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M Broch

Publications and source records attributed to M Broch.

25 records · Page 2Linked to original sources
PubMed1998

Beta 3-adrenoreceptor gene polymorphism and leptin. Lack of relationship in type 2 diabetic patients.

INTRODUCTION: The beta 3-Adrenergic receptor (beta 3AR) and leptin are molecules involved in the regulation of energy balance. Recently, a mutation in the beta 3AR gene (Trp64Arg) has been reported to be associated with features of insulin resistance, weight gain and early onset of Type 2 Diabetes Mellitus. The aim of this study was to determine the frequency and clinical characteristics of the Trp64Arg mutation in the beta 3AR gene in Type 2 diabetic patients, its relationship with leptin levels, and its role in microangiopathic complications. SUBJECTS AND METHODS: 187 Type 2 diabetic patients and 100 unrelated non-diabetic subjects were studied. There was no difference between the diabetic and nondiabetic subjects in the frequency of the Trp64 and Arg64 alleles (92.5% vs. 92.3% and 7.5% vs. 7.7%, respectively). Type 2 diabetic patients were divided into two groups according to the presence (n = 27) or absence of the mutation (n = 160). RESULTS: Mutation of the beta 3AR gene was not associated with any differences either in the clinical and metabolic parameters or microangiopathic complications. Type 2 diabetic patients carrying the Arg64 allele tended to have a lower diabetes duration, but this was not statistically significant. Plasma leptin levels were not different according to the beta 3AR genotype. CONCLUSIONS: The Trp64Arg mutation is not a major determinant of Type 2 diabetes and its microangiopathic complications. Moreover, this mutation was not clinically relevant in leptin regulation.

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PubMed1998

Plasma levels of the soluble fraction of tumor necrosis factor receptor 2 and insulin resistance.

Recent studies have shown that the tumor necrosis factor (TNF) system is implicated in the insulin resistance of human obesity. Plasma concentrations of the soluble fraction of the TNF receptors 1 and 2 (sTNFR1 and sTNFR2) are thought to reflect the degree of activation of the TNF system. The purpose of this study was to explore whether this activation, as measured by the levels of circulating sTNFR1 and sTNFR2, is associated with insulin resistance. A total of 19 men (mean age 36.2 +/- 1.9; BMI 28.8 +/- 1.2, range 22.2-35.7) and 17 premenopausal women (age 34.9 +/- 1.4; BMI 28.1 +/- 0.8, range 19-37.9) were studied. Men showed higher levels of plasma sTNFR1 and sTNFR2 than women. However, obese men showed increased levels of sTNFR2 but similar levels of sTNFR1 in comparison with obese women. In fact, sTNFR2 levels correlated with BMI (r = 0.50, P = 0.002), fat-free mass (FFM) (r = 0.61, P < 0.0001), and waist-to-hip ratio (WHR) (r = 0.39, P = 0.02), but not with fat mass or percent fat mass. sTNFR2 levels correlated with basal glucose levels (r = 0.45, P = 0.007), area under the curve (AUC) for glucose during an oral glucose tolerance test (r = 0.42, P = 0.013), and with the quotient AUC glucose/log AUC insulin (r = 0.41, P = 0.015). sTNFR2 also correlated negatively with insulin sensitivity (S(I)), evaluated using the frequently sampled intravenous glucose tolerance test with minimal model analysis (r = -0.38, P = 0.02). Plasma sTNFR1 levels were not associated with any of these variables. Because WHR influenced both S(I) and sTNFR2 levels, we constructed a multiple linear regression to predict S(I), with WHR and sTNFR2 as independent variables. In this model, both WHR (P = 0.0078) and sTNFR2 levels (P = 0.025) contributed to 47% of the variance in S(I). In parallel with higher FFM, lean and obese men showed a lower S(I) (2.9 +/- 0.9 vs. 5.2 +/- 1.3 min(-1) x mU x l(-1), P = 0.001; and 1.15 +/- 1.1 vs. 1.8 +/- 0.8 min(-1) x mU x l(-1), P = 0.035, respectively) and higher sTNFR2 levels in comparison with lean and obese women, respectively. After controlling for FFM, the correlation between S(I) and sTNFR2 levels disappeared, indicating that FFM was significantly influencing these associations. In summary, plasma sTNFR2 levels, but not sTNFR1, were proportional to BMI, WHR, FFM (a well-known confounder in the evaluation of insulin sensitivity), basal and postload glucose levels, and insulin resistance. These findings support TNF-alpha as a system regulating insulin action in human obesity.

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PubMed1997

The TNF-beta gene Nco I polymorphism is not associated with hypertriglyceridemia or insulin resistance in lean and obese subjects.

Interindividual differences in TNF-alpha monocyte responses can be accounted for by genetic polymorphisms at the TNF-beta locus defined by the Nco I restriction enzyme. Higher triglyceride levels in non-insulin-dependent diabetic patients homozygous at the 10.5-kb fragment of the TNF-beta gene have been described. The aim of this study was to investigate whether the Ncol polymorphism of the TNF-beta gene influences the relationship between insulin resistance and triglyceride levels. Thirty-eight healthy volunteers were divided into two groups according to the absence [homozygous for class 1 allele (1/1), n=16] or presence of the class 2 allele [n=22; 19 heterozygous (1/2), and 3 homozygous (2/2)]. Both groups were comparable in sex, age, BMI, waist/hip ratio, fat mass and percentage of body fat as measured by bioelectric impedance, skinfold measurements, and blood pressure (all p>0.05). There were no differences in serum cholesterol (total, or HDL and VLDL fractions) or in total or VLDL triglycerides between the groups (all p>0.05). The insulin sensitivity index (Minimal Model method) was comparable for the two groups. In summary, the 10.5-kb homozygous genotype of the TNF-beta locus does not contribute to differences in triglyceride levels or insulin sensitivity among nondiabetic subjects.

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PubMed1997

Angiotensin I-converting enzyme and angiotensinogen gene polymorphisms in non-insulin-dependent diabetes mellitus. Lack of relationship with diabetic nephropathy and retinopathy in a Caucasian Mediterranean population.

Genotypic abnormalities of the renin-angiotensin system have been suggested as a risk factor for the development of microangiopathic complications in diabetic patients. We studied the relationship of either an insertion-deletion polymorphism in the angiotensin-converting enzyme (ACE) gene and the M235T and T174M variant polymorphisms of the angiotensinogen (AGT) gene in non-insulin-dependent diabetes mellitus (NIDDM) patients and its relationship with cardiovascular complications. A total of 193 NIDDM patients (89 men and 104 women aged 59.2 +/- 10.0 years; diabetes duration, 13.2 +/- 6.2 years) and 90 control subjects (42 men and 48 women aged 45.4 +/- 12.6 years) were recruited for the association study. Distribution of the genotype or allelic frequencies for all the studied polymorphisms did not differ significantly between controls and NIDDM patients. ACE and AGT genes did not display any difference in clinical or metabolic parameters according to each gene's genotype for either the control or the NIDDM group. For evaluation of nephropathy and retinopathy, NIDDM patients were matched with subjects not having microangiopathic complications. Thus, a total of 60 patients had diabetic nephropathy and were compared with 100 patients with normoalbuminuria. Sixty-eight NIDDM patients had diabetic retinopathy, and 92 patients presented no signs of retinopathy. There were no differences in genotypic or allelic distribution between NIDDM patients for either the presence or absence of retinopathy or nephropathy. We conclude that the ACE and AGT polymorphisms do not contribute to the genetic susceptibility to diabetic nephropathy and retinopathy in a caucasian Mediterranean population.

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PubMed1996

[Apolipoprotein AI-CIII, B, and CII gene polymorphisms in patients with non-insulin dependent diabetes mellitus. Association with hyperlipemia].

BACKGROUND: Dislipidaemia is an usual feature in patients affected by non insulin dependent diabetes mellitus. Several studies show that this disease could be genetically determined. The aim of this study was to ascertain whether any of the genetic polymorphism remaining in three apolipoprotein loci (apolipoprotein AI-CIII, B100 and CII) is related with the presence of dislipidaemia in non insulin dependent diabetes mellitus patients. PATIENTS AND METHODS: 53 non insulin dependent diabetes mellitus patients with less than 5 years evolution and treated only with diet, were included. 86 healthy persons were included as the control group. The lipidic parameters analyzed were: cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, apolipoprotein AI, B and lipoprotein (a). The following polymorphic variants were analyzed: RFLP-Sacl of the apolipoprotein AI-CIII-AIV cluster, RFLP-Xbal of the apolipoprotein B100 region and the RFLP-Taql of the apolipoprotein E-CI-CII cluster. RESULTS: There were no genetic nor allelic differences in the distribution of the genes, between controls and diabetic patients. Regarding the apolipoprotein CII gen, the diabetic patients with the T2T2 genotype had higher triglyceride levels (p < 0.01) compared with the remaining genotypes and compared with the control group having the same genotype (p < 0.01) matched for sex, age and body mass index. There was no difference in the metabolic parameters' distribution related to the genotypic distribution of the apolipoproteins AI-CIII and B100 genes. CONCLUSIONS: The apolipoprotein CII can be related with the presence of hypertriglyceridaemia in non insulin dependent diabetes mellitus patients.

Adult↗
PubMedDate not supplied

Left ventricular hypertrophy in hypertensive patients with autosomal dominant polycystic kidney disease: influence of blood pressure and humoral and neurohormonal factors.

Left ventricular hypertrophy (LVH) is a common finding in hypertensive autosomal dominant polycystic kidney disease (ADPKD) patients. There are few studies on the influence of blood pressure (BP) and nonhemodynamic factors on LVH in these patients. The aim of this study was to evaluate the relationship between BP, humoral and neurohormonal factors and left ventricular mass (LVM) in hypertensive ADPKD patients. In 20 hypertensive ADPKD patients, ambulatory BP was monitored for 24 h, left ventricular dimensions were estimated by echocardiography, and plasma renin activity (PRA), plasma noradrenaline (NA), angiotensin II (Ang II), aldosterone, atrial natriuretic peptide (ANP) and insulin-like growth factor I (IGF-I) were also determined. Twenty age- and sex-matched essential hypertensive subjects served as controls. Ambulatory BP and LVM index were similar in the two groups, although male ADPKD patients had higher LVM indices than their matched controls. Eight ADPKD patients (40%) and 6 essential hypertensives (30%) showed LVH. PRA, Ang II, aldosterone, ANP and IGF-I levels were similar in the two groups, but plasma NA levels were higher in ADPKD patients than in controls (281 +/- 158 vs. 160 +/- 62 pg/ml, p = 0.004). ADPKD patients with LVH did not differ from those without LVH with regard to humoral and neurohormonal parameters, but had higher ambulatory BP levels. In ADPKD patients, correlation analysis revealed a significant association between LVM index and 24-hour systolic and diastolic BP, but not with any of the hormonal factors evaluated. On multiple regression analysis, 24-hour diastolic BP was the only independent variable linked to LVM index. In conclusion, ambulatory BP is one of the most important determinants of LVM in hypertensive ADPKD patients. Further studies are warranted to elucidate the role of nonhemodynamic factors in the pathogenesis of LVH in this population.

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