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Biomedical subjects

F Berthezène

Publications and source records attributed to F Berthezène.

At least 19 recordsLinked to original sources
PubMed2004

[The quality-of-life questionnaire QLS-H: validation of the French language version of the questionnaire in patients with growth hormone deficiency and collection of reference data in the general population].

The QLS-H(c) (Questions on Life Satisfaction- Hypopituitarism) is new a quality of life (QoL) self-administered questionnaire addressing the complaints of adult patients with growth hormone deficiency. The French version of the QLS-H(c) (16 items) has been psychometrically evaluated during a randomized, open label study comparing two strategies of growth hormone (GH) replacement therapy. Seventy-three patients were included and received an 8-month GH replacement therapy. QoL was explored at baseline, 4 and 8 months using the QLS-H(c) questionnaire and the Nottingham Health Profile (NHP) reference scale. Acceptance of the QLS-H(c) was excellent as 92% of the questionnaires were suitable for analysis. All the items demonstrated good selectivity. The homogeneity of the questionnaire was confirmed (Cronbach's alpha, 0.87). The external validity construct was assessed and confirmed using the NHP scores. Sensitivity to change was confirmed. Following an 8-month replacement therapy, the perception of the QoL assessed with the QLS-H(c) questionnaire was significantly improved, irrespective to the treatment strategy. Finally, redundant items of the questionnaire were removed. As a result, the final version of the QLS-H(c) contained 9 items. In a parallel study, reference data of the QLS-H(c) (9 items) were collected from a representative sample of 989 subjects from the French population. With these reference ranges, algorithms to calculate Z scores adjusted for age and gender were developed as a measure for the deviation of patients' scores from those of the general population, and also to evaluate changes along time. In summary, the French version of the quality of life QLS-H(c) questionnaire is a relevant, validated investigational tool for the evaluation and follow-up of an adult patient with growth hormone deficiency.

Adult↗
PubMed2001

Excessive body weight as a new independent risk factor for clinical and pathological progression in primary IgA nephritis.

Experimental evidence suggests a role for obesity in the formation and progression of some glomerular lesions, but data for human glomerulonephritis are lacking. In a cohort of 162 incident patients with biopsy-proven immunoglobulin A (IgA) nephropathy, we assessed whether the presence of an elevated body mass index (BMI >/= 25 kg/m(2)) at the time of the first renal biopsy (RB1) correlated with clinical data at RB1 (24-hour proteinuria, arterial hypertension, and renal function), pathological data (global optical score [GOS] with detailed pathological indices), and clinical progression to both arterial hypertension and chronic renal failure (CRF). In both univariate and multivariate analyses, the presence of an elevated BMI at RB1 was significantly associated with the severity of pathological renal lesions (GOS and vascular, tubular, and interstitial indices). Hypertension-free survival was significantly less in overweight patients (P: < 0.0001) compared with those with normal weight. In a Cox regression analysis for hypertension-free survival including 24-hour proteinuria greater than 1 g, GOS, and metabolic parameters, only elevated BMI and GOS were independent factors for the development of arterial hypertension. CRF-free survival was also significantly less in patients with an excessive BMI. In a multivariate Cox regression analysis for CRF-free survival, hypertension, GOS, and BMI at RB1 were independent risk factors for CRF. In IgA nephropathy, excessive body weight and/or BMI are underestimated predictive factors for the development of arterial hypertension and, ultimately, CRF.

Adult↗
PubMed2001

PROP1 gene screening in patients with multiple pituitary hormone deficiency reveals two sites of hypermutability and a high incidence of corticotroph deficiency.

Alterations of the gene encoding the pituitary transcription factor PROP1 were associated with congenital forms of multiple pituitary hormone deficiencies in several families. Among 23 patients with multiple pituitary hormone deficiencies screened for a PROP1 gene abnormality, nine belonging to eight unrelated families had homozygous PROP1 gene defects. All mutations were located in exon 2 and affected only two different sites: a homozygous AG deletion at codons 99/100/101 (n = 5); homozygous point mutations affecting codon 73: R73C (n = 2) or R73H (n = 1), and a R73C/R99X double-heterozygous mutation (n = 1). R73H and R99X were never described. All patients were born to unaffected parents, and consanguinity was documented in two patients. They had complete GH, LH-FSH, and TSH deficiencies and normal basal levels of PRL. Delayed ACTH deficiency was diagnosed in four of nine patients. At magnetic resonance imaging the anterior pituitary was hypoplastic in seven patients and hyperplastic in two. This study found two novel mutations (R73H and R99X) and underlines the high incidence of PROP1 gene alterations in patients with multiple pituitary hormone deficiencies. A corticotroph deficiency was frequently observed in association with GH, TSH, and gonadotropin deficiencies and should be carefully sought during follow-up.

Adolescent↗
PubMed2001

[Hormone replacement therapy at menopause in the diabetic woman].

Epidemiological: higher coronary risk in female diabetic patients than in male diabetic patients. Physiopathological: disturbance of lipid metabolism and endothelial nitric oxide (NO) production, seen in both menopausal and diabetic subjects. Hormonal: hyperandrogenism and excessively high blood oestradiol levels in diabetic menopausal women in relation to non-diabetic menopausal women. HRT in menopausal diabetic women Efficacy against climacteric disorders and osteoporosis. No major risks since the effects on lipoproteins are not significant and there are some positive effects on hepatic glucose production during hyperinsulinaemic clamp, provided triglycerides are below 2 mmol/l. Relatively positive effects have been noted in cohort studies such as the Nurses' Health Study and in a study measuring carotid intima-media thickness, but marked bias occurred in recruitment. HRT and coronary disease in diabetic and non-diabetic women Harmful effects were noted, particularly in the HERS study, with a higher incidence of fatal and non-fatal thromboembolic and/or coronary events. Other studies are underway using both conjugated equine estrogens (Women's Health Initiative) and SERMs (raloxifen and tamoxifen).

Blood Glucose↗
PubMed2000

Postmenopause hormone treatment in women with NIDDM or impaired glucose tolerance: the MEDIA randomized clinical trial.

OBJECTIVE: To assess the biological safety of four hormone replacement treatment (HRT) combinations in women with non insulin dependent diabetes mellitus (NIDDM) or impaired glucose tolerance (IGT). SUBJECTS AND METHODS: Randomized, double-blind, placebo-controlled trial to analyze the variation of fibrinogen, factor VII, PAI1, and TG blood levels in women (n=99), with NIDDM or IGT, receiving a 3-month course of either oral oestradiol (1 or 2 mg) combined with Chlormadinone Acetate 5 mg, or transdermal oestradiol 50 microg/24 h in association with Norethisterone Acetate (11.2 or 22.4 mg), or placebo. Follow-up lasted 3 months. RESULTS: Ninety nine patients, mean age 56 years (SD 5), mean diabetes duration 7 years (S.D. 7), mean glycated hemoglobin (7.3%) were enrolled. There was no significant difference between the groups for any of the primary hemostasis criteria (n=77). Triglycerides (TG) variation significantly differed between groups, P=0.01, from -21% in the large patch group, to +22% in the placebo group (n=82). Treatment administration routes did not significantly differ for any of the criteria. There was a significant difference in the total cholesterol variation between groups, from +8.7% in the placebo group to -10.8% in the oral 1 mg group (P=0.001). CONCLUSION: The treatments had no highly deleterious effect in these patients with NIDDM or with IGT. Long-term trials can be performed with such patients, and an hormone treatment can be prescribed to relieve symptoms. Since these patients had a well-controlled NIDDM, results might be different in less well-controlled diabetes. The data do not support the hypothesis of an impaired oestrogen effect in patients with NIDDM.

Biomarkers↗
PubMed2000

Association between microsomal triglyceride transfer protein gene polymorphism and the biological features of liver steatosis in patients with type II diabetes.

AIMS/HYPOTHESIS: Non-alcoholic steatohepatitis is frequent in Type II (non-insulin-dependent) diabetes mellitus and can lead to fibrosis and cirrhosis. The interindividual variability in the occurrence of nonalcoholic steatohepatitis suggests, however, a genetic modulation. Microsomal triglyceride transfer protein (MTP) is necessary for the assembly and secretion of VLDL and when the protein is not functional, such as in abetalipoproteinaemia, a steatohepatitis occurs. We therefore assessed the association between a functional polymorphism in the promoter region of MTP gene (-493 G/T) and the biological features of steatohepatitis in Type II diabetic patients. METHODS: We studied 271 patients with Type II diabetes. Determination of -493 G/T polymorphism was made by PCR-RFLP. Increased liver enzymes were used as surrogates of liver steatosis and alanine aminotransferase concentration was the outcome variable for the multivariate analysis. Liver ultrasonography was available for a subgroup of patients with newly diagnosed diabetes. RESULTS: The proportion of patients with increased alanine aminotransferase was higher in GG than in GT and TT subgroups (23%, 11% and 6%, respectively, p = 0.01). Additionally, patients with high alanine aminotransferase concentrations were more likely to be young (p = 0.01), male (p = 0.001), obese (p = 0.04) and have low HDL-cholesterol (p = 0.01). In multivariate analysis, the MTP genotype was independently associated with alanine aminotransferase concentration (p = 0.0023) as well as sex and body mass index but not HDL-cholesterol. CONCLUSION/INTERPRETATION: The -493 G/T MTP gene polymorphism is associated with biological surrogates of steatohepatitis in patients with Type II diabetes. The G allele which is responsible for a decrease in MTP gene transcription is prone to increase the intrahepatic triglycerides content, conferring by this a genetic susceptibility for steatohepatitis.

Adult↗
PubMed1999

[Surveillance of uncomplicated type 2 diabetes].

Follow up in type 2 diabetes must be regular with an annual check-up and pluriannual consultations of adapted frequency. It's important to consider the diabetic patient in totality: reaching the previous objectives of weight and glycaemia, all vascular risk factors and evolution to complications. Some tests are necessary (retin exam, microalbuminuria, ECG...), but with an attentive clinic exam we can avoid many useless and expensive paraclinic explorations. It's also a motivation tool for patients.

Aftercare↗
PubMed1999

Decrease in carotid intima-media thickness after one year growth hormone (GH) treatment in adults with GH deficiency.

An increased carotid arterial intima-media thickness (IMT) has been reported in hypopituitary adults untreated for GH deficiency. In the present study, the effect of GH replacement on IMT and cardiovascular risk factors was prospectively investigated, in GH deficiency patients treated at a mean dose of 1 UI/day during 1 yr (n = 22) and 2 yr (n = 11). The IMT measurements were performed by the same experienced physician, and the coefficient of variation (calculated in two control groups) was below 6.5%. IMT at baseline was related to conventional risk factors. After 1 yr GH treatment, IMT decreased from 0.78 +/- 0.03 mm to 0.70 +/- 0.03 mm (P < 0.001). The decrement was observed in 21 of 22 patients. After 2 yr GH treatment, IMT had stabilized at 0.70 +/- 0.04 mm and remained significantly different from baseline values (P < 0.003). GH treatment resulted in a moderate decrease in waist circumference and body fat mass and an increase in VO2 max. Conventional cardiovascular risk factors were unmodified except for a transient 10% decrease in low-density lipoprotein cholesterol at 6 months. The contrast between the limited metabolic effect of treatment and the importance and precocity of the changes in IMT suggests that the decrease in IMT was not exclusively attributable to a reversal in the atherosclerotic process. A direct parietal effect of GH replacement on the arterial wall might also be involved. The consequences, in terms of cardiovascular risk, should be established by randomized prospective trials.

Adult↗
PubMed1999

VLDL-bound lipoprotein lipase facilitates the cholesteryl ester transfer protein-mediated transfer of cholesteryl esters from HDL to VLDL.

In recent years, it has been established that lipoprotein lipase (LPL) is partly associated with circulating lipoproteins. This report describes the effects of physiological amounts of very low density lipoprotein (VLDL)-bound LPL on the cholesteryl ester transfer protein (CETP)-mediated cholesteryl ester transfer (CET) from high density lipoprotein (HDL) to VLDL. Three patients with severe LPL deficiency exhibited a strong decrease in net mass CET that was more than 80% lower than that of common hypertriglyceridemic subjects. Recombination experiments showed that this was due to an abnormal behavior of the VLDL fraction. Replacement of the latter by normal VLDL totally normalized net mass CET. We therefore prepared VLDL containing controlled amounts of bound LPL that we used as CE acceptors in experiments involving unidirectional radioisotopic CET measurements. These were carried out either in the absence or in the presence of inhibitors of LPL lipolytic activity. When LPL-induced lipolysis was totally blocked, the stimulating effect of the enzyme on the CETP-dependent CET was only reduced by about 50%, showing that it did not entirely result from its lipolytic action. These data were dependent upon neither the type of LPL inhibitor (E600 or THL) nor the source of CETP (delipidated plasma or partially purified CETP). Thus, in addition to the well-known stimulating effect of LPL-dependent lipolysis on CET, our work demonstrates that physiological amounts of VLDL-bound LPL may facilitate CET through a mechanism partially independent of its lipolytic activity.

Animals↗
PubMed1998

Association between plasma HDL-cholesterol concentration and Taq1B CETP gene polymorphism in non-insulin-dependent diabetes mellitus.

The effects of CETP gene Taq1B polymorphism on plasma lipoproteins were investigated in 176 patients with non-insulin-dependent diabetes mellitus. The distribution of CETP genotypes was similar to that previously described in the general population. A significant association was found between CETP genotype and both CETP and HDL cholesterol (HDL-c) concentrations. B1B1 had the highest CETP and the lowest HDL-c whereas B2B2 had the lowest CETP and the highest HDL-c. However, HDL-c was not correlated with CETP concentration, even when genetic groups were separately considered. By multivariate analysis, the determinants of HDL were body mass index, triglycerides concentration, net mass CE transfer, and CETP genotype. No association was found between CETP genetic groups and HDL or LDL size distribution. In contrast, net mass CET was positively and HDL and LDL sizes were negatively correlated with plasma triglyceride concentration. Overall, our work demonstrates that, in a population of diabetic patients where lipoprotein-related parameters vary over a large range, the association of CETP gene polymorphism with HDL-c is independent of plasma CETP concentration.

Adult↗
PubMed1997

Efficacy of low-dose pravastatin in patients with mild hyperlipidemia associated with type II diabetes mellitus.

A 16 week, randomized, double-blind, parallel, placebo-controlled study was designed to determine the effects of low-dose pravastatin on cholesterol concentrations in patients with mild hypercholesterolemia and non-insulin-dependent diabetes mellitus (NIDDM). Following a 6-to 8-week dietary run-in period, a mean serum total cholesterol (TC) level > 5.2 mmol/L (200 mg/dL), but < 7.8 mmol/L (300 mg/dL) was required for entry. Metabolic control of diabetes was determined by a hemoglobin Alc (HbAlc) level less than twice the upper limit of normal on two occasions. Eighty six (86) patients recruited in 5 French diabetic clinics, were randomized in a ratio of 1:1 (pravastatin 10 mg or placebo), and 74 completed the study. There were 12 discontinuations: 5 (11.6%) in the pravastatin group and 7 (16.3%) in the placebo group. Drop-out was due to an adverse event in 1 patient (2.3%) in the pravastatin group and in 5 patients (11.6%) in the placebo group. Thirty five (35) placebo patients and 14 pravastatin patients had their dose of treatment doubled at week 8: the dose of treatment was to be doubled at week 8 in the event of non-response to treatment (TC at week 7 > 5.2 mmol/L and TC decrease < 15% from baseline). At week 16, pravastatin lowered TC from 6.4 to 5.6 mmol/L (-13.8%, p < 0.001 versus placebo), low-density lipoprotein cholesterol (LDL-C) from 4.3 to 3.4 mmol/L (-20.4%, p < 0.001 versus placebo) and slightly increased high-density lipoprotein cholesterol (HDL-C) from 1.18 to 1.25 mmol/L (+6.7%). Side effects were similar in both groups. Blood glucose control was not altered as assessed by serial HbAlc measurements which were unchanged during treatment. This study demonstrated that low-dose pravastatin is effective in lowering cholesterol levels in patients with hypercholesterolemia and NIDDM.

Adult↗
PubMed1996

Alterations in composition and concentration of lipoproteins and elevated cholesteryl ester transfer in non-insulin-dependent diabetes mellitus (NIDDM).

Cholesteryl esters (CE) exchange between lipoproteins through the action of cholesteryl ester transfer protein (CETP). Situations at high risk for atherosclerosis are often accompanied by an accelerated net mass CE transfer (CET) from high density lipoproteins (HDL) to very low (VLDL) and low density lipoproteins (LDL). However, the question as to whether the net mass CET is increased or decreased in non-insulin-dependent diabetes mellitus (NIDDM) has led to controversial data. To clarify this point, we have undertaken a detailed study of CET in 105 NIDDM patients by comparison with 17 control subjects. Net mass CET was approximately doubled in NIDDM. Plasma CETP activity and unidirectional CET from HDL to VLDL + LDL (CETHDL-->VLDL + LDL) or from VLDL + LDL to HDL (CETVLDL + LDL-->HDL) were measured under controlled lipoprotein concentrations using radioisotopic assays. No difference was observed in plasma CETP activity between NIDDM and controls. In NIDDM, CETHDL-->VLDL + LDL and CETVLDL + LDL-->HDL were decreased by 25% and 20%, respectively, as a consequence of alterations in lipoprotein compositions. Net mass CET was highly correlated with plasma triglyceride (TG) concentration (r = 0.66, P < 0.001) but not with that of LDL-cholesterol (r = 0.06, P > 0.6). When TG levels were decreased following dietetic recommendations or insulinotherapy, the net mass CET was lowered accordingly. We conclude that net mass CET is accelerated in NIDDM in spite of a decreased unidirectional CETHDL-->VLDL + LDL. This results from a lowered CETVLDL + LDL-->HDL and from elevated TG concentration, and the latter probably reflects a concentration effect of VLDL.

Adult↗
PubMed1996

Minimally oxidised LDL as estimated by a new method increase in plasma of type 2 diabetic patients with atherosclerosis or nephropathy.

A new sensitive and reproducible method was used to assess LDL oxidative status in Type 2 diabetic patients and control subjects, and the relationships between LDL oxidation and atherosclerosis or nephropathy were determined. LDL oxidation was measured in 35 patients with Type 2 diabetes and 15 control subjects 40 to 60 years of age. Atherosclerosis was assessed by clinical examination, vascular ultrasound, and measurement of intima-media thickness (IMT). Twenty-four hour urinary albumin excretion measurements were performed. Although no differences in lipid values were found between the 22 diabetic patients with atherosclerosis (ATS+) and the 13 without (ATS-), LDL oxidation was significantly higher in ATS+ than ATS- patients (p = 0.009) or control subjects (p = 0.007). LDL oxidation was also increased in the 15 patients with nephropathy (p = 0.003). Oxidation was correlated with IMT in patients with normal to moderately increased IMT ( < or = 1.05 mm). Determination of LDL oxidative status could thus be very helpful in assessing cardiovascular risk, especially in high-risk subjects such as patients with diabetes mellitus.

Adult↗
PubMed1993

[Estrogens, progestins and glucido-lipid metabolism].

Estrogen and progestogen effects on lipid and carbohydrate metabolism are reviewed. Their actions depend on the type and dosage of molecules and their route of administration. Steroid replacement therapy in post menopausal women results in most cases in beneficial effect on lipids without alteration of carbohydrate metabolism. Therapeutic implications in women with metabolic disturbances as hyperlipidemia or diabetes are discussed.

Carbohydrate Metabolism↗