The increased risk of microvascular complications in South Asians with type 1 diabetes is influenced by migration

People with type 1 diabetes have an increased risk of developing microvascular complications, which have a negative impact on the quality of life and reduce life expectancy. Numerous studies in animals with experimental diabetes show that c-peptide supplementation exerts beneficial effects on diabetes-induced damage in peripheral nerves and kidneys. There is substantial evidence that c-peptide counteracts the detrimental changes caused by hyperglycemia at the cellular level, such as decreased activation of endothelial nitric oxide synthase and sodium potassium ATPase, and increase in formation of pro-inflammatory molecules mediated by nuclear factor kappa-light-chain-enhancer of activated B cells: cytokines, chemokines, cell adhesion molecules, vascular endothelial growth factor, and transforming growth factor beta. However, despite positive results from cell and animal studies, no successful c-peptide replacement therapies have been developed so far. Therefore, it is important to improve our understanding of the impact of c-peptide on the pathophysiology of microvascular complications to develop novel c-peptide-based treatments. This article aims to review current knowledge on the impact of c-peptide on diabetic neuro- and nephropathy and to evaluate its potential therapeutic role.

Download Full-text

Associations of Microvascular Complications With the Risk of Cardiovascular Disease in Type 1 Diabetes

10.2337/figshare.14356943.v1 ◽

2021 ◽

Author(s):

Rose Gubitosi-Klug ◽

Xiaoyu Gao ◽

Rodica Pop-Busui ◽

Ian H de Boer ◽

Neill White ◽

...

Keyword(s):

Myocardial Infarction ◽

Cardiovascular Disease ◽

Type 1 Diabetes ◽

Kidney Disease ◽

Microvascular Complications ◽

Microvascular Disease ◽

Fundus Photography ◽

Increased Risk ◽

Subsequent Risk

Objective: We examined whether the presence of microvascular complications was associated with increased subsequent risk of cardiovascular disease (CVD) among participants with type 1 diabetes in the Diabetes Control and Complications Trial and Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study followed for over 35 years. Research Design and Methods: Standardized longitudinal data collection included: 1) stereoscopic seven-field retinal fundus photography centrally-graded for retinopathy stage and clinically significant macular edema; 2) urinary albumin excretion rate (AER) and estimated glomerular filtration rate (eGFR); 3) cardiovascular autonomic neuropathy (CAN) reflex testing; and 4) adjudicated CVD events, including death from cardiovascular disease, nonfatal myocardial infarction, stroke, subclinical myocardial infarction on ECG, confirmed angina, or coronary artery revascularization. Cox proportional hazard models assessed the association of microvascular complications with subsequent risk of CVD. Results: 239 participants developed CVD, including 120 participants who suffered major adverse cardiovascular events (MACE) defined as non-fatal myocardial infarction, non-fatal stroke or cardiovascular death. The presence of microvascular disease (diabetic retinopathy, kidney disease, or CAN) was associated with increased risk of subsequent CVD and MACE (hazard ratios 1.86 to 3.18 and 2.09 to 3.63, respectively); associations that remained significant after adjusting for age and HbA1c. After adjustment for traditional CVD risk factors, however, only sustained AER≥30 mg/24hr occurring alone and/or with eGFR<60 ml/min/1.73m, and the presence of both retinal and kidney disease remained associated with CVD. Conclusions: Advanced microvascular disease, especially moderate to severe albuminuria or eGFR<60 ml/min/1.73m2, conveyed an increased risk of subsequent cardiovascular disease in the DCCT/EDIC cohort.

Download Full-text

Patients with Type 1 diabetes consuming alcoholic spirits have an increased risk of microvascular complications

Diabetic Medicine ◽

10.1111/dme.12307 ◽

2013 ◽

Vol 31 (2) ◽

pp. 156-164 ◽

Cited By ~ 11

Author(s):

V. Harjutsalo ◽

M. Feodoroff ◽

C. Forsblom ◽

P.-H. Groop ◽

Keyword(s):

Type 1 Diabetes ◽

Microvascular Complications ◽

Increased Risk

Download Full-text

Reduced expression of OXPHOS and DNA damage genes is linked to protection from microvascular complications in long-term type 1 diabetes: the PROLONG study

Scientific Reports ◽

10.1038/s41598-021-00183-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Türküler Özgümüş ◽

Oksana Sulaieva ◽

Leon Eyrich Jessen ◽

Ruchi Jain ◽

Henrik Falhammar ◽

...

Keyword(s):

Dna Repair ◽

Type 1 Diabetes ◽

Microvascular Complications ◽

Vascular Complications ◽

Diabetes Duration ◽

Chronic Hyperglycemia ◽

Increased Risk ◽

Term Type

AbstractType 1 diabetes is a chronic autoimmune disease requiring insulin treatment for survival. Prolonged duration of type 1 diabetes is associated with increased risk of microvascular complications. Although chronic hyperglycemia and diabetes duration have been considered as the major risk factors for vascular complications, this is not universally seen among all patients. Persons with long-term type 1 diabetes who have remained largely free from vascular complications constitute an ideal group for investigation of natural defense mechanisms against prolonged exposure of diabetes. Transcriptomic signatures obtained from RNA sequencing of the peripheral blood cells were analyzed in non-progressors with more than 30 years of diabetes duration and compared to the patients who progressed to microvascular complications within a shorter duration of diabetes. Analyses revealed that non-progressors demonstrated a reduction in expression of the oxidative phosphorylation (OXPHOS) genes, which were positively correlated with the expression of DNA repair enzymes, namely genes involved in base excision repair (BER) machinery. Reduced expression of OXPHOS and BER genes was linked to decrease in expression of inflammation-related genes, higher glucose disposal rate and reduced measures of hepatic fatty liver. Results from the present study indicate that at transcriptomic level reduction in OXPHOS, DNA repair and inflammation-related genes is linked to better insulin sensitivity and protection against microvascular complications in persons with long-term type 1 diabetes.

Download Full-text

Associations of Microvascular Complications With the Risk of Cardiovascular Disease in Type 1 Diabetes

10.2337/figshare.14356943 ◽

2021 ◽

Author(s):

Rose Gubitosi-Klug ◽

Xiaoyu Gao ◽

Rodica Pop-Busui ◽

Ian H de Boer ◽

Neill White ◽

...

Keyword(s):

Myocardial Infarction ◽

Cardiovascular Disease ◽

Type 1 Diabetes ◽

Kidney Disease ◽

Microvascular Complications ◽

Microvascular Disease ◽

Fundus Photography ◽

Increased Risk ◽

Subsequent Risk

Objective: We examined whether the presence of microvascular complications was associated with increased subsequent risk of cardiovascular disease (CVD) among participants with type 1 diabetes in the Diabetes Control and Complications Trial and Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study followed for over 35 years. Research Design and Methods: Standardized longitudinal data collection included: 1) stereoscopic seven-field retinal fundus photography centrally-graded for retinopathy stage and clinically significant macular edema; 2) urinary albumin excretion rate (AER) and estimated glomerular filtration rate (eGFR); 3) cardiovascular autonomic neuropathy (CAN) reflex testing; and 4) adjudicated CVD events, including death from cardiovascular disease, nonfatal myocardial infarction, stroke, subclinical myocardial infarction on ECG, confirmed angina, or coronary artery revascularization. Cox proportional hazard models assessed the association of microvascular complications with subsequent risk of CVD. Results: 239 participants developed CVD, including 120 participants who suffered major adverse cardiovascular events (MACE) defined as non-fatal myocardial infarction, non-fatal stroke or cardiovascular death. The presence of microvascular disease (diabetic retinopathy, kidney disease, or CAN) was associated with increased risk of subsequent CVD and MACE (hazard ratios 1.86 to 3.18 and 2.09 to 3.63, respectively); associations that remained significant after adjusting for age and HbA1c. After adjustment for traditional CVD risk factors, however, only sustained AER≥30 mg/24hr occurring alone and/or with eGFR<60 ml/min/1.73m, and the presence of both retinal and kidney disease remained associated with CVD. Conclusions: Advanced microvascular disease, especially moderate to severe albuminuria or eGFR<60 ml/min/1.73m2, conveyed an increased risk of subsequent cardiovascular disease in the DCCT/EDIC cohort.

Download Full-text

Fibrin clot properties and haemostatic function in men and women with type 1 diabetes

Thrombosis and Haemostasis ◽

10.1160/th14-05-0404 ◽

2015 ◽

Vol 113 (02) ◽

pp. 312-318 ◽

Cited By ~ 5

Author(s):

Gun Jörneskog ◽

Anna Ågren ◽

Per-Eric Lins ◽

Håkan Wallén ◽

Aleksandra Antovic ◽

...

Keyword(s):

Cardiovascular Disease ◽

Type 1 Diabetes ◽

Thrombin Generation ◽

Microvascular Complications ◽

Fibrin Clot ◽

Men And Women ◽

Increased Risk ◽

Fibrin Clots

SummaryThe increased risk of vascular complications in type 1 diabetes may in part be explained by changes in haemostatic function. In the present study, we investigated the fibrin clot properties in patients with type 1 diabetes in relation to sex and microvascular complications. The study included 236 patients (107 women) aged between 20–70 years and without any history of cardiovascular disease. Fibrin clot properties, assessed by determination of the permeability coefficient (Ks) and turbidimetric clotting and lysis assays, did not differ between men and women. Compared with men, women had worse glycaemic control as well as higher levels of prothrombin fragment 1+2 and peak thrombin generation in vitro, indicating increased thrombin generation both in vivo and in vitro. Subgroup analyses of patients younger than 30 years revealed less permeable fibrin clots and prolonged lysis time in females compared with age-matched men. Patients with microvascular complications had higher fibrinogen concentrations and denser and less permeable fibrin clots. Thus, we conclude that in vitro fibrin clot properties in patients with type 1 diabetes without cardiovascular disease are not different between the sexes, but associate with prevalence of microvascular complications. Tighter fibrin clot formation in younger women, as suggested by our results, may affect their future cardiovascular risk and should be investigated in a larger population.

Download Full-text

Type 1 diabetes mellitus and associated risk factors in patients with or without CHD: a case–control study

Cardiology in the Young ◽

10.1017/s1047951117000968 ◽

2017 ◽

Vol 27 (9) ◽

pp. 1670-1677

Author(s):

Anna Björk ◽

Ann-Marie Svensson ◽

Mir Nabi Pirouzi Fard ◽

Peter Eriksson ◽

Mikael Dellborg

Keyword(s):

Diabetes Mellitus ◽

Type 1 Diabetes ◽

Type 1 Diabetes Mellitus ◽

Microvascular Complications ◽

Stress Strain ◽

Mortality And Morbidity ◽

Increased Risk ◽

Co Morbidity ◽

Associated Risk Factors

AbstractBackgroundApproximately 1% of children are born with CHD, and 90–95% reach adulthood. Increased exposure to infections and stress-strain can contribute to an increased risk of developing type 1 diabetes mellitus. CHD may increase the risk of more serious infections, stress-strain, and increased risk of developing type 1 diabetes mellitus.MethodsWe analysed the onset of and the risk of mortality and morbidity associated with concurrent CHD in patients with type 1 diabetes mellitus compared with patients with type 1 diabetes mellitus without CHD. The study combined data from the National Diabetes Register and the National Patient Register.ResultsA total of 104 patients with CHD and type 1 diabetes mellitus were matched with 520 controls. Patients with CHD and type 1 diabetes mellitus had an earlier onset of diabetes (13.9 versus 17.4 years, p<0.001), longer duration of diabetes (22.4 versus 18.1 years, p<0.001), higher prevalence of retinopathy (64.0 versus 43.0%, p=0.003), higher creatinine levels (83.5 versus 74.1 µmol/L, p=0.03), higher mortality (16 versus 5%, p=0.002), and after onset of type 1 diabetes mellitus higher rates of co-morbidity (5.28 versus 3.18, p⩽0.01), heart failure (9 versus 2%, p=0.02), and stroke (6 versus 2%, p=0.048) compared with controls.ConclusionsFrom a nationwide register of patients with type 1 diabetes mellitus, the coexistence of CHD and type 1 diabetes mellitus was associated with an earlier onset, a higher frequency of microvascular complications, co-morbidity, and mortality.

Download Full-text

Associations of TP53 codon 72 polymorphism with complications and comorbidities in patients with type 1 diabetes

Journal of Molecular Medicine ◽

10.1007/s00109-020-02035-1 ◽

2021 ◽

Author(s):

Bartosz Słomiński ◽

Maria Skrzypkowska ◽

Monika Ryba-Stanisławowska ◽

Małgorzata Myśliwiec ◽

Piotr Trzonkowski

Keyword(s):

Type 1 Diabetes ◽

Celiac Disease ◽

Autoimmune Thyroiditis ◽

Microvascular Complications ◽

List Type ◽

Codon 72 ◽

Codon 72 Polymorphism ◽

Increased Risk ◽

Increased Susceptibility

Abstract Wild-type TP53 plays an important role in the regulation of immune response and systemic inflammation. In type 1 diabetes (T1D), TP53 pathways are upregulated and an increased susceptibility to apoptosis is observed. We hypothesize that TP53 codon 72 polymorphism could be associated with complications and comorbidities in patients with T1D. We have investigated the associations of the TP53 codon 72 polymorphism with the T1D complications and comorbidities (retinopathy, nephropathy, hypertension, dyslipidemia, autoimmune thyroiditis, and celiac disease) in 350 patients. The key results of our approach are as follows: (1) In diabetic subjects, the Pro/Pro genotype is associated with an increased risk of microvascular complications, dyslipidemia, and celiac disease; (2) the Arg/Arg variant is associated with a decreased risk of autoimmune thyroiditis and celiac disease; (3) the Pro allele is associated with an increased risk of dyslipidemia, autoimmune thyroiditis, and celiac disease. Although further studies are required, our results for the first time indicate that the TP53 codon 72 polymorphism could be considered a genetic marker to predict the increased susceptibility to some T1D complications and comorbidities. Key messages We analyzed the TP53 codon 72 polymorphism in patients with T1D. Pro/Pro genotype is associated with an increased risk of microvascular complications, dyslipidemia, and celiac disease. The Arg/Arg variant is associated with a decreased risk of autoimmune thyroiditis and celiac disease. The Pro allele is associated with an increased risk of dyslipidemia, autoimmune thyroiditis, and celiac disease.

Download Full-text