The V16A polymorphism in SOD2 is associated with increased risk of diabetic nephropathy and cardiovascular disease in type 1 diabetes

Abstract Background Low levels of the soluble tumour necrosis factor-like weak inducer of apoptosis (sTWEAK) and depression are linked to cardiovascular disease. Galectin-3, inadequate glycemic control and low high-density lipoprotein (HDL)-cholesterol levels were previously linked to depression in these patients with type 1 diabetes mellitus (T1DM). The main aim was to explore whether sTWEAK was associated with depression. A secondary aim was to explore diabetes related variables associated with low sTWEAK. Methods Cross-sectional design. T1DM patients (n = 283, men 56%, age18–59 years) were consecutively recruited from one specialist diabetes clinic. Depression was defined as Hospital Anxiety and Depression Scale-Depression sub scale ≥8 points. Blood samples, anthropometrics and blood pressure were collected, supplemented with data from electronic health records. Enzyme linked immunosorbent assays were used to measure sTWEAK and galectin-3. Low sTWEAK was defined as < 7.2 ng/ml and high galectin-3 as ≥2.6 ng/ml. Multiple logistic regression analyses were performed, calibrated and validated for goodness of fit. We adjusted for age, sex, diabetes duration, galectin-3, metabolic variables, serum-creatinine, smoking, physical inactivity, medication, and cardiovascular complications. Results For 29 depressed versus 254 non-depressed patients the prevalence rates were for low sTWEAK: 93 and 68% (p = 0.003) and for high galectin-3: 34 and 13% (p = 0.005) respectively. HDL-cholesterol levels were lower for the depressed (p = 0.015). Patients with low sTWEAK versus high sTWEAK had lower usage of continuous subcutaneous insulin infusion (CSII) (6% versus 17%, p = 0.005). Low sTWEAK (adjusted odds ratio (AOR) 9.0, p = 0.006), high galectin-3 (AOR 6.3, p = 0.001), HDL-cholesterol (per mmol/l) (AOR 0.1, p = 0.006), use of antidepressants (AOR 8.4, p < 0.001), and age (per year) (AOR 1.05, p = 0.027) were associated with depression. CSII (AOR 0.3, p = 0.003) and depression (AOR 7.1, p = 0.009) were associated with low sTWEAK. Conclusions Lower levels of sTWEAK and HDL-cholesterol and higher levels of galectin-3 were independently associated with depression in T1DM. These factors might all contribute to the increased risk for cardiovascular disease and mortality previously demonstrated in patients with depression. CSII (inversely) and depression were independently associated with low sTWEAK levels.

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Diabetic Retinopathy May Indicate an Increased Risk of Cardiovascular Disease in Patients With Type 1 Diabetes—A Nested Case-Control Study in Brazil

Frontiers in Endocrinology ◽

10.3389/fendo.2019.00689 ◽

2019 ◽

Vol 10 ◽

Cited By ~ 1

Author(s):

Laura Gomes Nunes Melo ◽

Paulo Henrique Morales ◽

Karla Rezende Guerra Drummond ◽

Deborah Conte Santos ◽

Marcela Haas Pizarro ◽

...

Keyword(s):

Cardiovascular Disease ◽

Type 1 Diabetes ◽

Diabetic Retinopathy ◽

Case Control Study ◽

Case Control ◽

Increased Risk ◽

Nested Case Control ◽

Control Study

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Risk Factors for Cardiovascular Disease (CVD) in Adults with Type 1 Diabetes: Findings from Prospective Real-life T1D Exchange Registry

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa015 ◽

2020 ◽

Vol 105 (5) ◽

pp. e2032-e2038 ◽

Cited By ~ 4

Author(s):

Viral N Shah ◽

Ryan Bailey ◽

Mengdi Wu ◽

Nicole C Foster ◽

Rodica Pop-Busui ◽

...

Keyword(s):

Risk Factors ◽

Cardiovascular Disease ◽

Type 1 Diabetes ◽

Diabetic Nephropathy ◽

The United States ◽

Cvd Risk Factors ◽

Cvd Risk ◽

The Impact

Abstract Context Cardiovascular disease (CVD) is a major cause of mortality in adults with type 1 diabetes. Objective We prospectively evaluated CVD risk factors in a large, contemporary cohort of adults with type 1 diabetes living in the United States. Design Observational study of CVD and CVD risk factors over a median of 5.3 years. Setting The T1D Exchange clinic network. Patients Adults (age ≥ 18 years) with type 1 diabetes and without known CVD diagnosed before or at enrollment. Main Outcome Measure Associations between CVD risk factors and incident CVD were assessed by multivariable logistic regression. Results The study included 8,727 participants (53% female, 88% non-Hispanic white, median age 33 years [interquartile ratio {IQR} = 21, 48], type 1 diabetes duration 16 years [IQR = 9, 26]). At enrollment, median HbA1c was 7.6% (66 mmol/mol) (IQR = 6.9 [52], 8.6 [70]), 33% used a statin, and 37% used blood pressure medication. Over a mean follow-up of 4.6 years, 325 (3.7%) participants developed incident CVD. Ischemic heart disease was the most common CVD event. Increasing age, body mass index, HbA1c, presence of hypertension and dyslipidemia, increasing duration of diabetes, and diabetic nephropathy were associated with increased risk for CVD. There were no significant gender differences in CVD risk. Conclusion HbA1c, hypertension, dyslipidemia and diabetic nephropathy are important risk factors for CVD in adults with type 1 diabetes. A longer follow-up is likely required to assess the impact of other traditional CVD risk factors on incident CVD in the current era.

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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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Resistant hypertension and risk of adverse events in individuals with type 1 diabetes: A nationwide prospective study

10.2337/figshare.12137604.v1 ◽

2020 ◽

Author(s):

Raija Lithovius ◽

Valma Harjutsalo ◽

Stefan Mutter ◽

Daniel Gordin ◽

Carol Forsblom ◽

...

Keyword(s):

Type 1 Diabetes ◽

Diabetic Nephropathy ◽

Prospective Study ◽

Resistant Hypertension ◽

Antihypertensive Drugs ◽

Increased Risk ◽

All Cause Mortality ◽

Nationally Representative ◽

Reduced Kidney Function

Objectives. To estimate the risk of diabetic nephropathy (DN) progression, incident coronary heart disease (CHD) and stroke, and all-cause mortality associated with resistant hypertension (RH) in individuals with type 1 diabetes stratified by stages of DN, renal function and sex. Research Design and Methods This prospective study included a nationally representative cohort of individuals with type 1 diabetes from the Finnish Diabetic Nephropathy Study who had purchases of antihypertensive drugs at (±6 months) baseline visit (1995–2008). Individuals (N=1,103) were divided into three groups: (a) RH, (b) uncontrolled BP, but no RH and (c) controlled BP. DN progression, cardiovascular events and deaths were identified from the individuals’ healthcare records and national registries, until 31 December 2015. Results At baseline 18.7% of the participants had RH, while 23.4% had controlled BP. After full adjustments for clinical confounders, RH was associated with increased risk of DN progression (HR 1.95 [95% CI 1.37, 2.79], p=0.0002), while no differences were observed in those with no RH (1.05 [0.76, 1.44], p=0.8), compared with those who had controlled BP. The risk of incident CHD, incident stroke and all-cause mortality was higher in individuals with RH compared with those who had controlled BP, but not beyond albuminuria and reduced kidney function. Notably, in those with normo- and microalbuminuria the risk of stroke remained higher in the RH compared to controlled BP group (3.49 [81.20, 10.15], p=0.02). Conclusion Our findings highlight importance to identify and provide diagnostic and therapeutic counseling to these very high risk individuals with RH.

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Resistant hypertension and risk of adverse events in individuals with type 1 diabetes: A nationwide prospective study

10.2337/figshare.12137604.v2 ◽

2020 ◽

Author(s):

Raija Lithovius ◽

Valma Harjutsalo ◽

Stefan Mutter ◽

Daniel Gordin ◽

Carol Forsblom ◽

...

Keyword(s):

Type 1 Diabetes ◽

Diabetic Nephropathy ◽

Prospective Study ◽

Resistant Hypertension ◽

Antihypertensive Drugs ◽

Increased Risk ◽

All Cause Mortality ◽

Nationally Representative ◽

Reduced Kidney Function

Objectives. To estimate the risk of diabetic nephropathy (DN) progression, incident coronary heart disease (CHD) and stroke, and all-cause mortality associated with resistant hypertension (RH) in individuals with type 1 diabetes stratified by stages of DN, renal function and sex. Research Design and Methods This prospective study included a nationally representative cohort of individuals with type 1 diabetes from the Finnish Diabetic Nephropathy Study who had purchases of antihypertensive drugs at (±6 months) baseline visit (1995–2008). Individuals (N=1,103) were divided into three groups: (a) RH, (b) uncontrolled BP, but no RH and (c) controlled BP. DN progression, cardiovascular events and deaths were identified from the individuals’ healthcare records and national registries, until 31 December 2015. Results At baseline 18.7% of the participants had RH, while 23.4% had controlled BP. After full adjustments for clinical confounders, RH was associated with increased risk of DN progression (HR 1.95 [95% CI 1.37, 2.79], p=0.0002), while no differences were observed in those with no RH (1.05 [0.76, 1.44], p=0.8), compared with those who had controlled BP. The risk of incident CHD, incident stroke and all-cause mortality was higher in individuals with RH compared with those who had controlled BP, but not beyond albuminuria and reduced kidney function. Notably, in those with normo- and microalbuminuria the risk of stroke remained higher in the RH compared to controlled BP group (3.49 [81.20, 10.15], p=0.02). Conclusion Our findings highlight importance to identify and provide diagnostic and therapeutic counseling to these very high risk individuals with RH.

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Pulse Pressure Predicts Incident Cardiovascular Disease but Not Diabetic Nephropathy in Patients With Type 1 Diabetes (The FinnDiane Study)

Diabetes Care ◽

10.2337/dc10-2013 ◽

2011 ◽

Vol 34 (4) ◽

pp. 886-891 ◽

Cited By ~ 25

Author(s):

D. Gordin ◽

J. Waden ◽

C. Forsblom ◽

L. Thorn ◽

M. Rosengard-Barlund ◽

...

Keyword(s):

Cardiovascular Disease ◽

Type 1 Diabetes ◽

Diabetic Nephropathy ◽

Pulse Pressure ◽

Incident Cardiovascular Disease

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Resistant hypertension and risk of adverse events in individuals with type 1 diabetes: A nationwide prospective study

10.2337/figshare.12137604 ◽

2020 ◽

Author(s):

Raija Lithovius ◽

Valma Harjutsalo ◽

Stefan Mutter ◽

Daniel Gordin ◽

Carol Forsblom ◽

...

Keyword(s):

Type 1 Diabetes ◽

Diabetic Nephropathy ◽

Prospective Study ◽

Resistant Hypertension ◽

Antihypertensive Drugs ◽

Increased Risk ◽

All Cause Mortality ◽

Nationally Representative ◽

Reduced Kidney Function

Objectives. To estimate the risk of diabetic nephropathy (DN) progression, incident coronary heart disease (CHD) and stroke, and all-cause mortality associated with resistant hypertension (RH) in individuals with type 1 diabetes stratified by stages of DN, renal function and sex. Research Design and Methods This prospective study included a nationally representative cohort of individuals with type 1 diabetes from the Finnish Diabetic Nephropathy Study who had purchases of antihypertensive drugs at (±6 months) baseline visit (1995–2008). Individuals (N=1,103) were divided into three groups: (a) RH, (b) uncontrolled BP, but no RH and (c) controlled BP. DN progression, cardiovascular events and deaths were identified from the individuals’ healthcare records and national registries, until 31 December 2015. Results At baseline 18.7% of the participants had RH, while 23.4% had controlled BP. After full adjustments for clinical confounders, RH was associated with increased risk of DN progression (HR 1.95 [95% CI 1.37, 2.79], p=0.0002), while no differences were observed in those with no RH (1.05 [0.76, 1.44], p=0.8), compared with those who had controlled BP. The risk of incident CHD, incident stroke and all-cause mortality was higher in individuals with RH compared with those who had controlled BP, but not beyond albuminuria and reduced kidney function. Notably, in those with normo- and microalbuminuria the risk of stroke remained higher in the RH compared to controlled BP group (3.49 [81.20, 10.15], p=0.02). Conclusion Our findings highlight importance to identify and provide diagnostic and therapeutic counseling to these very high risk individuals with RH.

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