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Biomedical subjects

P J Lefèbvre

Publications and source records attributed to P J Lefèbvre.

At least 19 recordsLinked to original sources
PubMed2005

[Proactive study: secondary cardiovascular prevention with pioglitazione in type 2 diabetic patients].

PROactive is a prospective, randomised controlled trial in 5238 patients with type 2 diabetes who had evidence of macrovascular disease. Patients were assigned to oral pioglitazone titrated from 15 mg to 45 mg or matching placebo, to be taken in addition to their glucose-lowering drugs and other medications. After a mean follow up of 34.5 months, pioglitazone reduced the composite of all-cause mortality, non-fatal myocardial infarction, and stroke (intention to treat analysis: hazard ratio = 0.84; 95% CI: 0.72-0.98; p = 0.027). Various favourable metabolic effects could contribute to this cardiovascular protection, i.e. an absolute 0.5 % reduction in HbA1c, a 9% increase in HDL cholesterol, a 13% decline of triglycerides, and a 3 mm Hg reduction in systolic blood pressure in the pioglitazone group compared to placebo. The requirement of insulin was reduced by almost 50% in the pioglitazone group as compared to the placebo group. The incidence of cases of oedema and congestive heart failure was higher in the pioglitazone group. In conclusion, in patients with type 2 diabetes who are at high cardiovascular risk, pioglitazone improves cardiovascular outcome, and reduces the need to add insulin to glucose-lowering regimens compared to placebo.

Administration, Oral↗
PubMed2004

Intact cross-talk between insulin secretion and insulin action after postgastroplasty recovery of ideal body weight in severely obese patients.

Most reports investigating the hormonal and metabolic effects of bariatric surgery studied obese subjects after partial weight loss only. Nevertheless, all studies showed significant improvements of insulin secretion, action, clearance and inhibition of its own secretion, although the parallel kinetics of all these changes remained questionable. Using the intravenous glucose tolerance test, we demonstrated a full normalization of insulin secretion, action on glucose metabolism and clearance in eight obese women who recovered and maintained ideal body weight following gastroplasty. Reciprocal changes were observed between postglucose acute insulin secretion and insulin-mediated glucose disposal so that the so-called disposition index (product of these two variables) remained unchanged after vs before gastroplasty in those individuals with normal glucose tolerance. These favourable results should encourage obtaining a drastic and sustained weight loss in patients with severe obesity at risk of developing type II diabetes.

Body Weight↗
PubMed2004

[Reactive hypoglycaemia, a mysterious, insidious but non dangerous critical phenomenon].

Numerous individuals complain of malaise attributed to hypoglycaemia. However, the diagnosis of hypoglycaemia is rarely documented and most often overstated. Reactive hypoglycaemia in the postprandial state is rather exceptional. The diagnosis relies upon the measurement of plasma glucose concentration (< 3 mmol/l or 55 mg/dl) at the time of the malaise. Reactive hypoglycaemia is generally associated with adrenergic symptoms and, less often, with cognitive disturbances. Importantly, a plasma glucose concentration below 3 mmol/l during an oral glucose tolerance test is not sufficient to decide that the patient suffers from reactive hypoglycaemia. Treatment is based on dietary advices including frequent small split meals and limitation of carbohydrates with high glycaemic index. Acarbose, a specific inhibitor of gut alpha-glucosidase enzymes, may be helpful in case of diet failure. As compared with true reactive hypoglycaemia, a postprandial hyperadrenergic reaction without real concomitant hypoglycaemia is much more prevalent. Careful anamnesis may suspect such a diagnosis, but other diagnoses such as panic attack or vasovagal reaction should be excluded. Treatment is purely symptomatic and essentially empiric.

Acarbose↗
PubMed2003

Factors predictive of nephropathy in DCCT Type 1 diabetic patients with good or poor metabolic control.

AIMS: The study aim was to assess the time-related risk of developing diabetic nephropathy [albumin excretion rate (AER) > or =40 mg/24 h] from baseline covariates in Type 1 diabetic patients with either good or poor metabolic control (MC). METHODS: Based on material from the Diabetes Control and Complications Trial study (n=1441), patients were considered as under good or poor MC if their HbA1c mean level up to last visit fell in the lowest (< or =6.9%) or highest (>or =9.5%) quintile of the overall HbA1c distribution, respectively. Prevalence cases of nephropathy were excluded from the study. Survival analysis and Cox regression were applied to the data. RESULTS: Among patients with good MC (n=277), 15% had developed nephropathy at the end of the study. Conversely, among patients with poor MC (n=268), the proportion without the complication was 52%. When adjusting for MC, time to diabetic nephropathy was related to age (P<0.0001), AER (P<0.001), duration of diabetes (P<0.005), body mass index (BMI) (P<0.005), all at baseline, and to gender (P<0.01). Patients with upper normal range AER levels, longer duration of diabetes and lower BMI were at higher risk, regardless of MC. The adverse effect of younger age on diabetic nephropathy was more marked in good than in poor MC. Although women tended to develop the complication more often under good MC, they appeared to be better protected under poor MC. CONCLUSIONS: This study confirms occurrence of diabetic nephropathy under good MC and non-occurrence of the complication despite poor MC. It also demonstrates that some baseline covariates can affect, in a differential manner, time to diabetic nephropathy depending on MC.

Adolescent↗
PubMed2003

[Prevention of cardiovascular diseases using a combined pharmacological approach: is there any place for a "polypill"?].

In the June 28, 2003 issue of the British Medical Journal, an extensive literature survey based on various large meta-analyses of the efficacy and safety of the reduction of four cardiovascular risk factors (cholesterol, arterial blood pressure, platelet aggregation, homocysteine) leads to the conclusion that a combined pharmacological intervention should reduce ischaemic heart disease events by 88% and strokes by 80% in at risk individuals. Therefore, a new paradigm is proposed for the prevention of cardiovascular diseases. This new strategy would consist in the systematic prescription to people with a history of heart attack or stroke, those with any form of obliterative atherosclerotic vascular disease or diabetes, and everyone aged 55 and older of a fixed combination of 6 pharmacological agents independently of initial risk factor profile.... Such pharmacological formulation, called "polypill", should contain a statin, three blood pressure lowering drugs (each at half standard dose), aspirin (75 mg/day) and folic acid (0.8 mg/day). We discuss the pros and cons of this new paradigm. However, the efficacy of such "polypill" remains to be demonstrated in a large controlled clinical trial as well as its superiority as compared to a classical approach of cardiovascular prevention based upon the individual optimal correction of each risk factor thanks a dose titration of each pharmacological compound.

Antihypertensive Agents↗
PubMed2002

[Postprandial hyperglycemia. I. Physiopathology, clinical consequences and dietary management].

Postprandial hyperglycaemia depends on the amount and type of ingested carbohydrates and/or the degree of inhibition of hepatic glucose output following a meal. The kinetics of carbohydrate absorption is directly influenced by the type of food (carbohydrates with variable glycaemic indices, fibre content of the meal) and by the speed of gastric emptying. Hepatic glucose output is remarkably inhibited by insulin and strongly stimulated by glucagon. It remains abnormally high after a meal in diabetic patients because of insufficient portal insulin concentrations, hepatic insulin resistance and/or hyperglucagonaemia. In diabetic patients, postprandial hyperglycaemia contributes to the aggravation of chronic hyperglycaemia, and thus to the increase of glycated haemoglobin levels. Furthermore, it has been recently demonstrated that postprandial hyperglycaemia increases the cardiovascular risk, even in nondiabetic subjects, probably by inducing endothelial dysfunction. Appropriate dietary counselling plays a key-role in the control of postprandial hyperglycaemia. Generally speaking, it includes a selection of carbohydrates with low glycaemic index and a higher fibre intake. Pharmacological interventions may also be considered when necessary.

Absorption↗
PubMed2001

Obesity: causes and new treatments.

The prevalence of obesity increases rapidly in developed and developing countries. Obesity results from a cumulative positive energy balance and is favoured by both genetic and environmental factors. Preventing obesity requires a major investment in nutritional and lifestyle education, particularly in children and adolescents.--The pharmacological approach to obesity includes drugs that reduce food intake (noradrenergic and serotoninergic agents), drugs that increase energy expenditure and compounds that affect nutrient partitioning. In all instances, the benefit-to-risk ratio needs to be carefully assessed. In some patients (severe obesity or obesity accompanied by serious high-risk comorbid conditions), gastric surgery (gastric restriction or gastric bypass) should be considered. In our own experience, it is safe and effective.

Energy Metabolism↗
PubMed2000

Assessment of postprandial hepatic glycogen synthesis from uridine diphosphoglucose kinetics in obese and lean non-diabetic subjects.

BACKGROUND: Obese patients are frequently characterized by insulin resistance and decreased insulin-mediated glycogen synthesis in skeletal muscle. Whether they also have impaired postprandial hepatic glycogen synthesis remains unknown. AIM: To determine whether postprandial hepatic glycogen synthesis is decreased in obese patients compared to lean subjects. METHODS: Lean and obese subjects with impaired glucose tolerance were studied over 4h after ingestion of a glucose load. Hepatic uridine diphosphoglucose kinetics were assessed using 13C-galactose infusion, with monitoring of urinary acetaminophen-glucuronide isotopic enrichment to estimate hepatic glycogen kinetics. RESULTS: Estimated net hepatic glycogen synthesis amounted to 18.6 and 22.6% of the ingested load in lean and obese subjects, respectively. CONCLUSION: Postprandial hepatic glycogen metabolism is not impaired in non-diabetic obese subjects.

Adult↗
PubMed2000

No increased insulin sensitivity after a single intravenous administration of a recombinant human tumor necrosis factor receptor: Fc fusion protein in obese insulin-resistant patients.

Inhibition of tumor necrosis factor (TNF)-alpha results in a marked increase in insulin sensitivity in obese rodents. We investigated the influence of a TNF antagonist [Ro 45-2081, a recombinant fusion protein that consists of the soluble TNF-receptor (p55) linked to the Fc portion of human IgG1] on insulin sensitivity of patients with android obesity. Seven patients (five women and two men; mean +/- SD age, 41 +/- 4 yr; body mass index, 36.1 +/- 4.7 kg/m2; waist to hip ratio, 0.99 +/- 0.11) were studied (three patients with normal glucose tolerance and four patients with impaired glucose tolerance or mild diabetes; all were hyperinsulinemic). Each patient underwent two consecutive euglycemic hyperinsulinemic glucose-clamp tests: 48 h after injection of placebo and 48 h after a single i.v. injection of 50 mg Ro 45-2081. In both tests, steady-state plasma glucose and insulin levels were similar. Insulin-mediated glucose disposal (2.23 +/- 0.74 vs. 2.38 +/- 0.99 mg/kg(-1) x min(-1)) and glucose metabolic clearance rate (2.28 +/- 0.85 vs. 2.48 +/- 1.03 mL/kg(-1) x min(-1)) were similar after placebo and after the drug. Indirect calorimetry showed no difference in substrate oxidation rates between the two experimental conditions. In conclusion, under the conditions of this study, no improvement in insulin sensitivity was observed in obese insulin-resistant patients following a single i.v. administration of a recombinant TNF receptor: Fc fusion protein.

Adult↗
PubMed2000

[GLycemic control in the diabetic patient. Recommendations after the DCCT and UKPDI studies].

Diabetes mellitus is a chronic disorder characterized by microvascular and cardiovascular complications that substantially increase the morbidity and mortality associated with the disease. Several studies showed the association between the complications of diabetes and elevated blood glucose levels. Clinical trials have also demonstrated that treatment that lowers blood glucose reduces the risks of diabetic complications (mainly microvascular complications). The control of diabetes is assessed by frequent measurements of HbA1c. A reasonable goal in type 1 diabetes is a value of HbA1c < or = 7.2%. In type 2 diabetes, the optimal goal is a value of HbA1c < or = 6.5%, but a value < or = 8% seems to be an acceptable goal in these patients.

Diabetes Complications↗
PubMed2000

[Guidelines for the treatment of arterial hypertension in diabetic patients].

Diabetes mellitus is frequently associated with arterial hypertension and the combination of the two entities markedly increases the cardiovascular risk and accelerates the progression of microangiopathy (more particularly nephropathy) in both type 1 and type 2 diabetic patients. Numerous international guidelines have been published during the last few years to help the practitioner in targeting ideal arterial blood pressure levels (lower in diabetic than in non-diabetic patients) and in selecting first-choice antihypertensive agents. We will concisely summarize the main messages of these recommendations and insist upon the persistence of uncertainties, or even the existence of inconsistencies, more particularly regarding preferential indications of antihypertensive agents in diabetic patients.

Antihypertensive Agents↗
PubMed1999

Glucose metabolism and the postprandial state.

Disturbances of postprandial glucose metabolism are now thought to contribute to cardiovascular disease. Postprandial glucose excursions can be affected by a number of factors, such as the types of carbohydrates ingested and the way they are metabolized. In Type 2 diabetes, factors that contribute to excessive postprandial glucose excursions include disruption of insulin secretion, insufficient inhibition of hepatic glucose production and defective glucose storage in muscle. A number of measures may attenuate excessive postprandial blood glucose excursions. These include a diet high in 'low glycaemic index' foods and treatment with drugs that improve or restore the hormonal response (e.g. the sulphonylureas and the newer beta-cell mediated insulinotropic drugs such as repaglinide), that improve insulin sensitivity or that delay gastric emptying.

Diabetes Mellitus, Type 1↗
PubMed1999

Severe/extreme obesity: a medical disease requiring a surgical treatment?

Obesity poses a serious health hazard and its treatment is often disappointing. Surgical approaches have been proposed for treating severe obesity (body mass index or BMI > or = 35 kg/m2) with comorbidities or extreme obesity (BMI > or = 40 kg/m2). Before accepting bariatric surgery as alternative treatment, the four following prerequisites should be met: 1. the medical condition is serious enough; 2. it can not be treated satisfactorily with classical means; 3. the surgical treatment is effective in improving the clinical situation; and 4. bariatric surgery is safe enough, so that the benefits clearly outweigh the risks. On the basis of the literature and our own experience, it appears that gastric reduction surgery may be considered as a valuable alternative for treating severe/extreme obesity, despite the possible occurrence of perioperative and, more frequently, late complications, provided that it is performed by an experienced and multidisciplinary team in well-selected patients.

Anti-Obesity Agents↗
PubMed1999

Troglitazone: antihyperglycemic activity and potential role in the treatment of type 2 diabetes.

Insulin resistance is a major component of type 2 diabetes; therefore, an insulin sensitizer agent like the thiazolidinedione compound troglitazone is considered a very promising drug. Troglitazone exerts an antihyperglycemic activity in a dose-dependent manner between 200 and 600 mg/day in type 2 diabetic patients treated with diet alone, sulfonylureas, or insulin. Additive antihyperglycemic effect may also be obtained by combining troglitazone and metformin. The antihyperglycemic effect of troglitazone as monotherapy is rather modest (reduction of HbA1c by 0.5-1.0%), but it appears to be somewhat greater when it is combined with other antidiabetic drugs. No double-blind studies have directly compared the activity of troglitazone with that of sulfonylureas or metformin. Troglitazone has been shown to exert additional beneficial effects on serum lipid profile and arterial blood pressure. It may be considered as a valuable alternative in insulin-resistant (obese and hyperinsulinemic) diabetic patients who appear to be the best responders to the drug. However, the efficacy of troglitazone is challenged by its safety profile, and the risk of hepatotoxicity still remains a major concern in clinical practice.

Administration, Oral↗
PubMed1999

[How I treat ... an individual with severe obesity and metabolic abnormalities with gastroplasty].

Severe obesity, defined as a body mass index > or = 35 kg/m2, is frequently associated with various biological abnormalities, particularly in the presence of intra-abdominal adiposity. The most important disorders belong to the so-called insulin resistance syndrome, metabolic syndrome or syndrome X: hyperinsulinaemia, impaired glucose tolerance or type 2 diabetes, dyslipidaemias, hyperuricaemia, hyperfibrinogenaemia. All these metabolic abnormalities are considered as cardiovascular risk factors. They are also correlated with the severity of the liver steatosis which is commonly observed in individuals with severe obesity. We report our experience of the evolution of these metabolic abnormalities after a marked weight loss induced by gastroplasty. We will analyse the favourable effects of bariatric surgery on insulin sensitivity, biological components of the metabolic syndrome, type 2 diabetes and liver steatosis.

Cardiovascular Diseases↗
PubMed1999

[Obesity and women: esthetic preoccupation or medical problem?].

Women more and more frequently refer to medical doctors for treating weight excess. Even if the primum movens is usually a pure esthetic concern, medical aspects should not be neglected. Indeed, if obesity with gynoid adipose tissue distribution is less deleterious than android obesity from a metabolic point of view, severe obesity is frequently associated with cardiovascular risk factors which may hinder the prognosis of these female patients. Other complications are common in obese women, such as oestrogen-related cancers, osteoarticular problems and psychological disturbances. Various therapeutic approaches are available which permit an encouraging weight loss and a rapid improvement of risk factors. Unfortunately, long-term results are often disappointing, essentially because of the difficulty to follow on the long term a strict diet regimen and practice physical exercise and because of the usual unrealistic expectations of the obese women who consult medical doctors.

Adult↗