Lack of effect of apolipoprotein C3 polymorphisms on indices of liver steatosis, lipid profile and insulin resistance in obese Southern Europeans.

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.BACKGROUND: Apolipoprotein C3 (APOC3) is a component of triglyceride-rich lipoproteins, and APOC3 rs2854116 and rs2854117 polymorphisms have been associated with non-alcoholic fatty liver disease, hypertriglyceridaemia, and insulin-resistance. OBJECTIVE: To determine if the APOC3 variants alter the susceptibility of obese subjects to develop liver damage, hypertrigliceridaemia, and insulin-resistance. METHODS: The study was carried out on 585 unrelated obese Italians (median body mass index BMI = 41 kg/m2) who were genotyped for the rs2854116 and rs2854117 variants. All participants underwent oral glucose tolerance tests (OGTT), with measurement of glucose, insulin, lipid parameters. Indices of insulin-resistance (HOMA and ISI) were calculated. Alanine transaminase (ALT) and aspartate transaminase (AST) were used as markers of liver injury. RESULTS: The study subjects were divided into two groups: those homozygous for the wild-type alleles at both SNPs (-482C and -455T alleles) and those who were carriers of at least one variant allele or both (-482T, -455C or both). Also each SNP was analysed independently. No significant differences were found in ALT and AST levels and in the lipid profile between the two groups. Insulin concentrations, glucose tolerance and insulin sensitivity were similar in the two groups. CONCLUSION: We did not identify any significant association between APOC3 polymorphisms and fatty liver disease, lipids, and insulin-resistance in obese subjects, thus not confirming the suggested role of these APOC3 gene sequence variants

Effects of metformin and exercise training, alone or in combination, on cardiac function in individuals with insulin resistance

Introduction: In patients affected by insulin resistance (IR), metformin (MET) therapy has been shown to exert its positive effects by improving glucose tolerance and preventing the evolution to diabetes. Recently, it was shown that the addition of metformin to physical training did not improve sensitivity to insulin or peak oxygen consumption (peak VO2). The purpose of this study was to establish the effect of metformin and exercise, separately or in combination, on systolic left ventricular (LV) function in individuals with IR. Methods: Seventy-five patients with IR were enrolled and subsequently assigned to MET, combination MET and exercise, or exercise alone. The LV systolic and diastolic functions were evaluated with standard echocardiography tissue Doppler imaging (TDI) and speckle tracking echocardiography at baseline and after 12 weeks of treatment. Results: MET, administered alone or in association with exercise, improved longitudinal LV function, as evidenced by an increase in systolic (S) wave on TDI, alongside increases in longitudinal global strain and strain rate in comparison to the group undergoing physical training alone. The traditional echocardiographic parameters showed no statistically significant differences among the three groups before or after the different cycles of therapy. Conclusions: Treatment with MET, either with or without exercise, but not exercise alone, produced a significant increase in global longitudinal LV systolic function at rest. These findings validate the observation that the use of MET alone or in association with exercise has a crucial role to counteract the negative effects of IR on cardiovascular function

Association of FTO Polymorphisms with Early Age of Obesity in Obese Italian Subjects

Obesity is recognized as a major health problem worldwide. Genetic factors play a major role in obesity, and genomewide association studies have provided evidence that several common variants within the fat mass- and obesity-associated (FTO) gene are significantly associated with obesity. Very limited data is available on FTO in the Italian population. Aims of our study are to investigate: (1) the association of FTO gene SNPs rs9939609 and rs9930506 with body mass index (BMI) and obesity-related parameters in a large cohort (n = 752) of Italian obese subjects; (2) the association between the two FTO SNPs and age of onset of obesity. Our results demonstrate a strong association between FTO SNPs rs9939609 (P < 0.043) and rs9930506 (P < 0.029) with BMI in the Italian population. FTO rs9930506 was significantly associated with higher BMI in a G allele dose-dependent manner (BMI + 1.4 kg/m2 per G allele). We also observed that the association with BMI of the two FTO variants varied with age, with the carriers of the risk alleles developing an increase in body weight earlier in life. In conclusion, our study further demonstrates a role of the genetic variability in FTO on BMI in a large Italian population

Glycated hemoglobin for the diagnosis of diabetes and prediabetes: Diagnostic impact on obese and lean subjects, and phenotypic characterization

Aims/Introduction Measurement of glycated hemoglobin (HbA1c) has been recommended for the diagnosis of diabetes and prediabetes. However, epidemiological studies have shown significant discordance between HbA1c and glucose-based tests. Of the factors that could influence agreement between HbA1c and the oral glucose tolerance test (OGTT), bodyweight has not been fully evaluated. The aims of the present study were to evaluate the impact of HbA1c criteria to diagnose diabetes and prediabetes compared with OGTT, and to examine HbA1c in relation to body mass index. Materials and Methods Two cohorts were studied, one from an obesity clinic (n = 592) and one from subjects undergoing screening for diabetes (n = 462). All underwent OGTT and HbA1c measurement. Results In the obese cohort, HbA1c ≥6.5% (≥48 mmol/mol) showed a sensitivity of 69.3% for diabetes, whereas HbA1c 5.7–6.4% (39–46 mmol/mol) did not identify prediabetes well (sensitivity 39.1%). In the diabetes screening cohort, HbA1c h

Association of FTO Polymorphisms with Early Age of Obesity in Obese Italian Subjects

Obesity is recognized as a major health problem worldwide. Genetic factors play a major role in obesity, and genomewide association studies have provided evidence that several common variants within the fat mass-and obesity-associated (FTO) gene are significantly associated with obesity. Very limited data is available on FTO in the Italian population. Aims of our study are to investigate: (1) the association of FTO gene SNPs rs9939609 and rs9930506 with body mass index (BMI) and obesity-related parameters in a large cohort (n = 752) of Italian obese subjects; (2) the association between the two FTO SNPs and age of onset of obesity. Our results demonstrate a strong association between FTO SNPs rs9939609 (P &lt; 0.043) and rs9930506 (P &lt; 0.029) with BMI in the Italian population. FTO rs9930506 was significantly associated with higher BMI in a G allele dose-dependent manner (BMI + 1.4 kg/m 2 per G allele). We also observed that the association with BMI of the two FTO variants varied with age, with the carriers of the risk alleles developing an increase in body weight earlier in life. In conclusion, our study further demonstrates a role of the genetic variability in FTO on BMI in a large Italian population

Variability in genes regulating vitamin D metabolism is associated with vitamin D levels in type 2 diabetes

Mortality rate is increased in type 2 diabetes (T2D). Low vitamin D levels are associated with increased mortality risk in T2D. In the general population, genetic variants affecting vitamin D metabolism (DHCR7 rs12785878, CYP2R1 rs10741657, GC rs4588) have been associated with serum vitamin D. We studied the association of these variants with serum vitamin D in 2163 patients with T2D from the "Sapienza University Mortality and Morbidity Event Rate (SUMMER) study in diabetes". Measurements of serum vitamin D were centralised. Genotypes were obtained by Eco™ Real-Time PCR. Data were adjusted for gender, age, BMI, HbA1c, T2D therapy and sampling season. DHCR7 rs12785878 (p = 1 x 10-4) and GC rs4588 (p = 1 x 10-6) but not CYP2R1 rs10741657 (p = 0.31) were significantly associated with vitamin D levels. One unit of a weighted genotype risk score (GRS) was strongly associated with vitamin D levels (p = 1.1 x 10-11) and insufficiency (&lt;30 ng/ml) (OR, 95%CI = 1.28, 1.16-1.41, p = 1.1 x 10-7). In conclusion, DHCR7 rs12785878 and GC rs4588, but not CYP2R1 rs10741657, are significantly associated with vitamin D levels. When the 3 variants were considered together as GRS, a strong association with vitamin D levels and vitamin D insufficiency was observed, thus providing robust evidence that genes involved in vitamin D metabolism modulate serum vitamin D in T2D

Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P &lt; .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients

Studio genetico del Diabete MODY (Maturity Onset Diabetes of the Young): approcci diagnostici in fenotipi diversi

Il MODY è la forma più comune di diabete monogenico. Mutazioni nel gene GCK (MODY2) e nel gene HNF1α (MODY3) sono responsabili da sole del 70% di tutti i casi MODY. OBIETTIVO: validare in modo prospettico l’utilizzo di linee guida recentemente proposte, usando i criteri di inclusione per la selezione dei soggetti da sottoporre allo screening. METODI: Criteri di inclusione: Per GCK, iperglicemia persistente a digiuno >100 mg/dl, lieve aumento dell’HbA1c e della glicemia dopo OGTT < 54 mg/dl. Per HNF1α, esordio precoce in almeno un membro della famiglia, presenza di secrezione insulinica dopo 3 anni dalla diagnosi, assenza di chetoacidosi e valori testabili di c-peptide. Casistica: Sono state studiate due coorti: la prima composta da 53 bambini è stata selezionata in base alla presenza di alterazioni nel metabolismo dei carboidrati e assenza di autoanticorpi circolanti, la seconda è costituita da 14 soggetti adulti diabetici, con familiarità e precoce età di insorgenza. Per l’indagine genetica sono stati sequenziati 10 esoni e il promoter per GCK e 10 esoni per HNF1α. RISULTATI: Nella coorte costituita da bambini sono state identificate 2 mutazioni nel gene GCK: L271fsdel22 e V222D. In tre soggetti con familiarità per diabete è stato inoltre analizzato il gene HNF1α e sono state identificate le varianti G31D e T354M. Nella coorte costituita da adulti 35,7% sono risultati positivi allo screening per MODY. H50R, M235I e c.1079-1080insCCTC sono mutazioni nel gene GCK; R278Q e R131Q nel gene HNF1α. Tutte le mutazioni identificate sono state confermate nei familiari. CONCLUSIONI: l’utilizzo di linee guida per la diagnosi di MODY si è dimostrato uno strumento di notevole supporto nella pratica clinica. Nei soggetti adulti è stata riportata un’alta prevalenza di soggetti MODY (35,7%). Nella coorte costituita da bambini e adolescenti selezionati per la presenza di iperglicemia la prevalenza di MODY2 è stata del 4,1% non molto differente da quella riportata in popolazioni non selezionate. E’ interessante notare che quando si selezione anche per familiarità e BMI, come proposto nei criteri generali di inclusione per lo studio del MODY, la prevalenza di MODY2 aumenta fino al 40%, segno che questi due parametri non sono da sottovalutare in un approccio di questo tipo

Studio genetico del Diabete MODY (Maturity Onset Diabetes of the Young): approcci diagnostici in fenotipi diversi

Il MODY è la forma più comune di diabete monogenico. Mutazioni nel gene GCK (MODY2) e nel gene HNF1α (MODY3) sono responsabili da sole del 70% di tutti i casi MODY. OBIETTIVO: validare in modo prospettico l’utilizzo di linee guida recentemente proposte, usando i criteri di inclusione per la selezione dei soggetti da sottoporre allo screening. METODI: Criteri di inclusione: Per GCK, iperglicemia persistente a digiuno >100 mg/dl, lieve aumento dell’HbA1c e della glicemia dopo OGTT < 54 mg/dl. Per HNF1α, esordio precoce in almeno un membro della famiglia, presenza di secrezione insulinica dopo 3 anni dalla diagnosi, assenza di chetoacidosi e valori testabili di c-peptide. Casistica: Sono state studiate due coorti: la prima composta da 53 bambini è stata selezionata in base alla presenza di alterazioni nel metabolismo dei carboidrati e assenza di autoanticorpi circolanti, la seconda è costituita da 14 soggetti adulti diabetici, con familiarità e precoce età di insorgenza. Per l’indagine genetica sono stati sequenziati 10 esoni e il promoter per GCK e 10 esoni per HNF1α. RISULTATI: Nella coorte costituita da bambini sono state identificate 2 mutazioni nel gene GCK: L271fsdel22 e V222D. In tre soggetti con familiarità per diabete è stato inoltre analizzato il gene HNF1α e sono state identificate le varianti G31D e T354M. Nella coorte costituita da adulti 35,7% sono risultati positivi allo screening per MODY. H50R, M235I e c.1079-1080insCCTC sono mutazioni nel gene GCK; R278Q e R131Q nel gene HNF1α. Tutte le mutazioni identificate sono state confermate nei familiari. CONCLUSIONI: l’utilizzo di linee guida per la diagnosi di MODY si è dimostrato uno strumento di notevole supporto nella pratica clinica. Nei soggetti adulti è stata riportata un’alta prevalenza di soggetti MODY (35,7%). Nella coorte costituita da bambini e adolescenti selezionati per la presenza di iperglicemia la prevalenza di MODY2 è stata del 4,1% non molto differente da quella riportata in popolazioni non selezionate. E’ interessante notare che quando si selezione anche per familiarità e BMI, come proposto nei criteri generali di inclusione per lo studio del MODY, la prevalenza di MODY2 aumenta fino al 40%, segno che questi due parametri non sono da sottovalutare in un approccio di questo tipo

Testing for type 1 diabetes autoantibodies in gestational diabetes mellitus (GDM): Is it clinically useful?

Gestational Diabetes Mellitus (GDM) is the most common metabolic disorder in pregnancy, and it is associated with increased risk of morbidity in maternal-fetal outcomes. GDM is also associated with a higher risk to develop diabetes in the future. Diabetes-related autoantibodies (AABs) have been detected in a small percentage (usually less than 10%) of women with gestational diabetes. The prevalence in gestational diabetes of these autoimmune markers of type 1 diabetes (T1D) has been assessed in many studies, together with the risk of progression of AABs-positive GDM towards impaired glucose regulation (IFG or IGT) and overt diabetes after pregancy. The question whether it is necessary to test for T1D autoantibodies in all pregnancies with GDM is still debated. Here we examine the epidemiology of T1D autoantibodies in GDM, their clinical relevance in term of future risk of diabetes or impaired glucose regulation and in term of maternal-fetal outcomes, and discuss when it may be the most appropriate time to search for T1D autoantibodies in women with gestational diabetes