Antonio Pacilli

IRCCS Ospedale Casa Sollievo della Sofferenza, Giovanni Rotondo, Apulia, Italy

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Publications (15)47.79 Total impact

  • No preview · Article · Apr 2016 · Acta Diabetologica
  • [Show abstract] [Hide abstract] ABSTRACT: The high mortality risk of patients with type 2 diabetes mellitus may well be explained by the several comorbidities and/or complications. Also the intrinsic genetic component predisposing to diabetes might have a role in shaping the risk of diabetes-related mortality. Among type 2 diabetes mellitus SNPs, rs1801282 is of particular interest because (i) it is harbored by peroxisome proliferator-activated receptor-γ2 (PPARγ2), which is the target for thiazolidinediones which are used as antidiabetic drugs, decreasing all-cause mortality in type 2 diabetes mellitus, and (ii) it is associated with insulin resistance and related traits, risk factors for overall mortality in type 2 diabetes mellitus. We investigated the role of PPARγ2 P12A, according to a dominant model (PA + AA vs. PP individuals) on incident all-cause mortality in three cohorts of type 2 diabetes mellitus, comprising a total of 1672 patients (462 deaths) and then performed a meta-analysis of ours and all available published data. In the three cohorts pooled and analyzed together, no association between PPARγ2 P12A and all-cause mortality was observed (HR 1.02, 95 % CI 0.79-1.33). Similar results were observed after adjusting for age, sex, smoking habits, and BMI (HR 1.09, 95 % CI 0.83-1.43). In a meta-analysis of ours and all studies previously published (n = 3241 individuals; 666 events), no association was observed between PPARγ2 P12A and all-cause mortality (HR 1.07, 95 % CI 0.85-1.33). Results from our individual samples as well as from our meta-analysis suggest that the PPARγ2 P12A does not significantly affect all-cause mortality in patients with type 2 diabetes mellitus.
    No preview · Article · Mar 2016 · Endocrine
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    Full-text · Article · Jan 2016 · Acta Diabetologica
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    [Show abstract] [Hide abstract] ABSTRACT: Serum uric acid may predict the onset and progression of kidney disease, but it is unclear whether uric acid is an independent risk factor for diabetic nephropathy. Our aim was to study the relationship between uric acid levels and the development of CKD components in patients with type 2 diabetes. Longitudinal study of a cohort of patients with type 2 diabetes from the database of the Italian Association of Clinical Diabetologists network. From a total of 62,830 patients attending the diabetes centers between January 1, 2004, and June 30, 2008, we considered those with baseline eGFR values ≥60 ml/min per 1.73 m(2) and normal albumin excretion (n=20,142). Urinary albumin excretion, GFR, and serum uric acid were available in 13,964 patients. We assessed the association of serum uric acid quintiles with onset of CKD components by multinomial logistic regression model adjusting for potential confounders. We calculated the relative risk ratios (RRRs) for eGFR <60 ml/min per 1.73 m(2), albuminuria, and their combination at 4 years. At 4-year follow-up, 1109 (7.9%) patients developed GFR <60 ml/min per 1.73 m(2) with normoalbuminuria, 1968 (14.1%) had albuminuria with eGFR ≥60 ml/min per 1.73 m(2), and 286 (2.0%) had albuminuria with eGFR <60 ml/min per 1.73 m(2). The incidence of eGFR <60 ml/min per 1.73 m(2) increased in parallel with uric acid quintiles: Compared with the lowest quintile, RRRs were 1.46 (95% confidence interval [CI], 1.14 to 1.88; P=0.003), 1.44 (95% CI, 1.11 to 1.87; P=0.006), 1.95 (95% CI, 1.48 to 2.58; P<0.001), and 2.61 (95% CI, 1.98 to 3.42; P<0.001) for second, third, fourth, and fifth quintiles, respectively. Serum uric acid was significantly associated with albuminuria only in presence of eGFR <60 ml/min per 1.73 m(2). Mild hyperuricemia is strongly associated with the risk of CKD in patients with type 2 diabetes. Copyright © 2015 by the American Society of Nephrology.
    Full-text · Article · Sep 2015 · Clinical Journal of the American Society of Nephrology
  • [Show abstract] [Hide abstract] ABSTRACT: Diabetes is very common among the elderly. In Italy, more than 20% of people older than 75 suffer from the disease. Many of them are frail, with extensive comorbid conditions, or long-standing diabetes in whom the risk of hypoglycemia is very high. An appropriate multidimensional approach is therefore needed when assessing geriatric syndromes, including frailty, cognitive impairment, poor mobility, reduced vision and hearing, depression, and chronic pain. Although in the last few years the benefits of intensive glucose treatment have been described, it is becoming increasingly clear that over-treatment, particularly in older adults, is a significant problem given the fact that hypoglycemia is related to a number of adverse conditions, including mortality. Consequently, and in the light of a “patient-centered approach”, less stringent A1c goals (such as < 8.0-8.5%) may be appropriate for these patients. The risk of hypoglycemia is highest with insulin and sulphonyl - ureas, mainly glibenclamide. These latter drugs should be avoid in older diabetics. New hypoglycemic agents with a very low risk of hypoglycemia have recently been introduced on the market. This review assesses these drugs and insulin analogs.
    No preview · Article · Sep 2015 · Giornale Italiano di Diabetologia e Metabolismo
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    [Show abstract] [Hide abstract] ABSTRACT: Background: To investigate prospectively the relationship between target values of glycated hemoglobin, blood pressure and LDL-cholesterol, as considered in a combined fashion, and all-cause mortality in patients with type 2 diabetes mellitus. Methods: Two cohorts of patients with type 2 diabetes mellitus, the Gargano Mortality Study (n=810) and the Foggia Mortality Study (n=929), were investigated. A weighted target risk score was built as a weight linear combination of the recommended targets reached by each patient. Results: In the Gargano Mortality Study and in the Foggia Mortality Study (mean follow up=7.4 and 5.5 years, respectively), 161 (19.9%) and 220 (23.7%) patients died, with an age and sex adjusted annual incidence rate of 2.1 and 2.8 per 100 person-years, respectively. In both study samples the weighted target risk score tended to be linearly associated with all-cause mortality (HR for one point increment=1.30, 95% CI: 1.11-1.53, p=0.001, and HR=1.08, 95% CI: 0.95-1.24, p=0.243, respectively). When the two cohorts were pooled and analyzed together, a clear association between weighted target risk score and all-cause mortality was observed (HR for one point increment=1.17, 95% CI:1.05-1.30, p=0.004). This counterintuitive association was no longer observable in a model including age, sex, body mass index, smoking habit, estimated glomerular filtration rate, albuminuria and anti-diabetic, anti-hypertensive and anti-dyslipidemic treatment as covariates (HR for one point increment=0.99, 95% CI: 0.87-1.12, p=0.852). Conclusions: In a real life clinical set of patients with type 2 diabetes mellitus, the combination of recommended target values of established cardiovascular risk factors is not associated with all-cause mortality.
    Preview · Article · Apr 2015 · PLoS ONE
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    [Show abstract] [Hide abstract] ABSTRACT: Chronic kidney disease (CKD) entails a worse cardiovascular outcome. The aim of our work was to study the relationship between CKD and the achievement of recommended targets for glycated haemoglobin (HbA1c), low-density lipoprotein cholesterol (LDL-c) and blood pressure (BP) in a real-life sample of patients with type 2 diabetes mellitus (T2DM). We analysed a sample of 116 777 outpatients from the Network of the Italian Association of Clinical Diabetologists; all patients had T2DM and at least one measurement of HbA1c, LDL-c, BP, serum creatinine and albuminuria in the year 2010. The outcome was the achievement of HbA1c, LDL-c and BP values as recommended by International Guidelines. In the entire sample, the mean value of HbA1c was 7.2 ± 1.2%, of LDL-c was 102 ± 33 mg/dL and of BP was 138/78 ± 19/9 mmHg. CKD and its components were associated with poor glycaemic and BP control, notwithstanding greater use of glucose and BP-lowering drugs, while no association was found with LDL-c values. Factors independently related to unsatisfactory glycaemic control included female gender, body mass index, duration of disease and high albuminuria. Men, older people and those taking statins were more likely to reach LDL-c target levels. Male gender, age and high albuminuria strongly affected the achievement of BP targets. CKD or its components, mainly high albuminuria, are associated with failure to reach therapeutic targets, especially for HbA1c and BP, despite a greater use of drugs in patients with T2DM. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
    Full-text · Article · Apr 2015 · Nephrology Dialysis Transplantation
  • [Show abstract] [Hide abstract] ABSTRACT: Metabolink is a smartphone-based telemedicine solution that allows the proactive participation of elderly people or patients with chronic diseases to the monitoring of their own lifestyles. The patient uses a smartphone to collect and to send to doctors or caregivers information about his/her lifestyle or about physiological parameters measured using integrated medical devices. The doctors use a tablet or a computer to communicate with their patients, to check real-time their health, to receive alerts about unsafe health conditions and to update the treatment. The data collected by the patients populates the personal health records and can be used afterwards to find correlations between lifestyles and the onset or progression of chronic diseases. This solution empowers the patients for active ageing and enables them to easily cooperate with the doctors in the management of their wellness or chronic diseases.
    No preview · Chapter · Jan 2015
  • No preview · Article · Mar 2014 · Acta Diabetologica
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    [Show abstract] [Hide abstract] ABSTRACT: OBJECTIVE To develop and validate a parsimonious model for predicting short-term all-cause mortality in patients with type 2 diabetes mellitus (T2DM).RESEARCH DESIGN AND METHODS Two cohorts of patients with T2DM were investigated. The Gargano Mortality Study (GMS, n = 679 patients) was the training set and the Foggia Mortality Study (FMS, n = 936 patients) represented the validation sample. GMS and FMS cohorts were prospectively followed-up for 7.40 ± 2.15 and 4.51 ± 1.69 years, respectively, and all-cause mortality was registered. A new forward variable selection within a multivariate Cox regression was implemented. Starting from the empty model, each step selected the predictor that, once included into the multivariate Cox model, yielded the maximum continuous net reclassification improvement (cNRI). The selection procedure stopped when no further statistically significant cNRI increase was detected.RESULTSNine variables (age, BMI, diastolic blood pressure, LDL cholesterol, triglycerides, HDL cholesterol, urine albumin-to-creatinine ratio, and antihypertensive and insulin therapy) were included in the final predictive model with a C statistic of 0.88 (95% CI 0.82-0.94) in the GMS and 0.82 (0.76-0.87) in the FMS. Finally, we used a recursive partition and amalgamation algorithm to identify patients at intermediate and high mortality risk (hazard ratio 7.0 and 24.4, respectively, as compared with those at low risk). A web-based risk calculator was also developed.CONCLUSIONS We developed and validated a parsimonious all-cause mortality equation in T2DM, providing also a user-friendly web-based risk calculator. Our model may help prioritize the use of available resources for targeting aggressive preventive and treatment strategies in a subset of very high-risk individuals.
    Full-text · Article · May 2013 · Diabetes care
  • [Show abstract] [Hide abstract] ABSTRACT: Objective: To assess the impact of relationship between glycated hemoglobin (HbA(1c)), fibrinogen and HDL-cholesterol (HDL-c) on cardiovascular disease in type 2 diabetes. Methods: We investigated i) the relationship of HbA1c, fibrinogen and HDL-c in 375 coronary artery disease (CAD)-negative and 320 CAD-positive diabetic patients and ii) the association between clustering of these three factors and incident major cardiovascular events in 317/320 CAD-positive patients. Results: i) The relationships between HbA1c and both fibrinogen and HDL-c and between HDL-c and fibrinogen were significant only in CAD-positive patients (β = 10.655, p = 0.002; β = -1.056, p = 0.013; β = -1.751, p = 0.000008, respectively); ii) patients with worse-than-median levels of the three factors showed higher risk for major cardiovascular events than others (HR: 2.22, 95%CI = 1.23-4.02, p = 0.008). Both findings were independent of LDL-c, blood pressure or ongoing therapies. Conclusion: Our findings suggest interwoven actions of poor glycemic control, low grade inflammation and low HDL-c on atherosclerotic processes in type 2 diabetes.
    No preview · Article · Feb 2013 · Atherosclerosis
  • No preview · Chapter · Oct 2012
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    [Show abstract] [Hide abstract] ABSTRACT: Insulin resistance (IR) and cardiovascular disease may share a common genetic background. We investigated the role of IR-associated ENPP1 K121Q polymorphism (rs1044498) on cardiovascular disease in high-risk individuals. A prospective study (average follow-up, 37 months) was conducted for major cardiovascular events (myocardial infarction [MI], stroke, cardiovascular death) from the Gargano Heart Study (GHS; n = 330 with type 2 diabetes and coronary artery disease), the Tor Vergata Atherosclerosis Study (TVAS; n = 141 who had MI), and the Cardiovascular Risk Extended Evaluation in Dialysis (CREED) database (n = 266 with end-stage renal disease). Age at MI was investigated in cross-sectional studies of 339 type 2 diabetic patients (n = 169 from Italy, n = 170 from the U.S.). Incidence of cardiovascular events per 100 person--years was 4.2 in GHS, 10.8 in TVAS, and 11.7 in CREED. Hazard ratios (HRs) for KQ+QQ versus individuals carrying the K121/K121 genotype (KK) individuals were 1.47 (95% CI 0.80-2.70) in GHS, 2.31 (95% CI 1.22-4.34) in TVAS, and 1.36 (95% CI 0.88-2.10) in CREED, and 1.56 (95% CI 1.15-2.12) in the three cohorts combined. In the 395 diabetic patients, the Q121 variant predicted cardiovascular events among obese but not among nonobese individuals (HR 5.94 vs. 0.62, P = 0.003 for interaction). A similar synergism was observed in cross-sectional studies, with age at MI being 3 years younger in Q121 carriers than in KK homozygotes among obese but not among nonobese patients (P = 0.035 for interaction). The ENPP1 K121Q polymorphism is an independent predictor of major cardiovascular events in high-risk individuals. In type 2 diabetes, this effect is exacerbated by obesity. Future larger studies are needed to confirm our finding.
    Full-text · Article · Feb 2011 · Diabetes
  • [Show abstract] [Hide abstract] ABSTRACT: The International Diabetes Federation (IDF) indicates age above 45 years as a major risk factor for diabetes and predicts that the number of persons with the disease, which currently stands at 190 million, will double by the year 2025. Several recent trials suggest that tighter glucose control reduces long-term complications in diabetic patients; however, outcomes of tight blood sugar control in the elderly are not known. Nevertheless, the principles of management of type 2 diabetes in the elderly are not different from those in middle-aged patients. There are several reasons to keep glucose control on target, also in the elderly; nonetheless, it should be considered that the risk of hypoglycemia is more deleterious in the elderly and should be avoided. The old and more recent oral glucose-lowering agents, along with the newer types of insulin, will be discussed in this review.
    No preview · Article · Sep 2010 · Journal of nephrology
  • No preview · Article · Sep 2010 · Nutrition, metabolism, and cardiovascular diseases: NMCD