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G C Viberti

Publications and source records attributed to G C Viberti.

At least 37 records · Page 2Linked to original sources
PubMed2000

Determinants of elevated urinary albumin in the 4,937 type 2 diabetic subjects recruited for the DIABHYCAR Study in Western Europe and North Africa.

OBJECTIVE: Whether ACE inhibition is useful for type 2 diabetic patients with micro- and macroalbuminuria remains unknown. The Non-Insulin-Dependent Diabetes, Hypertension, Microalbuminuria, Cardiovascular Events and Ramipril (DIABHYCAR) Study was set up to address this issue through a multicenter double-blind parallel placebo-controlled > or = 3-year trial in Europe and North Africa. In this article, we report the characteristics of the randomized patients. RESEARCH DESIGN AND METHODS: The main selection criteria were as follows: men or women aged > or = 50 years with type 2 diabetes treated with oral antidiabetic drugs, with or without hypertension, with a plasma creatinine level < 150 mumol/l, and with persistent micro- or macroalbuminuria, as assessed centrally by two successive urine samples containing a urinary albumin concentration > or = 20 mg/l. Patient characteristics were studied by comparing patients who were randomized to those who were not, taking their geographical origin into account. RESULTS: There were 25,455 patients screened for urinary albumin (20,296 from France, 918 from Germany, 1,019 from Northwest Europe, 969 from Central Europe, 959 from Mediterranean Europe, and 1,294 from North Africa). Of these patients, 4,937 were randomized. Compared with the nonrandomized patients, the randomized patients were older, more often men, more obese, had higher systolic/diastolic blood pressure and plasma glucose, smoked more tobacco, drank more alcohol, and had complications more frequently. Using a logistic regression analysis, all the above-mentioned items appeared as independent determinants for randomization into the study, with the exception of alcohol intake. The contribution of each item varied slightly from one geographical origin to another. CONCLUSIONS: The physical, biological, and behavioral characteristics create a poor renal and cardiovascular prognosis for the type 2 diabetic patients randomized to the DIABHYCAR Study because of micro- and macroalbuminuria. Testing the usefulness of ACE inhibition for the type 2 diabetic patients with microalbuminuria seems feasible through the DIABHYCAR Study.

Africa, Northern↗
PubMed1999

Serum leptin concentration in moderate and severe obesity: relationship with clinical, anthropometric and metabolic factors.

OBJECTIVE: To study clinical, anthropometric and metabolic determinants of serum leptin concentrations in a series of patients with a wide range of obesity. SUBJECTS: 400 patients, 116 males and 284 females, aged 44+/-12.3 years with body mass index (BMI) ranging from 31 to 82 kg/m2 (mean 41.4+/-7.1). MEASUREMENTS: Energy intake by 7-day recall, resting energy expenditure (REE) by indirect calorimetry, body composition determined by bioelectrical impedance; C index, an anthropometric index of abdominal fat distribution, and waist-hip ratio (WHR), blood glucose serum leptin concentrations, total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, uric acid, and insulin concentrations HOMA IRI (homeostastis model assessment of insulin resistance index). RESULTS: Leptin concentrations were higher in obese than in normal subjects and in females than in males without differences between diabetic and non-diabetic patients; leptin concentrations were not related to age and showed a strong negative association with energy intake only in the group of women with BMI less than 40. Leptin concentrations showed a direct correlation with BMI and body fat values (expressed either as percentage of total body mass or absolute fat mass) independent of age and sex. After adjustment for fat mass, leptin values higher than predicted were found in women whereas concentrations lower than predicted were found predominantly in men. Leptin showed an inverse correlation with WHR and C-index, the latter persisting also after correction for gender and fat mass. REE, but not REE/kg fat-free mass (FFM) was inversely related to leptin also after correction for sex and absolute fat mass. Leptin concentrations were directly associated with HOMA IRI, insulin and HDL cholesterol and inversely associated with triglycerides and uric acid. The relationship of leptin with HOMA IRI was still evident after adjusting for sex but was lost when absolute fat mass was added to the model; HDL cholesterol and triglycerides appeared to be variables independent of leptin concentrations even when both sex and fat mass were added to the model. CONCLUSIONS: In a large group of obese patients (half of whom had severe obesity, gender, BMI and fat mass accounted for the largest proportion of serum leptin concentrations variability. We found that in obese subjects there is an effect of fat distribution on leptin concentrations and that, after excluding variability due to absolute fat mass, patients with a greater amount of abdominal fat have relatively low leptin concentrations which in turn relates to a metabolic profile compatible with an increased cardiovascular risk. Women with milder obesity may retain some degree of control of food intake by leptin.

Abdomen↗
PubMed1999

Neovascularization at the vascular pole region in diabetic glomerulopathy.

BACKGROUND: Diabetic nephropathy is associated with renal structural changes involving all of the compartments. Most characteristic is the diabetic glomerulopathy. Studies of the histological changes during the early phases of nephropathy have included the glomerulopathy and also the juxtaglomerular structures. Neovascularization, well-known in diabetic retinopathy, has also been observed in the kidney. The present study concerns estimates of frequency of neovascularization at the vascular pole region in early stages of diabetic nephropathy. METHODS: Extra efferent arterioles at the glomerular vascular pole were detected during measurements of the vascular pole area applying 1-microm serial sections through kidney biopsies. It was observed that more than one efferent arteriole existed occasionally. The present study was carried out with the aim of estimating the frequency of this phenomenon in diabetic patients and in non-diabetic controls, the diabetic patients categorized according to the level of albumin excretion rate. RESULTS: Neovascularization was first observed in IDDM patients with microalbuminuria. Some of the cases presented the phenomenon in all of the glomeruli studied. As the examinations of many kidney biopsies continued the phenomenon was observed also in the non-diabetic control group and in one IDDM patient with normoalbuminuria. However, the frequency was statistically highly significantly increased in patients with elevated albumin-excretion. Within this group a strong correlation between frequency of neovascularization and the severity of diabetic glomerulopathy is seen. CONCLUSIONS: The vascular abnormality localized to the vascular pole region is observed occasionally in the normal kidney, but the frequency is increased in patients with diabetic glomerulopathy. The abnormality may develop as a consequence of a long-standing diabetic glomerulopathy and might lead to less pronounced elevation of albumin excretion.

Adolescent↗
PubMed1997

Premature cell ageing and evolution of diabetic nephropathy.

The rate of development and progression of renal disease varies greatly in insulin-dependent diabetic (IDDM) patients. The cellular and molecular reasons for this difference are largely unknown but could be related to early cell differentiation, a phenomenon recently reported in IDDM patients with nephropathy. In this study we compared cell differentiation and cell volume between IDDM patients with and without nephropathy and investigated the cell ageing characteristics in relation to the rate of evolution of renal disease in the IDDM patients with diabetic nephropathy. Cell volume was larger and the percentage of post-mitotic fibrocytes was higher in skin fibroblasts derived from IDDM patients with diabetic nephropathy compared to those from IDDM patients without kidney disease (mean +/- SD in arbitrary units 817.3 +/- 25.7 vs 760 +/- 32.8; p = 0.005; and mean +/- SD % 33.6 +/- 11.8 vs 20.8 +/- 10; p = 0.02 respectively). Analysis of the interaction of the time to proteinuria (TTP) and the rate of change of glomerular filtration rate (GFR) with glycaemic control, arterial blood pressure and cell volume and the state of cell differentiation showed that glycated haemoglobin and the percentage of post-mitotic fibrocytes were negatively correlated to TTP (r = -0.68; p = 0.008; r = 0.52; p = 0.05 respectively) and positively associated with the rate of change of GFR (r = 0.76; p = 0.03; r = 0.56; p = 0.037 respectively). Cell volume was negatively correlated to TTP (r = -0.53; p = 0.05). Diastolic blood pressure was also related to the rate of GFR change (r = 0.56; p = 0.039). In a multiple linear regression analysis glycated haemoglobin maintained its significance independent relationship with TTP at the 1% level, while the strength of the association between the percentage of post-mitotic cells and cell volume was reduced to the 11 and 9% level, respectively. Cultured skin fibroblasts from IDDM patients with nephropathy show signs of early differentiation. Glycaemic control is a key factor in the rate of onset of proteinuria and different rates of cell ageing appear to contribute to the rate of development and progression of diabetic nephropathy. Their interaction may be responsible for the severity of renal involvement in susceptible IDDM patients.

Adult↗
PubMed1997

High prevalence of risk factors for cardiovascular disease in parents of IDDM patients with albuminuria.

Life expectancy is shorter in the subset of insulin-dependent diabetic (IDDM) patients who are susceptible to kidney disease. Familial factors may be important. In this study the prevalence of cardiovascular disease mortality and morbidity and of risk factors for cardiovascular disease was compared in the parents of 31 IDDM patients with elevated albumin excretion rate (AER > 45 microg/min; group A) with that of parents of 31 insulin-dependent diabetic patients with normoalbuminuria (AER < 20 microg/min; group B). The two diabetic patient groups were matched for age and duration of disease. Information on deceased parents was obtained from death certificates and clinical records and morbidity for cardiovascular disease was ascertained using the World Health Organization questionnaire and Minnesota coded ECG. Hyperlipidaemia was defined as serum cholesterol higher than 6 mmol/l and/or plasma triglycerides higher than 2.3 mmol/l and/or lipid lowering therapy; arterial hypertension as systolic blood pressure higher than 140 mmHg and/or diastolic blood pressure higher than 90 mmHg and/or antihypertensive treatment. The percentage of dead parents was similar in the two groups (26 vs 20% for parents of group A vs group B, respectively), but the parents of the diabetic patients with elevated AER had died at a younger age (58 +/- 10 vs 70 +/- 14 years; p < 0.05). Parents of diabetic patients with nephropathy had a more than three times greater frequency of combined mortality and morbidity for cardiovascular disease than that of the parents of diabetic patients without nephropathy (26 vs 8%; odds ratio 3.96, 95% CI 1.3 to 12.2; p < 0.02). Living parents of group A had a higher prevalence of arterial hypertension (42 vs 14% p < 0.01) and hyperlipidaemia (49 vs 26% p < 0.05) as well as higher levels of lipoprotein (a) [median (range) 27.2 (1-107) vs 15.6 (0.2-98) mg/dl; p < 0.05]. They also had reduced insulin sensitivity [insulin tolerance test: median (range) K(itt) index: 3.7 (0.7-6.2) vs 4.8 (0.7-6.7)% per min; p < 0.05]. In the families of IDDM patients with elevated AER there was a higher frequency of risk factors for cardiovascular disease as well as a predisposition to cardiovascular disease events. This may help explain, in part, the high prevalence of cardiovascular disease mortality and morbidity in those IDDM patients who develop nephropathy.

Adult↗
PubMed1997

Modelling and costing the consequences of using an ACE inhibitor to slow the progression of renal failure in type I diabetic patients.

Antihypertensive drugs slow the progressive decline in renal function seen in patients with insulin-dependent diabetes and nephropathy. In a recent study, the ACE inhibitor captopril protected against this deterioration in renal function. We developed an economic model to analyse the cost impact of ACE inhibitor treatment on progression to endstage renal failure (ESRF) in diabetic patients over 4 years. Two scenarios were compared: one describing the progression of a cohort of 1000 patients receiving 25 mg captopril three times daily, and the other for an equivalent cohort without such prophylactic treatment. Previously published data were used to estimate the transition rates for each stage from the onset of renal failure until death. All direct costs were discounted by an annual rate of 6%, and were subjected to sensitivity analysis. The discounted cost saving of ACE inhibitor treatment for a cohort of 1000 patients was estimated as 0.95 million pounds over 4 years. Under sensitivity analysis, these results were very robust to variations in the costs of ESRF treatment. Prophylactic treatment with ACE inhibitors was predicted to provide substantial increases in life expectancy and reduction in the incidence of ESRF, while also providing significant economic savings.

Adolescent↗
PubMed1997

Renal functional response to protein loading in type 1 (insulin-dependent) diabetic patients on normal or high salt intake.

Insulin-dependent diabetes mellitus (IDDM) patients may have an increased intrarenal angiotensin II activity. In diabetic patients, captopril increases the renal hemodynamic response to an amino acid infusion. We investigated the effects of two salt diets on arterial pressure and renal response to a protein load in 10 normotensive (blood pressure < 140/90 mm Hg) IDDM patients (aged 30 +/- 3 years) who had diabetes for 7 +/- 4 years and normoalbuminuria levels [albumin excretion rate 4.8 (2.5-19.1) microg/min]. After 1 week of normal (approximately 100 mmol/day; approximately 100 mEq/l) and 1 week of high (approximately 300 mmol/day; approximately 300 mEq/l) salt intake, renal hemodynamic studies were performed at baseline and after a protein load (meat meal) of 100 g/1.73 m2. The mean 24-hour urinary sodium excretion levels were 99 +/- 27 and 293 +/- 80 mmol (mEq) with normal and high salt intake, respectively. No significant changes were seen in plasma sodium and glucose control with the normal and high salt diets, respectively: plasma sodium 135 +/- 3 vs. 137 +/- 1 mmol/l (mEq/l), (p = 0.08) and glycated hemoglobin 9.1 +/- 1.9 vs. 9.4 +/- 2.1% (p = 0.36). The body weight (70.9 +/- 12 vs. 71.8 +/- 13 kg; p = 0.015) was significantly higher with a high salt diet. The mean arterial pressure was similar with both diets (normal vs. high salt diet 91 +/- 9 vs. 89 +/- 6 mm Hg, p = 0.25). The plasma renin concentration [28 +/- 15 vs. 16 +/- 6 microU/ml(168 +/- 90 vs. 96 +/- 36 pmol/l), p = 0.013] and angiotensin II [8.8 +/- 4.4 vs. 6.4 +/- 3.5 pg/ml (0.052 +/- 0.025 vs. 0.038 +/- 0.021 nmol/l), p = 0.016] were significantly lower with the high salt diet. Following protein loading, the glomerular filtration rate increased with both diets: normal salt diet 114 +/- 26 vs. 128 +/- 30 ml/min/1.73 m2(1.9 +/- 0.43 vs. 2.13 +/- 0.50 ml/s/1.73 m2), p = 0.04; high salt diet 118 +/- 23 vs. 127 +/- 29 ml/min/1.73 m2 (1.97 +/- 0.38 vs. 2.12 +/- 0.48 ml/s/1.73 m2), p = 0.13. The change in renal plasma flow was similar to that of the glomerular filtration rate with normal and high salt intake, respectively: 566 +/- 94 vs. 617 +/- 142 ml/min/1.73 m2 (9.44 +/- 1.57 vs. 10.29 +/- 2.37 ml/s/173 m2), p = 0.0017; 572 +/- 125 vs. 600 +/- 110 ml/min/1.73 m2 (9.54 +/- 2.08 vs. 10.00 +/- 1.83 ml/s/1.73 m2), p = 0.057. In this subset of normotensive normoalbuminuric IDDM patients, a high salt intake did not promote an exaggerated renal response to the protein load despite inhibition of the renin-angiotensin system.

Adolescent↗
PubMed1997

Multicenter evaluation of the Micral-Test II test strip, an immunologic rapid test for the detection of microalbuminuria.

OBJECTIVE: To assess the performance of the Micral-Test II immunologic test strip for the detection of microalbuminuria, a multicenter evaluation in eight European study sites was performed. RESEARCH DESIGN AND METHODS: Using both the Micral-Test II test strip and the routine method for the determination of albumin concentration, we investigated 2,228 urine samples from diabetic patients. Additionally, interperson variability, color stability, and possible interfering factors (temperature, pH, leucocyturia, erythrocyturia, and drugs) were tested. RESULTS: For a cutoff concentration of 20 mg/l with respect to the routine methods, a sensitivity of 96.7% and a specificity of 71% were calculated for the Micral-Test II test strip. The negative predictive value was 0.95, and the positive predictive value was 0.78, with a prevalence of positive samples (laboratory method) of 52%. The interperson variability of color interpretation showed 93% concordant readings. The interference study showed an influence of oxytetracycline, leading to higher readings. There was no interference from pH. A sample temperature of < 10 degrees C led to lower readings. In the case of samples with massive leucocyturia and erythrocyturia that may delete the chromatographic process, waiting an additional 1-2 min is needed before reading. CONCLUSIONS: The results of the multicenter evaluation show that the Micral-Test II test strip permits an immediate and reliable semiquantitative determination of low albumin concentrations in urine samples with an almost user-independent color interpretation.

Albuminuria↗
PubMed1997

Promoters of progression of diabetic nephropathy: the relative roles of blood glucose and blood pressure control.

BACKGROUND AND AIMS: Hyperglycaemia is a strong risk factor for the development of renal disease in insulin dependent diabetes mellitus but it is uncertain whether it contributes to the progression of incipient or established nephropathy. The rigorous treatment of blood pressure in recent years may help uncover the contribution of hyperglycaemia, if any, to the progression of renal failure. Our aim therefore, was to assess in a current cohort of insulin dependent diabetic patients with diabetic nephropathy the relative importance of glycaemic control and blood pressure on disease progression. METHODS: All insulin dependent diabetic patients with persistent albuminuria (> 300 mg/24 h) attending the diabetic clinic at Guy's Hospital between 1977 and 1993 were recruited. Serial measurements of blood pressure, HbA1 and GFR were performed every 6 months until end-stage renal disease or death. Only patients with at least 1 year of follow up were analysed. The mean follow up period was 8 years (range 1.5-15.5 years). Baseline and time dependent variables were related to the rate of change of GFR using weighted linear regression and stepwise multiple regression analysis. The impact of each variable on the change of GFR with time was adjusted for the effect of other potentially confounding variables by analysis of co-variance. RESULTS: Patients had well-controlled blood pressure throughout the observation period (mean arterial pressure 97 +/- 8 mmHg) and the average rate of decline of GFR was 4.32 +/- 4.08 ml/min/year. In univariate analysis baseline and mean HbA1 were linearly related to the rate of decline of GFR (baseline r5-0.565, P < 0.001; mean r-0.5107, P < 0.001) with those with a higher HbA1 having a faster rate of progression. In stepwise multivariate analysis both mean HbA1 mean diastolic blood pressure (P < 0.0001 and P = 0.019, respectively) was significantly and independently related with a faster rate of decline of GFR. CONCLUSIONS: Worse glycaemic control is associated with a faster rate of progression of diabetic nephropathy once blood pressure is controlled. Thus improvement of glycaemic control in patients where good blood pressure control has been achieved may potentially further delay the progression of nephropathy.

Adolescent↗
PubMed1996

Elevated serum levels of macrophage-derived cytokines precede and accompany the onset of IDDM.

To determine whether cytokines could have a role in the development of insulin-dependent diabetes mellitus (IDDM), we measured serum levels of cytokines derived from T helper 1 (interleukin-2 and interferon-gamma), T helper 2 (interleukin-4 and interleukin-10) lymphocytes and macrophages (tumour necrosis factor-alpha, interleukin-1 alpha and interleukin-1 beta) in patients before and after the onset of IDDM. Recently diagnosed IDDM patients had significantly higher levels of interleukin-2, interferon-gamma, tumour necrosis factor-alpha and interleukin-1 alpha than patients with either long-standing IDDM, non-insulin-dependent diabetes (NIDDM), Graves' disease, or control subjects (p < 0.05 for all). Compared with control subjects, patients with long-standing IDDM and those with NIDDM had higher interleukin-2 and tumour necrosis factor-alpha levels (p < 0.01 for all). Interleukin-4 and interleukin-10 were detectable in sera of patients with Graves' disease only, while interleukin-1 beta was not detectable in the serum of any control or test subject. To investigate whether high cytokine levels precede the onset of IDDM, we studied 28 non-diabetic identical co-twins of patients with IDDM, followed-up prospectively for up to 6 years after the diagnosis of the index. Levels of tumour necrosis factor-alpha and interleukin-1 alpha were elevated above the normal range more frequently in the eight twins who developed diabetes than in those 20 who did not (p < 0.005). Analysis of T helper 1 and T helper 2 profiles of the twin groups did not reveal a clear difference between prediabetic twins and twins remaining non-diabetic. These results support the notion that T helper 1 lymphocytes may play a role in the development of IDDM. This is associated with release of macrophage-derived cytokines, which is also a feature of the prediabetic period. The lack of evidence of a dominant T helper 1 profile of cytokine release before diabetes onset suggests that additional events, activating this arm of the cellular immune response, are required in the immediate prediabetic period.

Autoantibodies↗
PubMed1996

Microalbuminuria as a marker of silent myocardial ischaemia in IDDM patients.

Insulin-dependent diabetic (IDDM) subjects with microalbuminuria have an increased long-term risk of overt cardiovascular disease; however, the early exposure to cardiovascular risk factors may increase their predisposition to current silent myocardial ischaemia. The frequency of silent myocardial ischaemia detected by stress echocardiography and electrocardiography was significantly greater in 32 asymptomatic IDDM patients with microalbuminuria compared to 32 normoalbuminuric IDDM patients (25% [n = 8] vs 6.3% [n = 2]; p = 0.03, odds ratio [95% CI] 6.3 [1.2, 37.8]). Elective coronary artery bypass grafting was required in 1 patient with microalbuminuria and silent myocardial disease. Microalbuminuria and poorer autonomic function were independently associated with silent myocardial ischaemia in multivariate analysis (p = 0.03 and p = 0.02, respectively). Screening for silent myocardial ischaemia using these non-invasive tests may be warranted in microalbuminuric IDDM which patients could be of considerable clinical importance.

Adolescent↗
PubMed1996

Multiple lipoprotein abnormalities in type I diabetic patients with renal disease.

The aim of this study was to characterize abnormalities of triglyceride-rich apolipoprotein (apo) B-containing lipoproteins in type I diabetic patients with elevated albumin excretion rates (AERs). Sixty-four patients (31 men, 33 women) with normoalbuminuria (AER <20 microg/min), 52 (35 men, 17 women) with microalbuminuria (AER 20-200 microg/min), and 37 (17 men, 20 women) with albuminuria (AER >200 microg/min) and 56 healthy control subjects matched for age and body weight were studied. The major finding was increased mass concentrations of the highly atherogenic intermediate-density lipoprotein fraction in patients with microalbuminuria (P < 0.05) and albuminuria (P < 0.05), compared with those with normoalbuminuria. Triglyceride, free cholesterol, cholesterol ester, and phospholipid concentrations in the VLDL, intermediate-density lipoprotein, and LDL (P < 0.05-0.01), as well as total cholesterol, total triglyceride, and apoB concentrations were higher in patients with renal disease than in those without. Notably, there were no differences between patients with microalbuminuria and albuminuria. Only minor compositional changes could be detected. Postheparin plasma lipoprotein lipase (LPL) activities were identical, but hepatic lipase activities were higher in microalbuminuric and albuminuric patients than in normoalbuminuric patients (P < 0.01). LPL activity and VLDL1, (Sf 60-400) (r = -0.528; P < 0.001) and VLDL2 (Sf 20-60) mass concentrations (r = -0.471; P < 0.001) were negatively related. In conclusion, in type I diabetic patients with early renal disease, there are multiple lipoprotein changes, which are potentially atherogenic and may contribute to the excess of macrovascular complications seen in such patients.

Adult↗
PubMed1995

Blood pressure, retinopathy and urinary albumin excretion in IDDM: the EURODIAB IDDM Complications Study.

Several studies have shown an association between blood pressure and nephropathy, but few have been large enough to examine whether, or how, this relation is influenced by retinopathy. We have therefore examined the independent relations of blood pressure to urinary albumin excretion and retinopathy in a cross-sectional observational study of over 3000 insulin-dependent diabetic patients (the EURODIAB IDDM Complications Study). The relation of blood pressure to urinary albumin excretion differed strikingly between patients with (46%) and without (54%) retinopathy. In those with retinopathy, mean urinary albumin excretion rate was normal (< 20 micrograms/min) below median diastolic pressure (75 mmHg) and increased steeply (p < 0.001) with blood pressure above this level. However, in patients without retinopathy, mean albumin excretion rate was normal across the range of diastolic pressure. This finding could not be explained by differences in glycaemic control or duration of diabetes between patients with and without retinopathy. These data identify a subgroup of patients whose high risk of nephropathy may reflect abnormal renal vulnerability to mildly raised blood pressure. Retinopathy is a close correlate of this vulnerability. Detection of even mild retinopathy, together with raised blood pressure, may be important in assessing nephropathy risk.

Adult↗