Abstract: Basic and Clinical Science
Topic: Diabetes management 

Abstract title: Glycemic variability in idiopathic chronic pancreatitis : Association with pancreatic exocrine insufficiency and GLP-1

N. Tandon1, N. Pandey1, M. Kalaivani2, P. Garg3

1All India Institute of Medical Sciences, Department of Endocrinology, New Delhi, India.
2All India Institute of Medical Sciences, Department of Biostatistics, New Delhi, India.
3All India Institute of Medical Sciences, Department of Gastroenterology, New Delhi, India.


Background
Diabetes mellitus associated with chronic pancreatitis (CP) with coexistent pancreatic exocrine disease often shows poor metabolic control.
Exocrine insufficiency causes malabsorption, which, through several mechanisms including interference with glucagon like peptide -1 (GLP-1) secretion, may contribute to glycemic variability (GV). 

Aim
To study impact of exocrine insufficiency on GV as estimated using continuous glucose monitoring system (CGMS) and to assess post-prandial GLP-1 responses as a contributory factor to GV in diabetic patients with idiopathic chronic pancreatitis with exocrine insufficiency

Method
21 insulin treated CP patients had CGMS installed for 3 consecutive days. CGMS data was computed for the first 48 hours of insertion.
Glycemic variables -SD, M-value, mean amplitude of glycemic excursions (MAGE), Lability Index (LI), J-Index, Low Blood Glucose Index (LBGI), High Blood Glucose Index (HBGI), continuous overlapping net glycemic action (CONGA), and mean of daily differences (MODD), were calculated using Software.  

A mixed meal test was conducted on all patients and 10 healthy controls. Blood samples for GLP-1 Total, Glucagon and C-peptide at 0, 30 and 60 minutes were collected and analyzed. Patients with idiopathic CP were further categorized as those with pancreatic enzyme insufficiency (PEI) and with pancreatic exocrine sufficiency (PES), based on fecal fat excretion (> or <7gm/day) and their GV and post-prandial hormonal responses were compared. 

Results
While most CGM measures were comparable between the two CP groups, we observed frequent glycemic excursions (beyond the euglycemic range of 3.8-7.6 mmol/l){ 6(4-13) vs. 5(4-7), p=0.147}, increased percentage of time spent in hypoglycemia in 48 hours {6.5 (0-25) vs. 2.0 (0-13), p=0.562)}, and higher hypoglycemia risk indices in the PEI group when compared with the PES group.  Postprandial GLP-1 response expressed as area under curve was similar across both groups of CP and controls (p=0.144) 


Discussion
There was no statistically signifcant difference in  CGMS data of PEI 
and PES groups. There was a trend towards more glycemic excursions
 and increased time spent in hypoglycemia in the PEI group, possibly 
as a result of unpredictability of meal absorption and inconsistent gut response to  food products with variable fat content.
 Preserved post prandial GLP-1 response was observed in both exocr
ine sufficient and deficient groups, probably consequent to the stim
ulation of L cells by undigested food reaching the distal gut in CP patients.  Similar observations were reported  by  Knop et al ( 2007) in a small study on eight CP patients.
 
Our data suggest that exocrine insufficiency modestly influences glycemic variability and does not significantly impact circulating GLP-1 levels and postprandial hormone responses in patients with idiopathic chronic pancreatitis.


Conflict of interest
 I have no potential conflict of interest to disclose

Glycemic variability in idiopathic chronic pancreatitis: association with pancreatic exocrine insufficiency and GLP-1