-year between the trial arms was observed ( p =1.8x10 -7 and p =8.79x10 -8, respectively), with risk scores either remaining stable or decreasing in the intervention arm over the trial duration. Furthermore, in DiRECT there was a significant ( p =9.06x10 -3 ) association between the amount of weight lost and the reduction in dementia risk in the intervention arm with greater weight loss associating with a greater reduction in dementia risk. These results support epidemiological evidence that non-pharmacological weight loss may protect against dementia risk, particularly in those with cardiometabolic features. Furthermore, the proteomic dementia risk test was robust to identifying changes in dementia risk in response to intentional weight loss. These findings suggest that the proteomic model has value to evaluate pharmacologic and non-pharmacological interventions to reduce dementia.

Long COVID (LC) is a complex multisymptom condition with no known disease-modifying treatments. This wait-list-controlled open-label trial tested whether a remotely delivered structured weight management program could improve respective LC symptoms in people living with overweight. Adults with LC (symptoms >12 weeks) and body mass index >27 kg m−2 (>25 kg m−2 for South Asians) were randomized (n = 234, 1:1) to control (n = 116, usual care) or the remotely delivered structured weight management (n = 118, total diet replacement (850 kcal per day) for 12 weeks, followed by food reintroduction and weight loss maintenance support) via minimization and randomization (80:20) to balance dominant LC symptom, sex, age, ethnicity and postcode-based index of multiple deprivation between groups. The control group received the intervention after 6 months. Participants selected the dominant LC symptom they would most like to improve (fatigue, breathlessness, pain, anxiety/depression or other) as the prespecified respective primary outcome. Individual symptoms were assessed using validated questionnaires and a visual analog scale for those without prespecified scales. At 6 months, the primary outcome improved in the intervention group (change −1.16 (s.d. 1.42), n = 97 analyzed) compared with the control group (change −0.83 (s.d. 1.14), n = 117 analyzed) with a treatment effect of −0.34 (95 12595520 . In a randomized trial, a remotely delivered weight management intervention for people with long COVID and excess weight improved respective long COVID symptoms and quality of life and resulted in substantial weight loss when compared with a control group, with no serious adverse effects reported.

Long-term effects of COVID-19 infection, termed Long COVID (LC), are associated with reduced quality of life. Symptoms associated with overweight/obesity overlap with and may aggravate those of LC. This paper reports the economic evaluation alongside the ReDIRECT Trial, which evaluated the impact of an evidence-based, remotely-delivered weight management programme on self-reported symptoms of LC in those living with overweight/obesity in the United Kingdom. Recruited participants (n = 234) were randomly allocated to the intervention group (weight management) or control group (usual care). Incremental costs and Quality-Adjusted Life Years (QALYs) were calculated using intervention cost, healthcare resource use and EQ-5D-5L data collected at baseline, three and 6 months. In this work, we show that the ReDIRECT intervention is likely cost-effective in improving LC symptoms from an NHS/PSS perspective, compared to usual care (Incremental Cost-Effectiveness Ratio of £14,754/QALY). Adopting a broader societal perspective, the intervention becomes potentially cost saving compared to usual care.

BackgroundIn DiRECT, a randomised controlled effectiveness trial, weight management intervention after 2 years resulted in mean weight loss of 7·6 kg, with 36% of participants in remission of type 2 diabetes. Of 36 in the intervention group who maintained over 10 kg weight loss at 2 years, 29 (81%) were in remission. Continued low-intensity dietary support was then offered up to 5 years from baseline to intervention participants, aiming to maintain weight loss and gain clinical benefits. This extension study was designed to provide observed outcomes at 5 years.MethodsThe DiRECT trial took place in primary care practices in the UK. Participants were individuals aged 20–65 years who had less than 6 years’ duration of type 2 diabetes, a BMI greater than 27 kg/m2, and were not on insulin. The intervention consisted of withdrawal of antidiabetic and antihypertensive drugs, total diet replacement (825–853 kcal per day formula diet for 12–20 weeks), stepped food reintroduction (2–8 weeks), and then structured support for weight-loss maintenance. After sharing the 2-year results with all participants, UK National Health Service data were collected annually until year 5 from remaining intervention participants who received low-intensity dietary support, intervention withdrawals, and the original randomly allocated groups. The primary outcome was remission of type 2 diabetes; having established in the DiRECT trial that sustained weight loss was the dominant driver of remission, this was assumed for the Extension study. The trial is registered with the ISRCTN registry, number 03267836.FindingsBetween July 25, 2014, and Aug 5, 2016, 149 participants were randomly assigned to the intervention group and 149 were assigned to the control group in the original DiRECT study. After 2 years, all intervention participants still in the trial (101 [68%] of 149) were approached to receive low-intensity support for a further 3 years. 95 (94%) of 101 were able to continue and consented and were allocated to the DiRECT extension group. 54 participants were allocated to the non-extension group, where intervention was withdrawn. At 5 years, DiRECT extension participants (n=85) lost an average of 6·1 kg, with 11 (13%) of 85 in remission. Compared with the non-extension group, DiRECT extension participants had more visits with HbA1c <48 mmol/mol (<6·5%; 36% vs 17%, p=0·0004), without glucose-lowering medication (62% vs 30%, p<0·0001), and in remission (34% vs 12%, p<0·0001). Original control participants (n=149) had mean weight loss 4·6 kg (n=82), and 5 (5%) of 93 were in remission. Compared with control participants, original intervention participants had more visits with weight more than 5% below baseline (61% vs 29%, p<0·0001), HbA1c below 48 mmol/mol (29% vs 15%, p=0·0002), without antidiabetic medication (51% vs 16%, p<0·0001), and in remission (27% vs 4%, p<0·0001). Of those in remission at year 2, 26% remained in remission at 5 years. Serious adverse events in the original intervention group (4·8 events per 100 patient-years) were under half those in the control group (10·2 per 100 patient-years, p=0·0080).InterpretationThe extended DiRECT intervention was associated with greater aggregated and absolute weight loss, and suggested improved health status over 5 years.FundingDiabetes UK.

Background Obesity-associated asthma results in increased morbidity and mortality. We report one-year asthma outcomes with the Counterweight-Plus weight management programme (CWP) compared to usual care (UC) in a single-centre, randomised, controlled trial in patients with difficult-to-treat asthma and obesity. Research Question Can CWP use result in improved asthma control and quality of life compared to UC at one-year in patients with difficult-to-treat asthma and obesity? Study design and methods We randomised (1:1 CWP:UC) adults with difficult-to-treat asthma and body mass index ≥30kg/m2. CWP with dietitian support: 12-week total diet replacement phase (850kcal/day low-energy formula); food reintroduction and maintenance phases up to one-year. Outcomes include Asthma Control Questionnaire (ACQ-6), Asthma Quality of Life Questionnaire (AQLQ) and healthcare usage. Minimal clinically important difference (MCID) is 0.5 for ACQ-6 and AQLQ. Results Of 36 recruited, 29 attended at 52-weeks: 13 CWP, 16 UC. CWP resulted in greater weight change (median –14kg [IQR –15, –9]) compared to UC (2kg [-7, 8]; p=0.015) at 52-weeks. A greater proportion achieved MCID with CWP vs UC in AQLQ (71% vs 6% respectively; p<0.001). No between-group differences were observed in ACQ-6. Median exacerbation frequency reduced over 52-weeks with CWP from 4 (IQR 2, 5) to 0 (0, 2) (p<0.001), though no between-group difference was observed. 70% of the CWP group lost ≥10% body weight and had improvement in ACQ-6 (mean difference –1.1, 95%CI –1.9, -0.3; p=0.018) and AQLQ (1.2, 95%CI 0.4, 2.1; p=0.011) across 52-weeks. Interpretation Use of a dietitian-supported weight management programme results in sustained weight-loss and is a potential treatment for obesity in asthma. CWP resulted in a higher proportion achieving MCID improvement in AQLQ compared to UC. Within group differences in AQLQ and exacerbation frequency suggest potential with CWP. These encouraging signals justify a larger sample study to further assess asthma-related outcomes.

Empirical evidence for a low normal or reference interval for serum prolactin (PRL) is lacking for men, while the implications of very low PRL levels for human health have never been studied. A clinical state of “PRL deficiency” has not been defined except in relation to lactation. Using data from the European Male Ageing Study (EMAS), we analyzed the distribution of PRL in 3,369 community-dwelling European men, aged 40–80 years at phase-1 and free from acute illnesses. In total, 2,948 and 2,644 PRL samples were collected during phase-1 and phase-2 (3 to 5.7 years later). All samples were analysed in the same centre with the same assay. After excluding individuals with known pituitary diseases, PRL ≥ 35 ng/ml, and PRL-altering drugs including antipsychotic agents, selective serotonin reuptake inhibitors, or dopamine agonists, 5,086 data points (2,845 in phase-1 and 2,241 in phase-2) were available for analysis. The results showed that PRL declined minimally with age (slope = -0.02) and did not correlate with BMI. The positively skewed PRL distribution was log-transformed to a symmetrical distribution (skewness reduced from 13.3 to 0.015). Using two-sigma empirical rule (2[]SD about the mean), a threshold at 2.5

BACKGROUND:The UK Diabetes Remission Clinical Trial (DiRECT) study was replicated in an Australian primary care setting. This qualitative study aimed to explore and understand the perceptions and experiences of both participants and healthcare professionals (HCPs) involved in the DiRECT-Australia Type 2 Diabetes Remission Service.METHODS:All participants and HCPs delivering the service were invited to participate in semi-structured interviews via online videoconferencing. The interview guides explored perceptions and experiences in DiRECT-Australia, covering aspects such as barriers and facilitators to recruitment and participation, motivations and challenges across service phases, adequacy of support provided and the overall acceptability of the service. All interviews were audio-recorded, transcribed verbatim and analysed using thematic analysis.RESULTS:Eight DiRECT-Australia participants and six HCPs (three general practitioners, two practice nurses and one dietitian) participated. Four overarching themes were identified: (1) Enablers and barriers to recruitment and continuous participation in DiRECT-Australia; (2) Motivators and overcoming barriers across the total diet replacement, food reintroduction and weight maintenance phases; (3) Importance of participant-HCP interactions and continuous support; (4) Acceptance and long-term need for DiRECT-Australia. Adherence to total diet replacement was less challenging than anticipated by participants. Transitioning to the food reintroduction phase was difficult but overcome through HCP support. DiRECT-Australia was well accepted by both participants and HCPs, and participants expressed willingness to continue with the service, if provided on a long-term basis.CONCLUSIONS:Both participants and HCPs were highly interested in the new diabetes remission service set up in an Australian primary care setting. The acceptability of DiRECT-Australia was underscored by participants emphasising the effectiveness of the service in achieving significant weight loss and diabetes remission. There is a need for long-term and wider implementation of the service to ensure that anyone with recent onset type 2 diabetes is offered the best possible chance to achieve remission.

BackgroundAn effective prescribing pathway for liraglutide 3 mg, an approved obesity pharmacotherapy, may improve treatment access. This trial compared a targeted prescribing pathway for liraglutide 3 mg with multiple stopping rules in specialist weight management services (SWMS) to standard SWMS care.MethodsThis phase four, two-year, multicentre, open-label, parallel-group, real-world randomized clinical trial (ClinicalTrials.gov: NCT03036800) enrolled adults with BMI ≥35 kg/m2 plus prediabetes, type 2 diabetes, hypertension or sleep apnoea from five SWMS in Ireland and UK. Participants were randomly allocated (2:1, stratified by centre and BMI) to SWMS care plus a targeted prescribing pathway for once daily subcutaneous liraglutide 3 mg (intervention) with stopping rules at 16 (≥5% weight loss, WL), 32 (≥10% WL) and 52 weeks (≥15% WL) or to SWMS care alone (control) through an online randomization service. The primary outcome was WL ≥15% at 52 weeks, assessed by complete cases analysis. All randomized participants were included in safety analysis.FindingsFrom November 28, 2017 to February 28, 2020, 434 participants were screened, and 392 randomized (260 intervention; 132 control), while 294 (201 intervention; 93 control) included in the 52 weeks complete case analysis. More intervention than control participants achieved WL ≥15% at 52 weeks [51/201 (25.4%) vs 6/93 (6.5%); odds ratio 5.18; 95% CI 2.09, 12.88; p < 0.0001]. More adverse events occurred in the intervention (238/260, 91.5%; two deaths) than control (89/132, 67.4%; no deaths) group.InterpretationA targeted prescribing pathway for liraglutide 3 mg helps more people achieve ≥15% WL at 52 weeks than standard care alone.FundingNovo Nordisk A/S.

Introduction: Management of difficult-to-treat asthma is particularly challenging in people with elevated body mass index (BMI). Our randomised controlled trial of pulmonary rehabilitation (PR) showed improved outcomes at 8 weeks. Here we assess immediate and one-year effects of asthma-tailored PR in participants with difficult-to-treat asthma and BMI >= 25 kg/m(2), and identify response predictors. Methods: A prospective observational study of PR, tailored to asthma, comparing outcomes at baseline (V1), immediately after 8 weeks of PR (V2), and at 1 year (V3). Baseline characteristics were compared in responders/non-responders defined by achievement of minimum clinically important difference (MCID) for asthma control questionnaire (ACQ6) (0.5) at 8 weeks and 1 year. Results: Of 92 participants, 56 attended V2 and 45 attended V3. Mean age was 60 (SD 13) years, 60% were female, and median (IQR) BMI was 33.8 (29.5- 38.7) kg/m(2). At V1, V2, and V3, respectively, there were significant differences in ACQ6 (mean (95% CI): 2.5 (2.1- 2.9), 2.2 (1.8- 2.5), and 2.3 (1.9- 2.7), p< 0.003), Borg breathlessness score post-6-minute walk test (median (IQR): 2 (0.5- 3), 1 (0- 2), and 1 (0.5- 2), p< 0.035), and annualised exacerbations requiring prednisolone (median (IQR): 3 (2- 5), 0 (0- 4.7), and 1.5 (0- 4.2), p< 0.003). A total of 27/56 (48%) had improvements >MCID for ACQ6 at V2 and 16 (33%) at V3. Participants with higher ACQ6 scores at baseline (suggesting poorer asthma control) were more likely to achieve MCID. Baseline BMI, within the range studied, was not predictive. Conclusion: Pulmonary rehabilitation induced improvements in asthma-related outcomes including perception of breathlessness, asthma control, and exacerbation frequency at 1 year. Those with poorer baseline asthma control were more likely to benefit.

Low-carbohydrate diets (LCD) are popular for weight loss but lack evidence about micronutrient sufficiency in real-life use. This study assessed the intake and biochemical status of selected micronutrients in people voluntarily following LCDs. A cross-sectional study was conducted (2018-20) among 98 adults recruited as self-reporting either LCD (n = 49) or diets not restricting carbohydrates (controls; n = 49). Diets were assessed using the 130-item EPIC-Norfolk food-frequency questionnaire. Red-blood-cell thiamine diphosphate (TDP) was measured for thiamine status using HPLC. Plasma magnesium, zinc, copper, and selenium were measured using inductively coupled plasma mass spectrometry. Between-group biomarker comparisons were conducted using ANCOVA and adjusted for age, sex, body mass index (BMI), and diabetes status. LCD-followers (26

Evidence indicates growing demand on community health and social care services by people with severe obesity (BMI ≥40 kg/m2), often due to functional limitations. The experiences of this population are largely unexplored. As part of a larger mixed‐methods study, this qualitative study explored the lived experience of people with severe obesity using community health and social care services. Participants were recruited via community professionals and visited at home. They consented to individual, audio‐recorded, semistructured interviews, which were transcribed and analysed using thematic analysis. Nine women and three men (n = 12) participated, aged 40–76 (mean 60) years, BMI ranged from 45 to 74 (mean 59) kg/m2, and eight were housebound. Three overarching themes were identified. Firstly, the hidden struggles of living with a larger body affected all participants, including functional limitations affecting mobility and personal care. These contributed to a sense of being stuck physically, socially, and biographically. Secondly, most participants reported implicit weight bias by a system structurally unprepared to care for people with larger bodies. The majority of participants showed strong internalised weight bias, linked to shame and self‐blame for their poor function and larger bodies. Thirdly, a day‐to‐day coping theme highlighted strategies regularly used by participants: resigned acceptance, avoidance and denial, exercising choice, and support from informal carers. These findings demonstrate that participants experienced unmet physical and psychological care needs associated with living with a larger body, leading to poor quality of care and life. Given rising prevalence, changes to care services are needed. Specific recommendations include staff training about the needs of people with severe obesity, ensuring that the physical infrastructure of care services can safely accommodate people with severe obesity, and improving access to effective, person‐centred weight management treatments.

The concept of type 2 diabetes remission is evolving rapidly, and gaining wide public and professional interest, following demonstration that with substantial intentional weight loss almost nine in ten people with type 2 diabetes can reduce their HbA 1c level below the diagnostic criterion (48 mmol/mol [6.5%]) without glucose-lowering medications, and improve all features of the metabolic syndrome. Pursuing nomoglycaemia with older drugs was dangerous because of the risk of side effects and hypoglycaemia, so the conventional treatment target was an HbA 1c concentration of 53 mmol/mol (7%), meaning that diabetes was still present and allowing disease progression. Newer agents may achieve a normal HbA 1c safely and, by analogy with treatments that send cancers or inflammatory diseases into remission, this might also be considered remission. However, although modern glucagon-like peptide-1 receptor agonists and related medications are highly effective for weight loss and glycaemic improvement, and generally safe, many people do not want to take drugs indefinitely, and their cost means that they are not available across much of the world. Therefore, there are strong reasons to explore and research dietary approaches for the treatment of type 2 diabetes. All interventions that achieve sustained weight loss of >10–15 kg improve HbA 1c , potentially resulting in remission if sufficient beta cell capacity can be preserved or restored, which occurs with loss of the ectopic fat in liver and pancreas that is found with type 2 diabetes. Remission is most likely with type 2 diabetes of short duration, lower HbA 1c and a low requirement for glucose-lowering medications. Relapse is likely with weight regain and among those with a poor beta cell reserve. On current evidence, effective weight management should be provided to all people with type 2 diabetes as soon as possible after diagnosis (or even earlier, at the stage of prediabetes, defined in Europe, Australasia, Canada [and most of the world] as ≥42 and <48 mmol/mol [≥6.0 and <6.5%], and in the USA as HbA1c ≥39 and <48 mmol/mol [≥5.7 and <6.5%]). Raising awareness among people with type 2 diabetes and their healthcare providers that remission is possible will enable earlier intervention. Weight loss of >10 kg and remission lasting 1–2 years may also delay vascular complications, although more evidence is needed. The greatest challenge for research is to improve long-term weight loss maintenance, defining cost-effective approaches tailored to the preferences and needs of people living with type 2 diabetes. Graphical Abstract

This review synthesized the evidence from randomized controlled trials comparing the effect of meal replacements (MRs) as part of a weight loss intervention with conventional food-based weight loss diets on cardiometabolic risk in individuals with pre-diabetes and features of metabolic syndrome. MEDLINE, EMBASE, and Cochrane Library were searched through January 16, 2024. Data were pooled using the generic inverse variance method and expressed as mean difference [95% confidence intervals]. The overall certainty of the evidence was assessed using GRADE. Ten trials (n = 1254) met the eligibility criteria. MRs led to greater reductions in body weight (-1.38 kg [-1.81, -0.95]), body mass index (BMI, -0.56 kg/m2 [-0.78, -0.34]), waist circumference (-1.17 cm [-1.93, -0.41]), HbA1c (-0.11% [-0.22, 0.00]), LDL-c (-0.18 mmol/L [-0.28, -0.08]), non-HDL-c (-0.17 mmol/L [-0.33, -0.01]), and systolic blood pressure (-2.22 mmHg [-4.20, -0.23]). The overall certainty of the evidence was low to moderate owing to imprecision and/or inconsistency. The available evidence suggests that incorporating MRs into a weight loss intervention leads to small important reductions in body weight, BMI, LDL-c, non-HDL-c, and systolic blood pressure, and trivial reductions in waist circumference and HbA1c, beyond that seen with conventional food-based weight loss diets.

Prolactin (PRL) is secreted throughout life in men and women. At elevated levels, its physiological role in pregnancy and lactation, and pathological effects, are well known. However clinical implications of low circulating PRL are not well established. We conducted a meta-analysis to examine the relationship between low PRL levels and type 2 diabetes. Five papers included cross-sectional studies comprising 8,720 men (mean age range 51.4–60 years) and 3,429 women (49.5–61.6 years), and four papers included cohort studies comprising 2,948 men (52.1–60.0 years) and 3,203 women (49.2–60.1 years). Individuals with pregnancy, lactation and hyperprolactinemia, drugs known to alter circulating PRL levels, or pituitary diseases had been excluded. Although most studies used quartiles to categorize PRL groups for analysis, PRL cut-off values (all measured by chemiluminescence immunoassay) were variably defined between studies: the lowest PRL quartiles ranged from 3.6 ng/ml to 7.2 ng/ml in men and between 4.5 ng/ml to 8 ng/ml in women; and the highest PRL quartiles ranged from 6.9 ng/ml to 13 ng/ml in men and 9.6 ng/ml to 15.8 ng/ml in women. Type 2 diabetes was defined variably using self-reported physician’s diagnosis, fasting blood glucose, oral glucose tolerance test or glycated hemoglobin (HbA1C). In cross-sectional studies, compared to individuals in the highest PRL groups (reference), those in the lowest PRL groups had greater risk of type 2 diabetes both in men: odds ratio (OR) and 95