Postprandial hyperglycaemia and cardiovascular disease.
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Acarbose↗
Biomedical subjects
J S Yudkin
Publications and source records attributed to J S Yudkin.
Vitamin B12 deficiency and hyperhomocysteinemia in rural and urban Indians.
BACKGROUND: Low vitamin B12 concentration in South Asian Indians is common, but the exact prevalence is not known. AIM: To investigate prevalence and associations of low vitamin B12 concentration and hyperhomocysteinemia in rural and urban Indian men living in and around Pune, Maharashtra. METHOD: We studied 441 middle-aged men (149 rural, 142 slum and 150 urban middle-class residents, mean age 39 y). Data on lifestyle, socio-economic status, nutrition and medical history were obtained. Circulating concentrations of vitamin B12, folate, ferritin, total homocysteine (tHcy), and haematological indices, and cardiovascular risk variables were measured. RESULTS: Median plasma B12 concentration was low (110 pmol/L): Overall, 67% of men had low vitamin B12 concentration (<150 pmol/L) and 58% had hyperhomocysteinemia (>15 micromol/L). Of the urban middle class, 81% had low vitamin B12 concentration and 79% had hyperhomocysteinemia. Low vitamin B12 concentration contributed 28% to the risk of hyperhomocysteinemia (population attributable risk) while low red cell folate contributed 2%. Vegetarians had 4.4 times (95% CI 2.1, 9.4) higher risk of low vitamin B12 concentrations and 3.0 times (95% CI 1.4, 6.5) higher risk of hyperhomocysteinemia compared to those who ate non-vegetarian foods frequently. Urban middle-class residence was an additional independent risk factor of hyperhomocysteinemia (odds ratio 7.6 (95% CI 2.5, 22.6), compared to rural men). Low vitamin B12 concentration was related to lower blood haemoglobin concentration and higher mean corpuscular volume, but macrocytic anemia was rare. CONCLUSION: Low vitamin B12 concentration and hyperhomocysteinemia are common in Indian men, particularly in vegetarians and urban middle class residents. Further studies are needed to confirm these findings in other parts of India.
Adult↗
EPCR Ser219Gly: elevated sEPCR, prothrombin F1+2, risk for coronary heart disease, and increased sEPCR shedding in vitro.
We have progressively analysed three studies of coronary heart disease (CHD) for a variant in EPCR (Ser219Gly). Initially, in a prospective study, NPHSII, while no overall CHD-risk was identified in heterozygotes, homozygotes for 219Gly exhibited a three-fold elevated risk (HR 3.3, CI 1.22-8.96). In diabetics within NPHSII, there was a suggestion that 219Gly+ was associated with elevated CHD-risk (HR 1.89, CI 0.39-9.06) although numbers were small. To further assess the effect of the variant in diabetes, a case-control study of MI, HIFMECH, was used, in which previous analysis had defined a group with metabolic syndrome, by factor analysis. A significant CHD-risk interaction was identified between genotype and the 'metabolic syndrome' factor (interaction p=0.009). To further assess CHD-risk for this variant in type-2 diabetes and to assess the effect of the variant upon thrombin generation and plasma levels of soluble EPCR, a cross-sectional study of type-2 diabetes was used. A significant CHD-risk was identified for European Whites (OR 2.84, CI 1.38-5.85) and Indian Asians in this study (OR 1.6, CI 1.00-2.57) and the frequency of 219Gly was two-fold higher in Indian Asians. Soluble EPCR levels were strongly associated with genotype, with homozygotes for 219Gly having four-fold higher levels (p<0.0001). In vitro studies of EPCR-transfected cells suggested increased basal release of sEPCR from cells expressing the 219Gly EPCR phenotype. Furthermore, in base-line samples from NPHSII and in the diabetic study, a significant increase in prothrombin F1+2 level was observed for 219Gly. The increased CHD-risk and thrombin generation appears to be acting through increased shedding of the Gly allele from the cell surface.
Animals↗
Body fat measurement in Indian men: comparison of three methods based on a two-compartment model.
UNLABELLED: Obesity is a major risk factor for diabetes and related disorders. The current classification of obesity is based on body mass index (BMI, kg/m(2)), which is a surrogate for the total body fat. Since the relationship between BMI and body fat varies in different populations, an independent validation of the BMI-body fat relationship in the population of interest is desirable. OBJECTIVES: (1) To study the validity of field methods of measuring body fat (multiple skinfolds and bioimpedance) against a criterion method (deuterium dilution) and (2) To compare the prevalence of obesity (WHO 2000 criteria for BMI) with adiposity (body fat >25%) in middle-aged Indian men in rural and urban Pune. DESIGN: Community-based multistage stratified random sampling of middle-aged men from rural and urban Pune for study of body composition and cardiovascular risk. A third of these men, selected to represent wide BMI distribution, were studied for body fat measurements by specific methods. SUBJECTS: A total of 141 healthy men, approximately similar number from rural, urban slums and middle class from Pune. They were 39.3 (+/-6.2) y old and had a BMI of 21.9 (+/-3.7) kg/m(2). MEASUREMENTS: Anthropometry (height, weight and multiple skinfold thicknesses) by trained observers using standardised technique to calculate body fat by Durnin and Womersley's equation. Total body water and body fat by bioelectrical impedance analysis (BIA) and deuterium oxide dilution (D(2)O). RESULTS: Mean total body fat was 14.3 kg (23.0%) by anthropometry, 16.5 kg (26.0%) by BIA and 15.3 kg (24.6%) by D(2)O method. Although there was a good correlation between fat estimation by three methods (r= approximately 0.9, P<0.001 all), compared to D(2)O method anthropometry underestimated body fat by 1.0 kg and BIA overestimated fat by 1.2 kg (P<0.001 both). Using the standard cut-point of 25% body fat for 'adiposity' 29.5% rural, 46.0% slum and 75.0% middle class men were adipose. These proportions were considerably higher than the number of men who were 'preobese' (BMI> or =25-29.9 kg/m(2), 9.0% rural, 22.0% urban slums and 27.0% urban middle class) and 'obese' (BMI >30 kg/m(2), 4.0% urban slums, none in rural and urban middle class). CONCLUSION: We recommend that future studies assessing risk for chronic diseases in Indians should measure adiposity by anthropometry (multiple skinfolds) or BIA (calibrated for Indians) rather than relying only on BMI cut-points.
Adult↗
Prognostic value of admission plasma glucose and HbA in acute myocardial infarction.
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Blood Glucose↗
Interaction between the C-260T polymorphism of the CD14 gene and the plasma IL-6 concentration on the risk of myocardial infarction: the HIFMECH study.
Experimental and clinical observations suggest that innate immunity plays a major role in the pathogenesis and progression of atherosclerosis. A common C-260T polymorphism in the promoter of the CD14 gene, the trans-membrane receptor of lipopolysaccharides, has been inconsistently associated with coronary heart disease. Our objective was to evaluate the contribution of the CD14 polymorphism to the inflammatory response and to the risk of myocardial infarction (MI). We used an European case-control study, the HIFMECH study, comparing 533 men with MI and 575 sex- and age-matched controls. Associations between genotype and disease outcome, according to interleukin-6 (IL-6) and C-reactive protein (CRP) levels, were assessed using conditional logistic regression. The CD14/C-260T polymorphism was associated with plasma IL-6 levels, T/T subjects having higher plasma levels than C/C in cases but not in controls (mean+/-S.D.: 2.04+/-1.37 versus 1.70+/-1.15, p=0.01; 1.20+/-0.75 versus 1.35+/-0.88, p=0.31, respectively). Overall, the CD14/C-260T polymorphism was not associated with the risk of MI. However, in individuals with IL-6 plasma levels in the highest tertile, T allele carriers had a higher risk of MI than C/C (OR: 1.85; CI 95 1.05-3.25). IL-6 increased the risk of MI in carriers of the T allele (OR for first versus third IL-6 tertile: 4.02; CI 95 2.24-7.21), but not in C/C (OR: 0.75; CI 95 0.32-1.74, p=0.004 for interaction). The data indicate a role for CD14/C-260T in MI. The risk mediated by the polymorphism is highly dependent on IL-6 plasma levels.
Arteriosclerosis↗
Low-grade inflammation may play a role in the etiology of the metabolic syndrome in patients with coronary heart disease: the HIFMECH study.
Risk of coronary heart disease has been related to insulin resistance, but the mechanism for this is incompletely understood. Variables attributed to insulin resistance are associated with low-grade inflammation. A case-control study was performed of 469 male myocardial infarction (MI) survivors aged < 60 years and 575 control subjects recruited from centers in northern and southern Europe. Principal factor analysis was used to explore correlations between insulin resistance and inflammatory variables. Three factors resulted: (a) "Metabolic Syndrome" (insulin/proinsulin/ triglyceride/body mass index [BMI]); (b) "Inflammation" (fibrinogen/C-reactive protein [CRP]/interleukin-6 [IL-6]); and (c) "Blood Pressure" (systolic and diastolic blood pressure). The "Metabolic Syndrome" factor was related to the "Inflammation" factor (largely independently of obesity), the "Blood Pressure" factor, smoking, and south location (all P < or = .0002). There were significant relationships between all 3 factors and case status (P < or = .0002). Markers of low-grade inflammation are strongly related to metabolic syndrome variables independently of obesity. This raises the possibility that links between insulin resistance and cardiovascular disease could, in part, represent common consequences of low-grade inflammation.
Aged↗
Adipose tissue, insulin action and vascular disease: inflammatory signals.
Insulin resistance, both in nondiabetic and diabetic subjects, is frequently associated with obesity, particularly an excess of central fat. Many of the features that have been ascribed to the metabolic or insulin-resistance syndrome are also more commonly found in obese subjects. These phenotypes include diabetic dyslipidaemia, elevation of levels of plasminogen activator inhibitor-1, microalbuminuria and endothelial dysfunction. More recently, features of acute-phase activation and low-grade inflammation, including elevated levels of fibrinogen, C-reactive protein and interleukin-6, have been associated with (central) obesity. Adipose tissue generation of cytokines has been shown in vitro and in vivo, and a number of novel cytokine-like molecules, collectively termed adipocytokines, have been identified as adipocyte products. While several of these, such as tumour necrosis factor-alpha, may act predominantly in autocrine or paracrine fashion, others are released into the systemic circulation, acting as signalling molecules to remote tissues, including liver, skeletal muscle and endothelium. A clearer understanding of adipose tissue signalling, and its contribution to the state of low-grade inflammation of obesity, will require physiological, as well as cellular and molecular, studies.
Adipose Tissue↗
The plasminogen activator inhibitor-1 -675 4G/5G genotype influences the risk of myocardial infarction associated with elevated plasma proinsulin and insulin concentrations in men from Europe: the HIFMECH study.
UNLABELLED: Although the potential role of plasminogen activator inhibitor-1 (PAI-1) in the development of coronary artery disease is strongly supported by its biological characteristics, results of clinical studies remain controversial. OBJECTIVES: To investigate whether plasma PAI-1 concentrations and the -675 4G/5G polymorphism located in the PAI-1 gene could constitute risk markers for myocardial infarction (MI). PATIENTS AND METHODS: We used a European case-control study, the HIFMECH study, comparing 598 men with MI and 653 age-matched controls. RESULTS: Insulin resistance explained a major part of the variation in PAI-1 (24%) whereas inflammation had only a minor contribution (0.01%). For both cases and controls plasma PAI-1 concentrations were significantly higher in the North than the South, and in both regions were higher in individuals with MI compared with control subjects [overall odds ratio (OR) for a 1 SD increase=1.54, 95% confidence interval (CI) 1.34, 1.77]. This difference was observed in all the centers studied. Overall, the difference between cases and control subjects remained significant after controlling for inflammation variables (OR=1.30, 95% CI 1.08, 1.57), but lost significance after controlling for insulin resistance variables (OR=1.17, 95% CI 0.98, 1.40). The 4G allele was associated with significantly higher PAI-1 levels in cases but not controls and, taken independently, did not modify the risk of MI (P=0.9). However, a significant interaction was observed with both insulin or proinsulin and the risk of MI (P=0.05 and 0.02, respectively), but not with triglycerides or body mass index (BMI). The insulin or proinsulin effect on risk was observed only in the carriers of the 4G/4G genotype. This interaction appeared not to be mediated by plasma PAI-1 antigen concentrations (P=0.01 and 0.02 after adjustment for PAI-1 plasma levels). The interaction with proinsulin but not insulin remained statistically significant after further adjustment for other factors associated with insulin resistance (triglycerides and BMI) and C-reactive protein (P=0.01). CONCLUSION: This study suggests that PAI-1 has a role in risk of MI in the presence of underlying insulin resistance. A significant interaction between insulin or proinsulin and the -675 4G/5G polymorphism was observed in risk for MI. The mechanisms for these interactions remain to be determined.
Case-Control Studies↗
Leptin levels in type 2 diabetes: associations with measures of insulin resistance and insulin secretion.
Interactions between leptin and insulin have been shown previously, in vitro and in vivo. In this study, we evaluate the associations of leptin levels with insulin secretion and insulin sensitivity in type 2 diabetes. Fasting leptin levels, HbA 1c, glucose, insulin, C-peptide, intact and des-31,32-proinsulin were measured in 100 non-insulin-treated type 2 diabetic patients. Glucose, insulin and C-peptide were measured 2 hours after an oral glucose load. Insulin resistance and beta-cell function were calculated using HOMA. Leptin levels were found to be associated with all measures of beta-cell secretion: with fasting and 2 hours insulin and C-peptide, with intact and des-31,32-proinsulin concentrations, and with beta-cell secretion estimated with HOMA. This association was independent of age and body fat in women, but in men, associations with insulin and C-peptide weakened after controlling for fat mass, whereas those with intact and des-31,32-proinsulin disappeared. Fasting insulin and C-peptide levels were also significant in multiple regression analyses, besides gender and fat mass. Insulin resistance, as assessed by HOMA, was strongly correlated with leptin, also after correction for age and fat mass in both genders. We conclude that, besides fat mass and gender - the main determinants for leptin levels in type 2 diabetic subjects as in healthy subjects - insulin secretion and the degree of insulin resistance also seem to contribute significantly to leptin levels.
Adipose Tissue↗
Concentrations of proinsulin like molecules predict coronary heart disease risk independently of insulin: prospective data from the Caerphilly Study.
AIMS/HYPOTHESIS: Higher concentrations of insulin correlate with several coronary heart disease (CHD) risk factors and have been shown to predict incident CHD in several studies, leading to hypotheses concerning the proatherogenic properties of insulin. However, in cross-sectional studies, relationships of concentrations of the insulin precursor molecules, proinsulin and des 31, 32 proinsulin, relate as strongly, or more strongly, to levels of risk factors and to (prevalent) CHD. METHODS: We investigated the relationship between concentrations of insulin, measured with a specific assay, and of proinsulin-like molecules, and risk factors in 1181 non-diabetic men 50-64 years old during Phase II of the Caerphilly Study. We also related concentrations of these molecules to incident CHD during the 10-14 years follow-up. RESULTS: The relationship between concentrations of insulin, of proinsulin and of des 31, 32 proinsulin and BMI ( r = 0.36-0.45), triglyceride (r = 0.25-0.31), high density lipoprotein- (HDL-) cholesterol (r = -0.17 to -0.21), systolic ( r = 0.05-0.11) and diastolic blood pressure ( r = 0.11-0.15) were similarly close, those with risk factors being somewhat and similarly reduced after adjustment for BMI. The correlation between insulin and of proinsulin-like molecules and those plasminogen activator inhibitor-1 (PAI-1) antigen was also similar (r = 0.28-0.29). There was a negative correlation between concentrations of proinsulin-like molecules - but not insulin - and birth weight. Insulin concentrations correlated positively with height ( r = 0.12). In logistic regression models, concentrations of proinsulin-like molecules, but not insulin, predicted incident of CHD over a follow-up of 10-14 years (insulin - standardised odds ratio (SOR) 1.30 (95 %-CI) 0.91, 1.85), p = 0.15; des 31, 32 proinsulin - SOR 1.38 (95 %-CI 1.02, 1.85), p = 0.034; sum of proinsulin-like molecules - SOR 1.54 (95 %-CI 1.07, 2.20), p = 0.019 after adjusting for age and BMI. The predictive ability of these molecules was reduced by around one third after adjustment for standard risk factors and concentrations of tryglyceride and HDL-cholesterol, and by about half after further adjustment for PAI-1 concentrations. CONCLUSION/INTERPRETATION: We conclude that concentrations of proinsulin-like molecules provide a better way to predict the incidence of CHD than those of insulin. However, the lack of biological evidence for a causative relationship suggests an association through a common antecedent, and this antecedent is not likely to be intrauterine growth retardation.
Biomarkers↗
The central roles of obesity-associated dyslipidaemia, endothelial activation and cytokines in the Metabolic Syndrome--an analysis by structural equation modelling.
HYPOTHESIS: The multi-faceted components of the metabolic syndrome now include markers of inflammation and endothelial activation. Despite this growing body of epidemiological data, standard statistical methods fail to evaluate the nature of these associations adequately. In this pilot study, we hypothesize that obesity may lead to endothelial activation which is in part mediated by dyslipidaemia and proinflammatory cytokines. These factors interact to give rise to hyperinsulinaemia, hypertension and an anti-fibrinolytic state. To test this hypothesis, we used confirmatory factor analysis and structural equation modelling to fit these data to a model designed on theoretical grounds. METHODS: Metabolic syndrome variables, cytokines (IL6 and TNFalpha), markers of inflammation and endothelial activation were measured in 107 Caucasian non-diabetic subjects aged 40-75 y. Using confirmatory factor analysis, we identified six factors to represent composite measurements of blood pressure, obesity, dyslipidaemia, hyperinsulinaemia, endothelial activation and the anti-fibrinolytic state. We fitted these variables to two separate models, one using IL-6 and the other TNFalpha as the cytokine, and examined the inter-relationships (path analysis) amongst these variables, based on the above hypothesis. RESULTS: Men were centrally more obese and had increased markers of endothelial activation, inflammation and the anti-fibrinolytic state as well as hyperinsulinaemia and dyslipidaemia, compared with women. Obesity indexes (both body mass index and waist-hip ratio) were strongly associated with multiple cardiovascular risk factors. Both IL6 and TNFalpha were correlated with age, male gender, obesity indexes and markers of endothelial activation. Only IL-6 was associated with smoking while TNFalpha was correlated with hyperinsulinaemia. In the TNFalpha model, 61% of the obesity variance was explained by male gender, 36% of TNFalpha variance by age and dyslipidaemia, 43% of dyslipidaemia variance by age and obesity, 33% of hyperinsulinaemia variance by dyslipidaemia and a non-smoking state, 29% of anti-fibrinolytic state variance by hyperinsulinaemia, 65% of endothelial activation variance by TNFalpha, dyslipidaemia and hyperinsulinaemia, 34% of blood pressure variance by hyperinsulinaemia and endothelial activation. In the IL-6 model, we observed similar relationships except that 23% of IL6 variance was explained by smoking and age. CONCLUSIONS: Using confirmatory factor analysis and structural equation modelling, we found that obesity, dyslipidemia and cytokines were the principal explanatory variables for the various components of the metabolic syndrome, with IL6 and TNFalpha having different explanatory variables and effects. These complex inter-relationships were in part mediated by hyperinsulinaemia and endothelial activation. While this hypothetical model was based on scientific evidence, supported by rigorous analysis, it requires further confirmation in large-scale prospective studies. Given the complexity of the biological system and its interactions with exogenous factors, structural equation modelling provides a useful scientific tool for hypothesis testing, complementary to the more traditional experimental and cohort studies.
Adult↗
Effects of tumour necrosis factor-alpha in the human forearm: blood flow and endothelin-1 release.
Increased circulating concentrations of tumour necrosis factor-alpha (TNF-alpha) are seen in several pathological conditions associated with vascular disease. TNF-alpha induces the synthesis of endothelin-1 (ET-1), a potent vasoconstictor, by the endothelium. However, there is profound vasodilatation in sepsis, where circulating levels of both ET-1 and TNF-alpha are elevated. The details of the interaction between ET-1 and TNF-alpha and the predominant resulting haemodynamic effect in healthy humans are unclear. The aim of the present study was to determine the effects of intra-arterial TNF-alpha on ET-1 spillover, vascular tone and endothelial function in the healthy human forearm. Brachial arterial and deep venous blood samples, forearm plasma flow measurements and blood flow responses to acetylcholine and sodium nitroprusside were obtained in six healthy subjects before and during a 6 h infusion of TNF-alpha into the brachial artery. Forearm blood flow was significantly greater than baseline during exposure to TNF-alpha [median (lower quartile, upper quartile): baseline, 2.6 (2.1, 2.8) ml.min(-1).100 ml(-1); TNF-alpha, 4.6 (4.5, 5.1) ml.min(-1).100 ml(-1); P <0.05]. The rate of release of ET-1 was significantly greater than baseline after 30 and 260 min of TNF-alpha infusion [median (lower quartile, upper quartile): baseline, 0.8 (0.6, 1.1) pg.min(-1).100 ml(-1); 30 min, 2.4 (1.9, 3.2) pg.min(-1).100 ml(-1); 260 min, 4.1 (3.1, 4.2) pg.min(-1).100 ml(-1); P <0.05]. The vasodilatory response to acetylcholine was diminished during TNF-alpha infusion, whereas the response to sodium nitroprusside remained unchanged. We thus demonstrate for the first time that local TNF-alpha increases ET-1 spillover from the human forearm and impairs endothelium-dependent vasodilatation. In spite of this action, TNF-alpha has a vasodilatory effect, resulting in an increase in forearm blood flow.
Acetylcholine↗
Adiposity and hyperinsulinemia in Indians are present at birth.
We studied body size and cord blood leptin and insulin concentrations in newborn urban Indian (Pune, India) and white Caucasian (London, UK) babies to test the hypothesis that the adiposity and hyperinsulinemia of Indians are present at birth. Indian babies (n = 157) were lighter in weight compared with white Caucasian babies [n = 67; median weight, 2805 g vs. 3475 g, respectively; P < 0.001, adjusted for gestational age and sex; -1.52 SD score; confidence interval (CI), -1.66, -1.42] and had smaller abdominal (-2.39 SD score; CI, -2.52, -2.09), midarm (-1.47 SD score; CI, -1.58, -1.34), and head (-1.23 SD score; CI, -1.42, -1.13) circumferences. However, their skinfolds were relatively preserved: subscapular (central) skinfold (-0.32 SD score; CI, -0.43, -0.20) was better preserved than triceps (peripheral) skinfold (-0.86 SD score; CI, -0.97, -0.75). Cord plasma leptin (median, 6.2 ng/ml Pune and 6.4 ng/ml London) and insulin (median, 34.7 pmol/liter Pune and 20.8 pmol/liter London) concentrations were comparable in the two populations but were higher in Indians when adjusted for birth weight, confirming relative adiposity and hyperinsulinemia of Indian babies. Indian mothers were smaller in all respects, compared with white Caucasian mothers, except subscapular skinfold, which was similar in the two populations. Our results support the intrauterine origin of adiposity, central adiposity, and hyperinsulinemia in Indians. Further research should concentrate on elucidating genetic and environmental influences on fetal growth and body composition. Prevention of insulin resistance syndrome in Indians will need to address regulation of fetal growth in addition to prevention of obesity in later life.
Adipose Tissue↗
Intracellular pH, intrauterine growth and the insulin resistance syndrome.
Defects of both sodium-hydrogen exchange (NHE) and sodium-lithium countertransport (SLC) have been described in subjects at increased risk of coronary heart disease (CHD). Sodium transport is linked to the regulation of cell volume, intracellular pH and cell growth, which may explain aspects of this association. However, impaired growth in early life is also linked to adult CHD, and 'programmed' alterations of cell behaviour are postulated to be responsible for this. In this study, therefore, we examined whether NHE or SLC in adults are predicted by anthropometric measures at birth, as well as being associated with insulin resistance syndrome (IRS) variables in adulthood. Red cell SLC was measured in 26 adults, and NHE in dermal fibroblasts from another 15 subjects characterized anthropometrically at birth. SLC activity correlated with LDL cholesterol, triglycerides and urate (r=0.42 - 0.49; 0.05 > P>0.01), but not birth anthropometry. NHE V(max) correlated with plasma insulin (r=0.80; P<0.001), but birth weight was unrelated to V(max), K(m) or Hill coefficient for H(i)(+). However, pH(i) correlated with birth weight (r=0.74; P=0.002), insulin sensitivity (r=0.52; P<0.05), fasting glucose (r=-0.52; P<0.05) 2 h insulin (r=0.51; P<0.05) 2 h glucose (r=-0.54; P<0.05). In conclusion, red cell SLC is related to IRS variables, but not with birth weight measures. In contrast, low intracellular pH(i) is related to both low birth weight and adult insulin resistance, suggesting it might be a 'programmed' cell phenotype, although this is not apparently explained by altered NHE kinetics.
Anthropometry↗
A case for lipid lowering? Response to Dr Paul Durrington.
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Decision Making↗
Variation in the progression of diabetic nephropathy according to racial origin.
BACKGROUND: In the United Kingdom, diabetic nephropathy is a leading cause of end-stage renal disease. There is a higher incidence amongst subjects of Indo-Asian and African-Caribbean origin compared with Caucasians that is not wholly explained by the differences in the prevalence of diabetes. Therefore, we postulated that this observation could be related to variations in the rate of progression of renal disease according to racial origin. METHODS: We conducted a retrospective case-note review of 1684 adult attendees of the diabetes clinic. Forty-five patients were found with renal impairment (serum creatinine > or = 170 micromol/l) due to diabetic nephropathy. The patients were of Indo-Asian (n=10), African-Caribbean (n=11), and Caucasian (n=24) origin. Progression of nephropathy was assessed by analysing (i) the doubling of serum creatinine through construction of Kaplan-Meier curves and (ii) the slope (beta) of the rate of change in serum creatinine using linear regression analysis in relation to demographic variables, putative risk factors for nephropathy and antihypertensive drug therapy. RESULTS: There were no statistically significant differences between systolic and diastolic blood pressure, glycaemic control, smoking habit, baseline proteinuria, and usage of angiotensin-converting enzyme inhibitors between the three groups. The proportion of patients doubling their creatinine was significantly higher in the Indo-Asian compared with the African-Caribbean and Caucasian groups (100, 45 and 50%; P=0.025 respectively). In addition, the mean (95% CI) of beta (micromol/l/month) was highest in the Indo-Asian (5.36 (2.21-8.52)) compared with the African-Caribbean (3.14 (0.82-5.46)) and Caucasian (2.22 (1.31-3.14)) groups (P=0.035). The mean ranks of beta were highest in the Indo-Asian group (P=0.038) after adjusting for marginal differences in blood pressure age, gender, baseline proteinuria, anti-hypertensive treatment, and smoking habit. CONCLUSIONS: In this small cohort of type 2 diabetic subjects with established renal disease, the rate of decline in renal function is accelerated in Indo-Asian subjects. This observation could be related to differences in renoprotection from antihypertensive therapy.
Black or African American↗
Associations of micro-albuminuria with intra-uterine growth retardation.
BACKGROUND/AIM: Micro-albuminuria is associated with insulin resistance and a high blood pressure and predicts an increased risk of cardiovascular disease in both diabetic and non-diabetic populations. Relationships have been described for micro-albuminuria with both low birth weight and short stature in adulthood. We have tested the hypothesis that micro-albuminuria in non-diabetic adults may be associated with markers of intra-uterine growth retardation. METHODS: We measured the urinary albumin excretion rate in 818 men and women from three populations, in whom detailed records of birth weight were available, of whom 354 had records of length at birth to provide an estimate of the ponderal index. RESULTS: The albumin excretion rates were higher in men than in women (5.1 vs. 3.8 microg/min) and were related to age (r = 0.23, p < 0.001) and body mass index (r = 0.08, p = 0.02) as well as fasting plasma glucose and blood pressure. Considered as a continuous variable, the albumin excretion rate was not related to any measure of size at birth or to adult height. Fifty-four subjects (6.6%) were micro-albuminuric (albumin excretion rate > or = 20 microg/min), and these subjects were thinner at birth than normo-albuminuric subjects (12.9 vs. 13.8 oz/in3, p = 0.09). Compared to those subjects whose ponderal index had been in the upper third of the distribution, people whose ponderal index had been in the lower third of the distribution had an odds ratio for micro-albuminuria of 3.1 (p for trend 0.05). CONCLUSION: The association between micro-albuminuria, insulin resistance, and coronary heart disease may be a consequence of growth retardation representing a common antecedent.
Age Factors↗