Incretins in fibrocalculous pancreatic diabetes: A unique subtype of pancreatogenic diabetes

Abstract

Background: Studies evaluating endocrine and exocrine functions in fibrocalculous pancreatic diabetes (FCPD) are scarce. Methods: Insulin, C-peptide, glucagon, incretin hormones (glucagon-like peptide 1 [GLP-1] and gastric inhibitory peptide [GIP]), and dipeptidyl peptidase IV (DPP-IV) were estimated in patients with FCPD (n = 20), type 2 diabetes mellitus (T2DM) (n = 20), and controls (n = 20) in fasting and 60 minutes after 75 g glucose. Results: Fasting and post-glucose C-peptide and insulin in FCPD were lower than that of T2DM and controls. Plasma glucagon decreased after glucose load in controls (3.72, 2.29), but increased in T2DM (4.01, 5.73),and remained unchanged in FCPD (3.44, 3.44). Active GLP-1 (pmol/L) after glucose load increased in FCPD (6.14 to 9.72, P = <.001), in T2DM (2.87 to 4.62, P < .001), and in controls (3.91 to 6.13, P < .001). Median active GLP-1 in FCPD, both in fasting and post-glucose state (6.14, 9.72), was twice that of T2DM (2.87, 4.62) and 1.5 times that of controls (3.91, 6.13) (P < .001 for all). Post-glucose GIP (pmol/L) increased in all: FCPD (15.83 to 94.14), T2DM (21.85 to 88.29), and control (13.00 to 74.65) (P < .001 for all). GIP was not different between groups. DPP-IV concentration (ng/mL) increased in controls (1578.54, 3012.00) and FCPD (1609.95, 1995.42), but not in T2DM (1204.50, 1939) (P = .131). DPP-IV between the three groups was not different. Fecal elastase was low in FCPD compared with T2DM controls. Conclusions:In FCPD, basal C-peptide and glucagon are low, and glucagon does not increase after glucose load. GLP-1, but not GIP, in FCPD increases 1.5 to 2 times as compared with T2DM and controls (fasting and post glucose) without differences in DPP-IV.

The Cause and Effect Relationship of Diabetes after Acute Pancreatitis

“…It has been shown that in fibrocalculous pancreatic diabetes, basal C-peptide and glucagon are low, and glucagon concentration is not increased after glucose load. Glucagon-like peptide 1 (but not gastric inhibitory peptide) increased 1.5 to 2 times in fibrocalculous pancreatic diabetes as compared with T2DM and controls (fasting and post glucose), without differences in dipeptidyl peptidase IV [ 38 ].…”

“…T3cDM is associated with an incidence ranging from 25% to 80% with chronic pancreatitis [ 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 ]. The risk of diabetes in patients with chronic pancreatitis increases with the duration of the disease and with the severity of damage to the pancreas, especially in the early form of pancreatic calcifications.…”

“…Several studies have also been published on the prevention and treatment of newly diagnosed diabetes after AP, but risk factors remain controversial [ 3 , 9 , 45 ]. Therefore, a mechanism of T3cDM has been proposed, including inflammation, fibrosis, and hardening of the endocrine tissue of the pancreas, which leads to a gradual reduction and loss of β-cell function, leading to impaired or non-insulin secretion [ 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ] ( Figure 3 ).…”

Diagnosis of the Pancreatic Functional Insufficiency

“…При СД2 уровень глюкагона остается выше в базальном состоянии и повышается с увеличением глюкозной нагрузки. При СД3с уровень глюкагона остается низким в базальном состоянии и не повышается после нагрузки глюкозой, что отличает его от других типов СД [79].…”