Main determinants for increased risk for diabetic foot in an adult Bulgarian population with type 1 and type 2 diabetes

Abstract Context Common genetic susceptibility may underlie the frequently observed co-occurrence of type 1 and type 2 diabetes in families. Given the role of HLA class II genes in the pathophysiology of type 1 diabetes, the aim of the present study was to test the association of high density imputed human leukocyte antigen (HLA) genotypes with type 2 diabetes. Objectives and Design Three cohorts (Ntotal = 10 413) from Leipzig, Germany were included in this study: LIFE-Adult (N = 4649), LIFE-Heart (N = 4815) and the Sorbs (N = 949) cohort. Detailed metabolic phenotyping and genome-wide single nucleotide polymorphism (SNP) data were available for all subjects. Using 1000 Genome imputation data, HLA genotypes were imputed on 4-digit level and association tests for type 2 diabetes, and related metabolic traits were conducted. Results In a meta-analysis including all 3 cohorts, the absence of HLA-DRB5 was associated with increased risk of type 2 diabetes (P = 0.001). In contrast, HLA-DQB*06:02 and HLA-DQA*01:02 had a protective effect on type 2 diabetes (P = 0.005 and 0.003, respectively). Both alleles are part of the well-established type 1 diabetes protective haplotype DRB1*15:01~DQA1*01:02~DQB1*06:02, which was also associated with reduced risk of type 2 diabetes (OR 0.84; P = 0.005). On the contrary, the DRB1*07:01~DQA1*02:01~DQB1*03:03 was identified as a risk haplotype in non–insulin-treated diabetes (OR 1.37; P = 0.002). Conclusions Genetic variation in the HLA class II locus exerts risk and protective effects on non–insulin-treated type 2 diabetes. Our data suggest that the genetic architecture of type 1 diabetes and type 2 diabetes might share common components on the HLA class II locus.

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Diabetes increases the risk of breast cancer: a meta-analysis

Endocrine Related Cancer ◽

10.1530/erc-12-0242 ◽

2012 ◽

Vol 19 (6) ◽

pp. 793-803 ◽

Cited By ~ 58

Author(s):

Prue J Hardefeldt ◽

Senarath Edirimanne ◽

Guy D Eslick

Keyword(s):

Breast Cancer ◽

Type 2 Diabetes ◽

Reference Lists ◽

Meta Analysis ◽

Statistical Significance ◽

Increased Risk ◽

And Gender ◽

Study Participants

The aim of this meta-analysis was to collate and analyse all primary observational studies investigating the risk of breast cancer (BC) associated with diabetes. In addition, we aimed to complete subgroup analyses by both type of diabetes and gender of study participants to further clarify the origin of any such association between the two. Studies were obtained from a database search of MEDLINE, EMBASE, PubMed, Current Contents Connect and Google Scholar with additional cross-checking of reference lists. Collated data were assessed for heterogeneity and a pooled odds ratio (OR) calculated. Forty-three studies were included in the meta-analysis with 40 studies investigating BC in women and six studies investigating BC in men. Overall, we found a significantly increased risk of BC associated with diabetes in women (OR 1.20, 95% confidence interval (CI) 1.13–1.29). After subgroup analysis by type of diabetes, the association was unchanged with type 2 diabetes (OR 1.22, 95% CI 1.07–1.40) and nullified with gestational diabetes (OR 1.06, 95% CI 0.79–1.40). There were insufficient studies to calculate a pooled OR of the risk of BC associated with type 1 diabetes. There was an increased risk of BC in males with diabetes mellitus; however, the results did not reach statistical significance (OR 1.29, 95% CI 0.99–1.67). In conclusion, diabetes increases the risk of BC in women. This association is confirmed in women with type 2 diabetes and supports the hypothesis that diabetes is an independent risk factor for BC.

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Comparative risk factors of diabetic foot complications for type 1 and type 2 diabetes mellitus

Endocrine Abstracts ◽

10.1530/endoabs.70.ep213 ◽

2020 ◽

Author(s):

Tenu Irina Afrasinei ◽

Cornelia Bala ◽

Silvia Iancu ◽

Gabriela Roman

Keyword(s):

Diabetes Mellitus ◽

Risk Factors ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Diabetic Foot ◽

Foot Complications ◽

Comparative Risk

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DIABETIC ENCEPHALOPATHY IN TYPE 2 DIABETES

Journal of Medicine and Pharmacy ◽

10.34071/jmp.2016.6.8 ◽

2017 ◽

pp. 52-58

Author(s):

Van Vy Hau Nguyen ◽

Hai Thuy Nguyen ◽

Dinh Toan Nguyen

Keyword(s):

Type 2 Diabetes ◽

Cognitive Deficits ◽

Organ Damage ◽

Diabetic Encephalopathy ◽

Downstream Effects ◽

Increased Risk ◽

Underlying Mechanisms ◽

The Brain

Type 2 diabetes is a common metabolic disease with a rising global prevalence. It is associated with slowly progressive end-organ damage in the eyes and kidneys, but also in the brain. The latter complication is often referred to as "diabetic encephalopathy" and is characterized by mild to moderate impairments in cognitive functioning. It is also associated with an increased risk of dementia. Diabetic encephalopathies are now accepted complications of diabetes. To date, its pathogenetic mechanisms are largely unclear. They appear to differ in type 1 and type 2 diabetes as to underlying mechanisms and the nature of resulting cognitive deﬁcits. The increased incidence of Alzheimer’s disease in type 2 diabetes is associated with insulin resistance, hyperinsulinemia and hyperglycemia, and commonly accompanying attributes such as hypercholesterolemia, hypertension and obesity. However, cognitive impairement in type 1 diabetes have other differences with type 2 diabetes. The major underlying component here appears to be insulin deﬁciency with downstream effects on the expression of neurotrophic factors, neurotransmitters, oxidative and apoptotic stressors resulting in defects in neuronal integrity, connectivity and loss commonly occurring in the still developing brain.

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P2489What are the main determinants of an increase in bnp level in asymptomatic diabetic patients without known cardiac disease?

European Heart Journal ◽

10.1093/eurheartj/ehz748.0819 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Cited By ~ 1

Author(s):

C Patin ◽

T Vidal Trecan ◽

J G Dillinger ◽

E Paven ◽

A Cohen Solal ◽

...

Keyword(s):

Heart Failure ◽

Type 2 Diabetes ◽

Renal Function ◽

Cardiac Disease ◽

Diabetic Patients ◽

Duration Of Diabetes ◽

History Of ◽

Main Determinants

Abstract Background Diabetes mellitus is associated with a high risk of heart failure. The predictors of futures heart failure events in diabetic patients are not clearly understood. BNP measurement can be used as a surrogate endpoint for the diagnosis of heart failure. We investigated the determinants of an increase in BNP level in a large cohort of asymptomatic diabetic patients without known cardiac disease Methods This prospective study included consecutive stable diabetic (type 1 or 2) patients coming for yearly check-up between March 2015 and July 2018 in the university center for the study of diabetes and its complications. Patients with an history of cardiac disease (coronary artery disease, atrial fibrillation, cardiomyopathy, previous heart failure ...) were excluded. All patients had a complete clinical exam, blood pressure measurement (3 consecutive times – mean of 2 lasts measurements), ECG, and blood sample including HbA1C, risk factors assessment, renal function (CKD-EPI) and BNP measurement. Data are presented as mean±SD or median - Spearman's rank and multivariate regression were used for analysis. Results 3743 patients (mean age 57±14 y.o. – 57% male – 78% / 18% / 4% of type 2, type 1 or other type of diabetes respectively – Mean duration of diabetes 17 [1–63] y. – 44% treated with insulin) were studied. Mean±SD / median [min-max] BNP level was 25±39 / 12 [4–737] ng/L. BNP was <20 / 21–35 / 36–50 / 51–100 / 101–400 / >400 ng/L in 69 / 15 / 6 / 7 / 3 / 0.1% of the population respectively. The parameters most correlated with BNP level in type 1 and type 2 diabetes were age, duration of diabetes, renal function, HbA1C, and pulsed pressure. For multivariate analysis, renal function was removed of the model as it was highly correlated with age (r=−0.68). Multivariate analysis demonstrated that in type 1 diabetes, high BNP level was linked to age (p<0.001), pulsed pressure (p<0.001), duration of diabetes (p=0.003) and HbA1C (p=0.02). In type 2 diabetes, high BNP level was linked to age (p<0.0001), pulsed pressure (p<0.0001), duration of diabetes (p=0.005) but not HbA1C (p=0.09). Interestingly the type of treatment (mainly insulin treatment) was not independently related to an increase in BNP level. Conclusion Age, pulsed pressure and duration of diabetes are the main determinants of an increased level of BNP in asymptomatic diabetic patients without any history of cardiac disease. This result could help to select a population who could benefit to a more extensive follow up concerning heart failure.

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Coagulatory Defects in Type-1 and Type-2 Diabetes

International Journal of Molecular Sciences ◽

10.3390/ijms20246345 ◽

2019 ◽

Vol 20 (24) ◽

pp. 6345 ◽

Cited By ~ 3

Author(s):

Amélie I. S. Sobczak ◽

Alan J. Stewart

Keyword(s):

Type 2 Diabetes ◽

Lipid Metabolism ◽

Cardiovascular Diseases ◽

Metal Ion ◽

Ion Homeostasis ◽

Physiological Changes ◽

Metal Ion Homeostasis ◽

Increased Risk

Diabetes (both type-1 and type-2) affects millions of individuals worldwide. A major cause of death for individuals with diabetes is cardiovascular diseases, in part since both types of diabetes lead to physiological changes that affect haemostasis. Those changes include altered concentrations of coagulatory proteins, hyper-activation of platelets, changes in metal ion homeostasis, alterations in lipid metabolism (leading to lipotoxicity in the heart and atherosclerosis), the presence of pro-coagulatory microparticles and endothelial dysfunction. In this review, we explore the different mechanisms by which diabetes leads to an increased risk of developing coagulatory disorders and how this differs between type-1 and type-2 diabetes.

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Increased Tau Phosphorylation and Cleavage in Mouse Models of Type 1 and Type 2 Diabetes

Endocrinology ◽

10.1210/en.2009-0695 ◽

2009 ◽

Vol 150 (12) ◽

pp. 5294-5301 ◽

Cited By ~ 145

Author(s):

Bhumsoo Kim ◽

Carey Backus ◽

SangSu Oh ◽

John M. Hayes ◽

Eva L. Feldman

Keyword(s):

Type 2 Diabetes ◽

Mouse Models ◽

The United States ◽

Tau Phosphorylation ◽

Age Related ◽

Increased Risk ◽

And Gender ◽

Tau Cleavage

Abstract As the population of the United States ages, the incidence of age-related neurodegenerative and systemic diseases including Alzheimer’s disease (AD) and diabetes is increasing rapidly. Multiple studies report that patients with diabetes have a 50–75% increased risk of developing AD compared with age- and gender-matched patients without diabetes. Abnormally phosphorylated tau is a major building block of neurofibrillary tangles, a classic neuropathological characteristic of AD. In addition, proteolytic tau cleavage promotes AD progression due to cleaved tau serving as a nucleation center for the pathological assembly of tau filaments. The current study examines tau modification in type 1 (streptozotocin-injected) and type 2 (db/db) mouse models of diabetes. Tau phosphorylation is increased in the cortex and hippocampus of db/db mice compared with db+ control mouse brain. Interestingly, there is an age-dependent increase in tau cleavage that is not observed in age-matched control db+ animals. Streptozotocin injection also increased tau phosphorylation; however, the increase was less significant compared with the type 2 mouse model, and more importantly, no tau cleavage was detected. Our results suggest tau modification caused by insulin dysfunction and hyperglycemia may contribute to the increased incidence of AD in diabetes. We hypothesize that type 1 and type 2 diabetes may contribute to AD through different mechanisms; in type 2 diabetes, hyperglycemia-mediated tau cleavage may be the key feature, whereas insulin deficiency may be the major contributing factor in type 1 diabetes.

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