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Biomedical subjects

N G Forouhi

Publications and source records attributed to N G Forouhi.

12 recordsLinked to original sources
PubMed2006

Do known risk factors explain the higher coronary heart disease mortality in South Asian compared with European men? Prospective follow-up of the Southall and Brent studies, UK.

AIMS/HYPOTHESIS: We examined prospectively whether measured risk factors can explain the higher CHD mortality in South Asians compared with Europeans. MATERIALS AND METHODS: Conventional CHD risk factors and those associated with insulin resistance were measured in 1,787 European and 1,420 South Asian men aged 40 to 69 years at baseline in the population-based Southall and Brent studies (London) between 1988 and 1990. Participants were followed up for mortality. RESULTS: By February 2006, there were 202 CHD deaths (108 Asian, 94 European). South Asian men had double the CHD mortality of European men in Cox regression analyses adjusted for age, smoking, and cholesterol (hazard ratio [HR] 2.14, 95% CI 1.56-2.94, p<0.001). Nearly half of all South Asian CHD deaths versus 13% of deaths among Europeans were among persons with diabetes. Asian men had greater CHD mortality than Europeans, both in the with- and the without-diabetes categories at baseline. CHD mortality remained significantly higher in South Asian men in multivariable models that adjusted for conventional risk factors and diabetes and/or impaired glucose regulation, features of insulin resistance, or the metabolic syndrome (HR 1.6-1.9). Accounting for co-morbidity and socio-economic status did not materially alter the findings. CONCLUSIONS/INTERPRETATION: These data confirm that South Asian men have significantly higher CHD mortality than their European counterparts, while indicating that neither conventional risk factors, nor insulin resistance parameters or metabolic syndrome criteria as currently defined can account for this excess risk. The contribution of unmeasured factors to the elevated vascular risk in South Asians should be addressed in future studies.

Asian People↗
PubMed2006

The threshold for diagnosing impaired fasting glucose: a position statement by the European Diabetes Epidemiology Group.

The category of IFG was introduced in the late 1990s to denote a state of non-diabetic hyperglycaemia defined by a fasting plasma glucose (FPG) concentration between 6.1 and 6.9 mmol/l. In 2003 the American Diabetes Association recommended that this diagnostic threshold be lowered to 5.6 mmol/l. The justification for lowering the threshold has been questioned. This simple change in cut-off value creates a pandemic of IFG, with a two- to five-fold increase in the prevalence of IFG across the world. Such a change in threshold has far-reaching public health implications. The European Diabetes Epidemiology Group (EDEG) has reviewed the evidence for this lower cut-off point for the definition of IFG and concludes that the previous definition should not be altered. EDEG further recommends that the value of all categorical definitions of non-diabetic hyperglycaemia should be reconsidered.

Blood Glucose↗
PubMed2006

A comparison of glycaemic and metabolic control over time among South Asian and European patients with Type 2 diabetes: results from follow-up in a routine diabetes clinic.

AIMS: Although South Asians have a higher prevalence of diabetes which develops at a younger age, data on change in metabolic parameters post-diagnosis are relatively sparse. We therefore wished to determine whether South Asians with diabetes had similar or greater year-on-year deterioration in metabolic parameters compared with Europeans. METHODS: We analysed longitudinal change in metabolic parameters [glycated haemoglobin (HbA(1c)), blood pressure, body mass index (BMI), lipids] among South Asian (n = 210) and European (n = 1557) patients consecutively attending the same diabetes clinic over a mean period of 5.3 years. RESULTS: South Asians were younger than Europeans at first recorded diagnosis of diabetes (mean age 45.9 vs. 57.3 years, P < 0.001) and had significantly lower ( approximately 1.2 units) BMI and blood pressure. Mean HbA(1c) was not different across ethnic groups at first visit, but with time glycaemic control was worse in South Asians than Europeans, with average deterioration 1.31% (= 0.23%/year) in Asians vs. 0.82% (0.16%/year) in Europeans, P = 0.003. This ethnic difference in mean change in HbA(1c) persisted after adjustment for age, sex, baseline HbA(1c), and weight change in linear regression analysis (beta = 0.46, 95% CI 0.24-0.69, P < 0.001), and with additional adjustment for time to referral and duration of diabetes (P = 0.01). Moreover, South Asians had significantly smaller improvements in blood pressure (P < 0.001) and cholesterol (P = 0.044) over the follow-up period in keeping with fewer prescriptions of anti-hypertensive agents and lipid-lowering agents. CONCLUSIONS: These data suggest the need to be more aggressive in the management of diabetes and related risk factors in South Asians.

Age Distribution↗
PubMed2006

Diabetes prevalence in England, 2001--estimates from an epidemiological model.

AIMS: To estimate the total prevalence of diabetes mellitus (diagnosed and undiagnosed) at national, regional and local level in England to support health-care planning and delivery. METHODS: An epidemiological model was constructed by applying age-sex-ethnic-specific reference prevalence rates from epidemiological studies to resident populations (2001 census) of England at national, regional, and local authority/Primary Care Trust levels. RESULTS: Estimated prevalence of total diabetes for all persons in England was 4.41% in 2001, equating to 2 168 000 persons. Type 2 diabetes was estimated to affect 2 002 000 persons (92.3%) and Type 1 diabetes 166 000 persons (7.7%). Diabetes prevalence was estimated to be higher in women (5.17%) than men (3.61%). People from ethnic minority groups had higher crude prevalence than White Europeans (4.29, 5.69, 6.63 and 2.13% among White Europeans, Black African/Caribbeans, South Asians and 'other' groups, respectively). Prevalence increased sharply with age (0.33, 3.37 and 13.92%, respectively, in those aged 0-29, 30-59 and 60+ years). The model allows use of user-defined population denominator estimates to derive numbers and prevalence of people with diabetes for a given local population group, such as at ward or general practice level. CONCLUSIONS: Self-reported diabetes prevalence estimates from community surveys underestimate the true burden of diabetes. The model can be used to derive the expected total prevalence of diabetes in health areas that lack reliable data to facilitate the implementation of the National Service Framework for diabetes. It will also allow estimates of future diabetes prevalence to be derived, and can potentially be used for prevalence estimates in all of the UK.

Adolescent↗
PubMed2001

Relation of C-reactive protein to body fat distribution and features of the metabolic syndrome in Europeans and South Asians.

OBJECTIVE: To investigate the association between circulating C-reactive protein (CRP) concentrations and indices of body fat distribution and the insulin resistance syndrome in South Asians and Europeans. DESIGN: : Cross-sectional study. SUBJECTS: A total of 113 healthy South Asian and European men and women in West London (age 40-55 y, body mass index (BMI) 17-34 kg/m(2)). MEASUREMENTS: Fatness and fat distribution parameters (by anthropometry, dual-energy X-ray absorptiometry and abdominal CT scan); oral glucose tolerance test with insulin response; modified fat tolerance test; and CRP concentration by sensitive ELISA. RESULTS: Median CRP level in South Asian women was nearly double that in European women (1.35 vs 0.70 mg/1, P=0.05). Measures of obesity and CRP concentration were significantly associated in both ethnic groups. The correlation to CRP was especially strong among South Asians (P<0.01) for measures of central obesity (waist girth and visceral fat area), whereas BMI and percentage fat were more significantly associated with CRP in Europeans (P<0.05). In South Asians the associations of CRP with visceral fat area and waist girth persisted after adjustment for either BMI or percent fat (all, P<0.05). In age-, sex- and smoking-adjusted regression analyses CRP concentrations were significantly associated with fasting and 2 h insulin and lipid levels in both ethnic groups (P<0.05). When further statistical adjustment was made for visceral fat area these associations were abolished (P>0.15). CONCLUSION: We suggest that adiposity and in particular visceral adipose tissue is a key promoter of low-grade chronic inflammation. This observation may in part account for the association of CRP with markers of the metabolic syndrome. Future studies should confirm whether CRP concentrations are elevated in South Asians and whether losing weight by exercise or diet, or reduction in visceral fat mass, is associated with reduction in plasma CRP concentrations.

Adipose Tissue↗
PubMed2000

Endothelial dysfunction as a possible link between C-reactive protein levels and cardiovascular disease.

Low-grade chronic inflammation, characterized by elevated plasma concentrations of C-reactive protein (CRP), is associated with an increased risk of atherosclerotic cardiovascular disease. Endothelial cell activation is an early event in atherogenesis, and previous studies have reported correlations between indirect markers of endothelial cell activation and CRP concentration. Therefore, in the present study, we measured CRP concentration (and leptin concentration as an index of fat mass) in nine healthy subjects (mean age 53+/-8.1 years; body mass index 27+/-3.2 kg/m(2); mean arterial blood pressure 101+/-9.0 mmHg) undergoing measurement of basal endothelial nitric oxide (NO) synthesis using intra-brachial infusions of N(G)-monomethyl-L-arginine (L-NMMA; a substrate inhibitor of endothelial NO synthase) and noradrenaline (a non-specific control vasoconstrictor). In univariate analysis, CRP concentration was correlated with (i) the percentage decrease in forearm blood flow (FBF) during L-NMMA infusion (r=0.85, P=0.004); and (ii) the serum leptin concentration (r=0.65, P=0.05). In multivariate analysis, the relationship between CRP concentration and the FBF response to L-NMMA remained significant when age and leptin (t=2.65, P=0.045), age and BMI (t=3.69, P=0.014), or age and low-density-lipoprotein-cholesterol plus high-density-lipoprotein-cholesterol (t=3.37, P=0.044), were included in regression models. In contrast, the response of FBF to noradrenaline was not significantly related to CRP concentration. These data demonstrate for the first time a relationship between low-grade chronic inflammation and basal endothelial NO synthesis (measured using an invasive method), and support the notion that endothelial dysfunction is a critical intermediate phenotype in the relationship between inflammation and cardiovascular disease.

Adult↗
PubMed1999

Relation of triglyceride stores in skeletal muscle cells to central obesity and insulin sensitivity in European and South Asian men.

AIMS/HYPOTHESIS: To compare the relation between intramyocellular lipid content, central obesity and insulin sensitivity in Europeans and South Asians. METHODS: Cross-sectional study of 40 South Asian and European non-diabetic men matched for age and body mass index. We measured intramyocellular lipid by proton magnetic resonance spectroscopy of soleus muscle, insulin sensitivity by the short insulin tolerance test, per cent body fat by dual-energy x-ray absorptiometry and visceral fat by single-slice computed tomography of the abdomen. RESULTS: South Asians compared with Europeans had a higher mean per cent body fat (26.8% vs 22.5%, p = 0.05) and lower insulin sensitivity (mean +/- SEM 2.4 +/- 0.2 vs 3.4%/min +/- 0.3, p = 0.013). Mean (+/- SEM) intramyocellular lipid content was higher in South Asians than in Europeans (72.1 +/- 7.5 vs 53.6 +/- 4.9 mmol/kg dry weight, p = 0.046). In Europeans intramyocellular lipid was correlated with per cent body fat (r = 0.50, p = 0.028), waist:hip ratio (r = 0.74, p < 0.001), visceral fat (r = 0.62, p = 0.004) and insulin sensitivity (r = -0.53, p = 0.016). In South Asians intramyocellular lipid was not significantly related to insulin sensitivity or obesity, and the strongest associations of insulin sensitivity were with fasting plasma triglyceride and waist:hip ratio. CONCLUSION/INTERPRETATION: The association of intramyocellular lipid with insulin sensitivity and obesity in Europeans is consistent with the hypothesis that muscle triglyceride mediates the effect of obesity on insulin sensitivity. The absence of a similar relation of insulin sensitivity to intramyocellular lipid in South Asians suggests that other mechanisms underlie the high insulin resistance observed in this group.

Absorptiometry, Photon↗
PubMed1987

ELISA measurement of IgG subclass production in culture supernatants using monoclonal antibodies.

Specific and sensitive ELISA to quantitate the human IgG subclasses in cell culture supernatants are described. These assays detect a minimum of 5 ng/ml IgG1, 90 ng/ml IgG2, 8 ng/ml IgG3 and 8 ng/ml IgG4 and can generally measure IgG subclasses in lymphocyte cultures containing a minimum of 200 ng/ml of total IgG. The isotype specificity of these ELISA is demonstrated and each individual ELISA shown to react with a number of paraproteins of the relevant subclass independently of their light chain type or their (major Caucasian) allotype. These assays have been used to determine the IgG subclass response of normal human lymphocytes to pokeweed mitogen in vitro.

Antibodies, Monoclonal↗
PubMed1987

T cell regulation of thyroglobulin autoantibody IgG subclasses in Hashimoto's thyroiditis.

Microsomal and thyroglobulin (Tg) antibodies in patients with autoimmune thyroid disease are usually predominantly of subclasses IgG1 and/or IgG4 and the distribution pattern is characteristic for the serum of an individual. We have studied the role of T cells in synthesis of total IgG and Tg antibody IgG subclasses (measured by ELISA) in cultures of peripheral blood lymphocytes (PBL) from Hashimoto patients. Unfractionated PBL incubated with the T dependent activator pokeweed mitogen (PWM) synthesized IgG of all four IgG subclasses in the proportions 69% IgG1, 20% IgG2, 8% IgG3 and 3% IgG4; these values are similar to the proportions of the subclasses in serum. In contrast, the IgG subclass of Tg antibody was predominantly IgG1 in one patient, approximately equal proportions of IgG1 and IgG4 in four patients, and almost completely restricted to IgG4 in one patient; these patterns were similar to the subclass distribution of the autoantibodies in the individual patients' serum. B cells incubated alone secreted little Tg antibody but the response could be restored to the original levels and proportions of IgG1 and/or IgG4 Tg antibody by the addition of T cells either from the same individual or from another donor. Further, removal of suppressor T cells had little effect on the proportions of IgG1 and IgG4 Tg antibody although the total amounts of Tg antibody of both subclasses were sometimes increased. Our studies indicate that T cells are required in this in vitro system to elicit Tg antibody synthesis and to control the magnitude of the antibody response. However, the characteristic IgG subclass distribution of Tg antibody in an individual is determined at the level of the B cell.

Autoantibodies↗