Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Current Diabetes Reports
Published in: Current Diabetes Reports 10/2016

01-10-2016 | Pathogenesis of Type 1 Diabetes (A Pugliese, Section Editor)

Biomarkers of β-Cell Stress and Death in Type 1 Diabetes

Authors: Raghavendra G. Mirmira, Emily K. Sims, Farooq Syed, Carmella Evans-Molina

Published in: Current Diabetes Reports | Issue 10/2016

Login to get access

Abstract

The hallmark of type 1 diabetes (T1D) is a decline in functional β-cell mass arising as a result of autoimmunity. Immunomodulatory interventions at disease onset have resulted in partial stabilization of β-cell function, but full recovery of insulin secretion has remained elusive. Revised efforts have focused on disease prevention through interventions administered at earlier disease stages. To support this paradigm, there is a parallel effort ongoing to identify circulating biomarkers that have the potential to identify stress and death of the islet β-cells. Whereas no definitive biomarker(s) have been fully validated, several approaches hold promise that T1D can be reliably identified in the pre-symptomatic phase, such that either β-cell preservation or immunomodulatory agents might be employed in at-risk populations. This review summarizes the most promising protein- and nucleic acid-based biomarkers discovered to date and reviews the context in which they have been studied.
Literature
1.
Lehuen A, Diana J, Zaccone P, Cooke A. Immune cell crosstalk in type 1 diabetes. Nat Rev Immunol. 2010;10:501–13.CrossRefPubMed
2.
Herold KC, Gitelman SE, Masharani U, Hagopian W, Bisikirska B, Donaldson D, et al. A single course of anti-CD3 monoclonal antibody hOKT3gamma1(Ala-Ala) results in improvement in C-peptide responses and clinical parameters for at least 2 years after onset of type 1 diabetes. Diabetes. 2005;54:1763–9.CrossRefPubMed
3.
Herold KC, Hagopian W, Auger JA, Poumian-Ruiz E, Taylor L, Donaldson D, et al. Anti-CD3 monoclonal antibody in new-onset type 1 diabetes mellitus. N Engl J Med. 2002;346:1692–8.CrossRefPubMed
4.
Orban T, Bundy B, Becker DJ, DiMeglio LA, Gitelman SE, Goland R, et al. Co-stimulation modulation with abatacept in patients with recent-onset type 1 diabetes: a randomised, double-blind, placebo-controlled trial. Lancet. 2011;378:412–9.CrossRefPubMedPubMedCentral
5.
Pescovitz MD, Greenbaum CJ, Krause-Steinrauf H, Becker DJ, Gitelman SE, Goland R, et al. Rituximab, B-lymphocyte depletion, and preservation of beta-cell function. N Engl J Med. 2009;361:2143–52.CrossRefPubMed
6.
Rigby MR, DiMeglio LA, Rendell MS, Felner EI, Dostou JM, Gitelman SE, et al. Targeting of memory T cells with alefacept in new-onset type 1 diabetes (T1DAL study): 12 month results of a randomised, double-blind, placebo-controlled phase 2 trial. Lancet Diab Endocrinol. 2013;1:284–94.CrossRef
7.
Gregg BE, Moore PC, Demozay D, Hall BA, Li M, Husain A, et al. Formation of a human β-cell population within pancreatic islets is set early in life. J Clin Endocrinol Metab. 2012;97:3197–206.CrossRefPubMedPubMedCentral
8.
Meier JJ, Butler AE, Saisho Y, Monchamp T, Galasso R, Bhushan A, et al. Beta-cell replication is the primary mechanism subserving the postnatal expansion of beta-cell mass in humans. Diabetes. 2008;57:1584–94.CrossRefPubMedPubMedCentral
9.
Atkinson MA, Bluestone JA, Eisenbarth GS, Hebrok M, Herold KC, Accili D, et al. How does type 1 diabetes develop?: the notion of homicide or β-cell suicide revisited. Diabetes. 2011;60:1370–9.CrossRefPubMedPubMedCentral
10.
11.
12.
Insel RA, Dunne JL, Atkinson MA, Chiang JL, Dabelea D, Gottlieb PA, et al. Staging presymptomatic type 1 diabetes: a scientific statement of JDRF, the endocrine society, and the American Diabetes Association. Diabetes Care. 2015;38:1964–74.CrossRefPubMed
13.
Butler AE, Cao-Minh L, Galasso R, Rizza RA, Corradin A, Cobelli C, et al. Adaptive changes in pancreatic beta cell fractional area and beta cell turnover in human pregnancy. Diabetologia. 2010;53:2167–76.CrossRefPubMedPubMedCentral
14.
Eizirik DL, Miani M, Cardozo AK. Signalling danger: endoplasmic reticulum stress and the unfolded protein response in pancreatic islet inflammation. Diabetologia. 2013;56:234–41.CrossRefPubMed
15.
Engin F, Yermalovich A, Nguyen T, Hummasti S, Fu W, Eizirik DL, et al. Restoration of the unfolded protein response in pancreatic beta cells protects mice against type 1 diabetes. Sci Transl Med. 2013;5:211ra156.CrossRefPubMedPubMedCentral
16.
Tersey SA, Nishiki Y, Templin AT, Cabrera SM, Stull ND, Colvin SC, et al. Islet β-cell endoplasmic reticulum stress precedes the onset of type 1 diabetes in the nonobese diabetic mouse model. Diabetes. 2012;61:818–27.CrossRefPubMedPubMedCentral
17.
Yang C, Diiorio P, Jurczyk A, O’Sullivan-Murphy B, Urano F, Bortell R. Pathological endoplasmic reticulum stress mediated by the IRE1 pathway contributes to pre-insulitic beta cell apoptosis in a virus-induced rat model of type 1 diabetes. Diabetologia. 2013;56:2638–46.CrossRefPubMedPubMedCentral
18.
Marhfour I, Lopez XM, Lefkaditis D, Salmon I, Allagnat F, Richardson SJ, et al. Expression of endoplasmic reticulum stress markers in the islets of patients with type 1 diabetes. Diabetologia. 2012;55:2417–20.CrossRefPubMed
19.
Liu M, Wright J, Guo H, Xiong Y, Arvan P. Proinsulin entry and transit through the endoplasmic reticulum in pancreatic beta cells. Vitam Horm. 2014;95:35–62.CrossRefPubMed
20.
Engin F. ER stress and development of type 1 diabetes. J Investig Med. 2016;64:2–6.PubMed
21.
Ludvigsson J, Heding L. Abnormal proinsulin/C-peptide ratio in juvenile diabetes. Acta Diabetol Lat. 1982;19:351–8.CrossRefPubMed
22.
Snorgaard O, Hartling SG, Binder C. Proinsulin and C-peptide at onset and during 12 months cyclosporin treatment of type 1 (insulin-dependent) diabetes mellitus. Diabetologia. 1990;33:36–42.CrossRefPubMed
23.
Watkins RA, Evans-Molina C, Terrell JK, Day KH, Guindon L, Restrepo IA, et al. Proinsulin and heat shock protein 90 as biomarkers of beta-cell stress in the early period after onset of type 1 diabetes. Transl Res. 2016;168:96–106.e1.CrossRefPubMed
24.
Schölin A, Nyström L, Arnqvist H, Bolinder J, Björk E, Berne C, et al. Proinsulin/C-peptide ratio, glucagon and remission in new-onset type 1 diabetes mellitus in young adults. Diabet Med. 2011;28:156–61.CrossRefPubMed
25.
Røder ME, Knip M, Hartling SG, Karjalainen J, Akerblom HK, Binder C. Disproportionately elevated proinsulin levels precede the onset of insulin-dependent diabetes mellitus in siblings with low first phase insulin responses. The Childhood Diabetes in Finland Study Group. J Clin Endocrinol Metab. 1994;79:1570–5.PubMed
26.
Truyen I, De Pauw P, Jørgensen PN, Van Schravendijk C, Ubani O, Decochez K, et al. Proinsulin levels and the proinsulin:C-peptide ratio complement autoantibody measurement for predicting type 1 diabetes. Diabetologia. 2005;48:2322–9.CrossRefPubMed
27.••
Sims EK, Chaudhry Z, Watkins RA, Syed F, Blum J, Fangqian O, et al. Elevations in the fasting serum proinsulin:C-peptide ratio precede the onset of type 1 diabetes. Diabetes Care. 2016. doi:10.​2337/​dc15-2849. Sims and colleagues demonstrated an increase in the PI:C ratio 12 months prior to T1D diagnosis in subjects followed in the TrialNet Pathway to Prevention study, with the most pronounced elevations observed in subjects ≤10 years of age. Logistic regression analysis, adjusted for age and body mass index, demonstrated an increased odds of progression to T1D with higher PI:C ratios.PubMed
28.
Erener S, Mojibian M, Fox JK, Denroche HC, Kieffer TJ. Circulating miR-375 as a biomarker of β-cell death and diabetes in mice. Endocrinology. 2013;154:603–8.CrossRefPubMed
29.••
Kanak MA, Takita M, Shahbazov R, Lawrence MC, Chung WY, Dennison AR, et al. Evaluation of MicroRNA375 as a novel biomarker for graft damage in clinical islet transplantation. Transplantation. 2015;99:1568–73. Circulating levels of miR-375 in persons undergoing autologous or allogeneic islet transplantation were analyzed and plasma miR-375 levels were found to be significantly higher in recipients of islet transplants compared to a control group who had not undergone transplantation.CrossRefPubMed
30.
Roggli E, Britan A, Gattesco S, Lin-Marq N, Abderrahmani A, Meda P, et al. Involvement of microRNAs in the cytotoxic effects exerted by proinflammatory cytokines on pancreatic beta-cells. Diabetes. 2010;59:978–86.CrossRefPubMedPubMedCentral
31.
Nielsen LB, Wang C, Sørensen K, Bang-Berthelsen CH, Hansen L, Andersen M-LM, et al. Circulating levels of microRNA from children with newly diagnosed type 1 diabetes and healthy controls: evidence that miR-25 associates to residual beta-cell function and glycaemic control during disease progression. Exp Diabetes Res. 2012;2012:896362.PubMedPubMedCentral
32.
Kim KW, Ho A, Alshabee-Akil A, Hardikar AA, Kay TWH, Rawlinson WD, et al. Coxsackievirus B5 infection induces dysregulation of microRNAs predicted to target known type 1 diabetes risk genes in human pancreatic islets. Diabetes. 2016;65:996–1003.CrossRefPubMed
33.
Husseiny MI, Kaye A, Zebadua E, Kandeel F, Ferreri K. Tissue-specific methylation of human insulin gene and PCR assay for monitoring beta cell death. PLoS ONE. 2014;9:e94591.CrossRefPubMedPubMedCentral
34.••
Lehmann-Werman R, Neiman D, Zemmour H, Moss J, Magenheim J, Vaknin-Dembinsky A, et al. Identification of tissue-specific cell death using methylation patterns of circulating DNA. Proc Natl Acad Sci U S A. 2016;113:E1826–34. In this article, Lehmann-Werman and colleagues introduced a cell-free insulin DNA assay based on detection of the methylation status of 6 regional CpG sites in the insulin promoter. The authors found that demethylation at all 6 sites was present in ∼80% of DNA molecules from β cells compared to less than 0.01% of DNA from other tissues. The assay was subsequently validated in samples from subjects with T1D and in persons undergoing islet transplantation.CrossRefPubMed
35.
Akirav EM, Lebastchi J, Galvan EM, Henegariu O, Akirav M, Ablamunits V, et al. Detection of β cell death in diabetes using differentially methylated circulating DNA. Proc Natl Acad Sci U S A. 2011;108:19018–23.CrossRefPubMedPubMedCentral
36.••
Fisher MM, Watkins RA, Blum J, Evans-Molina C, Chalasani N, DiMeglio LA, et al. Elevations in circulating methylated and unmethylated preproinsulin DNA in new-onset type 1 diabetes. Diabetes. 2015;64:3867–72. Utilizing a droplet digital PCR-based assay, Fisher and colleagues demonstrated that circulating levels of both unmethylated and methylated insulin DNA were elevated in subjects with new onset T1D. Methylated insulin DNA remained elevated up to 8 weeks after T1D onset, while unmethylated insulin DNA levels decreased after diagnosis.CrossRefPubMed
37.••
Herold KC, Usmani-Brown S, Ghazi T, Lebastchi J, Beam CA, Bellin MD, et al. β cell death and dysfunction during type 1 diabetes development in at-risk individuals. J Clin Invest. 2015;125:1163–73. Herold and colleagues analyzed samples from the TrialNet Pathway to Prevention Cohort and found that individuals at high risk for T1D had increased levels of unmethylated insulin DNA during the presymptomatic phase of T1D.CrossRefPubMedPubMedCentral
38.
Olsen JA, Kenna LA, Spelios MG, Hessner MJ, Akirav EM. Circulating differentially methylated amylin DNA as a biomarker of β-cell loss in type 1 diabetes. PLoS ONE. 2016;11:e0152662.CrossRefPubMedPubMedCentral
39.
Hartling SG, Knip M, Røder ME, Dinesen B, Akerblom HK, Binder C. Longitudinal study of fasting proinsulin in 148 siblings of patients with insulin-dependent diabetes mellitus. Study Group on Childhood Diabetes in Finland. Eur J Endocrinol. 1997;137:490–4.CrossRefPubMed
40.
Heding LG, Ludvigsson J. Human proinsulin in insulin-treated juvenile diabetics. Acta Paediatr Scand Suppl 1977;48–52.
41.
Hartling SG, Lindgren F, Dahlqvist G, Persson B, Binder C. Elevated proinsulin in healthy siblings of IDDM patients independent of HLA identity. Diabetes 1989;38:1271–1274.
42.
Lindgren FA, Hartling SG, Dahlquist GG, Binder C, Efendic S, Persson BE. Glucose-induced insulin response is reduced and proinsulin response increased in healthy siblings of type 1 diabetic patients. Diabet Med 1991;8:638–643.
43.
Spinas GA, Snorgaard O, Hartling SG, Oberholzer M, Berger W. Elevated proinsulin levels related to islet cell antibodies in first-degree relatives of IDDM patients. Diabetes Care 1992;15:632–637.
44.
Heaton DA, Millward BA, Gray P, Tun Y, Hales CN, Pyke DA, Leslie RD. Evidence of beta cell dysfunction which does not lead on to diabetes: a study of identical twins of insulin dependent diabetics. Br Med J (Clin Res Ed) 1987;294:145–146.
45.
Heaton DA, Millward BA, Gray IP, Tun Y, Hales CN, Pyke DA, Leslie RD. Increased proinsulin levels as an early indicator of B-cell dysfunction in non-diabetic twins of type 1 (insulin-dependent) diabetic patients. Diabetologia 1988;31:182–184.
46.
Lindgren FA, Hartling SG, Persson BE, Roder ME, Snellman K, Binder C, Dahlquist G. Proinsulin levels in newborn siblings of type 1 (insulin-dependent) diabetic children and their mothers. Diabetologia 1993;36:560–563.
47.
Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T. Identification of novel genes coding for small expressed RNAs. Science. 2001;294:853–8.CrossRefPubMed
48.
Lau NC, Lim LP, Weinstein EG, Bartel DP. An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans. Science. 2001;294:858–62.CrossRefPubMed
49.
Ørom UA, Nielsen FC, Lund AH. MicroRNA-10a binds the 5′UTR of ribosomal protein mRNAs and enhances their translation. Mol Cell. 2008;30:460–71.CrossRefPubMed
50.
Vasudevan S, Tong Y, Steitz JA. Switching from repression to activation: microRNAs can up-regulate translation. Science. 2007;318:1931–4.CrossRefPubMed
51.
52.
Kozomara A, Griffiths-Jones S. miRBase: annotating high confidence microRNAs using deep sequencing data. Nucleic Acids Res. 2014;42:D68–73.CrossRefPubMed
53.
Guay C, Menoud V, Rome S, Regazzi R. Horizontal transfer of exosomal microRNAs transduce apoptotic signals between pancreatic beta-cells. Cell Commun Signal. 2015;13:17.CrossRefPubMedPubMedCentral
54.
Lakhter AJ, Sims EK. Minireview: emerging roles for extracellular vesicles in diabetes and related metabolic disorders. Mol Endocrinol. 2015;29:1535–48.CrossRefPubMed
55.
Lee Y, El Andaloussi S, Wood MJA. Exosomes and microvesicles: extracellular vesicles for genetic information transfer and gene therapy. Hum Mol Genet. 2012;21:R125–34.CrossRefPubMed
56.
Barutta F, Tricarico M, Corbelli A, Annaratone L, Pinach S, Grimaldi S, et al. Urinary exosomal microRNAs in incipient diabetic nephropathy. PLoS One. 2013;8:e73798.CrossRefPubMedPubMedCentral
57.
Bijkerk R, Duijs JMGJ, Khairoun M, Ter Horst CJH, van der Pol P, Mallat MJ, et al. Circulating microRNAs associate with diabetic nephropathy and systemic microvascular damage and normalize after simultaneous pancreas-kidney transplantation. Am J Transplant. 2015;15:1081–90.CrossRefPubMed
58.
Figliolini F, Cantaluppi V, Lena MD, Beltramo S, Romagnoli R, Salizzoni M, et al. Isolation, characterization and potential role in beta cell-endothelium cross-talk of extracellular vesicles released from human pancreatic islets. PLoS ONE. 2014;9:e102521.CrossRefPubMedPubMedCentral
59.
de la Torre García N, Fernández-Durango R, Gómez R, Fuentes M, Roldán-Pallarés M, Donate J, et al. Expression of angiogenic microRNAs in endothelial progenitor cells from type 1 diabetic patients with and without diabetic retinopathy. Invest Ophthalmol Vis Sci. 2015;56:4090–8.CrossRef
60.
Guay C, Regazzi R. Circulating microRNAs as novel biomarkers for diabetes mellitus. Nat Rev Endocrinol. 2013;9:513–21.CrossRefPubMed
61.
Zampetaki A, Willeit P, Burr S, Yin X, Langley SR, Kiechl S, et al. Angiogenic microRNAs linked to incidence and progression of diabetic retinopathy in type 1 diabetes. Diabetes. 2016;65:216–27.PubMed
62.
63.
van de Bunt M, Gaulton KJ, Parts L, Moran I, Johnson PR, Lindgren CM, et al. The miRNA profile of human pancreatic islets and beta-cells and relationship to type 2 diabetes pathogenesis. PLoS ONE. 2013;8:e55272.CrossRefPubMedPubMedCentral
64.
Poy MN, Eliasson L, Krutzfeldt J, Kuwajima S, Ma X, Macdonald PE, et al. A pancreatic islet-specific microRNA regulates insulin secretion. Nature. 2004;432:226–30.CrossRefPubMed
65.
Poy MN, Hausser J, Trajkovski M, Braun M, Collins S, Rorsman P, et al. miR-375 maintains normal pancreatic alpha- and beta-cell mass. Proc Natl Acad Sci U S A. 2009;106:5813–8.CrossRefPubMedPubMedCentral
60.••
Latreille M, Herrmanns K, Renwick N, Tuschl T, Malecki MT, McCarthy MI, et al. miR-375 gene dosage in pancreatic β-cells: implications for regulation of β-cell mass and biomarker development. J Mol Med. 2015;93:1159–69. This article found that only a relatively small proportion (∼1%) of circulating miR-375 originates from β cells, suggesting utility of this miRNA as a biomarker of β cell death but not β cell mass.CrossRefPubMedPubMedCentral
67.
Osipova J, Fischer D-C, Dangwal S, Volkmann I, Widera C, Schwarz K, et al. Diabetes-associated microRNAs in pediatric patients with type 1 diabetes mellitus: a cross-sectional cohort study. J Clin Endocrinol Metab. 2014;99:E1661–5.CrossRefPubMed
68.
Sebastiani G, Grieco FA, Spagnuolo I, Galleri L, Cataldo D, Dotta F. Increased expression of microRNA miR-326 in type 1 diabetic patients with ongoing islet autoimmunity. Diabetes Metab Res Rev. 2011;27:862–6.CrossRefPubMed
69.
Wu G-C, Pan H-F, Leng R-X, Wang D-G, Li X-P, Li X-M, et al. Emerging role of long noncoding RNAs in autoimmune diseases. Autoimmun Rev. 2015;14:798–805.CrossRefPubMed
70.
71.
Hakonarson H, Grant SFA, Bradfield JP, Marchand L, Kim CE, Glessner JT, et al. A genome-wide association study identifies KIAA0350 as a type 1 diabetes gene. Nature. 2007;448:591–4.CrossRefPubMed
72.
Plagnol V, Howson JMM, Smyth DJ, Walker N, Hafler JP, Wallace C, et al. Genome-wide association analysis of autoantibody positivity in type 1 diabetes cases. PLoS Genet. 2011;7:e1002216.CrossRefPubMedPubMedCentral
73.
Todd JA, Walker NM, Cooper JD, Smyth DJ, Downes K, Plagnol V, et al. Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes. Nat Genet. 2007;39:857–64.CrossRefPubMedPubMedCentral
74.
Wallace C, Smyth DJ, Maisuria-Armer M, Walker NM, Todd JA, Clayton DG. The imprinted DLK1-MEG3 gene region on chromosome 14q32.2 alters susceptibility to type 1 diabetes. Nat Genet. 2010;42:68–71.CrossRefPubMed
75.
Motterle A, Gattesco S, Caille D, Meda P, Regazzi R. Involvement of long non-coding RNAs in beta cell failure at the onset of type 1 diabetes in NOD mice. Diabetologia. 2015;58:1827–35.CrossRefPubMed
76.
Carter G, Miladinovic B, Patel AA, Deland L, Mastorides S, Patel NA. Circulating long noncoding RNA GAS5 levels are correlated to prevalence of type 2 diabetes mellitus. BBA Clin. 2015;4:102–7.CrossRefPubMedPubMedCentral
77.
Schwarzenbach H, Hoon DSB, Pantel K. Cell-free nucleic acids as biomarkers in cancer patients. Nat Rev Cancer. 2011;11:426–37.CrossRefPubMed
78.
79.
Stebbing J, Bower M, Syed N, Smith P, Yu V, Crook T. Epigenetics: an emerging technology in the diagnosis and treatment of cancer. Pharmacogenomics. 2006;7:747–57.CrossRefPubMed
80.
Grady WM, Rajput A, Lutterbaugh JD, Markowitz SD. Detection of aberrantly methylated hMLH1 promoter DNA in the serum of patients with microsatellite unstable colon cancer. Cancer Res. 2001;61:900–2.PubMed
81.
Kuroda A, Rauch TA, Todorov I, Ku HT, Al-Abdullah IH, Kandeel F, et al. Insulin gene expression is regulated by DNA methylation. PLoS One. 2009;4:e6953.CrossRefPubMedPubMedCentral
82.
Yang BT, Dayeh TA, Kirkpatrick CL, Taneera J, Kumar R, Groop L, et al. Insulin promoter DNA methylation correlates negatively with insulin gene expression and positively with HbA1c levels in human pancreatic islets. Diabetologia. 2010;54:360–7.CrossRefPubMedPubMedCentral
83.
Husseiny MI, Kuroda A, Kaye AN, Nair I, Kandeel F, Ferreri K. Development of a quantitative methylation-specific polymerase chain reaction method for monitoring beta cell death in type 1 diabetes. PLoS One. 2012;7:e47942.CrossRefPubMedPubMedCentral
84.
Lebastchi J, Deng S, Lebastchi AH, Beshar I, Gitelman S, Willi S, et al. Immune therapy and β-cell death in type 1 diabetes. Diabetes. 2013;62:1676–80.CrossRefPubMedPubMedCentral
85.
Fisher MM, Perez Chumbiauca CN, Mather KJ, Mirmira RG, Tersey SA. Detection of islet β-cell death in vivo by multiplex PCR analysis of differentially methylated DNA. Endocrinology. 2013;154:3476–81.CrossRefPubMedPubMedCentral
86.
Usmani-Brown S, Lebastchi J, Steck AK, Beam C, Herold KC, Ledizet M. Analysis of β-cell death in type 1 diabetes by droplet digital PCR. Endocrinology. 2014;155:3694–8.CrossRefPubMedPubMedCentral
81.•
Rui J, Deng S, Lebastchi J, Clark PL, Usmani-Brown S, Herold KC. Methylation of insulin DNA in response to proinflammatory cytokines during the progression of autoimmune diabetes in NOD mice. Diabetologia. 2016;59:1021–9. The authors showed that during progression to Type 1 diabetes, the methylation status of the insulin gene in islets from NOD mice changed in a dynamic fashion. The authors also demonstrated that treatment of isolated islets with a cocktail of pro-inflammatory cytokines led to increased methylation of the insulin gene.CrossRefPubMed
Metadata
Title
Biomarkers of β-Cell Stress and Death in Type 1 Diabetes
Authors
Raghavendra G. Mirmira
Emily K. Sims
Farooq Syed
Carmella Evans-Molina
Publication date
01-10-2016
Publisher
Springer US
Published in
Current Diabetes Reports / Issue 10/2016
Print ISSN: 1534-4827
Electronic ISSN: 1539-0829
DOI
https://doi.org/10.1007/s11892-016-0783-x

Other articles of this Issue 10/2016

Current Diabetes Reports 10/2016 Go to the issue

Obesity (J McCaffery, Section Editor)

Salivary Amylase: Digestion and Metabolic Syndrome

Treatment of Type 1 Diabetes (M Pietropaolo, Section Editor)

Immune Intervention and Preservation of Pancreatic Beta Cell Function in Type 1 Diabetes

Microvascular Complications—Retinopathy (JK Sun and PS Silva, Section Editors)

Surgery for Diabetic Eye Complications

Lifestyle Management to Reduce Diabetes/Cardiovascular Risk (C Shay and B Conway, Section Editors)

Viral Hepatitis and Diabetes: Clinical Implications of Diabetes Prevention Through Hepatitis Vaccination

Microvascular Complications—Retinopathy (JK Sun and PS Silva, Section Editors)

Fenofibrate and Diabetic Retinopathy

Health Care Delivery Systems and Implementation in Diabetes (EB Morton-Eggleston and ME McDonnell, Section Editors)

Academic Detailing in Diabetes: Using Outreach Education to Improve the Quality of Care
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits