Baseline High-Sensitivity C-Reactive Protein Predicts Macrovascular and Microvascular Complications of Type 2 Diabetes: A Population-Based Study

Background/Aims: This prospective study is aimed at examining the predictive value of high-sensitivity C-reactive protein (hs-CRP) for coronary heart disease (CHD) events and microvascular complications of type 2 diabetes mellitus (T2DM). Methods: A population-based study (NCT02958579) was conducted on 1,301 participants with T2DM (mean follow-up of 7.5 years). Risk assessment for vascular events was done at baseline, and serum hs-CRP was measured. End points of this study include CHD events, diabetic retinopathy, neuropathy, and diabetic kidney disease. Individuals with unavailable data or hs-CRP >20 mg/L were excluded. The discrimination and reclassification improvement of study end points were tested after addition of hs-CRP to traditional risk factors. Results: Median serum hs-CRP was 2.00 ranging from 0.1 to 17 mg/L. Hazards ratio of each SD increment in baseline hs-CRP was 1.028 (1.024–1.032) for CHD, 1.025 (1.021–1.029) for diabetic neuropathy, 1.037 (1.030–1.043) for diabetic retinopathy, and 1.035 (1.027–1.043) for diabetic kidney disease. The addition of hs-CRP to traditional risk factors of vascular complications of T2DM improved discrimination of all end points (p < 0.001). Net reclassification improvement ranged from 8% for diabetic neuropathy to 31% for diabetic kidney disease (p < 0.05). Conclusion: Baseline hs-CRP predicts both of CHD events and microvascular complications of patients with T2D.

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Serum cell-free DNA and progression of diabetic kidney disease: a prospective study

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2019-001078 ◽

2020 ◽

Vol 8 (1) ◽

pp. e001078 ◽

Cited By ~ 3

Author(s):

Xuan Li ◽

RenZhi Hu ◽

Ting Luo ◽

Chuan Peng ◽

Lilin Gong ◽

...

Keyword(s):

Kidney Disease ◽

Prospective Study ◽

Diabetic Kidney Disease ◽

High Sensitivity ◽

Cell Free Dna ◽

Diabetic Kidney ◽

Reactive Protein ◽

Free Dna ◽

A Prospective Study

AimsCell-free DNA (cfDNA) is associated with diabetes and cardiovascular diseases. Our study was to evaluate whether serum cfDNA could predict the progression of diabetic kidney disease (DKD).MethodsIn this prospective study, a total of 160 patients with DKD were enrolled, and the kidney function was followed up by measurement of estimated glomerular filtration rate (eGFR) and urinary albumin–creatinine ratio (UACR) for three consecutive years. At baseline, concentrations of serum cfDNA were measured. DKD progression was defined as two-continuous decrease in eGFR and changes of UACR from less than 300 mg/g at baseline to higher than 300 mg/g at last follow-up. Regression models were used to analyze associations of serum cfDNA with the DKD progression.ResultsIn total, 131 patients finished all the follow-up visits. At the end of the study, 64 patients showed decreased eGFR and 29 patients had changes of UACR from less than 300 mg/g at baseline to higher than 300 mg/g at follow-up. At baseline, the progression group had higher serum cfDNA levels than the non-progression group (960.49 (816.53, 1073.65) ng/mL vs 824.51 (701.34, 987.06) ng/mL, p=0.014). Serum cfDNA levels were significantly negatively associated with the 1.5-year eGFR change (r=−0.219 p=0.009) and 3-year eGFR change (r=−0.181, p=0.043). Multivariate logistic analyses showed that after adjustment of age, gender, body mass index, fast plasma glucose, smoking, triglycerides, total cholesterol, duration of diabetes, systolic blood pressure, diabetic retinopathy, eGFR, high sensitivity C-reactive protein, angiotensin receptor blocker/ACE inhibitor usage, with the increase of one SD of serum cfDNA levels, the risk of DKD progression increased by 2.4 times (OR, 2.46; 95% CI 1.84 to 4.89).ConclusionSerum cfDNA is closely associated with DKD, and it might be a predictor of DKD progression in patients with type 2 diabetes.

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Non-Hepatic Alkaline Phosphatase, hs-CRP and Progression of Vertebral Fracture in Patients with Rheumatoid Arthritis: A Population-Based Longitudinal Study

Journal of Clinical Medicine ◽

10.3390/jcm7110439 ◽

2018 ◽

Vol 7 (11) ◽

pp. 439 ◽

Cited By ~ 6

Author(s):

Jih-Chen Yeh ◽

Chang-Chin Wu ◽

Cheuk-Sing Choy ◽

Shu-Wei Chang ◽

Jian-Chiun Liou ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Alkaline Phosphatase ◽

Cox Regression ◽

High Sensitivity ◽

Population Based ◽

Reactive Protein ◽

Prognostic Assessment ◽

Product Term ◽

Hs Crp ◽

Stratified Analysis

Background: Interactions and early warning effects of non-hepatic alkaline phosphatase (NHALP) and high-sensitivity C-reactive protein (hs-CRP) on the progression of vertebral fractures (VFs) in patients with rheumatoid arthritis (RA) remain unclear. We aim to explore whether serum concentrations of NHALP and hs-CRP could serve as a promising dual biomarker for prognostic assessment of VF progression. Methods: Unadjusted and adjusted hazard ratios (aHRs) of VF progression were calculated for different categories of serum NHALP and hs-CRP using the Cox regression model in RA patients. The modification effect between serum NHALP and hs-CRP on VF progression was determined using an interaction product term. Results: During 4489 person-years of follow-up, higher NHALP (>125 U/L) and hs-CRP (>3.0 mg/L) were robustly associated with incremental risks of VF progression in RA patients (aHR: 2.2 (95% confidence intervals (CIs): 1.2–3.9) and 2.0 (95% CI: 1.3–3.3) compared to the lowest HR category, respectively). The interaction between NHALP and hs-CRP on VF progression was statistically significant (p < 0.05). In the stratified analysis, patients with combined highest NHALP and hs-CRP had the greatest risk of VF progression (aHR: 4.9 (95% CI: 2.5–9.6)) compared to the lowest HR group (NHALP < 90 U/L and hs-CRP < 1 mg/L). Conclusions: In light of underdiagnoses of VFs and misleading diagnosis by single test, NHALP and hs-CRP could serve as compensatory biomarkers to predict subclinical VF progression in RA patients.

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Diabetic Kidney Disease in Childhood and Adolescence: Conventional and Novel Renoprotective Strategies

EMJ Nephrology ◽

10.33590/emjnephrol/20-00077 ◽

2020 ◽

pp. 68-77

Author(s):

Samuel N Uwaezuoke ◽

Adaeze C Ayuk

Keyword(s):

Diabetes Mellitus ◽

Kidney Disease ◽

Diabetic Kidney Disease ◽

Microvascular Complications ◽

Clinical Syndrome ◽

Clinical Staging ◽

Childhood And Adolescence ◽

Diabetic Kidney ◽

Haemodynamic Changes ◽

End Stage

Diabetic kidney disease (DKD) is defined as a clinical syndrome consisting of persistent macroalbuminuria, progressive decline in glomerular filtration rate (GFR), hypertension, increased cardiovascular disease events, and the associated mortality of these conditions. The disease evolves from the microvascular complications of poorly controlled Type 1 diabetes mellitus (T1DM) and Type 2 diabetes mellitus (T2DM). The pathogenic pathways comprise renal haemodynamic changes, ischaemia and inflammation, and overactive renin–angiotensin–aldosterone system (RAAS), through which several events cascade down from hyperglycaemia to renal fibrosis. Conventional and novel renoprotective strategies target modifiable DKD risk factors and specific stages of the pathogenic pathways, respectively. Although these strategies may slow DKD progression to end-stage kidney disease (ESKD), novel drugs are still undergoing trials for validation in human participants. This narrative review appraises these renoprotective strategies and highlights the current clinical staging and pathogenesis of the disease.

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GLP-1 receptor agonists in diabetic kidney disease: from the patient-side to the bench-side

AJP Renal Physiology ◽

10.1152/ajprenal.00211.2018 ◽

2018 ◽

Vol 315 (6) ◽

pp. F1519-F1525 ◽

Cited By ~ 16

Author(s):

Brad P. Dieter ◽

Radica Z. Alicic ◽

Katherine R. Tuttle

Keyword(s):

Kidney Disease ◽

Diabetic Kidney Disease ◽

Microvascular Complications ◽

Renin Angiotensin System ◽

Diabetic Kidney ◽

Receptor Agonists ◽

Patients With Diabetes ◽

Glucagon Like Peptide 1 ◽

Patient Side ◽

End Stage

Diabetic kidney disease (DKD), one of the most common and severe microvascular complications of diabetes, is the leading cause of chronic kidney disease and end-stage kidney disease worldwide. Since the development of renin-angiotensin system inhibition nearly three decades ago, no new therapeutic agents have received regulatory approval for treatment of DKD. Glucagon-like peptide-1 (GLP-1) receptor agonists, a class of newer antihyperglycemic agents, have shown promise for prevention of DKD onset and progression. This perspective summarizes clinical and experimental observations to give insight into biological mechanisms beyond glycemic control, such as natriuresis and anti-inflammatory actions, for preservation of kidney function in patients with diabetes.

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A population-based dietary inflammatory index predicts levels of C-reactive protein in the Seasonal Variation of Blood Cholesterol Study (SEASONS)

Public Health Nutrition ◽

10.1017/s1368980013002565 ◽

2013 ◽

Vol 17 (8) ◽

pp. 1825-1833 ◽

Cited By ~ 279

Author(s):

Nitin Shivappa ◽

Susan E Steck ◽

Thomas G Hurley ◽

James R Hussey ◽

Yunsheng Ma ◽

...

Keyword(s):

Seasonal Variation ◽

High Sensitivity ◽

Population Based ◽

Blood Cholesterol ◽

Dietary Inflammatory Index ◽

C Reactive Protein ◽

Dietary Recall ◽

Inflammatory Index ◽

Reactive Protein ◽

Hs Crp

AbstractObjectiveTo perform construct validation of the population-based Dietary Inflammatory Index (DII) using dietary data from two different dietary assessments and serum high-sensitivity C-reactive protein (hs-CRP) as the construct validator.DesignUsing data derived from (i) three 24 h dietary recalls (24HR) at baseline and at the end of each subsequent quarter (i.e. up to fifteen over a year) and (ii) a 7 d dietary recall (7DDR) measured at baseline and then quarterly, regression analyses were conducted to test the effect of the DII score on serum hs-CRP as dichotomous (≤3 mg/l, >3 mg/l), while controlling for important potential confounders.SettingExisting data from the Seasonal Variation of Blood Cholesterol Study (SEASONS), a longitudinal observational study of healthy participants recruited in Worcester, MA, USA and participants were followed for 1 year.SubjectsParticipants who had at least one hs-CRP measurement over her/his 1-year participation (n495 for 24HR,n559 for 7DDR).ResultsHigher DII scores were associated with values of hs-CRP >3 mg/l (OR = 1·08; 95 % CI 1·01, 1·16,P= 0·035 for the 24HR; and OR = 1·10; 95 % CI 1·02, 1·19,P= 0·015 for the 7DDR).ConclusionsThe population-based DII was associated with interval changes in hs-CRP using both the 24HR and 7DDR. The success of this first-of-a-kind attempt at relating individuals’ intakes of inflammation-modulating foods using this refined DII, and the finding that there is virtually no drop-off in predictive capability using a structured questionnaire in comparison to the 24HR standard, sets the stage for use of the DII in a wide variety of other epidemiological and clinical studies.

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C-reactive protein promotes diabetic kidney disease in a mouse model of type 1 diabetes

Diabetologia ◽

10.1007/s00125-011-2237-y ◽

2011 ◽

Vol 54 (10) ◽

pp. 2713-2723 ◽

Cited By ~ 40

Author(s):

F. Liu ◽

H. Y. Chen ◽

X. R. Huang ◽

A. C. K. Chung ◽

L. Zhou ◽

...

Keyword(s):

Type 1 Diabetes ◽

Kidney Disease ◽

Mouse Model ◽

Diabetic Kidney Disease ◽

C Reactive Protein ◽

Diabetic Kidney ◽

Reactive Protein

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Association of C-Reactive Protein, Interleukin-1 Receptor Antagonist and Adiponectin with the Metabolic Syndrome

Mediators of Inflammation ◽

10.1155/2007/93573 ◽

2007 ◽

Vol 2007 ◽

pp. 1-8 ◽

Cited By ~ 17

Author(s):

Juha Saltevo ◽

Mauno Vanhala ◽

Hannu Kautiainen ◽

Esko Kumpusalo ◽

Markku Laakso

Keyword(s):

Metabolic Syndrome ◽

Receptor Antagonist ◽

Interleukin 1 ◽

High Sensitivity ◽

Population Based ◽

C Reactive Protein ◽

Reactive Protein ◽

Interleukin 1 Receptor Antagonist ◽

The Metabolic Syndrome ◽

Hs Crp

This Finnish population-based study, mean age 46 years, evaluates the association of high-sensitivity C-reactive protein (hs-CRP), interleukin-1 receptor antagonist (IL-1Ra), and adiponectin with the NCEP and IDF definitions of metabolic syndrome (MetS). Adiponectin levels were higher, hs-CRP and IL-1Ra levels lower in subjects without MetS compared to subjects with MetS. If MetS was present according to both IDF and NCEP criteria, BMI, waist, triglycerides, hs-CRP, and IL-1Ra were significantly higher compared to subjects who had MetS according to either only IDF or only NCEP criteria. The hs-CRP, IL-1Ra, and adiponectin linearly correlated with the number of the components of MetS according to both definitions. Decreased levels of adiponectin and increased levels of hs-CRP and IL-1Ra are tightly associated with the components of MetS. Individuals who had MetS according to both criteria had the most adverse changes in cardiovascular risk factors.

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ApoD and ApoA-IV, novel proteomic components in HDL of diabetic kidney disease without dialysis

10.21203/rs.3.rs-33407/v2 ◽

2020 ◽

Author(s):

Monique FM Santana ◽

Aécio LA Lira ◽

Raphael Pinto ◽

Carlos A Minanni ◽

Amanda RM Silva ◽

...

Keyword(s):

Risk Factors ◽

Kidney Disease ◽

Chemical Modification ◽

Diabetic Kidney Disease ◽

Albumin Excretion Rate ◽

Ldl Oxidation ◽

Control Group ◽

Loss Of Function ◽

Diabetic Kidney ◽

Traditional Risk Factors

Abstract Background and aims: Diabetic kidney disease (DKD) is associated with lipid derangements worsening kidney function and enhancing cardiovascular (CVD) risk. The management of dyslipidemia, hypertension and other traditional risk factors does not completely prevent CVD complications bringing up the participation of untraditional risk factors such as advanced glycation end products (AGEs), carbamoylation and changes in HDL proteome and functionality. We analyzed HDL composition, proteome, chemical modification and functionality in non-dialytic DKD subjects categorized according to estimated glomerular filtration rate (eGFR) and urinary albumin excretion rate (AER). Methods: DKD individuals were divided in eGFR>60 mL/min/1.73 m2 plus AER stages A1 and A2 (n=10) and eGFR<60 plus A3 (n=25) and matched by age with control subjects (eGFR>60; n=8). Results: Targeted proteomic analyses quantified 28 proteins associated with HDL in all groups, although only 2 were more expressed in eGFR<60+A3 group in comparison to controls: apolipoprotein D (apoD) and apoA-IV. HDL from eGFR<60+A3 presented higher levels of total AGEs (20%), pentosidine (6.3%) and carbamoylation (4.2 x) and a reduced ability in removing 14C-cholesterol from macrophages (33%) in comparison to controls. The antioxidant role of HDL (lag time for LDL oxidation) was similar among groups but HDL from eGFR<60+A3 presented a higher ability in inhibiting the secretion of IL6 and TNF alpha (95%) in LPS-elicited macrophages in comparison to control group. Conclusion: The increment in ApoD and ApoA-IV seems to counteract the HDL chemical modification by AGE and carbamoylation that contributes for HDL loss of function in well-established DKD.

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Obstructive sleep apnoea and the risk for coronary heart disease and type 2 diabetes: a longitudinal population-based study in Finland

BMJ Open ◽

10.1136/bmjopen-2018-022752 ◽

2018 ◽

Vol 8 (10) ◽

pp. e022752 ◽

Cited By ~ 8

Author(s):

Satu Strausz ◽

Aki S. Havulinna ◽

Tiinamaija Tuomi ◽

Adel Bachour ◽

Leif Groop ◽

...

Keyword(s):

Coronary Heart Disease ◽

Heart Disease ◽

Kidney Disease ◽

Diabetic Kidney Disease ◽

Population Based ◽

Sleep Apnoea ◽

Population Based Study ◽

Diabetic Kidney ◽

Obstructive Sleep

ObjectiveTo evaluate if obstructive sleep apnoea (OSA) modifies the risk of coronary heart disease, type 2 diabetes (T2D) and diabetic complications in a gender-specific fashion.Design and settingA longitudinal population-based study with up to 25-year follow-up data on 36 963 individuals (>500 000 person years) from three population-based cohorts: the FINRISK study, the Health 2000 Cohort Study and the Botnia Study.Main outcome measuresIncident coronary heart disease, diabetic kidney disease, T2D and all-cause mortality from the Finnish National Hospital Discharge Register and the Finnish National Causes-of-Death Register.ResultsAfter adjustments for age, sex, region, high-density lipoprotein (HDL) and total cholesterol, current cigarette smoking, body mass index, hypertension, T2D baseline and family history of stroke or myocardial infarction, OSA increased the risk for coronary heart disease (HR=1.36, p=0.0014, 95% CI 1.12 to 1.64), particularly in women (HR=2.01, 95% CI 1.31 to 3.07, p=0.0012). T2D clustered with OSA independently of obesity (HR=1.48, 95% CI 1.26 to 1.73, p=9.11×10−7). The risk of diabetic kidney disease increased 1.75-fold in patients with OSA (95% CI 1.13 to 2.71, p=0.013). OSA increased the risk for coronary heart disease similarly among patients with T2D and in general population (HR=1.36). All-cause mortality was increased by OSA in diabetic individuals (HR=1.35, 95% CI 1.06 to 1.71, p=0.016).ConclusionOSA is an independent risk factor for coronary heart disease, T2D and diabetic kidney disease. This effect is more pronounced even in women, who until now have received less attention in diagnosis and treatment of OSA than men.

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