Validation of a model for the prediction of retinopathy in persons with type 1 diabetes

Background/AimTo validate a previously developed model for prediction of diabetic retinopathy (DR) for personalised retinopathy screening in persons with type 1 diabetes.MethodsRetrospective medical data of persons with type 1 diabetes treated in an academic hospital setting were used for analysis. Sight-threatening retinopathy (STR) was defined as the presence of severe non-proliferative DR, proliferative DR or macular oedema. The presence and grade of retinopathy, onset of diabetes, systolic blood pressure, and levels of haemoglobin A1c were used to calculate an individual risk estimate and personalised screening interval. In persons with STR, the occurrence was compared with the calculated date of screening. The model’s predictive performance was measured using calibration and discrimination techniques.ResultsOf the 268 persons included in our study, 24 (9.0%) developed STR during a mean follow-up of 4.6 years. All incidences of STR occurred after the calculated screening date. By applying the model, the mean calculated screening interval was 30.5 months, which is a reduction in screening frequency of 61% compared with annual screening and 21% compared with biennial screening. The discriminatory ability was good (Harrell’s C-statistic=0.82, 95% CI 0.74 to 0.90), and calibration showed an overestimation of risk in persons who were assigned to a higher risk for STR.ConclusionThis validation study suggests that a screening programme based on the previously developed prediction model is safe and efficient. The use of a personalised screening frequency could improve cost-effectiveness of diabetic eye care.

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Transcriptional networks in at-risk individuals identify signatures of type 1 diabetes progression

Science Translational Medicine ◽

10.1126/scitranslmed.abd5666 ◽

2021 ◽

Vol 13 (587) ◽

pp. eabd5666

Author(s):

Louis-Pascal Xhonneux ◽

Oliver Knight ◽

Åke Lernmark ◽

Ezio Bonifacio ◽

William A. Hagopian ◽

...

Keyword(s):

Gene Expression ◽

Type 1 Diabetes ◽

Disease Risk ◽

Killer Cell ◽

Predictive Performance ◽

Islet Autoimmunity ◽

Individual Risk ◽

Transcriptional Networks ◽

Prediction And Prevention

Type 1 diabetes (T1D) is a disease of insulin deficiency that results from autoimmune destruction of pancreatic islet β cells. The exact cause of T1D remains unknown, although asymptomatic islet autoimmunity lasting from weeks to years before diagnosis raises the possibility of intervention before the onset of clinical disease. The number, type, and titer of islet autoantibodies are associated with long-term disease risk but do not cause disease, and robust early predictors of individual progression to T1D onset remain elusive. The Environmental Determinants of Diabetes in the Young (TEDDY) consortium is a prospective cohort study aiming to determine genetic and environmental interactions causing T1D. Here, we analyzed longitudinal blood transcriptomes of 2013 samples from 400 individuals in the TEDDY study before both T1D and islet autoimmunity. We identified and interpreted age-associated gene expression changes in healthy infancy and age-independent changes tracking with progression to both T1D and islet autoimmunity, beginning before other evidence of islet autoimmunity was present. We combined multivariate longitudinal data in a Bayesian joint model to predict individual risk of T1D onset and validated the association of a natural killer cell signature with progression and the model’s predictive performance on an additional 356 samples from 56 individuals in the independent Type 1 Diabetes Prediction and Prevention study. Together, our results indicate that T1D is characterized by early and longitudinal changes in gene expression, informing the immunopathology of disease progression and facilitating prediction of its course.

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Independent Association of a Metabolic Syndrome Severity Score with All-Cause Mortality in Type 1 Diabetes—A 10-Year Follow-Up

Diabetes ◽

10.2337/db18-618-p ◽

2018 ◽

Vol 67 (Supplement 1) ◽

pp. 618-P

Author(s):

GIUSEPPE PENNO ◽

MONIA GAROFOLO ◽

ROSA GIANNARELLI ◽

FABRIZIO CAMPI ◽

DANIELA LUCCHESI ◽

...

Keyword(s):

Metabolic Syndrome ◽

Type 1 Diabetes ◽

Severity Score ◽

All Cause Mortality ◽

Independent Association

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Beneficial Effect of Flash Glucose Monitoring Persists in a Two-Year Perspective—A Clinical Follow-Up Study of 334 Individuals with Type 1 Diabetes

Diabetes ◽

10.2337/db18-958-p ◽

2018 ◽

Vol 67 (Supplement 1) ◽

pp. 958-P ◽

Cited By ~ 1

Author(s):

MAGNUS LONDAHL ◽

KATARINA FAGHER ◽

PER KATZMAN ◽

KARIN FILIPSSON

Keyword(s):

Type 1 Diabetes ◽

Beneficial Effect ◽

Glucose Monitoring ◽

Flash Glucose Monitoring ◽

Follow Up Study

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Estimated Glucose Disposal Rate as a Predictor of All-Cause Mortality in Type 1 Diabetes—A 10-Year Follow-Up Study

Diabetes ◽

10.2337/db18-1694-p ◽

2018 ◽

Vol 67 (Supplement 1) ◽

pp. 1694-P

Author(s):

MONIA GAROFOLO ◽

ALESSANDRA BERTOLOTTO ◽

FABRIZIO CAMPI ◽

DANIELA LUCCHESI ◽

LAURA GIUSTI ◽

...

Keyword(s):

Type 1 Diabetes ◽

Glucose Disposal ◽

Follow Up Study ◽

All Cause Mortality ◽

Estimated Glucose Disposal Rate ◽

Glucose Disposal Rate

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322-OR: Risk Factors for Peripheral and Cardiovascular Autonomic Neuropathy in Type 1 Diabetes: Thirty Years of Follow-Up in DCCT/EDIC

Diabetes ◽

10.2337/db19-322-or ◽

2019 ◽

Vol 68 (Supplement 1) ◽

pp. 322-OR

Author(s):

BARBARA BRAFFETT ◽

ROSE GUBITOSI-KLUG ◽

JAMES W. ALBERS ◽

EVA L. FELDMAN ◽

CATHERINE MARTIN ◽

...

Keyword(s):

Risk Factors ◽

Type 1 Diabetes ◽

Autonomic Neuropathy ◽

Cardiovascular Autonomic Neuropathy

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A Decade of Disparities in Diabetes Technology Use and HbA1c in Pediatric Type 1 Diabetes: A Trans-Atlantic Comparison

10.2337/figshare.12808301 ◽

2020 ◽

Author(s):

Ananta Addala ◽

Marie Auzanneau ◽

Kellee Miller ◽

Werner Maier ◽

Nicole Foster ◽

...

Keyword(s):

Type 1 Diabetes ◽

Technology Use ◽

Hemoglobin A1c ◽

Diabetes Technology ◽

Design And Methods ◽

Relationship Of ◽

The Relationship ◽

Pediatric Type 1 Diabetes

Objective: As diabetes technology use in youth increases worldwide, inequalities in access may exacerbate disparities in hemoglobin A1c (HbA1c). We hypothesized an increasing gap in diabetes technology use by socioeconomic status (SES) would be associated with increased HbA1c disparities. Research Design and Methods: Participants aged <18 years with diabetes duration ≥1 year in the Type 1 Diabetes Exchange (T1DX, US, n=16,457) and Diabetes Prospective Follow-up (DPV, Germany, n=39,836) registries were categorized into lowest (Q1) to highest (Q5) SES quintiles. Multiple regression analyses compared the relationship of SES quintiles with diabetes technology use and HbA1c from 2010-2012 and 2016-2018. Results: HbA1c was higher in participants with lower SES (in 2010-2012 & 2016-2018, respectively: 8.0% & 7.8% in Q1 and 7.6% & 7.5% in Q5 for DPV; and 9.0% & 9.3% in Q1 and 7.8% & 8.0% in Q5 for T1DX). For DPV, the association between SES and HbA1c did not change between the two time periods, whereas for T1DX, disparities in HbA1c by SES increased significantly (p<0.001). After adjusting for technology use, results for DPV did not change whereas the increase in T1DX was no longer significant. Conclusions: Although causal conclusions cannot be drawn, diabetes technology use is lowest and HbA1c is highest in those of the lowest SES quintile in the T1DX and this difference for HbA1c broadened in the last decade. Associations of SES with technology use and HbA1c were weaker in the DPV registry.

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Faculty Opinions recommendation of Genetic liability of type 1 diabetes and the onset age among 22,650 young Finnish twin pairs: a nationwide follow-up study.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1012861.187509 ◽

2003 ◽

Author(s):

Jin-Xiong She

Keyword(s):

Type 1 Diabetes ◽

Onset Age ◽

Genetic Liability ◽

Follow Up Study

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One repeated transplantation of allogeneic umbilical cord mesenchymal stromal cells in type 1 diabetes: an open parallel controlled clinical study

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02417-3 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Jing Lu ◽

Shan-mei Shen ◽

Qing Ling ◽

Bin Wang ◽

Li-rong Li ◽

...

Keyword(s):

Type 1 Diabetes ◽

Stromal Cells ◽

Treated Group ◽

Control Group ◽

Adult Onset ◽

Β Cell ◽

Juvenile Onset ◽

C Peptide

Abstract Background The preservation or restoration of β cell function in type 1 diabetes (T1D) remains as an attractive and challengeable therapeutic target. Mesenchymal stromal cells (MSCs) are multipotent cells with high capacity of immunoregulation, which emerged as a promising cell-based therapy for many immune disorders. The objective of this study was to examine the efficacy and safety of one repeated transplantation of allogeneic MSCs in individuals with T1D. Methods This was a nonrandomized, open-label, parallel-armed prospective study. MSCs were isolated from umbilical cord (UC) of healthy donors. Fifty-three participants including 33 adult-onset (≥ 18 years) and 20 juvenile-onset T1D were enrolled. Twenty-seven subjects (MSC-treated group) received an initial systemic infusion of allogeneic UC-MSCs, followed by a repeat course at 3 months, whereas the control group (n = 26) only received standard care based on intensive insulin therapy. Data at 1-year follow-up was reported in this study. The primary endpoint was clinical remission defined as a 10% increase from baseline in the level of fasting and/or postprandial C-peptide. The secondary endpoints included side effects, serum levels of HbA1c, changes in fasting and postprandial C-peptide, and daily insulin doses. Results After 1-year follow-up, 40.7% subjects in MSC-treated group achieved the primary endpoint, significantly higher than that in the control arm. Three subjects in MSC-treated group, in contrast to none in control group, achieved insulin independence and maintained insulin free for 3 to 12 months. Among the adult-onset T1D, the percent change of postprandial C-peptide was significantly increased in MSC-treated group than in the control group. However, changes in fasting or postprandial C-peptide were not significantly different between groups among the juvenile-onset T1D. Multivariable logistic regression assay indicated that lower fasting C-peptide and higher dose of UC-MSC correlated with achievement of clinical remission after transplantation. No severe side effects were observed. Conclusion One repeated intravenous dose of allogeneic UC-MSCs is safe in people with recent-onset T1D and may result in better islet β cell preservation during the first year after diagnosis compared to standard treatment alone. Trial registration ChiCTR2100045434. Registered on April 15, 2021—retrospectively registered, http://www.chictr.org.cn/

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Continuous subcutaneous insulin infusion alters microRNA expression and glycaemic variability in children with type 1 diabetes

Scientific Reports ◽

10.1038/s41598-021-95824-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Emma S. Scott ◽

Andrzej S. Januszewski ◽

Luke M. Carroll ◽

Gregory R. Fulcher ◽

Mugdha V. Joglekar ◽

...

Keyword(s):

Type 1 Diabetes ◽

Continuous Subcutaneous Insulin Infusion ◽

Insulin Infusion ◽

Diabetes Diagnosis ◽

Subcutaneous Insulin ◽

Glycaemic Variability ◽

Altered Expression ◽

C Peptide

AbstractTo determine whether continuous subcutaneous insulin infusion (CSII) vs. multiple daily injections (MDI) therapy from near-diagnosis of type 1 diabetes is associated with reduced glycaemic variability (GV) and altered microRNA (miRNAs) expression. Adolescents (74% male) within 3-months of diabetes diagnosis (n = 27) were randomized to CSII (n = 12) or MDI. HbA1c, 1-5-Anhydroglucitol (1,5-AG), high sensitivity C-peptide and a custom TaqMan qPCR panel of 52 miRNAs were measured at baseline and follow-up (median (LQ-UQ); 535 (519–563) days). There were no significant differences between groups in baseline or follow-up HbA1c or C-peptide, nor baseline miRNAs. Mean ± SD 1,5-AG improved with CSII vs. MDI (3.1 ± 4.1 vs. − 2.2 ± − 7.0 mg/ml respectively, P = 0.029). On follow-up 11 miRNAs associated with diabetes vascular complications had altered expression in CSII-users. Early CSII vs. MDI use is associated with lower GV and less adverse vascular-related miRNAs. Relationships with future complications are of interest.

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