The multifaceted nature of diabetes mellitus induced by checkpoint inhibitors

AbstractImmune checkpoint inhibitors (CPI) are increasingly being used in oncology, and many autoimmune side effects have been described. Diabetes mellitus (DM) has been reported in approximately 1% of subjects treated with programmed cell death-1 and programmed death ligand 1 (PD-1/PD-L1) inhibitors, alone or in association with CTLA-4 inhibitors. In the present mini-review, we aimed to describe different clinical pictures and pathophysiology associated with these forms of diabetes. Data on CPI-related DM was gathered from the largest case series in the literature and from our centre dedicated to immunotherapy complications (ImmuCare —Hospices Civils de Lyon). Most cases are acute autoimmune insulin-dependent diabetes which are similar to fulminant diabetes (extremely acute onset with concomitant near-normal HbA1c levels). Other cases, however, have a phenotype close to type 2 diabetes or appear as a decompensation of previous ly known type 2 diabetes. The occurrence of diabetes can also be a complication of autoimmune pancreatitis induced by CPI use. Finally, two cases of diabetes in a context of autoimmune lipoatrophy have recently been described. Regarding the wide variety of CPI-induced diabetes, the discovery of a gl ucose disorder under CPI should motivate specialised care for aetiological diagnosis and appropriate treatment.
Source: Acta Diabetologica - Category: Endocrinology Source Type: research

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Abstract We monitored serum amylase level in patients with type 2 diabetes mellitus (T2DM) prescribed either dipeptidyl peptidase-4 inhibitor or GLP-1 analog (GLP-1 group) as monotherapy. Patients were treated for a 36-month period. All subjects were non-smoker and did not take any alcoholic beverages. Forty-nine patients were prescribed DPP4is (DPP4i group), and 9 patients were prescribed GLP-1 analogs (GLP-1 group). The median of serum amylase levels in DPP4is group was 73 U/mL and the median of serum amylase levels in GLP-1 analog group was 76. Thus, there was no statistical significance between the two ...
Source: Journal of Health, Population, and Nutrition - Category: International Medicine & Public Health Authors: Tags: J Health Popul Nutr Source Type: research
Conclusion: Pancreatic atrophy may be more common among children with DM, suggesting more advanced exocrine disease. However, data in this exploratory cohort also suggest increased autoimmunity and hypertriglyceridemia in children with DM, suggesting that risk factors for type 1 and type 2 DM, respectively may play a role in mediating DM development in children with pancreatitis.
Source: Journal of Pediatric Gastroenterology and Nutrition - Category: Gastroenterology Tags: Original Article: Pancreatology Source Type: research
AbstractThe dipeptidyl peptidase-4 inhibitor (DPP-4i) alogliptin is an oral, antidiabetic treatment that is approved in many countries to treat patients with type 2 diabetes mellitus (T2DM), including the USA, Europe, and Japan. Alogliptin is efficacious both as monotherapy and as add-on/combination therapy with other commonly prescribed T2DM treatments, such as metformin and pioglitazone. Overall, alogliptin is well-tolerated in patients with T2DM, including older patients, those with renal and/or hepatic impairment, and those at high risk of cardiovascular events. There is a low risk of hypoglycemia, weight gain, acute p...
Source: Drug Safety - Category: Drugs & Pharmacology Source Type: research
CONCLUSION: The relationship between gout and PPDM is bidirectional in the postpancreatitis setting. A prior history of gout is a risk factor of PPDM, particularly in women. PMID: 31615915 [PubMed - as supplied by publisher]
Source: J Rheumatol - Category: Rheumatology Authors: Tags: J Rheumatol Source Type: research
The objective of this study was to compare the preoperative serum levels of DPP-4 in patients with and without surgical finding of perivesicular inflammation. Materials and methods: a cross-sectional analytical study nested in a prospective cohort, including patients scheduled for elective cholecystectomy, without surgical complications, that were 18-70 years of age, with low cardiovascular risk, without a history of peritonitis, pancreatitis, or jaundice and underwent ERCP protocol, type 2 diabetes mellitus, acute inflammatory (Protein C Reactive
Source: Medicina (Kaunas) - Category: Universities & Medical Training Authors: Tags: Medicina (Kaunas) Source Type: research
ConclusionIn this pooled analysis of 10,058 patients among studies comparing exenatide with other glucose-lowering medications or placebo, pancreatitis was rare. The EAIRs of pancreatitis were low and similar between exenatide and non-exenatide treatment groups. No evidence of an association between exenatide and pancreatitis was observed.FundingBristol-Myers Squibb and AstraZeneca.Plain Language SummaryPlain language summary available for this article.
Source: Diabetes Therapy - Category: Endocrinology Source Type: research
From the Incretin Concept and the Discovery of GLP-1 to Today's Diabetes Therapy Jens Juul Holst* Department of Biomedical Sciences, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark Researchers have been looking for insulin-stimulating factors for more than 100 years, and in the 1960ties it was definitively proven that the gastrointestinal tract releases important insulinotropic factors upon oral glucose intake, so-called incretin hormones. The first significant factor identified was the duodenal glucose-dependent insulinotropic polypeptide, GIP, wh...
Source: Frontiers in Endocrinology - Category: Endocrinology Source Type: research
In conclusion, FGF21 belongs to a promising class of cytokines that are induced in response to stress and that can be used as a drug, drug target, or through a biomarker, depending on the physio-pathological context. All these findings will become clear when FGF21 will be used as a therapeutic molecule, exploiting the beneficial effects of FGF21 for treating metabolic disease or when it will be blocked to ameliorate disease progression and the onset of disease. Author Contributions CT and MS wrote the manuscript. VR contributed to the discussion. Funding This work was supported from the AFM-Telethon (19524), Italian Mi...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
Authors: Jansson L, Carlsson PO Abstract The pancreatic islets are more richly vascularized than the exocrine pancreas, and possess a 5- to 10-fold higher basal and stimulated blood flow, which is separately regulated. This is reflected in the vascular anatomy of the pancreas where islets have separate arterioles. There is also an insulo-acinar portal system, where numerous venules connect each islet to the acinar capillaries. Both islets and acini possess strong metabolic regulation of their blood perfusion. Of particular importance, especially in the islets, is adenosine and ATP/ADP. Basal and stimulated blood fl...
Source: Comprehensive Physiology - Category: Physiology Tags: Compr Physiol Source Type: research
Objective The aim of this study was to determine the association of the pancreatic steatosis with obesity, chronic pancreatitis (CP), and type 2 diabetes mellitus. Methods Patients (n = 118) were retrospectively identified and categorized into no CP (n = 60), mild (n = 21), moderate (n = 27), and severe CP (n = 10) groups based on clinical history and magnetic resonance cholangiopancreatography using the Cambridge classification as the diagnostic standard. Visceral and subcutaneous compartments were manually segmented, and fat tissue was quantitatively measured on axial magnetic resonance imaging. Results Pancreati...
Source: Pancreas - Category: Gastroenterology Tags: Original Articles Source Type: research
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