Luca Scaglione

Low birthweight and metabolic abnormalities in twins with increased susceptibility to Type 2 diabetes mellitus

Aims To evaluate the role of environmental intra‐uterine factors in determining the birthweights of twins with increased susceptibility to diabetes and discordant for abnormal responses to the oral glucose tolerance test (OGTT) and verify the possible association of within‐pair birthweight differences and metabolic abnormalities in adult life.

Plasma homocysteine, methylenetetrahydrofolate reductase gene polymorphism and carotid intima-media thickness in Italian type 2 diabetic patients.

Abstract Background Moderately elevated levels of homocysteine have been associated with an increased cardiovascular risk in type 2 diabetic patients. The role of methylenetetrahydrofolate reductase gene polymorphism is less clear.

Insulin resistance shows selective metabolic and hormonal targets in the elderly.

Abstract. There has been no simultaneous evaluation of different aspects of insulin action in ageing. We studied 12 elderly (77 ± 2 years) and 12 young (26 ±1 years) subjects with normal glucose tolerance and matched for sex, body mass index, lean body mass (LBM), blood pressure and physical activity, using a euglycaemic‐hyperinsulinaemic clamp at about 350 pmol L‐1 in combination with [3H]‐glucose infusion. In the elderly group, hepatic glucose production was normal, fasting serum insulin and C‐peptide were significantly increased (P= 0.001) and glucose utilization (34.4 ±2.4 vs. 44.4± 3.2 μmol kg‐1 LBM min‐1, P= 0.02) and the percentage maximal suppression of C‐peptide (58 ± 6% vs. 79 ±5%, P= 0.02) during the clamp were reduced. Fasting plasma free fatty acid (FFA) and glycerol levels were similar in the two groups, but their percentage maximal suppression during the clamp was reduced in the elderly group (FFA 45± 5% vs. 77 ± 6%, P= 0.001; glycerol 43 ± 5% vs. 76± 3%, P= 0.001). Branched‐chain amino acids (valine, leucine, isoleucine) and glucagon levels were similar in the two groups, both while fasting and during the clamp. Thus, insulin resistance in ageing appears selective on glucose utilization, inhibition of lipolysis and feedback inhibition of the B‐cell secretion.

THE STORM (acute coronary Syndrome in paTients end Of life and Risk assesMent) study

Introduction Elderly patients with coexisting frailty and multiple comorbidities frequently present to the emergency department (ED). Because non-cardiovascular comorbidities and declining health status may affect their life expectancy, management of these patients should start in the ED. This study evaluated the role of Gold Standards Framework (GSF) criteria for identifying patients with acute coronary syndromes (ACS) approaching end of life. Methods All consecutive patients admitted to the ED and hospitalised with a diagnosis of ACS between May 2012 and July 2012 were included. According to GSF criteria, patients were labelled as positive GSF status when they met at least one general criterion and two heart disease criteria; furthermore, traditional cardiovascular risk scores (the Global Registry for Acute Coronary Events (GRACE) score and the Age, Creatinine and Ejection Fraction (ACEF) score) were calculated and WHOQOL-BREF was assessed. Mortality and repeat hospitalisation due to cardiovascular and non-cardiovascular causes were evaluated at 3-month and 12-month follow-up. Results From a total of 156 patients with ACS enrolled, 22 (14%) had a positive GSF. A positive GSF was associated with higher rate of non-cardiovascular events (22.7% vs 6.7%; p=0.03) at 3 months and higher rates of both cardiovascular and non-cardiovascular events (36% vs 16.4%; p=0.04 and 27.3% vs 6.7%; p=0.009, respectively) at 12 months. In multivariate analysis, an in-hospital GRACE score was a predictor of cardiovascular events, while a positive GSF independently predicted non-cardiovascular events. Conclusions The GSF score independently predicts non-cardiovascular events in patients presenting with ACS and may be used along with traditional cardiovascular risk scores in choosing wisely the most appropriate treatment. The present results need to be externally validated on larger samples.

Implementing hospital guidelines improves warfarin use in non-valvular atrial fibrillation: a before-after study

BackgroundThe use of oral anticoagulant therapy (OAT) to prevent non-valvular atrial fibrillation (NVAF) related-strokes is often sub-optimal. We aimed to evaluate whether implementing guidelines on antithrombotic therapy (AT) by a multifaceted strategy may improve appropriateness of its prescription in NVAF-patients discharged from a large tertiary-care hospital.MethodsA survey was conducted on all consecutive NVAF patients discharged before (1st January–30th June 2000, n = 313) and after (1st January–30th June 2004, n = 388) guideline development and implementation.ResultsWhen strongly recommended, OAT use increased from 56.6% (60/106 in 2000) to 81.9% (86/105 in 2004), with an absolute difference of +25.3% (95%CI: 15% 35%). In patients for whom the choice OAT/acetylsalicylic acid should be individualised, those discharged without any AT were 33.7% (34/101) in 2000 and 16.9% (21/124) in 2004 (-16.7%;95%CI: -26.2% -7.2%). In a logistic regression model, OAT prescription in 2004 was increased by 2.11 times (95%CI: 1.47 3.04), after accounting for stroke risk, presence of contraindications (OR = 0.18; 0.13 0.27), older age (OR = 0.30; 0.21 0.45), prophylaxis at admission (OR = 3.03; 2.08 4.43). OAT was positively associated with the stroke risk in the 2004 sample only.ConclusionThe guideline implementation has substantially improved the appropriateness of OAT at discharge, through a better evaluation at patients individual level of the benefit-to-risk ratio.

Human lipoprotein lipase HindIII polymorphism in young patients with myocardial infarction

We investigated the possibility that the DNA HindIII polymorphism of human lipoprotein lipase (LPL) is associated with the severity of coronary artery disease (CAD) determined by angiography in young patients who survived a myocardial infarction (MI). Conflicting studies have explored the relationship linking CAD severity to the HindIII restriction site polymorphism at the LPL gene locus, and to our knowledge, no data are available from Italy. The patients were aged less than 45 years (mean age, 40.1 +/- 3.9 years); 83 were male and four were female. The 87 case-patients had a Q-wave or non-Q-wave infarction (67.3% and 32.7%, respectively); the MI was anterior (50.5%), lateral (41.7%), or inferior (7.8%). Analysis of coronary angiograms showed the absence of critical stenosis in 13.8% and the presence of monovessel disease in 50.6% and multivessel disease in 35.6% of the case-patients. The allelic frequency of the HindIII H(-) and H(+) allele was 0.37 and 0.63, respectively. There was a striking association between the HindIII polymorphism and the number of diseased vessels. The patients with HindIII(+/+) genotypes were significantly more likely to have double- or triple-vessel disease and less likely to have no significantly diseased vessels. In this study, we demonstrated that the homozygous form of the LPL HindIII(+) allele increases the risk of multivessel disease by a factor of 4 in an Italian group of young MI survivors. This association was independent from the smoking status and a positive family history for CAD and hypertension, which are known to predict CAD severity. The discrepancies in the results of these studies are difficult to explain. The lack of homogeneity in the study populations (age at which CAD occurred, number of enrolled patients, and geographical origin) and differences in the assessment of CAD severity may account for these conflicting results.

Heritability of cardiovascular risk parameters in subjects with increased susceptibility to non-insulin-dependent diabetes mellitus

Abstract To evaluate the inheritance of cardiovascular risk parameters in subjects with increased susceptibility for non-insulin-dependent diabetes mellitus, we compared 25 pairs of healthy twins who were offspring of diabetic parents with 25 pairs without a parental history for type 2 diabetes mellitus (12 monozygotic and 13 dizygotic in each group). Environmental factors were also evaluated to avoid bias in the assessment of concordance. No significant difference was found in concordance between monozygotic and dizygotic twins for physical activity, diet, smoking, alcohol intake and living together or apart. Genetic analysis revealed a substantial heritability for weight, body mass index, percentage of body fat, lipoprotein(a), high density lipoprotein (HDL)- and HDL2-cholesterol, without significant differences between the two groups. We conclude that heritability of several cardiovascular risk parameters is not increased in subjects with increased susceptibility to type 2 diabetes mellitus.