scholarly journals Biological Activity of c-Peptide in Microvascular Complications of Type 1 Diabetes—Time for Translational Studies or Back to the Basics?

2020 ◽  
Vol 21 (24) ◽  
pp. 9723
Author(s):  
Aleksandra Ryk ◽  
Aleksandra Łosiewicz ◽  
Arkadiusz Michalak ◽  
Wojciech Fendler
Keyword(s):  
Type 1 Diabetes ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Negative Impact ◽  
Current Knowledge ◽  
Microvascular Complications ◽  
C Peptide ◽  
Increased Risk ◽  
The Impact

People with type 1 diabetes have an increased risk of developing microvascular complications, which have a negative impact on the quality of life and reduce life expectancy. Numerous studies in animals with experimental diabetes show that c-peptide supplementation exerts beneficial effects on diabetes-induced damage in peripheral nerves and kidneys. There is substantial evidence that c-peptide counteracts the detrimental changes caused by hyperglycemia at the cellular level, such as decreased activation of endothelial nitric oxide synthase and sodium potassium ATPase, and increase in formation of pro-inflammatory molecules mediated by nuclear factor kappa-light-chain-enhancer of activated B cells: cytokines, chemokines, cell adhesion molecules, vascular endothelial growth factor, and transforming growth factor beta. However, despite positive results from cell and animal studies, no successful c-peptide replacement therapies have been developed so far. Therefore, it is important to improve our understanding of the impact of c-peptide on the pathophysiology of microvascular complications to develop novel c-peptide-based treatments. This article aims to review current knowledge on the impact of c-peptide on diabetic neuro- and nephropathy and to evaluate its potential therapeutic role.

scholarly journals Regulatory T-Cells Protect From Type 1 Diabetes After Induction by Coxsackievirus Infection in the Context of Transforming Growth Factor- 

Diabetes ◽  
2008 ◽  
Vol 57 (5) ◽  
pp. 1302-1311 ◽  
Author(s):  
M. J. Richer ◽  
N. Straka ◽  
D. Fang ◽  
I. Shanina ◽  
M. S. Horwitz
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
Growth Factor ◽  
Regulatory T Cells ◽  
Transforming Growth Factor

scholarly journals Association of glycemic variability and hypoglycemia with distal symmetrical polyneuropathy in adults with type 1 diabetes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ziyang Shen ◽  
Hemin Jiang ◽  
Rong Huang ◽  
Yunting Zhou ◽  
Qian Li ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Glycemic Variability ◽  
Mean Amplitude ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
C Peptide ◽  
Nocturnal Hypoglycemia ◽  
Increased Risk ◽  
Distal Symmetrical Polyneuropathy

AbstractPrevious studies exploring the influence of glycemic variability (GV) on the pathogenesis of distal symmetrical polyneuropathy (DSPN) in type 1 diabetes (T1DM) produced conflicting results. The aim of this study was to assess the relationship between GV and DSPN in T1DM. Adults with T1DM were included in this cross-sectional study and asked to undergo 3-day CGM. GV quantified by coefficient of variation (CV) and mean amplitude of glucose excursions (MAGE) were obtained from CGM. Clinical characteristics and biochemical assessments were collected for analysis. The study comprised 152 T1DM patients (53.9% males) with mean age of 44.2 year. Higher levels of age and duration of diabetes and lower levels of total cholesterol, LDL, fasting C-peptide and postprandial C-peptide were observed in DSPN subjects. DSPN groups displayed a higher blood glucose between 00:00 and 12:59 according to the CGM profile. Higher MAGE and CV were associated with increased risk of DSPN in the fully adjusted model. Meanwhile, a significant association between measurements of hypoglycemia, especially nocturnal hypoglycemia, and DSPN was found after multiple tests. CGM parameters describing the glycemic variability and hypoglycemia were potential risk factors for DSPN in adults with T1DM.

scholarly journals The increased risk of microvascular complications in South Asians with type 1 diabetes is influenced by migration

2019 ◽  
Vol 37 (12) ◽  
pp. 2136-2142
Author(s):  
M.R. Chetan ◽  
J.K. Miksza ◽  
I. Lawrence ◽  
R.M. Anjana ◽  
R. Unnikrishnan ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
South Asians ◽  
Microvascular Complications ◽  
Increased Risk

scholarly journals Serum Concentrations of Transforming Growth Factor-Beta 1 in Predicting the Occurrence of Diabetic Retinopathy in Juvenile Patients with Type 1 Diabetes Mellitus

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Katarzyna Zorena ◽  
Ewa Malinowska ◽  
Dorota Raczyńska ◽  
Małgorzata Myśliwiec ◽  
Krystyna Raczyńska
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Diabetic Retinopathy ◽  
Growth Factor ◽  
Type 1 Diabetes Mellitus ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Serum Concentrations ◽  
Growth Factor Beta

In the present study, we have decided to evaluate if serum transforming growth factor-beta 1 (TGF-β1) concentrations may have diagnostic value in predicting the occurrence of diabetic retinopathy (DR) in juvenile patients with type 1 diabetes mellitus (T1DM). The study included 81 children and adolescents with T1DM and 19 control subjects. All study participants had biochemical parameters examined, underwent an eye examination, and 24-hour blood pressure monitoring. Moreover, serum concentrations of TGF-β1 were measured. The group of patients with T1DM and nonproliferative diabetic retinopathy (NPDR) had statistically significant higher serum levels of TGF-β1 (P=0.001) as compared to T1DM patients without retinopathy as well as the healthy control subject. The threshold serum TGF-β1 concentrations which had a discriminative ability to predict the presence of DR were calculated using the receiver operating characteristic (ROC) curves analysis and amounted to 443 pg/ml. The area under the ROC curve (AUCROC) was 0.80, and its population value was in the range of 0.66 to 0.94. The sensitivity and specificity were calculated to be 72% and 88%, respectively. Our results suggest that TGF-β1 serum concentrations may be an additional parameter in predicting the occurrence of DR in juvenile patients with T1DM.

scholarly journals Associations of Microvascular Complications With the Risk of Cardiovascular Disease in Type 1 Diabetes

2021 ◽  
Author(s):  
Rose Gubitosi-Klug ◽  
Xiaoyu Gao ◽  
Rodica Pop-Busui ◽  
Ian H de Boer ◽  
Neill White ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiovascular Disease ◽  
Type 1 Diabetes ◽  
Kidney Disease ◽  
Microvascular Complications ◽  
Microvascular Disease ◽  
Fundus Photography ◽  
Increased Risk ◽  
Subsequent Risk

<b>Objective:</b> We examined whether the presence of microvascular complications was associated with increased subsequent risk of cardiovascular disease (CVD) among participants with type 1 diabetes in the Diabetes Control and Complications Trial and Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study followed for over 35 years. <p><b>Research Design and Methods:</b> Standardized longitudinal data collection included: 1) stereoscopic seven-field retinal fundus photography centrally-graded for retinopathy stage and clinically significant macular edema; 2) urinary albumin excretion rate (AER) and estimated glomerular filtration rate (eGFR); 3) cardiovascular autonomic neuropathy (CAN) reflex testing; and 4) adjudicated CVD events, including death from cardiovascular disease, nonfatal myocardial infarction, stroke, subclinical myocardial infarction on ECG, confirmed angina, or coronary artery revascularization. Cox proportional hazard models assessed the association of microvascular complications with subsequent risk of CVD. </p> <p><b>Results:</b> 239 participants developed CVD, including 120 participants who suffered major adverse cardiovascular events (MACE) defined as non-fatal myocardial infarction, non-fatal stroke or cardiovascular death. The presence of microvascular disease (diabetic retinopathy, kidney disease, or CAN) was associated with increased risk of subsequent CVD and MACE (hazard ratios 1.86 to 3.18 and 2.09 to 3.63, respectively); associations that remained significant after adjusting for age and HbA1c. After adjustment for traditional CVD risk factors, however, only sustained AER≥30 mg/24hr occurring alone and/or with eGFR<60 ml/min/1.73m, and the presence of both retinal and kidney disease remained associated with CVD. </p> <p><b>Conclusions:</b> Advanced microvascular disease, especially moderate to severe albuminuria or eGFR<60 ml/min/1.73m<sup>2</sup>, conveyed an increased risk of subsequent cardiovascular disease in the DCCT/EDIC cohort. </p>

scholarly journals Clinical Impact of Residual C-Peptide Secretion in Type 1 Diabetes on Glycemia and Microvascular Complications

Diabetes Care ◽  
2020 ◽  
pp. dc200567
Author(s):  
Anita Jeyam ◽  
Helen Colhoun ◽  
Stuart McGurnaghan ◽  
Luke Blackbourn ◽  
Timothy J. McDonald ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Microvascular Complications ◽  
Clinical Impact ◽  
C Peptide ◽  
Peptide Secretion

scholarly journals A Phase II, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study Evaluating the Efficacy and Safety of Alpha-1 Antitrypsin (AAT) (Glassia®) in the Treatment of Recent-Onset Type 1 Diabetes

2019 ◽  
Vol 20 (23) ◽  
pp. 6032 ◽  
Author(s):  
Lebenthal ◽  
Brener ◽  
Hershkovitz ◽  
Shehadeh ◽  
Shalitin ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Therapeutic Modality ◽  
Β Cell ◽  
C Peptide ◽  
Recent Onset ◽  
Onset Type ◽  
Alpha 1 Antitrypsin ◽  
The Impact ◽  
Cell Preservation

Our aim was to assess the efficacy, safety, and tolerability of alpha-1 antitrypsin (AAT) as a therapeutic modality for β-cell preservation in patients with recent-onset type 1 diabetes. Seventy type 1 diabetes patients (37 males; mean age 13.1 ± 4.1years) were randomized to treatment with 22 infusions of AAT (Glassia®) (60 or 120 mg/kg) or placebo. The primary outcome was the area under the curve (AUC) of C-peptide from a 2-h mixed-meal tolerance test after 52 weeks. At week 52, C-peptide was 0.9, 0.45, and 0.48 pmol/mL in the AAT-120, AAT-60, and placebo groups (p = 0.170 and p = 0.866 vs. placebo, respectively). The declines in C-peptide glycated hemoglobin (HbA1c) and the total insulin dose (U/kg) were similar across groups. Within the predefined 12–18-years subgroup, the C-peptide AUC decreased significantly in the placebo and AAT-60 groups (−0.34 and −0.54 pmol/mL, respectively, p < 0.01), with a borderline decrease in the AAT-120 group (−0.29 pmol/mL, p = 0.047). The mean HbA1c level was significantly lower in the AAT-120 group compared to the placebo (6.7% ± 0.9% vs. 8.2 ± 1.4%, p = 0.05), and a higher percentage of patients attained HbA1c ≤ 7% (75% vs. 25%, p = 0.05). AAT was tolerated well, with a similar safety profile between groups. The AAT intervention showed promise in the subgroup of adolescents with recent-onset type 1 diabetes. Further studies are warranted to determine the impact and proposed mechanism of action of AAT in β-cell preservation.

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