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.

IntroductionThis study aimed to identify the associations between lifestyle factors and intrapancreatic fat deposition in patients with type 2 diabetes.Research design and methodsThe participants were 185 patients with type 2 diabetes who were hospitalized at Osaka University Hospital between 2008 and 2020 and underwent abdominal CT during hospitalization. Information regarding lifestyle factors, including the number of meals consumed per day, snacking habits, exercise habits, exercise at work, smoking habits, alcohol intake, insomnia, sleep apnea syndrome, and night-shift working, was acquired from self-administered questionnaires or medical records. We measured the mean CT values for the pancreas (P), liver (L), and spleen (S), and the visceral fat area (VFA), and quantified intrapancreatic and liver ectopic fat accumulation as P−S and L−S, respectively.ResultsAfter adjustment for age, sex, hemoglobin A1c, and body mass index (BMI), participants who consumed two meals per day had significantly lower P−S (higher intrapancreatic fat deposition, p=0.02) than those who consumed three meals per day. There were no significant associations between the number of meals consumed and liver ectopic fat accumulation and VFA (p=0.73 and p=0.67, respectively).ConclusionsPatients with diabetes who consumed two meals per day showed greater intrapancreatic fat deposition than those who consumed three meals per day, even after adjustment for BMI. These findings support the current guideline for diabetes treatment that skipping meals should be avoided.

Background: Prior reports have suggested that pancreatic fat is related to type 2 diabetes. Sodium-glucose co-transporter-2 (SGLT-2) inhibitors are expected to reduce ectopic fat accumulation.Aim: This study assessed the effect of SGLT-2 inhibitors on pancreatic and liver fat accumulations in patients with type 2 diabetes. Materials and Methods:Retrospective analyses of indices of pancreatic and liver fat accumulations were conducted in 22 type 2 diabetes outpatients who were receiving SGLT-2 inhibitors for more than 12 weeks. The differences between the pancreatic (P) or liver (L) and splenic (S) computed tomography values were evaluated.Results: Fatty pancreas was defined as PÀ S < À 8 Hounsfield Unit (HU), and the number of patients with fatty pancreas was 11 (50%). Fatty pancreas significantly improved after SGLT-2 inhibitor use (median, À 20.8; IQR, À 34.8 to À 14.3 HU vs. median, À 14.6; IQR, À 29.5 to À 7.8 HU; p ¼ 0.041). Fatty liver was defined as LÀ S ≤ 3.9 HU, and the number of patients with fatty liver was 11 (50%). Fatty liver significantly improved after SGLT-2 inhibitor use (median, À 4.3; IQR, À 23.0 to 3.0 HU vs. median, À 0.7; IQR, À 5.2 to 6.3 HU; p ¼ 0.016). Conclusion:Pancreatic fat and liver fat accumulations might be reduced after treatment with SGLT-2 inhibitors in type 2 diabetes patients with intense cumulative fat depositions in these organs. K E Y W O R D S pancreatic fat, SGLT-2 inhibitor, terms: type 2 diabetesThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Background and objectivePancreatic fat is a form of ectopic fat. Lipid droplets (LDs) are also observed in β cells; however, the pathophysiological significance, especially for β cell function, has not been elucidated. Our aim was to assess LD accumulation in β cells in various stages of glucose intolerance and to clarify its relationship with clinical and histological parameters.MethodsWe examined 42 Japanese patients who underwent pancreatectomy. The BODIPY493/503-positive (BODIPY-positive) area in β cells was measured in pancreatic sections from 32 patients. The insulin granule numbers were counted in an additional 10 patients using electron microscopy.ResultsThe BODIPY-positive area in β cells in preexisting type 2 diabetes patients was higher than that in normal glucose tolerance patients (p = 0.031). The BODIPY-positive area in β cells was positively correlated with age (r = 0.45, p = 0.0097), HbA1c (r = 0.38, p = 0.0302), fasting plasma glucose (r = 0.37, p = 0.045), and homeostasis model assessment insulin resistance (r = 0.41, p = 0.049) and negatively correlated with an increase in the C-peptide immunoreactivity level by the glucagon test (r = -0.59, p = 0.018). The ratio of mature insulin granule number to total insulin granule number was reduced in the patients with rich LD accumulation in β cells (p = 0.039).ConclusionsType 2 diabetes patients had high LD accumulation in β cells, which was associated with insulin resistance, hyperglycemia, aging and β cell dysfunction involving decreased mature insulin granules.