[The heart in diabetics].
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Biomedical subjects
Publications and source records attributed to A Fontbonne.
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A total of 57 bitches of various breeds were inseminated with frozen semen [the extender used being Tris-fructose-egg yolk-6.4% (v/v) glycerol] under controlled conditions. The optimum time of insemination was determined using vaginal smears and progesterone assays. Of 38 bitches inseminated one to three times in the vagina using a technique employing a commercial intravaginal pipette, 20 (52.6%) became pregnant, with a mean litter size of 4.2. Of 19 bitches inseminated one to three times using a transcervical technique, the conception rate was 73.6% with a mean litter size of 5.5. These data show, for the freezing method used, that the results of artificial insemination with frozen semen in the bitch are better with intrauterine than with intravaginal deposition.
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Seven bitches of several breeds were monitored during oestrus by vaginal smears and luteinizing hormone (LH), oestradiol and progesterone plasma assays. Each bitch was inseminated into the uterus with frozen spermatozoa from seven dogs of different breeds. Each female was inseminated daily with about 200 x 10(6) motile spermatozoa. Six bitches delivered. The paternity of puppies (which indicated the fertilization time) was determined by morphological analysis. Two bitches were fertilized with one artificial insemination (AI) only and four bitches with two successive AIs. Fertilization occurred 84-180 h after the LH peak and 1-3 days before the first day of metoestrus. The gestation length, from fertilization to birth, was 58-63 days or 56-60 days after the first day of metoestrus.
We performed a clinical and physiological study in diabetic patients with distal symmetrical sensory neuropathy in an attempt to correlate the extension of sensory loss with alterations of cardiocirculatory tests. These tests included measurement of blood pressure and heart rate in the recumbent and upright positions, Valsalva's manoeuvre and respiratory variations of R-R intervals. We thus studied 56 patients with distal sensory neuropathy. We found that all three tests were impaired in all patients with sensory loss above the knee level. We found a highly significant correlation between the level of sensory loss and impairment of physiological tests (p < 0.001). We conclude that both sensory loss above the knee and impairment of all three cardiocirculatory tests result from a severe neuropathy, but this correlation may not be sufficient to assert that cardiocirculatory impairment that occurs in diabetic neuropathy is a length dependent phenomenon.
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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.
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.
The Paris Prospective Study is a long-term investigation of the factors predicting coronary heart disease in a large population of middle-aged men. The first follow-up examination involved 7,152 subjects, who were natives of metropolitan France and were free of any cardiovascular history. At that time, the usual cardiovascular risk factors and plasma insulin levels were recorded. An index of body fat distribution, the iliac-to-thigh ratio, was entered into the list of predictive variables, despite the fact that it had been measured 1 year before the first follow-up examination. After 11 years of mean follow-up, 129 of the men had died of coronary heart disease. Univariate analysis showed that the iliac-to-thigh ratio (p < 0.0001) and plasma insulin level (both fasting [p < 0.003] and 2-hour postload [p < 0.02]), as well as the four major risk factors of coronary heart disease (age, smoking, blood pressure, and plasma cholesterol level) were significantly higher in subjects who died of coronary heart disease compared with those who had died of another cause or were alive at the end of follow-up. In multivariate stepwise logistic regression, the iliac-to-thigh ratio appeared as an independent predictor of coronary heart disease death, thereby causing the removal of fasting insulin level from the list of significant independent predictors. Nevertheless, in a model that entered 2-hour postload insulin in two classes (high or low), both the insulin level and iliac-to-thigh ratio were found as significant independent predictors.(ABSTRACT TRUNCATED AT 250 WORDS)
The prevalence of diabetes is known to be high in the West Indies, whereas CVD seems relatively rare. This apparently contradicts the existence of the insulin-resistance syndrome, a cluster of metabolic abnormalities supposedly favoring both diabetes and cardiovascular complications. To address the question of whether this contradiction could be accounted for by specific features of this syndrome, we compared 1505 Caucasian and 181 Afro-Caribbean men, all participants in the French Telecom Study. The Afro-Caribbeans were of the same age and had the same BMI as the Caucasians; they also had significantly higher subscapular skin-fold thickness and fasting insulin level, but similar BP and blood glucose level, and significantly lower plasma triglyceride level. Thus, although some features of the insulin-resistance syndrome were present (central adiposity and high insulin levels), none of the associated metabolic abnormalities were present. However, within the Afro-Caribbean group, subjects with plasma insulin concentrations above the median (> 52 pM) had higher mean BP and glucose and triglyceride levels compared with subjects with insulin concentrations < or = 52 pM (P < 0.001). After adjustment for age and BMI, these differences, though smaller, still were statistically significant. These findings confirm that higher insulin concentrations are associated with higher levels of potentially atherogenic and diabetogenic metabolic parameters. However, depending on ethnic origin, the mean levels of these parameters seem to be different, with the consequence that, even if they are elevated with increasing insulin levels, they may not reach values high enough to determine a substantial risk of disease.
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The Paris Prospective Study is a long-term, large-scale study of the factors predicting coronary heart disease. The first follow-up examination included, for subjects not known as having diabetes mellitus, a 75 g oral glucose tolerance test with measurement of plasma insulin and glucose levels, fasting and 2 h post-load. Between 1968 and 1973, 6903 men aged 43-54 years were thus examined. Causes of death were ascertained within this group after 15 years of mean follow-up. The baseline variables were tested as predictors of death from coronary heart disease by a Cox regression analysis. Significant independent predictors of coronary heart disease death were: systolic blood pressure, number of cigarettes per day, plasma cholesterol level, and 2 h post-load plasma insulin level when entered as a categorical variable (below or above 452 pmol/l. i.e. the lower limit of the fifth quintile of the distribution). This dichotomization was performed to account for the non-linear univariate distribution of deaths with increasing post-load insulin values. Fasting plasma insulin level was not an independent predictor of death by coronary heart disease over this long-term follow-up. Levels of blood glucose were not significant independent predictors of death by coronary heart disease when plasma insulin levels were included in the model. The same applied to abnormalities of glucose tolerance when the 125 men with known non-insulin-treated diabetes at baseline were added to the group. Under the assumption that hyperinsulinaemia is a marker of insulin resistance, the results are consistent with the hypothesis that insulin resistance is associated with a higher risk of coronary heart disease mortality. However, it is doubtful that circulating insulin per se is a direct cause of arterial complications.
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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.
There seems to be a cluster of potentially atherogenic and diabetogenic abnormalities in subjects with central adiposity (high waist to hip ratio) and insulin resistance. To test whether reversing insulin resistance could lead to decreased vascular and diabetic risks, a trial using a drug to complement life-style modification measures is necessary. BIGPRO trial proposes to examine the efficacy of metformin, along with diet and exercise advice, in reducing over one year the metabolic abnormalities encountered in non-diabetic subjects with central adiposity. BIGPRO is designed as a randomized double blind one-year trial of metformin (2 tabs/d, i.e. 1,700 mg/d) versus matching placebo (2 tabs/d). Men aged 40-55 years, with a waist to hip ratio greater than or equal to 0.95 and women aged 45-65 years with a waist to hip ratio greater than or equal to 0.80, are eligible to enter the trial, unless they have diabetes, cardiovascular disease, kidney dysfunction, serious illness, or are receiving extensive medical treatment. Between the two treatment groups the changes in the following endpoints will be compared after one year study: waist to hip ratio, blood pressure, blood lipids, glucose, insulin, fibrinolytic activity. At least 400 subjects are expected to complete the trial. The recruitment and follow-up will be distributed among 33 medical centers from various University Hospitals in France. If metformin proves to be effective in reducing the metabolic abnormalities associated with insulin resistance, it may be a possible candidate for a long term trial for primary prevention of cardiovascular accidents and diabetes.