Chronic kidney disease in type 2 diabetes: lessons from the Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicentre Study.

The Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicentre Study is an ongoing observational survey that examines the role of estimated glomerular filtration rate (eGFR) as an independent predictor of cardiovascular and renal outcomes in 15,773 Italian subjects with type 2 diabetes. The analysis of data collected at the enrollment visit provided a picture of chronic kidney disease (CKD) and its association with other complications, risk factors for cardiovascular disease (CVD) and treatments in a large contemporary cohort. Main results of this analysis were that (a) non-albuminuric renal impairment is the predominant clinical phenotype in patients, particularly women, with reduced eGFR; (b) concordance between CKD and diabetic retinopathy is low, with only a minority of patients with renal dysfunction presenting with any or advanced retinal lesions; (c) the non-albuminuric form is associated with a significant prevalence of CVD, especially at the level of the coronary vascular bed; (d) CKD is associated with hemoglobin (Hb) A1c variability more than with average HbA1c, whereas retinopathy and CVD are not; (e) in elderly individuals with moderate-to-severe eGFR reduction, use of agents which are not recommended, such as sulphonylureas and metformin, is still frequent; and (f) though complications are generally more prevalent in men (except non-albuminuric renal impairment) women show a less favorable CVD risk profile and achieve therapeutic targets to a lesser extent than men, despite the fact that treatment intensity is not lower. These data update existing information on the natural history of CKD in patients with type 2 diabetes.

Gender differences in cardiovascular disease risk factors, treatments and complications in patients with type 2 diabetes: the RIACE Italian multicentre study.

OBJECTIVES: Poorer control of risk factors for cardiovascular disease (CVD) has been reported in diabetic women, as compared with diabetic men. It has been proposed that this finding is due to gender disparities in treatment intensity. We investigated this hypothesis in a large contemporary cohort of subjects with type 2 diabetes. DESIGN: Observational, cross-sectional study. SUBJECTS AND SETTING: Consecutive patients with type 2 diabetes from the Renal Insufficiency And Cardiovascular Events (RIACE) Italian multicentre study (n = 15 773), attending 19 hospital-based diabetes clinics in 2007-2008. MAIN OUTCOME MEASURES: Traditional CVD risk factors, macro- and microvascular complications and current glucose-, lipid- and blood pressure (BP)-lowering treatments were assessed. RESULTS: Although CVD was more prevalent in men, women showed a less favourable CVD risk profile and worse performance in achieving treatment targets for haemoglobin A1c , LDL, HDL and non-HDL cholesterol, systolic blood pressure (BP) and in particular obesity [body mass index (BMI) and waist circumference], but not for triglycerides and diastolic BP. However, women were more frequently receiving pharmacological treatment for hypertension and to a lesser extent hyperglycaemia and dyslipidaemia than men, and female gender remained an independent predictor of unmet therapeutic targets after adjustment for confounders such as treatments, BMI, duration of diabetes and, except for the systolic BP goal, age. CONCLUSIONS: In women with type 2 diabetes from the RIACE cohort, a more adverse CVD risk profile and a higher likelihood of failing treatment targets, compared with men, were not associated with treatment differences. This suggests that factors other than gender disparities in treatment intensity are responsible.

Generalised reduction of putative endothelial progenitors and CXCR4-positive peripheral blood cells in type 2 diabetes.

AIMS/HYPOTHESIS: In patients with type 2 diabetes, reduced levels of circulating endothelial progenitor cells have been reported and these have been correlated with disease severity. In this study, we examined a panel of markers widely used to identify progenitor and/or stem cells, and determined their association with disease severity in diabetic patients. Since expression of chemokine (C-X-C motif) receptor 4 (CXCR4) has been associated with mobilisation and recruitment of progenitor cells, CXCR4 expression was also analysed. METHODS: Peripheral blood mononuclear cells (PBMCs) from 98 patients with type 2 diabetes and 39 control individuals were analysed by flow cytometry for surface marker expression. RESULTS: Cells expressing different combinations of progenitor and/or stem cell markers were severely reduced in PBMCs of diabetic patients compared with those of control participants. Moreover, a number of these putative progenitor cell populations were negatively associated with disease severity. Reduced expression of CXCR4 and CD34/CXCR4-positive cells was also observed in diabetic patients. PBMCs expressing CXCR4 positively correlated with levels of progenitor cells in control participants but not in diabetic patients. Levels of putative progenitor and CXCR4-positive cells were further decreased in patients with diabetic complications, including cardiovascular and microvascular diseases. CONCLUSIONS/INTERPRETATION: A generalised decrease in a range of progenitor cell populations was observed in type 2 diabetic patients. This reduction was also negatively associated with disease severity.

[Effect of naloxone and naltrexone on the postprandial energy expenditure and endocrine pancreas response to a mixed meal in essential obesity]. / Effetto del naloxone e del naltrexone sulla spesa energetica post-prandiale e sulla risposta del pancreas endocrino ad un pasto misto nell'obesità essenziale.

It has been recently shown that the opioid antagonists naloxone and naltrexone are able to reduce appetite and to raise energy expenditure in animal models. The results of studies in humans are inconclusive. In 10 female obese patients we have evaluated the effects of naloxone infusion (2 mg/2 h) on energy expenditure, measured by indirect calorimetry (Deltatrac) and on plasmatic levels of glucose, insulin, glucagon and somatostatin, fasting and after the assumption of a standard 567 kcal meal (C = 20%, P = 20%, L = 60%). We have repeated the tests after a dietary period of 1 month, associated with naltrexone assumption. Acute administration of naloxone caused similar effects at the beginning and at the end of the study; we have observed a raise of caloric expenditure, a decrease of hyperinsulinemia and a high response of somatostatin to metabolic stimulus. After therapy, even with a weight reduction of 6%, we haven't observed either variations of energy expenditure or hormonal level changes. We conclude that in obese women opioid hypertone plays a role in thermic effect of meals and in the impaired response to the nutrients of the gastroenteropancreatic axis. The absence of any effects of naltrexone on the variables that we have studied is perhaps due to the difference in the dose, way of administration and of the different action on the target receptor by the two opioid antagonists.

Prevalence of glomerular hyperfiltration and nephromegaly in normo- and microalbuminuric type 2 diabetic patients.

Glomerular hyperfiltration, correlated with nephromegaly, is a frequent finding in type 1 (insulin-dependent) diabetes. In type 2 (non-insulin-dependent) diabetes, very few studies have been performed, and the results have been inconclusive. Glomerular filtration rate (GFR) and kidney volume, using 99mTc-DTPA scintigraphy and ultrasonography, respectively, were evaluated in 58 control subjects and 163 type 2 diabetic patients; 79 of whom were normoalbuminuric and 84 microalbuminuric. In the two groups of patients, these parameters did not differ significantly from those of controls, even when hypertensive subjects were excluded. Glomerular hyperfiltration was observed in 10 cases; all were normotensive (9.8%), of whom 7 were normoalbuminuric and 3 microalbuminuric. Nephromegaly was observed in 3 other normotensive microalbuminuric diabetic patients. Hypertensive subjects showed a lower GFR than normotensive patients and control subjects. Multivariate analysis showed a negative correlation between glomerular filtrate and systolic blood pressure (BP) in the overall population of patients and in normo- and microalbuminuric patients taken separately. It is concluded that the relationship between these variables forms a continuum in our type 2 diabetic patients; it may also be important in determining the low prevalence of hyperfiltration and nephromegaly found in our patients, who had BP levels higher than those of controls.

[Glomerular filtration and renal volume in type II diabetes (non-insulin-dependent): study in normal and microalbuminuria patients]. / La filtrazione glomerulare ed il volume renale nel diabete tipo II (non-insulino dipendente): studio nei pazienti normo e microalbuminurici.

In type 2 diabetes elevated glomerular filtration rate (GFR) and increased renal volume (RV), often accompanied to normo or microalbuminuria, were demonstrated. This condition is considered a pathogenetic factor for clinical nephropathy. As this topic is little studied in type 2 diabetes, we have investigated 73 type 2 diabetic patients (34 normo and 39 microalbuminuric), looking for a correlation between GFR, RV, hypertension, duration of diabetes and indexes of metabolic control. GFR was measured by a scintigraphy, after infusion of 99Tc-DTPA. Renal volume was determined by ultrasound scanning. Between the groups GFR and RV weren't different; elevated GFR was demonstrated in 3 patients; increased RV in 1 patient. In the hypertensive group GFR was lower than in normotensive group and in controls. Multivariate analysis in stepwise demonstrated that GFR presents a negative correlation to systolic blood pressure as in normo as in microalbuminuric patients. In the normotensive group GFR didn't correlate to the other variables. The present data suggest that in type 2 diabetes there is a little prevalence of glomerular hyperfiltration and increased renal volume and that hypertension plays a role on GFR of hypertensive diabetic patients.

[Validity of the first morning urine collection for screening for microalbuminuria in the diabetic]. / Validità della raccolta urinaria del primo mattino per lo screening della microalbuminuria nel diabete.

With the aim of evaluating the reliability of morning urine collection, compared to the overnight period, in the assessment of microalbuminuria, we measured albumin and creatinine concentration in overnight and morning urine of 125 diabetic outpatients. The overnight albumin excretion rate resulted in relation to morning albumin concentration and morning albumin/creatinine ratio. The sensitivity of this method of urine collection, compared to the overnight sample, was 55.5%, the specificity 96.6% and the predictive value 43% using, as a measure, the albumin concentration. These values improved by correcting albumin for creatinine concentration. Concerning high risk albuminuria (overnight excretion rate greater than 30 micrograms/min), we found a sensitivity and predictive value of the first morning collection highly improved by the albumin/creatinine ratio. It is concluded that the first morning urine collection can be used in the diagnosis of microalbuminuria in diabetic patients, especially when we calculate the albumin/creatinine ratio. This simple and reliable method allows the identification of microalbuminuric subjects and of the patients at risk to develop clinical nephropathy with a good sensitivity.