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Biomedical subjects

M Leutenegger

Publications and source records attributed to M Leutenegger.

At least 19 recordsLinked to original sources
PubMed1998

Added benfluorex in obese insulin-requiring type 2 diabetes.

To determine the effect of benfluorex on glycaemic control in obese insulin-requiring Type 2 diabetes, 76 patients (aged 53.8 +/- 12.8 years) receiving insulin (> or = 0.5 IU/kg) and an appropriate low-calorie diet were evaluated after a 1-month run-in followed by a 3-month double-blind treatment period (3 tablets daily) with benfluorex (B; n = 37) vs placebo (P; n = 39). At inclusion, the B and P groups respectively did not differ in body weight (80.9 +/- 10.3 vs 77.2 +/- 9.1 kg), body mass index (BMI) (30.1 +/- 4.6 vs 29.0 +/- 2.3 kg/m2) or fasting blood glucose (11.22 +/- 4.33 vs 10.35 +/- 4.42 mmol/l). However, daily insulin dose and HbA1c levels were higher in the B group (59.9 +/- 18.6 vs 50.4 +/- 12.8 IU, p = 0.012; and 7.72 +/- 1.60 vs 6.96 +/- 1.27%, p = 0.025, respectively). After 3 months of treatment, the decrease in daily insulin dose was greater in the B group (8.7 +/- 10.1 vs 2.7 +/- 8.1 IU; p = 0.032), with a decrease in HbA1c (-0.73 +/- 1.74%, p = 0.026), vs no change in the P group (+0.01 +/- 1.65%, NS) and a tendency towards a greater decrease in fasting blood glucose (-1.43 +/- 5.41 vs +0.42 +/- 3.78 mmol/l respectively). Body weight and BMI were also lower in the B group (1.77 ñ 2.27 vs 0.21 ñ 2.68 kg, p = 0.013; and 0.64 +/- 0.84 vs 0.07 +/- 1.07 kg/m2, p = 0.019, respectively) in parallel with the decrease in insulin dose. Triglycerides decreased in the B group vs an increase in the P group (-0.54 +/- 2.04 vs +0.21 +/- 0.70 mmol/l p = 0.06). Total cholesterol decreased within the B group (-0.47 +/- 1.01 mmol/l; p = 0.013) and vs the P group (intergroup p = 0.006). Adverse events were reported in 11 patients in the B group vs 5 in the P group (NS), causing dropout in only one case (intercurrent illness, P group). Addition of benfluorex in obese insulin-requiring Type 2 diabetes thus enhances glycaemic control and lowers both daily insulin requirement and body weight. Benfluorex + insulin is a valid alternative for obese patients who remain poorly controlled despite insulin or who require high doses of insulin.

Adolescent↗
PubMed1998

Influence of endogenous and environmental factors on variations of serum lipoprotein (a) concentrations in a large population of insulin-treated diabetic patients.

Variations of serum Lp(a) concentrations were studied in a large population of insulin-treated diabetic patients in relation to the type of diabetes, insulin treatment and long-term complications. Lp(a) concentrations were measured by immunonephelometry in 740 diabetic patients [493 insulin-dependent diabetic (IDDM) patients and 247 insulin-treated Type 2 diabetic (ITD) patients]. Concentrations and distributions were compared with those of 128 non-diabetic controls. Correlations were investigated with lipidic and glycaemic parameters, daily lipid intake, body mass index (BMI), macrovascular and nephropathic complications, and insulin therapy. Both groups of insulin-treated patients (IDDM and ITD) displayed significantly higher Lp(a) concentrations when compared to controls. No relationship was found with macrovascular complications and nephropathy, except in IDDM patients in whom Lp(a) was elevated when creatinine concentration was above 120 mumol/L. Mean variations of Lp(a) were correlated with BMI and triglyceride variations in IDDM patients and only with triglycerides in ITD patients. These results suggest a direct and/or indirect (via serum triglycerides) potential role of exogenous insulin in the modulation of serum Lp(a) concentrations. BMI and lipid daily fat intake could be considered as additional modulating factors of Lp(a) serum concentrations in ITD patients.

Adult↗
PubMed1997

Post-prandial metabolism of triglyceride-rich lipoproteins in non-insulin-dependent diabetic patients before and after bezafibrate treatment.

Retarded post-prandial (pp) lipid clearance is potentially a major component of the increased cardiovascular risk incurred by hypertriglyceridaemic non-insulin-dependent diabetic mellitus (NIDDM) patients. The effect of bezafibrate (Bz, 400 mg per day for 5 weeks on chylomicron (CM) and remnant clearance after loads of 100 g of fat and vitamin A was therefore explored in 10 male patients (glycaemia 11.9 +/- 3.3 TG 4.5 +/- 2.4 mmol L(-1)). In all subjects CM-TG and retinyl palmitate (RP) were reduced by 50%, but 8-h non-CM (remnant) RP decreased only in initially mildly hypertriglyceridaemic subjects (-35%, P < 0.05), while in three patients with very elevated initial TG (epsilon3/3, epsilon3/2 and epsilon2/2 genotypes) 8-h remnant RP increased by 100%. The decrease in pp CM-TG correlated with that of fasting Sf 20-400 (r = 0.686, P = 0.026), suggesting that improved lipolysis was a major determinant of hypolipidaemic effect. Apo CIII synthesis is known to be depressed by Bz: concentrations were lower under Bz (P < 0.05). A positive correlation (r = 0.880, P < 0.001) with fasting TG before treatment and its disappearance after treatment suggested an involvement of high concentrations with hypertriglyceridaemia. Post-prandial non-esterified fatty acids were decreased by 35 in correlation with a significant (-19%, P < 0.05) improvement in fasting glycaemia (r = 0.801, P < 0.005). These results suggest that Bz acts both on lipolysis and on removal of CM remnants, but that removal can become saturated when lipolysis is massively improved.

Aged↗
PubMed1997

Short-term intensive insulin therapy in insulin-requiring diabetes: effectiveness and factors predicting success.

Insulin-requiring diabetes (IRD) is a condition of permanent blood glucose imbalance which occurs despite a regulated diet and treatment with maximum doses of oral anti-diabetic drugs (glibenclamide 15 mg/d + metformin 1,700 mg/d). This report describes the results of a 2-year prospective study in 75 IRD patients treated to eliminate their insulin requirement. All had residual endogenous insulin secretion (REIS) (urinary C peptide > 80 micrograms/24 h and/or basal C peptide > 2.4 ng/ml) and were treated for 10 days by subcutaneous insulin infusion via a portable pump. REIS was measured, and insulin resistance was determined by an insulin tolerance test (ITT) to define their insulin sensitivity index (DG/G) before and after 10-day intensive therapy. The patients were monitored as outpatients, and the attempt at remission was considered to be a failure (F) or a success (S). Thirty of the 75 patients (40%) were in remission at 1 year, and 14/67 (21%) at 2 years. No clinical criterion differentiated successes from failures at 1 year, nor was the initial degree of blood glucose imbalance or the REIS predictive of the metabolic changes that occurred after insulin therapy. However, the drop in the insulin requirement (IR) (-26% for F and -39% for S, p < 0.05) and the increases in the DG/G index (+68 +/- 51% for F and 176 +/- 50% for S, p < 0.01) after insulin therapy were indicative of their condition 1 year later. Receiving operating characteristic curves showed that a 35% decrease in IR and an 80% increase in DG/G were indicative of a successful outcome at 1 year, with a specificity and sensitivity of about 70%. It is concluded that a decrease in daily IR and an increase in the DG/G index during insulin treatment are prognostic indicators of the course of insulin-requiring diabetics after temporary intensive insulin treatment.

Diabetes Mellitus, Type 1↗
PubMed1997

Silent myocardial ischaemia and left ventricle hypertrophy in diabetic patients.

The purpose of this study was to evaluate the ability of three noninvasive techniques to detect silent myocardial ischaemia and analyse the factors associated with this condition, particularly left ventricular hypertrophy, in diabetic patients. An ECG stress test, a thallium-201 myocardial scintigraphy with dipyridamole intravenous infusion, ambulatory 48 h ECG monitoring and an echocardiographic study were performed in 92 diabetic patients without cardiac symptoms but with > or = 2 additional cardiovascular risk factors. At least one of these tests was positive in 28 patients (30.4%), suggesting silent myocardial ischaemia. Twenty-four of these patients had a coronary angiography which showed significant coronary stenosis in only 9 cases. An accurate echocardiographic tracing was obtained in 79 patients, particularly in 7 of the 9 with coronary stenosis. Left ventricular hypertrophy was detected in 34 patients, 6 of whom had coronary stenosis. In patients with left ventricular hypertrophy, the positive predictive values of myocardial scintigraphy and the ECG stress test were respectively 50% and 100%, as compared to only 33% and 11% in those without hypertrophy. In summary, coronary stenoses were found in < 10% of asymptomatic diabetic patients with > or = 2 cardiovascular risk factors, but more frequently in individuals with left ventricular hypertrophy. Thus, silent myocardial ischaemia should be searched for first in diabetic patients with hypertrophy, for which the stress test was the most accurate detection method in this study.

Adult↗
PubMed1996

Postprandial cholesteryl ester transfer and high density lipoprotein composition in normotriglyceridemic non-insulin-dependent diabetic patients.

Altered postprandial HDL metabolism is a possible cause of defective reverse cholesterol transport and increased cardiovascular risk in diabetic patients with a normal fasting lipoprotein profile. Ten normolipidemic, normoponderal non-insulin dependent diabetes mellitus (NIDDM) patients and seven controls received a 980 kcal meal containing 78 g lipids with 100 000 IU vitamin A. Chylomicron clearance was not different, but area under the curve (AUC) for retinyl palmitate in chylimicron-free serum (remnant clearance) was greater in patients (P < 0.02). LCAT activity increased postprandially to the same extent in both groups. In control subjects, cholesteryl ester transfer protein (CETP) activity (CETA) also increased by 20% (P < 0.01 at 6 h) in parallel with a 20% decrease in HDL2-CE (r = -0.55, P = 0.009). In NIDDM patients, on the contrary, CETA which was 35% higher in the fasting state (P < 0.005), decreased postprandially yet HDL2-CE remained unchanged. Postprandial HDL3 of controls were enriched with phospholipid (PL) (30.3 +/- 2.6% at 6 h) with respect to fasting (25.6 +/- 2.5%, P < 0.01) and to NIDDM-HDL3 (25.8 +/- 1.7% at 6 h, P < 0.01). These results show that variation in plasma CETA has little impact on HDL2-CE in NIDDH subjects. They support the concept that, in controls, the combined enrichment of HDL3 with PL, increased LCAT and CETA create the conditions for stimulation of cell cholesterol efflux and CE transfer to apo B lipoproteins. In NIDDM, because of the lesser HDL3 enrichment with PL and of the inverse trend of CETA, these conditions fail to occur, depriving the patients of a potentially efficient mechanism of unesterified cholesterol (UC) clearance, despite their strictly normal preprandial profile.

Adult↗
PubMed1996

Serum lipoprotein (a) concentrations in a population of 819 non-insulin-dependent diabetic patients.

Variations in serum Lp(a) concentrations were studied in a large population of non-insulin-dependent diabetic (NIDDM) patients in relation to long-term complications. Lp(a) concentrations were measured by immunonephelometry in 819 NIDDM subjects and compared with those of 128 controls. Correlations were investigated relative to plasma lipid and glycaemic parameters, body mass index (BMI) and macro- and microvascular complications. Mean absolute and relative variations of Lp(a) concentrations were studied in a subgroup of 245 patients over a one-year period. No significant differences were found between Lp(a) concentrations in NIDDM and control subjects. No relationship was evidenced with macrovascular and microvascular complications or glycaemic control. Mean relative Lp(a) variations were correlated with BMI and absolute and relative variations in triglyceridaemia. These results confirm the absence of any alterations of Lp(a) concentrations in a large cohort of NIDDM patients, either with or without micro- and macrovascular complications, but suggest a particular modulatory role for BMI and serum triglyceride variations.

Adult↗
PubMed1995

[Diabetes mellitus and atherosclerosis. Physiopathology of diabetic macroangiopathy].

Numerous prospective epidemiological studies point out high mortality prevalence in diabetic subjects. Classical risk factors, especially arterial hypertension and hypertriglyceridaemia, are abnormally associated with diabetes mellitus. However, they don't account for overall surmortality in this disease. Additional markers of cardiovascular risk appeared as albuminuria, abdominal obesity, and the couple insulinoresistance/hyperinsulinism. Physiopathological intrinsic mechanisms inherent to macroangiopathy are multiple and intricate (hemostatic disorders, endothelial impairments, oxidative stress, quantitative and qualitative lipoproteins abnormalities, part of hyperinsulinism and growth factors). Strict normoglycaemia and exacting control of all other risk factors is essential. Use of other therapeutic agents as antioxidants and antiagregants, is discussed.

Arteriosclerosis↗
PubMed1995

[Respiratory burst of neutrophils and cytokine profile in the non-insulin-dependent diabetic].

Many clinical and experimental data are in favour of a participation of leukocytes in vascular disease. Diabetes, a risk factor, is associated with a dysfunction of neutrophils. If chemotaxis and phagocytosis are deficient, it is not clearly established whether superoxide generation is conserved in these patients. We have measured this function in 35 noninsulin dependent diabetic patients, compared with a control population. We have assessed, in parallel, a profile of the cytokines involved in vascular phenomenons including TNF alpha, IL-1 beta et IL-6. Our results indicate that the generation of free radicals is normal in diabetics, with a significant elevation of TNF alpha. These results suggest a possible participation of this cytokine in the modulation of granulocyte reactivity.

Adult↗
PubMed1995

[Respective value of glycated hemoglobin and fructosamine assays in the care of diabetes mellitus].

The monitoring of metabolic balance in diabetes mellitus involves the assay of cumulative markers of protein glycation. Glycated hemoglobin, particularly the major component HbA1c, and fructosamine, which reflects glycated plasma protein levels, are the most commonly used parameters. Nevertheless, their utilization is still under discussion with respect to methodologies used, as well as to their respective interest in clinical diabetology. This review shows current opinion concerning the analytical and physiopathological use of these biological indicators.

Chromatography, Ion Exchange↗
PubMed1994

[Insulin tolerance tests].

Impaired sensitivity to insulin is a frequent clinical situation and interest in measuring sensitivity to insulin has greatly increased since Reaven described the X syndrome in 1988. This syndrome is an association of increased serum triglycerides, high blood pressure, low levels of HDL and insulin resistance; affected patients have an increased risk of coronary artery disease. Several methods have been described to measure insulin resistance. They rely on the effect of insulin on glucose metabolism. The euglycaemic clamp interprets the interactive feedback control between insulin and glucose. Insulin is infused to reach a constant serum insulin level, then glucose is administered at predetermined levels. The blood glucose level thus corresponds to hepatic production and insulin sensitivity is expressed as the amount of glucose infused in mg/kglmin. Metabolic glucose clearance is the relationship between glucose consumption and blood glucose level during the test. This method is reliable, reproducible and eliminates the errors related to insulinindependent metabolism. Steady state plasma glucose relies on drugs which suppress endogenous insulin secretion. Glucose and insulin are then infused at constant rates and the resulting glucose and insulin levels express insulin sensitivity. This method is technically difficult to handle and is used less often. Bergman's minimal model and the modified insulin tolerance test offer other more practical and global methods with particular indications. Each method has its advantages and disadvantages in terms of precision, cost and duration. The choice of a method is basically made as a function of the clinical or research needs.

Glucose Clamp Technique↗
PubMed1993

Study of the rate of early glucose disappearance following insulin injection: insulin sensitivity index.

The euglycaemic hyperinsulinaemic glucose clamp is usually considered as the reference technique to evaluate insulin sensitivity. As it is an expensive and time-consuming tool, we therefore tried to validate a simple insulin tolerance test (ITT) (IV bolus of 0.1 IU/kg of regular insulin, with glucose sampling at -5, 0, 3, 5, 7, 10 and 15 min) and to demonstrate its usefulness. Insulin sensitivity was measured by DG/G0 ratio (G0 = initial glycaemia, DG is the variation between G0 and the glycaemia obtained at 15 min by the calculation of the regression plot). We confirmed the existence of a correlation between the glucose uptake (mg/kg per min) evaluated by glucose clamp and the DG/G0 index (r = 0.9, P < 0.01). There was no stimulation of hormonal counter regulation during the test. The ITT was significantly correlated both with fasting insulin (r = -0.43, P < 0.01), and post-glucose load insulin concentration (r = -0.67, P < 0.01); each measurement expressing insulin sensitivity. Four groups of patients with different insulin sensitivity: controls, NIDDM, gynoid and android obese subjects, were clearly separated by ITT. We showed that fasting glycaemia and DG/G0 were correlated (y = 2.63/x - 0.093; r = 0.82, P < 0.01). These results suggest that ITT could be an easy, quick and low cost method to evaluate insulin resistance in clinical practice and epidemiological studies.

Adult↗
PubMed1993

[Insulin-dependent diabetes and organ specific autoimmune diseases: a retrospective clinical and immunogenetic study of 165 consecutive cases].

We analysed clinical and immunological indexes in 165 caucasian adult patients presenting insulin-dependent diabetes mellitus associated with other organ-specific autoimmune diseases (type Ib IDDM). As diagnostic strategy, we recommend testing thyrogastric autoantibodies at diabetes onset and islet-cells antibodies three years after.

Adolescent↗