Browsing by Subject "Diabetes Mellitus, Type 1"

Now showing 1 - 10 of 26
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    Alcohol Use Trajectories after High School Graduation among Emerging Adults with Type 1 Diabetes
    (Elsevier, 2014-08) Hanna, Kathleen M.; Stupiansky, Nathan W.; Weaver, Michael T.; Slaven, James E.; Stump, Timothy E.; IU School of Nursing
    Objective Explore alcohol involvement trajectories and associated factors during the year post-high school (HS) graduation among emerging adults with type 1 diabetes. Methods Youth (N=181) self-reported alcohol use at baseline and every 3 months for 1 year post-HS graduation. Data were also collected on parent-youth conflict, diabetes self-efficacy, major life events, living and educational situations, diabetes management, marijuana use, cigarette smoking, and glycemic control. Trajectories of alcohol use were modeled using latent class growth analysis. Associations between trajectory class and specific salient variables were examined using analysis of variance, chi square, or generalized linear mixed model, as appropriate. Results Identified alcohol involvement trajectory classes were labeled as: 1) Consistent Involvement Group (n=25, 13.8%) with stable, high use relative to other groups over the 12 months; 2) Growing Involvement Group (n=55, 30.4%) with increasing use throughout the 12 months; and 3) Minimal Involvement Group (n=101, 55.8%) with essentially no involvement until month nine. Those with minimal involvement had the best diabetes management and better diabetes self-efficacy than those with consistent involvement. In comparison to those minimally involved, those with growing involvement were more likely to live independently of parents; those consistently involved had more major life events; and both the growing and consistent involvement groups were more likely to have tried marijuana and cigarettes. Conclusions This sample of emerging adults with type 1 diabetes has 3 unique patterns of alcohol use during the first year after high school. Implication and Contribution Among youth with type 1 diabetes in the year post-HS graduation, alcohol involvement knowledge was extended by identifying patterns of such use. Further research of alcohol use patterns is needed to guide health care professionals in their assessments and researchers in testing interventions that target unique patterns.
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    Alefacept provides sustained clinical and immunological effects in new-onset type 1 diabetes patients
    (American Society for Clinical Investigation, 2015-08-03) Rigby, Mark R.; Harris, Kristina M.; Pinckney, Ashley; DiMeglio, Linda A.; Rendell, Marc S.; Felner, Eric I.; Dostou, Jean M.; Gitelman, Stephen E.; Griffin, Kurt J.; Tsalikian, Eva; Gottlieb, Peter A.; Greenbaum, Carla J.; Sherry, Nicole A.; Moore, Wayne V.; Monzavi, Roshanak; Willi, Steven M.; Raskin, Philip; Keyes-Elstein, Lynette; Long, S. Alice; Kanaparthi, Sai; Lim, Noha; Phippard, Deborah; Soppe, Carol L.; Fitzgibbon, Margret L.; McNamara, James; Nepom, Gerald T.; Ehlers, Mario R.; Department of Pediatrics, IU School of Medicine
    BACKGROUND: Type 1 diabetes (T1D) results from destruction of pancreatic β cells by autoreactive effector T cells. We hypothesized that the immunomodulatory drug alefacept would result in targeted quantitative and qualitative changes in effector T cells and prolonged preservation of endogenous insulin secretion by the remaining β cells in patients with newly diagnosed T1D. METHODS: In a multicenter, randomized, double-blind, placebo-controlled trial, we compared alefacept (two 12-week courses of 15 mg/wk i.m., separated by a 12-week pause) with placebo in patients with recent onset of T1D. Endpoints were assessed at 24 months and included meal-stimulated C-peptide AUC, insulin use, hypoglycemic events, and immunologic responses. RESULTS: A total of 49 patients were enrolled. At 24 months, or 15 months after the last dose of alefacept, both the 4-hour and the 2-hour C-peptide AUCs were significantly greater in the treatment group than in the control group (P = 0.002 and 0.015, respectively). Exogenous insulin requirements were lower (P = 0.002) and rates of major hypoglycemic events were about 50% reduced (P < 0.001) in the alefacept group compared with placebo at 24 months. There was no apparent between-group difference in glycemic control or adverse events. Alefacept treatment depleted CD4+ and CD8+ central memory T cells (Tcm) and effector memory T cells (Tem) (P < 0.01), preserved Tregs, increased the ratios of Treg to Tem and Tcm (P < 0.01), and increased the percentage of PD-1+CD4+ Tem and Tcm (P < 0.01). CONCLUSIONS: In patients with newly diagnosed T1D, two 12-week courses of alefacept preserved C-peptide secretion, reduced insulin use and hypoglycemic events, and induced favorable immunologic profiles at 24 months, well over 1 year after cessation of therapy. TRIAL REGISTRATION: https://clinicaltrials.gov/ NCT00965458. FUNDING: NIH and Astellas.
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    CGM-measured glucose values have a strong correlation with C-peptide, HbA1c and IDAAC, but do poorly in predicting C-peptide levels in the two years following onset of diabetes
    (Springer-Verlag, 2015-06) Buckingham, Bruce; Cheng, Peiyao; Beck, Roy W.; Kollman, Craig; Ruedy, Katrina J.; Weinzimer, Stuart A.; Slover, Robert; Bremer, Andrew A.; Fuqua, John; Tamborlane, William; Diabetes Research in Children Network (DirecNet) and Type 1 Diabetes TrialNet Study Groups; Department of Pediatrics, IU School of Medicine
    AIMS/HYPOTHESIS: The aim of this work was to assess the association between continuous glucose monitoring (CGM) data, HbA1c, insulin-dose-adjusted HbA1c (IDAA1c) and C-peptide responses during the first 2 years following diagnosis of type 1 diabetes. METHODS: A secondary analysis was conducted of data collected from a randomised trial assessing the effect of intensive management initiated within 1 week of diagnosis of type 1 diabetes, in which mixed-meal tolerance tests were performed at baseline and at eight additional time points through 24 months. CGM data were collected at each visit. RESULTS: Among 67 study participants (mean age [± SD] 13.3 ± 5.7 years), HbA1c was inversely correlated with C-peptide at each time point (p < 0.001), as were changes in each measure between time points (p < 0.001). However, C-peptide at one visit did not predict the change in HbA1c at the next visit and vice versa. Higher C-peptide levels correlated with increased proportion of CGM glucose values between 3.9 and 7.8 mmol/l and lower CV (p = 0.001 and p = 0.02, respectively) but not with CGM glucose levels <3.9 mmol/l. Virtually all participants with IDAA1c < 9 retained substantial insulin secretion but when evaluated together with CGM, time in the range of 3.9-7.8 mmol/l and CV did not provide additional value in predicting C-peptide levels. CONCLUSIONS/INTERPRETATION: In the first 2 years after diagnosis of type 1 diabetes, higher C-peptide levels are associated with increased sensor glucose levels in the target range and with lower glucose variability but not hypoglycaemia. CGM metrics do not provide added value over the IDAA1c in predicting C-peptide levels.
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    Clinical Islet Xenotransplantation: A Step Forward
    (Elsevier, 2016-10) Ekser, Burcin; Bottino, Rita; Cooper, David K. C.; Department of Surgery, IU School of Medicine
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    Combined Analysis of GAD65, miR-375, and Unmethylated Insulin DNA Following Islet Transplantation in Patients With T1D
    (Endocrine Society, 2019-02) Roels, Sarah; Costa, Olivier R.; Tersey, Sarah A.; Stangé, Geert; De Smet, Dieter; Balti, Eric V.; Gillard, Pieter; Keymeulen, Bart; Ling, Zhidong; Pipeleers, Daniel G.; Gorus, Frans K.; Mirmira, Raghavendra G.; Martens, Geert A.; Pediatrics, School of Medicine
    Aim: Several biomarkers have been proposed to detect pancreatic β cell destruction in vivo but so far have not been compared for sensitivity and significance. Methods: We used islet transplantation as a model to compare plasma concentrations of miR-375, 65-kDa subunit of glutamate decarboxylase (GAD65), and unmethylated insulin DNA, measured at subpicomolar sensitivity, and study their discharge kinetics, power for outcome prediction, and detection of graft loss during follow-up. Results: At 60 minutes after transplantation, GAD65 and miR-375 consistently showed near-equimolar and correlated increases proportional to the number of implanted β cells. GAD65 and miR-375 showed comparable power to predict poor graft outcome at 2 months, with areas under the curve of 0.833 and 0.771, respectively (P = 0.53). Using receiver operating characteristic analysis, we defined likelihood ratios (LRs) for rationally selected result intervals. In GADA-negative recipients (n = 28), GAD65 <4.5 pmol/L (LR = 0.15) and >12.2 pmol/L (LR = ∞) predicted good and poor outcomes, respectively. miR-375 could be used in all recipients irrespective of GAD65 autoantibody status (n = 46), with levels <1.4 pmol/L (LR = 0.14) or >7.6 pmol/L (LR = 9.53) as dual thresholds. The posttransplant surge of unmethylated insulin DNA was inconsistent and unrelated to outcome. Combined measurement of these three biomarkers was also tested as liquid biopsy for β cell death during 2-month follow-up; incidental surges of GAD65, miR-375, and (un)methylated insulin DNA, alone or combined, were confidently detected but could not be related to outcome. Conclusions: GAD65 and miR-375 performed equally well in quantifying early graft destruction and predicting graft outcome, outperforming unmethylated insulin DNA.
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    Depressed basal hypothalamic neuronal activity in type-1 diabetic mice is correlated with proinflammatory secretion of HMBG1
    (Elsevier, 2016-02-26) Thinschmidt, Jeffrey S.; Colon-Perez, Luis M.; Febo, Marcelo; Caballero, Sergio; King, Michael A.; White, Fletcher A.; Grant, Maria B.; Department of Ophthalmology, School of Medicine
    We recently found indicators of hypothalamic inflammation and neurodegeneration linked to the loss of neuroprotective factors including insulin-like growth factor (IGF-1) and IGF binding protein-2 (IGFBP-3) in mice made diabetic using streptozotocin (STZ). In the current work, a genetic model of type-1 diabetes (Ins2(Akita) mouse) was used to evaluate changes in neuronal activity and concomitant changes in the proinflammatory mediator high-mobility group box-1 (HMBG1). We found basal hypothalamic neuronal activity as indicated by manganese-enhanced magnetic resonance imaging (MEMRI) was significantly decreased in 8 months old, but not 2 months old Ins2(Akita) diabetic mice compared to controls. In tissue from the same animals we evaluated the expression of HMBG1 using immunohistochemistry and confocal microscopy. We found decreased HMBG1 nuclear localization in the paraventricular nucleus of the hypothalamus (PVN) in 8 months old, but not 2 months old diabetic animals indicating nuclear release of the protein consistent with an inflammatory state. Adjacent thalamic regions showed little change in HMBG1 nuclear localization and neuronal activity as a result of diabetes. This work extends our previous findings demonstrating changes consistent with hypothalamic neuroinflammation in STZ treated animals, and shows active inflammatory processes are correlated with changes in basal hypothalamic neuronal activity in Ins2(Akita) mice.
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    Diabetes Care and Research: What Should Be the Next Frontier?
    (American Diabetes Association, 2016-02) Marrero, David G.; Department of Medicine, IU School of Medicine
    EDITOR'S NOTE: This article is adapted from the address of the American Diabetes Association (ADA) President, Health Care and Education, given in June 2015 at the Association's 75th Scientific Sessions in Boston, Mass. A webcast of this speech is available for viewing at the ADA website (http://professional.diabetes.org/webcasts).
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    Dysglycemia and Index60 as Prediagnostic End Points for Type 1 Diabetes Prevention Trials
    (American Diabetes Association, 2017-11) Nathan, Brandon M.; Boulware, David; Geyer, Susan; Atkinson, Mark A.; Colman, Peter; Goland, Robin; Russell, William; Wentworth, John M.; Wilson, Darrell M.; Evans-Molina, Carmella; Wherrett, Diane; Skyler, Jay S.; Moran, Antoinette; Sosenko, Jay M.; Type 1 Diabetes TrialNet and Diabetes Prevention Trial–Type 1 Study Groups; Medicine, School of Medicine
    OBJECTIVE: We assessed dysglycemia and a T1D Diagnostic Index60 (Index60) ≥1.00 (on the basis of fasting C-peptide, 60-min glucose, and 60-min C-peptide levels) as prediagnostic end points for type 1 diabetes among Type 1 Diabetes TrialNet Pathway to Prevention Study participants. RESEARCH DESIGN AND METHODS: Two cohorts were analyzed: 1) baseline normoglycemic oral glucose tolerance tests (OGTTs) with an incident dysglycemic OGTT and 2) baseline Index60 <1.00 OGTTs with an incident Index60 ≥1.00 OGTT. Incident dysglycemic OGTTs were divided into those with (DYS/IND+) and without (DYS/IND-) concomitant Index60 ≥1.00. Incident Index60 ≥1.00 OGTTs were divided into those with (IND/DYS+) and without (IND/DYS-) concomitant dysglycemia. RESULTS: The cumulative incidence for type 1 diabetes was greater after IND/DYS- than after DYS/IND- (P < 0.01). Within the normoglycemic cohort, the cumulative incidence of type 1 diabetes was higher after DYS/IND+ than after DYS/IND- (P < 0.001), whereas within the Index60 <1.00 cohort, the cumulative incidence after IND/DYS+ and after IND/DYS- did not differ significantly. Among nonprogressors, type 1 diabetes risk at the last OGTT was greater for IND/DYS- than for DYS/IND- (P < 0.001). Hazard ratios (HRs) of DYS/IND- with age and 30- to 0-min C-peptide were positive (P < 0.001 for both), whereas HRs of type 1 diabetes with these variables were inverse (P < 0.001 for both). In contrast, HRs of IND/DYS- and type 1 diabetes with age and 30- to 0-min C-peptide were consistent (all inverse [P < 0.01 for all]). CONCLUSIONS: The findings suggest that incident dysglycemia without Index60 ≥1.00 is a suboptimal prediagnostic end point for type 1 diabetes. Measures that include both glucose and C-peptide levels, such as Index60 ≥1.00, appear better suited as prediagnostic end points.
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