Rodolfo Nasti

High cardiovascular risk in patients with Type 2 diabetic nephropathy: the predictive role of albuminuria and glomerular filtration rate. The NID-2 Prospective Cohort Study

BACKGROUND In Type 2 diabetic patients, clinical diagnosis of diabetic nephropathy (DN) is generally based on the concomitant presence of abnormal albuminuria and severe retinopathy. In this high-risk population, cardiovascular (CV) outcome has never been evaluated. METHODS A cohort of 742 Type 2 diabetic patients with DN from 17 national centres was selected by the presence of persistent albuminuria ≥ 30 mg/day and severe diabetic retinopathy and was followed prospectively. Time to CV event (CV death, non-fatal myocardial infarction, non-fatal stroke, revascularization, major amputation) was the primary composite end point and it was analysed by multivariable Coxs proportional hazards model. The interaction between albuminuria and glomerular filtration rate (GFR) was specifically investigated. RESULTS Median follow-up was 4.6 years. Overall 242 events (26% of which fatal) were observed in 202 patients. The proportion of CV events increased from 19 to 40% as GFR declined from the highest (≥ 90 mL/min/1.73 m(2)) to the lowest (<45 mL/min/1.73 m(2)) category and was equal to 25 and 33% in microalbuminuria and macroalbuminuria, respectively. In multivariable analysis, the interaction between albuminuria and GFR was statistically significant (P = 0.012). Albuminuria, indeed, had a remarkable prognostic effect in subjects with high GFR that virtually disappeared as GFR became <30 mL/min/1.73 m(2). Age, smoking habit, previous occurrence of myocardial infarction or stroke and proliferative retinopathy were all found to have a statistically significant prognostic effect on CV outcome. CONCLUSIONS A clinically based diagnosis of DN in Type 2 diabetes allows the identification of subjects with high CV risk. Albuminuria has a relevant prognostic effect on CV morbidity and mortality; its effect is especially pronounced when GFR is normal or near normal.

Increased vascular endothelial growth factor mRNA expression in the heart of streptozotocin-induced diabetic rats.

The aim of the present study was to evaluate vascular endothelial growth factor (VEGF), fms-like tyrosine kinase 1 (flt-1), and fetal liver kinase (flk-1) expression in the heart of experimental diabetic rats. Ten young adult male Wistar rats (5 streptozotocin [STZ]-induced diabetic rats, without insulin treatment, and 5 controls) were studied. Ninety days after the induction of diabetes, semiquantitative reverse transcription (RT)-polymerase chain reaction (PCR) coamplification of VEGF/glyceraldehyde 3-phosphate dehydrogenase (GAPDH) transcription was performed. RT-PCR was also performed for VEGF receptors flk-1 and flt-1. VEGF mRNA expression, at 234 bp, was detectable in the heart of the rats and was significantly higher in those with diabetes. Densitometric analysis of PCR products showed that VEGF mRNA levels were meanly 4.8-fold higher in STZ-induced diabetic rats than controls (VEGF/GAPDH densitometric ratio, 3.46 +/- 0.20 v 0.74 +/- 0.10, P <.001). No significant difference was found in flt-1 and flk-1 amplification products between STZ-induced diabetic rats and controls (flt-1/GAPDH densitometric ratio, 0.58 +/- 0.01 v 0.64 +/- 0.05, P>.1; flk-1/GAPDH densitometric ratio, 0.66 +/- 0.10 v 0.7 +/- 0.06, P >.2). The increase in VEGF mRNA expression observed in this experimental diabetic model is in contrast with the typical impairment in collateral vessels of diabetic hearts. This apparent discrepancy might be explained by a resistance of cardiac tissue to VEGF. The lack of mRNA flt-1 and flk-1 overexpression in diabetic hearts could be one of the mechanisms for this resistance.

Lung ultrasound for diagnosis of pneumonia in emergency department.

Lung ultrasound (LUS) in the emergency department (ED) has shown a significant role in the diagnostic workup of pulmonary edema, pneumothorax and pleural effusions. The aim of this study is to assess the reliability of LUS for the diagnosis of acute pneumonia compared to chest X-ray (CXR) study. The study was conducted from September 2013 to March 2015. 107 patients were admitted to the ED with a clinical appearance of pneumonia. All the patients underwent a CXR study, read by a radiologist, and an LUS, performed by a trained ED physician on duty. Among the 105 patients, 68 were given a final diagnosis of pneumonia. We found a sensitivity of 0.985 and a specificity of 0.649 for LUS, and a sensitivity of 0.735 and specificity of 0.595 for CXR. The positive predictive value for LUS was 0.838 against 0.7 for CXR. The negative predictive value of LUS was 0.960 versus 0.550 for CXR. This study has shown sensitivity, positive predictive value and negative predictive value of LUS compared to the CXR study for the diagnosis of acute pneumonia. These results suggest the use of bedside thoracic US first-line diagnostic tool in patients with suspected pneumonia.

Coronary artery disease is detectable by multi-slice computed tomography in most asymptomatic type 2 diabetic patients at high cardiovascular risk

Objective: Non-invasive testing often does not identify coronary artery disease (CAD) in diabetic subjects. This study was designed in order to examine the prevalence of CAD in a cohort of asymptomatic type 2 diabetic patients at high cardiovascular risk and negative nuclear imaging, using multi-slice computed tomography (MSCT) angiography. Methods: In total, 770 type 2 diabetic patients were screened from January 2008 through July 2010. Of these, 132 Caucasians with diabetic nephropathy and asymptomatic for angina were eligible for a cross-sectional study. Patients underwent MSCT after ischaemia was excluded by myocardial Single Photon Emission Computed Tomography (SPECT) at rest and after dynamic exercise. When obstructive plaques were found (≥50% lumen narrowing), patients were sent to conventional coronary angiography (CCA). Results: Six subjects were not included in the analysis because of motion artefacts. MSCT was positive for CAD in 114 patients (90%). Within patients with positive MSCT, 60 (48% of all) showed one or more obstructive plaques. CCA confirmed significant stenosis (≥50%) in 48 of these 60 patients (80%). Some 21 (35%) showed stenosis ≥75% and were submitted to the revascularisation procedure. Conclusion: MSCT seems to better identify CAD than myocardial SPECT in asymptomatic patients with type 2 diabetes and diabetic nephropathy.

Kidney in diabetes: from organ damage target to therapeutic target.

Despite the growing of pharmacological options for the treatment of diabetes, epidemiological studies suggest that a substantial proportion of patients does not achieve glycemic goals and so suffers from the risk of chronic complications. This review explores the inhibition of renal glucose reabsorption as a novel approach to treat hyperglycemia. Sodium-glucose cotransporter 2 (SGLT2), a low-affinity high-capacity transporter located in the brush-border membrane of the early segment (S1) of the proximal renal tubule, accounts for about 90% of the reabsorption of glucose from tubular fluid. Competitive inhibitors of SGLT2 that are responsible for renal excretion of glucose provide a unique mechanism to potentially lower the elevated blood glucose levels in patients with diabetes. They act independently of insulin secretion, thereby minimizing the risk of hypoglycemia and weight gain, to control energy balance in a negative direction, a distinctive advantage of this class of drugs over existing oral hypoglycemic agents. Although this group of medications is still under investigation, it appears to be safe and generally well tolerated and it would be expected to improve the treatment of type 2 diabetes as monotherapy or in combination with other oral or parenteral agents. Dapagliflozin is the first agent within this class, which induces clinically meaningful reductions in FPG, PPG, HbA1c, and body weight in type 2 diabetes.

Perspectives of nuclear diagnostic imaging in diabetic cardiomyopathy

Diabetic cardiomyopathy is a ventricular dysfunction in the absence of coronary artery disease, valvular or hypertensive heart disease. The mechanisms underlying diabetic cardiomyopathy may involve metabolic disturbances, myocardial fibrosis, small vessel disease, microcirculation abnormalities, cardiac autonomic neuropathy and insulin resistance. Diagnostic problems emerge because no specific disease pattern characterizes the disease and because there may be coexistence in diabetes of coronary artery disease and hypertension as independent but compounding causes of biochemical, anatomical and functional alterations impairing cardiac function. In this paper we will review the role of nuclear imaging today, concentrating on the diagnostic capabilities of radionuclide ventriculography, to study the effect of insulin resistance and, more extensively, gated-single photon emission computed tomography with Tc-99m labelled agents. A broad analysis will be dedicated to: 1) positron emission tomography using perfusion agents, with the potential to quantify resting and stress blood flow and coronary flow reserve; 2) radionuclide procedures evaluating aerobic and anaerobic cardiac metabolism; and 3) cardiac neurotransmission imaging, studying the autonomic neuropathy.

Prevalence of diabetes in patients with nonacute CAD

The relationship between coronary artery disease (CAD) and diabetes is widely documented [1–3], and diabetic patients present a worse CV outcome in respect to nondiabetic patients [4]. Recently, the physiopathology of CV risk in patients affected by undiagnosed or newly detected diabetes is matter of great interest [5, 6]. Actually, the prevalence of diabetes in CAD patients is not clearly estimated because diagnosis is generally based on not exhaustive criteria, such as history of diabetes or hyperglycemia during acute events. We aimed to evaluate the true prevalence of diabetes in nonacute patients affected by CAD, as assessed by coronary angiography. Six hundred and seventy nine patients admitted from November 2008 to November 2009 in the Cardiology Ward of University of Naples to perform angiography for suspect CAD were assessed for eligibility. Patients with coronary acute events in the last 4 week and subjects without angiographically detectable CAD were excluded. Moreover, treatment with steroids, acute infections, fever, or any condition that could impair glycemic metabolism were further exclusion criteria. Finally, 510 Caucasian patients (301M, 209F; age 57 ± 13 years) were eligible. Ninety seven (19%) had known diabetes (history and/or use of antidiabetic agents or newly discovered by fasting glucose value C126 mg/dl). The other 413 were submitted to standardized oral glucose test tolerance (OGTT), repeated twice in case of abnormal response [7]. Diabetes was revealed in 151 subjects, while 72 were affected by prediabetes, a condition at high risk to develop overt diabetes. Thus, the overall prevalence of diabetes was 48.6%, and the prevalence of glycemic impairments (diabetes plus prediabetes) was 62.7%. Only 190 (37.2%) showed a normal glucose tolerance (Fig. 1). The number of vessels with obstructive plaque (C50% lumen narrowing) was higher in diabetic than in nondiabetic group (1.12 ± 1.13 vs. 1.68 ± 1.33; P \ 0.01),