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Biomedical subjects

P J Lefebvre

Publications and source records attributed to P J Lefebvre.

At least 19 recordsLinked to original sources
PubMed2006

[How to explore...the metabolic syndrome by its new IDF definition].

The International Diabetes Federation recently proposed a so-called consensus definition of metabolic syndrome. According to this new definition, a subject has the metabolic syndrome if he/she has abdominal obesity (considered as a prerequisite and assessed, in the European population, by a waist circumference > 80 cm in women and > 94 cm in men) and, in addition, at least two other risk factors among 1) elevated fasting triglycerides > or = 150 mg/dl; 2) low HDL cholesterol HDL < 50 mg/dl in women and < 40 mg/dl in men; 3) increased arterial blood pressure > or = 130/ 85 mm Hg; and 4) elevated fasting plasma glucose concentration > or = 100 mg/dl. We will discuss the advantages and limitations of this new definition as well as the consequences of its use on the prevalence of the metabolic syndrome in the Belgian population.

Abdominal Fat↗
PubMed2001

Changes in blood glucose and plasma insulin levels induced by bradykinin in anaesthetized rats.

1. The influence of bradykinin (BK) on blood glucose and plasma insulin levels was investigated in anaesthetized rats. 2. Blood glucose level was dose-dependently increased by intravenous infusion of BK. This effect of BK was enhanced by captopril, an inhibitor of angiotensin-converting enzyme (ACE). Des-Arg9-bradykinin (DABK), a kinin B1 receptor agonist, did not modify blood glucose levels while the effect of BK was inhibited by Hoe-140, a kinin B2 receptor antagonist. 3. The effect of BK was reduced by the NO-synthase inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME), and by the cyclo-oxygenase inhibitor, indomethacin. The effect of BK was suppressed by the association of propranolol with phentolamine or phenoxybenzamine. It was also reduced by hexamethonium, a ganglion-blocking drug. In adrenalectomized rats, the infusion of BK slightly decreased blood glucose levels. 4. The hyperglycaemic effect of adrenaline was suppressed by propranolol associated with phentolamine or phenoxybenzamine, but it was not modified by L-NAME. 5. Infusion of BK did not modify plasma insulin levels. However, after phentolamine and propranolol, BK induced a transient 2 fold rise in plasma insulin levels. The release of insulin was dose-dependent and inhibited by Hoe-140. 6. We conclude that infusion of BK induces, via a stimulation of B2 receptors, the release of NO and of prostanoids. The latter agents activate through a reflex pathway the release of catecholamines from the adrenal medulla. This release increases blood glucose levels and reduces plasma insulin levels. After adrenoceptor inhibition, BK induces a secretion of insulin, via the stimulation of B2 receptors.

Adrenergic alpha-Antagonists↗
PubMed2001

Risk of developing retinopathy in Diabetes Control and Complications Trial type 1 diabetic patients with good or poor metabolic control.

OBJECTIVE: The study goal was to assess and predict the risk of developing retinopathy in type 1 diabetic patients with extreme metabolic control. RESEARCH DESIGN AND METHODS: Based on material from the Diabetes Control and Complications Trial (DCCT) study (n = 1,441 patients), patients without retinopathy at baseline (DCCT primary cohort) were considered under good or poor metabolic control if the mean HbA(1c) level (until the last visit) fell in the lower or upper 20% of the overall HbA(1c) distribution, respectively. Retinopathy was recorded as either absent or present. Logistic regression was used to predict retinopathy from covariates used in the DCCT retinopathy study. RESULTS: Among the 153 DCCT patients with "good metabolic control" (mean HbA(1c) < or = 6.87%), three-step change retinopathy developed in 15 (9.8%), and 138 (90%) remained free of retinopathy. Conversely, among the 166 patients with "poor metabolic control" (mean HbA(1c) > or = 9.49%), the complication did not develop in 71 (43%) and did develop in 95 (57%). Whereas occurrence of diabetic retinopathy was primarily due to metabolic control (P < 0.0001) and duration of participation in the study (P < 0.0001), two other covariates were found to be significant prognostic factors of the complication: HbA(1c) at baseline (OR 1.37, P < 0.001) and BMI (OR 1.11, P < 0.05). CONCLUSIONS: This study confirms that retinopathy develops in approximately 10% of patients with type 1 diabetes under good metabolic control, whereas > 40% of patients with type 1 diabetes remain free of retinopathy despite poor metabolic control. After adjusting for metabolic control and duration of participation in the study, it was found that previous glycemic exposure (HbA(1c)) and BMI may provide a possible explanation to such paradoxical clinical situations.

Blood Glucose↗
PubMed2000

Non-alcoholic steatohepatitis: association with obesity and insulin resistance, and influence of weight loss.

Non-alcoholic steatohepatitis (NASH) is a disease of emerging identity and importance, and is now considered as one of the commonest liver diseases in western countries. It is frequently associated with severe obesity, especially abdominal adiposity, and is intimately related to various clinical and biological markers of the insulin resistance syndrome. Especially, both the prevalence and the severity of liver steatosis are related to male sex, body mass index, waist circumference, hyperinsulinaemia, hypertriglyceridaemia and impaired glucose tolerance or type 2 diabetes. A substantial weight loss following gastroplasty is accompanied by a marked reduction in the prevalence and the severity of the various biological abnormalities of the metabolic syndrome and, concomitantly, by an important regression of liver steatosis in most obese patients. However, in some patients, this rapid and drastic weight loss may result in a mild increase in inflammatory lesions (hepatitis), despite the regression of steatosis, which might result from the rapid mobilization of fatty acids or cytokines from adipose tissue, especially visceral fat. The intimate relationship between NASH and obesity leads to the concept that NASH may be considered as another disease of affluence, as is the insulin resistance syndrome and perhaps being part of it.

Diabetes Mellitus, Type 2↗
PubMed1999

Insulin sensitivity, clearance and release in kininogen-deficient rats.

Insulin sensitivity of kininogen-deficient rats was compared with that of normal rats using euglycaemic hyperinsulinaemic glucose clamping. Anaesthetized animals were infused with 2-50 mU kg-1 min-1 of insulin and the glucose infusion rates needed to maintain euglycaemia were determined. Maximum glucose uptake, insulin sensitivity index and insulin clearance were reduced in kininogen-deficient rats. Captopril increased the amount of glucose needed to maintain euglycaemia during infusion of 2 and 10 mU kg-1 min-1 of insulin in normal rats, but had no effect in kininogen-deficient rats. Anaesthetized rats of both strains were given an intraperitoneal injection of glucose and the evolution of blood glucose was followed for 120 min. The peak increase was higher in kininogen-deficient rats. Similar larger increases in blood glucose were observed after glucose injection in normal rats previously treated with HOE 140, a bradykinin B2 receptor antagonist. After glucose injection, plasma insulin increased in both groups of rats but reached lower levels in kininogen-deficient animals. These results suggest that bradykinin is involved not only in the clearance of glucose and insulin by the tissues during insulin infusion but also that bradykinin can affect the release of insulin after a glucose load.

Animals↗
PubMed1999

Long-term effects of oral estradiol and dydrogesterone on carbohydrate metabolism in postmenopausal women.

OBJECTIVE: To determine in postmenopausal women the long-term effects on carbohydrate metabolism of the administration of oral micronized 17 beta-estradiol (2 mg/day continuously) and cyclical dydrogesterone (10 mg/day for 14 days per 28-day cycle). METHODS: A 2-year open-label prospective, non-comparative study was carried out of 13 healthy postmenopausal women receiving cyclical estradiol and dydrogesterone and serving as their own controls. Concentrations of blood glucose, plasma insulin, C-peptide, glucagon and free fatty acids (FFAs) were determined before treatment (base-line) and at 6, 12 and 24 months of hormone replacement therapy under fasting conditions and during a standard 75-g, 3-h, oral glucose tolerance test (OGTT). RESULTS: Fasting blood glucose levels were unchanged throughout the study, and the mean areas under the curves (AUCs) for glucose response increased slightly but non-significantly versus baseline; fasting plasma insulin levels tended a decrease, and AUCs for insulin responses to the glucose load fell by 23% from baseline (not significant); fasting C-peptide levels and AUCs were unchanged; plasma glucagon fasting levels and responses were in the normal range and stable throughout the study; and plasma FFA fasting levels decreased significantly, as well as FFA AUCs during OGTTs, at the 12th and 24th months of the study. CONCLUSIONS: During a 2-year treatment with oral estradiol and cyclical dydrogesterone, a direct progesterone derivative, tolerance to glucose was unchanged, fasting plasma insulin and insulin response to repeated glucose loads were decreased, and C-peptide levels remained unchanged, indicating a potential improvement in insulin sensitivity and clearance, as in younger women; additionally, a slightly enhanced antilipolytic activity of insulin was observed.

Blood Glucose↗
PubMed1998

Effects of gastroplasty on body weight and related biological abnormalities in morbid obesity.

Obesity is a prevalent metabolic disorder associated with high morbidity and mortality rates. Medical treatment rarely succeeds, and bariatric surgery has been proposed as an alternative therapy. The purpose of this non-controlled retrospective study was to evaluate time-course changes in body weight in severely obese patients who underwent vertical ring gastroplasty or adjustable silicone gastric banding, and to assess the prevalence and potential reversibility of several of the biological abnormalities associated with morbid obesity. From an initial cohort comprising 658 patients, regular body weight measurements and biological data were obtained in 505 patients [419 females, 86 males; age 36 +/- 11 years; body mass index 42.7 +/- 6.9 kg/m2; (mean +/- SD)] with a mean follow-up of 26 +/- 14 months. Mean weight loss was 32 +/- 16 kg. Most weight reduction occurred within the first 6 months, followed by near-stabilisation or even slight weight regain. Most biological parameters were obtained before surgery and after at least 6 months of follow-up. The high prevalence and severity of metabolic disturbances associated with the insulin resistance syndrome (hyperglycaemia, hyperinsulinaemia, decreased HDL cholesterol, hypertriglyceridaemia, elevated fibrinogen levels and hyperuricaemia) before gastroplasty were significantly decreased after weight loss. No major biological deficiencies were observed following gastroplasty, except low iron serum levels. It is concluded that marked weight loss associated with gastroplasty involved a remarkable reduction in the prevalence and severity of several biological abnormalities classically considered as cardiovascular risk factors.

Adult↗
PubMed1998

[How I evaluate...diabetic nephropathy. First part: micro- and macroalbuminuria].

Diabetic nephropathy (DN) appears in about 30% of patients with type 1 diabetes (D1) and 15 to 60% of patients with type 2 diabetes (D2). It is preceded by microalbuminuria. Microalbuminuria is defined as an albumin excretion rate between 30 and 300 mg/24 h (on a 24-hour urine collection) or between 20 and 200 micrograms/min (on an overnight collection) in at least two out of three consecutive collections made within a 6-month period. Alternative screening techniques use either dipstick (Micral-Test II) or the albumin to creatinine ratio on an early morning urine sample (30-300 mg/g creatinine). Once persistent microalbuminuria is confirmed, 80% of type 1 diabetic patients and 20 to 50% of type 2 diabetic patients will progress to DN. In D2, microalbuminuria also represents a powerful predictor of early mortality from cardiovascular disease. Macroalbuminuria (AER > 300 mg/24 h, corresponding to a total protein excretion > 500 mg/24 h) will eventually lead to a end-stage renal insufficiency within 10 to 20 years. In D2, numerous patients will die from cardiovascular disease before reaching end-stage renal failure. Angiotensin-converting enzyme inhibitors can slow down the evolution toward DN when prescribed when microalbuminuria appears. Screening for microalbuminuria should therefore be a part of the annual clinical assessment in every diabetic patient.

Albuminuria↗
PubMed1997

[Bronchial reactivity in diabetic patients].

The data of the literature concerning bronchial reactivity in diabetic patients are controversial. Therefore, we studied the influence of the presence of a diabetic cardiac autonomic neuropathy (CAN) on the ventilatory parameters measured during a methacholine-induced bronchoconstriction test. Ten insulin-dependent diabetic patients without CAN, ten insulin-dependent diabetic patients with CAN and ten healthy volunteers, all non-smokers and free of respiratory symptoms, have undergone a functional respiratory check-up before the methacholine test. The presence of CAN was classically studied by the decrease in heart rate changes during three standardized tests (deep breathing at 6 cycles/min, Valsalva manoeuver, orthostatism) which all mainly explore the parasympathetic function. The bronchial response to methacholine was similar in the healthy subjects and in the diabetic patients without CAN. However, the fall in forced expiratory volume in 1 second induced by the highest dose of methacholine was significantly less marked in the diabetic subjects with CAN than in the two other groups. These results suggest that the diabetic autonomic neuropathy also involves the vagal innervation of the respiratory tract.

Adult↗
PubMed1996

The involvement of the opioid system in human obesity: a study in normal weight relatives of obese people.

The involvement of the opioid system in human obesity has been demonstrated, but whether the abnormalities in the endorphinergic system play a primary role in overfeeding and weight gain or represent a simple biochemical feature is still unclear. The objectives of this study were to investigate the effects of both physiological and pharmacological plasma beta-endorphin levels on some metabolic and hormonal parameters in a normal weight, but prone to obesity, young population consisting of first degree relatives of obese subjects and in body mass index-, sex, and age- matched control subjects without a family history of obesity. Each subject underwent a 1-h infusion of synthetic human beta-endorphin at a constant rate of 4.5 ng/kg.min (low rate), then after a 1-week interval, at a rate of 500 micrograms/h (high rate). Under basal conditions, there was no significant difference in plasma glucose and pancreatic hormones (insulin, C peptide, and glucagon) between the two groups, except for plasma beta-endorphin levels, which were significantly (P < 0.01) higher in relatives of obese individuals. The low rate of beta-endorphin infusion induced physiological elevations of plasma opioid levels in both groups; no significant change in plasma glucose and pancreatic products in control subjects; and a significant (at least P < 0.05) rise in plasma insulin, C peptide, and glucagon concentrations in relatives of the obese. The high rate of beta-endorphin infusion produced pharmacological elevations of opioid plasma levels in both groups; significant (at least P < 0.05) increments in plasma glucose and glucagon levels and no appreciable modification of plasma insulin and C peptide levels in the control group; and a significant (at least P < 0.05) positive response of plasma glucose, insulin, C peptide, and glucagon levels in relatives of obese subjects. These findings suggest that 1) opioid peptides at least in part play a primary, rather than secondary, role in some metabolic events of obesity; and 2) both physiological and pharmacological plasma levels of beta-endorphin are able to provoke marked islet hormone release in the early phase of human obesity.

Adult↗
PubMed1996

Exhaustion of blood glucose response and enhancement of insulin response after repeated glucagon injections in type-2 diabetes: potentiation by progressive hyperglycemia.

AIMS: To investigate the hyperglycemic and insulinemic response to repeated glucagon injections in Type-2 (non-insulin-dependent) diabetic patients. METHODS: In overnight fasted Type-2 diabetic patients, three i.v. glucagon (1 mg) injections were given as a bolus at two-hour intervals. In the hour preceding each glucagon injection, 6 patients received saline and they were tested at near-baseline blood glucose levels, while 8 patients received a glucose-controlled glucose infusion and they were tested at increasing blood glucose levels (7.5 +/- 0.2, 12.9 +/- 0.5 and 18.7 +/- 0.7 mmol/l). Blood samples were collected at 0, 3, 5, 10, 15, 30 and 60 min after each glucagon injection. RESULTS: In the patients tested at near-baseline blood glucose levels, the blood glucose rise induced by glucagon was smaller after repeated injections. By contrast, the B-cell response to glucagon was well preserved. In the patients tested at increasing blood glucose levels, the blood glucose response to glucagon was abolished after repeated injections. By contrast, the B-cell response was significantly potentiated. The respective areas under the curve of plasma insulin levels in response to glucagon were 563 +/- 72, 1047 +/- 154 and 1844 +/- 305 m U x 30 min/l (p < 0.001). CONCLUSION: In Type-2 (non-insulin-dependent) diabetic patients, repeated glucagon injections, even when administered in a short (4 h) period of time, do not exhaust the B-cell. Endogenous insulin secretion is even potentiated at increasing blood glucose levels. By contrast, the hyperglycemic response to glucagon is significantly abolished, particularly at high blood glucose levels.

Aged↗
PubMed1996

[Non-insulin-dependent diabetes: from physiopathology to treatment].

Non-insulin-dependent (or type 2) diabetes mellitus is a common, underdiagnosed and growing disease in our society. It is responsible for increased morbidity and mortality and represents an important public health problem. This polygenic disease is often expressed late in life and its evolution is accelerated by environmental factors leading to obesity. It combines defects in both insulin secretion and insulin action, and such defects are present in various proportions according to the type of patient and the stage of the disease. Diet and physical activity recommendations are the basis of the treatment. Current pharmacological approaches aim at improving insulin secretion and/or insulin cellular action. After secondary failure to oral drugs, insulin therapy should be initiated, the patient becoming "insulin-requiring". A synergy should be searched in the combination of various therapeutic modalities in order to improve the glycaemic control.

Combined Modality Therapy↗
PubMed1995

Cryptocrine signaling in the thymus network and T cell education to neuroendocrine self-antigens.

Both during phylogeny and ontogeny the thymus appears as a nodal point between the two major systems of cell-to-cell signaling, the neuroendocrine and immune systems. This review presents the experimental observations which support a dual role in T cell selection played by the thymic repertoire of neuroendocrine polypeptide precursors. Through the mode of cryptocrine intercellular signaling thymic neuroendocrine-related precursors synthesized in thymic epithelial cells have been shown to influence the early steps in T cell differentiation. In addition, thymic neuroendocrine-related polypeptides are a source of self-antigens which are presented by the major histocompatibility system of the thymic epithelium. Preliminary data also suggest that the intrathymic T cell education to neuroendocrine self-antigens is not strictly superimposible to the antigen presentation by dedicated presenting cells. Insulin-like growth factor-II (IGF-II) was identified as one dominant member of the insulin family expressed by thymic epithelial and nurse cells. The intrathymic presentation of IGF-II or IGF-II derived self-antigens is under current investigation. If further confirmed, the central tolerogenic properties of IGF-II could be considered in the elaboration of a strategy for an efficient and safe prevention of insulin-dependent diabetes.

Amino Acid Sequence↗
PubMed1995

Modified glucagon test allowing simultaneous estimation of insulin secretion and insulin sensitivity: application to obesity, insulin-dependent diabetes mellitus, and noninsulin-dependent diabetes mellitus.

The aim of this study was to describe an adaptation of the glucagon test allowing the simultaneous characterization of insulin secretion and sensitivity. A glucagon test (1 mg/m2) was performed in healthy subjects (n = 11), obese patients (n = 5), insulin-dependent diabetics (n = 9), nonobese noninsulin-dependent diabetics (n = 7), and overweight noninsulin-dependent diabetics (n = 8). Previously, they had been connected to the Biostator, modified for continuous blood collection. Endogenous insulin secretion induced by glucagon was derived from integrated C-peptide concentrations. An index of insulin sensitivity was obtained by dividing the rate of decrease in blood glucose by the total amount of insulin entering the circulation (secreted+infused by the Biostator). The indices of insulin sensitivity obtained in the above groups of subjects were, respectively, 0.064 +/- 0.006, 0.030 +/- 0.006, 0.037 +/- 0.007, 0.021 +/- 0.006, and 0.016 +/- 0.002 mmol/L.U.min (P < 0.001). The estimated insulin secretion values in the 20 min following glucagon injection were, respectively, 0.38 +/- 0.05, 0.65 +/- 0.08, 0.05 +/- 0.01, 0.26 +/- 0.15, and 0.30 +/- 0.07 U (P < 0.001). The insulin sensitivity index obtained from this test correlated with the glucose MCR obtained from a euglycemic glucose clamp (r = 0.816; P < 0.001; n = 12). C-Peptide levels after glucagon administration were also significantly correlated with the estimated endogenous insulin secretion (r = 0.808; P < 0.001; n = 30). This adaptation of the classical glucagon test is an efficient and simple method to simultaneously evaluate insulin secretion and insulin sensitivity.

Adult↗
PubMed1995

Retinopathy, but not neuropathy, is influenced by the level of residual endogenous insulin secretion in type 2 diabetes.

The files of 132 patients with Type 2 diabetes were retrospectively studied to characterize the influence of metabolic control and residual insulin secretion on neuropathy and retinopathy, the two most frequent degenerative diabetic complications. Patients were classified according to their metabolic control (mean HbA1C either < or > or = 8%; reference values: 3-6%) and residual endogenous insulin secretion (fasting plasma C-peptide levels either < or > or = 0.600 nmol/l). Neuropathy was more frequent in patients with poor metabolic control (32/64 = 50%) than in those adequately controlled (17/68 = 25%; p < 0.005). In both subgroups, the level of endogenous insulin secretion did not influence the prevalence of neuropathy. Retinopathy was less effected than neuropathy by the degree of metabolic control (37.5% in the subgroup with HbA1C > or = 8% v.s. 25% in the subgroup with HbA1C < 8%; p < 0.10), but was influenced by residual insulin secretion. Indeed, in patients with inadequate metabolic control, the prevalence of retinopathy was significantly increased in those with higher endogenous insulin secretion (51.4 versus 20.6%, p < 0.02) and thus probably higher insulin resistance. Furthermore, higher systolic arterial blood pressure was observed in the subgroups with a higher prevalence of retinopathy. Such conclusions were confirmed using multivariate analysis. Thus, in Type 2 diabetes, neuropathy is essentially affected by the degree of metabolic control, whereas retinopathy is also influenced by the level of residual endogenous insulin secretion and the presence of systolic hypertension.

Adult↗