The spectrum of diabetes in acute and chronic pancreatitis

Olesen, Søren Schou; Toledo, Frederico G. S.; Hart, Phil A.

doi:10.1097/mog.0000000000000864

Cited by 5 publications

(4 citation statements)

References 52 publications

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“…The progressive nature of DEP, especially associated with advanced chronic pancreatitis, often warrants treatment intensification, such that many patients initially controlled with metformin may ultimately require insulin once insulin deficiency develops. For example, a patient with PPDM-A who goes on to develop recurrent acute or chronic pancreatitis may also experience worsening glucose tolerance, necessitating changes in their antidiabetic regimen [ 17 ]. In a case series of 38 patients with DEP (6 associated with pancreatic cancer and 32 with benign pancreatic disease), metformin alone was the most common initial treatment, but 30 of the 38 patients required insulin within 12 months of diagnosis [ 18 ].…”

Section: Key Pharmacological Management Considerationsmentioning

confidence: 99%

Diabetes of the Exocrine Pancreas: Implications for Pharmacological Management

Goodarzi

Petrov

2023

Drugs

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Post-pancreatitis diabetes mellitus, pancreatic cancer-related diabetes, and cystic fibrosis-related diabetes are often underappreciated. As a result, a substantial proportion of people with these sub-types of diabetes receive antidiabetic medications that may be suboptimal, if not harmful, in the context of their underlying disease of the exocrine pancreas. The present article delineates both classical (biguanides, insulin, sulfonylureas, α-glucosidase inhibitors, thiazolidinediones, and meglitinides) and newer (glucagon-like peptide-1 receptor agonists, amylin analogs, dipeptidyl peptidase-4 inhibitors, sodium-glucose co-transporter-2 inhibitors, D2 receptor agonists, bile acid sequestrants, and dual glucagon-like peptide-1 receptor and glucose-dependent insulinotropic polypeptide receptor co-agonists) therapies and provides recommendations for managing people with diabetes of the exocrine pancreas based on the most up-to-date clinical evidence. Also, several emerging directions (lipid-enriched pathways, Y4 receptor agonism, glucagon-like peptide-1 and glucagon receptor co-agonism) are presented with a view to informing the process of new drug discovery and development.

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Section: Key Pharmacological Management Considerationsmentioning

confidence: 99%

Diabetes of the Exocrine Pancreas: Implications for Pharmacological Management

Goodarzi

Petrov

2023

Drugs

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“…The American Diabetes Association classifies CP‐related diabetes as type 3c diabetes, which shares many similarities with T2D in terms of clinical presentation and treatment 9 . According to a spectrum analysis of diabetes, in addition to the pathophysiological mechanisms associated with CP, many patients with CP‐related diabetes also have risk factors associated with T2D 10 . Another study showed that the combination of CP and T2D can lead to a mutually aggravating process involving insulin resistance, chronic low‐intensity inflammation, and dyslipidemia 11 .…”

Section: Introductionmentioning

confidence: 99%

“… 9 According to a spectrum analysis of diabetes, in addition to the pathophysiological mechanisms associated with CP, many patients with CP‐related diabetes also have risk factors associated with T2D. 10 Another study showed that the combination of CP and T2D can lead to a mutually aggravating process involving insulin resistance, chronic low‐intensity inflammation, and dyslipidemia. 11 Moreover, compared to comorbidity in CP‐T2D, patients with diabetes related to CP present a more aggressive phenotype (microangiopathy and infection) and higher need for glucose‐lowering treatment, and even patients who experience their first attack of pancreatitis may require long‐term management after being discharged from the hospital.…”

Section: Introductionmentioning

confidence: 99%

Transcriptomic analysis reveals the crosstalk between type 2 diabetes and chronic pancreatitis

Chen,

Hao,

Cong

et al. 2024

Health Science Reports

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Background and AimsMounting evidence highlights a strong association between chronic pancreatitis (CP) and type 2 diabetes (T2D), although the exact mechanism of interaction remains unclear. This study aimed to investigate the crosstalk genes and pathogenesis between CP and T2D.MethodsTranscriptomic gene expression profiles of CP and T2D were extracted from Gene Expression Omnibus, respectively, and the common differentially expressed genes (DEGs) were subsequently identified. Further analysis, such as Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein–protein interaction, transcription factors (TFs), microRNA (miRNAs), and candidate chemicals identification, was performed to explore the possible common signatures between the two diseases.ResultsIn total, we acquired 281 common DEGs by interacting CP and T2D datasets, and identified 10 hub genes using CytoHubba. GO and KEGG analyses revealed that endoplasmic reticulum stress and mitochondrial dysfunction were closely related to these common DEGs. Among the shared genes, EEF2, DLD, RAB5A, and SLC30A9 showed promising diagnostic value for both diseases based on receiver operating characteristic curve and precision‐recall curves. Additionally, we identified 16 key TFs and 16 miRNAs that were strongly correlated with the hub genes, which may serve as new molecular targets for CP and T2D. Finally, candidate chemicals that might become potential drugs for treating CP and T2D were screened out.ConclusionThis study provides evidence that there are shared genes and pathological signatures between CP and T2D. The genes EEF2, DLD, RAB5A, and SLC30A9 have been identified as having the highest diagnostic efficiency and could be served as biomarkers for these diseases, providing new insights into precise diagnosis and treatment for CP and T2D.

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“…However, treatment response in these patients has not been systematically assessed. Type 3c diabetes is a very heterogenous condition, [7,17] and therefore the different underlying causes could also potentially result in different treatment responses. In addition to the endocrine dysfunction that results in diabetes, the exocrine functions of the pancreas can be damaged resulting in pancreatic exocrine insufficiency (PEI).…”

Section: Introductionmentioning

confidence: 99%

Treatment outcomes with oral anti-hyperglycaemic therapies in people with diabetes secondary to a pancreatic condition (type 3c diabetes): A population-based cohort study

Hopkins,

Young,

Thomas

et al. 2024

Preprint

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ObjectivesDiabetes secondary to a pancreatic condition (type 3c diabetes) affects 5-10% of people with diabetes, but evidence on the efficacy and tolerability of oral therapies in this group are lacking. We aimed to assess short-term treatment outcomes with oral anti-hyperglycaemic therapies in people with type 3c diabetes.DesignPopulation-based cohort study.SettingUK primary care records (Clinical Practice Research Datalink; 2004-2020), linked hospital records.Participants7,084 people with a pancreatic condition (acute pancreatitis, chronic pancreatitis, pancreatic cancer, haemochromatosis) preceding diabetes diagnosis (type 3c cohort) initiating an oral glucose-lowering therapy (metformin, sulphonylureas, SGLT2-inhibitors, DPP4-inhibitors, or thiazolidinediones [TZDs]), without concurrent insulin treatment. This cohort was stratified by evidence of pancreatic exocrine insufficiency [PEI] (1,167 with PEI, 5,917 without) and matched to 97,227 type 2 diabetes (T2D) controls.Main outcome measures12-month HbA1c change and treatment discontinuation within 6 months, in the type 3c diabetes cohort compared to T2D controls.ResultsPeople with type 3c diabetes had a substantial mean HbA1c reduction with oral therapies in those with PEI (9.4 mmol/mol [95%CI 8.9 to 10.0]) and without (12.2 mmol/mol [12.0 to 12.4]). Compared to T2D controls, people with type 3c diabetes without PEI had a similar mean HbA1c reduction (0.7 mmol/mol [0.4 to 1.0] difference) and similar odds of early treatment discontinuation (Odds ratio [OR] 1.08 [0.98 to 1.19]). In contrast, people with type 3c diabetes and PEI had a lower mean HbA1c response (3.5 mmol/mol [2.9 to 4.1] lesser reduction), and greater discontinuation (OR 2.03 [1.73 to 2.36]). Results were largely consistent across type 3c subtypes and individual drug classes.ConclusionsOral anti-hyperglycaemic therapies are effective in people with type 3c diabetes, and could provide an important component of glycaemic management. However, the presence of PEI is associated with modestly reduced glycaemic response and reduced tolerability, meaning PEI could identify people that may benefit from closer monitoring after initiating oral therapy.What is already known on this topicDiabetes secondary to a pancreatic condition (type 3c diabetes) is common, affecting 5-10% of people with diabetes in Western populations.People with type 3c diabetes are commonly excluded from major diabetes drug trials, meaning there is a lack of management guidelines and evidence on the efficacy and tolerability of oral glucose-lowering therapies in this group.What this study addsOral glucose-lowering therapies are effective at treating hyperglycaemia in non-insulin treated type 3c diabetes, with largely similar responses to type 2 diabetes observed, and could provide an important component of glycaemic management.Pancreatic exocrine insufficiency is associated with modestly reduced glycaemic response and reduced tolerability.

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The spectrum of diabetes in acute and chronic pancreatitis

Cited by 5 publications

References 52 publications

Diabetes of the Exocrine Pancreas: Implications for Pharmacological Management

Diabetes of the Exocrine Pancreas: Implications for Pharmacological Management

Transcriptomic analysis reveals the crosstalk between type 2 diabetes and chronic pancreatitis

Treatment outcomes with oral anti-hyperglycaemic therapies in people with diabetes secondary to a pancreatic condition (type 3c diabetes): A population-based cohort study

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