Risk factors for NIDDM in white population. Paris prospective study.

Risk factors for non-insulin-dependent diabetes mellitus (NIDDM) were assessed in a population of 5042 middle-aged white men, initially nondiabetic, who were followed 3 yr. The subjects were participants in the Paris Prospective Study I. Sixty-three subjects developed diabetes during the follow-up. Plasma glucose concentration in the years before the occurrence of the disease was a major risk factor. Subjects with normal glucose tolerance but elevated fasting plasma glucose exhibited a similar risk of developing NIDDM as did subjects classified as having impaired glucose tolerance on the basis of 2-h postload glucose. In a multiple logistic regression, a high fasting plasma insulin concentration and a low 2-h plasma insulin concentration after a glucose load in association with a high body mass index were independent predictors of conversion to NIDDM from impaired glucose tolerance. Previously, this result had been found only in Nauruans, Pima Indians, and Japanese. This demonstrates for the first time in a white population that a high fasting and low 2-h insulin concentration is predictive of conversion to NIDDM from impaired glucose tolerance.

Abnormal color vision and reliable self-monitoring of blood glucose.

Color vision was assessed in 103 insulin-dependent diabetic patients using the Farnsworth-Münsell 100-Hue Test. All showed color vision impairment. Thirty-four had true dyschromatopsia while 22 suffered from tritanopia or other axial defects. We evaluated how accurately diabetic patients could monitor their own blood glucose by asking them to read a series of 30 precalibrated BM Test Glycemic Strips (Chemstrip, Boehringer, Mannheim, West Germany) without a meter. Patients with axial defects performed least well regardless of 100-Hue scores. Reading accuracy of patients with no axial defects was strongly correlated to 100-Hue scores, although patients having dyschromatopsia were consistently hesitant about their readings. Our results suggest that self-monitoring of blood glucose without a meter is indicated only after color vision has been examined by the 100-Hue Test. Self-monitoring should be voided with patients suffering from axial defects or having unsatisfactory 100-Hue scores.

Reproducibility of the diagnosis of diabetes over a 30-month follow-up: the Paris Prospective Study.

OBJECTIVE: To describe the change in diabetic status over 30 months. RESEARCH DESIGN AND METHODS: Cohort study of 5,400 Caucasian men from the Paris Prospective Study, aged 44-55 years, who were not known as having diabetes at baseline. Oral glucose tolerance tests were performed at baseline and after 30 months. RESULTS: At baseline, diabetes was diagnosed in 2.9% of the men by fasting plasma glucose (FPG) > or =7.0 mmol/l and in 0.9% by isolated postchallenge hyperglycemia (IPH) (FPG <7.0 mmol/l and 2-h plasma glucose concentration > or =11.1 mmol/l), i.e., one in four of all men with newly diagnosed diabetes. Thirty months later, 42% of the men with diabetes diagnosed by FPG reverted to nondiabetic status, compared with 72% of those with diabetes diagnosed by IPH (P < 0.0001). For the men with diabetes diagnosed by FPG at baseline, diabetes had been diagnosed by a physician at 30 months in 11.5%, in contrast to only 3.9% of those with diabetes diagnosed by IPH (P < 0.05). For the 51 men with diabetes diagnosed by IPH at baseline, those who reverted to nondiabetic status had a lower frequency of family history of diabetes (P < 0.1), a higher mean corpuscular volume (P < 0.08), and a significantly higher total cholesterol concentration (P < 0.006) at baseline; in contrast, for the 156 men with diabetes diagnosed by FPG at baseline, the men who reverted to nondiabetic status and those who remained diabetic had similar characteristics. CONCLUSIONS: In this epidemiological study, diabetes diagnosed by one FPG concentration was more stable than diabetes diagnosed by one IPH; in clinical practice, the diagnosis of diabetes requires confirmation of the hyperglycemia.

From policemen to policies: what is the future for 2-h glucose? The Kelly West Lecture, 2000.

OBJECTIVE: To describe the characteristics and vital prognosis of men with diabetes diagnosed by one fasting plasma glucose (FPG) concentration > or =7.0 mmol/l, with diabetes diagnosed by one isolated postchallenge hyperglycemia (IPH) (FPG <7.0 mmol/l and a 2-h plasma glucose concentration > or =11.1 mmol/l), or with impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS: This study involved a cohort of 6,881 Caucasian nondiabetic men from the Paris Prospective Study, aged 44-55 years, who were followed for cause of death for 20 years. RESULTS: Diabetes was diagnosed in 4.3% of the men (1.0% diabetes diagnosed by IPH), and IGT was diagnosed in 9% of the men. At baseline, the men with diabetes diagnosed by IPH had a lower cardiovascular risk profile than those with diabetes diagnosed by FPG, as did the men with IGT and a normal fasting glucose level (<6.1 mmol/l, IGT and normal fasting glucose), compared with men with impaired fasting glucose (6.1-6.9 mmol/l, IGT and impaired fasting glucose [IFG]). At 20 years of follow-up, all-cause and cancer death rates were higher in men with diabetes diagnosed by IPH than in men with diabetes diagnosed by FPG (55 vs. 44%, P < 0.1 and 31 vs. 17%, P < 0.01, respectively) but were not significantly different for coronary causes (6 vs. 11%). Men with IGT and normal fasting glucose also had significantly higher cancer death rates than men with IGT and IFG. CONCLUSIONS: The most likely explanation for the high cancer and low coronary death rates is that men with diabetes diagnosed by IPH consumed alcohol; the men in this study drank 49 g of pure alcohol on average per day, equivalent to 0.6 l of wine. If these results are confirmed by other prospective studies, screening subjects for isolated postchallenge hyperglycemia may not be worthwhile.

Quantification of early subclinical limited joint mobility in diabetes mellitus.

Limited joint mobility (LJM) has been described in juvenile diabetic patients by Rosenbloom et al.; similar abnormalities are also present in adult diabetes. This modification may be associated with a high risk of microvascular complications. We tested the use of a goniometer in measuring subclinical joint limitation in 50 adult diabetic patients without overt, i.e., clinically evident, LJM as described by these authors. This diabetic population was compared with 118 nondiabetic adult controls. We found significant changes in hand mobility between the two groups for wrist flexion and extension of the 3rd and 5th fingers (P less than 0.001). Age was correlated to wrist flexion, wrist extension, and proximal interphalangeal flexion of the little finger. Wrist extension correlated with duration of diabetes (r = -0.37, P less than 0.01). Heavy manual activities significantly limited all motions except wrist and 5th finger metacarpophalangeal flexion. Early systematic examination by goniometry may prove to be a sensitive, quantitative, and inexpensive way of detecting joint stiffness at an early stage.

Prognostic factors in polyarteritis nodosa and Churg-Strauss syndrome. A prospective study in 342 patients.

We undertook this study to determine the clinical, biologic, immunologic, and therapeutic factors associated with the prognoses of polyarteritis nodosa (PAN) and Churg-Strauss syndrome (CSS). Three hundred forty-two patients (260 with PAN, 82 with CSS) followed from 1980 to 1993 were included in a prospective study on prognostic factors. Two hundred eighty-eight of these patients were included in the prospective studies on PAN and CSS. Items to be considered for analysis were collected at the time of diagnosis, during the acute phase of the disease. A survival curve was plotted for each clinical and biologic symptom observed in PAN or CSS. Each treatment arm of the prospective therapeutic trials was also tested: 1) prednisone (CS) + oral cyclophosphamide (CYC) + plasma exchanges (PE) versus CS E, 2) CS + PE versus CS, 3) CS + oral CY versus CS + pulse CY, 4) CS + pulse CY + PE versus CS + pulse CY in severe PAN and CSS, and 5) PE + antiviral agents after short-term CS in hepatitis B virus-related PAN. Of the parameters thus evaluated, the following had significant prognostic value and were responsible for higher mortality: proteinuria > 1 g/d (p < 0.0001; relative risk [RR] 3.6), renal insufficiency with serum creatinine > 1.58 mg/DL (p < 0.02; RR 1.86), GI tract involvement (p < 0.008. RR 2.83 for surgery). Cardiomyopathy and CNS involvement were associated with a RR of mortality of 2.18 and 1.76, respectively; these were not statistically significant. Similar survival rates were obtained with the prospectively tested therapies. The five-factors score (FFS) we established considered the prognostic factors creatinemia, proteinuria, cardiomyopathy, GI tract involvement, and CNS signs. Multivariate analysis showed that proteinuria (due to vascular or glomerular disease) and GI tract involvement were independent prognostic factors. When FFS = 0 (none of the 5 prognostic factors present), mortality at 5 years was 11.9%; when FFS = 1 (1 of the 5 factors present), mortality was 25.9% (p < 0.005); when FFS > 2 (3 or more of the 5 factors present), mortality was 45.95% (p < 0.0001 between 0 and 2, p < 0.05 between 1 and 2). We conclude that an initial assessment of PAN or CSS severity enables outcome and mortality to be predicted. The FFS is a good predictor of death and can be used to help the clinician choose the most adequate treatment. Renal and GI signs are the most serious prognostic factors.

Time trend in height, weight, and obesity prevalence in school children from Northern France, 1992-2000.

OBJECTIVE: The aim of this study was to evaluate the changes in height, weight and in the prevalence of overweight and obesity between 1992 and 2000 in children living in two towns of northern France. METHODS: Two cross-sectional studies were performed in every pre-school (last section) and primary schools of the two towns in 1992 (383 girls and 421 boys enrolled) and 2000 (296 girls and 305 boys). Children were 5 to 12 year old in both studies. MEASUREMENTS: Body height and weight were measured, and BMI was calculated (weight/height(2)). Prevalence of overweight and obesity was determined according to the gender- and age- specific cut-offs of the new international reference (IOTF). We also used the 90(th) and the 97(th) percentiles of the French reference gender- and age-specific BMI curves to define two grades of overweight. RESULTS: After adjustment for age, boys were on average 1.5 cm taller in 2000 than in 1992 (p<0.001), and the same trend was observed in girls (+ 0.9 cm, p<0.075). Height-adjusted or age-adjusted weight and BMI were significantly higher in 2000 than in 1992. In girls, obesity defined by IOTF criteria increased from 1.6 to 4.4% (p<0.03) and overweight from 14.1 to 18.6% (p<0.11). In boys, the change in prevalences was significant only when the less stringent criteria (i.e. the 90(th) percentile of French references) was used (13.8% in 1992 vs 20% in 2000, p=0.03). CONCLUSION: Over an 8 years period, there was an increase in height and BMI in both boys and girls. These results show that the increase in the prevalence of obesity is accompanied by a global trend of accelerated growth.

Infant-feeding patterns are related to blood cholesterol concentration in prepubertal children aged 5-11 y: the Fleurbaix-Laventie Ville Santé study.

OBJECTIVE: Several studies, mainly in animals, but also in humans, have shown that diet in infancy is associated with differences in blood cholesterol concentrations later in life. The objective was to examine this relationship in children aged 5-11 y after taking into account their current diet and parental hypercholesterolemia. SETTING AND SUBJECTS: 251 prepubertal boys and 223 prepubertal girls enrolled in the schools in two little towns in northern France. DESIGN AND METHODS: Cross-sectional evaluation including measurements of cholesterol concentrations on capillary blood and a single weekday food intake record. Infant feeding patterns were obtained by questionnaire given to the mothers. RESULTS: 50% of the children had been breast-fed for a median duration of less than 2 months. Cow's milk was introduced in the diet as whole milk for 33% of the children. After adjustment for age, height, and sibship, capillary cholesterol concentration was lower in boys who had been breast fed (geometric mean: 4.4, 95% confidence interval of the mean: 4.2-4.6 mmol/L) than in those fed with formula (4.7, 4.5-4.8 mmol/L, P<0.03). In girls, breastfeeding had no significant effect on blood cholesterol concentration, which was associated with the type of cow's milk given in infancy: whole milk: 4.9 mmol/L (4.7-5. 2); totally or partially skimmed milk: 4.5 mmol/L (4.2-4.6), P<0.008. The current saturated fat and cholesterol intakes and parental hypercyholesterolemia were associated with current blood cholesterol concentration in children, but did not modify its relationship with infant feeding patterns. CONCLUSION: Results of the present study suggest that diet in infancy may have longstanding effect on lipid metabolism. SPONSORSHIP: The study was supported by funds from Eridania Béghin-Say, Groupe Fournier, Lesieur and Nestlé France, Roche Diagnostic and of the MGEN (Mutuelle Générale de l'Education Nationale, contract INSERM-MGEN #9158) and a grant from the Association de Langue Française pour l'Etude du Diabète et du Métabolisme (ALFEDIAM). European Journal of Clinical Nutrition (2000) 54, 114-119

Oral contraceptives, insulin resistance and ischemic vascular disease.

From a large prospective study on diabetes risks, 1112 professionally active, non-menopausal, non-pregnant, healthy women were cross-sectionally analysed according to their use of oral contraception. After adjustment for age, weight and diabetes risk factors, those taking the pill, compared to those who did not, had significantly higher fasting serum insulin, triglycerides and 2-h 75 g OGTT blood glucose levels. The insulin-resistance markers which have recently been cited as ischemic vascular disease risk factors should be carefully monitored in pill users.

[Does the size of esophageal varices have a prognostic significance in alcoholic cirrhosis?]. / La taille des varices oesophagiennes a-t-elle une signification pronostique au cours des cirrhoses alcooliques?

This study was designed to determine whether the size of esophageal varices were of prognostic value in patients with alcoholic cirrhosis. Esophageal varices were classified into 2 groups according to whether their size was larger or smaller than 4 mm. There was a total of 99 patients; 56 had small varices and 43 had large varices. Of the clinical and biological data collected at the time of determination of the size of the esophageal varices, only the duration of cirrhosis and the prevalence of gastrointestinal bleeding were significantly greater in patients with large esophageal varices. The one- and two-year cumulative rates of patients with large esophageal varices were 63 +/- 7 p. 100 and 42 +/- 8 p. 100, respectively; these results were not significantly different from those in patients with small esophageal varices, i.e. 68 +/- 6 p. 100 and 61 p. 100 respectively (p less than 0.5 for one-year survival; p less than 0.08 for two-year survival). Serum bilirubin and albumin as well as the presence of ascite were of significant prognostic value concerning death at two years while the presence of esophageal varices did not significantly increase the prognostic value of the above-mentioned variables (using Cox's regression model). In conclusion, the results of our study suggest that large esophageal varices, in spite of their association with a high incidence of gastrointestinal bleeding, do not influence prognosis at two years for patients with alcoholic liver cirrhosis.

[Diabetes, hyperglycemia, hyperinsulinemia and risk of cardiovascular mortality. Findings of the Paris Prospective Survey, 10 years later]. / Diabète, Hyperglycémie, Hyperinsulinémie et risque de mortalité cardiovasculaire. Données de l'Enquête Prospective Parisienne, 10 ans après.

The Paris Prospective Study is a long-term investigation of coronary heart disease (CHD) conducted on 7038 working men, aged 43-54 years and followed 11.2 years in mean. The first examination included a 0-2 h 75 g OGTT with measurement of plasma insulin and glucose levels, beside the major CHD risk factors. 651 deaths (CHD = 126) were recorded. The annual CHD mortality rates were respectively 1.4, 2.7 and 3.5 per 1000 for the 6055 normoglycaemic, 690 impaired glucose tolerance and 293 new and known diabetic subjects (1980 WHO classification) (p less than 0.001). It showed that the fasting plasma insulin was positively associated with risk independent of the other factors (p less than 0.05), whereas glucose tolerance, including overt diabetes, was not significantly associated. Thus, high insulin levels may constitute a more sensitive predictor of CHD than the degree of glucose intolerance and it could be useful to avoid excessive insulin plasma concentration, and even to lower its levels.

[Controlled cooperative trial. Secondary prevention of atherosclerosis-related cerebral ischemic accidents by aspirin dipyridamole. 2: Description of subjects at the beginning of the trial]. / Essai coopératif contrôlé "A.I.C.L.A." Prévention secondaire des accidents ischémiques cérébraux liés à l'athérosclérose par l'aspirine et le dipyridamole. 2e partie: Description des sujets à l'entrée dans l'essai.

This paper is the second devoted to the controlled trial "A.I.C.L.A." comparing aspirin, aspirin + dipyridamole and placebo in the secondary prevention of athero-thrombotic cerebral ischaemic events. It presents the description and distribution of baseline characteristics at entry. Six hundred and four patients (men: 70 p. 100, mean age : 63) were entered. Risk factors were distributed as follows: arterial hypertension: 63 p. 100, Diabetes: 24 p. 100, High blood lipids: 26 p. 100, high uric acid: 20 p. 100, hematocrit greater than 46 p. 100: 34 p. 100, cigarette smoking: 64 p. 100, angina pectoris and myocardial infarction: 15 p. 100, peripheral vascular disease: 7 p. 100, 37 p. 100 of patients had a stroke prior to entry. The ischemic event at entry occurred not more than one year prior to randomization and less than 3 months in 77 p. 100. It was much more often a completed stroke (84 p. 100) than a transient ischaemic attack (16 p. 100) and was referrable either to the carotid (46 p. 100) or the vertebrobasilar circulation (50 p. 100). On the whole patients are older and strokes more severe than in other similar studies. Randomization produced remarkably comparable treatment groups since almost no significant difference was observed between the 3 groups.

[The A.I.C.L.A. controlled cooperative trial. Secondary prevention of cerebral ischemic accidents due to atherosclerosis by aspirin and dipyridamole. 3: Results]. / Essai coopératif contrôle "A.I.C.L.A.". Prévention secondaire des accidents ischémiques cérébraux liés à l'athérosclérose par l'aspirine et le dipyridamole. 3e partie: Résultats.

As decided in the protocol, the AICLA study ended when all the 604 patients had completed a follow up of three years. Adhesion to the protocol and drug compliance were excellent. Side effects, particularly peptic ulcers and bleedings of various origins were more frequent in the 2 treatment groups containing aspirin. The number of fatal and non fatal cerebral infarction was 31 in the P group, 17 in the ASA group, and 18 in the ASA + D group. Taking into account the duration of follow up for each patient, these figures correspond to cummulate rates of 18 p. 100 in the P group and 10.5 p. 100 in the 2 others. Analysis with the Mantel Method showed: 1 - a difference at the 6 p. 100 level between the 3 groups and between P an AD; 2 - A difference at the 5 p. 100 level between P and A; 3 - No difference between A and AD; 4 - A difference at the 2 p. 100 level between the P group and the two treated groups taken together. Among other diseases occurring during the trial, the only significant difference concerned myocardial infarction, less frequent in the 2 treated groups (p less than 0.05). Subgroup analysis failed to show a significant sex difference in the efficacy of aspirin. It is concluded that, in patients such as those defined in the protocol, Aspirin (1 g) has a significant beneficial effect in the secondary prevention of atherothrombotic cerebral infarction.

[Lack of benefit of blood glucose autosurveillance in insulin-treated diabetics routinely followed up in a department specializing in diabetology]. / Absence de bénéfice de l'autosurveillance glycémique chez des diabétiques insulino-traités suivis en routine dans un service spécialisé en diabétologie.

Home blood glucose monitoring (HBGM) may be useful to achieve better metabolic control in type I diabetes. The aim of this study was to evaluate longterm results in a large population. A questionnaire was given to 282 routinely insulin-treated diabetics regularly attending our clinic. Home blood glucose testing was performed by 64.5% of the patients. Seventy nine percent of them continued to test urines. Mean HbA1 at the time of the visit was not statistically different in patients performing home blood glucose testing only (9.3 +/- 2.1%), in patients monitoring both blood and urines (9.2 +/- 2%), or urines only (9.3 +/- 1.7%) and in patients who did not practice self-monitoring (9.5 +/- 1.8%). The influence of HBGM on metabolic control as currently performed by diabetic patients in everyday life may be overemphasized. These disappointing results are mainly due to the fact that patients carry out passive home glucose testing and not home blood glucose monitoring which implies day-to-day adaptation of insulin dosage. Such an attitude seems to be due to incorrect selection of the patients, insufficient education and care and, for some patients, poor compliance with medical advice.

[Prevalence of smoking among diabetics and influence of tobacco on diabetic retinopathy]. / Prévalence du tabagisme chez les diabétiques et influence du tabac sur la rétinopathie.

Among 647 patent diabetics regularly followed who attended the out-patient clinic of a hospital Diabetology Department between December 1st, 1979 and June 30th, 1980, 35% were habitual smokers, 20% ex-smokers and 45% non-smokers. Insulin-treated diabetics did not smoke more than non insulin-treated diabetics. Only one-half of the smokers declared that they had been advised by a doctor to stop smoking. This study failed to demonstrate any effect of tobacco on the prevalence or severity of diabetic retinopathy.

[Controlled cooperative trial of secondary prevention of cerebral ischemic accidents caused by atherosclerosis, using aspirin and dipyridamole]. / Essai coopératif contrôlé de prévention secondaire des accidents ischémiques cérébraux liés à l'athérosclérose par l'aspirine et le dipyridamole.

Six hundred and four patients with atherothrombotic cerebral ischemic events (transient: 16% or completed: 84%) referable either to the carotid or to the vertebral-basilar circulation were entered into a double blind randomized clinical trial (AICLA) to determine whether aspirin (A) (1 g/day) or aspirin (1 g) + dipyridamole (225 mg) (AD) would produce a significant reduction in the subsequent (3 years) occurrence of fatal and non fatal cerebral infarction. Randomization produced remarkably comparable treatment groups and this good comparability was maintained throughout the study. Adherence to the protocol and drug compliance were excellent. Side effects, particularly peptic ulcers and bleedings of various origin, were significantly (p less than 0.03) more frequent in the two treatment groups containing aspirin. At the end of the study (3 years), the number of fatal and non fatal cerebral infarction was 31 in the P group (placebo), 17 in the A group and 18 in the AD group. Taking into account the duration of follow up for each patient, these figures correspond to cumulate rates of 18% in the P group and 10.5% in the 2 others. Analysis with the Mantel Method showed: a difference at the 6% level between the 3 groups and between P and AD; a difference at the 5% level between P and A; no difference between A and AD; a difference at the 2% level between the P group and the two treated groups taken together (A + AD).(ABSTRACT TRUNCATED AT 250 WORDS)

Body fat distribution and coronary heart disease mortality in subjects with impaired glucose tolerance or diabetes mellitus: the Paris Prospective Study, 15-year follow-up.

The Paris Prospective Study is a long-term, large-scale study of the factors predicting coronary heart disease in healthy middle-aged men. Subjects with impaired glucose tolerance or diabetes (not treated by insulin) at the first follow-up examination (n = 973) were selected from the total cohort for a separate analysis of the predictors of death from coronary heart disease. An index of body fat distribution, the iliac to thigh ratio, was entered into the list of potentially predictive variables, despite the fact that it had been measured one year before the first follow-up examination. After 15 years of mean follow-up, 41 of the selected subjects had died from coronary heart disease. Univariate analysis showed that these subjects differed from the subjects who died of another cause or who were alive at 15 years on the following variables: iliac to thigh ratio (p less than 0.0005), plasma triglyceride level (p less than 0.006), systolic blood pressure (p less than 0.01), and body mass index (p less than 0.04). In multivariate regression analysis using the Cox model, only iliac to thigh ratio and triglyceride plasma level achieved statistical significance as independent predictors. This result supports the current hypothesis that upper-body fat distribution, a characteristic trait of subjects with diabetes of glucose intolerance, plays an important role towards their high cardiovascular risk. However, it is unlikely that this role would be mediated through the lipid abnormalities that have been described as associated with upper-body fat deposition.