Obesity and Treatment of Diabetes With Glyburide May Both Be Risk Factors for Acute Pancreatitis

Blomgren, Kerstin B.; Sundström, Anders; Steineck, Gunnar; Wiholm, Bengt‐Erik

doi:10.2337/diacare.25.2.298

Cited by 99 publications

(78 citation statements)

References 13 publications

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“…Metformin, for example, which is frequently combined with incretin mimetics, is associated with a decreased cancer risk (Evans et al 2005), and decreased mortality in cancer patients (Gallagher & LeRoith 2011). Sulfonylurea on the other hand, might increase risk for pancreatitis (Blomgren et al 2002) and solid tumors (Currie et al 2009). …”

Section: Caveatsmentioning

confidence: 99%

GLP1 and cancer: friend or foe?

Vangoitsenhoven¹,

Mathieu²,

Schueren³

2012

Endocrine-Related Cancer

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The new incretin-based therapies, dipeptidyl peptidase-4 (DPP4) inhibitors and glucagon like peptide 1 (GLP1) receptor agonists are widely used for the treatment of type 2 diabetes because of their glucose-lowering capacity with low risk of hypoglycemia. As they are weight neutral or induce weight loss in this mostly overweight population, they are popular among clinicians and patients alike. Nonetheless, concerns have been raised about GLP1's trophic effects. While increased b cell mass observed in rodents sounds appealing for treatment of diabetes, there was also an increased incidence of medullary thyroid cancer (MTC) in some species. We reviewed literature available in the Medline database until March 2012. Safety signals have emerged for MTC and pancreatic carcinoma from adverse event databases in the United States and Europe. Considering the relatively short duration of these studies, it is more likely that premalignant lesions are stimulated in presence of GLP1, rather than new neoplasms induced. Moreover, interpreting results of animal studies is difficult because of species-specific differences in presence and density of GLP1 receptors. Furthermore, data are emerging suggesting beneficial effects of GLP1 on colon and breast cancer. In conclusion, presently, the benefits of using DPP4 inhibitors or GLP1 receptor agonists for treatment of type 2 diabetes outweigh the risks. Nonetheless, their safety profile should be monitored and their indications should be widened cautiously. At present they remain contra-indicated in patients with a personal or family history of MTC or multiple endocrine neoplasia type 2.

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Section: Caveatsmentioning

confidence: 99%

GLP1 and cancer: friend or foe?

Vangoitsenhoven¹,

Mathieu²,

Schueren³

2012

Endocrine-Related Cancer

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“…In addition, we did not compare the HbA1c level with the number of drugs used, a potential confounding situation, since few studies have shown a lower incidence of AP with lower HbA1c level due to metformin or glyburide use. 29,30 It is interesting to note that in 70.6% cases, alcohol was not found to be the predominant etiological risk factor. The diagnosis was based on patient evaluation at the time of enrollment.…”

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confidence: 99%

Demographic profile of Acute Pancreatitis in Eastern India: A Single Centre Experience

et al. 2017

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Background: Little is known about the etiological risk factors of acute pancreatitis (AP) in Eastern India. Aims and Objective: The aim of this study is to assess current trends etiology of AP in Eastern India. Materials and Methods: A retrospective study with cross-sectional design was undertaken based on available medical records of patients admit between January 2014 and January 2017 with physician-assigned diagnoses of AP at KPC Medical College & Hospital, Kolkata (n = 234). Multivariate analyses were done to identify risk factors, and distribution was compared on the basis gender. Groups were selected on the basis of a working diagnosis. A stratified comparison was done in 3 commonest etiology groups identified: ‘alcohol’, ‘non-alcohol’ and ‘idiopathic’.Results: The commonest etiology was attributed to alcohol (29.4%), idiopathic cause (20.5%), and obstructive cause (14.5%). Prevalence of AP was higher with alcoholism in men (37% vs. 10.8%; p < 00.1), however, other causes like idiopathic cause (12.3% vs. 37.8%), duct obstruction (1.2% vs. 43.2%), obesity (6.1% vs. 24.3%), and hypertriglyceridemia (6.1% vs. 14.8%) were higher among females ( p < 0.001 for all comparisons). Compared to non-alcoholics, patients with idiopathic AP were more likely to be overweight ( p = 0.019) and have T2 DM ( p = 0.021). Moreover, impact assessment of T2 DM status further revealed that the risk of AP was even greater with obesity (Odds Ratio [OR] 1.37; 95% Confidence Interval [CI] 0.57 – 3.26; p = 0.047) and smoking (OR 1.72; 95% CI 1.0 – 2.97; p = 0.049). Eighteen cases (7.7%) of ‘severe’ AP were identified, mostly due to: trauma in 6 (2.5%), idiopathic in 6 (2.5%), gallstones in 4 (1.7%), and alcoholism in 2 (0.8%).Conclusion: Alcohol intake is the predominant etiological risk factor for acute pancreatitis in Eastern India. Gender and type 2 diabetes mellitus are important contributory determinants.Asian Journal of Medical Sciences Vol.8(6) 2017 24-29

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“…Abdominal pain, ultrasound-confirmed pancreatic pathological changes and increased plasma amylase and lipase concentrations are the most common markers of acute pancreatitis in the clinic (21). Type 2 diabetes and/or obesity are risk factors for the development of pancreatitis, and obesity increases its severity and mortality rate (5,28,34). The cellular functions and molecular mechanisms responsible for initiating and modifying the severity of pancreatitis have not been fully elucidated.…”

mentioning

confidence: 99%

Exenatide does not evoke pancreatitis and attenuates chemically induced pancreatitis in normal and diabetic rodents

Tatarkiewicz

Smith

Sablan

et al. 2010

American Journal of Physiology-Endocrinology and Metabolism

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The risk of developing pancreatitis is elevated in type 2 diabetes and obesity. Cases of pancreatitis have been reported in type 2 diabetes patients treated with GLP-1 (GLP-1R) receptor agonists. To examine whether the GLP-1R agonist exenatide potentially induces or modulates pancreatitis, the effect of exenatide was evaluated in normal or diabetic rodents. Normal and diabetic rats received a single exenatide dose (0.072, 0.24, and 0.72 nmol/kg) or vehicle. Diabetic ob/ob or HF-STZ mice were infused with exenatide (1.2 and 7.2 nmol·kg Ϫ1 ·day Ϫ1 ) or vehicle for 4 wk. Post-exenatide treatment, pancreatitis was induced with caerulein (CRN) or sodium taurocholate (ST), and changes in plasma amylase and lipase were measured. In ob/ob mice, plasma cytokines (IL-1␤, IL-2, IL-6, MCP-1, IFN␥, and TNF␣) and pancreatitis-associated genes were assessed. Pancreata were weighed and examined histologically. Exenatide treatment alone did not modify plasma amylase or lipase in any models tested. Exenatide attenuated CRN-induced release of amylase and lipase in normal rats and ob/ob mice but did not modify the response to ST infusion. Plasma cytokines and pancreatic weight were unaffected by exenatide. Exenatide upregulated Reg3b but not Il6, Ccl2, Nfkb1, or Vamp8 expression. Histological analysis revealed that the highest doses of exenatide decreased CRN-or ST-induced acute inflammation, vacuolation, and acinar single cell necrosis in mice and rats, respectively. Ductal cell proliferation rates were low and similar across all groups of ob/ob mice. In conclusion, exenatide did not modify plasma amylase and lipase concentrations in rodents without pancreatitis and improved chemically induced pancreatitis in normal and diabetic rodents. diabetes; mouse; rat; caerulein; sodium taurocholate; pancreatic duct GLUCAGON-LIKE PEPTIDE-1 (GLP-1) exerts multiple glucoregulatory actions by enhancing glucose-dependent insulin secretion, regulating gastric emptying, decreasing postprandial glucagon secretion, and decreasing food intake. Moreover, GLP-1 has been observed to improve ␤-cell mass by augmenting ␤-cell survival and proliferation in rodents (7,19,42). In recent years, the therapeutic potential of GLP-1 receptor (GLP-1R) agonists or dipeptidyl peptidase IV (DPP IV) inhibitors for treatment of type 2 diabetes gained widespread attention, and several drugs affecting the GLP-1 pathway were approved to control hyperglycemia, including the GLP-1R agonists exenatide and liraglutide (12, 18) and the DPP IV inhibitors sitagliptin and saxagliptin.Cases of pancreatitis have been observed in patients treated with GLP-1 receptor agonists and DPP IV inhibitors (1, 9, 10, 13, 38). Acute pancreatitis is a complex clinical condition that ranges in severity from mild to life-threatening. Abdominal pain, ultrasound-confirmed pancreatic pathological changes and increased plasma amylase and lipase concentrations are the most common markers of acute pancreatitis in the clinic (21). Type 2 diabetes and/or obesity are risk factors for the development of pa...

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Obesity and Treatment of Diabetes With Glyburide May Both Be Risk Factors for Acute Pancreatitis

Cited by 99 publications

References 13 publications

GLP1 and cancer: friend or foe?

GLP1 and cancer: friend or foe?

Demographic profile of Acute Pancreatitis in Eastern India: A Single Centre Experience

Exenatide does not evoke pancreatitis and attenuates chemically induced pancreatitis in normal and diabetic rodents

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