Search results for "Insulin"

A phase I pharmacokinetic and pharmacodynamic study of dalotuzumab (MK-0646), an anti-insulin-like growth factor-1 receptor monoclonal antibody, in p…

2011

Abstract Purpose: Insulin-like growth factor-1 receptor (IGF-1R) mediates cellular processes in cancer and has been proposed as a therapeutic target. Dalotuzumab (MK-0646) is a humanized IgG1 monoclonal antibody that binds to IGF-1R preventing receptor activation. This study was designed to evaluate the safety and tolerability of dalotuzumab, determine the pharmacokinetic (PK) and pharmacodynamic (PD) profiles, and identify a recommended phase II dose. Experimental Design: Patients with tumors expressing IGF-1R protein were allocated to dose-escalating cohorts of three or more patients each and received intravenous dalotuzumab weekly, every 2 or 3 weeks. Plasma was collected for PK analysis…

Large-Scale Gene-Centric Meta-Analysis across 39 Studies Identifies Type 2 Diabetes Loci

2012

To identify genetic factors contributing to type 2 diabetes (T2D), we performed large-scale meta-analyses by using a custom ∼50,000 SNP genotyping array (the ITMAT-Broad-CARe array) with ∼2000 candidate genes in 39 multiethnic population-based studies, case-control studies, and clinical trials totaling 17,418 cases and 70,298 controls. First, meta-analysis of 25 studies comprising 14,073 cases and 57,489 controls of European descent confirmed eight established T2D loci at genome-wide significance. In silico follow-up analysis of putative association signals found in independent genome-wide association studies (including 8,130 cases and 38,987 controls) performed by the DIAGRAM consortium id…

Oxidative status in nondiabetic middle-aged subjects with metabolic syndrome: preliminary data.

2013

Polymorphisms of microRNA target genes

2016

AIM To evaluate associations between miRNA target genes IL12B, INSR, CCND1 and IL10 polymorphisms and gastric cancer (GC) in European population. METHODS Gene polymorphisms were analyzed in 508 controls and 474 GC patients from 3 tertiary centers in Germany, Lithuania and Latvia. Controls were patients from the out-patient departments, who were referred for upper endoscopy because of dyspeptic symptoms and had no history of previous malignancy. Gastric cancer (GC) patients had histopathological verification of gastric adenocarcinoma. Genomic DNA was extracted using salting out method from peripheral blood mononuclear cells. IL12B T>G (rs1368439), INSR T>C (rs1051690), CCND1 A>C (rs7177) and…

Perilipin polymorphism interacts with saturated fat and carbohydrates to modulate insulin resistance

2010

Macronutrient intakes and genetic variants have been shown to interact to alter the risk of insulin resistance, but replication of gene-nutrient interactions across independent populations may be difficult to achieve. Saturated fat and carbohydrate were previously shown to interact with genotype for insulin resistance for a variant of perilipin (PLIN), the major adipocyte-associated protein and a regulator of adipocyte metabolism. We investigated the same interaction for PLIN 11482G>A (rs894160) on insulin resistance in US men(n=462) and women(n=508) (mean ±SD, 49±16 years). In multivariate linear regression models, we found a significant (PA for HOMA-IR (homeostasis model assessment of ins…

Androgen excess and cardiovascular risk.

2007

Cardiovascular diseases represent the major cause of death in most of developed countries and ultimately kill as many men as women. Both genders are exposed to the same risk factors but their rates of cardiovascular morbidity and mortality are very different until old age. This represents a crucial point; in fact, only at age 75 and over cardiovascular rates of women approximate those of men. It has been suggested that differences in hormonal status and mainly in androgen levels may explain such gender disparity. Consistently with this hypothesis, it has been shown that women with polycystic ovary syndrome (PCOS) have elevated cardiovascular risk despite their young age. However, the possib…

Correlates of increased lean muscle mass in women with polycystic ovary syndrome.

2009

ObjectiveMuscle mass plays an important role in determining cardiovascular and metabolic risks in polycystic ovary syndrome (PCOS). In addition, whether lean mass influences carotid intima-media thickness (IMT) in PCOS has not been assessed.DesignProspective investigation.MethodsNinety-five women with PCOS were age- and weight-matched to 90 ovulatory controls. All women had dual X-ray absorptiometry for lean, fat and bone mass, and bone mass density (BMD). Serum testosterone, sex hormone-binding globulin, insulin, and glucose and carotid IMT were determined. Free androgen index (FAI) and insulin resistance (by QUICKI) were calculated.ResultsIn PCOS, waist circumference and insulin were high…

Associations of Birth Weight and Postnatal Weight Gain With Cardiometabolic Risk Parameters at 5 Years of Age

2014

The present prospective study assessed the impact of birth weight (BW) and postnatal weight gain on blood pressure and metabolic profile during the first 5 years of life. One hundred thirty-nine newborns (63 women) born at term after uncomplicated pregnancies and in the absence of perinatal illness were included. Subjects were divided according to size at birth in small, appropriate, and large for gestational age. After the initial evaluation on the second day of life, infants were followed up at 6 months and 2 and 5 years. Anthropometric parameters and blood pressure were measured at each visit and metabolic assessment was performed at 5 years of age. Among the BW groups, mothers did not d…

Whole-exome sequencing identifies the first French MODY 6 family with a new mutation in the NEUROD1 gene

2020

Abstract Aim The aim of the present study was to identify the affected gene in a French family with maturity-onset diabetes of the young (MODY) using whole-exome sequencing (WES). Methods WES was performed in one patient with MODY, and candidate variants were confirmed in members of the immediate family by Sanger sequencing. Results In the proband, a new heterozygous missense mutation (c.340A>C) was identified in the NEUROD1 gene by WES analysis and confirmed by Sanger sequencing. Additional Sanger sequencing of the proband's sister and mother revealed the same heterozygous mutation. The proband and his sister displayed typical clinical characteristics of MODY, while their mother had the sa…

Diabetes mellitus prevalence and control in sleep-disordered breathing: The European Sleep Apnea Cohort (ESADA) study

2014

BACKGROUND: OSA is associated with an increased risk of cardiovascular morbidity. A driver of this is metabolic dysfunction and in particular type 2 diabetes mellitus (T2DM). Prior studies identifying a link between OSA and T2DM have excluded subjects with undiagnosed T2DM, and there is a lack of population-level data on the interaction between OSA and glycemic control among patients with diabetes. We assessed the relationship between OSA severity and T2DM prevalence and control in a large multinational population.METHODS: We performed a cross-sectional analysis of 6,616 participants in the European Sleep Apnea Cohort (ESADA) study, using multivariate regression analysis to assess T2DM prev…