PubMed Health⌕ Search

Biomedical subjects

M de Courten

Publications and source records attributed to M de Courten.

31 records · Page 2Linked to original sources
PubMed1995

Familial relationships between obesity and NIDDM.

Obesity and family history of diabetes are both risk factors for non-insulin-dependent diabetes mellitus (NIDDM), but it has been proposed that lean individuals with NIDDM have a greater load of diabetes susceptibility genes. If this is the case, one might expect a high prevalence of NIDDM in relatives of diabetic individuals with a low body mass index (BMI). Among Pima Indians participating in an epidemiological study, prevalence of NIDDM was evaluated in relation to BMI of a diabetic parent or to the average parental BMI when both parents had diabetes in 1,535 offspring from 547 families. Prevalence of NIDDM was also evaluated in relation to BMI of a randomly selected index diabetic sibling in 1,722 siblings from 721 families. NIDDM was diagnosed by an oral glucose tolerance test. Compared with offspring of diabetic parent(s) at the 25th percentile of BMI, the odds ratio (OR) for diabetes in offspring of diabetic parents at the 75th percentile was 0.6 (95% confidence interval [CI] 0.5-0.7), adjusted for age, sex, BMI in offspring, number of diabetic parents, and age at onset of diabetes and sex of the diabetic parent(s). In the analysis according to BMI in a diabetic sibling, the corresponding OR was 0.8 (95% CI 0.6-0.9). Risk ratios were only modestly higher when the analysis was restricted to relatives of subjects whose BMI had been determined before the onset of diabetes. NIDDM in the presence of a low BMI is more strongly familial than that at a higher BMI.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

[Insulin resistance and arterial hypertension].

Insulin resistance and reactive hyperinsulinemia occur not only in patients with obesity, impaired glucose tolerance or non-insulin-dependent (Type 2) diabetes mellitus, but also in many non-obese, non-diabetic individuals with essentiell hypertension and their normotensive, lean young offsprings. The common coexistance of a genetic predisposition for hypertension with insulin resistance helps to explain the frequent occurrence of hypertension as well as dyslipidemia, obesity and diabetes Type 2 in a given individual. In the pathogenesis of hypertension, inappropriate vasoconstriction and/or a structural vasculopathy appears to be an important and ultimate causative event. Several pressor mechanisms are discussed and a distinct sodium retention appears to be almost obligatory associated with diabetes mellitus, while essential and particularly obesity-associated hypertension involves predominantly a tendency for sympathetic activation. Acute hyperinsulinemia on one hand causes arterial vasodilation and on the other hand enhances renal sodium reabsorption and sympathetic activity. Chronically, hyperinsulinemia may promote cardiovascular muscle cell proliferation and atherogenesis. Insulin resistance affecting certain transmembrane cation transporters might lead to an elevation of intracellular cytosolic calcium levels thereby inducing inappropriate vasoconstriction. Nevertheless, whether insulin resistance and hyperinsulinemia contribute to the pathogenesis of hypertension per se is still unproven. Considering antihypertensive drugs, thiazide diuretics given in medium or high dosage as well as beta-blockers appear to promote insulin resistance, reactive hyperinsulinemia and dyslipidemia. Almost all calcium antagonists and the conventional sympthatolytics are metabolically neutral, while ACE-inhibitors and alpha 1-blockers tend to improve insulin resistance. In Type 2 diabetic patients, ACE-inhibitors exert in addition to their antihypertensive a potentially useful anti-diabetic effect. Nevertheless, the prognostic relevance of the metabolic side effects of antihypertensive drugs awaits further clarification.

Antihypertensive Agents↗
PubMed1994

Comparative study of the effect of ACE-inhibitors and other antihypertensive agents on proteinuria in diabetic patients.

Several studies during the past 15 years have shown that antihypertensive therapy with different types of drugs can reduce microalbuminuria or clinical proteinuria and retard the progression toward end-stage renal failure. However, some authors reported disparate renal protective effects of different antihypertensive drugs in diabetic animals and humans. In an attempt to resolve the controversy surrounding this possibility, previously we reported a meta-analysis of published studies in diabetics with microalbuminuria or overt proteinuria treated with conventional agents, angiotensin-converting enzyme (ACE) inhibitors, or calcium antagonists (Ca2+ antagonists). Here we present an updated meta-analysis of published studies in diabetics with microalbuminuria or clinical proteinuria (UProt), treated during > or = 4 weeks with ACE inhibitors, Ca2+ antagonists, or conventional therapy (diuretic and/or beta-blocker). Despite similar blood pressure (BP) reductions, UProt tended to decrease more on ACE inhibitors (on average -45%) than on conventional therapy (on average -23%) or Ca2+ antagonists other than nifedipine (on average -35%); in contrast, UProt tended to increase slightly on nifedipine (on average 5%, P < .05). On the basis of multiple regression analysis, ACE inhibitor-induced UProt changes correlated with BP changes (r = 0.77, P < .00001), averaged -28% at zero BP change, and varied 1.5% for each percent BP change. On conventional therapy, UProt and BP changes also correlated (r = 0.62, P < .005), but UProt began to decrease only after a BP reduction of > 5% and the slope was steeper (4% UProt change per percent BP change) than on ACE inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS)

Albuminuria↗
PubMed1994

Insulin sensitivity and atrial natriuretic factor during beta-receptor modulation with celiprolol in normal subjects.

beta-Receptor blockers may exert a spectrum of metabolic and humoral effects, which might differ depending on the specific adrenoreceptor characteristics of the individual agents. We investigated the influence of celiprolol, a beta 1-blocker with beta 2-agonistic and, possibly, additional weak alpha-receptor antagonistic properties, on insulin sensitivity (SI), glucose homeostasis, and lipid profile in 20 young, healthy, normotensive individuals. SI, fasting plasma glucose and insulin, serum total triglycerides (TG), lipoprotein cholesterol (C) fractions, lipoprotein a [Lp(a)], and plasma atrial natriuretic factor (ANF) levels were determined before and after acute glucose loading under placebo conditions and after 3 weeks of celiprolol administration. The participants were instructed to follow a 3-day standard diet (2,500 kcal/day, 45% carbohydrates, 40% fat, and 15% protein) and an overnight fast before measurements were recorded. As compared with control values, SI, fasting plasma glucose and insulin, the areas under the glucose and insulin curves, the k value of glucose disappearance after glucose load, and serum cholesterol fractions, TG, and Lp(a) were unchanged during celiprolol administration. However, celiprolol significantly reduced plasma ANF levels (p < 0.02). The latter increased in response to acute hyperglycemia/hyperinsulinemia with placebo (p < 0.05) but not with celiprolol. Although diastolic blood pressure (DBP) decreased slightly during the first and second week of celiprolol administration, BP and heart rate (HR) did not differ significantly after 3 weeks on celiprolol treatment as compared with placebo conditions. Our findings demonstrate that in healthy lean humans beta-receptor modulation with celiprolol is neutral with regard to SI and lipoprotein metabolism. Moreover, glucose loading stimulates whereas celiprolol decreases plasma ANF levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-1 Receptor Antagonists↗
PubMed1993

Lack of effect of long-term amlodipine on insulin sensitivity and plasma insulin in obese patients with essential hypertension.

To evaluate the effects of long-term treatment antihypertensive with the dihydropyridine calcium antagonist amlodipine on insulin sensitivity, plasma insulin, and lipoprotein metabolism in obese hypertensive patients. We measured the insulin sensitivity index (SI), determined by the Minimal Model Method of Bergman, fasting plasma insulin and glucose concentrations, serum total triglyceride and lipoprotein cholesterol fractions, and blood pressure in 20 obese, non-diabetic patients with essential hypertension before and after 6 weeks of placebo and again after 6 months of amlodipine. Ten patients [mean body mass index (BMI) 30.2 kg.m-2] had been on prior treatment with a thiazide diuretic in low dosage and/or a beta-adrenoceptor blocker (group A), and 10 matched patients [BMI 31.8 kg.m-2] had been previously untreated (group B). Amlodipine was started in a dose of 5 mg and was increased to 10 mg once daily in 14 patients who were hypertensive after 8 weeks on the lower dosage. At entry (before placebo), SI was slightly but not significantly lower in group A than B [2.7 vs. 3.6 x 10(-4) ml.microU-4.min-1]; fasting plasma insulin was 13.6 vs. 12.9 microU.ml-1. After 6 weeks on placebo, S1 averaged 3.7 in group A and 4.4 x 10(-4) microU.ml-1.min-1 in group B; fasting plasma insulin was 14.6 vs. 15.1 microU.ml-1, and glucose 5.5 vs. 5.5 mmol.l-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Amlodipine↗
PubMed1993

Pathogenesis and treatment of hypertension associated with diabetes mellitus.

The pathogenesis of hypertension associated with diabetes mellitus (DM) involves an interplay of hereditary and acquired mechanisms. A familial trait for essential hypertension appears to be a risk factor for the development of both hypertension and nephropathy in type I DM and coexists commonly with impaired insulin sensitivity, relative hyperinsulinemia, and dyslipidemia, which can already be detected before the appearance of hypertension, obesity, or upper abdominal redistribution of body fat. The latter finding helps explain the frequent development of hypertension as well as dyslipidemia and/or type II DM in given individuals. Obesity is an important factor promoting these complications. Type I or II DM but not uncomplicated essential hypertension is characteristically accompanied by excess body Na+. This abnormality complements a tendency toward vascular hyperreactivity and a presumably morphologic and functional vasculopathy, thereby promoting the pathogenesis of hypertension in diabetic patients. For the treatment of hypertension in diabetic patients, nonpharmacologic measures are indispensable. If drugs are needed, angiotensin-converting enzyme (ACE) inhibitors and some but not all calcium antagonists are the preferred agents. Monotherapy or a combination of these drug types allows effective blood pressure control in most diabetic patients without further metabolic impairment; ACE inhibitors even tend to improve glucose control. Ketanserin may be a potential alternative, and if a diuretic is also needed, the metabolically neutral indapamide is a reasonable choice. If these agents do not allow satisfactory blood pressure highly selective beta 1-blockers or alpha 1-blockers may be introduced as a second choice. In diabetic patients with nephropathy, effective antihypertensive therapy can reduce proteinuria and slow the progression of the nephropathy; ACE inhibitors may improve diabetic proteinuria even at unchanged systemic blood pressure levels. Unless diuretics are needed for reasons other than hypertension, the treatment of diabetic patients with thiazides or loop diuretics in conventional dosage should probably be avoided until clarification of their influence on prognosis. Nevertheless, whether and to what extent other agents and nonpharmacologic measures can modify the prognosis in diabetic patients is also unclear, and the approach to antihypertensive therapy is therefore still largely empiric.

Antihypertensive Agents↗
PubMed1993

The pathogenesis of hypertension in obese subjects.

Obese subjects are at an increased risk of becoming hypertensive and vice versa. Essential hypertension and obesity are commonly accompanied by insulin resistance (defined as impaired insulin-mediated glucose disposal) and hyperinsulinaemia. In the offspring of patients with essential hypertension, insulin resistance and hyperinsulinaemia, as well as related increases in serum low density lipoproteins and triglycerides, often occur prior to the development of essential hypertension, overweight or central redistribution of body fat. Moreover, once obesity, and in particular central obesity, is present, insulin resistance is more marked in hypertensive than in normotensive obese subjects. Hyperinsulinaemia and/or insulin resistance in turn promote body fat deposition and impaired glucose tolerance. This cycle helps to explain why a familial predisposition to essential hypertension poses an increased risk of developing not only hypertension but also dyslipidaemia, obesity and non-insulin-dependent (type 2) diabetes. It is still unclear whether insulin resistance and/or hyperinsulinaemia also promote hypertension per se. Regardless of insulin's exact pathogenic role, obesity and/or a high dietary intake of carbohydrates, salt, etc. can induce several potential pressor mechanisms: 1) higher plasma noradrenaline (norepinephrine) and adrenaline (epinephrine) levels, suggesting a higher sympathetic tone in obese than in nonobese subjects, and in hypertensive obese than in normotensive obese subjects; 2) similarly, a tendency to hyperaldosteronism, with largely normal plasma renin activity, in obese hypertensive patients; 3) enhanced sensitivity of blood pressure to salt; 4) increased total blood volume (although it is normal relative to body surface area), leading to increased cardiac output and eventually eccentric left ventricular hypertrophy; and 5) increased cytosolic free Ca++ levels and reduced intracellular Mg++ levels in the blood cells of obese hypertensive patients and patients with non-insulin-dependent diabetes, although this finding cannot necessarily be extrapolated to cationic levels in vascular muscle cells. Total peripheral vascular resistance is usually low in normotensive obese subjects and rises with the development of hypertension; compared with lean patients with essential hypertension, obese hypertensive patients tend to have a slightly lower level of total peripheral vasoconstriction and a slightly higher cardiac output. Considering the intimate association between essential hypertension and obesity, as well as the prevalence and prognostic relevance of this combination, the spectrum of accompanying metabolic and cardiovascular abnormalities deserves careful consideration in the evaluation of therapeutic care for such patients.

Humans↗
PubMed1993

Serum lipoproteins during treatment with antihypertensive drugs.

Several drugs used for antihypertensive therapy may modify the lipoprotein metabolism. Thiazides in high dosage and loop diuretics can increase serum low-density lipoprotein (LDL) cholesterol and/or very-LDL cholesterol and the total cholesterol/high-density lipoprotein (HDL) cholesterol ratio, while HDL cholesterol is largely unchanged; triglycerides (Tg) are also often elevated. Premenopausal women may be protected from this side effect. Whether diuretic-induced dyslipidemia is dose-dependent and low thiazide doses (i.e., hydrochlorothiazide < or = 12.5 mg daily) are interacting less, awaits clarification. beta-Blockers without intrinsic sympathomimetic activity increase serum triglycerides and tend to lower the potentially antiatherogenic HDL cholesterol. The diuretic-antihypertensive agent indapamide, given at a dose of 2.5 mg/day, is neutral with regard to serum lipoprotein and glucose metabolism. The potassium-sparing diuretic spironolactone, conventional sympatholytic agents, calcium-channel blockers, and probably the serotonin2-receptor antagonist ketanserin, exert no relevant effects on the lipoprotein profile. Angiotensin-converting enzyme inhibitors may slightly decrease serum triglycerides. alpha 1-Receptor blockers slightly decrease LDL cholesterol and Tg and increase HDL cholesterol. Drug-induced development or aggravation of dyslipidemia represents a potentially adverse influence. In the hypertensive population, effective blood pressure control with traditional drug therapy based on thiazide-type diuretics in high dosage led to a distinct decrease in cerebrovascular morbidity and mortality, but failed to satisfactorily reduce coronary complications. The prognostic relevance of drug-induced changes in serum lipoproteins, carbohydrate metabolism and other risk factors or correlates awaits further clarification.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1993

Insulin resistance, hyperinsulinemia and hypertension.

Association between insulin resistance and hypertension: Insulin resistance and reactive hyperinsulinemia occur not only with obesity, impaired glucose tolerance or non-insulin-dependent (type 2) diabetes mellitus, but also in many non-obese, non-diabetic patients with essential hypertension and their currently normotensive, lean young offspring and in some other conditions known to promote hypertension. Insulin resistance impairs glucose tolerance, while insulin resistance and/or hyperinsulinemia promote dyslipidemia, body fat deposition and probably atherogenesis. Therefore, the common coexistence of a genetic predisposition for hypertension with insulin resistance helps to explain the frequent, although temporally often dissociated, occurrence of hypertension as well as dyslipidemia, obesity and type 2 diabetes in a given subject. Pathogenetic mechanisms: In the pathogenesis of hypertension, inappropriate vasoconstriction (due to dysbalance of vasoactive substances and/or raised cytosolic Ca2+) and/or a structural vasculopathy is a very important ultimate causative event. In the presumed mosaic of participating pressor mechanisms, distinct Na+ retention is almost obligatory with diabetes mellitus, while essential and particularly obesity-associated hypertension probably involves a tendency for sympathetic activation. Development of insulin resistance: Insulin resistance may develop as a consequence of an intracellular excess of Ca2+ or decrease in Mg2+, an impaired insulin-mediated rise in skeletal muscle blood flow, increased sympathetic activity or being overweight. Acute hyperinsulinemia on the one hand causes arterial vasodilation and on the other hand enhances renal sodium reabsorption and sympathetic activity. Chronically, hyperinsulinemia may promote cardiovascular muscle cell proliferation and atherogenesis, and it has been proposed that insulin resistance in certain transmembranous cation exchange systems may elevate cytosolic Ca2+. Nevertheless, whether insulin resistance and/or hyperinsulinemia itself contribute to the pathogenesis of hypertension is still unclear.

Animals↗
PubMed1992

[Diagnostic value of ambulatory daily blood pressure profile: comparison with measurements performed by a laboratory technician].

Office blood pressure measured by a physician is often higher than under the usual ambulatory conditions. Therefore, alternative methods such as self-assessment of blood pressure and ambulatory blood pressure measurements are increasingly promoted. The purposes of this study, covering 613 referred patients, were (1) compare office blood pressure with continuous ambulatory blood pressure measurements, (2) compare office blood pressure with blood pressure values recorded by a trained technician in the absence of a physician and (3) analyze the interpretation of the blood pressure profiles by the referring physicians. Office blood pressure exceeded average ambulatory blood pressure in 94% of the patients and also the blood pressure values recorded by a technician in 88%. According to the office blood pressure there were 523 patients with elevated blood pressure, 20 with isolated increased systolic blood pressure and 70 with normal blood pressure. Office blood pressure was higher (systolic +17 +/- 18 and diastolic +9 +/- 12 mm Hg, p less than 0.0001) than the average value of the ambulatory blood pressure profile, whereas the latter did not differ significantly from blood pressure values measured by the technician (systolic -1 +/- 12 and diastolic -2 +/- 9 mm Hg). 190 of the 523 (36%) patients had white-coat hypertension according to the ambulatory blood pressure measurements. Conventional blood pressure measurements by the technician yielded a high sensitivity (84%) and specificity (87%) for distinguishing white coat hypertension. Analysis of the questionnaires showed that opinions about normal limits of ambulatory blood pressure vary considerably.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure Determination↗
PubMed1992

Effect of diuretics on the plasma lipid profile.

Hypertension, dyslipidaemia, glucose intolerance (associated with insulin resistance and compensatory hyperinsulinaemia) and other abnormalities are complementary coronary risk factors which often occur in association. A familial trait for essential hypertension seems to coexist commonly with defects in carbohydrate and lipoprotein metabolism which can be detected before the appearance of hypertension. Diabetes mellitus as well as obesity promotes the development of hypertension and dyslipidaemia. Moreover, certain drugs used for antihypertensive therapy can further modify lipoprotein and glucose metabolism. Thiazides in high dosage and loop-diuretics can increase serum low-density-lipoprotein cholesterol (LDL-C) and/or very-LDL-C and the total C/high-density lipoprotein cholesterol (HDL-C) ratio, while HDL-C is largely unchanged; triglycerides (Tg) are also often elevated. Premenopausal women may be protected from this side effect. Whether diuretic-induced dyslipidaemia is dose-dependent and low thiazide doses (i.e. hydrochlorothiazide < or = 12.5 mg daily) are less active, awaits clarification. The diuretic-antihypertensive agent, indapamide, given at a dose of 2.5 mg.day-1, seems to exert no relevant effect on serum lipoprotein or glucose metabolism. The potassium-sparing diuretic, spironolactone, also may be largely neutral with regard to lipids. Moreover, potassium sparing diuretics may possibly counteract, at least in part, a dyslipidaemic influence of potassium-loosing diuretics in medium dose. Drug-induced dyslipidaemia, as well as glucose intolerance, represent potentially adverse influences. In the hypertensive population, effective blood pressure control with traditional drug therapy based on thiazide-type diuretics in high dosage led to a distinct decrease in cerebrovascular morbidity and mortality, but a lesser decrease in coronary events.(ABSTRACT TRUNCATED AT 250 WORDS)

Diuretics↗
PubMed1992

Antihypertensive therapy in diabetic patients.

Diabetes mellitus (DM)-linked metabolic alterations and hypertension concomitantly accelerate or precipitate cerebrovascular and coronary heart disease, nephropathy, retinopathy and widespread macroangiopathy, thereby conferring to diabetic patients a very high risk of morbidity, disability and early death. Therefore, the long-term care for diabetic patients should be aimed at concomitant metabolic and blood pressure (BP) control. Dietary measures are indispensable; a high fibre, low fat, low salt diet is recommended, complemented with caloric restriction and physical exercise when body weight is above the ideal. Antidiabetic pharmacotherapy involves an unresolved dilemma. The desired achievement of euglycemia necessitates effective levels of insulin, but hyperinsulinemia (due to parenteral [over]treatment in insulin-dependent DM) is suspected to promote atherogenesis and represents a coronary risk factor and perhaps even facilitates hypertension. Considering antihypertensive pharmacotherapy, thiazide-type or loop diuretics are problematic drugs in DM because they can aggravate metabolic alterations. These agents also seem to exert only a limited preventive or regressive effect on left ventricular hypertrophy (LVH); beta-blockers are also not considered ideal, since they decrease the awareness of hypoglycemia and tend to promote glucose intolerance. Unselective beta-blockers in particular promote peripheral ischemia and insulin-induced hypoglycemia, while beta-blockers without intrinsic sympathomimetic activity lower serum HDL-cholesterol. Calcium antagonists and ACE inhibitors have equivalent antihypertensive efficacy, do not impair carbohydrate and lipid homeostasis or peripheral perfusion and can effectively improve LVH. Certain ACE inhibitors may even slightly ameliorate abnormal insulin sensitivity and plasma glucose levels. While alpha-blockers share most of these desirable properties, these agents are more prone to precipitate orthostatic hypotension in the diabetic patient. The non-thiazide diuretic indapamide and the serotonin2-antagonist ketanserin also combine antihypertensive efficacy with metabolic neutrality. The ultimate goal of therapy is to improve life prognosis. In essential hypertension, conventional drug treatment based on diuretics in high dosage satisfactorily reduced cerebrovascular but not coronary complications or sudden death. In diabetic patients, the influence of antihypertensive therapy on prognosis has not been assessed prospectively. Based on retrospective analyses, Warram et al reported a 3.8 times higher mortality in diabetics treated with diuretics alone, than in diabetics with untreated hypertension (Arch Intern Med. 1991;151:1350). H. H. Parving calculated that effective BP control in patients with diabetic nephropathy might reduce 10 year-mortality from about 65 to 20 percent (J Hypertension. 1990; 8[Suppl 7]:187).(ABSTRACT TRUNCATED AT 400 WORDS)

Antihypertensive Agents↗