Diabetes mellitus and obesity among South Asians with ischemic stroke across three countries

Background: Diabetes mellitus and central obesity are more common among South Asian populations than among White British people. This study explores the differences in diabetes and obesity in South Asians with stroke living in the United Kingdom, India, and Qatar compared with White British stroke patients. Methods: The study included the UK, Indian, and Qatari arms of the ongoing large Bio-Repository of DNA in Stroke (BRAINS) international prospective hospital-based study for South Asian stroke. BRAINS includes 4580 South Asian and White British recruits from UK, Indian, and Qatar sites with first-ever ischemic stroke. Results: The study population comprises 1751 White British (WB) UK residents, 1165 British South Asians (BSA), 1096 South Asians in India (ISA), and 568 South Asians in Qatar (QSA). ISA, BSA, and QSA South Asians suffered from higher prevalence of diabetes compared with WB by 14.5% (ISA: 95% confidence interval (CI) = 18.6–33.0, p < 0.001), 31.7% (BSA: 95% CI = 35.1–50.2, p < 0.001), and 32.7% (QSA: 95% CI = 28.1–37.3, p < 0.001), respectively. Although WB had the highest prevalence of body mass index (BMI) above 27 kg/m2 compared with South Asian patients (37% vs 21%, p < 0.001), South Asian patients had a higher waist circumference than WB (94.8 cm vs 90.8 cm, p < 0.001). Adjusting for traditional stroke risk factors, ISA, BSA, and QSA continued to display an increased risk of diabetes compared with WB by 3.28 (95% CI: 2.53–4.25, p < 0.001), 3.61 (95% CI: 2.90–4.51, p < 0.001), and 5.24 (95% CI: 3.93–7.00, p < 0.001), respectively. Conclusion: South Asian ischemic stroke patients living in Britain and Qatar have a near 3.5-fold risk of diabetes compared with White British stroke patients. Their body composition may partly help explain that increased risk. These findings have important implications for public health policymakers in nations with large South Asian populations.


Introduction
One in five strokes in Britain are caused by type 2 diabetes which doubles the risk of stroke within the first 5 years of diagnosis. 1In the United Kingdom, 3.6 million persons, around 5% of the population, have been diagnosed with diabetes, with diabetes mellitus type 2 accounting for around 90% of cases, 2 while an additional million people are thought to suffer from undiagnosed diabetes.Diabetes and central obesity are twice as common among South Asians from India, Pakistan, and Bangladesh living in the United Kingdom than among White British people 3 often striking them earlier in life. 4outh Asian populations have a 15-27% greater prevalence of diabetes mellitus than White British populations. 3ender does not appear to influence differences between these two ethnic groups. 5Moreover, this elevated prevalence is still present in individuals with first-onset stroke. 6iabetes is 80 times more likely to occur in obese adults than in healthy individuals with body mass indices (BMIs) under 22. 7 South Asians generally have a lower prevalence of overweight/obesity than the White British population, men having the largest difference in ethnic prevalence (16.3%) and women having the smallest difference (1%), even though there is little, if any, data on prevalence among those who have ischemic stroke. 5South Asian infants born in the United Kingdom had lower birth weights, which may have a hereditary basis. 8It is important to note the differences in fat distribution that exist throughout the South Asian community, particularly in view of the effect that these measures have for the prevalence of obesity.South Asians have greater accumulation of visceral and subcutaneous fat around the abdomen as well as increased skinfold thickness compared with their White British counterparts. 9t has already been determined that increased central adiposity in South Asians increases ischemic stroke risk factors, such as elevated C-reactive protein (CRP) concentration. 10Furthermore, it has been hypothesized that South Asian's atherogenic lipid profile is a result of rising central adiposity. 11igration and cultural norms around nutrition and exercise have been presumed to significantly compound the increased prevalence of diabetes mellitus among ethnic South Asians.However, the assumption that South Asians who immigrate to other nations have a higher incidence of diabetes, obesity, and visceral fat location compared with local White populations has not been robustly tested using large and comparative international datasets.Demonstrating differences in disease occurrence following migration is likely to have important public health implications for nations with sizable South Asian populations.

International Journal of Stroke, 19(2)
We aimed to investigate the disparities in diabetes mellitus and obesity between South Asians in the United Kingdom, India, and Qatar with a White British population among patients who have had first-time an ischemic stroke using one of the largest such datasets currently available.

Data source
We used the UK, Indian, and Qatar arms of the ongoing large prospective international Bio-Repository of DNA in Stroke (BRAINS) study, the details of which have been previously published 12,13 but are described in detail in the Supplementary material.However, briefly, ischemic stroke patients of South Asian descent were recruited from 21 sites in the United Kingdom, 2 in India (North and South), and 1 in Qatar.Detailed phenotypic and demographic information was documented. 12,13Stroke in all patients was confirmed by computed tomography (CT) and/or magnetic resonance imaging (MRI) of the brain.All patients were reviewed by a stroke or neurology physician.

Statistical analysis
Descriptive statistics summarized data using mean with standard deviation (SD) or median with interquartile range (IQR) for continuous variables, and proportion for categorical variables.For single-factor analysis, chi-square (or Fisher exact test, where appropriate) was used for categorical variables, and independent t-test (or Mann-Whitney U test, where appropriate) for continuous variables.Univariate and multivariate logistic regression estimated the associations of covariates (age, sex, central obesity, smoking history, alcohol consumption, hypertension, hypercholesterolemia, and cardiovascular diseases) with diabetes mellitus status.The reliability (goodness-offit) of each model was quantified using the Hosmer and Lemeshow test.Models evaluated using Akaike's information criterion (AIC) and the likelihood ratio chi-square test.Rather than applying a correction for multiple testing at global significance level, for individual tests of association defined statistical significance was <0.01.
The prevalence of diabetes by BMI above or below 27 kg/m 2 and waist circumference above or below 102 cm in male and 88 cm in female are presented in Figure 2. The BSA and QSA had the highest prevalence of diabetes in all four combinations of BMI and waist circumference.This was followed by ISA who had the third highest prevalence.
The association between diabetes status and ethnic group among ischemic stroke patients was evaluated using logistic regression (Table 2).Univariate analysis showed that south Asian ethnicity (ISA, BSA, QSA) was associated with diabetes status.The odds ratio (OR) for diabetes presence was 3.41 (95% CI: 2.97-3.94,p < 0.001) for South Asians (ISA, BSA, QSA) versus WB.Multivariate logistic regression analysis modeling including traditional stroke risk factors (age, sex, central obesity, smoking history, alcohol consumption, hypertension, hypercholesterolemia, and cardiovascular diseases) showed that ethnicity independently associated with diabetes (Table 2).Multivariate adjusted OR for South Asian ethnicity (ISA, BSA, QSA)   International Journal of Stroke, 19 (2)   compared with WB was 3.68 (95% CI: 2.99-4.53,p < 0.001).

Discussion
South Asian ISA, BSA, and QSA ischemic stroke patients compared with their WB stroke counterparts suffer from higher prevalence of diabetes by 15%, 32%, and 33%, respectively, following adjustment for traditional risk factors (age, sex, central obesity, smoking history, alcohol consumption, hypertension, hypercholesterolemia, and cardiovascular diseases).Moreover, migrated South Asians present with a greater prevalence of diabetes compared with those who remain in the subcontinent.These results reflect differences in adiposity index, BMI, waist circumference, and central obesity among South Asian patients compared with WB and ISA, likely highlighting differences in lifestyle and environmental factors such as diet and exercise.The body composition of the South Asian patients may help to explain the increased risk of developing diabetes compared with the WB patients.A high visceral fat percentage has been highly correlated with having a greater waist circumference.South Asians tend to have higher amounts of abdominal adipose tissue, including both subcutaneous and visceral fat than their Caucasian counterparts at similar BMI values, although no differences were found at very high values of BMI. 14 Observational studies have shown that excessive amounts of visceral adipose tissue can increase the risk of developing diabetes due to it being the primary causal factor of insulin resistance. 15revious studies indicated that South Asian populations are more likely to have abdominal obesity and more body fat at a given BMI value than Caucasians. 16Due to this, they are at an increased risk of developing diabetes and other comorbidities, including hypertension, stroke, cardiovascular disease, and hypercholesterolemia. 17 Several studies have demonstrated that South Asians are at risk of developing obesity-related comorbidities at lower BMI levels or smaller waist circumference measures. 18MI does not distinguish between muscle and fat. 16A person with a high proportion of muscle may be considered overweight or even obese since muscle weighs more than fat.Moreover, BMI ignores the distribution of fat, despite that being important for predicting health outcomes. 16The risk of diabetes and heart disease is higher in people with "apple" shapes who carry fat around their middle but may be quite thin elsewhere. 16Individuals with this body type could be considered healthy according to the BMI calculation. 16"Pear" shapes obesity formally classified as "overweight," despite the fact that fat stored around the hips, bottom, and thighs is more secure.Asian-descent individuals have higher weight-related disease risks at lower BMIs and more likely to develop diabetes and heart disease, due to central fat. 16This requires separate standards for various ethnic groups.As waist circumference is a stronger predictor of type 2 diabetes risk, regardless of BMI, 19 it presents a powerful argument for a wider adoption of more ethnicspecific criteria. 20elease of adipokines and their associated metabolic consequences may partly explain why South Asians have a higher risk of diabetes due to an excessive build-up of adipose tissue.A secreted adipokine known as adiponectin is thought to play a role in the modulation of glucose and lipid metabolism in insulin-sensitive tissues with lower levels of blood adiponectin implicated in the pathogenesis of insulin resistance and diabetes. 21Unlike their Caucasian counterparts, South Asian men have been found to have lower levels of adiponectin despite their body fat content and body fat distribution. 22A correlation between lower levels of adiponectin and insulin has been previously identified, as well as the identification of lower levels of adiponectin in South Asians with diabetes. 21,22Adipocytes also produce leptin which is known to have insulin-sensitizing effects as well International Journal of Stroke, 19 (2)   as causing a reduction in a person's appetite. 23Obese individuals tend to develop hyperleptinemia which causes them to become leptin resistant which contributes to insulin resistance as it suppresses insulin action. 23South Asians have been found to have higher levels of leptin in the system than their Caucasian counterparts, despite their body fat distribution or body composition. 21Leptin levels have been found to be higher in South Asians with diabetes than those with only an impaired glucose tolerance or normal glucose tolerance. 22he higher prevalence of diabetes in South Asians in the United Kingdom and Qatar compared with Indian South Asians highlights the possible changes in lifestyle and environmental factors, including nutrition and exercise that may occur when people migrate.The traditional South Asian carbohydrates heavy diet of rice and bread is better suited to a physically demanding rural environment. 24Yet South Asians in the United Kingdom continue to eat a highcarbohydrate diet and engage in less exercise than the WB population. 25The World Health Organization (WHO) has recommended special standards for determining obesity in South Asians due to a tendency toward visceral adiposity in the truncal region. 20Another potential element in the variation in diabetes risk is most likely the impact of migration on environmental and lifestyle factors.In migration studies, access to healthcare is a crucial component of diabetes prevention that is frequently ignored.Despite having access to healthcare facilities that can help prevent disease, BSA have demonstrably limited awareness of the risk factors that contribute to disease.South Asian patients in the United Kingdom and Qatar may be less informed of the typical complications linked to diabetes mellitus, the significance of screening clinics, and the necessity of consulting chiropodists. 26In addition, sociocultural and religious factors might compound this diminished awareness by creating false notions of social stigma and failure to self-care. 27iabetes mellitus may be prevented in South Asian communities using programs that promote health-protective lifestyle changes and comprise multi-component interventions that encompass parts of health promotion and behavioral change that are passive (lecture-based), active (activity-based), and individualized (such as targeted counseling). 28These programs should focus on cultural values related to lifestyle aspects such as food, which reduces carbohydrate intake, and exercise, which raising aerobic exercise at a moderate intensity.

Limitations
As with all studies, a number of limitations need to be noted.The BRAINS project has been ongoing for several years and in that time risk factor thresholds and management approaches have evolved.However, those changes would have led to a non-differential ethnic bias and are unlikely to have an impact on the significance of the findings in this study.The prevalence of comorbidities is recorded at the time of the event.Most of the prevalence data was gathered from treatment regimens documented on the patient's health record even though we are unable to comment on how long these comorbidities were prevalent before the diabetic event.The large sample size (n = 4580) accurately reflects the current influence of these risk factors on diabetes in the South Asian population, even though this may result in an underestimation of the real effect size on the diabetes event.Grandparent origin defined ethnicity.Although this was self-reported, prior research has shown that this methodology is accurate. 29Due to the lack of socioeconomic data collection, we are unable to determine how socioeconomic status may affect morbidity and mortality or the occurrence of developing diabetes.Using the larger BRAINS dataset which includes both ischemic and hemorrhagic events, we evaluated how well subjects were represented in our study.We discovered similar stroke subtype prevalence in all four of our study's groups. 30In addition, because long-term follow-up was not conducted, we are unable to report on specific migratory effects and how they develop.The recruitment sites in the United Kingdom, India, and Qatar were selected to provide a representative sample.Twenty-one hospital locations with a strong South Asian population were identified in the United Kingdom.All India Institute of Medical Sciences and Sree Chitra Tirunal Institute for Medical Sciences and Technology were chosen as the two hospital locations since they are situated in the north and south of the nation, respectively.Different cultures have different responses and access to seeking emergency healthcare support services.However, all our recruitment sites across three countries provide free access to medical services, making it likely to draw people from a wide range of socioeconomic backgrounds.Nevertheless, this is a hospitalbased study and is dependent on recruitment for patients attending hospital.

Conclusion
South Asian ischemic stroke patients in India (ISA), Britain (BSA), and Qatar (ISQ) have higher prevalence of diabetes mellitus compared with White British stroke patients, with migrants being most affected.Body composition of South Asian patients may help to explain the increased risk of developing diabetes.These findings have important implications for public health policymakers in nations with large migrant South Asian populations.

Figure 2 .
Figure 2. Prevalence of diabetes among BMI above or below 27 kg/m 2 and waist circumference above or below 102 cm in male and 88 cm in female.

Table 1 .
Population characteristics and comorbidities by ethnicity and diabetes status.White British individuals living in the United Kingdom; BSA: British South Asians living in the United Kingdom; ISA: South Asians living in India; QSA: South Asians living in Qatar; SD: standard deviation; BMI: body mass index; MI: myocardial infarction.Central obesity was defined by waist circumference (men: n: sample size; WB:

Table 2 .
Multivariate logistic regression analysis of diabetes status.: odds ratio; CI: confidence interval; WB: White British individuals living in the United Kingdom; ISA: South Asians living in India; BSA: British South Asians living in the United Kingdom; QSA: South Asians living in Qatar.Model 1: Unadjusted.Model 2: Adjusted for age and sex.Model 3: Adjusted for age, sex, central obesity, smoking history, alcohol consumption, hypertension, hypercholesterolemia, and cardiovascular diseases. OR