Background: To examine the effects of liraglutide, a glucagon-like peptide-1 (GLP-1) analogue, on visceral fat adiposity, appetite, food preference, and biomarkers of cardiovascular system in Japanese patients with type 2 diabetes. Methods: The study subjects were 20 inpatients with type 2 diabetes treated with liraglutide [age; 61.2 ± 14.0 years, duration of diabetes; 16.9 ± 6.6 years, glycated hemoglobin (HbA1c); 9.1 ± 1.2%, body mass index (BMI); 28.3 ± 5.2 kg/m², mean ± SD]. After improvement in glycemic control by insulin or oral glucose-lowering agents, patients were switched to liraglutide. We assessed the estimated visceral fat area (eVFA) by abdominal bioelectrical impedance analysis, glycemic control by the 75-g oral glucose tolerance test (OGTT) and eating behavior by the Japan Society for the Study of Obesity questionnaire. Results: Treatment with liraglutide (dose range: 0.3 to 0.9 mg/day) for 20.0 ± 6.4 days significantly reduced waist circumference, waist/hip ratio, eVFA. It also significantly improved the scores of eating behavior, food preference and the urge for fat intake and tended to reduce scores for sense of hunger. Liraglutide increased serum C-peptide immunoreactivity and disposition index. Conclusions: Short-term treatment with liraglutide improved visceral fat adiposity, appetite, food preference and the urge for fat intake in obese Japanese patients with type 2 diabetes.

Background: We recently reported that short-term treatment with liraglutide (20.0 ± 6.4 days) reduced body weight and improved some scales of eating behavior in Japanese type 2 diabetes inpatients. However, it remained uncertain whether such liraglutide-induced improvement is maintained after discharge from the hospital. The aim of the present study was to determine the long-term effects of liraglutide on body weight, glycemic control, and eating behavior in Japanese obese type 2 diabetics. Methods: Patients with obesity (body mass index (BMI) >25 kg/m²) and type 2 diabetes were hospitalized at Osaka University Hospital between November 2010 and December 2011. BMI and glycated hemoglobin (HbA1c) were examined on admission, at discharge and at 1, 3, and 6 months after discharge. For the liraglutide group (BMI; 31.3 ± 5.3 kg/m², n = 29), patients were introduced to liraglutide after correction of hyperglycemic by insulin or oral glucose-lowering drugs and maintained on liraglutide after discharge. Eating behavior was assessed in patients treated with liraglutide using The Guideline For Obesity questionnaire issued by the Japan Society for the Study of Obesity, at admission, discharge, 3 and 6 months after discharge. For the insulin group (BMI; 29.1 ± 3.0 kg/m², n = 28), each patient was treated with insulin during hospitalization and glycemic control maintained by insulin after discharge. Results: Liraglutide induced significant and persistent weight loss from admission up to 6 months after discharge, while no change in body weight after discharge was noted in the insulin group. Liraglutide produced significant improvements in all major scores of eating behavior questionnaire items and such effect was maintained at 6 months after discharge. Weight loss correlated significantly with the decrease in scores for recognition of weight and constitution, sense of hunger, and eating style. Conclusion: Liraglutide produced meaningful long-term weight loss and significantly improved eating behavior in obese Japanese patients with type 2 diabetes.

Triglyceride deposit cardiomyovasculopathy (TGCV) is a phenotype primarily reported in patients carrying genetic mutations in PNPLA2 encoding adipose triglyceride lipase (ATGL) which releases long chain fatty acid (LCFA) as a major energy source by the intracellular TG hydrolysis. These patients suffered from intractable heart failure requiring cardiac transplantation. Moreover, we identified TGCV patients without PNPLA2 mutations based on pathological and clinical studies. We provided the diagnostic criteria, in which TGCV with and without PNPLA2 mutations were designated as primary TGCV (P-TGCV) and idiopathic TGCV (I-TGCV), respectively. We hereby report clinical profiles of TGCV patients. Between 2014 and 2018, 7 P-TGCV and 18 I-TGCV Japanese patients have been registered in the International Registry. Patients with I-TGCV, of which etiologies and causes are not known yet, suffered from adult-onset severe heart disease, including heart failure and coronary artery disease, associated with a marked reduction in ATGL activity and myocardial washout rate of LCFA tracer, as similar to those with P-TGCV. The present first registry-based study showed that TGCV is an intractable, at least at the moment, and heterogeneous cardiovascular disorder.

Background and objective: Pancreatic 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.Methods: We 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.Results: The 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).Conclusions: Type 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.

Aims/Introduction:  Recently, glucagon‐like peptide‐1 (GLP‐1) receptor agonists of liraglutide have become available in Japan. It has not yet been clarified what clinical parameters could discriminate liraglutide‐effective patients from liraglutide‐ineffective patients.Materials and Methods:  We reviewed 23 consecutive patients with type 2 diabetes admitted to Osaka University Hospital for glycemic control. All of the patients were treated with diet plus insulin (or plus oral antidiabetic drugs) to improve fasting plasma glucose (FPG) and postprandial glucose below 150 and 200 mg/dL, respectively. After insulin secretion and insulin resistance were evaluated, insulin was replaced by liraglutide. The efficacy of liraglutide was determined according to whether glycemic control was maintained at the target levels.Results:  Liraglutide was effective in 13 of 23 patients. There were significant differences in the parameters of insulin secretion, including fasting C‐peptide (F‐CPR), C‐peptide index (CPI), insulinogenic index (I.I.) and urine C‐peptide (U‐CPR), between liraglutide‐effective and ‐ineffective patients. The duration of diabetes was significantly shorter in liraglutide‐effective patients than in liraglutide‐ineffective patients. In receiver operating characteristic analyses, the cut‐off value for predicting the efficacy of liraglutide was 0.14 for I.I., 1.1 for CPI, 1.5 ng/mL for F‐CPR, 33.3 μg/day for U‐CPR and 19.5 years for duration of type 2 diabetes.Conclusions:  Insulin secretion evaluated by F‐CPR, CPI, I.I., U‐CPR and the duration of type 2 diabetes were useful parameters for predicting the efficacy of liraglutide in patients with type 2 diabetes. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2011.00168.x, 2011)

Aims/Introduction: The relationship between pancreatic fatty infiltration and diabetes is widely known, whereas the causal relationship is not clear. Furthermore, it is uncertain whether pathogenesis of pancreatic fat is similar to that of liver fat. We aimed to clarify the contribution of this type of fat to glucose metabolism in type 2 diabetes patients by cross‐sectional and longitudinal analyses.Material and Methods: A total of 56 patients with type 2 diabetes who had been hospitalized twice were analyzed. We evaluated the mean computed tomography values of the pancreas (P), liver (L) and spleen (S). Lower computed tomography values indicate a greater fat content. We defined indices of pancreatic or liver fat content as the differences between P or L and S. We assessed the associations among fat content for the two organs (P‐S, L‐S) and clinical parameters at the first hospitalization, and then analyzed the associations between these fat contents and changes in glycometabolic markers (the second data values minus the first).Results: In the cross‐sectional study, P‐S negatively correlated with the increment of C‐peptide in the glucagon stimulation test (r = −0.71, P < 0.0001) and body mass index (r = −0.28, P = 0.034). L‐S negatively correlated with homeostasis model assessment of insulin resistance (r = −0.73, P < 0.0001), body mass index (r = −0.62, P < 0.0001) and some other obesity‐related indicators, but not with the increment of C‐peptide in the glucagon stimulation test. In the longitudinal study, P‐S positively correlated with the change of the increment of C‐peptide in the glucagon stimulation test (r = 0.49, P = 0.021).Conclusions: In type 2 diabetes patients, pancreatic fat was less associated with obesity‐related indicators than liver fat, but was more strongly associated with the longitudinal decrease in endogenous insulin‐secreting capacity.