Fuminori Tatsumi

Vildagliptin preserves the mass and function of pancreatic β cells via the developmental regulation and suppression of oxidative and endoplasmic reticulum stress in a mouse model of diabetes

We investigated the molecular mechanisms by which vildagliptin preserved pancreatic β cell mass and function.

Self-inducible secretion of glucagon-like peptide-1 (GLP-1) that allows MIN6 cells to maintain insulin secretion and insure cell survival.

Based on the hypothesis that MIN6 cells could produce glucagon-like peptide-1 (GLP-1) to maintain cell survival, we analyzed the effects of GLP-1 receptor agonist, exendin-4 (Ex4), and antagonist, exendin-(9-39) (Ex9) on cell function and cell differentiation. MIN6 cells expressed proglucagon mRNAs and produced GLP-1, which was accelerated by Ex4 and suppressed by Ex9. Moreover, Ex4 further enhanced glucose-stimulated GLP-1 secretion, suggesting autocrine loop-contributed amplification of the GLP-1 signal. Ex4 up-regulated cell differentiation- and cell function-related CREBBP, Pdx-1, Pax6, proglucagon, and PC1/3 gene expressions. The confocal laser scanning images revealed that GLP-1 positive cells were dominant in the early stage of cells, but positive for insulin were more prominent in the mature stage of cells. Ex4 accelerated cell viability, while Ex9 and anti-GLP-1 receptor antibody enhanced cell apoptosis. MIN6 cells possess a mechanism of GLP-1 signal amplification in an autocrine fashion, by which the cells maintained insulin production and cell survival.

Association of GA/HbA1c ratio and cognitive impairment in subjects with type 2 diabetes mellitus

AIMS The aim of this study was to search for factors influencing cognitive impairment and to clarify the association between the fluctuation of blood glucose levels and cognitive impairment in elderly Japanese subjects with type 2 diabetes. METHODS We recruited 88 relatively elderly subjects (≥65years old) with type 2 diabetes who were hospitalized in Kawasaki Medical School from January 2014 to December 2015. We evaluated the fluctuation of blood glucose levels with glycoalbumin (GA)/hemoglobin A1c (HbA1c) ratio, and estimated cognitive impairment with Hasegawa dementia scale-revised (HDS-R) score and mini mental state examination (MMSE) score. RESULTS Multivariate analyses showed that GA/HbA1c ratio and urinary albumin excretion, but not hypoglycemia, were independent determinant factors for cognitive impairment in elderly Japanese subjects with type 2 diabetes. CONCLUSIONS The fluctuation of blood glucose levels per se is closely associated with cognitive impairment in elderly subjects with type 2 diabetes even when hypoglycemia is not accompanied. Since it is very easy to calculate GA/HbA1c ratio, we should check this ratio so that we can reduce the fluctuation of blood glucose levels especially in elderly subjects with type 2 diabetes.

Concomitant use of miglitol and mitiglinide as initial combination therapy in type 2 diabetes mellitus.

AIM To evaluate the efficacy of miglitol and mitiglinide alone or in combination on the metabolic profile and incretin secretion in Japanese type 2 diabetes patients. METHODS Patients on diet and exercise with or without metformin, were randomized to receive either miglitol, mitiglinide, or a combination, three times daily for 12 weeks. RESULTS At 12 weeks, HbA1c decreased significantly (p<0.001) and 1,5-AG increased significantly (p<0.001) in all three groups, with the greatest change seen with combination therapy. Effective improvement of postprandial hyperglycemia was demonstrated by a meal-loading test in all three interventions but serum insulin concentration was not increased by miglitol. In a subset of patients without prior metformin administration, faster and better glycemic control was achieved with the initial combination. After meal loading, serum total GLP-1 significantly increased only with miglitol monotherapy (p<0.05) and serum total GIP significantly decreased (p<0.01) in the arms employing miglitol after 12 weeks. CONCLUSION Miglitol/mitiglinide combination is more potent than monotherapy in improving glycemic control through the reduction of postprandial glucose excursion and the simultaneous sparing of additional insulin secretion. A marked difference in the effects of miglitol and mitiglinide on incretin secretion was also demonstrated.

Clinical effects of liraglutide are possibly influenced by hypertriglyceridemia and remaining pancreatic β-cell function in subjects with type 2 diabetes mellitus.

We searched for factors influencing the clinical effects of GLP-1 analogue liraglutide in subjects with type 2 diabetes. Multivariate analyses showed that hypertriglyceridemia and baseline HbA1c levels were independent predictors for the efficacy of liraglutide and that CPR index was an independent predictor for the durability of liraglutide.

Azelnidipine, but not amlodipine, reduces urinary albumin excretion and carotid atherosclerosis in subjects with type 2 diabetes: blood pressure control with olmesartan and azelnidipine in Type 2 diabetes (BOAT2 study).

To evaluate the efficacy of azelnidipine and amlodipine on diabetic nephropathy and atherosclerosis, we designed a prospective and randomized controlled clinical study in type 2 diabetic patients with stable glycemic control with fixed dose of anti-diabetic medication. Although there was no difference in blood pressure between both groups, urinary albumin excretion and maximum carotid intima-media thickness were reduced in azelnidipine group, but not in amlodipine group. In addition, inflammatory cytokine levels were decreased only in azelnidipine group which possibly explains such beneficial effects of azelnidipine on urinary albumin excretion and carotid atherosclerosis.

Advanced breast cancer in a relatively young man with severe obesity and type 2 diabetes mellitus

It is known that male breast cancer is extremely rare and obesity is a strong risk factor of breast cancer in both male and female. In general, the prognosis in breast cancer in males is known to be very poor compared to that in females as it tends to be more advanced stage due to delayed initial diagnosis. Therefore, we should be aware of the possibility that breast cancer could be developed even in relatively young males without any specific risk factors especially when the subjects have severe obesity.

Werner Syndrome and Diabetes Mellitus Accompanied by Adrenal Cortex Cancer

Werner syndrome is a rare genetic disease characterized by progeria, diabetes mellitus, cataracts and various types of malignancy. However, there are few reports showing adrenal cortex cancer in subjects with Werner syndrome. We herein report an extremely rare case of Werner syndrome accompanied by adrenal cortex cancer. Based on the data obtained from blood samples, computed tomography, magnetic resonance imaging and 131I adosterol scintigraphy, we diagnosed this subject with adrenal cortex cancer and Cushings syndrome. Since the prognosis of adrenal cancer is very poor, we should be aware of the possibility of adrenal cancer occurring in subjects with Werner syndrome.

Case of iliopsoas abscess that was markedly recovered after percutaneous and surgical drainage in a patient with poorly controlled type 2 diabetes.

We experienced a case of iliopsoas abscess which was markedly recovered after percutaneous and surgical drainage in a subject with poorly controlled type 2 diabetes. When iliopsoas abscess is suspected, physicians should survey patients by CT scan or MRI and should consider invasive treatment including surgical drainage.

Optimal cut-off value of alanine aminotransferase level to precisely estimate the presence of fatty liver in patients with poorly controlled type 2 diabetes.

Optimal cut‐off value of ALT level to precisely estimate the presence of fatty liver was as low as 28.0 U/L. We should consider the possibility of fatty liver even when ALT level is within normal range in subjects with poorly controlled type 2 diabetes.