Angiopoietin 2 and Neuropeptide Y are Associated with Diabetic Kidney
                    Disease in Type 1 Diabetes Mellitus

Abstract Background Serum angiopoietin 2 levels have been associated with endothelial dysfunction and diabetic kidney disease. Derangements in autonomous nervous system lead to increased production of vasoconstrictory and angiogenic mediators such as norepinephrine and neuropeptide Y and are associated with increased risk of microvascular complications. Aim To investigate associations between angiopoietin 2, neuropeptide Y and diabetic kidney disease in patients with type 1 diabetes mellitus. Methods 289 patients with type 1 diabetes mellitus duration > 1 year were included. Patients were stratified according to presence of diabetic nephropathy (macroalbuminuria, estimated glomerular filtration rate<60 ml/min/1.73 m2 or end-stage renal disease). Angiopoietin 2 was measured by Luminex technology. Neuropeptide Y was measured by ELISA. Results Patients with diabetic nephropathy had significantly increased levels of angiopoietin 2 (4020.5 (2172.4–5778.1) pg/ml vs. 2001.0 (1326.7–2862.7) pg/ml) and neuropeptide Y (18.22 (14.85–21.85) ng/ml vs. 12.91 (9.96–17.07) ng/ml). Higher levels of angiopoietin 2 and neuropeptide Y were observed also in patients with arterial hypertension. Angiopoietin 2 and neuropeptide Y correlated significantly (ρ=0.245, p<0.001). Both biomarkers were significant predictors of estimated glomerular filtration rate and diabetic nephropathy in univariate regression models. In the fully adjusted regression models and after application of a stepwise selection regression method, angiopoietin 2 demonstrated a stronger predictive power for diabetic nephropathy compared to neuropeptide Y. Conclusion Diabetic nephropathy is associated with increased serum concentrations of angiopoietin 2 (marker of endothelial dysfunction) and neuropeptide Y (marker of sympathetic activity) in type 1 diabetes. Angiopoietin 2 is a more potent predictor of diabetic nephropathy compared to neuropeptide Y.

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B cells in type 1 diabetes mellitus and diabetic kidney disease

Nature Reviews Nephrology ◽

10.1038/nrneph.2017.138 ◽

2017 ◽

Vol 13 (11) ◽

pp. 712-720 ◽

Cited By ~ 17

Author(s):

Mia J. Smith ◽

Kimber M. Simmons ◽

John C. Cambier

Keyword(s):

Diabetes Mellitus ◽

Type 1 Diabetes ◽

B Cells ◽

Kidney Disease ◽

Type 1 Diabetes Mellitus ◽

Diabetic Kidney Disease ◽

Diabetic Kidney

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Urinary Extracellular Vesicles as a Source of NGAL for Diabetic Kidney Disease Evaluation in Children and Adolescents With Type 1 Diabetes Mellitus

Frontiers in Endocrinology ◽

10.3389/fendo.2021.654269 ◽

2022 ◽

Vol 12 ◽

Author(s):

Francisca Ugarte ◽

Daniela Santapau ◽

Vivian Gallardo ◽

Carolina Garfias ◽

Anahí Yizmeyián ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 1 Diabetes ◽

Kidney Disease ◽

Type 1 Diabetes Mellitus ◽

Extracellular Vesicles ◽

Diabetic Kidney Disease ◽

Tubular Damage ◽

Activated T Cells ◽

Diabetic Kidney

BackgroundTubular damage has a role in Diabetic Kidney Disease (DKD). We evaluated the early tubulointerstitial damage biomarkers in type-1 Diabetes Mellitus (T1DM) pediatric participants and studied the correlation with classical DKD parameters.MethodsThirty-four T1DM and fifteen healthy participants were enrolled. Clinical and biochemical parameters [Glomerular filtration Rate (GFR), microalbuminuria (MAU), albumin/creatinine ratio (ACR), and glycated hemoglobin A1c (HbA1c)] were evaluated. Neutrophil gelatinase-associated lipocalin (NGAL), Hypoxia-inducible Factor-1α (HIF-1α), and Nuclear Factor of Activated T-cells-5 (NFAT5) levels were studied in the supernatant (S) and the exosome-like extracellular vesicles (E) fraction from urine samples.ResultsIn the T1DM, 12% had MAU >20 mg/L, 6% ACR >30 mg/g, and 88% had eGFR >140 ml/min/1.72 m2. NGAL in the S (NGAL-S) or E (NGAL-E) fraction was not detectable in the control. The NGAL-E was more frequent (p = 0.040) and higher (p = 0.002) than NGAL-S in T1DM. The T1DM participants with positive NGAL had higher age (p = 0.03), T1DM evolution (p = 0.03), and serum creatinine (p = 0.003) than negative NGAL. The NGAL-E correlated positively with tanner stage (p = 0.0036), the median levels of HbA1c before enrollment (p = 0.045) and was independent of ACR, MAU, and HbA1c at the enrollment. NFAT5 and HIF-1α levels were not detectable in T1DM or control.ConclusionUrinary exosome-like extracellular vesicles could be a new source of early detection of tubular injury biomarkers of DKD in T1DM patients.

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Optical Coherence Tomography Angiography in Type 1 Diabetes Mellitus—Report 2: Diabetic Kidney Disease

Journal of Clinical Medicine ◽

10.3390/jcm11010197 ◽

2021 ◽

Vol 11 (1) ◽

pp. 197

Author(s):

Aníbal Alé-Chilet ◽

Carolina Bernal-Morales ◽

Marina Barraso ◽

Teresa Hernández ◽

Cristian Oliva ◽

...

Keyword(s):

Diabetes Mellitus ◽

Optical Coherence Tomography ◽

Type 1 Diabetes ◽

Kidney Disease ◽

Type 1 Diabetes Mellitus ◽

Diabetic Kidney Disease ◽

Optical Coherence Tomography Angiography ◽

Optical Coherence ◽

Diabetic Kidney

The purpose of this study is to investigate potential associations between optical coherence tomography angiography (OCTA) parameters and diabetic kidney disease (DKD) categories in type 1 diabetes mellitus (T1DM) patients and controls. A complete ocular and systemic examination, including OCTA imaging tests and bloods, was performed. OCTA parameters included vessel density (VD), perfusion density (PD), foveal avascular zone area (FAZa), perimeter (FAZp) and circularity (FAZc) in the superficial vascular plexus, and DKD categories were defined according to glomerular filtration rate (GFR), albumin-creatinine ratio (ACR) and KDIGO prognosis risk classifications. A total of 425 individuals (1 eye/1 patient) were included. Reduced VD and FAZc were associated with greater categories of GFR (p = 0.002, p = 0.04), ACR (p = 0.003, p = 0.005) and KDIGO risk prognosis classifications (p = 0.002, p = 0.005). FAZc was significantly reduced in greater KDIGO prognosis risk categories (low risk vs. moderate risk, 0.65 ± 0.09 vs. 0.60 ± 0.07, p < 0.05). VD and FAZc presented the best diagnostic performance in ROCs. In conclusion, OCTA parameters, such as VD and FAZc, are able to detect different GFR, ACR, and KDIGO categories in T1DM patients and controls in a non-invasive, objective quantitative way. FAZc is able to discriminate within T1DM patients those with greater DKD categories and greater risk of DKD progression.

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Vitamin D on Early Stages of Diabetic Kidney Disease: A Cross-sectional Study in Patients with Type 1 Diabetes Mellitus

Frontiers in Endocrinology ◽

10.3389/fendo.2016.00149 ◽

2016 ◽

Vol 7 ◽

Cited By ~ 2

Author(s):

João Soares Felício ◽

Rafael Mendonça Luz ◽

Franciane Trindade Cunha de Melo ◽

Fabricio de Souza Resende ◽

Alana Ferreira de Oliveira ◽

...

Keyword(s):

Diabetes Mellitus ◽

Vitamin D ◽

Type 1 Diabetes ◽

Kidney Disease ◽

Type 1 Diabetes Mellitus ◽

Diabetic Kidney Disease ◽

Cross Sectional Study ◽

Sectional Study ◽

Cross Sectional

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Mannan-Binding Lectin in Diabetic Kidney Disease: The Impact of Mouse Genetics in a Type 1 Diabetes Model

Experimental Diabetes Research ◽

10.1155/2012/678381 ◽

2012 ◽

Vol 2012 ◽

pp. 1-9 ◽

Cited By ~ 11

Author(s):

Jakob Appel Østergaard ◽

Mette Bjerre ◽

Satish Posettihalli RamachandraRao ◽

Kumar Sharma ◽

Jens Randel Nyengaard ◽

...

Keyword(s):

Type 1 Diabetes ◽

Diabetic Nephropathy ◽

Kidney Disease ◽

Genetic Background ◽

Diabetic Kidney Disease ◽

Diabetic Kidney ◽

Mannan Binding Lectin ◽

The Impact ◽

Binding Lectin

Background. Mannan-binding lectin (MBL) is involved in the development of diabetic nephropathy. MBL is a part of the innate immune system where it can activate the complement system. Serum MBL level predicts later renal impairment in diabetes patients. Direct involvement of MBL in the development of diabetic kidney disease is observed in one animal strain. However, this involvement may differ among the animal strains. We thus examined the impact of the genetic background on the role of MBL in diabetic nephropathy.Materials/Methods. C57BL/6JBomTac and 129S6/SvEvTac mice were compared. In both strains, experimental type 1 diabetes was induced in wild-type (WT) and MBL-knockout (MBL-KO) mice by streptozotocin. Nondiabetic WT and MBL-KO mice were used as controls. We tested if MBL modified the diabetes-induced kidney changes by two-way ANOVA allowing for interaction.Results. MBL aggravated diabetes-induced kidney growth and glomerulus enlargement in C57BL/6JBomTac mice. MBL did not modify diabetes effects on glomerular basement membrane thickness or mesangial volume in any strain. Diabetes-induced changes in renal gene transcription of growth factors and matrix components were unaffected by MBL.Conclusions. Strain-specific MBL effects were found on downstream diabetic kidney changes. This emphasizes the importance of genetic background in this model of diabetic complications.

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