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.

Feasibility pilot study of a Japanese teaching kitchen program.

Background: This pilot study examined the feasibility of a new lifestyle modification program involving a "Teaching Kitchen" in Japan. Our goal was to explore (1) feasibility of the program; (2) acceptability for class frequency (weekly vs. bi-weekly); and (3) changes in biometrics, dietary intakes, and lifestyle factors. Methods: A total of 24 employees with obesity in a Japanese company were recruited. Participants were randomly divided into two groups (weekly or bi-weekly group), each attending the program consisting of four two-hour classes (lectures on nutrition, exercise, mindfulness, and culinary instructions). Participants were observed for changes in dietary intakes, biometrics, and health related quality of life over the subsequent 3 months. We tested the between-group differences in changes using linear mixed-effect models. Results: The program completion rates were 83.3% in total (91.7% for weekly group and 75.0% for bi-weekly group). From baseline to post-intervention, significant decreases were observed in weight (p < 0.001), body mass index (p < 0.001), diastolic blood pressure (p = 0.03), body fat mass (p < 0.001), and dietary intakes in total fat (p = 0.03) and sodium (p = 0.008) among 17 participants who were available for measurements. Improvements in biometrics remained significant 1 month after the intervention (all p ≤ 0.03 in 14 participants). Participants' health related quality of life was significantly improved in bodily pain, general health, vitality, and mental component score (all p ≤ 0.047). Conclusions: The new Japanese Teaching Kitchen program is feasible with high program completion rates in Japanese office workers with obesity. While this was a small feasibility study, significant multiple improvements in dietary intakes, biometrics, and health related quality of life suggest that this line of inquiry warrants further exploration to address obesity and obesity-related diseases in Japan.

Relationships between intra-pancreatic fat deposition and lifestyle factors: a cross-sectional study.

Aims: The excess deposition of intra-pancreatic fat deposition (IPFD) has been reported to be associated with type 2 diabetes, chronic pancreatitis, and pancreatic ductal adenocarcinoma. In the current study, we aimed to identify a relationship between lifestyle factors and IPFD. Materials and methods: 99 patients admitted to the Osaka University Hospital who had undergone abdominal computed tomography were selected. We evaluated the mean computed tomography values of the pancreas and spleen and then calculated IPFD score. Multiple regression analyses were used to assess the associations between IPFD score and lifestyle factors. Results: Fast eating speed, late-night eating, and early morning awakening were significantly associated with a high IPFD score after adjusting for age, sex, diabetes status and Body Mass Index (p=0.04, 0.01, 0.01, respectively). Conclusion: The current study has elucidated the significant associations of fast eating speed, late-night eating, and early morning awakening with IPFD.

Myocardial fat accumulation is associated with cardiac dysfunction in patients with type 2 diabetes, especially in elderly or female patients: a retrospective observational study.

BACKGROUND: Ectopic fat is fat that accumulates in or around specific organs or compartments of the body including myocardium. The clinical features of type 2 diabetes patients with high fat accumulation in the myocardium remain unknown. Moreover, little is known about the influence of myocardial fat accumulation in type 2 diabetes on coronary artery disease and cardiac dysfunction. We aimed to clarify the clinical features, including cardiac functions, of type 2 diabetes patients with myocardial fat accumulation. METHODS: We retrospectively enrolled type 2 diabetes patients who underwent ECG-gated coronary computed tomography angiography (CCTA) and abdominal computed tomography (CT) scan examinations within 1 year of CCTA from January 2000 to March 2021. High fat accumulation in the myocardium was defined as the low mean myocardial CT value of three regions of interest, and the associations between CT values and clinical characteristics or cardiac functions were assessed. RESULTS: In total, 124 patients were enrolled (72 males and 52 females). The mean age was 66.6 years, the mean BMI was 26.2 kg/m2, the mean ejection fraction (EF) was 67.6%, and the mean myocardial CT value was 47.7 Hounsfield unit. A significant positive correlation was found between myocardial CT value and EF (r = 0.3644, p = 0.0004). The multiple regression analyses also showed that myocardial CT value was independently associated with EF (estimate, 0.304; 95% confidence interval (CI) 0.092 to 0.517; p = 0.0056). Myocardial CT value showed significant negative correlations with BMI, visceral fat area and subcutaneous fat area (r = - 0.1923, - 0.2654, and -0.3569, respectively, p < 0.05). In patients who were ≥ 65 years or female, myocardial CT value showed significant positive correlations with not only EF (r = 0.3542 and 0.4085, respectively, p < 0.01) but also early lateral annular tissue Doppler velocity (Lat e') (r = 0.5148 and 0.5361, respectively, p < 0.05). The multiple regression analyses showed that myocardial CT value was independently associated with EF and Lat e' in these subgroups (p < 0.05). CONCLUSIONS: Patients with type 2 diabetes, especially in elderly or female patients, who had more myocardial fat had more severe left ventricular systolic and diastolic dysfunctions. Reducing myocardial fat accumulation may be a therapeutic target for type 2 diabetes patients.

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.

Maximum body mass index before onset of type 2 diabetes is independently associated with advanced diabetic complications.

INTRODUCTION: The maximum body mass index (BMI) before onset of type 2 diabetes (MBBO) might be used to estimate a patient's insulin secretion capacity. There have been few factors that can predict future diabetic complications at the time of diagnosis of diabetes mellitus. This study aimed to clarify the clinical usefulness of MBBO for predicting the development of advanced diabetic microvascular complications. RESEARCH DESIGN AND METHODS: This was a cross-sectional observational study. Of 1304 consecutively admitted patients with type 2 diabetes, we enrolled 435 patients for whom we could confirm their MBBO. Univariate and multivariate logistic regression analyses were performed to examine whether MBBO or BMI on admission was associated with advanced diabetic retinopathy or nephropathy. To evaluate the predictive performance of these indexes, we performed cross-validation in various models with MBBO or BMI and evaluated the areas under the curve (AUCs) yielded by these analyses. RESULTS: Univariate analyses suggested that MBBO was associated with advanced retinopathy and nephropathy, while BMI on admission was associated only with advanced nephropathy. In multivariate analyses, MBBO was significantly associated with advanced complications, while BMI on admission was not. For advanced diabetic retinopathy, the AUCs were 0.70-0.72, and for advanced nephropathy, the AUCs were 0.81-0.83. When comparing the AUCs among models, the models with MBBO sustained high predictive performance for diabetic complications. CONCLUSIONS: MBBO was independently associated with advanced diabetic complications, while BMI on admission was not. Diabetic microvascular complications in patients with high MBBO could progress more rapidly. At the time of the diagnosis of diabetes mellitus, MBBO would enable us to predict the progress of diabetic complications.

Clinical Significance of the Maximum Body Mass Index Before Onset of Type 2 Diabetes for Predicting Beta-Cell Function.

OBJECTIVE: This study aimed to clarify the clinical significance of the maximum body mass index (BMI) before the onset of type 2 diabetes (MBBO) for predicting pancreatic beta-cell function. METHODS: This was a cross-sectional observational study. Of 1304 consecutively admitted patients with type 2 diabetes, we enrolled 410 patients satisfying the criteria in this study. The correlations between the C-peptide index (CPI), which is one of the parameters that reflects beta-cell function, and various clinical parameters, including MBBO and duration of diabetes, were analyzed in multiple linear regression analyses. RESULTS: The analyses revealed that MBBO was correlated with CPI independently after adjustment for age, sex, HbA1c, and duration of diabetes. When we divided the subjects into three subgroups by MBBO (MBBO < 25 kg/m2; 25 kg/m2 ≤ MBBO < 30 kg/m2; MBBO ≥ 30 kg/m2), CPI was negatively correlated with duration of diabetes in each subgroup, while the rates of CPI based on the duration of diabetes were not different among the three MBBO subgroups. In contrast, the declining rates of CPI were higher in the BMI ≥ 25 kg/m2 group on admission than in the BMI < 25 kg/m2 group on admission. CONCLUSIONS: MBBO may be an independent factor correlating with beta-cell function and may predict insulin secretion capacity at diagnosis, but it does not seem to affect the rate of decline in insulin secretion capacity after diagnosis. It is important to preserve beta-cell function by decreasing a patient's BMI during treatment after diagnosis regardless of MBBO.