scholarly journals Fetuin-A and risk of diabetes-related vascular complications: a prospective study

2022 ◽  
Vol 21 (1) ◽  
Author(s):  
Anna Birukov ◽  
Elli Polemiti ◽  
Susanne Jäger ◽  
Norbert Stefan ◽  
Matthias B. Schulze

Abstract Background Fetuin-A is a hepatokine which has the capacity to prevent vascular calcification. Moreover, it is linked to the induction of metabolic dysfunction, insulin resistance and associated with increased risk of diabetes. It has not been clarified whether fetuin-A associates with risk of vascular, specifically microvascular, complications in patients with diabetes. We aimed to investigate whether pre-diagnostic plasma fetuin-A is associated with risk of complications once diabetes develops. Methods Participants with incident type 2 diabetes and free of micro- and macrovascular disease from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort (n = 587) were followed for microvascular and macrovascular complications (n = 203 and n = 60, respectively, median follow-up: 13 years). Plasma fetuin-A was measured approximately 4 years prior to diabetes diagnosis. Prospective associations between baseline fetuin-A and risk of complications were assessed with Cox regression. Results In multivariable models, fetuin-A was linearly inversely associated with incident total and microvascular complications, hazard ratio (HR, 95% CI) per standard deviation (SD) increase: 0.86 (0.74; 0.99) for total, 0.84 (0.71; 0.98) for microvascular and 0.92 (0.68; 1.24) for macrovascular complications. After additional adjustment for cardiometabolic plasma biomarkers, including triglycerides and high-density lipoprotein, the associations were slightly attenuated: 0.88 (0.75; 1.02) for total, 0.85 (0.72; 1.01) for microvascular and 0.95 (0.67; 1.34) for macrovascular complications. No interaction by sex could be observed (p > 0.10 for all endpoints). Conclusions Our data show that lower plasma fetuin-A levels measured prior to the diagnosis of diabetes may be etiologically implicated in the development of diabetes-associated microvascular disease.

Diabetologia ◽  
2021 ◽  
Author(s):  
Elli Polemiti ◽  
Julia Baudry ◽  
Olga Kuxhaus ◽  
Susanne Jäger ◽  
Manuela M. Bergmann ◽  
...  

Abstract Aims/hypothesis Studies suggest decreased mortality risk among people who are overweight or obese compared with individuals with normal weight in type 2 diabetes (obesity paradox). However, the relationship between body weight or weight change and microvascular vs macrovascular complications of type 2 diabetes remains unresolved. We investigated the association between BMI and BMI change with long-term risk of microvascular and macrovascular complications in type 2 diabetes in a prospective cohort study. Methods We studied participants with incident type 2 diabetes from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort, who were free of cancer, cardiovascular disease and microvascular disease at diagnosis (n = 1083). Pre-diagnosis BMI and relative annual change between pre- and post-diagnosis BMI were evaluated in multivariable-adjusted Cox models. Results There were 85 macrovascular (myocardial infarction and stroke) and 347 microvascular events (kidney disease, neuropathy and retinopathy) over a median follow-up of 10.8 years. Median pre-diagnosis BMI was 29.9 kg/m2 (IQR 27.4–33.2), and the median relative annual BMI change was −0.4% (IQR −2.1 to 0.9). Higher pre-diagnosis BMI was positively associated with total microvascular complications (multivariable-adjusted HR per 5 kg/m2 [95% CI]: 1.21 [1.07, 1.36], kidney disease 1.39 [1.21, 1.60] and neuropathy 1.12 [0.96, 1.31]) but not with macrovascular complications (HR 1.05 [95% CI 0.81, 1.36]). Analyses according to BMI categories corroborated these findings. Effect modification was not evident by sex, smoking status or age groups. In analyses according to BMI change categories, BMI loss of more than 1% indicated a decreased risk of total microvascular complications (HR 0.62 [95% CI 0.47, 0.80]), kidney disease (HR 0.57 [95% CI 0.40, 0.81]) and neuropathy (HR 0.73 [95% CI 0.52, 1.03]), compared with participants with a stable BMI; no clear association was observed for macrovascular complications (HR 1.04 [95% CI 0.62, 1.74]). The associations between BMI gain compared with stable BMI and diabetes-related vascular complications were less apparent. Associations were consistent across strata of sex, age, pre-diagnosis BMI or medication but appeared to be stronger among never-smokers compared with current or former smokers. Conclusions/interpretation Among people with incident type 2 diabetes, pre-diagnosis BMI was positively associated with microvascular complications, while a reduced risk was observed with weight loss when compared with stable weight. The relationships with macrovascular disease were less clear. Graphical abstract


2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Sara Sokooti ◽  
Jose L. Flores-Guerrero ◽  
Hiddo J. L. Heerspink ◽  
Margery A. Connelly ◽  
Stephan J. L. Bakker ◽  
...  

Abstract Background Triglyceride-rich lipoproteins particles (TRLP) and low density lipoprotein particles (LDLP) vary in size. Their association with β-cell function is not well described. We determined associations of TRLP and LDLP subfractions with β-cell function, estimated as HOMA-β, and evaluated their associations with incident T2D in the general population. Methods We included 4818 subjects of the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study without T2D at baseline. TRLP and LDLP subfraction concentrations and their average sizes were measured using the LP4 algorithm of the Vantera nuclear magnetic resonance platform. HOMA-IR was used as measure of insulin resistance. HOMA-β was used as a proxy of β-cell function. Results In subjects without T2D at baseline, very large TRLP, and LDL size were inversely associated with HOMA-β, whereas large TRLP were positively associated with HOMA-β when taking account of HOMA-IR. During a median follow-up of 7.3 years, 263 participants developed T2D. In multivariable-adjusted Cox regression models, higher concentrations of total, very large, large, and very small TRLP (reflecting remnants lipoproteins) and greater TRL size were associated with an increased T2D risk after adjustment for relevant covariates, including age, sex, BMI, HDL-C, HOMA-β, and HOMA-IR. On the contrary, higher concentrations of large LDLP and greater LDL size were associated with a lower risk of developing T2D. Conclusions Specific TRL and LDL particle characteristics are associated with β-cell function taking account of HOMA-IR. Moreover, TRL and LDL particle characteristics are differently associated with incident T2D, even when taking account of HOMA-β and HOMA-IR.


2019 ◽  
Vol 26 (2_suppl) ◽  
pp. 47-54 ◽  
Author(s):  
JWJ Beulens ◽  
F Rutters ◽  
L Rydén ◽  
O Schnell ◽  
L Mellbin ◽  
...  

Type 2 diabetes mellitus (T2DM) is associated with a two- to four-fold increased risk of developing cardiovascular disease (CVD) and microvascular complications, which may already be present before diagnosis. It is, therefore, important to detect people with an increased risk of T2DM at an early stage. In order to identify individuals with so-called ‘pre-diabetes’, comprising impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), current guidelines have developed definitions based on fasting plasma glucose, two-hour glucose concentrations and haemoglobin A1c. Subjects with pre-diabetes are at an increased risk of developing T2DM and CVD. This elevated risk seems similar according to the different criteria used to define pre-diabetes. The risk of progression to T2DM or CVD does, however, depend on other risk factors such as sex, body mass index and ethnicity. Based on the risk factors to develop T2DM, many risk assessment models have been developed to identify those at highest risk. These models perform well to identify those at risk and could be used to initiate preventive interventions. Many studies have shown that lifestyle modification and metformin are effective in preventing the development of T2DM, although lifestyle modification seems to have a more sustainable effect. In addition, lifestyle modification seems more effective in those with IGT than those with IFG. In this review, we will describe the different definitions used to define pre-diabetes, progression from pre-diabetes to T2DM or other vascular complications, risk factors associated with progressions and the management of progression to T2DM, ending with clinical recommendations.


2020 ◽  
pp. 239719832095755
Author(s):  
Sofia Furtado ◽  
Bertrand Dunogué ◽  
Georges Jourdi ◽  
Benjamin Chaigne ◽  
Aziza Chibah ◽  
...  

Objective: To determine the frequency of elevated D-dimer plasma concentration (>500 ng/mL) in patients with systemic sclerosis and evaluate its association with systemic sclerosis–specific microvascular and macrovascular complications. Methods: Retrospective observational study of patients with systemic sclerosis followed in a tertiary referral center with at least one measurement of D-dimer between 2010 and 2018. Results: A total of 214 patients were analyzed. Mean age at inclusion was 55.1 ± 14.7 years; 180 (84.1%) were female; 74 (34.6%) had diffuse cutaneous systemic sclerosis. Anti-Scl70 and anti-centromere antibodies were positive in 74 (34.6%) and 75 (35.0%) patients, respectively. D-dimer level was elevated in 93 (43.5%) patients, independently of cutaneous subtype (44.6% in diffuse cutaneous systemic sclerosis vs 42.9% in limited cutaneous systemic sclerosis, p = 0.81). At least one microvascular complication was found in 108 (50.5%) patients: 105 (49.1%) with previous or current digital ulcers, 6 (2.8%) with renal crisis, and 4 (1.9%) with pulmonary arterial hypertension. Microvascular complications were more frequent in patients with elevated D-dimer (57.0% vs 45.5%, p = 0.09), significantly so after exclusion of patients with a history of cancer and/or venous thromboembolism (60.5% vs 44.8%, p = 0.04). Macrovascular complications were detected in 15 (7.0%) patients and were associated with a high D-dimer level (11.8% vs 3.3%, p = 0.03). Over a median follow-up of 2.3 years [1.1–3.3] after D-dimer measurement, new macrovascular complications occurred only in patients with high D-dimer (n = 8). Conclusion: High D-dimer levels are frequently found in systemic sclerosis patients and seem to be associated with the occurrence of macrovascular and microvascular complications after adjustment for confounding factors.


2017 ◽  
Vol 3 (1) ◽  
pp. 6-10
Author(s):  
N Bhavya ◽  
V Ajith Kumar

ABSTRACT Introduction India is claimed to be the diabetes capital of the world. Many studies had proven that persistent hyperglycemia and associated metabolic syndrome features like hypertension, dyslipidemia, and obesity contribute to the development of vascular complications. The risk of chronic complications increases as a function of the duration of hyperglycemia; they usually become apparent in the second decade of hyperglycemia. Since type II diabetes mellitus (DM) often has a long asymptomatic period of hyperglycemia, many individuals with type II DM have complications at the time of diagnosis. The vascular complications of DM are subdivided into microvascular (retinopathy, neuropathy, nephropathy) and macrovascular (coronary artery disease, peripheral arterial disease, cerebro-vascular disease) complications. The present study aims to study the occurrence of microalbuminuria in patients with type II DM and note its association with the duration of diabetes since diagnosis and microvascular complications of DM. Study design Prospective observational study. Materials and methods The study is a clinical, prospective, and observational study of 100 type II diabetics attending the medicine department outpatient/inpatient of RajaRajeswari Medical College & Hospital, Bengaluru, Karnataka, India, who form the subjects for the study conducted from August 2015 to July 2016 (12 months) and who matched the inclusion criteria. Data were collected after obtaining informed/written consent from patient. After detailed history, detailed clinical examination, and general physical and systemic examinations, fundoscopy was carried out and relevant laboratory investigations were done. Results and conclusion The overall occurrence of microalbuminuria was 38%. The occurrence of microalbuminuria showed a direct relationship with increasing age (p = 0.053) and increasing duration of diabetes since diagnosis. A hemoglobin (Hb)A1c value above 7% is associated with 50% or higher incidence of microalbuminuria (p = 0.018). Patients with a body mass index of more than 25kg/m2 have increased risk of developing type II DM and significant increase in microalbuminuria. The incidence of microalbuminuria is significantly associated with How to cite this article Bhavya N, Kumar VA. A Study of Association between Microalbuminuria and Microvascular Complications in Type II Diabetes Mellitus Patients in RajaRajeswari Medical College and Hospital, Karnataka. J Med Sci 2017;3(1):6-10.


Author(s):  
Sarah Wild ◽  
Jackie Price

Diabetes mellitus represents a group of metabolic disorders characterized by hyperglycaemia, which may or may not be associated with symptoms. The chronic hyperglycaemia of diabetes results from defects in insulin secretion, insulin action, or both, and is associated with long-term organ damage, particularly in the eyes, kidneys, nerves, heart, and blood vessels. Patients with type 2 diabetes have a higher prevalence of obesity (particularly abdominal obesity), hypertension, and lipid disorders, as well as an increased risk of macrovascular disease in coronary, peripheral, and cerebral arterial circulations, than people without diabetes. Microvascular complications of diabetes include retinopathy, which can lead to loss of vision, nephropathy (leading to renal failure), neuropathy (with an increased risk of foot ulcers, amputations, and foot deformations), and autonomic neuropathy, causing cardiovascular, gastrointestinal, genitourinary, and sexual dysfunction. Diabetes may have a serious emotional and social impact on affected individuals and their families, and has major economic implications for society as a whole in both developed and developing countries.


2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Mee Kyoung Kim ◽  
Kyungdo Han ◽  
Han Na Joung ◽  
Ki-Hyun Baek ◽  
Ki-Ho Song ◽  
...  

Abstract Background The aim of the present study was to identify a threshold for the cholesterol level at which the risk of cardiovascular disease (CVD) begins to increase in people with type 2 diabetes mellitus (DM). Methods Using the Korean National Health Insurance Service database, 2,077,135 people aged ≥ 40 years with type 2 DM who underwent regular health checks between 2009 and 2012 were included. Subjects with previous CVD were excluded. Cox regression analyses were performed to estimate the risk of CVD for each low-density lipoprotein cholesterol (LDL-C) group using the < 70 mg/dL as the reference group. Results There were 78,560 cases of stroke (3.91%), and 50,791 myocardial infarction (MI, 2.53%) during a median follow-up of 7.1 years. Among participants not taking statins, LDL-C levels of 130–159 mg/dL and ≥ 160 mg/dL were significantly associated with the risk of MI: the hazard ratios (HRs) (95% confidence interval) were 1.19 (1.14–1.25) and 1.53 (1.46–1.62), respectively. Among participants taking statins, all categories of LDL-C level ≥ 70 mg/dL were significantly associated with increased risk of stroke and MI. Conclusions We identified an increased risk of CVD in people with an LDL-C level ≥ 130 mg/dL among individuals with type 2 DM not taking statins. The risk of CVD was significantly higher in those taking statins with an LDL-C level ≥ 70 mg/dL.


2020 ◽  
Author(s):  
Nicola J Adderley ◽  
Anuradhaa Subramanian ◽  
Konstantinos Toulis ◽  
Krishna Gokhale ◽  
Thomas Taverner ◽  
...  

<div><b>Objective</b>: To determine risk of cardiovascular diseases (CVD), microvascular complications and mortality in patients with type 2 diabetes who subsequently develop obstructive sleep apnoea(OSA) compared to patients with type 2 diabetes without a diagnosis of OSA.</div><div><b>Research Design and Methods</b>: An age-, sex-, body mass index- and diabetes duration-matched cohort study using data from a UK primary care database from 01/01/2005 to 17/01/2018. Participants aged ≥16 years with type 2 diabetes were included. Exposed participants were those who developed OSA after their diabetes diagnosis; unexposed participants were those without diagnosed OSA. Outcomes were composite CVD (ischaemic heart disease(IHD), stroke/transient ischaemic attack(TIA), heart failure(HF)); peripheral vascular disease(PVD); atrial fibrillation(AF); peripheral neuropathy(PN); diabetes-related foot disease(DFD); referable retinopathy; chronic kidney disease(CKD); all-cause mortality. The same outcomes were explored in patients with pre-existing OSA before a diagnosis of type 2 diabetes versus diabetes without diagnosed OSA.</div><div><b>Results</b>: 3,667 exposed participants and 10,450 matched controls were included. Adjusted hazard ratios for the outcomes were: composite CVD 1.54(95%CI 1.32,1.79); IHD 1.55(1.26,1.90); HF 1.67(1.35,2.06); stroke/TIA 1.57(1.27,1.94); PVD 1.10(0.91,1.32); AF 1.53(1.28,1.83); PN 1.32(1.14,1.51); DFD 1.42(1.16,1.74); retinopathy 0.99(0.82,1.21); CKD (stage 3-5) 1.18(1.02,1.36); albuminuria 1.11(1.01,1.22); all-cause mortality 1.24(1.10,1.40). In the prevalent OSA cohort the results were similar but some associations not observed.<br></div><div><b>Conclusions</b>: Patients with type 2 diabetes who develop OSA are at increased risk of CVD, AF, PN, DFD, CKD, and all-cause mortality compared to patients without diagnosed OSA. Patients with type 2 diabetes who develop OSA are a high-risk population and strategies to detect OSA and prevent cardiovascular and microvascular complications should be implemented.</div>


2020 ◽  
Author(s):  
Anna Birukov ◽  
Fabian Eichelmann ◽  
Olga Kuxhaus ◽  
Elli Polemiti ◽  
Andreas Fritsche ◽  
...  

<b>Objective:</b> Circulating N-terminal pro b-type natriuretic peptide (NT-proBNP) is a classic diagnostic and prognostic marker for heart failure. However, it is inversely associated with diabetes risk. We aimed to investigate relationships of NT-proBNP with risk of diabetes-related complications in initially healthy individuals. <p><b>Research Design and Methods:</b> <a>We performed a case-cohort study within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort including a random subcohort (n=1294) and incident cases of type 2 diabetes (n=649) and cardiovascular diseases (CVD, n=478). Incident cases of type 2 diabetes (n=545) were followed up for micro- (n=133) and macrovascular (n=50) complications. Plasma NT-proBNP was measured at baseline in initially healthy participants.</a></p> <p><b>Results: </b><a></a><a>In multivariable models, NT-proBNP was linearly inversely associated with incident type 2 diabetes, HR (95% CI) per doubling in NT-proBNP: 0.91 (0.86; 0.98). The association was only observable in women, HR (95%CI): 0.80 (0.72; 0.90), compared to 0.98 (0.91; 1.07) in men. Among persons with incident diabetes, NT-proBNP was positively associated with diabetes complications, HR (95% CI): 1.31 (1.13; 1.53) for overall, 1.20 (1.01; 1.43) for micro- and 1.37 (1.03; 1.83) for macrovascular complications. </a></p> <b>Conclusions: </b><a>Although higher NT-proBNP levels are associated with lower diabetes risk, in persons who develop diabetes NT-proBNP is a biomarker for vascular complications independent of potential confounders. </a><a>Thus, NT-proBNP might be informative to monitor risk for diabetes-related micro- and macrovascular complications, which should be further explored in future prospective studies.</a>


2021 ◽  
Author(s):  
Sara Sokooti Oskooei ◽  
Jose L Flores-Guerrero ◽  
Hiddo J.L Heerspink ◽  
Margery A Connelly ◽  
Stephan J.L Bakker ◽  
...  

Abstract Background: Triglyceride-rich lipoproteins particles (TRLP) and low density lipoprotein particles (LDLP) vary in size. Their association with β-cell function is not well described. We determined associations of TRLP and LDLP subfractions with β-cell function, and evaluated their associations with incident T2D in the general population.Methods: We included 4818 subjects of the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study without T2D at baseline. TRLP and LDLP subfraction concentrations and their average sizes were measured using the LP4 algorithm of the Vantera nuclear magnetic resonance platform. HOMA-IR was used as measure of insulin resistance. HOMA-β was used as a proxy of β-cell function.Results: In subjects without T2D at baseline, very large TRLP, large LDLP and LDL size were inversely associated with HOMA-β, whereas large TRLP, medium TRLP and TRL size were positively associated with HOMA-β taking account of HOMA-IR. During a median follow-up of 7.3 years, 263 individuals developed T2D. In multivariable-adjusted Cox regression models, higher concentrations of total, very large, large, and very small TRLP and TRL size were associated with an increased T2D risk after adjustment for relevant covariates, including age, sex, BMI, HDL-C, HOMA-β, and HOMA-IR. On the contrary, higher concentrations of large LDLP and LDL size were associated with a lower risk of developing T2D.Conclusions: Specific TRL and LDL particle characteristics are associated with β-cell function taking account of HOMA-IR. Moreover, TRL and LDL particle characteristics are differently associated with incident T2D, even when taking account of HOMA-β and HOMA-IR.


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