Glycemic variability in chronic calcific pancreatitis with diabetes mellitus and its possible determinants

Aims

To study glycemic patterns and variability in patients with pancreatic diabetes or type 3c Diabetes mellitus (DM) due to chronic pancreatitis and its subtypes and assess the role of pancreatic enzyme replacement therapy (ERT) in modulating glycemic variability.

Methods

Patients having type 3c DM due to chronic pancreatitis, and on insulin underwent Flash continuous-glucose-monitoring (CGM) for 14 days. Parameters were compared between patients with fibrocalculous pancreatic diabetes (FCPD) and non-FCPD-chronic calcific pancreatitis (non-FCPD) and between the recipients and non-recipients of pancreatic enzyme-replacement-therapy (ERT).

Results

Out of 54 patients with pancreatic diabetes, 35 patients had chronic calcific pancreatitis. They underwent CGM, median HbA1c 9.20 % (77 mmol/mol) and mean Time-In-Range (TIR) being 41.21 % (23.48). Only 5 (15.2 %) patients achieved target TIR>70 % while 16 (48.5 %) patients had high glycemic-variability [Coefficient-of-variation (CV) > 36 %]. Patients with FCPD (n = 14) had higher hypoglycemia-indices like Time-Below-Range (18.92 % vs 8.20 %; p = 0.03) and Low-Blood-Glucose-Index (18.14 % vs 6.04 %; p = 0.02) compared to non-FCPD (n = 21). HbA1c% and hyperglycemic excursions were similar in both groups. Recipients of ERT (n = 20) had lower glycemic-variability [Standard Deviation (SD) 52.15 % vs 68.14 % and CV 32.59 % vs 41.79 %, p < 0.05 for both) than non-recipients. ERT-recipients had no serious hypoglycemia within the 14 days. On subgroup analysis, lower glycemic-variability and hypoglycemia with ERT were seen only in FCPD but not in non-FCPD subgroup (50.13 vs 77.91, 30.09 vs 48.36 for SD and CV respectively, p < 0.05).

Conclusion

Patients with type 3c DM due to chronic pancreatitis have high frequency of hyperglycemic and hypoglycemic excursions, with those with FCPD having a particularly higher risk of hypoglycemia and glycemic-variability. Those receiving pancreatic ERT had lesser glycemic variability and hypoglycemia. The small sample size and lack of objective markers of documentation of exocrine pancreatic insufficiency like fecal elastase highlight the need for further larger studies in this field.