Kirti Kain

Ferritin levels and risk of type 2 diabetes mellitus: an updated systematic review and meta-analysis of prospective evidence.

Emerging evidence suggests that a strong link that exists between elevated baseline body iron stores and high risk of incident type 2 diabetes mellitus (T2DM) in general populations, but the precise magnitude of the associations remains uncertain.

Ethnic differences in cardiovascular risk factors in healthy Caucasian and South Asian individuals with the metabolic syndrome

Summary.  Background:  The metabolic syndrome is a cluster of atherothrombotic risk factors that are commonly associated with insulin resistance.

Ferritin levels and risk of type 2 diabetes mellitus

Emerging evidence suggests that a strong link that exists between elevated baseline body iron stores and high risk of incident type 2 diabetes mellitus (T2DM) in general populations, but the precise magnitude of the associations remains uncertain.

Impaired fibrinolysis and increased fibrinogen levels in South Asian subjects

The potential role of haemostatic risk markers is largely unexplored in South Asians, who have increased morbidity and mortality from cardiovascular disease and an increased prevalence of insulin resistance. To investigate differences in thrombotic risk markers between South Asian and White populations, 42 Asian and 50 White males and 96 Asian and 80 White females, clinically free from vascular disease, were recruited. Venous blood samples were taken for measures of haemostasis and determination of blood lipids. South Asian females showed lower fasting blood glucose than White females (4.6 vs. 4.8 mmol/l, P<0.008). In the South Asian population, total cholesterol was lower in females, with a similar trend in males (females 5.0 vs. 5.5 mmol/l, P<0.001; males 5.1 vs. WM 5.5 mmol/l, P=0.09), but no difference in triglyceride levels. South Asian subjects of both genders had markedly higher levels of fibrinogen (females 3.3 vs. 2.8 mg/dl, P<0.0005; males 3.0 vs. 2.5 mg/dl P<0.002) and PAI-1 activity (females 14.6 vs. 8.7 ng/ml, P<0.0005, males 21.3 vs. 12.2 ng/ml, ) P<0.0005). Factor VII:C was lower in both South Asian groups (females 110.9 vs. 122.4%, P<0.005; males 103.3 vs. 125%, P<0.0005). Factor XII was lower in South Asian females and there were no differences in Factor XII levels in male populations. These results suggest that elevated PAI-1 and fibrinogen in Asians of both genders may contribute to the increased vascular risk experienced in this population; however, the role of dyslipidaemia and Factor VII are not clear in these processes.

Associations between insulin resistance and thrombotic risk factors in high‐risk South Asian subjects

Aims There is recognized association of thrombotic factors to insulin resistance in White Europeans. South Asians are more insulin resistant compared with white Europeans and express increased metabolic features of insulin resistance. The aim of the study was to determine whether there was any relationship between insulin resistance and thrombotic risk factors in healthy South Asian subjects.

Decreased fibrinolytic potential in South Asian women with ischaemic cerebrovascular disease

To investigate gender differences in conventional, coagulation and fibrinolytic factors in South Asian ischaemic stroke patients, we compared these variables in 50 South Asian females (SAFP) with 90 South Asian males (SAMP) with ischaemic stroke and in 52 females (SAFC) and 38 males (SAMC) without stroke. Plasminogen activator inhibitor‐1 (PAI‐1) antigen levels were significantly higher in SAFP compared with SAMP (18·2 vs. 13·3 U/ml, P = 0·04) even after adjustment for known covariates, but there was no difference in PAI‐1 antigen levels between males and females in the control group. South Asian females exhibited higher levels of factor VII antigen and FVII:C activity in both stroke patients (114 vs. 99% in males, P = 0·01; 116 versus 104% in males, P = 0·04) and controls (116 vs. 97% in males, P = 0·004; 115 vs. 93% in males, P = 0·01). There were no significant differences in the levels of fibrinogen (3·8 vs. 3·7 g/l), FXIIa (2·2 vs. 2·4 ng/ml), von Willebrand factor (1·8 vs. 1·9 IU/ml) and tissue plasminogen activator (11·4 vs. 12·0 ng/ml) in SAMP and SAFP respectively. These results suggest that South Asian females have increased FVII levels and that females with a history of ischaemic stroke have a decreased fibrinolytic potential in comparison with males.

Complement C3 and C-Reactive Protein Are Elevated in South Asians Independent of a Family History of Stroke

Background and Purpose— Complement components are emerging risk factors for cardiovascular disease. In this study, we examined the relation among C3, C-reactive protein (CRP), factor B, and features of the insulin resistance (IR) syndrome in 143 first-degree relatives of South Asian subjects with ischemic stroke, 141 South Asian controls, and 121 white controls. Methods— C3, CRP (high-sensitivity assay), and factor B levels were measured by ELISAs, and their relation to features of the IR syndrome were assessed. Data are presented as geometric mean (95% CI). Results— There was no significant difference in the levels of C3 between South Asian relatives (1.25 [1.21, 1.29] g/L) and South Asian controls (1.20 [1.15, 1.24] g/L, P=0.2). Levels in both South Asian groups were significantly higher than in white controls (0.95 [0.92, 0.98] g/L; P<0.001 for both comparisons). These differences remained significant after adjustment for covariates. Similarly, levels of CRP were not different between the 2 South Asian groups, but levels in both South Asian groups, after adjustment for covariates, were significantly higher than in white controls. There was no difference in the levels of factor B among the 3 groups. South Asian subjects with elevated C3 levels clustered risk factors associated with IR to a greater extent than those with high CRP. Conclusions— These results suggest that South Asians have a greater level of chronic subclinical inflammation than do whites, independent of a family history of stroke. In addition, C3 is more likely to cluster with features of the IR syndrome compared with CRP in South Asians.

Insulin Resistance and Elevated Levels of Tissue Plasminogen Activator in First-Degree Relatives of South Asian Patients With Ischemic Cerebrovascular Disease

Background and Purpose South Asians in the United Kingdom suffer from an increased mortality from cerebrovascular disease compared with whites. Evidence suggests that the relatives of white stroke patients are at increased risk of vascular disease. The aim of this study was to investigate atherothrombotic risk factors in the first-degree relatives of South Asian patients suffering from ischemic cerebrovascular disease and to compare them with South Asian subjects free from clinically detectable cerebrovascular disease. Methods We compared 143 relatives of South Asians with ischemic stroke (South Asian relatives group) with 146 South Asian control subjects from West Yorkshire, UK. Results The ages and ethnic and sex distributions of South Asian relatives and South Asian controls were similar. There were no significant differences in body mass index, waist-hip ratio, number of current smokers, and past medical history of hypertension, diabetes mellitus, or myocardial infarction between the 2 groups. Fasting blood glucose, glycosylated hemoglobin (HbA1c), total cholesterol, triglycerides, and HDL cholesterol were similar in the 2 groups. Fasting insulin (South Asian relatives, 12.0; South Asian controls, 8.5 mU/L;P <0.0001) (independent of tissue plasminogen activator) and insulin resistance (derived by Homeostasis Model Assessment) (South Asian relatives, 2.7; South Asian controls, 1.9;P =0.001) were significantly raised in stroke relatives. Stroke relatives showed elevated levels of tissue plasminogen activator (South Asian relatives, 11.6; South Asian controls, 8.4 ng/mL;P <0.0001), which was independent of plasma insulin. There were no differences in plasminogen activator inhibitor antigen or activity between the groups. Conclusions South Asians stroke relatives exhibit hyperinsulinemia, increased insulin resistance, and increased tissue plasminogen activator levels. These observations might account for increased susceptibility to atherothrombotic disease in this ethnic group.

Determinants of Plasminogen Activator Inhibitor-1 in South Asians with Ischaemic Stroke

To investigate the relationship of circulating plasminogen activator inhibitor-1 (PAI-1) levels with features of insulin resistance and genotype at a single nucleotide insertion/deletion (4G/5G) polymorphism in the promoter region of the PAI-1 gene in 101 South Asian ischaemic stroke patients and 102 symptom-free reference subjects. The allele frequencies were 4G-0.51, 5G-0.49 and 4G-0.61, 5G-0.39 in patients and reference subjects, respectively. There was a significant association between PAI-1 promoter genotype and PAI-1 antigen levels in patients. Regression analysis with significant correlates in the model demonstrated age, gender and triglycerides in patients and fasting insulin and HDL cholesterol in reference subjects as independent predictors of PAI-1 antigen.

Alanine aminotransferase is associated with atherothrombotic risk factors in a British South Asian population

Summary.  Background: Alanine aminotransferase (ALT) predicts the development of Type 2 diabetes mellitus and cardiovascular disease in Caucasian subjects. Objectives: This study aimed to determine the incidence of an elevated ALT and its relationship to metabolic and atherothrombotic risk factors in a healthy British South Asian population. Patients/methods: One hundred and forty‐three participants from the West Yorkshire community were recruited randomly from general practice registers and were grouped according to whether their ALT was above or within the normal range (cut‐off 35 IU L−1) and examined for differences in metabolic and atherothrombotic risk factors. All participants were originally from South Asia, with their grandparents being born in India, Pakistan, or Bangladesh. Results: The incidence of a raised ALT was 24%. Those with a raised ALT had a more adverse metabolic profile, with significantly higher body mass index, waist/hip ratio, fasting insulin, glucose, homeostasis model assessment homeostasis model assessment insulin resistance (HOMA‐IR), and triglycerides, and lower high‐density lipoprotein (HDL) cholesterol. Fifty per cent had the metabolic syndrome [International Diabetes Federation (IDF) criteria]. They also had a more adverse atherothrombotic profile, with higher tissue‐type plasminogen activator and plasminogen activator inhibitor‐1 (PAI‐1) antigen. In accordance, the group as a whole showed a positive correlation of ALT (age‐adjusted) with waist/hip ratio, insulin, glucose, triglycerides, PAI‐1 antigen, factor XIII B subunit, and FXII, and a negative correlation with HDL cholesterol. Conclusion: Raised ALT is common in apparently healthy British South Asians, and is significantly associated with an adverse metabolic and atherothrombotic risk profile.