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Book: Type I diabetes

Gottlieb, Peter A.

(Endocrinology and metabolism clinics of North America ; 33,1)

2004

Author's details	guest ed. Peter A. Gottlieb
Series title	Endocrinology and metabolism clinics of North America ; 33,1
Collection
Language	English
Size	XII, 266 S. : Ill., graph. Darst.
Publisher	Saunders
Publishing place	Philadelphia u.a.
Publishing country	United States
Document type	Book
HBZ-ID	HT014017450
Database	Catalogue ZB MED Medicine, Health

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Article ; Online: Advances in Diabetes Treatment - Once-Weekly Insulin.

Gottlieb, Peter A / Michels, Aaron W

The New England journal of medicine

2020 Volume 383, Issue 22, Page(s) 2171–2172

MeSH term(s)	Diabetes Mellitus, Type 2/drug therapy ; Glucagon-Like Peptides ; Humans ; Hypoglycemic Agents/administration & dosage ; Insulin/administration & dosage ; Insulin, Regular, Human
Chemical Substances	Hypoglycemic Agents ; Insulin ; Insulin, Regular, Human ; Glucagon-Like Peptides (62340-29-8)
Language	English
Publishing date	2020-12-20
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	207154-x
ISSN	1533-4406 ; 0028-4793
ISSN (online)	1533-4406
ISSN	0028-4793
DOI	10.1056/NEJMe2031596
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Article ; Online: What defines disease in an age of genetics and biomarkers?

Gottlieb, Peter A

Current opinion in endocrinology, diabetes, and obesity

2015 Volume 22, Issue 4, Page(s) 296–299

Abstract: Purpose of review: The purpose of this review was to discuss the evidence suggesting that our definition of type 1 diabetes (T1D) needs to change to incorporate new data about risk of disease and how we should intervene in this wider spectrum of disease. ...

Abstract	Purpose of review: The purpose of this review was to discuss the evidence suggesting that our definition of type 1 diabetes (T1D) needs to change to incorporate new data about risk of disease and how we should intervene in this wider spectrum of disease. Recent findings: Autoantibodies can predict the development of T1D within defined periods of time. Other biomarkers are being developed that may further characterize stages of disease, as well as help define new pathways for treatment to prevent the development of hyperglycemia and full-blown diabetes. Summary: We have entered a new age in which prevention of disease is now possible based on changing the definition of diabetes to one that incorporates immunological markers that bring with them high risk. Further advances in our knowledge will continue to refine our ability to predict and hopefully eventually prevent T1D.
MeSH term(s)	Biomarkers ; Diabetes Mellitus, Type 1/diagnosis ; Diabetes Mellitus, Type 1/genetics ; Diabetes Mellitus, Type 1/immunology ; Humans
Chemical Substances	Biomarkers
Language	English
Publishing date	2015-08
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2272017-0
ISSN	1752-2978 ; 1752-296X
ISSN (online)	1752-2978
ISSN	1752-296X
DOI	10.1097/MED.0000000000000172
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Article ; Online: Learning From Past Failures of Oral Insulin Trials.

Michels, Aaron W / Gottlieb, Peter A

Diabetes

2018 Volume 67, Issue 7, Page(s) 1211–1215

Abstract: Very recently one of the largest type 1 diabetes prevention trials using daily administration of oral insulin or placebo was completed. After 9 years of study enrollment and follow-up, the randomized controlled trial failed to delay the onset of clinical ...

Abstract	Very recently one of the largest type 1 diabetes prevention trials using daily administration of oral insulin or placebo was completed. After 9 years of study enrollment and follow-up, the randomized controlled trial failed to delay the onset of clinical type 1 diabetes, which was the primary end point. The unfortunate outcome follows the previous large-scale trial, the Diabetes Prevention Trial-Type 1 (DPT-1), which again failed to delay diabetes onset with oral insulin or low-dose subcutaneous insulin injections in a randomized controlled trial with relatives at risk for type 1 diabetes. These sobering results raise the important question, "Where does the type 1 diabetes prevention field move next?" In this Perspective, we advocate for a paradigm shift in which smaller mechanistic trials are conducted to define immune mechanisms and potentially identify treatment responders. The stage is set for these interventions in individuals at risk for type 1 diabetes as Type 1 Diabetes TrialNet has identified thousands of relatives with islet autoantibodies and general population screening for type 1 diabetes risk is under way. Mechanistic trials will allow for better trial design and patient selection based upon molecular markers prior to large randomized controlled trials, moving toward a personalized medicine approach for the prevention of type 1 diabetes.
MeSH term(s)	Administration, Oral ; Clinical Trials as Topic/history ; Clinical Trials as Topic/methods ; Diabetes Mellitus, Type 1/blood ; Diabetes Mellitus, Type 1/drug therapy ; History, 20th Century ; History, 21st Century ; Humans ; Hypoglycemic Agents/administration & dosage ; Hypoglycemic Agents/adverse effects ; Insulin/administration & dosage ; Insulin/adverse effects ; Preventive Medicine/history ; Preventive Medicine/methods ; Preventive Medicine/trends ; Treatment Failure
Chemical Substances	Hypoglycemic Agents ; Insulin
Language	English
Publishing date	2018-06-19
Publishing country	United States
Document type	Historical Article ; Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	80085-5
ISSN	1939-327X ; 0012-1797
ISSN (online)	1939-327X
ISSN	0012-1797
DOI	10.2337/dbi17-0043
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Article ; Online: Endotypes in T1D: B lymphocytes and early onset.

Smith, Mia J / Cambier, John C / Gottlieb, Peter A

Current opinion in endocrinology, diabetes, and obesity

2020 Volume 27, Issue 4, Page(s) 225–230

Abstract: Purpose of review: Although type 1 diabetes (T1D) is characterized by destruction of the pancreatic beta cells by self-reactive T cells, it has become increasingly evident that B cells also play a major role in disease development, likely functioning as ...

Abstract	Purpose of review: Although type 1 diabetes (T1D) is characterized by destruction of the pancreatic beta cells by self-reactive T cells, it has become increasingly evident that B cells also play a major role in disease development, likely functioning as antigen-presenting cells. Here we review the biology of islet antigen-reactive B cells and their participation in autoimmune diabetes. Recent findings: Relative to late onset, individuals who develop T1D at an early age display increased accumulation of insulin-reactive B cells in islets. This B-cell signature is also associated with rapid progression of disease and responsiveness to B-cell depletion therapy. Also suggestive of B-cell participation in disease is loss of anergy in high-affinity insulin-reactive B cells. Importantly, loss of anergy is seen in patient's healthy first-degree relatives carrying certain T1D risk alleles, suggesting a role early in disease development. Summary: Recent studies indicate that islet-reactive B cells may play a pathogenic role very early in T1D development in young patients, and suggest utility of therapies that target these cells.
MeSH term(s)	Age of Onset ; Animals ; B-Lymphocytes/physiology ; Diabetes Mellitus, Type 1/epidemiology ; Diabetes Mellitus, Type 1/genetics ; Diabetes Mellitus, Type 1/immunology ; Diabetes Mellitus, Type 1/pathology ; Humans ; Insulin/immunology ; Insulin-Secreting Cells/immunology ; Islets of Langerhans/immunology ; T-Lymphocytes/physiology ; Time Factors
Chemical Substances	Insulin
Language	English
Publishing date	2020-06-18
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	2272017-0
ISSN	1752-2978 ; 1752-296X
ISSN (online)	1752-2978
ISSN	1752-296X
DOI	10.1097/MED.0000000000000547
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Article ; Online: Teplizumab: A Disease-Modifying Therapy for Type 1 Diabetes That Preserves β-Cell Function.

Herold, Kevan C / Gitelman, Stephen E / Gottlieb, Peter A / Knecht, Laura A / Raymond, Ralph / Ramos, Eleanor L

Diabetes care

2023 Volume 46, Issue 10, Page(s) 1848–1856

Abstract: Objective: In November 2022, teplizumab-mzwv became the first drug approved to delay the onset of stage 3 type 1 diabetes in adults and children age ≥8 years with stage 2 type 1 diabetes on the basis of data from the pivotal study TN-10.: Research ... ...

Abstract	Objective: In November 2022, teplizumab-mzwv became the first drug approved to delay the onset of stage 3 type 1 diabetes in adults and children age ≥8 years with stage 2 type 1 diabetes on the basis of data from the pivotal study TN-10. Research design and methods: To provide confirmatory evidence of the effects of teplizumab on preserving endogenous insulin production, an integrated analysis of C-peptide data from 609 patients (n = 375 patients receiving teplizumab and n = 234 control patients) from five clinical trials in stage 3 type 1 diabetes was conducted. Results: The primary outcome of the integrated analysis, change from baseline in stimulated C-peptide, was significantly improved at years 1 (average increase 0.08 nmol/L; P < 0.0001) and 2 (average increase 0.12 nmol/L; P < 0.0001) after one or two courses of teplizumab. An analysis of exogenous insulin use was also conducted, showing overall reductions of 0.08 (P = 0.0001) and 0.10 units/kg/day (P < 0.0001) at years 1 and 2, respectively. An integrated safety analysis of five clinical trials that enrolled 1,018 patients with stage 2 or 3 type 1 diabetes (∼1,500 patient-years of follow-up for teplizumab-treated patients) was conducted. Conclusions: These data confirm consistency in the preservation of β-cell function, as measured by C-peptide, across multiple clinical trials. This analysis showed that the most common adverse events included lymphopenia, rash, and headache, a majority of which occurred during and after the first few weeks of teplizumab administration and generally resolved without intervention, consistent with a safety profile characterized by self-limited adverse events after one or two courses of teplizumab treatment.
MeSH term(s)	Adult ; Child ; Humans ; Diabetes Mellitus, Type 1/drug therapy ; C-Peptide ; Insulin, Regular, Human ; Antibodies, Monoclonal, Humanized/therapeutic use ; Insulin/therapeutic use
Chemical Substances	teplizumab (S4M959U2IJ) ; C-Peptide ; Insulin, Regular, Human ; Antibodies, Monoclonal, Humanized ; Insulin
Language	English
Publishing date	2023-08-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	441231-x
ISSN	1935-5548 ; 0149-5992
ISSN (online)	1935-5548
ISSN	0149-5992
DOI	10.2337/dc23-0675
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Article ; Online: Lower Prevalence of Diabetic Ketoacidosis at Diagnosis in Research Participants Monitored for Hyperglycemia.

Sooy, Morgan G Q / Pyle, Laura / Alonso, G Todd / Broncucia, Hali C / Rewers, Arleta / Gottlieb, Peter A / Simmons, Kimber M W / Rewers, Marian J / Steck, Andrea K

The Journal of clinical endocrinology and metabolism

2024

Abstract: Context: In Colorado children, the prevalence of diabetic ketoacidosis (DKA) at diagnosis of type 1 diabetes (T1D) has been increasing over time.: Objective: Evaluate the prevalence of and factors involved in DKA at T1D diagnosis among participants ... ...

Abstract	Context: In Colorado children, the prevalence of diabetic ketoacidosis (DKA) at diagnosis of type 1 diabetes (T1D) has been increasing over time. Objective: Evaluate the prevalence of and factors involved in DKA at T1D diagnosis among participants followed in monitoring research studies before diagnosis compared to patients from the community. Setting and participants: Patients < 18 years diagnosed with T1D between 2005 and 2021 at the Barbara Davis Center for Diabetes. Outcome: Prevalence of and factors associated with DKA at diagnosis among participants in preclinical monitoring studies compared to those diagnosed in the community. Results: Of 5049 subjects, 164 were active study participants, 42 inactive study participants, and 4843 were community patients. Active study participants, compared to community patients, had lower HbA1c (7.3% vs 11.9%]; P < 0.001) and less frequently experienced DKA (4.9% vs 48.5%; P < 0.001), including severe DKA (1.2% vs 16.2%; P < 0.001). Inactive study participants had intermediate levels for both prevalence and severity of DKA. DKA prevalence increased in community patients, from 44.0% to 55%, with less evidence for a temporal trend in study participants. DKA prevalence was highest in children <2 years (13% in active study participants vs 83% in community patients). In community patients, younger age (P = 0.0038), public insurance (P < 0.0001), rural residence (P < 0.0076), higher HbA1c (P < 0.0001), and ethnicity minority status (P < 0.0001) were associated with DKA at diagnosis. Conclusions: While DKA prevalence increases in community patients over time, it stayed <5% in active research participants, who have a 10 times lower prevalence of DKA at diagnosis, including in minorities.
Language	English
Publishing date	2024-03-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	3029-6
ISSN	1945-7197 ; 0021-972X
ISSN (online)	1945-7197
ISSN	0021-972X
DOI	10.1210/clinem/dgae158
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Article ; Online: An Insulin-Chromogranin A Hybrid Peptide Activates DR11-Restricted T Cells in Human Type 1 Diabetes.

Callebaut, Aïsha / Guyer, Perrin / Baker, Rocky L / Gallegos, Joylynn B / Hohenstein, Anita C / Gottlieb, Peter A / Mathieu, Chantal / Overbergh, Lut / Haskins, Kathryn / James, Eddie A

Diabetes

2024 Volume 73, Issue 5, Page(s) 743–750

MeSH term(s)	Humans ; Animals ; Mice ; Insulin ; T-Lymphocytes ; Proinsulin ; Diabetes Mellitus, Type 1 ; C-Peptide ; Chromogranin A ; Peptides ; Insulin, Regular, Human ; Epitopes ; Peptide Fragments
Chemical Substances	Insulin ; Proinsulin (9035-68-1) ; C-Peptide ; Chromogranin A ; Peptides ; Insulin, Regular, Human ; Epitopes ; Peptide Fragments
Language	English
Publishing date	2024-02-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	80085-5
ISSN	1939-327X ; 0012-1797
ISSN (online)	1939-327X
ISSN	0012-1797
DOI	10.2337/db23-0622
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Article ; Online: Genetic Associations with C-peptide Levels before Type 1 Diabetes Diagnosis in At-Risk Relatives.

Triolo, Taylor M / Parikh, Hemang M / Tosur, Mustafa / Ferrat, Lauric / You, Lu / Gottlieb, Peter A / Oram, Richard A / Onengut-Gumuscu, Suna / Krischer, Jeffrey P / Rich, Stephen S / Steck, Andrea K / Redondo, Maria J

The Journal of clinical endocrinology and metabolism

2024

Abstract: Objective: We sought to determine whether the type 1 diabetes genetic risk score-2 (T1D-GRS2) and single nucleotide polymorphisms (SNPs) are associated with C-peptide preservation before type 1 diabetes diagnosis.: Methods: We conducted a ... ...

Abstract	Objective: We sought to determine whether the type 1 diabetes genetic risk score-2 (T1D-GRS2) and single nucleotide polymorphisms (SNPs) are associated with C-peptide preservation before type 1 diabetes diagnosis. Methods: We conducted a retrospective analysis of 713 autoantibody-positive participants who developed type 1 diabetes in the TrialNet Pathway to Prevention Study who had T1DExomeChip data. We evaluated the relationships of 16 known SNPs and T1D-GRS2 with area under the curve (AUC) C-peptide levels during oral glucose tolerance tests conducted in the 9 months before diagnosis. Results: Higher T1D-GRS2 was associated with lower C-peptide AUC in the 9 months before diagnosis in univariate (β=-0.06, P<0.0001) and multivariate (β=-0.03, P=0.005) analyses. Participants with the JAZF1 rs864745 T allele had lower C-peptide AUC in both univariate (β=-0.11, P=0.002) and multivariate (β=-0.06, P=0.018) analyses. Conclusions: The type 2 diabetes-associated JAZF1 rs864745 T allele and higher T1D-GRS2 are associated with lower C-peptide AUC prior to diagnosis of type 1 diabetes, with implications for the design of prevention trials.
Language	English
Publishing date	2024-05-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	3029-6
ISSN	1945-7197 ; 0021-972X
ISSN (online)	1945-7197
ISSN	0021-972X
DOI	10.1210/clinem/dgae349
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Article ; Online: Editorial: cystic fibrosis.

Gottlieb, Peter A

Current opinion in endocrinology, diabetes, and obesity

2010 Volume 17, Issue 4, Page(s) 313

MeSH term(s)	Atherosclerosis/complications ; Autoimmunity/physiology ; Cystic Fibrosis/complications ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/genetics ; Diabetes Mellitus, Type 2/immunology ; Humans ; Inflammation/complications
Language	English
Publishing date	2010-08
Publishing country	England
Document type	Editorial ; Introductory Journal Article
ZDB-ID	2272017-0
ISSN	1752-2978 ; 1752-296X
ISSN (online)	1752-2978
ISSN	1752-296X
DOI	10.1097/MED.0b013e32833c2ffd
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