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Biomedical subjects

P C Perin

Publications and source records attributed to P C Perin.

7 recordsLinked to original sources
PubMed2006

The MCP-1/CCR2 system has direct proinflammatory effects in human mesangial cells.

Both inflammatory and haemodynamic factors have been implicated in the pathogenesis of diabetic and other progressive glomerulopathies. Mesangial cell exposure to mechanical stretch induces both intercellular adhesion molecule 1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1) expression. CC Chemokine receptor 2 (CCR2), the cognate MCP-1 receptor, has been recently demonstrated in human mesangial cells (HMCs). We tested whether MCP-1 binding to CCR2 affects ICAM-1 expression in HMCs and, secondly, if stretch-induced ICAM-1 is mediated by MCP-1 via an autocrine mechanism. Serum-deprived HMCs were exposed to either rh-MCP-1 (0.1-1-10-50-100 ng/ml) or mechanical stretch in the presence and in the absence of RS102895, a specific CCR2 inhibitor. ICAM-1 expression was assessed both by immunofluorescence and cytofluorimetry. Monocyte-HMC interaction was tested by adhesion assay. CCR2 expression was studied by reverse transcriptase-polymerase chain reaction, immunoblotting, and flow cytometry. HMCs exposure to rh-MCP-1 induced a significant twofold increase in ICAM-1 expression at 24 h, leading to enhanced monocyte adhesion. This effect occurred via the CCR2 receptor as CCR2 was expressed in HMCs and CCR2 blockade prevented ICAM-1 upregulation. Stretch-induced ICAM-1 expression was not altered by CCR2 blockade and stretch significantly reduced CCR2 mRNA and protein expression via an MCP-1-independent mechanism. In conclusion, stretch and MCP-1 independently induce ICAM-1 expression in HMCs. Stretch-induced CCR2 downregulation may favour MCP-1 paracrine activity.

Cell Adhesion↗
PubMed2000

A PC-1 amino acid variant (K121Q) is associated with faster progression of renal disease in patients with type 1 diabetes and albuminuria.

Insulin resistance characterizes type 1 diabetes in patients with albuminuria. A PC-1 glycoprotein amino acid variant, K121Q, is associated with insulin resistance. We examined the impact of the PC-1 K121Q variant on the rate of decline of the glomerular filtration rate (GFR) by creatinine clearance derived from the Cockroft-Gault formula in 77 type 1 diabetic patients with albuminuria who were followed for an average of 6.5 years (range 2.5-15). Patients carrying the Q allele (n = 22; 20 with KQ and 2 with QQ genotypes) had a faster GFR decline than those patients with the KK genotype (n = 55) (median 7.2 vs. 3.7 ml x min(-1) x year(-1); range 0.16 to 16.6 vs. -3.8 to 16.0 ml x min(-1) x year(-1); P < 0.001). Significantly more patients carrying the Q allele belonged to the highest tertile of GFR decline (odds ratio = 5.7, 95% CI 4.1-7.2, P = 0.02). Levels of blood pressure, HbA1c, and albuminuria were comparable in the two genotype groups. Albuminuria (P = 0.001), mean blood pressure (P = 0.046), and PC-1 genotype (P = 0.036) independently correlated with GFR decline. Because all patients were receiving antihypertensive treatment, the faster GFR decline in the patients carrying the Q allele could be the result of reduced sensitivity to the renoprotective effect of antihypertensive therapy. PC-1 genotyping identifies type 1 diabetic patients with a faster progression of diabetic nephropathy.

Adult↗
PubMed1999

The relation between QTc interval prolongation and diabetic complications. The EURODIAB IDDM Complication Study Group.

The prevalence of QT interval prolongation is higher in people with diabetes and its complications. Sudden death has been reported as a common cause of death in insulin-dependent diabetic patients affected by autonomic neuropathy. It has been postulated that QT prolongation predisposes to cardiac arrhythmias and sudden death. In this analysis the prevalence of QT interval prolongation and its relation with diabetic complications were evaluated in the EURODIAB IDDM Complications Study (3250 insulin-dependent diabetic patients attending 31 centres in 16 European countries). Five consecutive RR and QT intervals were measured with a ruler on the V5 lead of the resting ECG tracing and the QT interval corrected for the previous cardiac cycle length was calculated according to the Bazett's formula. The prevalence of an abnormally prolonged corrected QT was 16% in the whole population, 11% in males and 21 % in females (p < 0.001). The mean corrected QT was 0.412 s in males and 0.422 s in females (p < 0.001). Corrected QT duration was independently associated with age, HbA1c and blood pressure. Corrected QT was also correlated with ischaemic heart disease and nephropathy but this relation appeared to be stronger in males than in females. Male patients with neuropathy or impaired heart rate variability or both showed a higher mean adjusted corrected QT compared with male patients without this complication. The relation between corrected QT prolongation and autonomic neuropathy was not observed among females. In conclusion we have shown that corrected QT in insulin-dependent diabetic female patients is longer than in male patients, even in the absence of diabetic complications known to increase the risk of corrected QT prolongation.

Adult↗
PubMed1996

Is autonomic neuropathy a risk factor for severe hypoglycaemia? The EURODIAB IDDM Complications Study.

The hypothesis that diabetic patients with autonomic neuropathy are at increased risk of severe hypoglycaemia was examined in an epidemiological study of over 3000 IDDM patients in Europe (EURODIAB IDDM Complications Study). Autonomic function was assessed by two standard cardiovascular tests: change in heart rate and systolic blood pressure on standing. Severe hypoglycaemia was defined as an attack serious enough to require the help of another person. Compared to patients (68%) reporting no attacks in the last year, those reporting one or more attacks were older (34.0 +/- 10.7 vs 32.1 +/- 9.9 years, mean +/- SD, p < 0.0001), had had diabetes for a longer period (16.6 +/- 9.5 vs 13.8 +/- 9.1 years, p < 0.0001), had better glycaemic control (HbA1c 6.4 +/- 1.8 vs 6.9 +/- 1.9%, p < 0.0001) and were more likely (p = 0.002) to have abnormal responses to both autonomic tests (13.0 vs 7.7%). A single abnormal autonomic response was not associated with an increased risk of severe hypoglycaemia. The odds ratio for severe hypoglycaemia in people with abnormal responses to both autonomic tests, compared to those with normal responses, was 1.7 (95% confidence interval 1.3, 2.2) after controlling for age, duration of diabetes, glycaemic control and study centre. In conclusion, a combined autonomic deficit in heart rate and blood pressure responses to standing is associated with only a modest increase in the risk of severe spontaneous hypoglycaemia. Although the increase in risk is not large, severe hypoglycaemia was a frequently reported event in this study. IDDM patients with deficient autonomic responses who strive for tight glycaemic control may therefore be at particular risk of severe hypoglycaemia.

Adult↗
PubMed1995

Does abnormal QT interval prolongation reflect autonomic dysfunction in diabetic patients? QTc interval measure versus standardized tests in diabetic autonomic neuropathy.

The question as to whether the QTc interval correlates with five cardiovascular tests (deep breathing test, 30/15 ratio test, lying to standing test, cough test, and postural blood pressure test) for the diagnosis of diabetic autonomic neuropathy (DAN) was investigated in 168 (38 Type 1, 130 Type 2) consecutive outpatients (mean age 54.9 +/- 11.2 years). QT interval was measured on an ECG recorded at rest and QTc calculated according to Bazett's formula. The percentage of patients with a QTc greater than 0.440 s was: absent DAN = 11% (n = 7), probable DAN = 7% (n = 4), definite DAN = 23% (n = 12) (p < 0.05), and the mean (+/- SD) QTc values were 0.403 +/- 0.028 s, 0.405 +/- 0.023 s, and 0.421 +/- 0.026 s, respectively. A significant correlation between QTc duration and DAN score of autonomic cardiovascular test results (r = 0.34, p < 0.0001) was observed. The calculated specificity, sensitivity, positive and negative predictive values were 89%, 15%, 70% and 37%, respectively. In conclusion, QTc can be considered as an additional specific test in the assessment of diabetic autonomic neuropathy, but cannot replace the standard battery of cardiovascular tests.

Analysis of Variance↗
PubMedDate not supplied

Sympathetic nervous system, diabetes, and hypertension.

Hypertension is twice as frequent in diabetic patients than in the general population. Its prevalence is higher in Type 2 than in Type 1 diabetes: in the former, the onset of hypertension often precedes the diagnosis of diabetes, whereas, in the latter it is strictly related to the presence of nephropathy. Sympathetic nerve overactivity is crucial in the pathogenesis of hypertension in diabetes. It can be related to the activation of the renin-angiotensin-aldosterone (RAA) system in Type 1 diabetic patients with chronic renal failure, or to a condition of insulin resistance/hyperinsulinemia in Type 2 patients with the metabolic syndrome. In patients with early autonomic neuropathy, vagal impairment can lead to a relative predominance of sympathetic activity in the sympatho-vagal balance. In these patients, the onset of hypertension is frequently preceded by reduced nocturnal dipping. Sympathetic overactivity stimulates RAA activity, promotes sodium reabsorption, and increases heart rate, stroke volume and peripheral vascular resistance, thus inducing hypertension and increasing cardiovascular risk. A number of drugs acting either directly or indirectly on sympathetic activity are available for the treatment of hypertension in diabetic subjects. Opinions on the potential advantages of the metabolic profile of some of these drugs are as yet conflicting.

Adrenergic Antagonists↗