Interrelationships among accumulations of intra- and peri-organ fat, visceral fat, and subcutaneous fat.

We aimed to clarify the relationship between intra- and peri-organ fat, visceral fat, and subcutaneous fat. We used abdominal CT to evaluate intra- and peri-organ fat accumulations in the pancreas, liver, spleen, renal parenchyma, renal sinus, and skeletal muscle. The relationships between these fats, visceral fat, and subcutaneous fat were examined by using the partial correlation and covariance analysis, adjusting for BMI. We found that visceral fat and each intraand peri-organ fat accumulation were positively correlated, whereas subcutaneous fat and the accumulation of each intra- and peri-organ fat and visceral fat were negatively correlated. Pancreas fat, liver fat, renal sinus fat, and skeletal muscle fat accumulated significantly more in people with excessive visceral fat accumulation than in those without excessive visceral fat accumulation (p = 0.01, 0.006, 0.008, 0.02, respectively). In conclusion, intra- and peri-organ fat accumulation in each organ shows a positive correlation with visceral fat and a negative correlation with subcutaneous fat, independent of BMI.

Effects of liraglutide on intrapancreatic fat deposition in patients with type 2 diabetes.

BACKGROUND & AIMS: Ectopic fat deposition is associated with worsening of glycemic control. This study was conducted to determine whether liraglutide reduces ectopic fat deposition, especially in pancreas, in patients with type 2 diabetes (T2D). METHODS: We retrospectively recruited T2D patients who underwent abdominal unenhanced CT scans both before and after administration of liraglutide (N = 13) or glimepiride (N = 29). Using CT values of pancreas (P), liver (L) and spleen (S), we defined the indices of intrapancreatic and liver fat as P-S value and L-S value, respectively. Increase of each value suggests the reduction of each fat deposition. RESULTS: The values of HbA1c (p = 0.0017) and body weight (p = 0.0081) decreased, and L-S (p = 0.0024) increased significantly after administration of liraglutide compared with those at baseline. Similarly, P-S tended to increase in the liraglutide group (p = 0.0547) and increased significantly in the liraglutide subgroup with fatty pancreas (p = 0.0303), defined as having baseline P-S less than -5. In the glimepiride group, P-S did not increase regardless of baseline P-S. Among patients with fatty pancreas, administration of liraglutide tended to be a significant factor for the change in P-S after adjustment for the change in HbA1c (p = 0.1090) and the change in visceral fat area (p = 0.1030). CONCLUSIONS: Intrapancreatic fat deposition was decreased after treatment with liraglutide, but not glimepiride, in T2D patients with fatty pancreas. Liraglutide might reduce intrapancreatic fat deposition independently of decreases in HbA1c and visceral fat volume.

Lipid droplet accumulation in ß cells in patients with type 2 diabetes is associated with insulin resistance, hyperglycemia and ß cell dysfunction involving decreased insulin granules.

Background and objective: Pancreatic fat is a form of ectopic fat. Lipid droplets (LDs) are also observed in ß cells; however, the pathophysiological significance, especially for ß cell function, has not been elucidated. Our aim was to assess LD accumulation in ß cells in various stages of glucose intolerance and to clarify its relationship with clinical and histological parameters. Methods: We examined 42 Japanese patients who underwent pancreatectomy. The BODIPY493/503-positive (BODIPY-positive) area in ß cells was measured in pancreatic sections from 32 patients. The insulin granule numbers were counted in an additional 10 patients using electron microscopy. Results: The BODIPY-positive area in ß cells in preexisting type 2 diabetes patients was higher than that in normal glucose tolerance patients (p = 0.031). The BODIPY-positive area in ß 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 ß cells (p = 0.039). Conclusions: Type 2 diabetes patients had high LD accumulation in ß cells, which was associated with insulin resistance, hyperglycemia, aging and ß cell dysfunction involving decreased mature insulin granules.

Consumption of two meals per day is associated with increased intrapancreatic fat deposition in patients with type 2 diabetes: a retrospective study.

INTRODUCTION: This study aimed to identify the associations between lifestyle factors and intrapancreatic fat deposition in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: The 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. RESULTS: After 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). CONCLUSIONS: Patients 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.

Amelioration of pancreatic fat accumulation in Japanese type 2 diabetes patients treated with sodium-glucose cotransporter 2 inhibitors: a retrospective study.

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 P-S < -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, -20.8; IQR, -34.8 to -14.3 HU vs. median, -14.6; IQR, -29.5 to -7.8 HU; p = 0.041). Fatty liver was defined as L-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, -4.3; IQR, -23.0 to 3.0 HU vs. median, -0.7; IQR, -5.2 to 6.3 HU; p = 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.

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

INTRODUCTION: Chronic 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 METHODS: We 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. RESULTS: The 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 (ß=0.600, p=0.0027) and AUCglucose (ß=0.453, p=0.0042) were the independent and significant determinants of CD68+ cells per islet. CONCLUSION: The inflammation of islets is associated with pancreatic fatty infiltration and hyperglycemia, which may further aggravate glucose tolerance.