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Abstract Background The genetic basis of type 2 diabetes (T2D) is under-investigated in the Middle East, despite the rapidly growing disease prevalence. We aimed to define the genetic determinants of T2D in Qatar. Methods Using whole genome sequencing of 11,436 participants (2765 T2D cases and 8671 controls) from the population-based Qatar Biobank (QBB), we conducted a genome-wide association study (GWAS) of T2D with and without body mass index (BMI) adjustment. Results We replicated 93 known T2D-associated loci in a BMI-unadjusted model, while 96 known loci were replicated in a BMI-adjusted model. The effect sizes and allele frequencies of replicated SNPs in the Qatari population generally concurred with those from European populations. We identified a locus specific to our cohort located between the APOBEC3H and CBX7 genes in the BMI-unadjusted model. Also, we performed a transethnic meta-analysis of our cohort with a previous GWAS on T2D in multi-ancestry individuals (180,834 T2D cases and 1,159,055 controls). One locus in DYNC2H1 gene reached genome-wide significance in the meta-analysis. Assessing polygenic risk scores derived from European- and multi-ancestries in the Qatari population showed higher predictive performance of the multi-ancestry panel compared to the European panel. Conclusion Our study provides new insights into the genetic architecture of T2D in a Middle Eastern population and identifies genes that may be explored further for their involvement in T2D pathogenesis.

Abstract There is variability in the metabolic health status among individuals presenting with obesity; some may be metabolically healthy, while others may have developed the metabolic syndrome, a cluster including insulin resistance, hypertension, dyslipidemia, and increased risk of cardiovascular disease and type 2 diabetes. The mechanisms contributing to this metabolic heterogeneity are not fully understood. To address this question, plasma samples from 48 individuals with BMI ≥ 35 kg/m2 were examined (27 with and 21 without metabolic syndrome). Fasting plasma samples were subjected to Olink proteomics analysis for 184 cardiometabolic and inflammation-enriched proteins. Data analysis showed a clear differentiation between the two groups with distinct plasma protein expression profiles. Twenty-four proteins were differentially expressed (DEPs) between the two groups. Pathways related to immune cell migration, leukocyte chemotaxis, chemokine signaling, mucosal inflammatory response, tissue repair and remodeling were enriched in the group with metabolic syndrome. Functional analysis of DEPs revealed upregulation of 15 immunological pathways. The study identifies some of the pathways that are altered and reflect metabolic health in individuals with obesity. This provides valuable insights into some of the underlying mechanisms and can lead to identification of therapeutic targets to improve metabolic health in individuals with obesity.

Abstract Background The burden of non‐communicable diseases, including diabetes, is high in the Middle East and North Africa (MENA) region. Qatar (a MENA country) has a high prevalence of diabetes (16.7%). Over the past 20 years, Qatar has made significant investment to establish a biomedical research infrastructure. This article documents the processes adopted for the development of a national diabetes research agenda for Qatar. Methods To develop the diabetes research agenda, a three‐step process was adopted. First, a bibliometric analysis of diabetes‐related research publications was conducted to understand current research and funding patterns. Second, through in‐depth interviews and a national consultative workshop, the challenges associated with diabetes research and their potential solutions were documented. Third, an expert team assimilated the recommendations to finalise the diabetes research agenda for the State of Qatar. Results A steadily increasing number of diabetes research publications and collaboration with researchers from 48 different countries was noted. Aetiological research (49%), mainly from cohort studies, dominated research publications. The national diabetes research agenda prioritised five research areas focused on diabetes prevention, early detection, reversal, treatment development and evaluation and system research for improved outcomes. Under each area, a set of research questions were identified to guide the research community to align their research interests with high‐priority research in diabetes. Conclusion The national research agenda development process has uncovered some important knowledge gaps and outlined the most impactful areas for diabetes research. Achievement of the objectives of the research agenda requires enhanced collaboration among the research community, sustained research funding and enabling a robust regulatory framework.

Abstract Objectives To examine the hypothesis that obesity complicated by the metabolic syndrome, compared to uncomplicated obesity, has distinct molecular signatures and metabolic pathways. Methods We analyzed a cohort of 39 participants with obesity that included 21 with metabolic syndrome, age-matched to 18 without metabolic complications. We measured in whole blood samples 754 human microRNAs (miRNAs), 704 metabolites using unbiased mass spectrometry metabolomics, and 25,682 transcripts, which include both protein coding genes (PCGs) as well as non-coding transcripts. We then identified differentially expressed miRNAs, PCGs, and metabolites and integrated them using databases such as mirDIP (mapping between miRNA-PCG network), Human Metabolome Database (mapping between metabolite-PCG network) and tools like MetaboAnalyst (mapping between metabolite-metabolic pathway network) to determine dysregulated metabolic pathways in obesity with metabolic complications. Results We identified 8 significantly enriched metabolic pathways comprising 8 metabolites, 25 protein coding genes and 9 microRNAs which are each differentially expressed between the subjects with obesity and those with obesity and metabolic syndrome. By performing unsupervised hierarchical clustering on the enrichment matrix of the 8 metabolic pathways, we could approximately segregate the uncomplicated obesity strata from that of obesity with metabolic syndrome. Conclusions The data suggest that at least 8 metabolic pathways, along with their various dysregulated elements, identified via our integrative bioinformatics pipeline, can potentially differentiate those with obesity from those with obesity and metabolic complications.

Abstract Background Mobile health (mHealth) is increasingly advocated for diabetes management. It is unclear if mobile applications are effective in improving glycaemic control, clinical outcomes, quality of life and overall patient satisfaction in patients with type 2 diabetes (T2DM). A new mobile application was specifically built for people with T2DM with the help of the local expertise. The objective of the study was to evaluate the effectiveness of the mobile app. Methods The planned study is an ongoing open-label randomised controlled trial in which adults living with T2DM treated with insulin will be randomised 1:1 to the use of this diabetes application versus current standard care. The primary outcome will be the difference in mean HbA1c from baseline to 6 months. Other outcome measures include anthropometric measures, hypoglycaemic events, medication adjustments, number of clinical interactions and missed appointments and patient perceptions of their disease and diabetes self-management. The study will randomise 180 subjects for assessment of the primary outcome. Discussion We hypothesise that the diabetes-specific mobile application will improve glycaemic control, increase patient empowerment for self-management of diabetes and improve interaction between patients and healthcare providers. If the Qatar Diabetes Mobile Application Trial (QDMAT) demonstrates this, it will inform clinical services for the future self-management of T2DM. Trial registration ClinicalTrials.gov Identifier: NCT03998267 . Registered on 26 June 2019

Abstract In recent years, there has been a significant expansion in the development and use of multi-modal sensors and technologies to monitor physical activity, sleep and circadian rhythms. These developments make accurate sleep monitoring at scale a possibility for the first time. Vast amounts of multi-sensor data are being generated with potential applications ranging from large-scale epidemiological research linking sleep patterns to disease, to wellness applications, including the sleep coaching of individuals with chronic conditions. However, in order to realise the full potential of these technologies for individuals, medicine and research, several significant challenges must be overcome. There are important outstanding questions regarding performance evaluation, as well as data storage, curation, processing, integration, modelling and interpretation. Here, we leverage expertise across neuroscience, clinical medicine, bioengineering, electrical engineering, epidemiology, computer science, mHealth and human–computer interaction to discuss the digitisation of sleep from a inter-disciplinary perspective. We introduce the state-of-the-art in sleep-monitoring technologies, and discuss the opportunities and challenges from data acquisition to the eventual application of insights in clinical and consumer settings. Further, we explore the strengths and limitations of current and emerging sensing methods with a particular focus on novel data-driven technologies, such as Artificial Intelligence.

BackgroundSeveral tools have been developed for health care professionals to monitor the physical activity of their patients, but most of these tools have been considering only the needs of users in North American and European countries and applicable for only specific analytic tasks. To our knowledge, no research study has utilized the participatory design (PD) approach in the Middle East region to develop such tools, involving all the stakeholders in the product development phases, and no clear use cases have been derived from such studies that could serve future development in the field. ObjectiveThis study aims to develop an interactive visualization tool (ActiVis) to support local health care professionals in monitoring the physical activity of their patients measured through wearable sensors, with the overall objective of improving the health of the Qatari population. MethodsWe used PD and user-centered design methodologies to develop ActiVis, including persona development, brainwriting, and heuristic walkthrough as part of user evaluation workshops; and use cases, heuristic walkthrough, interface walkthrough, and survey as part of expert evaluation sessions. ResultsWe derived and validated 6 data analysis use cases targeted at specific health care professionals from a collaborative design workshop and an expert user study. These use cases led to improving the design of the ActiVis tool to support the monitoring of patients’ physical activity by nurses and family doctors. The ActiVis research prototype (RP) compared favorably with the Fitbit Dashboard, showing the importance of design tools specific to end users’ needs rather than relying on repurposing existing tools designed for other types of users. The use cases we derived happen to be culturally agnostic, despite our assumption that the local Muslim and Arabic culture could impact the design of such visualization tools. At last, taking a step back, we reflect on running collaborative design sessions in a multicultural environment and oil-based economy. ConclusionsBeyond the development of the ActiVis tool, this study can serve other visualization and human–computer interaction designers in the region to prepare their design projects and encourage health care professionals to engage with designers and engineers to improve the tools they use for supporting their daily routine. The development of the ActiVis tool for nurses, and other visualization tools specific to family doctors and clinician researchers, is still ongoing and we plan to integrate them into an operational platform for health care professionals in Qatar in the near future.

Objectives Diabetes Intervention Accentuating Diet and Enhancing Metabolism-I (DIADEM-I) is the first randomised controlled trial (RCT) in the Middle East and North Africa (MENA) region testing the effectiveness of an intensive lifestyle intervention (ILI) for weight loss and diabetes remission. We report on the recruitment process and baseline characteristics of the DIADEM-I cohort based on origin (Middle East vs North Africa), and waist circumference.Design DIADEM-I is an open-label randomised, controlled, parallel group RCT recruiting young individuals (18–50 years) with early type 2 diabetes (≤3 years since diagnosis) originating from MENA. Individuals from primary care were randomised to usual medical care or ILI (total dietary replacement phase using meal replacement products, followed by staged food reintroduction and physical activity support). The primary outcome is weight loss at 12 months. Other outcomes are glycaemic control and diabetes remission.Setting Primary care, Qatar.Participants 147 (73% men) randomised within DIADEM-I who were included in the final trial data analysis.Outcome measures Recruitment metrics, and baseline clinical and metabolic characteristics.Results Of 1498 people prescreened, 267 (18%) were invited for screening and 209 (78%) consented. 173 (83%) were eligible. 15 (7%) withdrew before randomisation and the remaining 158 were randomised. Mean age was 42.1 (SD 5.6) years and mean body mass index was: 36.3 (5.5) kg/m2 (women) and 34.4 (5.4) kg/m2 (men). Mean diabetes duration was 1.8 (1.0) years and mean glycosylated haemoglobin (HbA1c) was 7.0% (1.30) (52.5 mmol/mol (SD 14.3)). Participants originated from 13 countries. Those from North Africa reported greater physical activity and had lower family history of diabetes. 90% of subjects were taking diabetes medications and 31% antihypertensives. Those with greater waist circumference had significantly higher insulin resistance and lower quality of life.Conclusion Recruitment of participants originating from the MENA region into the RCT was successful, and study participation was readily accepted. While DIADEM-I participants originated from 13 countries, there were few baseline differences amongst participants from Middle East versus North Africa, supporting generalisability of RCT results.Trial registration number ISRCTN20754766; NCT03225339

ObjectivesThe management of patients with long-standing type 2 diabetes and obesity receiving insulin therapy (IT) is a substantial clinical challenge. Our objective was to examine the effect of a low-energy total diet replacement (TDR) intervention versus standardized dietetic care in patients with long-standing type 2 diabetes and obesity receiving IT.Research design and methodsIn a prospective randomized controlled trial, 90 participants with type 2 diabetes and obesity receiving IT were assigned to either a low-energy TDR (intervention) or standardized dietetic care (control) in an outpatient setting. The primary outcome was weight loss at 12 months with secondary outcomes including glycemic control, insulin burden and quality of life (QoL).ResultsMean weight loss at 12 months was 9.8 kg (SD 4.9) in the intervention and 5.6 kg (SD 6.1) in the control group (adjusted mean difference −4.3 kg, 95% CI −6.3 to 2.3, p

Abstract Background Type 2 diabetes mellitus (T2DM) and obesity are syndemic and will have a significant impact on affected individuals and healthcare services worldwide. Evidence shows that T2DM remission can be achieved with significant weight loss in those who are younger with early diabetes and requiring fewer medications for glycaemic control. DIADEM-I aims to examine the impact of an intensive lifestyle intervention (ILI) using a low-energy diet (LED) meal replacement approach combined with physical activity in younger individuals with early T2DM. Methods The planned study is an ongoing, non-blinded, pragmatic, randomised controlled, parallel-group trial examining the impact of an LED-based ILI on body weight and diabetes remission in younger (18–50 years) T2DM individuals with early diabetes (≤ 3-year duration). The ILI will be compared to usual medical care (UMC). The primary outcome will be weight loss at 12 months. Other key outcomes of interest include diabetes remission, glycaemic control, diabetes complications, cardiovascular health, physical activity, mental health, and quality of life. It is planned for the study to include 138 subjects for assessment of the primary outcome. Safety will be assessed throughout. Discussion If DIADEM-I demonstrates a clinically significant effect for younger individuals with early T2DM, it will inform clinical guidelines and services of the future for management of T2DM. Trial registration ISRCTN: ISRCTN20754766 (date assigned: 7 June 2017); ClinicalTrials.gov, ID: NCT03225339 Registered on 26 June 2017.

Abstract Background The prevalence of type 2 diabetes mellitus (T2DM) is increasing worldwide. T2DM is associated with serious macro- and microvascular complications. In particular, diabetic kidney disease (DKD), which begins with excessive urinary albumin excretion, has a significant impact on affected individuals and is costly to healthcare services. Inhibition of the renin–angiotensin–aldosterone system (RAAS) with angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) significantly reduces albuminuria in diabetes, but this effect is not observed in all those treated. Active vitamin D analogues have been observed to be reno-protective through inhibition of RAAS in animal and human studies. Therefore, it can be hypothesised that an active vitamin D analogue will have an additional benefit to ACEI/ARB treatment for albuminuria reduction in DKD. Methods The planned study is an ongoing non-blinded randomised controlled parallel-group trial examining the impact, in individuals with T2DM, of the addition of bioactive vitamin D (calcitriol) to RAAS inhibition treatment using ACI or ARB on urinary albumin excretion over a period of 26 weeks. The primary outcome measure is the urinary albumin creatinine ratio. It is planned for the study to recruit 320 participants. Other outcome measures of interest include 24-h urine albumin (24 h UA) excretion, estimated glomerular filtration rate (eGFR), blood pressure and quality of life. Safety will be assessed throughout. Discussion If the addition of calcitriol to RAAS inhibition with ACEI or ARB safely results in a significant reduction in albuminuria, the study adds to the body of evidence supporting a role for vitamin D in reno-protection, will inform clinical practice and could result in significant reduction of healthcare costs associated with DKD. Trial registration ISRCTN, ISRCTN86739609. Registered on 7 June 2017. ClinicalTrials.gov, NCT03216564. Registered on 13 July 2017.

Recruitment into clinical research studies is a major challenge. This study was carried out to explore the perceptions and attitudes towards clinical research participation among the general public in Qatar. A population based questionnaire study was carried out at public events held in Qatar. Residents of Qatar, 18 years or above in age were surveyed, anonymously, following verbal consent. Descriptive and multivariate analyses were conducted. We administered 2517 questionnaires to examine clinical research participation, of which 2379 complete forms were analyzed. Those who had previously been approached to participate in research completed a more detailed assessment. Data showed that only 5.7% participants (n = 134) had previously been approached to participate in a clinical research study. Of these 63.4% (n = 85) had agreed to participate while 36.6% (n = 49) had declined. The main reasons for declining participation included: time constraint (47.8%, n = 11), ‘fear’ (13.0%, n = 3), lack of awareness about clinical research (8.7%, n = 2) and lack of interest (8.7%, n = 2). ‘To help others’ (31.8%, n = 27) and ‘thought it might improve my access to health care’ (24.7%, n = 21) were the prime motivators for participation. There was a general agreement among participants that their previous research experience was associated with positive outcomes for self and others, that the research conduct was ethical, and that opportunities for participation will be welcomed in future. More than ten years of stay within Qatar was a statistically significant determinant of willingness to participate, adjusted odds ratio 5.82 (95% CI 1.93–17.55), p = 0.002. Clinical research participation in Qatar needs improvement. Time constraints, lack of trust in and poor awareness about clinical research are main barriers to participation. Altruism, and improved health access are reported as prime motivators. Deeper insight in to the factors affecting clinical research participation is needed to devise evidence based policies for improvement in recruitment strategies.

Background Aspirin is of uncertain benefit for primary prevention in patients with type 2 diabetes mellitus (T2D). We assessed whether primary prevention with aspirin is beneficial in patients with T2D and heart failure (HF). Methods and Results Data from The Health Improvement Network, a UK multicenter prospective primary care database, were analyzed. Those with T2D and HF, age ≥55 years, and no previous history of myocardial infarction and/or coronary artery disease, stroke, peripheral artery disease, or atrial fibrillation were included. We compared outcomes for those on aspirin to no aspirin after diagnosis of HF and T2D and assessed the role of a >75‐mg dose. The primary outcome was a composite of all‐cause mortality and hospitalization for HF; secondary outcomes were nonfatal stroke, nonfatal myocardial infarction, or major bleeding. There were 5967 participants on aspirin and 6567 not on aspirin. The mean age (SD) was 75.3 (9.6) years, 53.9% were men, and the mean follow‐up (SD) was for 5 (4.2) years. After propensity‐score matching and further multivariable adjustment, aspirin was significantly associated with a decrease in the primary outcome and all‐cause mortality (hazard ratio=0.88, 95% confidence interval 0.82‐0.93; 0.88, 0.83‐0.94], respectively); and an increased risk of nonfatal myocardial infarction (hazard ratio=1.66; 95% confidence interval 1.49‐1.85) and nonfatal stroke (hazard ratio=1.23, 1.01‐1.50). Major bleedings and hospitalization for HF were not significantly higher with aspirin (hazard ratio=0.68, 0.45‐1.03; 0.87, 0.66‐1.15, respectively). There was no additional benefit for a dose >75 mg. Conclusions Primary prevention with aspirin in patients with T2D and HF is associated with lower all‐cause mortality.

Objectives: To examine direct and indirect associations of sleep duration and quality with insulin resistance, considering body mass index (BMI) as a potential mediator in newly diagnosed type 2 diabetes mellitus patients. Methods: Cross-sectional data from patients enrolled in the Early Activity in Diabetes study. We studied 522 newly diagnosed type 2 diabetes mellitus patients, 65.9% male, mean age 63.5 ± 10.1 years. Of the total sample 53% had a BMI of ⩾30 kg/m 2 . Participants completed a 7-day sleep diary and sleep questionnaire. Average sleep duration (minutes), average nap duration (minutes) and average number of night awakenings were derived. Objective measures of height and body weight were obtained for the BMI calculation (kg/m 2 ). Insulin resistance was obtained using the homeostatic model assessment – insulin resistance (HOMA2-IR) standardized technique. Results: Average number of night awakenings was positively correlated with BMI ( r= 0.22, p < 0.001) and negatively associated with logged HOMA2-IR ( r= -0.16, p = 0.04). Path analysis demonstrated night awakenings were directly associated with BMI and indirectly associated with insulin resistance, whilst considering BMI as a potential mediator ( p < 0.05). Sleep duration was not associated with BMI or insulin resistance ( p > 0.05). Conclusions: Sleep quality, not sleep duration, plays an important role in insulin resistance in newly diagnosed type 2 diabetes mellitus patients. BMI may mediate the relationship between indicators of sleep quality and insulin resistance. There is a need to examine the impact of improving sleep quality on obesity and insulin resistance in patients with type 2 diabetes mellitus.

BACKGROUND:Qatar is experiencing rapid population expansion with increasing demands on healthcare services for both acute and chronic conditions. Sourcing accurate information about health conditions is crucial, yet the methods used for sourcing health information in Qatar are currently unknown. Gaining a better understanding of the sources the Qatari population use to recognize and manage health and/or disease will help to develop strategies to educate individuals about existing and emerging health problems. OBJECTIVE:To investigate the methods used by the Qatari population to source health information. We hypothesized that the Internet would be a key service used to access health information by the Qatari population. METHODS:A researcher-led questionnaire was used to collect information from Qatari adults, aged 18-85 years. Participants were approached in shopping centers and public places in Doha, the capital city of Qatar. The questionnaire was used to ascertain information concerning demographics, health status, and utilization of health care services during the past year as well as sources of health information used. RESULTS:Data from a total of 394 eligible participants were included. The Internet was widely used for seeking health information among the Qatari population (71.1%). A greater proportion of Qatari females (78.7%) reported searching for health-related information using the Internet compared to Qatari males (60.8%). Other commonly used sources were family and friends (37.8%) and Primary Health Care Centers (31.2%). Google was the most commonly used search engine (94.8%). Gender, age and education levels were all significant predictors of Internet use for heath information (P

To explore the cross-sectional association between adiposity, mental well-being, and quality of life in extreme obese individuals entering a UK specialist weight management service prior to treatment commencement.The sample comprised 263 extreme obese individuals who were referred to the service as a result of having a body mass index (BMI) ≥40 kg/m2 or ≥35 kg/m2 with a co-morbid health condition. In a retrospective analysis, routinely collected baseline clinical examination data and self-report questionnaires (Impact of Weight on Quality of Life: IWQOL-Lite, EQ5D-3L, and Hospital Anxiety and Depression Scale: HADS) were analysed to examine the cross-sectional association between adiposity and quality of life.The sample was predominantly female (74.8%) with mean BMI 47.0±7.9 kg/m2. Increasing adiposity was significantly negatively associated with quality of life, with an increase of 1 BMI unit associated with decreases of 1.93 in physical function (95% CI -2.86 - -1.00, p

Study objectivesThe majority of adolescent sleep research has utilized self-reported sleep duration and some have based information on a solitary question. Whilst some have claimed to have validated sleep survey data with objective actigraphy measures in adolescents, the statistical approach applied only demonstrates the strength of the association between subjective and objective sleep duration data and does not reflect if these different methods actually agree.MethodsData were collected as part of the Midlands Adolescents Schools Sleep Education Study (MASSES). Adolescents (n=225) aged 11-13 years provided estimates for weekday, weekend and combined sleep duration based on self-reported survey data, a 7-day sleep diary, and wrist-worn actigraphy.ResultsWe assessed the strength of the relationship as well as agreement levels between subjective and objectively determined sleep duration (weekday, weekend and combined). Subjective diary sleep duration was significantly correlated with actigraphy estimates for weekday and weekend sleep duration r=0.30, p ≤ 0.001 and r=0.31, p ≤ 0.001 respectively. Pitman's test demonstrated no significant difference in the variance between weekend sleep duration (r=0.09, p=0.16) and combined sleep duration (r=0.12, p=0.08) indicating acceptable agreement between actigraphy and sleep diary sleep duration only. Self-reported sleep duration estimates (weekday, weekend and combined) did not agree with actigraphy determined sleep duration.ConclusionsSleep diaries are a cost-effective alternative to survey/questionnaire data. Self-reported measures of sleep duration in adolescents do not agree with actigraphy measures and should be avoided where possible. Previous adolescent sleep studies that have utilized self-reported survey data may not provide a complete representation of sleep on the outcome measure of interest.

Obstructive sleep apnea (OSA) is common in obese patients with type 2 diabetes mellitus (DM) and may contribute to diabetic microvascular complications.To investigate the association between OSA, hypoxemia during sleep, and diabetic retinal complications in severe obesity. This was a prospective observational study of 93 obese patients mean (SD) age: 52(10) years; mean (SD) body mass index (BMI): 47.3(8.3) kg/m(2)) with DM undergoing retinal screening and respiratory monitoring during sleep. OSA was defined as apnea-hypopnea index (AHI) of ≥15 events/hour, resulting in two groups (OSA+ vs. OSA-).Forty-six patients were OSA+: median (95% CI) AHI = 37(23-74)/hour and 47 were OSA-ve (AHI = 7(4-11)/hour). Both groups were similar for ethnicity, BMI, cardiovascular co-morbidities, diabetes duration, HbA1c, and insulin treatment (p>0.05). The OSA+ group was significantly more hypoxemic. There was no significant difference between OSA+ and OSA- groups for the presence of retinopathy (39% vs. 38%). More OSA+ subjects had maculopathy (22% vs. 13%), but this did not reach statistical significance. Logistic regression analyses showed that AHI was not significantly associated with the presence of retinopathy or maculopathy (p>0.05). Whilst minimum oxygen saturation was not significantly associated with retinopathy, it was an independent predictor for the presence of maculopathy OR = 0.79 (95% CI: 0.65-0.95; p

The rising challenge of diabetes requires novel service delivery approaches. In the UK, Local Enhanced Services (LES) have been commissioned for diabetes. Health professionals from general practices (GPs) who signed up to LES were given additional training (and a monetary incentive) to improve management of patients with diabetes. All practices in the PCT were invited to the LES initiative, which ensured avoiding selection bias. The aim of the study was to examine the impact of LES in terms of diabetes Quality Outcome Framework (QOF) indicators: DM23(glycaemia), DM17(lipid) and DM12(blood pressure; BP).QOF diabetes indicators were examined using data from 76 general practices for 2009-2010 in a large primary care trust area in Birmingham, UK. Data were extracted from Quality Management Analysis System. The primary outcome was a difference in achievement of QOF indicators between LES and NLES practices. A secondary outcome was the difference between LES and non-LES practices for hospital first and follow-up appointments.We did not find any difference for DM12(BP) and DM17(lipid) outcomes between LES and NLES practices. However, LES practices were more likely to achieve the DM23(glycaemia) outcome (estimated odds 1.459;95% CI:1.378-1.544; P=0.0001). The probability of achieving satisfactory level of DM23(glycaemia) increased by almost 10% when GPs belonged to LES groups compared with GPs in NLES group. LES practices were less likely to refer patients to secondary care.Overall, LES practices performed better in the achievement of DM23(glycaemia) and also referred fewer patients to hospital, thereby meeting their objectives. This suggests that the LES approach is beneficial and needs to be further explored in order to ascertain whether the impact exerted was due to LES.

Efficacy of dietary intervention for treatment and prevention of HIV-related lipid disturbances has not been well established.We conducted a systematic search of electronic databases supplemented with manual searches and conference abstracts, without language restriction. All randomised controlled trials (RCTs) with blood lipid outcomes, involving dietary intervention or supplementation for the treatment or prevention of adult HIV dyslipidaemia, versus no or other intervention were included. Two authors using predefined data fields, including study quality indicators, extracted data independently.Eighteen studies (n = 873) met our inclusion criteria. Seven RCTs for omega-3 supplementation (n = 372), and four RCTs for dietary intervention (n = 201) were meta-analysed using random-effects models. Mild statistical heterogeneity was observed. Dietary intervention reduced triglyceride levels by -0·46 mmol/l (95%CI: -0·85 to -0·07 mmol/l) compared to control. Omega-3 supplementation reduced triglyceride levels by -1.12 mmol/l, (95%CI: -1·57 to -0·67 mmol/l) and total cholesterol, -0·36 mmol/l (95%CI: -0·67 to -0·05 mmol/l) compared to placebo/control.Both omega-3 supplementation and dietary intervention reduced triglyceride level, with the latter possibly to a smaller extent. While dietary interventions are beneficial, more stringent dietary approaches may be necessary to fully address lipid disturbances in HIV patients.PROSPERO 2011:CRD42011001329.

Disruption of endogenous circadian rhythms has been shown to increase the risk of developing type 2 diabetes, suggesting that circadian genes might play a role in determining disease susceptibility. We present the results of a pilot study investigating the association between type 2 diabetes and selected single nucleotide polymorphisms (SNPs) in/near nine circadian genes. The variants were chosen based on their previously reported association with prostate cancer, a disease that has been suggested to have a genetic link with type 2 diabetes through a number of shared inherited risk determinants.The pilot study was performed using two genetically homogeneous Punjabi cohorts, one resident in the United Kingdom and one indigenous to Pakistan. Subjects with (N = 1732) and without (N = 1780) type 2 diabetes were genotyped for thirteen circadian variants using a competitive allele-specific polymerase chain reaction method. Associations between the SNPs and type 2 diabetes were investigated using logistic regression. The results were also combined with in silico data from other South Asian datasets (SAT2D consortium) and white European cohorts (DIAGRAM+) using meta-analysis. The rs7602358G allele near PER2 was negatively associated with type 2 diabetes in our Punjabi cohorts (combined odds ratio [OR] = 0.75 [0.66-0.86], p = 3.18 × 10(-5)), while the BMAL1 rs11022775T allele was associated with an increased risk of the disease (combined OR = 1.22 [1.07-1.39], p = 0.003). Neither of these associations was replicated in the SAT2D or DIAGRAM+ datasets, however. Meta-analysis of all the cohorts identified disease associations with two variants, rs2292912 in CRY2 and rs12315175 near CRY1, although statistical significance was nominal (combined OR = 1.05 [1.01-1.08], p = 0.008 and OR = 0.95 [0.91-0.99], p = 0.015 respectively).None of the selected circadian gene variants was associated with type 2 diabetes with study-wide significance after meta-analysis. The nominal association observed with the CRY2 SNP, however, complements previous findings and confirms a role for this locus in disease susceptibility.

Behavior modification necessary to tackle obesity and type 2 diabetes mellitus (T2DM) requires individual awareness of the existing problem. Objectives: This study aimed to assess body weight perception, awareness of the relation between adiposity and T2DM, and the relation between adiposity and weight loss attempts. Methods: Male drivers were recruited randomly from motorway service stations between May and July 2007, completed a questionnaire and had body mass index (BMI), waist circumference (WC), and body composition. Results: Participants included 266 men, median age 52 years, and BMI 28.25 kg/m2. Obesity prevalence was 46% based on BMI and 73% based on WC. Participants underestimated their WC (94.3 ± 10.2 vs. 102.9 ± 11.41 cm, estimated vs. actual, p < .001). Of participants with normal BMI, 18% thought they were overweight, whereas 26% of overweight thought they were “just right” and 19% of obese recognized their obesity. Based on WC, 30% of participants with normal WC thought they were obese and 9% of obese realized they were obese. Only 25% and 42% of participants recognized that T2DM is associated with large waist and obesity, respectively. A total of 81% of overweight and 62% of obese participants (based on BMI) believed that they were not at increased risk of T2DM. Self-perception of adiposity weakly predicted weight loss attempts (λ = 0.28, p = .008). Conclusion: Male drivers significantly underestimate their adiposity and risk of T2DM. Further public education regarding obesity, its associated health risks, and the benefits of weight loss is needed.

The sleep disorder narcolepsy is caused by a vast reduction in neurons producing the hypocretin (orexin) neuropeptides. Based on the tight association with HLA, narcolepsy is believed to result from an autoimmune attack, but the cause of hypocretin cell loss is still unknown. We performed gene expression profiling in the hypothalamus to identify novel genes dysregulated in narcolepsy, as these may be the target of autoimmune attack or modulate hypocretin gene expression.We used microarrays to compare the transcriptome in the posterior hypothalamus of (1) narcoleptic versus control postmortem human brains and (2) transgenic mice lacking hypocretin neurons versus wild type mice. Hypocretin was the most downregulated gene in human narcolepsy brains. Among many additional candidates, only one, insulin-like growth factor binding protein 3 (IGFBP3), was downregulated in both human and mouse models and co-expressed in hypocretin neurons. Functional analysis indicated decreased hypocretin messenger RNA and peptide content, and increased sleep in transgenic mice overexpressing human IGFBP3, an effect possibly mediated through decreased hypocretin promotor activity in the presence of excessive IGFBP3. Although we found no IGFBP3 autoantibodies nor a genetic association with IGFBP3 polymorphisms in human narcolepsy, we found that an IGFBP3 polymorphism known to increase serum IGFBP3 levels was associated with lower CSF hypocretin-1 in normal individuals.Comparison of the transcriptome in narcolepsy and narcolepsy model mouse brains revealed a novel dysregulated gene which colocalized in hypocretin cells. Functional analysis indicated that the identified IGFBP3 is a new regulator of hypocretin cell physiology that may be involved not only in the pathophysiology of narcolepsy, but also in the regulation of sleep in normal individuals, most notably during adolescence. Further studies are required to address the hypothesis that excessive IGFBP3 expression may initiate hypocretin cell death and cause narcolepsy.

BackgroundSleep duration may be an important regulator of body weight and metabolism. An association between short habitual sleep time and increased body mass index (BMI) has been reported in large population samples. The potential role of metabolic hormones in this association is unknown.Methods and findingsStudy participants were 1,024 volunteers from the Wisconsin Sleep Cohort Study, a population-based longitudinal study of sleep disorders. Participants underwent nocturnal polysomnography and reported on their sleep habits through questionnaires and sleep diaries. Following polysomnography, morning, fasted blood samples were evaluated for serum leptin and ghrelin (two key opposing hormones in appetite regulation), adiponectin, insulin, glucose, and lipid profile. Relationships among these measures, BMI, and sleep duration (habitual and immediately prior to blood sampling) were examined using multiple variable regressions with control for confounding factors. A U-shaped curvilinear association between sleep duration and BMI was observed. In persons sleeping less than 8 h (74.4% of the sample), increased BMI was proportional to decreased sleep. Short sleep was associated with low leptin (p for slope = 0.01), with a predicted 15.5% lower leptin for habitual sleep of 5 h versus 8 h, and high ghrelin (p for slope = 0.008), with a predicted 14.9% higher ghrelin for nocturnal (polysomnographic) sleep of 5 h versus 8 h, independent of BMI.ConclusionParticipants with short sleep had reduced leptin and elevated ghrelin. These differences in leptin and ghrelin are likely to increase appetite, possibly explaining the increased BMI observed with short sleep duration. In Western societies, where chronic sleep restriction is common and food is widely available, changes in appetite regulatory hormones with sleep curtailment may contribute to obesity.