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Biomedical subjects

B Balkau

Publications and source records attributed to B Balkau.

At least 19 recordsLinked to original sources
PubMed2006

High plasma leptin predicts an increase in subcutaneous adiposity in children and adults.

OBJECTIVE: To investigate the hypothesis that plasma leptin may predict adiposity changes. DESIGN: A population-based cohort study. SETTING: Fleurbaix and Laventie, in the north of France. SUBJECTS: In all, 1175 subjects participated, of whom 946 completed measurements at baseline (1999) and follow-up (2001). After excluding 64 subjects obese at baseline, 882 subjects (478 adults, 404 children 8 years and over) were included in the analysis. INTERVENTIONS: We measured plasma leptin concentrations at baseline and various adiposity parameters at baseline and follow-up. Partial correlation coefficients (r(p)) between baseline plasma leptin and each adiposity indicator at follow-up were calculated with adjustment for baseline age, pubertal stage, adiposity and familial correlations between siblings. RESULTS: Changes in body mass index and percentage body fat were not related to baseline plasma leptin. High baseline plasma leptin predicted an increase (r(p) (P-value)) in the sum of the four skinfolds (0.18 (<0.0001)), the waist circumference (0.16 (0.0003)) and the waist-to-hip ratio (0.29 (<0.0001)) in adults only, and in the hip circumference in adults (0.20 (<0.0001)) and children (0.22 (<0.0001)). After adjustment for a set of four adiposity variables at baseline (percentage body fat, skinfolds, waist and hip circumferences), baseline plasma leptin predicted only changes in the sum of the four skinfolds in adults (0.15 (0.001)), with similar tendency although not significant in children (0.08 (0.13)). CONCLUSIONS: A high leptin relative to baseline fat mass predicts fat mass gain over time, mainly in the subcutaneous location.

Adult↗
PubMed2006

Three-year increase of gamma-glutamyltransferase level and development of type 2 diabetes in middle-aged men and women: the D.E.S.I.R. cohort.

AIMS/HYPOTHESIS: Among hepatic markers, gamma-glutamyltransferase (GGT) is the main predictor for development of type 2 diabetes, but there are no data to date on changes in GGT and type 2 diabetes incidence. METHODS: Data at baseline and at 3 years from the D.E.S.I.R. cohort were used, comprising 2,071 men and 2,130 women without baseline diabetes. RESULTS: Changes in GGT level were correlated with changes in markers of insulin resistance (fasting insulin, homeostasis model assessment of insulin resistance), as well as with the following elements of the metabolic syndrome: central obesity, and increased fasting glucose, triglycerides and blood pressure (systolic and diastolic). The 3-year increase in GGT was associated with incident type 2 diabetes in both sexes, after adjusting for age and baseline GGT. After further adjustment for baseline confounding factors, including alanine-aminotransferase, alcohol intake, obesity and fasting insulin, the odds ratios (95% CI) for an association between incident type 2 diabetes and unchanged or increased (as opposed to decreased) GGT levels were 2.54 (1.38-4.68) in men (p=0.003) and 2.78 (1.20-6.42) in women (p=0.02). These associations were slightly attenuated after adjusting for the 3-year change in BMI, alcohol consumption and fasting insulin, the odds ratios being 2.49 (1.28-4.86) in men and 2.53 (1.01-6.40) in women. This relationship was not dependent on intra-individual variability. CONCLUSIONS/INTERPRETATION: An unchanged or increased GGT level over time, even when GGT is in the normal range, is correlated with increasing insulin resistance and is associated with a risk of incident type 2 diabetes in both sexes, independently of baseline GGT, which is itself a diabetes risk factor.

Body Mass Index↗
PubMed2006

Practical way to assess metabolic syndrome using a continuous score obtained from principal components analysis.

AIMS/HYPOTHESIS: We devised a practical continuous score to assess the metabolic syndrome, and assessed whether this syndrome score predicts incident diabetes and cardiovascular disease. SUBJECTS AND METHODS: Among 5,024 participants of the Data from an Epidemiological Study on the Insulin Resistance Syndrome (D.E.S.I.R.) cohort, we defined a metabolic syndrome score by the first principal component (PC1), using only the correlations between continuous metabolic syndrome measures (glucose, waist circumference, triglycerides, and systolic blood pressure). This metabolic syndrome score was highly correlated with a similar score also including insulin and HDL cholesterol (r ( s )=0.94). Over 9 years of follow-up, incident diabetes and cardiovascular disease (CVD) were predicted by logistic regression using the simpler metabolic syndrome score. RESULTS: The means of the metabolic syndrome measures differed between men and women. Nevertheless, as the degree of variance explained and the PC1 coefficients were remarkably similar, we used a common metabolic syndrome score. The metabolic syndrome score explained 50% of the variance of the metabolic syndrome measures, and waist circumference had the highest correlation (0.59) with this score. Each standard deviation increase in the metabolic syndrome score was associated with a markedly increased age-adjusted risk of developing diabetes (odds ratios: men 3.4 [95% CI 2.6-4.4]; women 5.1 [3.6-7.2]) and with increased incident CVD of 1.7 (1.4-2.1) in men and 1.7 (1.0-2.7) in women. CONCLUSIONS/INTERPRETATION: Our results, which should be confirmed in other populations, suggest that it is possible to evaluate the risk of the metabolic syndrome in a pragmatic fashion with a continuous score, obtained from principal components analysis of the basic, continuous syndrome measures.

Adult↗
PubMed2006

Diagnostic thresholds for diabetes: the association of retinopathy and albuminuria with glycaemia.

AIM: We examined the association of fasting plasma glucose (FPG), 2-h plasma glucose (2hPG) and HbA1c with retinopathy and microalbuminuria using both deciles of glycaemia and change point models, to validate current diagnostic criteria for diabetes and to identify therapeutic thresholds for glycaemic control. METHODS: The Australian Diabetes Obesity and Lifestyle study (AusDiab), conducted in 1999-2000, included adults aged > or =25 years from 42 randomly selected areas of Australia. Retinopathy and albuminuria were assessed in participants identified as having diabetes (based on self report and oral glucose tolerance test), impaired fasting glucose, impaired glucose tolerance and in a random sample with normal glucose tolerance. Data were available for 2,182 participants with retinal photographs and 2,389 with urinary albumin/creatinine results. RESULTS: The prevalence of retinopathy in the first 8 deciles of FPG and HbA1c and the first 9 deciles of 2hPG were 7.2, 6.6, and 6.3%, respectively and showed no variation with increasing glucose or HbA1c. Above these levels, the prevalence rose markedly to 18.6% in the top 2 deciles of FPG, 21.3% in the top 2 deciles of HbA1c and 10.9% in the top decile of 2hPG. The thresholds for increasing prevalence of retinopathy were 7.1 mmol/l for FPG, 6.1% for HbA1c and 13.1 mmol/l for 2hPG. The prevalence of microalbuminuria rose gradually across deciles of each glycaemic measure. Thresholds were less clear than for retinopathy, but were seen at a FPG of 7.2 mmol/l and HbA1c of 6.1%, with no evidence of a threshold effect for 2hPG. CONCLUSIONS: The prevalence of retinopathy rose dramatically in the highest deciles of each glycaemic measure, while for microalbuminuria the increase of prevalence was more gradual. The FPG values corresponded well with the WHO diagnostic cut-point for diabetes, however the 2hPG value did not. HbA1c thresholds were similar for both retinopathy and microalbuminuria and compared well to values shown in other studies. These results support current targets for FPG and HbA1c in preventing microvascular complications.

Aged↗
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

Prescreening tools for diabetes and obesity-associated dyslipidaemia: comparing BMI, waist and waist hip ratio. The D.E.S.I.R. Study.

OBJECTIVE: To compare the sensitivities of BMI, waist circumference and waist hip ratio (WHR) in identifying subjects who should be screened for diabetes and/or for obesity-associated dyslipidaemia. DESIGN: Cross-sectional study. SETTING: Central-western France. PARTICIPANTS: More than 3000 men and women, aged 40-64 years, from the French study: data from an epidemiological study on the insulin resistance syndrome (D.E.S.I.R.). MAIN OUTCOME MEASURES: Sensitivity and specificity for screened diabetes (fasting plasma glucose>or=7.0 mmol/l) and screened dyslipidaemia (triglycerides>or=2.3 mmol/l and/or HDL-cholesterol <0.9/1.1 mmol/l (men/women)) according to BMI, waist circumference and WHR. RESULTS: Sensitivities increased as more corpulent subjects were screened, but they increased slowly after screening the top 30%: body mass index (BMI)>or=27/26 kg/m(2) (men/women) or waist >or=96/83 cm or WHR>or=0.96/0.83. These values were chosen as thresholds. In men, BMI had a nonsignificantly higher sensitivity than waist or WHR for both diabetes and dyslipidaemia (77 vs 74 and 66% P<0.3, 0.09; 56 vs 54 and 49% P<0.5, 0.16). For women, waist had a slightly higher sensitivity than BMI or WHR (82 vs 77 and 77% P<0.8, 0.7) for diabetes; for dyslipidaemia, waist and WHR had similar sensitivities, higher than for BMI (65 and 67 vs 54% P<0.16, 0.13). CONCLUSIONS: We propose that for screening in a French population 40-64 years of age, the more obese 30% of the population, identified either by BMI, waist or WHR be screened for diabetes and obesity-associated dyslipidaemia.

Adult↗
PubMed2006

Assessment of diabetes screening by general practitioners in France: the EPIDIA Study.

AIM: To audit Type 2 diabetes screening in general practice in France and to determine the frequency of undiagnosed diabetes in patients at high risk, after systematic screening and diagnosis. METHODS: For this study, 288 general practitioners volunteered to include all consecutive non-diabetic patients aged < 65 years who had at least two risk factors for diabetes, whatever the reason for consultation. If a plasma glucose had not been recorded in the previous 12 months, a fasting plasma glucose (FPG) was performed, with a second test if FPG >or= 7.0 mmol/l. RESULTS: There were 5950 patients included. The most frequent diabetes risk factors were: age >or= 40 years, 92%; overweight [body mass index (BMI) >or= 27 kg/m2], 59%; treated hypertension, 48%; treated dyslipidaemia, 37%; family history of diabetes, 24%. Of these subjects at high risk for diabetes, 88% had a FPG measurement in their medical record (75% measured during the preceding 12 months). In the 1499 patients in whom FPG was measured, diabetes was diagnosed in 40 patients (2.7% 95% CI 1.9-3.5) and 22% had impaired fasting glucose (IFG). Thus, the frequency of undiagnosed diabetes in the 5950 high-risk patients was 0.67% (0.46-0.88). CONCLUSION: Screening for diabetes by general practitioners in France appears to be adequate and undiagnosed diabetes is rare in patients with risk factors for diabetes, at least in those consulting the general practitioners studied.

Blood Glucose↗
PubMed2005

Weight change and changes in the metabolic syndrome as the French population moves towards overweight: the D.E.S.I.R. cohort.

BACKGROUND: How weight change affects the metabolic syndrome (MS) and its parameters is unknown, particularly, in a leaner European population such as the French prospective D.E.S.I.R. cohort. METHODS: In 3770 D.E.S.I.R. participants (sex ratio=1) averaging 47.5 years (range 30-64), with measured weight and MS parameters at baseline (D0) and at 6 year follow-up (D6), we assessed this relationship across five weight-change classes, using stable weight as the referent group (-2 to +2 kg). We used analysis-of-covariance to assess changes in each MS parameter and logistic regression to assess incident MS, according to the National Cholesterol Education Program (NCEP). We also assessed weight-change effect on MS status between D0 and D6. RESULTS: At D0, average weight was 68.4 kg (SD 12.3); BMI was 24.8 kg/m2 (SD 3.5). From D0-D6, the cohort gained a mean 2.1 kg (median 2.0; SD 4.4). After adjustment for age and D0 weight, there was a strong linear relationship with weight change and worsening of the following MS parameters at D6: fasting insulin, waist girth, fasting glucose, fasting triglycerides, HDL cholesterol, and systolic and diastolic blood pressure (P<0.0001). After age adjustment, for every kilogram gained over 6 years, risk of developing the NCEP Syndrome increased 22% (OR 1.22; 95% CI 1.18-1.25). NCEP-MS was incident in 3% of those with stable weight compared with 21% among those gaining >9 kg; 10% of those who lost >2 kg reverted to non-NCEP-MS. CONCLUSIONS: All continuous MS measures are linearly related to weight change, and MS can resolve with modest weight loss, underscoring the importance of maintaining lifelong normal weight.

Adult↗
PubMed2005

Polymorphisms of the receptor of advanced glycation endproducts (RAGE) and the development of nephropathy in type 1 diabetic patients.

OBJECTIVES: We investigated the association of the RAGE (Receptor for Advanced Glycation End products) exon3 gene polymorphisms with stages of nephropathy in type 1 diabetes. METHODS: The RAGE exon 3 genotype was assessed by Denaturing Gradient Gel Electrophoresis (DGGE) procedure in 487 type 1 diabetic patients with proliferative retinopathy subdivided into four groups according to their level of renal involvement and in 351 control subjects (GENEDIAB study). RESULTS: We reported here three main low frequency dimorphisms, previously submitted to data banks, Gly82Ser, Val89 CTC/CTG, and Arg77Cys. The genotype distribution of these polymorphisms was not statistically different in type 1 diabetic patients compared to healthy controls (p=0.37). Among the three described polymorphisms, only the RAGE Gly82Ser genotype frequency was significantly increased in the group with advanced nephropathy (11%) defined by a chronic renal failure compared to the three others groups: no nephropathy, 5%; incipient (microalbuminuria) 5%; established (macroalbuminuria), 2%) (P=0.04). The 82 Ser allele was identified as an independent risk marker for the stage of advanced nephropathy: adjusted odds ratio 3.17(95% CI 1,32-7,85, p=0.008). CONCLUSION: These data suggest that the 82 Ser allele of the RAGE gene is a risk allele for developing advanced nephropathy. This suggests that some RAGE gene polymorphisms may be associated with progression to diabetic advanced nephropathy in Caucasian type 1 diabetic patients.

Amino Acid Substitution↗
PubMed2005

Hepatic markers and development of type 2 diabetes in middle aged men and women: a three-year follow-up study. The D.E.S.I.R. Study (Data from an Epidemiological Study on the Insulin Resistance syndrome).

AIM: It has been shown, mainly in men, that gamma-glutamyltransferase (gammaGT) and alanine-aminotransferase (ALT) predict the development of type 2 diabetes. This study investigates the association between hepatic markers and the 3-year risk of diabetes. METHODS: Incident diabetes was studied in 2071 men and 2130 women without diabetes at baseline from the D.E.S.I.R. cohort. RESULTS: Adjusting on age, only gammaGT was predictive of diabetes in both sexes, whereas ALT and aspartate-aminotransferase (AST) were only predictive in men, and bilirubin was not predictive. After adjustment on classical confounding factors and on ALT activity, the odds ratios (OR) for incident diabetes increased across baseline gammaGT quartiles: 1, 3.1, 2.6, 5.0 in men (P<0.0003) and 1, 0.9, 3.2, 3.5 in women (P<0.01). The relations with ALT and AST were not significant after adjusting on gammaGT. Additional adjustment on markers of insulin resistance, BMI or fasting plasma glucose attenuated the risk associated with gammaGT in both sexes, and it remained significantly predictive only in the men. Pooling men and women, those with gammaGT above the median had adjusted ORs of developing diabetes of 13.7 (1.8-99.8) if WHR > =0.85 and 1.7 (0.6-4.8) if WHR<0.85 (interaction P<0.007). CONCLUSION: gammaGT was the main hepatic risk marker for type-2 diabetes in both sexes, especially in subjects with central adiposity.

Biomarkers↗
PubMed2005

Are insulin resistance, impaired fasting glucose and impaired glucose tolerance all equally strongly related to age?

BACKGROUND: Insulin resistance (IR) has been considered an underlying cause of impaired glucose tolerance (IGT) and impaired fasting glucose (IFG). Whether IR increases with age has been debated. We investigated the age-associated deterioration in the homeostasis model assessment (HOMA) of IR and in glucose metabolism. METHODS: Ten (nine including women) European studies contributed data on 6314 men and 6393 women aged 30-88 years. The cohort- and sex-specific top 25% of HOMA of IR in non-diabetic subjects was used to define HOMA-IR. RESULTS: Compared with subjects aged 50-59 years, the cohort- and body mass index-adjusted odds ratio (95% confidence interval) for HOMA-IR was 0.83 (0.64, 1.08), 0.87 (0.74, 1.03), 1.20 (1.02, 1.42) and 1.45 (1.10, 1.92) in men and 0.84 (0.62, 1.14), 0.91 (0.77, 1.09), 1.38 (1.19, 1.62) and 1.71 (1.35, 2.17) in women, respectively, aged 30-39, 40-49, 60-69 and > or = 70 years (P < 0.0001 for trend test). The same increasing trend was also observed for IFG. In contrast, the corresponding odds ratios for IGT increased linearly and more strongly with age, being 0.37 (0.22, 0.63), 0.67 (0.52, 0.87), 1.55 (1.24, 1.92) and 2.96 (2.13, 4.13) in men and 0.51 (0.31, 0.85), 0.66 (0.52, 0.86), 1.92 (1.57, 2.35) and 3.85 (2.89, 5.12) in women, respectively. CONCLUSIONS: Age is more strongly associated with IGT than with HOMA-IR or IFG in non-diabetic European populations.

Adult↗
PubMed2004

Prediction of the risk of cardiovascular mortality using a score that includes glucose as a risk factor. The DECODE Study.

AIMS/HYPOTHESIS: Risk scores have been developed to predict cardiovascular or coronary risk, and while most have included diabetes as a risk factor, none have included lower glucose concentrations, either at fasting or following a 2-h oral glucose tolerance test. This article develops 5- and 10-year risk scores for cardiovascular mortality that include glucose concentrations as well as known diabetes status. METHODS: Data is from the DECODE cohort: 16,506 men and 8,907 women from 14 European studies. The risk factors studied were as follows: age, fasting and 2-h glucose (including cases of known diabetes), fasting glucose alone (including cases of known diabetes), cholesterol, smoking status, systolic blood pressure and BMI. For an absolute risk score the 1995 country- and sex-specific cardiovascular death rates were used. RESULTS: In men, for both 5- and 10-year cardiovascular mortality, after adjusting for age and study centre, all studied risk factors, except BMI, were significantly associated with cardiovascular mortality (p<0.05). These results were unchanged in multivariate models with all factors included. In women, after adjusting for age and centre, glucose categories, systolic blood pressure and BMI were predictive of 5-year cardiovascular mortality. With all factors in the model, only age and glucose categories were predictive. In terms of 10-year cardiovascular mortality, smoking status and blood pressures were also predictive in the women. For men and women, the same scores were used for the risk factors, except for age and glucose categories where the hazard ratios differed significantly. CONCLUSIONS/INTERPRETATION: Including glucose concentrations as well as diabetic status provides quantitative information on cardiovascular risk prediction.

Adult↗
PubMed2004

Creating a pandemic of prediabetes: the proposed new diagnostic criteria for impaired fasting glycaemia.

AIMS/HYPOTHESIS: In November 2003 the American Diabetes Association expert committee on the diagnosis and classification of diabetes mellitus suggested a revision of the diagnostic criteria for IFG, lowering the diagnostic threshold from 6.1 to 5.6 mmol/l. The aim of the present study was to evaluate the consequences of this change with respect to: (i) the prevalence of IFG in five different countries; (ii) the concordance between IFG and IGT (classification of individuals); and (iii) the cardiovascular risk profile of these groups. Finally we discuss the likelihood that intervention for cardiovascular risk and prevention strategies developed for individuals with IGT are applicable to subjects with IFG. METHODS: The first part of the study is based on the population-based Danish Inter99 study, where 6265 individuals, aged 30 to 60 years and without previously diagnosed diabetes, underwent an oral glucose tolerance test. The second part is based on the DETECT-2 project, in which studies from China, India, France and USA were used to analyse the impact of the proposed revision of the diagnostic criteria in different ethnic groups. RESULTS: The proposed change in diagnostic criteria would increase the prevalence of IFG in Denmark from 11.8 to 37.6%. The proposed IFG category would identify 60.0% of all subjects with IGT compared to 29.2% with the old criteria, but among individuals with the new IFG category only 18.5% would also have IGT. Individuals with isolated IFG had lower insulin levels and a lower cardiovascular risk profile with the proposed criteria compared with the current WHO criteria. Data from the DETECT-2 study confirmed the marked increase in the prevalence of IFG, and the estimated number of individuals in the age range 40 to 64 years with IFG in urban India, urban China and the USA would increase by 78%, 135% and 193% respectively. CONCLUSIONS/INTERPRETATION: The proposed revised diagnostic criteria will lead to a dramatic increase in the prevalence of IFG, but the concordance rate between IFG and IGT remains low. This new IFG group will have a more favourable cardiovascular risk profile than the current IFG group as defined by the WHO. This seriously questions whether the existing intervention strategies are applicable to the new category of individuals with IFG.

Adult↗
PubMed2004

The EGIR-RISC STUDY (The European group for the study of insulin resistance: relationship between insulin sensitivity and cardiovascular disease risk): I. Methodology and objectives.

AIMS/HYPOTHESES: Insulin resistance is thought to be a key predictor for the development of Type 2 diabetes mellitus and cardiovascular disease (CVD), a leading cause of morbidity and premature mortality in Europe. Insulin resistance is influenced by both genetic and lifestyle factors (e.g. obesity and physical inactivity). The RISC (Relationship between Insulin Sensitivity and Cardiovascular disease) Study is using the infrastructure of an extended European collaborative research group to study insulin resistance and CVD risk in 1500 healthy people aged 30 to 60 years from 20 centres in 13 countries. METHODS: Baseline measurements of glucose tolerance and insulin sensitivity are made by the oral glucose tolerance test and the euglycaemic insulin clamp, respectively; carotid artery intima-medial thickness (by ultrasound), ankle/brachial pressure index and electrocardiography will enable evaluation of subclinical CVD at baseline and at follow-up. Classic CVD risk factors, as well as socioeconomic and lifestyle factors will be recorded at baseline; samples for measurement of biochemical and genetic markers will be collected and stored for future analyses. Investigations will be repeated after 3 and 10 years to evaluate the relationship between insulin resistance and the development of atherosclerosis as measured by carotid artery intima-media thickness. Development of Type 2 diabetes, dyslipidaemia, obesity, hypertension and cardiovascular events are additional endpoints. CONCLUSIONS: This study will evaluate the importance of insulin resistance in the development of CVD and diabetes, and has implications for the development of prevention and treatment strategies.

Adult↗
PubMed2004

What does postprandial hyperglycaemia mean?

AIMS: The potential importance of postprandial glucose (PPG) control in the development of complications in Type 2 diabetes is much debated. The recent American Diabetes Association (ADA) consensus statement discussed the role of postprandial hyperglycaemia in the pathogenesis of diabetic complications and concluded that the relationship between PPG excursions and the well-established risk factors for cardiovascular disease (CVD) should be further examined. Using the ADA statement as a starting point and including the more recent American College of Endocrinology guidelines on glycaemic control, a panel of experts in diabetes met to review the role of PPG within the context of the overall metabolic syndrome, in the development of complications in Type 2 diabetes. RESULTS: Post-prandial hyperglycaemia is a risk indicator for micro- and macrovascular complications, not only in patients with Type 2 diabetes but also in those with impaired glucose tolerance. In addition, the metabolic syndrome confers an increased risk of CVD morbidity and mortality. The debate focused on the relative contributions of postprandial hyperglycaemia, the metabolic syndrome and, in particular, raised triglyceride levels in the postprandial state, to the development of cardiovascular complications of diabetes. CONCLUSIONS: The panel recommended that in the prevention and management of microvascular complications of Type 2 diabetes, targeting both chronic and acute glucose fluctuations is necessary. Lowering the macrovascular risk also requires control of (postprandial) triglyceride levels and other components of the metabolic syndrome.

Blood Glucose↗