Liver, visceral and subcutaneous fat in men and women of South Asian and white European descent: a systematic review and meta-analysis of new and published data.

AIMS/HYPOTHESIS: South Asians have a two- to fivefold higher risk of developing type 2 diabetes than those of white European descent. Greater central adiposity and storage of fat in deeper or ectopic depots are potential contributing mechanisms. We collated existing and new data on the amount of subcutaneous (SAT), visceral (VAT) and liver fat in adults of South Asian and white European descent to provide a robust assessment of potential ethnic differences in these factors. METHODS: We performed a systematic review of the Embase and PubMed databases from inception to August 2021. Unpublished imaging data were also included. The weighted standardised mean difference (SMD) for each adiposity measure was estimated using random-effects models. The quality of the studies was assessed using the ROBINS-E tool for risk of bias and overall certainty of the evidence was assessed using the GRADE approach. The study was pre-registered with the OSF Registries ( https://osf.io/w5bf9 ). RESULTS: We summarised imaging data on SAT, VAT and liver fat from eight published and three previously unpublished datasets, including a total of 1156 South Asian and 2891 white European men, and 697 South Asian and 2271 white European women. Despite South Asian men having a mean BMI approximately 0.5-0.7 kg/m2 lower than white European men (depending on the comparison), nine studies showed 0.34 SMD (95% CI 0.12, 0.55; I2=83%) more SAT and seven studies showed 0.56 SMD (95% CI 0.14, 0.98; I2=93%) more liver fat, but nine studies had similar VAT (-0.03 SMD; 95% CI -0.24, 0.19; I2=85%) compared with their white European counterparts. South Asian women had an approximately 0.9 kg/m2 lower BMI but 0.31 SMD (95% CI 0.14, 0.48; I2=53%) more liver fat than their white European counterparts in five studies. Subcutaneous fat levels (0.03 SMD; 95% CI -0.17, 0.23; I2=72%) and VAT levels (0.04 SMD; 95% CI -0.16, 0.24; I2=71%) did not differ significantly between ethnic groups in eight studies of women. CONCLUSIONS/INTERPRETATION: South Asian men and women appear to store more ectopic fat in the liver compared with their white European counterparts with similar BMI levels. Given the emerging understanding of the importance of liver fat in diabetes pathogenesis, these findings help explain the greater diabetes risks in South Asians. FUNDING: There was no primary direct funding for undertaking the systematic review and meta-analysis.

Understanding the stigma: a novel quantitative study comparing mental health attitudes and perceptions between young British Muslims and their non-Muslims peers.

BACKGROUND: A significant proportion of young British Muslims identify themselves by religious identity rather than ethnicity however very few mental health studies have focused on this cohort. AIMS: To explore whether young British Muslims' knowledge, awareness and perceptions of mental illness differ to their non-Muslim peers. METHOD: Population based survey of second generation Muslims (n = 83) and non-Muslims (n = 76) aged 18-35. Anonymised 38-item questionnaire on mental health attitudes, perceptions and help seeking behaviours. RESULTS: Muslims were less likely to correctly identify symptoms of mental illness compared to their non-Muslim peers. Stigma and awareness remains a major issue. A third of Muslims would consider stopping medication on advice of a religious leader. Nearly half of Muslims were more likely to attend a dedicated ethnic/religious mental health service. CONCLUSIONS: British Muslim views and attitudes of mental health differ from their non-Muslim counterparts. Services should ensure they are religiously sensitive.

Fasting with adrenal insufficiency: Practical guidance for healthcare professionals managing patients on steroids during Ramadan.

There are limited recommendations for fasting in many chronic diseases such as adrenal insufficiency (AI). Research in such situations highlights potential for complications and need for education for patients with AI undertaking fasting during Ramadan. This article aimed to provide up-to-date guidance for healthcare professionals to educate, discuss and manage patients with AI who are considering fasting in Ramadan and is religiously compatible. Latest guidance on this topic and the evidence base for steroid dosing are reviewed and discussed. Risk stratification for patients with AI and optimal strategies for management, including steroid dosing, are detailed. Our review highlights that patients with AI wishing to fast should undergo a thorough risk assessment ideally several months before Ramadan. 'High risk' and 'Very high risk' patients should be encouraged to explore alternative options to fasting discussed below. Prior to the commencement of Ramadan, all patients must receive up-to-date education on sick day rules, instructions on when to terminate their fast or abstain from fasting, carry steroid warning information and must have a valid intramuscular (IM) hydrocortisone pack and know how to administer this. Switching patients with AI desiring to fast from multiple daily hydrocortisone replacement to prednisolone 5 mg once daily at dawn (during Suhoor or Sehri) is recommended and discussed. Patients on fludrocortisone for AI should be advised to take their total dose at dawn. We provide practically relevant case-based scenarios to help with the application of this guidance. Future efforts need to focus on healthcare professional awareness and further research in this setting.

Managing epilepsy in Ramadan: Guidance for healthcare providers and patients.

Ramadan is a regularly recurring period of fasting that takes place in the ninth month of the Islamic calendar. For this period, adult Muslims refrain from eating and drinking between dawn and sunset. The variation in summer daylight hours means that at temperate latitudes, fasting can last up to 20 h. It is already recognized that epilepsy control can deteriorate during Ramadan, and this may be explained by fasting-related changes to adherence to antiseizure drug regimes. This article provides specific advice to help Muslim patients prepare for Ramadan and reduce chances of exacerbation in epilepsy. In addition to advice around sleep hygiene, it explores the use of drugs or preparations of drugs that will demonstrate reduced variation during periods of fasting.

Gaining an advantage by sitting an OSCE after your peers: A retrospective study.

Purpose: To investigate if final year medical students undertaking an OSCE station at a later stage during examination diet were advantaged over their peers who undertook the same station at an earlier stage, and whether any such effect varies by the student's relative academic standing. Methods: OSCE data from six consecutive final year cohorts totaling 1505 students was analyzed. Mixed effects logistic regression was used to model factors associated with the probability of passing each individual station (random effects for students and circuits; and fixed effects to assess the association with day of examination, time of day, gender and year). Results: Weaker students were more likely to pass if they took their OSCE later in the examination period. The odds of passing a station increased daily by 20%. Overall, the mean number of stations passed by each student increased over the 5 days. Conclusions: Students undertaking the same OSCE stations later in examination period statistically had higher chances of passing compared to their peers, and the weaker students appear to be particularly advantaged. These findings have major implications for OSCE design, to ensure students are not advantaged by examination timing, and weaker students are not "passing in error".

Ethnicity and risk of cardiovascular disease (CVD): 4.8 year follow-up of patients with type 2 diabetes living in Scotland.

AIMS/HYPOTHESIS: Potential differences in cardiovascular risk by ethnicity remain uncertain. We evaluated the association of ethnicity with cardiovascular disease (CVD) incidence in a large cohort of people with type 2 diabetes living in Scotland. METHODS: Data from Scottish Care Information-Diabetes (SCI-Diabetes) were linked to Scottish Morbidity Records (SMR01) and National Records of Scotland data for mortality for dates between 2005 and 2011. Of 156,991 people with type 2 diabetes with coded ethnicity, 121,535 (77.4%) had no CVD at baseline (White: 114,461; Multiple Ethnic: 2,554; Indian: 797; Other Asian: 319; Pakistani: 2,250; Chinese: 387; African-Caribbean: 301 and Other: 466) and were followed up (mean ± SD: 4.8 ± 2.3 years) for the development of fatal and non-fatal CVD. RESULTS: During follow-up, 16,265 (13.4%) patients developed CVD (ischaemic heart or cerebrovascular diseases). At baseline, Pakistanis were younger and had developed diabetes earlier, had higher HbA1c and longer duration of diabetes, but had lower BP, BMI, creatinine, proportion of smokers and proportion on antihypertensive therapy than whites. The age and sex adjusted HRs for CVD were HR 1.31 (CI 1.17, 1.47), p < 0.001 in Pakistanis and HR 0.66 (CI 0.47, 0.92), p = 0.014 in Chinese compared with whites. Adjusting additionally for an area measure of deprivation, duration of diabetes, conventional CVD and other risk factors, the HR for Pakistanis (HR 1.45 [CI 1.14, 1.85], p = 0.002) was significantly higher, and that for Chinese (HR = 0.58 [CI 0.24, 1.40], p = 0.228) lower, compared with whites. CONCLUSIONS/INTERPRETATION: Compared with whites with type 2 diabetes, those of Pakistani ethnicity in Scotland were at increased risk of CVD, whereas Chinese were at lower risk, with these differences unexplained by known risk factors.

Weight gain leads to greater adverse metabolic responses in South Asian compared with white European men: the GlasVEGAS study.

South Asians (SAs) develop type 2 diabetes at lower body mass index values than white Europeans (WEs). This basic human experimental study aimed to compare the metabolic consequences of weight gain in SA and WE men without overweight or obesity. Fourteen SAs and 21 WEs had assessments of body composition, metabolic responses to mixed-meal ingestion, cardiorespiratory fitness and physical activity, and a subcutaneous abdominal adipose tissue biopsy, before and after 4-6 weeks of overfeeding to induce 5-7% weight gain. Here we show that body mass index and whole-body adipose tissue volume increases similarly between ethnic groups, but SAs gain less lean tissue. SAs experience a substantially greater decrease in insulin sensitivity compared with WEs (38% versus 7% decrease, P = 0.009), have fewer small (37.1% versus 60.0%, P = 0.003) and more large (26.2% versus 9.1%, P = 0.005) adipocytes at baseline and have a smaller decrease in very small adipocytes with weight gain (-0.1% versus -1.9%, P < 0.0001). Ethnic differences in adipocyte morphology are associated with SA's greater adverse metabolic changes with weight gain. ClinicalTrials.gov registration: NCT02399423 .

Digitising diabetes education for a safer Ramadan: Design, delivery, and evaluation of massive open online courses in Ramadan-focused diabetes education.

AIMS: Ramadan-focused diabetes education is critical to facilitate safer Ramadan fasting amongst Muslim people living with diabetes. We present the design, delivery, and evaluation of two parallel massive open online courses (MOOCs) in Ramadan-focused diabetes education for people with diabetes and HCPs. METHODS: Two Ramadan-focused diabetes education MOOCs were developed and delivered for Ramadan 2023: one for HCPs in English, and another for people with diabetes in English, Arabic and Malay. A user-centred iterative design process was adopted, informed by user feedback from a 2022 pilot MOOC. Evaluation comprised a mixed-methods evaluation of pre- and post-course user surveys. RESULTS: The platform was utilised by people with diabetes and their family, friends and healthcare professionals. Overall, a total of 1531 users registered for the platform from 50 countries, 809 started a course with a 48% subsequent completion rate among course starters. Qualitative analysis showed users found the course a user-friendly and authoritative information source. In the HCP MOOC, users reported improved post-MOOC Ramadan awareness, associated diabetes knowledge and ability to assess and advise patients in relation to their diabetes during Ramadan (p<0.01). CONCLUSIONS: We demonstrate the potential of MOOCs to deliver culturally tailored, high-quality, scalable, multilingual Ramadan-focused diabetes education to HCPs and people with diabetes.

Circulating IL-6 concentrations and associated anthropometric and metabolic parameters in South Asian men and women in comparison to European whites.

OBJECTIVE: To determine any ethnic differences in circulating interleukin (IL)-6 concentrations among SAs and Europeans, and to assess their relationship with body composition and insulin resistance measures. METHODS: Body composition was assessed among 80 SA and European men and women using anthropometry, dual-energy X-ray absorptiometry and abdominal CT scan. Oral glucose tolerance tests with insulin response were performed to assess insulin resistance measures. IL-6 levels were measured by high sensitivity ELISA. RESULTS: Median IL-6 values were higher in SA compared with European women: 1.94 mg/l versus 1.51 mg/l, p=0.041, but not so in men (1.56 mg/l versus 1.57 mg/l). Only measures of obesity, in particular percentage fat area (r=0.6, p=0.003), were positively correlated with IL-6 in SAs. Differences in body fat percentage (visceral and total) could explain up to 30% of the IL-6 difference between Asian and European women. CONCLUSION: SA women have elevated circulating IL-6 levels, in part due to greater visceral and percent fat levels compared with European women. This observation may in part explain why Asians are at elevated cardiovascular disease risk. Future studies should address the effects of lifestyle factors (physical activity, diet) on plasma IL-6 concentrations in SA women.

Underrepresentation of ethnic minorities in hypertension research-a survey of enablers and barriers among South Asian and African communities in Glasgow.

BACKGROUND: Hypertension is the biggest contributor to the global cardiovascular burden with evidence for ethnic differences in treatment response and outcomes. Under-representation of ethnic minorities in clinical research is well known, and despite wide-ranging public engagement events by the Glasgow Blood Pressure Clinic team, there was a lack of participation of ethnic minorities in both engagement activities and clinical trials conducted by them. This study aims to explore the awareness and knowledge of hypertension and the facilitators and barriers to participation in hypertension clinical research among South Asian (SA) and African (AFR) communities in Glasgow. METHODS: A survey questionnaire was co-developed with representatives from South Asian (SA) and African (AFR) patients and community members in Glasgow to understand awareness and knowledge of hypertension and enablers and barriers to participation in clinical research. The survey was distributed to adults (aged > 18) years of SA or AFR ancestry at public engagement events at venues that were frequently visited by these two communities in Glasgow. RESULTS: The survey response rate was 337 (67.4%) consisting of 242 (71.8%) South Asian (SA) and 56 (16.9%) African (AFR) respondents. Thirty-nine questionnaires were excluded because of incompletion. Most of the respondents were not born in the UK and were in the 35-53-year group (AFR 29 (51%), SA 113 (47%)). The proportion living in the most deprived (SIMD 1) and least deprived (SIMD 5) was respectively 26 (12.4%) and 34 (16.2%) for SA and 20 (42.6%) and 2 (4.3%) for AFR. There was a considerable recognition that treatment needs to be ethnicity-specific (SA/AFR = 107 (48%)/23 (45.1%)) and that current cardiovascular disease treatment guidelines were not tailored for different ethnicities 84 (38.5%)/23 (45.1%). The key enablers encouraging research participation are enhanced health information, conducting aspects of their clinical research visits/appointments at a location they frequently visited and allowing a family member to accompany them. Barriers included concerns about the use of personal information and side effects of the new treatment. CONCLUSION: Our survey confirmed enablers and barriers to ethnic minority participation in research. We find improving and evolving awareness and beliefs among the ethnic minority population including community leaders. Thus, continual review of researchers' beliefs and attitudes is also essential to ensure engagement activities keep up with these changing perceptions.

Ramadan fasting: recommendations for patients with cardiovascular disease.

Ramadan fasting is observed by most of the 1.8 billion Muslims around the world. It lasts for 1 month per the lunar calendar year and is the abstention from any food and drink from dawn to sunset. While recommendations on 'safe' fasting exist for patients with some chronic conditions, such as diabetes mellitus, guidance for patients with cardiovascular disease is lacking. We reviewed the literature to help healthcare professionals educate, discuss and manage patients with cardiovascular conditions, who are considering fasting. Studies on the safety of Ramadan fasting in patients with cardiac disease are sparse, observational, of small sample size and have short follow-up. Using expert consensus and a recognised framework, we risk stratified patients into 'low or moderate risk', for example, stable angina or non-severe heart failure; 'high risk', for example, poorly controlled arrhythmias or recent myocardial infarction; and 'very high risk', for example, advanced heart failure. The 'low-moderate risk' group may fast, provided their medications and clinical conditions allow. The 'high' or 'very high risk' groups should not fast and may consider safe alternatives such as non-consecutive fasts or fasting shorter days, for example, during winter. All patients who are fasting should be educated before Ramadan on their risk and management (including the risk of dehydration, fluid overload and terminating the fast if they become unwell) and reviewed after Ramadan to reassess their risk status and condition. Further studies to clarify the benefits and risks of fasting on the cardiovascular system in patients with different cardiovascular conditions should help refine these recommendations.

Liver enzymes, nonalcoholic fatty liver disease, and incident cardiovascular disease: a narrative review and clinical perspective of prospective data.

UNLABELLED: In recent years, a strong link has been established between nonalcoholic fatty liver disease (NAFLD) and the pathogenesis of type 2 diabetes mellitus. The potential role of NAFLD in cardiovascular disease (CVD) has also attracted interest. Published studies have tended to use biochemical and imaging surrogate markers of NAFLD, such as elevated gamma glutamyl transpeptidase (GGT) and alanine aminotransferase (ALT) and fatty liver on ultrasound, when investigating associations with incident CVD events. Positive associations between both baseline GGT and temporal change in GGT, as well as cardiovascular events and cardiovascular mortality independent of alcohol intake, have been reported in several prospective studies. However, adjustment for confounders is often incomplete, and there is scant evidence of improvement in cardiovascular risk prediction beyond established risk scores when incorporating such data. There also appears to be a strong and underrecognized age interaction, with associations between GGT and incident coronary heart disease (CHD) being strong in young individuals but relatively weak in the elderly. By contrast, ALT appears to be only weakly associated with incident CHD and may exhibit a U-shaped association with total mortality. Finally, although some studies have linked imaging-defined and biopsy-confirmed NAFLD with CVD risk, the evidence is inconsistent, with few incident events and/or insufficient potential confounders. CONCLUSION: A diagnosis of NAFLD is insufficient to consider patients as being at high risk for CVD. The presence of NAFLD should be a clear indication for diabetes screening, but cardiovascular risk screening should be performed with the use of existing risk calculators and should be guided by established cardiovascular risk factors.

Pharmacological Management of Diabetes for Reducing Glucose Levels and Cardiovascular Disease Risk: What Evidence in South Asians?

INTRODUCTION: South Asians experience more type 2 diabetes, which is earlier in onset and with more rapid glycaemic deterioration, although average body mass indices are lower than in whites. Cardiovascular outcomes from diabetes drug trials are now reported as standard, with data from newer therapies influencing patient management. However, less is known of the effect of such therapies in South Asians. The aim of this narrative review was to extract, wherever possible, the glucose-lowering efficacy and cardiovascular and renal outcome data for these therapies in South Asians. DISCUSSION: Despite the higher prevalence and global burden of type 2 diabetes and adverse outcomes in South Asians, they remain underrepresented in global trials. Even when recruited, the current method of classifying ethnicity does not commonly allow South Asian data to be extracted and reported separately from all Asians. Interrogation of available trial data suggests broadly comparable effects on glycaemia and weight in Asians to other ethnicities with use of glucagon-like peptide 1 receptor agonists (GLP-1 RAs), but a potentially early, albeit marginally, greater glycaemia benefit with Dipeptidyl peptidase-4 inhibitors (DPP4is) which may not be sustained. Furthermore, there appears a potentially greater glycaemia benefit with use of sodium-glucose transport protein 2 inhibitors (SGLT2is) in Asians compared to whites. Whether such findings are true in all Asians subgroups requires further direct study. For cardiovascular outcomes, available data suggest at least comparable and potentially greater outcome benefits in Asians; point estimates were more favourable for Asians in the vast majority of GLP-1 RAs and SGLT2is outcome trials. It was, however, impossible to determine whether the effects were similar across all Asian subgroups. CONCLUSION: We conclude that trialists should be encouraged to record ethnicity with better granularity to allow differing ethnic groups data to be better interrogated. In the meantime, doctors should, where possible, confidently follow newer guidelines for the use of newer glucose lowering agents for treating glycaemia and for the prevention of cardiovascular and cardiorenal complications in South Asian people with type 2 diabetes.

Meta-analyses of Results From Randomized Outcome Trials Comparing Cardiovascular Effects of SGLT2is and GLP-1RAs in Asian Versus White Patients With and Without Type 2 Diabetes.

BACKGROUND: Results of cardiovascular outcome trials (CVOTs) suggest Asians may derive greater benefit than Whites from newer classes of antihyperglycemic medications. PURPOSE: To provide summary hazard ratio (HR) estimates for cardiovascular efficacy of sodium-glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide 1 receptor agonists (GLP-1RAs) stratified by race (Asian vs. White). DATA SOURCES: A systematic review performed in PubMed from 1 January 2015 to 8 December 2020. STUDY SELECTION: Randomized placebo-controlled CVOTs of SGLT2is and GLP-1RAs that reported HRs (95% CIs) for 1) major adverse cardiovascular event (MACE) in patients with diabetes and 2) cardiovascular (CV) death/hospitalization for heart failure (HHF) in patients with HF and reduced ejection fraction (HFrEF). DATA EXTRACTION AND SYNTHESIS: HRs (95% CIs) for selected outcomes in Asians and Whites were extracted from each trial, adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Random-effects meta-analyses were performed to examine differences between the selected outcomes in Asians versus Whites. RESULTS: In four SGLT2i trials in type 2 diabetes, the MACE outcome HR (95% CI) in 3,298 Asians versus 20,258 Whites was 0.81 (0.57, 1.04) vs. 0.90 (0.80, 1.00), respectively (P interaction = 0.46). In two SGLT2i trials in patients with HFrEF, the CV death/HHF outcome HR in 1,788 Asians versus 5,962 Whites was 0.60 (0.47, 0.74) vs. 0.82 (0.73, 0.92), respectively (P interaction = 0.01). In six GLP-1RA trials, the MACE outcome HR in 4,195 Asians versus 37,530 Whites was 0.68 (0.53, 0.84) vs. 0.87 (0.81, 0.94), respectively (P interaction = 0.03). LIMITATIONS: Lack of individual patient-level data, relatively short duration of trial observation, and lack of granular categorization of race within broadly defined Asian subgroups. CONCLUSIONS: Compared with Whites, Asians may derive greater CV death/HHF benefit from SGLT2is in patients with HFrEF, and MACE benefit from GLP-1RAs in patients with type 2 diabetes.

Changing how we risk-categorise in Ramadan: Does the IDF-DAR scoring system achieve the requirements for people with diabetes internationally?

The IDF-DAR guidance was most recently updated this year. The most notable change is the moving to a scoring system from a tabulated risk categorization to determine and classify the risk of harm from fasting derived from an online survey. This change may be appealing and is welcomed. However, such a system and the methodology underpinning it is not without limitations. This commentary highlights some of these limitations and the associated limited safe options available to individuals with diabetes desiring to fast during Ramadan. Overlooked clinical considerations that deserve formal recognition include the role of technology (aspects relating to glucose monitoring and/or insulin delivery) and previous experience of safe Ramadan fasting. Further, duration of fast (which can almost double in temperate regions from winter to summer) needs greater emphasis. We also advocate separate scoring systems for people with type 1 diabetes and complex type 2 diabetes. The guidance acknowledges fasting is an individual's decision, however the general message needs to be more person-centred and currently only presents a binary approach to fasting - all or nothing choices. We propose and discuss addition options including, trial fasting of voluntary fasts, starting the fast and terminating due to health and/or safety, intermittent fasting and winter fasting.