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B Balkau

Publications and source records attributed to B Balkau.

At least 109 records · Page 6Linked to original sources

Risk factors and their identification. Third Part: Examples.

This is the final of a series of three articles in Diabete & Metabolisme which reviews the identification of risk factors of a disease, here: diabetes or complications of diabetes. In the first of the series [1], we gave the definition of a risk factor, along with measures of its force-relative risk and odds ratio, followed by the epidemiological definitions of the diseases: diabetes, coronary heart disease and hypertension. Risk factors were further discussed and we completed the discussion by some observations on the bias which can arise from a study or from its analysis, which can lead the researcher to the wrong conclusion. The three types of epidemiological studies which are used to determine whether factors are associated with a disease: observational or cross-sectional studies, cohort studies and case-cohort studies are described in the second of the series [2]. Examples were provided of each of these study types and their advantages and disadvantages were discussed. This final paper provides some examples of the study types and the identification of risk factors from the literature. The first examples involve diabetes and pancreatic cancer, the second birth weight and non-insulin dependent diabetes. Having found an association between a risk factor and a disease, we then discuss whether it can be considered to be a risk factor, and if so and whether it is likely to be a cause of the disease.

Adult↗

Ursodiol for the long-term treatment of primary biliary cirrhosis. The UDCA-PBC Study Group.

BACKGROUND: Ursodiol (ursodeoxycholic acid) therapy leads to major improvements in patients with primary biliary cirrhosis. The benefit of long-term treatment is uncertain. METHODS: We randomly assigned 145 patients with biopsy-proved primary biliary cirrhosis to receive ursodiol (13 to 15 mg per kilogram of body weight per day) (72 patients) or placebo (73 patients). After two years of follow-up, because of the benefit from ursodiol, all patients completing the study received ursodiol in an open trial and were monitored for two more years. The end points in the assessment of efficacy were as follows: progression of disease, as defined by the presence of hyperbilirubinemia, variceal bleeding, ascites, or encephalopathy; liver transplantation or a referral for that procedure; and liver transplantation (or a referral) or death. RESULTS: Disease progressed significantly less frequently in the ursodiol group than in the placebo group (P < 0.002; relative risk, 0.28; 95 percent confidence interval, 0.12 to 0.63). The probability of liver transplantation or a referral for that procedure and the probability of transplantation or death were significantly lower in the group assigned to ursodiol than in the group assigned to placebo (for transplantation alone, P = 0.003; relative risk, 0.21; 95 percent confidence interval, 0.07 to 0.66; for transplantation or death, P = 0.005; relative risk, 0.32; 95 percent confidence interval, 0.14 to 0.74). High bilirubin levels and, to a lesser extent, signs of cirrhosis at entry into the trial were predictive of disease progression, liver transplantation or a referral, and transplantation or death. CONCLUSIONS: Long-term ursodiol therapy slows the progression of primary biliary cirrhosis and reduces the need for liver transplantation.

Double-Blind Method↗

Blood glucose distribution and prevalence of diabetes in Hanoi (Vietnam).

Few epidemiologic surveys have been performed to assess the prevalence of diabetes in representative samples, and few data are available on the epidemiologic features of diabetes in Southeast Asia. We report the results of a 1990 study performed in the Hanoi area (Vietnam) on 4,912 subjects (95.0% of the eligible population), aged 15 years or over, selected by a stratified random cluster procedure using the 1989 census list. A two-step design was used: 1) screening for diabetes by measuring capillary blood glucose (CBG) before dinner with a Glucometer II device; and 2) for subjects with a CBG measurement of > or = 105 mg/dl, a diagnostic test on the following morning, using a 75-g oral glucose tolerance test and World Health Organization criteria (93.9% of the positive screenees took this test). CBG values before dinner were unimodally distributed and skewed to the right, increasing with age in both sexes. Women had a significantly higher level of age-adjusted CBG than did men before dinner (p < 0.0001) as well as when fasting (p < 0.0001) and 2 hours after the oral glucose tolerance test (p = 0.013). The prevalence of diabetes was 1.2% (95% confidence interval (CI) 0.9-1.5) and of impaired glucose tolerance, 1.6% (95% CI 1.3-2.0). Women had a significantly higher age-adjusted prevalence of diabetes than did men (relative risk = 2.3; 95% CI 1.3-4.1). Of the 63 diabetic subjects, nine (14.3%) had been diagnosed before the study, only one was obviously insulin dependent, and only one was obese with a body mass index of > or = 27 kg/m2. The subjects living in the urban areas had higher levels of fasting and 2-hour CBG and a higher diabetes prevalence than did the rural inhabitants (relative risk = 1.3; 95% CI 1.04-3.23). Diabetes appears to be a rare disease in the Hanoi area (1.4% for subjects aged 30-64 years, after age standardization using the Segi distribution), affecting women two times as often as men. Typical insulin-dependent (type I) or obese non-insulin-dependent (type II) diabetes mellitus patients are uncommon.

Adolescent↗

Predictive factors in ursodeoxycholic acid-treated patients with primary biliary cirrhosis: role of serum markers of connective tissue.

The aim of this study was to define factors predictive of the onset of the terminal phase, defined by hyperbilirubinemia or the occurrence of a severe clinical complication, in patients with primary biliary cirrhosis treated with ursodeoxycholic acid. The 97 primary biliary cirrhosis patients in this study participated in a 2-yr clinical trial. Four of the 49 patients treated with ursodeoxycholic acid (13 to 15 mg/kg/day) entered the terminal phase of the disease, compared with 9 of the 48 patients assigned to placebo. In addition to clinical, conventional biological and histological parameters, we analyzed three serum markers of connective tissue components--type III procollagen aminoterminal peptide, hyaluronic acid and laminin. In the ursodeoxycholic acid-treated group, hyaluronic acid, type III procollagen aminoterminal peptide, bilirubin and splenomegaly were the factors most closely associated with entry into the terminal phase of the disease. In multivariate analysis, after adjustment for age, the hyaluronic acid level was the only predictive factor. In the placebo-treated group, the bilirubin level, total bile acid level, Mayo score, type III procollagen aminoterminal peptide, hyaluronic acid, splenomegaly and pruritus were associated with aggravation of disease. In multivariate analysis, high bilirubin level, high type III procollagen aminoterminal peptide or hyaluronic acid levels and low prothrombin time independently implied poor prognosis. In conclusion, when patients with primary biliary cirrhosis are treated with ursodeoxycholic acid, bilirubinemia loses, in part, its predictive value. It is replaced by hyaluronic acid and type III procollagen aminoterminal peptide. This suggests that models used in deciding on the need for liver transplantation require adaptation for patients receiving ursodeoxycholic acid.

Adult↗

Serum bile acids and cholestasis in alcoholic hepatitis. Relationship with usual liver tests and histological features.

Cholestasis is a biochemical and/or histological feature observed in some patients with alcoholic liver disease and is mainly related to alcoholic hepatitis. Accumulation of bile acids in the liver could be pathogenic in alcoholic hepatitis. The aim of this study was to assay serum bile acids in patients with alcoholic hepatitis and to assess the relationship between these parameters, the usual liver tests and the histological features of alcoholic hepatitis. Thirty-six patients (median 51 years, 19 females and 17 males) with biopsy-proven alcoholic hepatitis were included in the study. Cirrhosis was present in 27 patients. Serum bile acids were assayed by high performance liquid chromatography. Three histological scores (alcoholic hepatitis, fibrosis, and cholestasis) were established on each liver sample by two independent pathologists. Serum bile acid concentrations were increased in 35 patients (97%). The median concentration of total serum bile acids was 41.6 mumol/l (range 3-293), with an increase in primary bile acids (95.7% of total bile acids), mainly chenodeoxycholic acid (median 27.5 mumol/l, range 3-184). In contrast, serum bilirubin levels were increased in only 26 patients (72%). Histological cholestasis was present in 14 patients (38%). There was no significant correlation between the alcoholic hepatitis and cholestasis scores (r = 0.01, p = 0.9). A significant correlation was noted between the alcoholic hepatitis score and serum total bile acid (r = 0.34, p = 0.04), cholic acid (r = 0.38, p = 0.03) and chenodeoxycholic acid (r = 0.32, p = 0.05) levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Relationship between procollagen III aminoterminal propeptide and hyaluronan serum levels and histological fibrosis in primary biliary cirrhosis and chronic viral hepatitis C.

The diagnostic values of aminoterminal propeptide of type III procollagen and hyaluronan serum levels were compared as markers of liver fibrosis in two chronic liver diseases of different etiologies and pathophysiologies, namely primary biliary cirrhosis and chronic viral hepatitis C. The results were analysed in terms of the histological extent of fibrosis. Both serum procollagen-III peptide and hyaluronan were elevated in patients with primary biliary cirrhosis and chronic viral hepatitis C (p < 0.0001) relative to control values. A positive correlation was found between serum procollagen-III peptide levels and the histological grade of fibrosis in primary biliary cirrhosis (p < 0.001) but not in chronic viral hepatitis C, while a strong correlation was found between serum hyaluronan levels and histological fibrosis in both primary biliary cirrhosis and chronic viral hepatitis C (p < 0.001), independent of age. These results suggest that, in chronic liver diseases, serum hyaluronan levels could be an important indicator of the extent of fibrosis and should be assayed to monitor the response to treatment in controlled clinical trials.

Adult↗

Maternal effect and familial aggregation in NIDDM. The CODIAB Study. CODIAB-INSERM-ZENECA Study Group.

Non-insulin-dependent diabetes mellitus (NIDDM) is known to have a strong genetic basis, but the mode of inheritance is still unknown. Recent studies have suggested that maternal inheritance is important; this complicates the transmission pattern of NIDDM. In our study, the familial aggregation of diabetes and the maternal effect were investigated through three generations. The CODIAB Study recruited 536 NIDDM patients between 35 and 74 years of age from 10 diabetes centers in France. Familial aggregation was confirmed: among 218 NIDDM patients, 66% had at least one diabetic relative. Mothers were implicated 2 times more frequently than fathers (P < 0.001). This maternal effect was confirmed because more diabetic cases were noted among maternal than paternal aunts and uncles (P < 0.02). When we considered the next generation, women had more diabetic offspring than men (P < 0.01). Other factors susceptible to modify the familial aggregation were considered. The maternal effect was not significantly related to the patients' ages (P > 0.2). The genetic component was more important when the diagnosis was made earlier, but the maternal effect was homogeneous (P > 0.3). In conclusion, we found a familial aggregation of diabetes that suggests a strong genetic component with a mode of inheritance that may be influenced by a maternal environment.

Adult↗

Epidemiology of peripheral arterial disease.

With the aging of the population of most developing nations, arteriosclerosis is becoming a major health problem. Although much research has concentrated on the coronary and cerebral forms of the disease, peripheral arterial disease has received little attention from epidemiologists. The "Rose questionnaire" has been used extensively to diagnose intermittent claudication; however, the current method of choice for the diagnosis of peripheral arterial disease in epidemiologic studies is the ankle brachial pressure index. The prevalence of intermittent claudication, diagnosed by the Rose questionnaire, differs according to age, sex, and geographical location varying between 0.4 and 14.4%; similar variability (from 4.2 to 35%) is seen for disease diagnosed by the ankle brachial pressure index. The major risk factor for peripheral arterial disease is cigarette smoking; hypertension and diabetes have been identified as risk factors in a number of studies; impaired glucose metabolism, dislipidemia, degree of physical activity, and coagulation factors have been identified in some populations. The coexistence of cardiocerebrovascular and peripheral vascular diseases enhances the risk of early death, which is more than double that in the general population: The most frequent cause of death is myocardial infarction. More work is required to document the natural history of the disease, the risk factors for its progression, its relationship with cardiovascular disease, and the effect of intervention strategies.

Age Factors↗

The epidemiology of coronary heart disease in glucose-intolerant and diabetic subjects.

Diabetes mellitus is usually recognized as a major risk factor for coronary heart disease (CHD) morbidity and mortality. As chronic hyperglycaemia defines diabetes mellitus, it is logical to think that hyperglycaemia itself is related to these complications. But, in diabetic patients, there appears to be no relation between CHD and the specific characteristics of diabetes, namely the duration of the disease and the level of blood glucose. Moreover, in the UGDP trial, the group of patients with the best-controlled glycaemia failed to demonstrate a reduction in CHD death, in comparison with the group with poor blood-glucose control. These results are reinforced by the data from 15 prospective studies, which failed to demonstrate a homogeneous and significant increase in CHD risk with asymptomatic hyperglycaemia. Coronary heart disease mortality depends on a constellation of risk factors which are interrelated to some extent; one of the risk factors, namely blood glucose, is not an independent risk factor, nor is diabetes mellitus. In patients with abnormal glucose tolerance, the factors contributing to CHD risk are hypertriglyceridaemia and also a central fat distribution. This central fat distribution could explain the low CHD risk in nondiabetic women, which contrasts with the high risk in diabetic women, who are characterized by central adiposity, as are diabetic men. Björntorp hypothesized that intra-abdominal fat, which has an exceedingly sensitive lipid mobilization capacity, could play a key role in the development of the cluster of metabolic abnormalities that are present in the plurimetabolic syndrome. Hyperglycaemia, one of the anomalies of the syndrome, could be an 'innocent bystander' rather than a 'partner in crime', in the manifestations of CHD.

Coronary Disease↗

Limitations of the correlation coefficient in the validation of diet assessment methods. CODIAB-INSERM-ZENECA Pharma Study Group.

Dietary assessment methods usually are validated one against the other, using the correlation coefficient between the methods to assess agreement. The correlation coefficient, however, is only an indicator of relative agreement and depends on the range of intakes. As this dependence can lead to misinterpretation, we propose that the standard deviation of the difference between methods should be used as an indicator of absolute agreement and the standard deviation of their average as an indicator of the range of intakes. We illustrate this method in a validation study of a diet history against a 3-day diet record in 58 non-insulin-dependent diabetes mellitus patients. A re-analysis of studies from the literature validating food frequency questionnaires against diet records showed that the absolute agreement between methods is very consistent and that the differences in the correlation coefficients are mostly due to the selection of subjects.

Adult↗

Risk factors for early death in non-insulin dependent diabetes and men with known glucose tolerance status.

OBJECTIVE: To identify risk factors for all cause mortality according to glucose tolerance status. DESIGN: Cohort study with an average 15.6 years' follow up. SETTING: Paris, France. SUBJECTS: 7166 working men aged 44-55 in 1968-72 in the Paris prospective study cohort, with non-insulin dependent diabetes or known result of two hour 75 g oral glucose tolerance test. MAIN OUTCOME MEASURES: Risk factors for death from all causes. RESULTS: 128 men were known to be diabetic, 180 had diabetes diagnosed, and 697 had impaired glucose tolerance diagnosed. Compared with normoglycaemic men the relative risks of death in these groups were 2.0 (95% confidence interval 1.4 to 3.0), 2.7 (2.0 to 3.6), and 1.6 (1.3 to 2.0) respectively. Obesity, smoking, high blood pressure, and high non-esterified fatty acid concentration were risk factors for death in all subjects and were unaffected by glucose tolerance. The risks for fasting and two hour insulin concentrations and mean corpuscular volume were two times higher in known diabetic men than in men not known to be diabetic. Central obesity was significant only in men not known to be diabetic (1.6 (1.4 to 1.9)). In known diabetic men a two hour glucose concentration higher than 11.1 mmol/l carried a relative risk of death of 3.8 (1.4 to 9.4). CONCLUSIONS: Diabetic men have similar risk factors for early mortality to other men but are at higher risk from hyperinsulinaemia, hyperglycaemia, and high mean corpuscular volume.

Adult↗

European study of the certification and coding of causes of death of six clinical case histories of diabetic patients. EURODIAB Subarea C Study Group.

This study was designed to investigate the large differences in diabetes mortality rates in Europe. In each of the participating countries (France, Germany, The Netherlands, Northern Ireland-UK, Republic of Ireland, Romania, Scotland-UK, Switzerland) a random sample of certifying physicians was asked to certify the causes of death of six case histories which described the deaths of diabetic patients; the responses from an average of 220 physicians per country were analysed. These registered causes were then coded nationally and the underlying cause was compared with that following a central recoding. Overall 28% of the physicians surveyed recorded diabetes on the death certificate as the underlying cause of death--France was 25% below this overall average and Germany 21% above. The national coding of diabetes as the underlying cause of death differed from the central recoding with a comparative undercoding of almost 40% in Romania, 30% in Northern Ireland and 25% in Switzerland; in contrast, there was an overcoding of diabetes by 80% in The Netherlands and 60% in the Republic of Ireland. After adjusting for central recoding, in part an adjustment for certification habits, the national coding from this simulation study was able to explain 35% of the variation in the diabetes mortality rates. With such differences in the coding of diabetes, the currently published mortality rates for diabetes are not directly comparable between European countries; some suggestions are made for the reduction of the intercountry differences in the collection and analysis of mortality data for diabetes.

Abstracting and Indexing↗

The relationship between behavioural pattern, overall and central adiposity in a population of healthy French men.

The relationship between obesity, both general obesity (BMI) and central obesity (measured by the ratio of iliac and thigh circumferences), and a behavioural pattern, which includes alcohol consumption, smoking, stress and lack of sporting activity, was investigated in 467 middle-aged French working men. BMI and central obesity were closely correlated (r = 0.34). Alcohol consumption was positively associated with central obesity (P < 0.001) but it did not significantly influence BMI. BMI decreased with cigarette smoking (P < 0.001), but central obesity only increased significantly after adjustment for BMI (P < 0.05); thus for a given BMI, smoking was associated with a greater degree of central adiposity. Resting heart rate (considered as a measure of stress) was positively associated with both BMI and the iliac-thigh ratio (P < 0.01, P < 0.05), the latter association being due to general obesity. Sporting activity and BMI were only marginally associated (P < 0.07) but central obesity decreased with activity (P < 0.01). Jointly, alcohol consumption, cigarette smoking, the resting heart rate and sporting activity explained 8% of the variance in the iliac-thigh ratio; after adjustment for BMI these behavioural variables still explained 6% of the variance. Central adiposity, which has recently been described as a risk factor for coronary heart disease, non-insulin dependent diabetes and hypertension, was significantly associated with a potentially modifiable behavioural pattern.

Adipose Tissue↗

Treatment of severe alcoholic hepatitis by infusion of insulin and glucagon: a multicenter sequential trial.

Severe alcoholic hepatitis is still a therapeutic challenge. It has been recently advocated that a 3-wk infusion with insulin and glucagon reduces its short-term mortality rate. A multicenter, randomized, single-blind, sequential trial was designed to compare this treatment with placebo. The triangular boundary was defined with alpha = 0.05, beta = 0.10 and estimated survival at 4 wk of 50% with placebo, 75% with treatment. Patients with biopsy-proven severe alcoholic hepatitis (presence of one or more of three criteria: encephalopathy, prothrombin activity less than or equal to 50%, bilirubinemia greater than or equal to 100 mumol/L) were randomized into two groups; one treatment group received an infusion (12 hr/day) of an association of insulin (30 IU) and glucagon (3 mg), and a control group received an infusion of glucose. Treatments were administered during a 3-wk period, and the mortality rate was noted at 4 wk. The decision to discontinue the trial was reached on the basis of results from the first 44 patients. Overall results were assessed in the 72 patients included at the time of this decision (treatment group: n = 37; control group: n = 35). Fifty-three patients had cirrhosis. No significant differences were noted between the two groups at inclusion on the basis of clinical, laboratory and histological criteria. The mortality rate was not significantly different in the two groups; 10 patients (27%) in the treatment group and 5 patients (14%) in the control group died. Causes of death were similar in the two groups and consisted primarily of gastrointestinal hemorrhage, hepatic failure and infectious events.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Cardiovascular and alcohol-related deaths in abnormal glucose tolerant and diabetic subjects.

The aim of this study was to compare the causes of death and parameters related to alcohol consumption, between subjects diagnosed as diabetic, clinically by their general practitioner, or glucose intolerant and in particular as diabetic, using the epidemiological criteria of an abnormal glucose level following an oral glucose tolerance test. The subjects in this study were 7035 working men, aged between 44 and 55 years, who attended the first follow-up examination of the Paris Prospective Study, between 1968 and 1973. They were classified as 'clinically diagnosed diabetic' or, following an oral glucose tolerance test and the World Health Organisation criteria, as having 'oral glucose tolerance test diagnosed diabetes', impaired glucose tolerance or normoglycaemia. The relative risk of death by cirrhosis, in comparison with the normoglycaemic group, was 21 (95% confidence interval: 9.1-49) in the group diagnosed diabetic by the oral glucose tolerance test, significantly different (p less than 0.02) from the group diagnosed diabetic clinically 3.1 (0.41-24); factors indicative of excessive alcohol consumption at baseline differed accordingly. In contrast, the relative risks for death by coronary heart disease were similar, 2.1 (1.0-4.1) and 2.7 (1.4-5.4) respectively; all of the factors defining the insulin resistance 'Syndrome X' (hyperglycaemia, hyperinsulinaemia, hypertension, hyperlipidaemia and also central obesity) and predictive of coronary heart disease were elevated in both groups of diabetic subjects. 'Diabetes', as diagnosed by the oral glucose tolerance test, might be the consequence of excessive alcohol consumption which could lead to insulin resistance, then to coronary heart disease, as well as to alcohol-related diseases.

Adult↗

Death certificate coding practices related to diabetes in European countries--the 'EURODIAB Subarea C' Study.

The objective of this study was to compare and analyse coding practices for diabetes mortality data in nine European countries (Belgium, Republic of Ireland, France, Germany, Malta, The Netherlands, Northern Ireland, Scotland and Switzerland). In each country, a sample of 200 coded death certificates, which mentioned diabetes, was randomly sampled. All death certificates were recoded at the WHO Collaborating Centre for the Classification of Diseases in the French language. The results show wide differences between national coding and central coding. Discrepancies in the underlying cause of death existed at the 3-digit coding level for 26% of all death certificates and for 44% at the 4-digit level. Coding in Northern Ireland and Malta was characterized by a marked tendency to choose diabetes less frequently. In contrast, in The Netherlands and, to a lesser extent, in the Republic of Ireland and France, diabetes was more frequently selected as the underlying cause of death. Most of the differences concerned the coding of an association involving diabetes and circulatory system diseases. In some countries, these coding differences influence the reported level of diabetes mortality. For Northern Ireland and Malta, the number of certificates with diabetes as the underlying cause of death was more than doubled after central recoding and for The Netherlands, in contrast, it was almost halved. To explain the differences a number of factors are considered: a lack of information from the International Classification of Diseases (ICD), on the application of the coding rules, between-country differences in cause of death certification practices, a divergence of opinion about the causal role of diabetes when it is associated with other conditions, a lack of homogeneity between countries in data collection procedures.(ABSTRACT TRUNCATED AT 250 WORDS)

Cause of Death↗

Certification of cause of death in French diabetic patients.

STUDY OBJECTIVE: The aim was to assess the level of mortality related to diabetes in France. In other countries, an underrecording of diabetes on the death certificates of diabetic patients has been reported. DESIGN AND SETTING: Estimated death rate of diabetic patients was calculated using (a) the actual number of death certificates where diabetes was registered either as an underlying or as a contributory cause of death, and (b) estimates of the prevalence of diabetes in the population, by sex and age group, from which expected numbers of diabetic deaths were determined. Standardised mortality ratios were calculated using 1988 French mortality statistics as reference. MAIN RESULTS: The estimated standardised mortality ratio for diabetic subjects, with diabetes registered as the underlying cause, was 0.36. This standardised mortality ratio increased to 0.92 if both the underlying and contributory causes were considered. The estimated death rate, by sex and age group, implies that diabetes has a protective effect between the ages of 45 and 64 years, particularly in men. CONCLUSIONS: Evidence suggests that diabetes is completely omitted on the death certificates of many diabetic subjects, especially for those between the ages of 45 and 64 years. Using mortality statistics underestimates the prevalence of diabetes and its effects on public health. The difference in diabetes mortality between countries will not be reliable until there is a better registration of the causes of death in diabetic patients, and contributory as well as the underlying cause are coded and published.

Adult↗