Translational research plays a crucial role in bridging the gap between fundamental and clinical research. The importance of integrating research training into medical education has been emphasized. Predictive factors that help to identify the most motivated medical students to perform academic research are unknown. In a cross-sectional study on a representative sample of 315 medical students, residents and attending physicians, using a comprehensive structured questionnaire we assessed motivations and obstacles to perform academic research curricula (ie, research initiation fellowship, Master 1, Research Master 2, and PhD). Independent predictive factors associated with high "motivation score" (top quartile on motivation score ranging from 0 to 10) to enroll in academic research curricula were derived using multivariate logistic regression analysis. Independent predictors of high motivation score for performing Master 1 curriculum were: "considering that the integration of translational research in medical curriculum is essential" (OR, 3.79; 95% CI, 1.49-9.59; P = 0.005) and "knowledge of at least 2 research units within the university" (OR, 3.60; 95% CI, 2.01-6.47; P < 0.0001). Independent predictors of high motivation score for performing Research Master 2 curriculum were: "attending physician" (OR, 4.60; 95% CI, 1.86-11.37; P = 0.001); "considering that the integration of translational research in medical curriculum is essential" (OR, 4.12; 95% CI, 1.51-11.23; P = 0.006); "knowledge of at least 2 research units within the university" (OR, 3.51; 95% CI, 1.91-6.46; P = 0.0001); and "male gender" (OR, 1.82; 95% CI, 1.02-3.25; P = 0.04). Independent predictors of high motivation score for performing PhD curriculum were: "considering that the integration of translational research in medical curriculum is essential" (OR, 5.94; 95% CI, 2.33-15.19; P = 0.0002) and "knowledge of at least 2 research units within the university" (OR, 2.63; 95% CI, 1.46-4.77; P = 0.001). This is the first study that has identified factors determining motivations and barriers to carry out academic research curricula among undergraduate and postgraduate medical students. Improving these 2 areas will certainly have an impact on a better involvement of the next generation of physicians in translational medicine.

Oxidative stress is involved in the pathophysiology of diabetic nephropathy. The superoxide dismutase (SOD) enzymes play a major role in detoxification of reactive oxygen species and have a protective effect against diabetic nephropathy. We investigated associations of allelic variations in SOD1 gene with nephropathy in patients with type 1 diabetes.

Epidemiological studies and randomized clinical trials have demonstrated in various populations that resting heart rate (RHR) was an independent predictor of cardiovascular (CV) risk and all-cause mortality. However, few data specifically evaluated the relationship between RHR and long-term CV and renal complications in a large population of type 2 diabetic (T2D) patients.

In order to identify epigenetic mechanisms through which hyperglycemia can affect gene expression durably in β cells, we screened DNA methylation changes induced by high glucose concentrations (25 mmol/L) in the BTC3 murine cell line, using an epigenome-wide approach. Exposure of BTC3 cells to high glucose modified the expression of 1612 transcripts while inducing significant methylation changes in 173 regions. Among these 173 glucose-sensitive differentially methylated regions (DMRs), 14 were associated with changes in gene expression, suggesting an epigenetic effect of high glucose on gene transcription at these loci. Among these 14 DMRs, we selected for further study Pp2ac, a gene previously suspected to play a role in β-cell physiology and type 2 diabetes. Using RT-qPCR and bisulfite pyrosequencing, we confirmed our previous observations in BTC3 cells and found that this gene was significantly demethylated in the whole blood cells (WBCs) of type 2 diabetic patients compared to controls.

Diabetic kidney disease, or diabetic nephropathy (DN), is a major complication of diabetes and the leading cause of end-stage renal disease (ESRD) that requires dialysis treatment or kidney transplantation. In addition to the decrease in the quality of life, DN accounts for a large proportion of the excess mortality associated with type 1 diabetes (T1D). Whereas the degree of glycemia plays a pivotal role in DN, a subset of individuals with poorly controlled T1D do not develop DN. Furthermore, strong familial aggregation supports genetic susceptibility to DN. However, the genes and the molecular mechanisms behind the disease remain poorly understood, and current therapeutic strategies rarely result in reversal of DN. In the GEnetics of Nephropathy: an International Effort (GENIE) consortium, we have undertaken a meta-analysis of genome-wide association studies (GWAS) of T1D DN comprising ~2.4 million single nucleotide polymorphisms (SNPs) imputed in 6,691 individuals. After additional genotyping of 41 top ranked SNPs representing 24 independent signals in 5,873 individuals, combined meta-analysis revealed association of two SNPs with ESRD: rs7583877 in the AFF3 gene (P = 1.2 × 10(-8)) and an intergenic SNP on chromosome 15q26 between the genes RGMA and MCTP2, rs12437854 (P = 2.0 × 10(-9)). Functional data suggest that AFF3 influences renal tubule fibrosis via the transforming growth factor-beta (TGF-β1) pathway. The strongest association with DN as a primary phenotype was seen for an intronic SNP in the ERBB4 gene (rs7588550, P = 2.1 × 10(-7)), a gene with type 2 diabetes DN differential expression and in the same intron as a variant with cis-eQTL expression of ERBB4. All these detected associations represent new signals in the pathogenesis of DN.

Hyperglycaemia in diabetes mellitus (DM) alters gene expression regulation in various organs and contributes to long term vascular and renal complications. We aimed to generate novel renal genome-wide gene transcription data in rat models of diabetes in order to test the responsiveness to hyperglycaemia and renal structural changes of positional candidate genes at selected diabetic nephropathy (DN) susceptibility loci.

A1C is widely considered the gold standard for monitoring effective blood glucose levels. Recently, a genome-wide association study reported an association between A1C and rs7072268 within HK1 (encoding hexokinase 1), which catalyzes the first step of glycolysis. HK1 deficiency in erythrocytes (red blood cells [RBCs]) causes severe nonspherocytic hemolytic anemia in both humans and mice.

To investigate the association between routine use of dipeptidyl peptidase-4 (DPP-4) inhibitors and the severity of coronavirus disease 2019 (COVID-19) infection in patient with type 2 diabetes in a large multicentric study.

The etiology of diabetic nephropathy depends partly on genetic factors. Elevated systemic and intraglomerular blood pressure and glomerular filtration rate, partly regulated by the renin-angiotensin system, increase the risk of diabetic nephropathy.

Glutathione peroxidase (GPX) is a class of antioxidant enzymes that catalyze the reduction of hydrogen peroxide to water. GPX1 is the most abundant isoform and is expressed in all kidney cells. Isoprostane and advanced oxidation protein products (AOPP) were identified as markers of oxidative stress in patients with kidney disease. We investigated associations of GPX1 genotypes with kidney complications, and with plasma concentrations of isoprostane and AOPP in type 1 diabetic patients.

Identifying rare coding variants associated with albuminuria may open new avenues for preventing chronic kidney disease and end-stage renal disease, which are highly prevalent in individuals with diabetes. Efforts to identify genetic susceptibility variants for albuminuria have so far been limited, with the majority of studies focusing on common variants.

Patients with type 1 diabetes and diabetic nephropathy are targets for intervention to reduce high risk of end-stage renal disease (ESRD) and deaths. This study compares risks of these outcomes in four international cohorts.

No abstract available

This is an update of the results from the previous report of the CORONADO (Coronavirus SARS-CoV-2 and Diabetes Outcomes) study, which aims to describe the outcomes and prognostic factors in patients with diabetes hospitalised for coronavirus disease-2019 (COVID-19).

Patients with type 1 diabetes are more at risk of coronary artery disease than the general population. Although evidence points to a genetic risk there have been no study investigating genetic risk factors of coronary artery disease specific to individuals with type 1 diabetes. To identify low frequency and common genetic variations associated with coronary artery disease in populations of individuals with type 1 diabetes.

Male sex is one of the determinants of severe coronavirus diseas-e-2019 (COVID-19). We aimed to characterize sex differences in severe outcomes in adults with diabetes hospitalized for COVID-19.

Oxidative stress is involved in development of diabetes complications. Extracellular superoxide dismutase (EC-SOD, SOD3) is a major extracellular antioxidant enzyme and is highly expressed in arterial walls. Advanced oxidation protein products (AOPP) and 8-iso-prostaglandin (isoprostane) are markers of oxidative stress. We investigated association of SOD3 gene variants, plasma concentrations of EC-SOD, AOPP and isoprostane with myocardial infarction and mortality in diabetic patients.

We evaluated the risks of renal and cardiovascular complications, and mortality associated with lower extremity amputation (LEA) in patients with type 1 diabetes.

Common diseases such as type 2 diabetes are phenotypically heterogeneous. Obesity is a major risk factor for type 2 diabetes, but patients vary appreciably in body mass index. We hypothesized that the genetic predisposition to the disease may be different in lean (BMI<25 Kg/m²) compared to obese cases (BMI≥30 Kg/m²). We performed two case-control genome-wide studies using two accepted cut-offs for defining individuals as overweight or obese. We used 2,112 lean type 2 diabetes cases (BMI<25 kg/m²) or 4,123 obese cases (BMI≥30 kg/m²), and 54,412 un-stratified controls. Replication was performed in 2,881 lean cases or 8,702 obese cases, and 18,957 un-stratified controls. To assess the effects of known signals, we tested the individual and combined effects of SNPs representing 36 type 2 diabetes loci. After combining data from discovery and replication datasets, we identified two signals not previously reported in Europeans. A variant (rs8090011) in the LAMA1 gene was associated with type 2 diabetes in lean cases (P = 8.4×10⁻⁹, OR = 1.13 [95% CI 1.09-1.18]), and this association was stronger than that in obese cases (P = 0.04, OR = 1.03 [95% CI 1.00-1.06]). A variant in HMG20A--previously identified in South Asians but not Europeans--was associated with type 2 diabetes in obese cases (P = 1.3×10⁻⁸, OR = 1.11 [95% CI 1.07-1.15]), although this association was not significantly stronger than that in lean cases (P = 0.02, OR = 1.09 [95% CI 1.02-1.17]). For 36 known type 2 diabetes loci, 29 had a larger odds ratio in the lean compared to obese (binomial P = 0.0002). In the lean analysis, we observed a weighted per-risk allele OR = 1.13 [95% CI 1.10-1.17], P = 3.2×10⁻¹⁴. This was larger than the same model fitted in the obese analysis where the OR = 1.06 [95% CI 1.05-1.08], P = 2.2×10⁻¹⁶. This study provides evidence that stratification of type 2 diabetes cases by BMI may help identify additional risk variants and that lean cases may have a stronger genetic predisposition to type 2 diabetes.

Akita mice are a genetic model of type 1 diabetes. In the present studies, we investigated the phenotype of Akita mice on the FVB/NJ background and examined urinary nephrin excretion as a marker of kidney injury. Male Akita mice were compared with non-diabetic controls for functional and structural characteristics of renal and cardiac disease. Podocyte number and apoptosis as well as urinary nephrin excretion were determined in both groups. Male FVB/NJ Akita mice developed sustained hyperglycemia and albuminuria by 4 and 8 weeks of age, respectively. These abnormalities were accompanied by a significant increase in systolic blood pressure in 10-week old Akita mice, which was associated with functional, structural and molecular characteristics of cardiac hypertrophy. By 20 weeks of age, Akita mice developed a 10-fold increase in albuminuria, renal and glomerular hypertrophy and a decrease in the number of podocytes. Mild-to-moderate glomerular mesangial expansion was observed in Akita mice at 30 weeks of age. In 4-week old Akita mice, the onset of hyperglycemia was accompanied by increased podocyte apoptosis and enhanced excretion of nephrin in urine before the development of albuminuria. Urinary nephrin excretion was also significantly increased in albuminuric Akita mice at 16 and 20 weeks of age and correlated with the albumin excretion rate. These data suggest that: 1. FVB/NJ Akita mice have phenotypic characteristics that may be useful for studying the mechanisms of kidney and cardiac injury in diabetes, and 2. Enhanced urinary nephrin excretion is associated with kidney injury in FVB/NJ Akita mice and is detectable early in the disease process.