Roberto Scicali

Cardiovascular Risk Profile in Subjects With Prediabetes and New-Onset Type 2 Diabetes Identified by HbA 1c According to American Diabetes Association Criteria

OBJECTIVE We investigated the cardiovascular risk profile in subjects with prediabetes and new-onset type 2 diabetes identified by glycated hemoglobin A1c (HbA1c) according to the new American Diabetes Association criteria. RESEARCH DESIGN AND METHODS Arterial stiffness, intima-media thickness (IMT), soluble receptor for advanced glycation end products (sRAGEs), and oral glucose tolerance test (OGTT) were evaluated in 274 subjects without a previous history of diabetes. The subjects were stratified into three groups according to the HbA1c levels. RESULTS The subjects with prediabetes (n = 117, HbA1c 5.7–6.4% [39–46 mmol/mol]) showed a higher augmentation (Aug), augmentation index (AugI), and IMT compared with those with lower HbA1c; however, these values were similar to those of subjects with HbA1c >6.5% (48 mmol/mol). When we further analyzed the subjects with prediabetes but included only subjects with normal glucose tolerance (NT) in the analysis, AugI and IMT still remained significantly higher than their levels in control subjects with HbA1c <5.7% (39 mmol/mol). After multiple regression analyses including several cardiovascular risk factors, only HbA1c, age, and sRAGE were significantly correlated with the IMT, whereas age and 1-h postload glucose were the major determinants of AugI. CONCLUSIONS Our data show that subjects with prediabetes according to HbA1c, but with both NT according to the OGTT and normal fasting glycemia, have an altered IMT and AugI. These data suggest that a simple, reproducible, and less expensive marker such as HbA1c may be better able to identify prediabetic subjects at high cardiovascular risk compared with fasting glycemia or OGTT alone.

Lipid and liver abnormalities in haemoglobin A1c-defined prediabetes and type 2 diabetes

BACKGROUND AND AIMS We aimed to investigate lipid abnormalities and liver steatosis in patients with HbA1c-defined prediabetes and type 2 diabetes compared to individuals with HbA1c-defined normoglycaemia. METHODS AND RESULTS Ninety-one subjects with prediabetes according to HbA1c, i.e. from 5.7 to 6.4% (39-46 mmol/mol), 50 newly diagnosed patients with HbA1c-defined type 2 diabetes (HbA1c ≥6.5% [≥48 mmol/mol]), and 67 controls with HbA1c lower than 5.7% (<39 mmol/mol), were studied. Fasting blood samples for lipid profiles, fatty liver index (FLI), bioimpedance analysis, ultrasound scan of the liver, and BARD (body mass index, aspartate aminotransferase/alanine aminotransferase ratio, diabetes) score for evaluation of liver fibrosis, were performed in all subjects. In comparison to controls, subjects with prediabetes were characterised by: lower apolipoprotein AI and HDL cholesterol levels, higher blood pressure, triglycerides levels and apolipoprotein B/apolipoprotein AI ratio, higher FLI, increased prevalence of and more severe hepatic steatosis, similar BARD score, and higher total body fat mass. In comparison to subjects with diabetes, subjects with prediabetes exhibited: similar blood pressure and apolipoprotein B/apolipoprotein AI ratio, similar FLI, reduced prevalence of and less severe hepatic steatosis, lower BARD score, increased percent fat and lower total body muscle mass. In comparison to controls, subjects with diabetes showed: lower apolipoprotein AI and HDL cholesterol levels, higher blood pressure and triglycerides levels, higher FLI, increased prevalence of and more severe hepatic steatosis, higher BARD score, and higher total body muscle mass. Moreover, HbA1c was correlated with BMI, HOMA-IR, triglycerides, HDL cholesterol, AST, and ALT. CONCLUSIONS Subjects with HbA1c-defined prediabetes and type 2 diabetes, respectively, are characterised by abnormalities in lipid profile and liver steatosis, thus exhibiting a severe risk profile for cardiovascular and liver diseases.

Atorvastatin but Not Pravastatin Impairs Mitochondrial Function in Human Pancreatic Islets and Rat β-Cells. Direct Effect of Oxidative Stress

Statins are a class of drugs widely prescribed as frontline therapy for lowering plasma LDL-cholesterol in cardiovascular risk prevention. Several clinical reports have recently suggested an increased risk of type 2 diabetes associated with chronic use of these drugs. The pathophysiology of this effect remains to be fully elucidated but impaired β-cell function constitutes a potential mechanism. The aim of this study was to explore the effect of a chronic treatment with lipophilic and hydrophilic statins on β-cell function, using human pancreatic islets and rat insulin-secreting INS-1 cells; we particularly focused on the role of mitochondria and oxidative stress. The present study demonstrates, for the first time, that atorvastatin (lipophilic) but not pravastatin (hydrophilic) affected insulin release and mitochondrial metabolism due to the suppression of antioxidant defense system and induction of ROS production in pancreatic β-cell models. Mevalonate addition and treatment with a specific antioxidant (N-AcetylCysteine) effectively reversed the observed defects. These data demonstrate that mitochondrial oxidative stress is a key element in the pathogenesis of statin-related diabetes and may have clinical relevance to design strategies for prevention or reduction of statin induced β-cell dysfunction and diabetes in patients treated with lipophilic statins.

HbA1c Identifies Subjects With Prediabetes and Subclinical Left Ventricular Diastolic Dysfunction

Context Prediabetes is associated with subclinical cardiac changes associated with heart failure development. Objective We investigated diastolic function and its association with markers of glycation and inflammation related to cardiovascular disease in patients with prediabetes. We focused on individuals with prediabetes identified only by glycated hemoglobin A1c [HbA1c; 5.7% to 6.4% and normal fasting glucose (NFG) and normal glucose tolerance (NGT) after an oral glucose tolerance test (OGTT)]. Design Cross-sectional study. Setting Departments of Clinical and Experimental Medicine and Cardiology, University of Catania, Catania, Italy. Main Outcome Measures HbA1c, OGTT, Doppler echocardiography, soluble receptor for advanced glycation end products (sRAGEs), and endogenous secretory RAGE (esRAGE) were evaluated. Patients We recruited 167 subjects with NFG/NGT who were stratified according to HbA1c level: controls (HbA1c <5.7%) and HbA1c prediabetes (HbA1c 5.7% to 6.4%). Results Patients with HbA1c prediabetes (n = 106) showed a lower peak mitral inflow in early diastole (E wave) to late diastolic atrial filling velocity (A wave) ratio (E/A ratio) than controls (n = 61) (1.10 ± 0.24 vs 1.18 ± 0.23; P < 0.05). They showed a higher left atrium volume (LAV) (28.4 ± 5 vs 22.1 ± 3; P < 0.05) and sphericity index (SI) (0.6 ± 0.06 vs 0.5 ± 0.05; P < 0.05). After multiple regression analyses, HbA1c, sRAGE, and esRAGE were the major determinants of E/A ratio, LAV, and SI. Conclusions Subjects with HbA1c prediabetes exhibited subclinical cardiac alterations associated with sRAGE, esRAGE, and HbA1c. These subjects would not have been classified as having prediabetes on the basis of fasting glycemia or post-OGTT values.

Apolipoprotein AI and HDL are reduced in stable cirrhotic patients with adrenal insufficiency: A possible role in glucocorticoid deficiency

Abstract Backgrounds and aims: Adrenal insufficiency (AI) has been reported in patients with stable cirrhosis. A lack of substrates has been suggested as a possible contributing pathogenic mechanism leading to glucocorticoid deficiency in these subjects. To better explore this hypothesis, we studied lipoproteins in cirrhotics with and without AI. Methods. A total of 81 cirrhotic patients and 30 normal volunteers were enrolled. The severity of liver disease was graded by Child-Pugh score. Total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglyceride (TG), and apolipoprotein AI (Apo-AI) levels were evaluated. HDL subfractions were measured by gradient gel electrophoresis. Adrenal function was assessed by the Low-Dose Short Synacthen Test. Results. Cirrhotic patients showed a significant reduction of TC, HDL, LDL, TG, and Apo-AI levels compared with controls. HDL3 was significantly lower, while HDL2 was higher, in cirrhotics compared with the controls. AI was observed in 26 patients. TC, TG, HDL, and Apo-AI were significantly reduced in cirrhotics with AI compared with those with normal adrenal function. HDL2 and HDL3 did not differ between these two groups. Delta cortisol was related to TC (r = 0.30, p < 0.01), TG (r = 0.22, p = 0.05), and Apo-AI (r = 0.37, p < 0.001). Multivariate analysis revealed that Apo-AI and HDL were independently associated with AI. Conclusion. Our study shows that TC, TG, HDL, and Apo-AI are reduced in cirrhotics with AI. In particular, because both HDL and Apo-AI play a primary role in providing substrates for steroidogenesis to adrenal cells, this deficiency may contribute to the pathogenesis of AI in these patients.

Left ventricular geometry and periodontitis in patients with the metabolic syndrome

ObjectiveThe presence of periodontal disease (PD) in subjects affected by the metabolic syndrome (MetS) may affect their risk of developing cardiovascular disease. The aim of this cross-sectional study was to investigate the systemic impact of PD in MetS, by assessing measures of sub-clinical atherosclerosis and left ventricular mass and geometry.Materials and methodsA total of 103 patients undergoing treatment for MetS were examined for confirmation of diagnosis, blood sampling, and measures of pulse wave velocity (PWV), carotid intima-media thickness (c-IMT), left ventricular mass index (LVM), and relative wall thickness (RWT). All subjects underwent a detailed dental assessment, including measurements of DMFT (decayed-missing-filled teeth) and periodontal parameters.ResultsTen patients (10%) were diagnosed with healthy-mild periodontitis, 38 patients (37%) were diagnosed in the moderate periodontitis group, and 55 (53%) had severe periodontitis. A total of 37% of subjects were affected by dental caries. Linear regression analysis revealed that patients with severe PD had increased average ventricular RWT (adjusted p = 0.032). Average full mouth probing pocket depth (PPD) was also associated with RWT (adjusted p = 0.006). No associations between PD and c-IMT, PWV, and LVM were detected after adjusted analyses.ConclusionThis study suggests that periodontitis may be associated with concentric left ventricular remodeling, a predictive index of cardiovascular events.Clinical relevanceThe presence of periodontitis in patients with MetS might have an effect on left ventricular geometry. These findings stress the importance of prevention, diagnosis, and management of periodontitis in patients with MetS.Trail registrationNCT03297749