ACE I/D Polymorphism, Plasma ACE Levels, and Long-term Kidney Outcomes or All-Cause Death in Patients With Type 1 Diabetes

10.2337/figshare.14109368.v1 ◽

2021 ◽

Author(s):

Yawa Abouleka ◽

Kamel Mohammedi ◽

Charlyne Carpentier ◽

Severine Dubois ◽

Pierre Gourdy ◽

...

Keyword(s):

Type 1 Diabetes ◽

Kidney Disease ◽

Primary Outcome ◽

Rapid Decline ◽

Genotype Distribution ◽

Net Reclassification Improvement ◽

Increased Risk ◽

Cox Analysis

Objective: The D-allele of ACE I/D polymorphism is a risk factor for diabetic kidney disease. We assessed its contribution to long-term kidney outcomes and all-cause death in patients with long-standing type 1 diabetes. Research Design and Methods: 1155 participants from 3 French and Belgian cohorts were followed for a median (interquartile range) duration of 14 (13) years. The primary outcome was the occurrence of end-stage kidney disease (ESKD) or a 40% drop in estimated glomerular filtration rate (eGFR). Secondary outcomes were the individual components of the primary outcome, rapid decline in eGFR (steeper than -3 ml/min/1.73m2/year), incident albuminuria, all-cause death, and a composite ESKD or all-cause death. Hazard ratios (HR) for XD versus II genotype and for baseline plasma ACE levels were computed by Cox analysis. Genotype performance in stratifying the primary outcome was tested. Results: Genotype distribution was 954 XD and 201 II. The primary outcome occurred in 20% of XD and 13% of II carriers: adjusted HR 2.07 (95%CI, 1.32-3.40), p=0.001. Significant associations were also observed for rapid decline in eGFR, incident albuminuria, ESKD, all-cause death, and ESKD or all-cause death. Baseline plasma ACE levels were higher in XD carriers and significantly associated with increased risk of the primary outcome. ACE genotype enhanced net reclassification improvement (0.154, 95%CI 0.007-0.279, p=0.04) and integrated discrimination improvement (0.012, 95%CI 0.001-0.021, p=0.02) for primary outcome stratification. Conclusions: The D-allele of ACE I/D polymorphism was associated with increased risk of major kidney events and all-cause death in patients with long-standing type 1 diabetes.

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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.

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Long-term Improvement of Metabolic Control Without Increased Risk of Hypoglycaemia by Intensive Insulin Regimens in Type 1 Diabetes Patients Treated in a Regular Clinical Setting

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/s-2007-956165 ◽

2007 ◽

Vol 115 (03) ◽

pp. 182-186 ◽

Cited By ~ 4

Author(s):

L. Pérez Méndez ◽

E. Álvarez-García ◽

P. Álvarez-Vázquez ◽

E. Hervás ◽

A. Casterás ◽

...

Keyword(s):

Type 1 Diabetes ◽

Metabolic Control ◽

Clinical Setting ◽

Increased Risk ◽

Diabetes Patients

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The importance of pulse wave velocity measurement in paediatric population with an increased risk of cardiovascular diseases - Type 1 diabetes and chronic kidney disease

Cor et Vasa ◽

10.1016/j.crvasa.2016.03.007 ◽

2016 ◽

Vol 58 (6) ◽

pp. e623-e630

Author(s):

Terezie Šuláková ◽

Janusz Feber ◽

Jiří Strnadel ◽

Jan Pavlíček ◽

Barbora Obermannová ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Type 1 Diabetes ◽

Cardiovascular Diseases ◽

Kidney Disease ◽

Pulse Wave Velocity ◽

Pulse Wave ◽

Paediatric Population ◽

Increased Risk ◽

Pulse Wave Velocity Measurement

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INSULIN RESISTANCE AND CHRONIC KIDNEY DISEASE IN PATIENTS WITH TYPE 1 DIABETES MELLITUS AT MEDICINE DEPARTMENT OF GMC, BETTIAH, BIHAR

10.36106/ijsr/9227019 ◽

2020 ◽

pp. 1-2

Author(s):

Sumit Kumar ◽

Dharmendra Prasad ◽

Parshuram Yugal ◽

Debarshi Jana

Keyword(s):

Diabetes Mellitus ◽

Insulin Resistance ◽

Chronic Kidney Disease ◽

Type 1 Diabetes ◽

Kidney Disease ◽

Glycosylated Hemoglobin ◽

Diabetic Patients ◽

Medicine Department ◽

Increased Risk

Background and Aims : Diabetes mellitus (DM) is a chronic disease which can evolve towards devastating micro- and macrovascular complications. DM is the most frequent cause of chronic kidney disease (CKD). Insulin resistance plays an important role in the natural history of type 1 diabetes. The purpose of the study was to determine the prevalence of CKD in T1DM and the correlation with insulin resistance (IR) in patients with CKD. Materials and Methods : The study was conducted over a period of two years (2014–2015) and included patients with DM admitted in Medicine Department of ANMMCH, Gaya, Bihar. The study design was an epidemiological, transversal, noninterventional type. Finally, the study group included 200 subjects with type 1 DM. Insulin resistance (IR) was estimated by eGDR. The subjects with eGDR ≤ 7.5mg/kg/min were considered with insulin resistance. Results : CKD was found in 44% of the patients. Analyzing statistically the presence of CKD, we found highly significant differences between patients with CKD and those without CKD regarding age and sex of the patients, the duration of diabetes, glycosylated hemoglobin (HbA1c), the estimated glucose disposal rate (eGDR), and the presence of hypertension, dyslipidemia, and hyperuricaemia. In patients with CKD, age and diabetes duration are significantly higher than in those who do not have this complication. CKD is more frequent in males than in females (50.9% men versus 34.5% women, ). From the elements of metabolic syndrome, high blood pressure, hyperuricemia, and dyslipidemia are significantly increased in diabetic patients with CKD. eGDR value (expressed as mg•kg−1•min−1) is lower in patients with CKD than in those without CKD (15.92 versus 6.42, ) indicating the fact that patients with CKD show higher insulin resistance than those without CKD. Conclusions. This study has shown that insulin resistance is associated with an increased risk of CKD, but, due to the cross-sectional design, the causal relationship cannot be assessed.

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Mortality in childhood-onset type 1 diabetes: Nationwide population based data from Norway

Norsk Epidemiologi ◽

10.5324/nje.v23i1.1607 ◽

2013 ◽

Vol 23 (1) ◽

Cited By ~ 2

Author(s):

Torild Skrivarhaug

Keyword(s):

Type 1 Diabetes ◽

Premature Mortality ◽

Diabetic Coma ◽

Diabetic Patients ◽

Childhood Onset ◽

Onset Type ◽

Treatment Type ◽

Increased Risk

Type 1 diabetes with onset in childhood (0-14.9 years) represents one of the most frequent chronic diseases in children and young adults. Norway has one of the highest incidences of childhood onset type 1 diabetes in the world. Before introduction of insulin therapy in 1922, few children survived more than one to two years after clinical onset. When insulin came available, a major shift occurred in the distribution of causes of death in type 1 diabetic patients away from diabetic coma, which dominated the pre-insulin era, to renal and cardiac diseases. The disease is related to a significant burden to society and patients because most cases require lifelong treatment with insulin as well as day-to-day monitoring. Type 1 diabetes also confers increased risk of severe late complications such as renal failure, blindness, amputations, heart disease and stroke. Despite advances in diabetes treatment, type 1 diabetes is still associated with considerable premature mortality resulting from acute and chronic complications of diabetes and an increase in mortality at every age. Although the main cause of death in type 1 diabetes is long-term complications, an excess death rate has also been reported in subjects with short duration without signs of long-term complications.

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Nonglycemic effects of incretins in patients with long-term type 1 diabetes mellitus and chronic kidney disease

Terapevticheskii arkhiv ◽

10.17116/terarkh2015871054-61 ◽

2015 ◽

Vol 87 (10) ◽

pp. 54 ◽

Cited By ~ 1

Author(s):

M. S. Arutyunova ◽

A. M. Glazunova ◽

O. V. Mikhaleva ◽

Z. T. Zuraeva ◽

S. A. Martynov ◽

...

Keyword(s):

Diabetes Mellitus ◽

Chronic Kidney Disease ◽

Type 1 Diabetes ◽

Kidney Disease ◽

Type 1 Diabetes Mellitus ◽

Term Type

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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.

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A Validated Prediction Model for End-Stage Kidney Disease in Type 1 Diabetes

10.2337/figshare.13526414 ◽

2021 ◽

Author(s):

Dorte Vistisen ◽

Gregers S. Andersen ◽

Adam Hulman ◽

Stuart J. McGurnaghan ◽

Helen M. Colhoun ◽

...

Keyword(s):

Type 1 Diabetes ◽

Kidney Disease ◽

Prediction Model ◽

Clinical Decision Making ◽

External Validation ◽

End Stage Kidney Disease ◽

Risk Of Death ◽

Increased Risk ◽

End Stage

OBJECTIVE End-stage kidney disease (ESKD) is a life-threatening complication of diabetes which can be prevented or delayed by intervention. Hence, early detection of persons at increased risk is essential. RESEARCH DESIGN AND METHODS From a population-based cohort of 5,460 clinically diagnosed Danish adults with type 1 diabetes followed 2001-2016, we developed a prediction model for ESKD accounting for the competing risk of death. Poisson regression analysis was used to estimate the model based on information routinely collected from clinical examinations. The effect of including an extended set of predictors (lipids, alcohol intake etc.) was further evaluated, and potential interactions identified in a survival tree analysis were tested. The final model was externally validated in 9,175 adults from Denmark and Scotland. RESULTS During a median follow-up of 10.4 years (interquartile limits: 5.1;14.7), 303 (5.5%) of the participants (mean (SD) age 42.3 (16.5) years) developed ESKD and 764 (14.0%) died without having developed ESKD. The final ESKD prediction model included age, male sex, diabetes duration, estimated glomerular filtration rate, micro- and macroalbuminuria, systolic blood pressure, HbA1c, smoking and previous cardiovascular disease. Discrimination was excellent for 5-year risk of ESKD event with a C-statistic of 0.888 (95%CI: 0.849;0.927) in the derivation cohort and confirmed at 0.865 (0.811;0.919) and 0.961 (0.940;0.981) in the external validation cohorts from Denmark and Scotland. CONCLUSIONS We have derived and validated a novel, high-performing ESKD prediction model for risk stratification in the adult type 1 diabetes population. This model may improve clinical decision making and potentially guide early intervention.

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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.

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