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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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.

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Risk for recurrent cardiovascular disease events among patients with diabetes and chronic kidney disease

Cardiovascular Diabetology ◽

10.1186/s12933-021-01247-0 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Demetria Hubbard ◽

Lisandro D. Colantonio ◽

Robert S. Rosenson ◽

Todd M. Brown ◽

Elizabeth A. Jackson ◽

...

Keyword(s):

Myocardial Infarction ◽

Cardiovascular Disease ◽

Chronic Kidney Disease ◽

Health Insurance ◽

High Risk ◽

Kidney Disease ◽

Peripheral Artery ◽

Increased Risk ◽

Patients With Diabetes ◽

Very High

Abstract Background Adults who have experienced multiple cardiovascular disease (CVD) events have a very high risk for additional events. Diabetes and chronic kidney disease (CKD) are each associated with an increased risk for recurrent CVD events following a myocardial infarction (MI). Methods We compared the risk for recurrent CVD events among US adults with health insurance who were hospitalized for an MI between 2014 and 2017 and had (1) CVD prior to their MI but were free from diabetes or CKD (prior CVD), and those without CVD prior to their MI who had (2) diabetes only, (3) CKD only and (4) both diabetes and CKD. We followed patients from hospital discharge through December 31, 2018 for recurrent CVD events including coronary, stroke, and peripheral artery events. Results Among 162,730 patients, 55.2% had prior CVD, and 28.3%, 8.3%, and 8.2% had diabetes only, CKD only, and both diabetes and CKD, respectively. The rate for recurrent CVD events per 1000 person-years was 135 among patients with prior CVD and 110, 124 and 171 among those with diabetes only, CKD only and both diabetes and CKD, respectively. Compared to patients with prior CVD, the multivariable-adjusted hazard ratio for recurrent CVD events was 0.92 (95%CI 0.90–0.95), 0.89 (95%CI: 0.85–0.93), and 1.18 (95%CI: 1.14–1.22) among those with diabetes only, CKD only, and both diabetes and CKD, respectively. Conclusion Following MI, adults with both diabetes and CKD had a higher risk for recurrent CVD events compared to those with prior CVD without diabetes or CKD.

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Low levels of soluble TWEAK, indicating on-going inflammation, were associated with depression in type 1 diabetes: a cross-sectional study

BMC Psychiatry ◽

10.1186/s12888-020-02977-3 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Eva O. Melin ◽

Jonatan Dereke ◽

Magnus Hillman

Keyword(s):

Cardiovascular Disease ◽

Type 1 Diabetes ◽

Goodness Of Fit ◽

Hdl Cholesterol ◽

Cross Sectional ◽

Cholesterol Levels ◽

Increased Risk ◽

Galectin 3 ◽

Low Levels

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

Diabetic Medicine ◽

10.1111/dme.14184 ◽

2019 ◽

Vol 37 (12) ◽

pp. 2136-2142

Author(s):

M.R. Chetan ◽

J.K. Miksza ◽

I. Lawrence ◽

R.M. Anjana ◽

R. Unnikrishnan ◽

...

Keyword(s):

Type 1 Diabetes ◽

South Asians ◽

Microvascular Complications ◽

Increased Risk

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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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Declining trends of diabetic nephropathy, retinopathy and neuropathy with improving diabetes care indicators in Japanese patients with type 2 and type 1 diabetes (JDDM 46)

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2018-000521 ◽

2018 ◽

Vol 6 (1) ◽

pp. e000521 ◽

Cited By ~ 13

Author(s):

Hiroki Yokoyama ◽

Shin-ichi Araki ◽

Koichi Kawai ◽

Katsuya Yamazaki ◽

Osamu Tomonaga ◽

...

Keyword(s):

Type 2 Diabetes ◽

Chronic Kidney Disease ◽

Type 1 Diabetes ◽

Kidney Disease ◽

Diabetes Care ◽

Microvascular Complications ◽

Treatment Target ◽

Younger Patients

ObjectiveWe examined changes in prevalence of diabetic microvascular/macrovascular complications and diabetes care indicators for adults in Japan with type 2 and type 1 diabetes over one decade.Research design and methodsTwo independent cohorts were recruited with the same inclusion criteria in 2004 (cohort 1: 3319 with type 2 and 286 with type 1 diabetes) and in 2014 (cohort 2: 3932 with type 2 and 308 with type 1 diabetes). Prevalence of complications and care indicators including achieving treatment targets for glycemia, blood pressure, lipid control, body mass index (BMI), and smoking were compared. In addition, patients in cohort 1 were re-examined in 2014 and their data were compared with the baseline data of each cohort.ResultsIn type 2 diabetes, the prevalence of nephropathy, retinopathy, neuropathy, chronic kidney disease, current smoking and stroke significantly decreased, with improvements in achieving treatment target rates in cohort 2 two as compared with cohort 1. In type 1 diabetes, the prevalence of nephropathy, retinopathy, chronic kidney disease, and hemoglobin A1Cvalues significantly decreased. Decreases in prevalence of microvascular complications in type 2 diabetes were similarly found in each age-matched and sex-matched group, whereas younger patients exhibited marked increase in BMI and lower treatment target achieving rates compared with elderly patients. Regarding normoalbuminuric renal impairment, only a slight increase in the prevalence was observed both in type 2 and type 1 diabetes. In cohort 1, re-examined in 2014, care indicators were significantly improved from 2004, while complications increased with getting 10 years older.ConclusionsWe observed declining trends of diabetic microvascular complications with improvement in diabetes care indicators in type 2 and type 1 diabetes. Younger patients with type 2 diabetes exhibited marked increase in BMI and lower rates of achieving treatment targets compared with elderly patients, which remains a concern.

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Predicting renal disease progression in a large contemporary cohort with type 1 diabetes mellitus

Diabetologia ◽

10.1007/s00125-019-05052-z ◽

2019 ◽

Vol 63 (3) ◽

pp. 636-647 ◽

Cited By ~ 3

Author(s):

Marco Colombo ◽

◽

Stuart J. McGurnaghan ◽

Samira Bell ◽

Finlay MacKenzie ◽

...

Keyword(s):

Cardiovascular Disease ◽

Type 1 Diabetes ◽

Kidney Disease ◽

Renal Disease ◽

Adult Population ◽

Diabetes Duration ◽

Research Network ◽

Diabetes Research ◽

Renal Disease Progression

Abstract Aims/hypothesis The aim of this study was to provide data from a contemporary population-representative cohort on rates and predictors of renal decline in type 1 diabetes. Methods We used data from a cohort of 5777 people with type 1 diabetes aged 16 and older, diagnosed before the age of 50, and representative of the adult population with type 1 diabetes in Scotland (Scottish Diabetes Research Network Type 1 Bioresource; SDRNT1BIO). We measured serum creatinine and urinary albumin/creatinine ratio (ACR) at recruitment and linked the data to the national electronic healthcare records. Results Median age was 44.1 years and diabetes duration 20.9 years. The prevalence of CKD stages G1, G2, G3 and G4 and end-stage renal disease (ESRD) was 64.0%, 29.3%, 5.4%, 0.6%, 0.7%, respectively. Micro/macroalbuminuria prevalence was 8.6% and 3.0%, respectively. The incidence rate of ESRD was 2.5 (95% CI 1.9, 3.2) per 1000 person-years. The majority (59%) of those with chronic kidney disease stages G3–G5 did not have albuminuria on the day of recruitment or previously. Over 11.6 years of observation, the median annual decline in eGFR was modest at −1.3 ml min−1 [1.73 m]−2 year−1 (interquartile range [IQR]: −2.2, −0.4). However, 14% experienced a more significant loss of at least 3 ml min−1 [1.73 m]−2. These decliners had more cardiovascular disease (OR 1.9, p = 5 × 10−5) and retinopathy (OR 1.3 p = 0.02). Adding HbA1c, prior cardiovascular disease, recent mean eGFR and prior trajectory of eGFR to a model with age, sex, diabetes duration, current eGFR and ACR maximised the prediction of final eGFR (r2 increment from 0.698 to 0.745, p < 10−16). Attempting to model nonlinearity in eGFR decline or to detect latent classes of decliners did not improve prediction. Conclusions These data show much lower levels of kidney disease than historical estimates. However, early identification of those destined to experience significant decline in eGFR remains challenging.

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Biological Activity of c-Peptide in Microvascular Complications of Type 1 Diabetes—Time for Translational Studies or Back to the Basics?

International Journal of Molecular Sciences ◽

10.3390/ijms21249723 ◽

2020 ◽

Vol 21 (24) ◽

pp. 9723

Author(s):

Aleksandra Ryk ◽

Aleksandra Łosiewicz ◽

Arkadiusz Michalak ◽

Wojciech Fendler

Keyword(s):

Type 1 Diabetes ◽

Growth Factor ◽

Transforming Growth Factor ◽

Negative Impact ◽

Current Knowledge ◽

Microvascular Complications ◽

C Peptide ◽

Increased Risk ◽

The Impact

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.

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Presence and Determinants of Cardiovascular Disease and Mortality in Individuals With Type 1 Diabetes of Long Duration: The FinnDiane 50 Years of Diabetes Study

10.2337/figshare.14626908.v1 ◽

2021 ◽

Author(s):

Valma Harjutsalo ◽

Drazenka Pongrac Barlovic ◽

Daniel Gordin ◽

Carol Forsblom ◽

George King ◽

...

Keyword(s):

Risk Factors ◽

Cardiovascular Disease ◽

Type 1 Diabetes ◽

Kidney Disease ◽

Cumulative Incidence ◽

Diabetes Duration ◽

Baseline Visit ◽

Background Population ◽

Long Duration

Objective The aim of this study was to determine the incidence of cardiovascular disease (CVD) and mortality as well as their risk factors in type 1 diabetes (T1D) with more than 50-years duration. Methods From 5,396 individuals included in the Finnish Diabetic Nephropathy Study, 729 diagnosed in 1967 or earlier survived with T1D for more than 50 years. In this FinnDiane 50-year cohort, cumulative incidence of CVD events was assessed from the diagnosis of diabetes, and the excess CVD risk, compared to matched 12,710 individuals without diabetes, was calculated by Fine and Gray’s method. In addition, at the baseline visit (median duration of diabetes of 39 years) risk factors for different types of CVD (both non-fatal and fatal) and mortality were analyzed and cause-specific hazard ratios were estimated during a median follow-up of 16.6 years from the baseline visit. Results In individuals with diabetes duration of more than 50 years, the 60-year cumulative incidence of CVD from the diagnosis of diabetes was 64.3% (62.5-66.0). Compared to individuals without diabetes, the standardized incidence ratio for CVD was 7.4 (6.5-8.3) and was in persons with normoalbuminuria 4.9 (4.0-5.9). Mean HbA1c and HbA1c variability, dyslipidemia, BMI, kidney disease, age and diabetes duration were the variables associated with incident CVD. In particular, HbA1c was associated with peripheral artery disease (PAD). Standardized mortality ratio compared with the Finnish background population was 3.2 (2.8-3.7). The factors, associated with mortality were diabetes duration, increased HbA1c variability, inflammation, insulin resistance, kidney disease and PAD. Conclusions Individuals with T1D of very long duration are at a high risk of CVD. In addition, throughout the lifespan, optimal glycemic control remains central to CVD and excess mortality prevention.

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