scholarly journals Profibrotic circulating proteins and risk of early progressive renal decline in Type 2 Diabetes patients with and without albuminuria

2020 ◽  
Author(s):  
Katsuhito Ihara ◽  
Jan Skupien ◽  
Hiroki Kobayashi ◽  
Zaipul I. Md Dom ◽  
Jonathan M. Wilson ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Core Domain ◽  
Fibrotic Process ◽  
Baseline Levels ◽  
Design And Methods ◽  
Circulating Levels ◽  
Index Combination

<b>OBJECTIVE</b>: The role of fibrosis in early progressive renal decline in type 2 diabetes is unknown. Circulating WFDC2 (WAP four-disulfide core domain protein 2) and MMP-7 (Matrilysin) are postulated to be biomarkers of renal fibrosis. This study examined an association of circulating levels of these proteins with early progressive renal decline. <p><b>RESEARCH DESIGN AND METHODS</b>: Individuals with type 2 diabetes enrolled in the Joslin Kidney Study with eGFR ≥60 ml/min/1.73m<sup>2</sup> were followed for 6-12 years to ascertain fast early progressive renal decline defined as eGFR loss ≥5 ml/min/1.73m<sup>2</sup>/year. </p> <p><b>RESULTS</b>: A total of 1,181 individuals were studied: 681 without and 500 with albuminuria. Median eGFR and ACR at baseline were 97 ml/min/1.73m<sup>2</sup> and 24 mg/g, respectively. During follow-up, 152 individuals experienced fast early progressive renal decline: 6.9% in those with normoalbuminuria and 21% with albuminuria. In both subgroups risk of renal decline increased with increasing baseline levels of WFDC2 (p <0.0001) and MMP-7 (p <0.0001). After adjustment for relevant clinical characteristics and known biomarkers, an increase by one quartile in the Fibrosis Index (combination of levels of WFDC2 and MMP-7) was associated with higher risk of renal decline (OR 1.63; 95% CI 1.30-2.04). The association was similar and statistically significant among patients with and without albuminuria. </p> <p><b>CONCLUSIONS: </b>Elevation of circulating profibrotic proteins is associated with the development of early progressive renal decline in type 2 diabetes. This association is independent from albuminuria status and points to the importance of the fibrotic process in development of early renal decline. </p>

scholarly journals Profibrotic circulating proteins and risk of early progressive renal decline in Type 2 Diabetes patients with and without albuminuria

2020 ◽  
Author(s):  
Katsuhito Ihara ◽  
Jan Skupien ◽  
Hiroki Kobayashi ◽  
Zaipul I. Md Dom ◽  
Jonathan M. Wilson ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Core Domain ◽  
Fibrotic Process ◽  
Baseline Levels ◽  
Design And Methods ◽  
Circulating Levels ◽  
Index Combination

<b>OBJECTIVE</b>: The role of fibrosis in early progressive renal decline in type 2 diabetes is unknown. Circulating WFDC2 (WAP four-disulfide core domain protein 2) and MMP-7 (Matrilysin) are postulated to be biomarkers of renal fibrosis. This study examined an association of circulating levels of these proteins with early progressive renal decline. <p><b>RESEARCH DESIGN AND METHODS</b>: Individuals with type 2 diabetes enrolled in the Joslin Kidney Study with eGFR ≥60 ml/min/1.73m<sup>2</sup> were followed for 6-12 years to ascertain fast early progressive renal decline defined as eGFR loss ≥5 ml/min/1.73m<sup>2</sup>/year. </p> <p><b>RESULTS</b>: A total of 1,181 individuals were studied: 681 without and 500 with albuminuria. Median eGFR and ACR at baseline were 97 ml/min/1.73m<sup>2</sup> and 24 mg/g, respectively. During follow-up, 152 individuals experienced fast early progressive renal decline: 6.9% in those with normoalbuminuria and 21% with albuminuria. In both subgroups risk of renal decline increased with increasing baseline levels of WFDC2 (p <0.0001) and MMP-7 (p <0.0001). After adjustment for relevant clinical characteristics and known biomarkers, an increase by one quartile in the Fibrosis Index (combination of levels of WFDC2 and MMP-7) was associated with higher risk of renal decline (OR 1.63; 95% CI 1.30-2.04). The association was similar and statistically significant among patients with and without albuminuria. </p> <p><b>CONCLUSIONS: </b>Elevation of circulating profibrotic proteins is associated with the development of early progressive renal decline in type 2 diabetes. This association is independent from albuminuria status and points to the importance of the fibrotic process in development of early renal decline. </p>

scholarly journals Low levels of circulating anti-ageing hormone Klotho predict the onset and progression of diabetic retinopathy

2020 ◽  
Vol 17 (6) ◽  
pp. 147916412097090
Author(s):  
Antonella Corcillo ◽  
Nikolaos Fountoulakis ◽  
Angela Sohal ◽  
Frederick Farrow ◽  
Salma Ayis ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Retinopathy ◽  
Primary Outcome ◽  
Increased Risk ◽  
Risk Of Progression ◽  
Diabetic Eye Disease ◽  
Circulating Levels

Background: Klotho is a circulating anti-ageing hormone that predicts progression of cardiovascular and renal disease. The role of Klotho in diabetic retinopathy is unknown. Methods: We performed a single-centre observational study of 81 people (males 62%) with type 2 diabetes followed for a median of 44 months. Circulating levels of Klotho and other markers, were measured from stored samples. The primary outcome was progression of retinopathy defined as new onset retinopathy or step change in retinopathy grading. Results: During follow-up, 46 (57%) people reached the primary outcome. People with progression of retinopathy had lower levels of serum Klotho as compared to those without (median (interquartile range) 226.9 (171.1–394.0) vs 484.5 (221.8–709.9) pg/ml, p = 0.001). In multivariable logistic regression analyses, baseline Klotho level was the only variable independently associated with reduced risk of progression of retinopathy. Our results suggest that a halving of circulating Klotho levels increases the risk of retinopathy progression by 44%. Conclusion: In people with type 2 diabetes, lower circulating levels of the vascular protective hormone Klotho are associated with increased risk of progression of diabetic retinopathy. Klotho may be a novel biomarker and potential treatment target for diabetic eye disease.

scholarly journals Role of vitamin D in energy and bone metabolism in postmenopausal women with type 2 diabetes mellitus: A 6-month follow-up evaluation

2017 ◽  
Vol 9 (1) ◽  
pp. 211-222 ◽  
Author(s):  
Makiko Ogata ◽  
Naoko Iwasaki ◽  
Risa Ide ◽  
Miho Takizawa ◽  
Mizuho Tanaka ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Vitamin D ◽  
Type 2 Diabetes Mellitus ◽  
Bone Metabolism ◽  
Postmenopausal Women

Role of probiotics for the treatment of peri-implant mucositis in patients with and without type-2 diabetes mellitus

2020 ◽  
Author(s):  
Fawaz Alqahtani ◽  
Maha Alshaikh ◽  
Abid Mehmood ◽  
Nasser Alqhtani ◽  
Fahad Alkhtani ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Patients ◽  
Treatment Procedure ◽  
Inflammatory Parameters ◽  
Probing Depth ◽  
Crestal Bone Loss ◽  
Group 2

The hypothesis was that probiotic therapy (PT) does not offer additional benefits to mechanical debridement (MD) for treatment of diabetic subjects with peri-implant mucositis (PM). This study compared the influence of PT as an adjunct to MD for the treatment of PM in type2 diabetic and non-diabetic patients over a 12-month follow-up period. Patients with and without type-2 diabetes were encompassed. Based upon treatment-procedure, PM patients were categorized into 2 groups: (a) Non-surgical + PT; and (b) Group-2: Non-surgical MD alone. Demographics and education statuses were recorded. Gingival (GI) and plaque (PI) indices, crestal bone loss (CBL) and probing depth (PD were measured at baseline and after 6- and 12-months. Significant differences were detected with P&lt;0.01. The HbA1c was significantly higher in diabetic patients at all time durations than patients without type-2 diabetes (P&lt;0.001). Baseline GI, PI, PD and CBL) were comparable in all groups. In patients with type-2-diabetes, there was no difference in PI, GI, PD and CBL at 6- and 12-months’ follow-up. In patients without type-2 diabetes, there was a significant reduction in PI (P&lt;0.01), GI (P&lt;0.01), and PD (P&lt;0.01) at 6-months and 1-year follow-up than their values at baseline. In patients without type-2 diabetes, MD with or without adjunct PT reduces soft tissue inflammatory parameters in patients with PM.

Abstract P274: Kidney Filtration Markers and the Risk of Clinical Outcomes in Individuals With Type 2 Diabetes in the Advance Trial

Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Hyunju Kim ◽  
Dan Wang ◽  
John Chalmers ◽  
Mark Woodward ◽  
Elizabeth Selvin ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Clinical Outcomes ◽  
Regression Models ◽  
Cox Regression ◽  
All Cause Mortality ◽  
Baseline Levels ◽  
Controlled Evaluation ◽  
Egfr Decline

Introduction: Creatinine-based estimated glomerular filtration rate (eGFR) is biased in the setting of obesity and other conditions. Alternative kidney filtration markers may be particularly useful in adults with diabetes, but few studies examined the risk of clinical outcomes associated with filtration markers in adults with type 2 diabetes. Objective: We evaluated whether baseline levels and change in eGFR based on creatinine (Cr), cystatin C (Cys), and B 2 -microglobulin (B2M) were associated with the risk of clinical outcomes among individuals with type 2 diabetes. Methods: In the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial, Cr, Cys, and B2M were measured in 7,217 participants at baseline and a random sample of 640 participants at the 1 year visit. We categorized baseline eGFR Cr , eGFR Cys , eGFR B2M , and the average across the 3 eGFR estimates (eGFR avg ) into quarters, and examined associations with major macrovascular and microvascular events together, and separately, and all-cause mortality using Cox regression models, adjusting for established risk factors. We also examined associations with continuous eGFR decline and increase (per 30%). Results: Over a median follow-up of 5 years, 1,313 combined major macrovascular (n=748) and microvascular events (n=637), and 743 deaths occurred. Lower levels of eGFR based on all three filtration markers individually and combined were associated with 1.5 to 2.2 times higher risk of combined major macrovascular and microvascular events, with similar patterns for other outcomes ( Table ). Per 30% decline in eGFR Cys and eGFR avg were associated with a >2-fold higher risk of all clinical outcomes, after additional adjustment of baseline eGFR. Conclusions: In adults with type 2 diabetes, baseline levels of eGFR based on alternative filtration markers and per 30% decline in eGFR Cys and eGFR avg were consistently associated with all clinical outcomes.

Role of glucose and insulin resistance in development of type 2 diabetes mellitus: results of a 25-year follow-up study

The Lancet ◽  
1992 ◽  
Vol 340 (8825) ◽  
pp. 925-929 ◽  
Author(s):  
B.C. Martin ◽  
J.H. Warram ◽  
A.S. Krolewski ◽  
J.S. Soeldner ◽  
C.R. Kahn ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Follow Up Study

scholarly journals The duration of obesity and the risk of type 2 diabetes

2010 ◽  
Vol 14 (1) ◽  
pp. 119-126 ◽  
Author(s):  
Asnawi Abdullah ◽  
Johannes Stoelwinder ◽  
Susan Shortreed ◽  
Rory Wolfe ◽  
Christopher Stevenson ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cox Models ◽  
Family History Of Diabetes ◽  
Heart Study ◽  
Diabetes Status ◽  
Relevant Risk Factor ◽  
History Of

AbstractObjectiveThe evidence for the association between obesity and the risk of type 2 diabetes has been derived mainly from the analysis of the degree of obesity. The role of the duration of obesity as an independent risk has not been fully explored. The objective of the present study was to investigate the association between the duration of obesity and the risk of type 2 diabetes.DesignProspective cohort study.SettingThe Framingham Heart Study (FHS), follow-up from 1948 to 1998.SubjectsA total of 1256 FHS participants who were free from type 2 diabetes at baseline, but were obese on at least two consecutive of the study’s twenty-four biennial examinations, were included. Type 2 diabetes status was collected throughout the 48 years of follow-up of the study. The relationship between duration of obesity and type 2 diabetes was analysed using time-dependent Cox models, adjusting for a number of covariates.ResultsThe unadjusted hazard ratio (HR) for the risk of type 2 diabetes for men was 1·13 (95 % CI 1·09, 1·17) and for women was 1·12 (95 % CI 1·08, 1·16) per additional 2-year increase in the duration of obesity. Adjustment for sociodemographic variables, family history of diabetes, health behaviour and physical activity made little difference to these HR. For women the evidence of a dose–response relationship was less clear than for men, particularly for women with an older age at obesity onset.ConclusionsThe duration of obesity is a relevant risk factor for type 2 diabetes, independent of the degree of BMI.

scholarly journals Plasma protein N-glycosylation is associated with cardiovascular disease, nephropathy, and retinopathy in type 2 diabetes

2021 ◽  
Vol 9 (1) ◽  
pp. e002345
Author(s):  
Elham Memarian ◽  
Leen M 't Hart ◽  
Roderick C Slieker ◽  
Roosmarijn F L Lemmers ◽  
Amber A van der Heijden ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Diabetes Complications ◽  
Cox Regression ◽  
Structural Features ◽  
Pngase F ◽  
High Level ◽  
Design And Methods

IntroductionAlthough associations of total plasma N-glycome (TPNG) with type 2 diabetes have been reported, little is known on the role of TPNG in type 2 diabetes complications, a major cause of type 2 diabetes-related morbidity and mortality. Here, we assessed TPNG in relation to type 2 diabetes complications in subsamples of two Dutch cohorts using mass spectrometry (n=1815 in DiaGene and n=1518 in Hoorn Diabetes Care System).Research design and methodsBlood plasma samples and technical replicates were pipetted into 96-well plates in a randomized manner. Peptide:N-glycosidase F (PNGase F) was used to release N-glycans, whereafter sialic acids were derivatized for stabilization and linkage differentiation. After total area normalization, 68 individual glycan compositions were quantified in total and were used to calculate 45 derived traits which reflect structural features of glycosylation. Associations of glycan features with prevalent and incident microvascular or macrovascular complications were tested in logistic and Cox regression in both independent cohorts and the results were meta-analyzed.ResultsOur results demonstrated similarities between incident and prevalent complications. The strongest association for prevalent cardiovascular disease was a high level of bisection on a group of diantennary glycans (A2FS0B; OR=1.38, p=1.34×10−11), while for prevalent nephropathy the increase in 2,6-sialylation on triantennary glycans was most pronounced (A3E; OR=1.28, p=9.70×10−6). Several other TPNG features, including fucosylation, galactosylation, and sialylation, firmly demonstrated associations with prevalent and incident complications of type 2 diabetes.ConclusionsThese findings may provide a glance on how TPNG patterns change before complications emerge, paving the way for future studies on prediction biomarkers and potentially disease mechanisms.

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