Islet inflammation is associated with pancreatic fatty infiltration and hyperglycemia in type 2 diabetes

Abstract

IntroductionChronic inflammation is observed in type 2 diabetes islets, and fat deposition in the pancreas affects insulin secretion and glucose tolerance. However, the relationship between this inflammation and pancreatic fat deposition has not been elucidated.Research design and methodsWe examined pancreatic sections from 60 Japanese patients obtained by pancreatectomy. We evaluated pancreatic fat-cell area (%) and CD68-positive (CD68+) cells per islet histologically and examined the relationships between these histological findings and various clinical parameters.ResultsThe number of CD68+ cells per islet in the diabetes group was significantly higher than that in the normal glucose tolerance group (p=0.026). Moreover, CD68+ cells per islet were significantly correlated with body mass index (r=0.33, p=0.0080), fasting C-peptide immunoreactivity (r=0.46, p=0.0042), homeostasis model assessment insulin resistance (r=0.38, p=0.016), C-peptide index (r=0.38, p=0.018), the area under the glucose concentration curve (AUCglucose) at the 75 g oral glucose tolerance test (r=0.49, p=0.0065) and fat-cell area (r=0.51, p<0.0001). In multiple regression analyses, fat-cell area (β=0.600, p=0.0027) and AUCglucose (β=0.453, p=0.0042) were the independent and significant determinants of CD68+ cells per islet.ConclusionThe inflammation of islets is associated with pancreatic fatty infiltration and hyperglycemia, which may further aggravate glucose tolerance.

Beta-Cell Mass in Obesity and Type 2 Diabetes, and Its Relation to Pancreas Fat: A Mini-Review

“…The results in humans regarding the relationship between pancreatic fat and glucose metabolism are inconsistent [ 74 ]. We have reported that there is no significant difference in the intrapancreatic fat area between subjects with and without diabetes in a histological analysis [ 90 ], which is consistent with other histological studies [ 65 , 91 ]. On the other hand, several reports have shown that pancreatic fat increased with the progression of glucose intolerance or T2DM [ 92 , 93 , 94 ].…”

Ectopic Fat Accumulation in Pancreas and Heart

“…We investigated pancreatic fat-cell infiltration in nondiabetic patients undergoing pancreatectomy. We found that fat-cell infiltration was associated with postoperative deterioration of glucose tolerance [ 19 ], and that this infiltration in addition to hyperglycemia was also associated with islet inflammation, which was evaluated by macrophage infiltration around or within islets [ 20 ]. Furthermore, it has been clarified that pancreatic fat evaluated by computed tomography value is involved in the decrease in endogenous insulin-secreting capacity in type 2 diabetic patients [ 21 ].…”

Urolithins: Diet-Derived Bioavailable Metabolites to Tackle Diabetes

“…Analysis of histological pancreatic sections has shown high numbers of macrophage marker CD68+ cells in the vicinity of islets derived from individuals with diabetes. Noteworthy, in other studies, the presence of these cells in islets was positively correlated with the occurrence of amyloid structures and fibrosis [26,35] as well as increased body mass index, fasting C-peptide immunoreactivity, fat cell area, and hyperglycemia [36]. In the reported amyloid-positive cases, CD68 + cells predominated over tissue repair-oriented macrophages (double-positive for CD163 and CD204 markers) [35].…”