Increased variability and abnormalities in pancreatic enzyme concentrations in otherwise asymptomatic subjects with type 2 diabetes

Abstract

Background

Recent studies have demonstrated an increased incidence of pancreatitis in patients with type 2 diabetes compared with obese nondiabetic individuals. Serum lipase and pancreatic amylase concentrations are used in conjunction with clinical findings to diagnose pancreatitis.

Methods

In two large clinical trials of overweight/obese nondiabetic and type 2 diabetic subjects, lipase and pancreatic amylase were measured at screening and 2–5 weeks later at baseline (prior to treatment with study medication).

Results

Lipase and pancreatic amylase concentrations were above the upper limit of normal (ULN) in 13% and 6% of type 2 diabetic subjects, respectively, and were approximately three-fold (3 ×) higher than the proportion of nondiabetic subjects with levels above ULN. Elevations exceeding ULN were seen in many subjects asymptomatic for pancreatitis; however, elevations >2 × ULN and >3 × ULN were uncommon, and elevations >3 × ULN were often associated with a history of dyslipidemia, hyperlipidemia, and gastrointestinal disorders. Additionally, enzyme concentrations varied within this 2–5-week screening period, including shifts between elevated and normal levels.

Conclusion

Results from this post hoc analysis suggest that, although pancreatic enzymes can be a useful marker for pancreatitis within the proper clinical context, diagnosis of pancreatitis may be confounded in populations known to have asymptomatic elevations associated with disease, such as type 2 diabetes. Further effort is needed to clarify the etiology and epidemiology of pancreatic enzyme elevations in type 2 diabetes.

Keywords:

• diabetes
• pancreatitis
• amylase
• lipase

Acknowledgments

We thank the patients and investigators who participated in the included studies. The authors also thank Carmelle V Remillard for her assistance in editing the manuscript and Maria Aisporna and Jenny Han for their assistance in data analysis.

Disclosure

This study was sponsored by Amylin Pharmaceuticals LLC. JM, KG, KS, and SC are employees and shareholders and PY is a previous employee of Amylin Pharmaceuticals LLC.