scholarly journals Evidence of Early Diabetic Nephropathy in Pediatric Type 1 Diabetes

2021 ◽  
Vol 12 ◽  
Author(s):  
Leena Mamilly ◽  
Lucy D. Mastrandrea ◽  
Claudia Mosquera Vasquez ◽  
Brett Klamer ◽  
Mahmoud Kallash ◽  
...  

BackgroundDiabetic nephropathy (DN) is one of the most common microvascular complications in type 1 diabetes Mellitus (T1D). Urinary markers of renal damage or oxidative stress may signal early stages of DN. The association of these markers with blood pressure (BP) patterns and glycemic variability (GV) in children is yet to be explored.MethodsSubjects between the ages of 10 and 21 years with T1D were enrolled. Continuous glucose monitoring (CGM) and ambulatory blood pressure monitoring (ABPM) were performed on each subject. Urine samples were collected and analyzed for albumin, creatinine, neutrophil gelatinase-associated lipocalin (NGAL) and pentosidine.ResultsThe study included 21 subjects (62% female) with median age of 16.8 (IQR: 14.5, 18.9). Median HbA1C was 8.4 (IQR: 7.5, 9.3). While microalbuminuria was negative in all but one case (4.8%), urinary NGAL/Cr and pentosidine/Cr ratios were significantly elevated (P<0.001) in diabetic patients despite having normal microalbuminuria, and they correlated significantly with level of microalbumin/Cr (r=0.56 [CI: 0.17, 0.8] and r=0.79 [CI: 0.54, 0.91], respectively). Using ABPM, none had hypertension, however, poor nocturnal systolic BP dipping was found in 48% of cases (95% CI: 28-68%). Urinary NGAL/Cr negatively correlated with nocturnal SBP dipping (r=-0.47, CI: -0.76, -0.03). Urine NGAL/Cr also showed a significant negative correlation with HbA1c measurements, mean blood glucose, and high blood glucose index (r=-0.51 [CI: -0.78, -0.09], r=-0.45 [CI: -0.74, -0.03], and r=-0.51 [CI: -0.77, -0.1], respectively). Median urinary NGAL/Cr and pentosidine/Cr ratios were higher in the high GV group but were not significantly different.DiscussionThis pilot study explores the role of ABPM and urinary markers of tubular health and oxidative stress in early detection of diabetic nephropathy. GV may play a role in the process of this diabetic complication.

2008 ◽  
Vol 27 (3) ◽  
pp. 376-382 ◽  
Author(s):  
Tatjana Cvetković ◽  
Predrag Vlahović ◽  
Vidosava đorđević ◽  
Lilika Zvezdanović ◽  
Dušica Pavlović ◽  
...  

The Significance of Urinary Markers in the Evaluation of Diabetic Nephropathy Oxidative stress is considered to be a unifying link between diabetes mellitus (DM) and its complications, including nephropathy (DN). The aim of this study was to determine the parameters of oxidative injury of lipids and proteins as well as the activity of ectoenzymes in the urine of DN patients. The study included 40 individuals: 10 patients with type 2 diabetes mellitus and microalbuminuria (DMT2-MIA), 10 type 2 diabetic patients with macroalbuminuria (DMT2-MAA), 10 patients with type 1 diabetes and microalbuminuria (DMT1-MIA) and 10 age- and sex-matched healthy subjects (control). In the urine we determined TBA reactive substances (TBARS), reactive carbonyl groups (RCG), and the activity of ectoenzymes N-acetyl-β-d-glucosaminidase (NAG), plasma cell differentiation antigen (PC-1), aminopeptidase N (APN) and dipeptidyl peptidase IV (DPP IV). A higher concentration of TBARS in the urine was found in DMT2-MIA and DMT1-MIA, compared to the control group (p<0.001 and P<0.05). The urine concentration of RCD shows similar results with a significant elevation in the groups with DMT2-MAA and DMT1-MIA, compared to the DMT2-MIA (p<0.001) and control group (p<0.001). Activities of NAG, APN and DPPIV were significantly higher in the urine of DMT2-MAA, compared to the control (p<0.01). The activity of PC-1 was slightly increased in that group, but not significantly. In conclusion, the level of oxidative stress markers and activities of brush border ectoenzymes in the urine may be a useful non-invasive and easily repeatable test in DN.


2020 ◽  
Vol 9 (7) ◽  
pp. 2155
Author(s):  
Francesca Iannantuoni ◽  
Aranzazu M. de Marañon ◽  
Zaida Abad-Jiménez ◽  
Francisco Canet ◽  
Pedro Díaz-Pozo ◽  
...  

Type 1 diabetes has been associated with oxidative stress. This study evaluates the rates of oxidative stress, mitochondrial function, leukocyte–endothelium interactions and adhesion molecules in type 1 diabetic patients. The study population consisted of 52 diabetic patients and 46 body-composition and age-matched controls. We assessed anthropometric and metabolic parameters, oxidative stress and mitochondrial function by evaluating reactive oxygen species (ROS) production, mitochondrial ROS production, mitochondrial membrane potential and superoxide dismutase (SOD) and catalase (CAT) expression in polymorphonuclear leukocytes from type 1 diabetic patients. In addition, we evaluated interactions between leukocytes and human umbilical vein endothelial cells (HUVEC), and serum expression of adhesion molecules (P-selectin, VCAM-1 and ICAM-1), proinflammatory cytokines (IL-6 and TNFα) and myeloperoxidase (MPO). HbA1C and glucose levels were higher in diabetic patients than in control subjects, as expected. Mitochondrial function was altered and leukocyte–endothelium interactions were enhanced in diabetic patients, which was evident in the increase in total and mitochondrial ROS production, higher mitochondrial membrane potential, enhanced leukocyte rolling and adhesion, and decreased rolling velocity. Furthermore, we observed an increase in levels of adhesion molecules P-selectin, VCAM-1, and ICAM-1 in these subjects. In addition, type 1 diabetic patients exhibited an increase in proinflammatory mediators TNFα and MPO, and a decreased expression of SOD. The enhancement of leukocyte–endothelium interactions and proinflammatory markers correlated with glucose and HbA1Clevels. Mitochondrial alteration, oxidative stress, and enhanced leukocyte–endothelium interactions are features of type 1 diabetes and may be related to cardiovascular implications.


2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Hana Ahmed ◽  
Tayseer Elshaikh ◽  
Mohamed Abdullah

Objective. Data on microvascular complications in children and adolescents with type 1 diabetes mellitus (T1DM) in Sudan are scarce. This study was aimed at determining the prevalence of diabetic nephropathy (DN) and retinopathy (DR) and their relationship to certain risk factors in children with T1DM attending the Sudan Childhood Diabetes Centre. Design and Methods. A clinic-based cross-sectional study of 100 patients with T1DM aged 10-18 years. Patients with disease duration exceeding 5 years if the onset of diabetes was prepubertal and 2 years if it was postpubertal were included. Relevant sociodemographic, clinical, and biochemical information was obtained. Blood pressure was measured. The patients were screened for DN and DR using urinary microalbumin estimation and fundus photography, respectively. Results. The frequency of microalbuminuria and diabetic retinopathy was 36% and 33%, respectively. Eleven percent had both retinopathy and microalbuminuria. Seven percent of the patients were found to be hypertensive. Patients with diabetic retinopathy had significantly higher HbA1c levels ( p = 0.009 ) and longer diabetes duration ( p = 0.02 ) than patients without retinopathy. Logistic regression showed that high HbA1c (odds ratio (OR) 0.83, confidence interval (CI) 0.68-1.00, p = 0.04 ), but not age, duration, ethnic group, BMI, blood pressure, and presence of nephropathy, was an independent risk factor for retinopathy. Likewise, high blood pressure (OR 6.89, CI 1.17-40.52, p = 0.03 ), but not age, duration, ethnic group, BMI, HbA1c, and presence of retinopathy, was a predictor for nephropathy. Conclusion. High prevalence of incipient DN and early stages of DR were observed in this study. Longer diabetes duration and higher HbA1c were associated with the presence of diabetic retinopathy. High blood pressure was a risk factor for DN. So regular screening for these complications and optimization of glycemic control are needed.


SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A352-A353
Author(s):  
S Griggs ◽  
N S Redeker ◽  
S Jeon ◽  
M Grey

Abstract Introduction The association between short sleep duration and poorer glycemic control in adolescents ages 10-16 with type 1 diabetes (T1D) is well established. Researchers have used cross-sectional, between-subjects’ methods, with limited focus on the potential intraindividual variation among these variables. The purpose of this analysis was to examine the within person associations between glucose variability indices (J index, low/high blood glucose index, time in range) and sleep characteristics (bedtime, waketime, total sleep time, sleep efficiency, wake after sleep onset [WASO], awakenings, and sleep fragmentation index) in adolescents with T1D. Methods Adolescents monitored their sleep and glucose patterns concurrently for 3-7 days with a wrist actigraph on their non-dominant wrist and either their own continuous glucose monitor (CGM) or a provided blinded CGM. General linear mixed models (GLMM) were used to determine within-person and day level associations. Results The sample included 38 adolescents (M age 13.4±1.8; 37.8% male; M A1C 8.2±1.2%). Average glucose levels were controlled in all GLMMs. Adolescents had earlier waketimes on days when more time was spent in hypoglycemia &lt;70mg/dL (β=-0.15, p&lt;0.001). At the person level, adolescents had greater WASO with more % time spent in severe hypoglycemia &lt;54mg/dL with more severe low blood glucose indices (β=0.35, p&lt;0.01 and β=0.34, p&lt;0.01 respectively). At the daily level, adolescents had greater WASO (β=0.20, p=0.01) and more awakenings (β=0.16, p=0.04) on the days they had more overall glucose variability (J index) and more severe high blood glucose indices (β=0.17, p=0.04), but were less likely to have more % time in hypoglycemia (β=-0.15, p=0.02). Conclusion Glucose variability was positively associated with poor sleep (e.g., WASO and awakenings) in adolescents with T1D both at the daily and intraindividual level. Monitoring over a longer period of time in subsequent studies would allow researchers to determine the within person associations between habitual short sleep duration and glucose variability. Support NINR T32NR0008346 & P20NR014126, Medtronic MiniMed provided CGMs at a discounted rate for the study.


2006 ◽  
Vol 154 (1) ◽  
pp. 75-81 ◽  
Author(s):  
Lars Melholt Rasmussen ◽  
Lise Tarnow ◽  
Troels Krarup Hansen ◽  
Hans-Henrik Parving ◽  
Allan Flyvbjerg

Objective: The bone-related peptide osteoprotegerin (OPG) has recently been found in increased amounts in the vasculature in diabetes. It is produced by vascular smooth muscle and endothelial cells, and may be implicated in the development of vascular calcifications. OPG is present in the circulation, where increased amounts have been observed in patients with diabetes. In this study, we examined whether plasma OPG is associated with the glycaemic and vascular status of patients with type 1 diabetes. Methods: Two gender-, age- and duration-comparable groups of type 1 diabetic patients either with (n = 199) or without (n = 192) signs of diabetic nephropathy were studied. Plasma OPG was determined by an ELISA. Results: The plasma OPG concentration was significantly higher in patients with nephropathy than those without (3.11 (2.49–3.99) vs 2.57 (2.19–3.21) (median (interquartiles), ng/ml), P < 0.001). Plasma OPG correlated with haemoglobin A1c (HbA1c), systolic blood pressure and age in both groups and, in addition, with kidney function in the nephropathic group. These correlations remained significant in multivariate models. In addition, we found that plasma OPG concentrations were increased among patients with cardiovascular diseases (CVD), both in the normoalbuminuric and the nephropathic groups. The differences between nephropathic and normoalbuminuric, as well as subgroups with and without CVD, could largely be ascribed to changes in HbA1c, age, systolic blood pressure and creatinine. Conclusion: OPG is associated with glycaemic control and CVD in patients with type 1 diabetes, compatible with the hypothesis that OPG is associated with the development of diabetic vascular complications.


2015 ◽  
Vol 61 ◽  
pp. 479-488
Author(s):  
Shawkia S. Abd El-Halim ◽  
Awatif M. Abd El-Maksoud ◽  
Mohammed A. Abdel-Rahman

2018 ◽  
Author(s):  
Mahsa Oroojeni Mohammad Javad ◽  
Stephen Olusegun Agboola ◽  
Kamal Jethwani ◽  
Ibrahim Zeid ◽  
Sagar Kamarthi

BACKGROUND Diabetes is a serious chronic disease marked by high levels of blood glucose. It results from issues related to how insulin is produced and/or how insulin functions in the body. In the long run, uncontrolled blood sugar can damage the vessels that supply blood to important organs such as heart, kidneys, eyes, and nerves. Currently there are no effective algorithms to automatically recommend insulin dosage level considering the characteristics of a diabetic patient. OBJECTIVE The objective of this work is to develop and validate a general reinforcement learning framework and a related learning model for personalized treatment and management of Type 1 diabetes and its complications. METHODS This research presents a model-free reinforcement learning (RL) algorithm to recommend insulin level to regulate the blood glucose level of a diabetic patient considering his/her state defined by A1C level, alcohol usage, activity level, and BMI value. In this approach, an RL agent learns from its exploration and response of diabetic patients when they are subject to different actions in terms of insulin dosage level. As a result of a treatment action at time step t, the RL agent receives a numeric reward depending on the response of the patient’s blood glucose level. At each stage the reward for the learning agent is calculated as a function of the difference between the glucose level in the patient body and its target level. The RL algorithm is trained on ten years of the clinical data of 87 patients obtained from the Mass General Hospital. Demographically, 59% of patients are male and 41% of patients are female; the median of age is 54 years and mean is 52.92 years; 86% of patients are white and 47% of 87 patients are married. RESULTS The performance of the algorithm is evaluated on 60 test cases. Further the performance of Support Vector Machine (SVM) has been applied for Lantus class prediction and results has been compared with Q-learning algorithm recommendation. The results show that the RL recommendations of insulin levels for test patients match with the actual prescriptions of the test patients. The RL gave prediction with an accuracy of 88% and SVM shows 80% accuracy. CONCLUSIONS Since the RL algorithm can select actions that improve patient condition by taking into account delayed effects, it has a good potential to control blood glucose level in diabetic patients.


Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 74-LB
Author(s):  
ALLYSON HUGHES ◽  
JEOFFREY BISPHAM ◽  
COLLEEN GAREY ◽  
JINGWEN LIU ◽  
LILY FULLER ◽  
...  

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