<div style="text-align:justify;"> <span style="font-family:Verdana;">Genome-wide association studies have identified numerous genetic variants for type 2 diabetes (T2D). Most genetic lo...<div style="text-align:justify;"> <span style="font-family:Verdana;">Genome-wide association studies have identified numerous genetic variants for type 2 diabetes (T2D). Most genetic loci discovered to date were studied in Caucasians or Asian ancestry, however, there are no data regarding a quite large Italian sample. Therefore, we investigated T2D genetic susceptibility of 143 single nucleotide polymorphisms (SNPs) within 30 genes involved in glucose metabolism in a large Italian case-control study. For the study, 1875 Caucasian patients were selected from three Italian cohorts. Age, gender, BMI and fasting plasma glucose (FPG) values were collected. Population was split in cases and controls based on FPG values or T2D diagnosis. T2D subjects and whom with FPG higher that 126 mg/dL were recruited as cases whereas subjects with normal values of FPG were considered controls. In each subject 143 SNPs were genotyped. To evaluate the association between genetic variations and diabetes status, a logistic regression analysis, adjusted for age, sex and BMI, was performed. Overall, 948 (50.6%) had T2D. Twenty out of 143 variants within 11 different genes resulted significantly associated to T2D. Four of them were located into <em>TCF7L2</em> gene and presented the highest odd ratio (from 1.42 to 1.57). At least two SNPs were located within <em>KCNJ11, WFS1, ABCC8, JAZF1</em> and <em>HNF1B</em> genes and one SNP each was identified in <em>ADAMTS9, IGF2BP2, FTO, G6PC2</em> and <em>GCK</em> genes. Our findings support the role of 11 genes involved in glucose homeostasis in T2D risk development in a large Italian population. We found that such genetic information may be advantageous for predicting T2D.</span> </div>展开更多
Background:We aimed to assess efficacy and safety,with a special focus on cardiovascular safety,of the novel dual GIP and GLP-1 receptor agonist tirzepatide versus insulin glargine in adults with type 2 diabetes and h...Background:We aimed to assess efficacy and safety,with a special focus on cardiovascular safety,of the novel dual GIP and GLP-1 receptor agonist tirzepatide versus insulin glargine in adults with type 2 diabetes and high cardiovascular risk inadequately controlled on oral glucose-lowering medications.Methods:This open-label,parallel-group,phase 3 study was done in 187 sites in 14 countries on five continents.Eligible participants,aged 18 years or older,had type 2 diabetes treated with any combination of metformin,sulfonylurea,or sodiumglucose co-transporter-2 inhibitor,a baseline glycated haemoglobin(HbA1c)of 7-5-10-5%(58-91 mmol/mol),body-mass index of 25 kg/m2 or greater,and established cardiovascular disease or a high risk of cardiovascular events.Participants were randomly assigned(1:1:1:3)via an interactive web-response system to subcutaneous injection of either once-per-week tirzepatide(5 mg,10 mg,or 15 mg)or glargine(100 U/mL),titrated to reach fasting blood glucose of less than 100 mg/dL.The primary endpoint was non-inferiority(0-3%non-inferiority boundary)of tirzepatide 10 mg or 15 mg,or both,versus glargine in HbA1c change from baseline to 52 weeks.All participants were treated for at least 52 weeks,with treatment continued for a maximum of 104 weeks or until study completion to collect and adjudicate major adverse cardiovascular events(MACE).Safety measures were assessed over the full study period.This study was registered with ClinicalTrials.gov,NCT03730662.展开更多
文摘<div style="text-align:justify;"> <span style="font-family:Verdana;">Genome-wide association studies have identified numerous genetic variants for type 2 diabetes (T2D). Most genetic loci discovered to date were studied in Caucasians or Asian ancestry, however, there are no data regarding a quite large Italian sample. Therefore, we investigated T2D genetic susceptibility of 143 single nucleotide polymorphisms (SNPs) within 30 genes involved in glucose metabolism in a large Italian case-control study. For the study, 1875 Caucasian patients were selected from three Italian cohorts. Age, gender, BMI and fasting plasma glucose (FPG) values were collected. Population was split in cases and controls based on FPG values or T2D diagnosis. T2D subjects and whom with FPG higher that 126 mg/dL were recruited as cases whereas subjects with normal values of FPG were considered controls. In each subject 143 SNPs were genotyped. To evaluate the association between genetic variations and diabetes status, a logistic regression analysis, adjusted for age, sex and BMI, was performed. Overall, 948 (50.6%) had T2D. Twenty out of 143 variants within 11 different genes resulted significantly associated to T2D. Four of them were located into <em>TCF7L2</em> gene and presented the highest odd ratio (from 1.42 to 1.57). At least two SNPs were located within <em>KCNJ11, WFS1, ABCC8, JAZF1</em> and <em>HNF1B</em> genes and one SNP each was identified in <em>ADAMTS9, IGF2BP2, FTO, G6PC2</em> and <em>GCK</em> genes. Our findings support the role of 11 genes involved in glucose homeostasis in T2D risk development in a large Italian population. We found that such genetic information may be advantageous for predicting T2D.</span> </div>
文摘Background:We aimed to assess efficacy and safety,with a special focus on cardiovascular safety,of the novel dual GIP and GLP-1 receptor agonist tirzepatide versus insulin glargine in adults with type 2 diabetes and high cardiovascular risk inadequately controlled on oral glucose-lowering medications.Methods:This open-label,parallel-group,phase 3 study was done in 187 sites in 14 countries on five continents.Eligible participants,aged 18 years or older,had type 2 diabetes treated with any combination of metformin,sulfonylurea,or sodiumglucose co-transporter-2 inhibitor,a baseline glycated haemoglobin(HbA1c)of 7-5-10-5%(58-91 mmol/mol),body-mass index of 25 kg/m2 or greater,and established cardiovascular disease or a high risk of cardiovascular events.Participants were randomly assigned(1:1:1:3)via an interactive web-response system to subcutaneous injection of either once-per-week tirzepatide(5 mg,10 mg,or 15 mg)or glargine(100 U/mL),titrated to reach fasting blood glucose of less than 100 mg/dL.The primary endpoint was non-inferiority(0-3%non-inferiority boundary)of tirzepatide 10 mg or 15 mg,or both,versus glargine in HbA1c change from baseline to 52 weeks.All participants were treated for at least 52 weeks,with treatment continued for a maximum of 104 weeks or until study completion to collect and adjudicate major adverse cardiovascular events(MACE).Safety measures were assessed over the full study period.This study was registered with ClinicalTrials.gov,NCT03730662.
