Diabetes In South Asians Research Articles

Elevated Properdin and Enhanced Complement Activation in First-Degree Relatives of South Asian Subjects With Type 2 Diabetes

OBJECTIVEEmerging data implicate activation of the complement cascade in the pathogenesis of type 2 diabetes. The objective of the current study was to evaluate the relationships between components of the complement system, metabolic risk factors, and family history of type 2 diabetes in healthy South Asians.RESEARCH DESIGN AND METHODSWe recruited 119 healthy, first-degree relatives of South Asian subjects with type 2 diabetes (SARs) and 119 age- and sex-matched, healthy South Asian control subjects (SACs). Fasting blood samples were taken for measurement of complement factors and standard metabolic risk factors.RESULTSSARs were characterized by significantly higher properdin (mean concentration 12.6 [95% CI 12.2–13.1] mg/L vs. SACs 10.1 [9.7–10.5] mg/L, P < 0.0001), factor B (187.4 [180.1–195.0] mg/L vs. SACs 165.0 [158.0–172.2] mg/L, P < 0.0001), and SC5b-9 (92.0 [86.1–98.3] ng/mL vs. SACs 75.3 [71.9–78.9] ng/mL, P < 0.0001) and increased homeostasis model assessment of insulin resistance (2.86 [2.61–3.13] vs. SACs 2.31 [2.05–2.61], P = 0.007). C-reactive protein did not differ between SARs and SACs (P = 0.17). In subgroup analysis of 25 SARs and 25 SACs with normal oral glucose tolerance tests, properdin, factor B, and SC5b-9 remained significantly elevated in SARs.CONCLUSIONSIncreased properdin and complement activation are associated with a family history of type 2 diabetes in South Asians independent of insulin resistance, and predate the development of impaired fasting glucose and impaired glucose tolerance. Properdin and SC5b-9 may be novel biomarkers for future risk of type 2 diabetes in this high-risk population and warrant further investigation.

Effects of 16 Genetic Variants on Fasting Glucose and Type 2 Diabetes in South Asians: ADCY5 and GLIS3 Variants May Predispose to Type 2 Diabetes

BackgroundThe Meta-Analysis of Glucose and Insulin related traits Consortium (MAGIC) recently identified 16 loci robustly associated with fasting glucose, some of which were also associated with type 2 diabetes. The purpose of our study was to explore the role of these variants in South Asian populations of Punjabi ancestry, originating predominantly from the District of Mirpur, Pakistan.Methodology/Principal FindingsSixteen single nucleotide polymorphisms (SNPs) were genotyped in 1678 subjects with type 2 diabetes and 1584 normoglycaemic controls from two Punjabi populations; one resident in the UK and one indigenous to the District of Mirpur. In the normoglycaemic controls investigated for fasting glucose associations, 12 of 16 SNPs displayed β values with the same direction of effect as that seen in European studies, although only the SLC30A8 rs11558471 SNP was nominally associated with fasting glucose (β = 0.063 [95% CI: 0.013, 0.113] p = 0.015). Of interest, the MTNR1B rs10830963 SNP displayed a negative β value for fasting glucose in our study; this effect size was significantly lower than that seen in Europeans (p = 1.29×10−4). In addition to previously reported type 2 diabetes risk variants in TCF7L2 and SLC30A8, SNPs in ADCY5 (rs11708067) and GLIS3 (rs7034200) displayed evidence for association with type 2 diabetes, with odds ratios of 1.23 (95% CI: 1.09, 1.39; p = 9.1×10−4) and 1.16 (95% CI: 1.05, 1.29; p = 3.49×10−3) respectively.Conclusions/SignificanceAlthough only the SLC30A8 rs11558471 SNP was nominally associated with fasting glucose in our study, the finding that 12 out of 16 SNPs displayed a direction of effect consistent with European studies suggests that a number of these variants may contribute to fasting glucose variation in individuals of South Asian ancestry. We also provide evidence for the first time in South Asians that alleles of SNPs in GLIS3 and ADCY5 may confer risk of type 2 diabetes.

An FTO variant is associated with Type 2 diabetes in South Asian populations after accounting for body mass index and waist circumference

A common variant, rs9939609, in the FTO (fat mass and obesity) gene is associated with adiposity in Europeans, explaining its relationship with diabetes. However, data are inconsistent in South Asians. Our aim was to investigate the association of the FTO rs9939609 variant with obesity, obesity-related traits and Type 2 diabetes in South Asian individuals, and to use meta-analyses to attempt to clarify to what extent BMI influences the association of FTO variants with diabetes in South Asians. We analysed rs9939609 in two studies of Pakistani individuals: 1666 adults aged ≥40 years from the Karachi population-based Control of Blood Pressure and Risk Attenuation (COBRA) study and 2745 individuals of Punjabi ancestry who were part of a Type 2 diabetes case-control study (UK Asian Diabetes Study/Diabetes Genetics in Pakistan; UKADS/DGP). The main outcomes were BMI, waist circumference and diabetes. Regression analyses were performed to determine associations between FTO alleles and outcomes. Summary estimates were combined in a meta-analysis of 8091 South Asian individuals (3919 patients with Type 2 diabetes and 4172 control subjects), including those from two previous studies. In the 4411 Pakistani individuals from this study, the age-, sex- and diabetes-adjusted association of FTO variant rs9939609 with BMI was 0.45 (95%CI 0.24-0.67) kg/m(2) per A-allele (P=3.0 × 10(-5) ) and with waist circumference was 0.88 (95% CI 0.36-1.41) cm per A-allele (P=0.001). The A-allele (30% frequency) was also significantly associated with Type 2 diabetes [per A-allele odds ratio (95%CI) 1.18 (1.07-1.30); P=0.0009]. A meta-analysis of four South Asian studies with 8091 subjects showed that the FTO A-allele predisposes to Type 2 diabetes [1.22 (95%CI 1.14-1.31); P=1.07 × 10(-8) ] even after adjusting for BMI [1.18 (95%CI 1.10-1.27); P=1.02 × 10(-5) ] or waist circumference [1.18 (95%CI 1.10-1.27); P=3.97 × 10(-5) ]. The strong association between FTO genotype and BMI and waist circumference in South Asians is similar to that observed in Europeans. In contrast, the strong association of FTO genotype with diabetes is only partly accounted for by BMI.

Rising Rates of All Types of Diabetes in South Asian and Non-South Asian Children and Young People Aged 0–29 Years in West Yorkshire, U.K., 1991–2006

OBJECTIVETo investigate incidence trends of all diabetes types in all children and young people and in the south Asian subpopulation.RESEARCH DESIGN AND METHODSAnnual incidence per 100,000 and time trends (1991–2006) were analyzed for 2,889 individuals aged 0–29 years diagnosed with diabetes while resident in West Yorkshire, U.K.RESULTSDiagnoses comprised type 1 (83%), type 2 (12%), maturity-onset diabetes of the young (0.7%), “J”-type/other (0.1%), and uncertain/unclassified (4%). There was a lower incidence of type 1 and a threefold excess of type 2 in south Asians compared with non-south Asians. Type 1 incidence leveled out and type 2 increased after the first south Asian case of type 2 was diagnosed in 1999. Type 2 and unclassified diabetes incidence rose in all population subgroups.CONCLUSIONSThe burden of diabetes increased over time for both ethnic groups, with a significant excess of type 2 diabetes in south Asians. The rising incidence of type 1 diabetes in south Asians attenuated as type 2 diabetes increased after 1999.

Low mannose-binding lectin (MBL) genotype is associated with future cardiovascular events in type 2 diabetic south asians. a prospective cohort study

BackgroundSouth Asians have a high burden of type 2 diabetes and vascular complications. Vascular inflammation is considered central in the pathophysiology of atherosclerosis, and the complement system is thought to play an important role. Mannose-Binding Lectin (MBL), which activates the lectin pathway of complement activation, has been introduced as a risk marker of vascular damage. The present study explores the association of MBL levels, genotype and cardiovascular events in type 2 diabetic South Asians.MethodsWe conducted a prospective observational study. A cohort consisting of 168 type 2 diabetic South Asians was followed for a median duration of 7.66 years. At baseline, MBL levels and genotype were determined. The association with future cardiovascular events was assessed by Cox proportional hazard regression.ResultsDuring follow-up, 31 cardiovascular events occurred in 22 subjects (11 men, 11 women). The O/O genotype was significantly associated with the occurrence of cardiovascular events (hazard ratio 3.42, 95%CI 1.24-9.49, P = 0.018). However, log MBL levels were not associated with the occurrence of cardiovascular events (hazard ratio 0.93, 95% CI 0.50-1.73).ConclusionsIn type 2 diabetic South Asians, the O/O MBL genotype is associated with cardiovascular events, although single serum MBL levels are not.

Cut‐points for Waist Circumference in Europids and South Asians

There is little strong evidence that currently recommended higher waist circumference cut-points for Europids compared with South Asians are associated with similar risk for type 2 diabetes. This study was designed to provide such evidence. Longitudinal studies over 5 years were conducted among 5,515 Europid and 2,214 ethnically South Asian participants. Age-standardized diabetes incidence at different levels of waist circumference and incidence difference relative to a reference value were calculated. The Youden Index was used to determine waist circumference cut-points. At currently recommended cut-points, estimated annual diabetes incidence for a 50-year-old Europid was <0.6% for both sexes, and for a 50-year-old South Asian, 5.8% for men and 2.1% for women. Annual diabetes incidence of 1% was observed for a 50 year old at a waist circumference 35-40cm greater in Europid compared to South Asian men and women. Incidence difference between recommended cut-points and a reference value (80cm in men, 70cm in women) was 0.3 and 4.4% per year for Europid and South Asian men, and 0.2 and 0.8% per year for Europid and South Asian women, respectively. Waist circumference cut-points chosen using the Youden Index were shown to be dependent on obesity levels in the population. The much higher observed risk of diabetes in South Asians compared to Europids at the respective recommended waist circumference cut-points suggests that differences between them should be greater. Approaches that use the Youden Index to select waist circumference cut-points are inappropriate and should not be used for this purpose.

South Asian diabetes, vitamin D and calcium supplements: a developing saga

South Asian diabetes, vitamin D and calcium supplements: a developing saga

Preventing premature mortality in chronic diseases for South Asians in the UK and beyond.

Whathaschangedinourunderstand-ing since ethnic disparities in coronary diseasemortalitywereinitiallyhighlighted?Wegivesomepast and future pointers in this field by citingexamples in the largest ethnic minority group inthe UK – people of SouthAsian origin.Biological differences are often first sought intrying to explain ethnic differences in diseasepatterns. The higher prevalence of diabetes inSouthAsians (predominately comprising peoplefrom India, Bangladesh, Pakistan and Sri Lanka)has been long known, and was thought to be themain driver behind the higher rates of coronaryheart disease mortality seen in this populationwhen compared to the majority indigenouspopulations in the developed societies to whichSouth Asians migrate to. Theories to explainthis have historically revolved around insulinresistance.

Enhanced complement activation is part of the unfavourable cardiovascular risk profile in South Asians

South Asian immigrants in western societies exhibit a high burden of diabetes and subsequent vascular complications. Diabetic vascular complications are associated with vascular inflammation. We hypothesize that enhanced complement activation is involved. Therefore, levels of complement C3 and SC5b-9 - the soluble end product of complement activation - in a group of 200 South Asians were compared with an age- and sex-matched control group of native Caucasians. In addition, the association between complement levels and albuminuria, an indicator of renal damage and a cardiovascular risk marker, was assessed in the diabetic South Asian group. Compared with native Caucasians, South Asians had significantly higher levels of both serum C3 and plasma SC5b-9, even when only non-diabetic South Asians were considered. Diabetic South Asians had significantly higher C3 levels compared with non-diabetic South Asians. In diabetic South Asians, higher levels of SC5b-9 were associated with an increased prevalence of albuminuria (odds ratio 5.4, 95% confidence interval 1.8-15.8). These results suggest that enhanced complement activation is part of the unfavourable cardiovascular risk profile in South Asians.

Coronary Heart Disease in South Asian Immigrants

Although the literature reflects that Asian Indians in the United States and globally have the highest rates of morbidity and mortality because of coronary heart disease (CHD) and diabetes, few studies have described the clinical implications in the United States. Traditional risk factors dictate practice, yet these risk factors do not fully explain the rates. Central obesity, lipoprotein (a), and insulin resistance may have a strong role. The literature suggests that proactive nursing using culturally specific clinical measures are necessary to reduce risk factors for CHD and diabetes in South Asians. Additional research and prevention strategies focused on immigrant South Asians in the United States are recommended.

Prevention and Management of Diabetes in South Asians

South Asians, the fastest growing immigrant population and the second-largest visible minority in Canada, are 3 to 5 times more likely to have diabetes than the white population. This review discusses challenges related to the prevention and management of diabetes in the South Asian population in Canada. Several studies have suggested that, despite their generally lower body mass index, South Asians have an increased incidence of abdominal obesity, insulin resistance and metabolic syndrome. In addition, although the incidence of diabetes among South Asians has increased in recent decades, the majority of cases are still undiagnosed and thus poorly controlled. Suboptimal treatment of diabetes in South Asians may be due to several barriers, including a lack of knowledge about diabetes, negative beliefs and attitudes relating to diabetes, and noncompliance with lifestyle changes such as diet, weight control and physical activity, all of which are compounded by a lack of culturally sensitive and ethnic-language-specific diabetes education centres in Canada. Improved efforts toward the primary prevention and optimal management of type 2 diabetes are necessary to reduce the burden of diabetes and its complications among South Asians in Canada.

Type 2 diabetes in people of South Asian origin: potential strategies for prevention

South Asians have a one in three lifetime risk for the development of diabetes, developing the condition ten years earlier than Europids. The high social and economic burden of diabetes in South Asians is augmented by greater rates of attrition from renal and cardiovascular disease. This article reviews the epidemiology and pathogenesis of diabetes in South Asians, and potential strategies by which the condition could be prevented or delayed in this high risk group.

Diabetes epidemic in the South Asian Diaspora: action before desperation

Diabetes epidemic in the South Asian Diaspora: action before desperation

Diabetes epidemic in the South Asian Diaspora: Action before desperation

Diabetes epidemic in the South Asian Diaspora: Action before desperation

Transient and persistent impaired glucose tolerance and progression to diabetes in South Asians and Europeans: new, large studies are a priority

Transient and persistent impaired glucose tolerance and progression to diabetes in South Asians and Europeans: new, large studies are a priority

Does Hypoadiponectinemia Explain the Increased Risk of Diabetes and Cardiovascular Disease in South Asians?

A substantial body of evidence has documented the high prevalence of type 2 diabetes and cardiovascular disease (CVD) among people of South-Asian descent, defined on the basis of ancestral origin from the Indian subcontinent comprised of India, Pakistan, Bangladesh, and Sri Lanka (1–7). These observations relate to both native South Asians in urban settings and those living overseas in different countries (including the U.K., Canada, the U.S., South Africa, Singapore, Fiji, and Trinidad), leading to the suggestion that members of this ethnic group may share an underlying predisposition to metabolic and vascular disease (3,4,6–10). It has been postulated that a gene-environment interaction between underlying genetic susceptibility and urbanization-induced lifestyle changes (such as increased caloric intake and decreased energy expenditure) may promote the clinical expression of a high-risk phenotype (7). Clinically, this phenomenon translates to a 1.5- to 10-fold–higher incidence of coronary artery disease (CAD) in immigrant South Asians compared with the general populations of the host countries (2–4,10,11). Furthermore, South Asians exhibit clinical features suggestive of a distinctly aggressive cardiovascular pathophysiology compared with other ethnic groups. These features include significantly higher cardiovascular mortality (4,12) and earlier onset of CAD in young adults (7,13). Thus, identification of the determinants of vascular disease in South Asians may be relevant to both 1 ) our understanding of the pathophysiology of CVD and 2 ) preventive health care for the approximately one-fifth of the world’s population that comes from the Indian subcontinent. A similarly worrisome problem is the rising prevalence of type 2 diabetes in South Asians. India currently has the highest number of cases of diabetes in the world (14). In addition, it has been projected that between 2000 and 2030, the number of patients with diabetes …

Role of Genetic Polymorphism Peroxisome Proliferator-Activated Receptor- 2 Pro12Ala on Ethnic Susceptibility to Diabetes in South-Asian and Caucasian Subjects: Evidence for heterogeneity

To determine whether the peroxisome proliferator-activated receptor (PPAR)-gamma Pro12ala polymorphism modulates susceptibility to diabetes in South Asians. South Asians (n = 697) and Caucasians (n = 457) living in Dallas/Forth Worth, Texas, and South Asians living in Chennai, India (n = 1,619), were enrolled for this study. PPAR-gamma Pro12Ala was determined using restriction fragment-length polymorphism. Insulin responsiveness to an oral glucose tolerance test (OGTT) was measured in nondiabetic subjects. The Caucasian diabetic subjects had significantly lower prevalence of PPAR-gamma 12Ala when compared with the Caucasian nondiabetic subjects (20 vs. 9%, P = 0.006). However, there were no significant differences between diabetic and nondiabetic subjects with reference to the Pro12Ala polymorphism among the South Asians living in Dallas (20 vs. 23%) and in India (19 vs. 19.3%). Although Caucasians carrying PPAR-gamma Pro12Ala had lower plasma insulin levels at 2 h of OGTT than the wild-type (Pro/Pro) carriers (76 +/- 68 and 54 +/- 33 microU/ml, respectively, P = 0.01), no differences in either fasting or 2-h plasma insulin concentrations were found between South Asians carrying the PPAR-gamma Pro12Ala polymorphism and those with the wild-type genotype at either Chennai or Dallas. Although further replication studies are necessary to test the validity of the described genotype-phenotype relationship, our study supports the hypothesis that the PPAR-gamma Pro12Ala polymorphism is protective against diabetes in Caucasians but not in South Asians.

Role of Genetic Polymorphism Peroxisome Proliferator–Activated Receptor-γ2 Pro12Ala on Ethnic Susceptibility to Diabetes in South-Asian and Caucasian Subjects

OBJECTIVE—To determine whether the peroxisome proliferator–activated receptor (PPAR)-γ Pro12ala polymorphism modulates susceptibility to diabetes in South Asians. RESEARCH DESIGN AND METHODS—South Asians (n = 697) and Caucasians (n = 457) living in Dallas/Forth Worth, Texas, and South Asians living in Chennai, India (n = 1,619), were enrolled for this study. PPAR-γ Pro12Ala was determined using restriction fragment–length polymorphism. Insulin responsiveness to an oral glucose tolerance test (OGTT) was measured in nondiabetic subjects. RESULTS—The Caucasian diabetic subjects had significantly lower prevalence of PPAR-γ 12Ala when compared with the Caucasian nondiabetic subjects (20 vs. 9%, P = 0.006). However, there were no significant differences between diabetic and nondiabetic subjects with reference to the Pro12Ala polymorphism among the South Asians living in Dallas (20 vs. 23%) and in India (19 vs. 19.3%). Although Caucasians carrying PPAR-γ Pro12Ala had lower plasma insulin levels at 2 h of OGTT than the wild-type (Pro/Pro) carriers (76 ± 68 and 54 ± 33 μU/ml, respectively, P = 0.01), no differences in either fasting or 2-h plasma insulin concentrations were found between South Asians carrying the PPAR-γ Pro12Ala polymorphism and those with the wild-type genotype at either Chennai or Dallas. CONCLUSIONS—Although further replication studies are necessary to test the validity of the described genotype-phenotype relationship, our study supports the hypothesis that the PPAR-γ Pro12Ala polymorphism is protective against diabetes in Caucasians but not in South Asians.

Coronary risk in South Asians: role of ethnicity and blood sugar

Studies of South Asian immigrants in different countries have reported an increased predisposition to cardiovascular disease in comparison with the native populations. This study is a systematic review of longitudinal studies investigating differences in established risk factors for coronary heart disease (CHD) between Caucasians and South Asians. The aim was to develop a practical tool to estimate CHD risk in individuals. Secondarily data from the Health Survey for England 1999 (HSE 1999) were used to explore a possible role of differences in blood glucose in risk variation. We used a systematic search to find relevant published papers. Data from the HSE 1999 were employed to study ethnic differences in blood glucose and glycosylated haemoglobin. Only two out of five longitudinal studies reported independent estimates of relative risks of CHD in South Asians compared to Caucasians. Risk in diabetic South Asians was predicted adequately by classical risk factors whilst risk in a non-diabetic study population was 79% greater than predicted. Non-diabetic South Asians have higher fasting blood glucose (FBG) and HbA1c than Caucasians after adjustment for CHD risk factors. The difference in risk of CHD between non-diabetic South Asian and Caucasians is not explained by differences in the impact of the traditional risk factors. Part may be due to higher blood sugar concentrations in non-diabetic South Asians.

Type 2 diabetes in South Asians: a pathophysiologic focus on the Asian-Indian epidemic.

There is a high prevalence of type 2 diabetes mellitus and coronary artery disease among urban and migrant Asian Indians, despite the absence of traditional risk factors. Evidence exists that Asian Indians are more insulin resistant than white persons and that insulin resistance may play an important role in the pathogenesis of these diseases. Increased visceral fat in Asian Indians is associated with increased generalized obesity, which is not apparent from their nonobese body mass index. Increased visceral fat is related to dyslipidemia and increased frequency of insulin resistance and may account for the increased prevalence of diabetes mellitus and cardiovascular disease in Asian Indians. In addition, early protein energy deprivation, as indicated by low weight at birth and at 1 year of age, may induce a state of vulnerability to the development of type 2 diabetes in later life, especially if the quantitative and qualitative aspects of nutrition and altered lifestyles during adult years pose an additional challenge.