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Biomedical subjects

G Viberti

Publications and source records attributed to G Viberti.

At least 37 records · Page 2Linked to original sources
PubMed1997

Glomerular volume and the glomerular vascular pole area in patients with insulin-dependent diabetes mellitus.

The vascular pole area (VPA) and glomerular volume were measured in renal biopsies from 9 insulin-dependent diabetes mellitus (IDDM) patients with normal albumin excretion rate (IDDM group 1), 38 IDDM patients with albumin excretion rate > 15 micrograms/min (IDDM group 2) and 10 living kidney donors (ND). The volume of individual glomeruli was estimated as the sum of profile areas factored by the measured distance between levels, t approximately 10 microns, and VPA as the sum of chords multiplied by t. Mean glomerular volume was increased in IDDM patients but reached statistical significance only in IDDM group 2 (P = 0.002 vs ND). VPA was significantly different among the groups, mean (CV%) was 2036 (29) microns2 in ND, 3555 (34) micron2 in IDDM group 1, and 3528 (48) microns2 in IDDM group 2, p = 0.004 and 0.001, IDDM versus ND. VPA calculated as a percentage of the surface area of the corresponding glomerulus was 2.4 (23)% in ND, 3.4 (27)% in IDDM group 1, and 3.3 (42)% in IDDM group 2; P = 0.007 and 0.01, IDDM versus ND. The intra-biopsy coefficient of variation was high (20-35%) and of the same order in all groups for all three measurements. Glomerular volume and absolute as well as relative size of VPA showed a positive correlation with estimates of mesangial expansion in IDDM group 2 and the VPA showed a negative correlation with GFR. Thus, part of the enlargement may represent a compensatory phenomenon triggered by the development of structural and functional abnormalities in the diabetic kidney.

Adolescent↗
PubMed1997

Sodium-hydrogen antiporter: its possible role in the genesis of diabetic nephropathy.

The epidemiological evidence that only a subset of diabetic patients are susceptible to renal damage and the demonstration of clear familiar clustering of diabetic nephropathy are consistent with the possibility that genetic factors may explain the liability to or protection from renal disease of diabetic patients. A predisposition to hypertension and cardiovascular disease may be an important determinant of susceptibility to renal disease and its cardiovascular complications in diabetes since raised blood pressure [1] and an increased frequency of cardiovascular disease [2] are more prevalent in parents of diabetic patients with nephropathy. These results have raised growing interest in the search for intermediate phenotypes significantly associated with diabetic nephropathy, poorly influenced by environment, stable with age, easy to quantify and possibly dependent upon a single major gene effect. Such intermediate phenotypes can be useful for early diagnosis and would help clarify the molecular mechanisms leading to diabetic nephropathy. An elevation of Na+/H+ antiporter activity has consistently been associated with diabetic renal disease both in insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM) patients, making this cell membrane exchanger system an ideal intermediate phenotype for the study of diabetic nephropathy.

Diabetes Mellitus, Type 1↗
PubMed1997

Permissive role of hypertension in the development of proteinuria and progression of renal disease in insulin-dependent diabetic patients.

BACKGROUND: In insulin-dependent diabetic subjects, heritable factors related to hypertension and cardiovascular disease are associated with nephropathy. OBJECTIVE: To determine the relationship of blood pressure, glycaemic control, family history of cardiovascular disease and sodium-lithium countertransport activity to the onset of proteinuria and decline in glomerular filtration. DESIGN: A retrospective analysis of the rate of onset of proteinuria and a longitudinal study of the progression of established renal disease. SETTING: Guy's Hospital Diabetes Renal Clinic, a secondary referral centre. PATIENTS: Fifty-four insulin-dependent diabetic patients with nephropathy, persistent total protein excretion rate > 500 mg/24 h, enrolled between 1978 and 1992. MAIN OUTCOME MEASURES: Rate of decline in glomerular filtration rate. Duration of diabetes at onset of nephropathy (time to proteinuria). Blood pressure and glycosylated haemoglobin at the time of diagnosis of nephropathy (baseline). Family history of cardiovascular disease and hypertension. Erythrocyte sodium-lithium countertransport activity in a subset of patients (n = 41) not being administered renal replacement therapy in 1992. RESULTS: The estimated (95% confidence interval) time to proteinuria was shortened in relation to increments in diastolic blood pressure at baseline and to a family history of cardiovascular disease in both parents [1.9 (0.2-3.2) years/10 mmHg, P < 0.05 and 6.7 (-0.3-13.7) years, P < 0.07, respectively]. During follow-up 15% (n = 8) of the patients who did not require antihypertensive therapy had slower rates of decline in glomerular filtration and lower rates of sodium-lithium countertransport activity than did those who had been administered treatment [median (range): 2.88 (0.2 to -11.28) versus 7.8 (0.1 to -20.4) ml/min per 1.73 m2/year, P < 0.05 and 0.28 (0.14-0.54) versus 0.43 (0.18-0.88) mmol/l per erythrocyte/h, P < 0.03, respectively]. In this group there was an inverse relationship between the time to proteinuria and glycosylated haemoglobin (r = -0.79, P = 0.018). For the whole group a multivariate analysis showed hypertension and initial glomerular filtration rate to be related independently to the rate of decline in renal function; glycaemic control just failed to attain statistical significance (P < 0.06). CONCLUSION: Elevation of blood pressure accelerates the onset of nephropathy and its progression; its absence, a reduced familial predisposition to cardiovascular disease, low sodium-lithium countertransport activity and good blood glucose control favour a more benign prognosis.

Adult↗
PubMed1997

Enhanced collagen synthesis in cultured skin fibroblasts from insulin-dependent diabetic patients with nephropathy.

Excessive production and deposition of extracellular matrix proteins are characteristic features of diabetic nephropathy. This study tests the hypothesis that cells from diabetic patients who develop nephropathy have a disturbance in collagen metabolism compared with cells from diabetic patients without complications. Kinetics of overall collagen metabolism and total protein synthesis were examined in serially passaged, subconfluent, quiescent skin fibroblasts cultured in either normal (5 mM) or high (25 mM) glucose concentrations from 14 insulin-dependent diabetic (IDDM) patients with nephropathy; 14 IDDM patients without nephropathy matched for age, diabetes duration, and body mass index; and 14 healthy subjects. Fibroblasts were incubated in the presence of 2 microCi/ml [3H]proline, and after labeling the incorporation of [3H]proline into total protein, collagen (collagenase-sensitive material), and noncollagen proteins (collagenase-resistant material) was determined at different time points. Collagen degradation was determined in pulse-chase experiments by following the residual collagen-bound radioactivity after incubation for 8 h with 10 microCi/ml [3H]proline. In high glucose concentrations (25 mM), overall collagen synthesis (measured as [3H]proline incorporation into extracellular and intracellular collagenase-sensitive material) was significantly greater in the patients with nephropathy (mean +/- SEM after a 24-h labeling period: 7189 +/- 671 dpm/10(6) cells) than in the patients without (4341 +/- 267 dpm/10(6) cells; P < 0.01) or healthy control subjects (3836 +/- 234 dpm/10(6) cells; P < 0.01). No significant differences were observed in noncollagen protein production or in collagen degradation rates among the three groups of subjects. In the presence of normal glucose concentrations (5 mM), collagen synthesis was lower in all groups studied, but the differences between IDDM patients with nephropathy and those without remained unaltered. These results suggest that long-term cultured fibroblasts derived from diabetic patients with nephropathy exhibit an abnormality in collagen metabolism. Cells from long-standing diabetic patients without nephropathy have normal collagen metabolism. The increased collagen synthesis is likely to be intrinsic to those diabetic patients susceptible to nephropathy and may play an important role in the sclerotic processes that occur in the kidneys, arteries, and heart.

Adult↗
PubMed1997

Angiotensin converting enzyme inhibitors in diabetic patients with microalbuminuria or normoalbuminuria.

In adult diabetic patients microalbuminuria is a marker of early vascular damage in the micro- and macrocirculation. Microalbuminuria is a powerful predictor of renal and cardiovascular disease outcome and is associated with other, potentially modifiable, risk factors of vascular damage. Studies of secondary prevention have shown that blood pressure lowering drugs effectively reduce albumin excretion rate. Angiotensin converting enzyme (ACE) inhibitors seem particularly effective in reducing the risk of progression to clinical albuminuria in both insulin dependent and non-insulin dependent diabetic patients and this beneficial effect appears to be long-lasting. Whether this postpones the onset of end-stage renal failure and/or reduces early mortality in these patients remains to be established. Recent studies of primary prevention in insulin-dependent diabetic patients predominantly with normoalbuminuria demonstrate that ACE inhibition reduces significantly the rate of progression of albumin excretion rate and, of great interest, seems to affect beneficially the progression of retinopathy. These results compare favorably with the beneficial effect of intensified insulin therapy and strict blood glucose control in this same group of patients. Thus, ACE inhibitors are a powerful tool to prevent progression of microalbuminuria in diabetes and may prove useful as an adjunct therapy to intensified insulin therapy in the prevention of development of microalbuminuria and of retinopathy progression in insulin dependent diabetes.

Adult↗
PubMed1996

Premature senescence of skin fibroblasts from insulin-dependent diabetic patients with kidney disease.

Diabetic glomerulopathy develops in a subset only of patients with insulin-dependent diabetes (IDDM) and early, in its course, is characterized by cell hypertrophy and by excessive extracellular matrix production. These observations suggest that an alteration in the control of cell growth processes may contribute to its pathogenesis and be related to the susceptibility to kidney disease. We therefore investigated whether the development of diabetic nephropathy is associated with abnormalities of cell growth and morphology. Cultured skin fibroblasts from 14 IDDM patients with nephropathy (DN) were compared with those of 10 IDDM patients without nephropathy (D) and of 14 control non-diabetic subjects (C). Cell volume (in arbitrary units) and total protein content (microgram/10, 000 cells) were increased in serially passaged skin fibroblasts of IDDM patients with nephropathy (DN = 809.5 +/- 33.1 and 1.93 +/- 0.38 vs. D = 764.4 +/- 31.5 and 1.5 +/- 0.37, P = 0.005 and P = 0.03, respectively; vs. C = 756.2 +/- 36.3 and 1.5 +/- 0.38, P = 0.0006 and P = 0.03, respectively). These hypertrophic cells had a tendency to a slower duplication rate and exhibited a dissociation of the DNA and cytoplasmic cell-cycles, resulting in a higher proportion of tetraploid cells (DN = 25 +/- 15% vs. D = 6 +/- 4%, P = 0.005; and vs. C = 10 +/- 8%, P = 0.04). The frequency of terminally differentiated post-mitotic fibrocytes, cells specialized for extracellular matrix production, was higher in patients with nephropathy compared to that of patients without nephropathy and normal controls (DN = 34 +/- 14% vs. D = 21 +/- 10%, P = 0.02; and vs. C = 19 +/- 12%, P = 0.008). That early differentiation was a specific feature of cells derived from patients with diabetic nephropathy was confirmed by the study of cell life-span which demonstrated that these cells aged prematurely (log rank test, chi 2 = 10,012; P = 0.0067). We conclude that an acceleration of cell aging is a peculiar feature of diabetic kidney disease and may contribute to its pathological tissue changes.

Adult↗
PubMed1996

Glomerular hyperfiltration in the prediction of nephropathy in IDDM: a 10-year follow-up study.

Glomerular hyperfiltration has been proposed as an independent risk factor for the development of diabetic nephropathy in patients with IDDM. In a case-controlled prospective study of IDDM patients without albuminuria, serial glomerular filtration rate (GFR) measurements were performed over an observation period of 10 years. A group of 25 IDDM patients (20 men, 5 women; initial age, 29 [17-49] years) with glomerular hyperfiltration (GFR >135 ml x min(-1) x 1.73 m(-2)) were matched for age, sex, and duration of diabetes with 25 IDDM patients (20 men, 5 women; initial age, 30 [17-48] years) with glomerular normofiltration (GFR 83-135 ml x min(-1) x 1.73 m(-2)). GFR, urinary albumin excretion rate (AER), blood pressure, and glycated hemoglobin were measured at baseline and at 5, 8, and 10 years. The two groups had similar entry levels of blood pressure, AER, and glycated hemoglobin. Metabolic control was similar in the two groups during follow-up. The final GFR remained higher in the group with hyperfiltration (122 [109-135] vs. 103 [95-111] ml x min(-1) x 1.73 m(-2); P = 0.02) despite a nonsignificantly faster rate of fall of GFR compared with that of the control group (2.54 [1.20-3.88] vs. 1.50 [1.01-1.99] ml x min(-1) x year(-1); P = 0.14). A similar number of patients in each group progressed to either microalbuminuria or macroalbuminuria (n = 4 vs. n = 3) or developed hypertension (blood pressure, >160/95 mmHg; n = 3 vs. n = 4). End-of-study AER was, however, higher in the group with hyperfiltration (geometric mean [95% CI]: 18.9 [11.3-31.6] vs. 11.0 [8.1-15.0]; P = 0.05), and baseline glomerular hyperfiltration was an independent determinant of end-of-study blood pressure (P = 0.04). The strongest predictors of end-of-study AER and blood pressure were their baseline values (P < 0.04 and P < 0.01, respectively). In conclusion, levels of AER and blood pressure are the main risk factors for renal outcome, while glomerular hyperfiltration appears to play a lesser role.

Adolescent↗
PubMed1995

A quantitative ultrastructural study of juxtaglomerular arterioles in IDDM patients with micro- and normoalbuminuria.

Hyalinization of juxtaglomerular arterioles is prominent in advanced diabetic nephropathy and may have important functional consequences. We studied the early stages of diabetic renal disease using kidney biopsy material from insulin-dependent diabetic patients, 8 with normal albumin excretion rate (< 15 micrograms/min) and 16 with microalbuminuria (15-200 micrograms/min). Ten living non-diabetic kidney donors served as a control group. Median duration of diabetes was 9.5 years (range 5-31) in patients with normoalbuminuria, and 12 years (7-22) in patients with microalbuminuria (p = 0.27). The tissue was sectioned systematically, 1-micron thick sections for light microscopy at 10-micron intervals, and thin sections for electron microscopy taken at 60-micron intervals. The arterioles were identified as afferent or efferent, and total profiles were photographed (magnification 7500x), providing a systematic independent sample for measurements using standard stereological methods. Patients with microalbuminuria had significantly increased arteriole parameters compared with the control group: for afferent and efferent arterioles the volume fraction of matrix/media, means and (co-efficient of variation, CV), was 0.47 (0.16) vs 0.33 (0.19) (p = 0.0009), and 0.62 (0.14) vs 0.45 (0.23) (p = 0.0004) and matrix-T, expressing amount of matrix per unit arteriolar surface, 2.38 (0.38) micron vs 1.44 (0.30) micron (p = 0.004), and 1.62 (0.28) micron vs. 1.03 (0.34) (p = 0.0009). Patients with normoalbuminuria showed no significant differences from the control group, and had lower values than microalbuminuric patients for all parameters except the afferent matrix-T. In the normoalbuminuric group a correlation was found between parameters for afferent arterioles and those for glomerular structure. In conclusion there is arteriolar accumulation of extracellular material in the early phase of diabetic nephropathy, concomitant with early glomerulopathy.

Adolescent↗
PubMed1995

Single-blind studies of the effects of improved periodontal health on metabolic control in type 1 diabetes mellitus.

Uncontrolled studies have suggested a beneficial effect of periodontal treatment on metabolic control of insulin-dependent diabetes mellitus (IDDM). We therefore conducted controlled single-blind studies, using current metabolic status indicators in IDDM subjects free of significant complications other than periodontal diseases. In the 1st study, 41 IDDM subjects with gingivitis and early periodontitis were randomly assigned to treatment (oral hygiene and scaling) or control groups. The study was completed by 16 experimental and 15 control subjects. Reassessment after 2 months showed a Hawthorne effect in the control group, and no difference between groups. However, further analysis showed a relationship between individual metabolic control variation and gingival inflammation. A 2nd study enrolled 23 IDDM subjects with advanced periodontitis, who were randomised to treatment (full initial therapy including root planning) or control groups. Only 1 subject failed to complete the study, owing to illness. In this study, a significant response to periodontal treatment was not accompanied by any improvement in metabolic control. These results support the concept that the effect of metabolic control may be predominant in the relationship between IDDM and periodontal health.

Adolescent↗
PubMed1995

Renal functional reserve in subjects with diabetes mellitus.

Diabetic nephropathy develops in approximately 35% of patients with insulin-dependent diabetes mellitus (IDDM) and in a similar proportion of patients with non-insulin-dependent diabetes mellitus (NIDDM). However, we remain at present unable to identify the susceptible subset prior to the development of microalbuminuria. Up to 25% of IDDM patients and a variable proportion of NIDDM patients manifest glomerular hyperfiltration in the first few years of diabetes. It has been debated whether this basal hyperfiltration is predictive of future renal disease and whether better prediction can be achieved by the use of the renal haemodynamic response to a protein meal, defined by some authors as renal reserve. The concept of renal functional reserve in patients with diabetes mellitus is complicated by the dependence of the GFR response on basal GFR, the influence of the prevailing metabolic conditions, and because the response differs to different stimuli. We review the factors affecting renal hemodynamics and renal hemodynamic responses in the context of supranormal, normal, and impaired renal function in diabetes. We conclude that although the measurement of renal functional reserve may help clarify important pathophysiological mechanisms, the assessment of basal GFR in clinical practice is all that is required for predictive and monitoring purposes.

Diabetes Mellitus, Type 1↗
PubMed1994

Effect of captopril on progression to clinical proteinuria in patients with insulin-dependent diabetes mellitus and microalbuminuria. European Microalbuminuria Captopril Study Group.

OBJECTIVES: To study the effect of angiotensin converting enzyme inhibition on the rate of progression to clinical proteinuria and the rate of change of albumin excretion rates in patients with insulin-dependent diabetes mellitus and persistent microalbuminuria. DESIGN AND SETTING: Randomized, double-blind, placebo-controlled clinical trial of 2 years' duration at 12 hospital-based diabetes centers. PATIENTS: Ninety-two patients with insulin-dependent diabetes mellitus and persistent microalbuminuria but no hypertension. INTERVENTION: The patients were randomly allocated in blocks of two to receive either captopril, 50 mg, or placebo twice per day. MEASUREMENTS: Albumin excretion rate, blood pressure, glycosylated hemoglobin level, and fructosamine level every 3 months; urinary urea nitrogen excretion every 6 months; and glomerular filtration rate every 12 months. RESULTS: Twelve patients receiving placebo and four receiving captopril progressed to clinical proteinuria, defined as an albumin excretion rate persistently greater than 200 micrograms/min and at least a 30% increase from baseline (P = .05). The probability of progression to clinical proteinuria was significantly reduced by captopril therapy (P = .03 by log-rank test). Albumin excretion rate rose from a geometric mean (95% confidence interval) of 52 (39 to 68) to 76 (47 to 122) micrograms/min in the placebo group but fell from 52 (41 to 65) to 41 (28 to 60) micrograms/min in the captopril group, a significant difference (P < .01). Mean blood pressure was similar at baseline in the two groups and remained unchanged in the placebo group but fell significantly, by 3 to 7 mm Hg, in the captopril group. Glycosylated hemoglobin levels and glomerular filtration rate remained stable in the two groups. CONCLUSIONS: Captopril therapy significantly impeded progression to clinical proteinuria and prevented the increase in albumin excretion rate in nonhypertensive patients with insulin-dependent diabetes mellitus and persistent microalbuminuria.

Adolescent↗
PubMed1994

Prognostic significance of microalbuminuria.

Diabetic nephropathy is the only increasing cause of renal failure in the Western world. It affects a large proportion of both insulin-dependent (IDDM) and non-insulin-dependent diabetic (NIDDM) patients. A critical stage in the development of diabetic renal disease is the onset of microalbuminuria, defined as an albumin excretion rate of 30 to 300 mg/day. Microalbuminuria predicts progression to renal failure and early cardiovascular mortality in both IDDM and NIDDM patients. Microalbuminuria is associated with a constellation of other risk factors for small and large vessel damage which include raised blood pressure, poor glycemic control, plasma lipid and clotting factor abnormalities, left ventricular hypertrophy, and insulin resistance. Treatment with angiotensin-converting enzyme inhibitors corrects microalbuminuria and prevents progression to persistent proteinuria. Good blood glucose control significantly reduces the risk of progression from normoalbuminuria to microalbuminuria. The treatment of microalbuminuria appears highly cost-beneficial and substantially increases life expectancy. The development of microalbuminuria, for which all diabetic patients aged 12 to 70 years should be screened, should alert the physician to set in motion a program of assessment, monitoring, and correction of all risk factors for renal and cardiovascular disease.

Adolescent↗
PubMed1994

Serum sialic acid, a risk factor for cardiovascular disease, is increased in IDDM patients with microalbuminuria and clinical proteinuria.

OBJECTIVE: An elevated serum sialic acid concentration has recently been shown to be a potent cardiovascular risk factor in the general population. Because clinical proteinuria is associated with a high frequency of cardiovascular disease, and because microalbuminuria predicts the development of renal and cardiovascular disease in diabetes, we investigated whether serum sialic acid levels are increased in insulin-dependent diabetes mellitus (IDDM) patients with microalbuminuria or clinical proteinuria. RESEARCH DESIGN AND METHODS: We studied 23 patients with IDDM who had a normal urinary albumin excretion rate, 23 patients who had microalbuminuria, and 23 patients with clinical proteinuria. The patients were matched for age, sex, duration of diabetes, GHb levels, and body mass index (BMI). Fasting blood samples were taken for measurement of sialic acid, cholesterol, triglyceride, creatinine, and GHb. RESULTS: Serum sialic acid was significantly higher in the microalbuminuric patients compared with the normoalbuminuric group (mean +/- SD: 1.93 +/- 0.26 vs. 1.76 +/- 0.27 mM, P < 0.01). Moreover, serum sialic acid was also significantly higher in the group with clinical proteinuria compared with the microalbuminuric patients (2.34 +/- 0.24 vs. 1.93 +/- 0.26 mM, P < 0.001). Serum sialic acid was not related independently to age, BMI, diabetes duration, GHb, blood pressure, serum cholesterol, triglyceride, or creatinine concentration in any of the diabetic groups. CONCLUSIONS: These observations suggest that the serum sialic acid concentration is raised in IDDM patients with both microalbuminuria and clinical proteinuria and may play a role as a cardiovascular risk factor or disease marker in these conditions.

Adult↗