Tomoe Kinoshita

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.

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.

Decreased glucagon-like peptide 1 receptor expression in endothelial and smooth muscle cells in diabetic db/db mice: TCF7L2 is a possible regulator of the vascular glucagon-like peptide 1 receptor

Aims: Incretin signalling is known to prevent the development of arteriosclerosis by relaxation response in endothelial cells via the glucagon-like peptide 1 receptor. It remains unclear, however, whether vascular glucagon-like peptide 1 receptor expression is altered under some conditions. The aim of this study is to examine whether vascular glucagon-like peptide 1 receptor expression is altered by diabetic state as reported in pancreatic β-cells. Methods: We used 18-week-old male diabetic db/db mice and control db/m mice. Excised thoracic artery was specifically collected, and vascular endothelial cells were cultured. We compared the glucagon-like peptide 1 receptor expression levels between the db/db and db/m mice. Results: Metabolic parameters were significantly worse in db/db mice. The glucagon-like peptide 1 receptor and transcription factor 7-like 2 expression levels in endothelial and smooth muscle cells were significantly lower in db/db mice. Furthermore, siRNA to transcription factor 7-like 2 decreased the transcription factor 7-like 2 levels and such reduction of the transcription factor 7-like 2 resulted in the downregulation of the glucagon-like peptide 1 receptor expressions in cultured vascular endothelial cells. Conclusion: The glucagon-like peptide 1 receptor expression level was significantly lower under diabetic condition which was accompanied by the reduction of the transcription factor 7-like 2 expression level. Furthermore, the transcription factor 7-like 2 is a possible regulator of the glucagon-like peptide 1 receptor expression in artery as reported in β-cells.

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.

Effect of mild exercise on glycemic and bodyweight control in Japanese type 2 diabetes patients: A retrospective analysis

We retrospectively evaluated the effects of mild physical exercise (P) in a routine clinical setting on glycemic and bodyweight control in Japanese type 2 diabetes patients with and without individualized nutritional therapy (D). We analyzed 49 patients who participated in P that measured 2.5 metabolic equivalents and was held once every 2 weeks, compared with 83 non‐participant controls, followed over a period of approximately 1.6 years. With a Cox model, the adjusted hazard ratio for improved glycated hemoglobin by numerical count of P was 1.03 (95% confidence interval [CI] 1.00–1.07; P = 0.025). Among four categories – with neither P nor D, only P, only D, and both P and D – the hazard ratios for reduced body mass index were 1.0, 0.87 (95% CI 0.46–1.67), 0.58 (95% CI 0.25–1.30) and 2.17 (95% CI 1.03–4.59), respectively. Even mild physical exercise contributed to glycemic control. The combination of P and D exerted beneficial effects on bodyweight control.

Onset of type 1 diabetes mellitus and heparin-induced thrombocytopenia in a patient with Basedow's disease and idiopathic thrombocytopenic purpura: Novel combination as autoimmune polyglandular syndrome

Type 1 diabetes mellitus is often complicated with some other autoimmune disorders, and the complication of various autoimmune disorders is known as autoimmune polyglandular syndrome (APS). We experienced a patient who developed type 1 diabetes mellitus and heparin-induced thrombocytopenia (HIT) in addition to Basedow’s disease and idiopathic thrombocytopenic purpura (ITP). To our best knowledge, this is the first report showing that HIT is observed in APS patients. When the patient was aged 65 years, she had Basedow’s disease. She was treated with thiamazole (30 mg) or propylthiouracil (300 mg), but agranulocytosis was induced after starting the treatment with propylthiouracil. Therefore, she had radioactive iodine treatment (I 6 mCi). After the treatment, she had secondary hypothyroidism and started taking levothyroxine (50 lg/day). During the treatment, her platelets were decreased to 40 9 10/lL and platelet-associated immunoglobulin G was positive. She was diagnosed with ITP, which was well treated with prednisolone. After starting the treatment with prednisolone, the plateletassociated immunoglobulin G level was decreased and after several months it was finally normalized. When she was aged 77 years, she felt thirst, general fatigue, nausea and appetite loss. As such symptoms persisted for several months, she was hospitalized at Kawasaki Medical School Hospital, Kurashiki, Japan. Her height and bodyweight were 150.0 cm and 37.2 kg, respectively. Blood pressure and heart rate were 153/96 mmHg and 140 b.p.m, respectively. Body temperature was 37.2°C, blood glucose level was 737 mg/ dL, glycated hemoglobin was 10.3% and glycoalbumin was 48.4%. Insulin secretion was markedly suppressed: immunoreactive insulin was <1.0 lIU/ mL and serum C-reactive protein was 0.3 ng/mL. Ketone bodies were markedly increased: 3-hydroxybutyric acid was 11,310 lmol/L and acetoacetic acid was 3,850 lmol/L. In an arterial blood gas test, the pH was 7.21. The value of antiglutamic acid decarboxylase antibody in this patient was ≤1.3U/mL. However, considered from the onset speed of diabetes and depletion of insulin secretion, we diagnosed this patient with acuteonset type 1 diabetes mellitus and diabetic ketoacidosis. In addition, as various auto-antibodies (anti-glutamic acid decarboxylase antibody, anti-islet antigen-2 antibody, islet cell autoantibody and zinc transporter 8) were negative, we diagnosed this patients with type 1B diabetes mellitus. Renal dysfunction, probably as a result of dehydration, was observed: creatinine was 1.68 mg/dL and blood urea nitrogen was 73 mg/dL. Liver function and other endocrine hormone levels were within the normal range. As she had various autoimmune disorders, such as Basedow’s disease, ITP and type 1 diabetes mellitus, we diagnosed her with APS type 3. Human leukocyte antigen typing was as follows: DRB1, *04:05, *08:03; DQB1 04:01, 06:01, which were also compatible with type 1 diabetes mellitus and APS type 3. Hyperglycemia and ketoacidosis gradually recovered with fluid replacement and insulin therapy. As the patient had atrial fibrillation, we gave her unfractionated heparin (5,000 U/day for 3 days). After that, her platelets markedly decreased from 90 9 10/lL to 40 9 10/lL within several days. In addition, anti-HIT antibody was positive. After starting the treatment with heparin, purpura was observed in both legs. Therefore, we stopped heparin, and after then the purpura disappeared. Furthermore, this patient had a past history of stroke. Although the patient had completely recovered from stroke without any sequela, it seemed that this stroke was also related to HIT. In addition, the 4Ts score in this patient was 4 points (thrombocytopenia 2 points, timing of platelet count fall 0 points, thrombosis or other sequela 1 point, other causes for thrombocytopenia 1 point). We finally diagnosed the patient with HIT based on its diagnosis criteria. HIT is a serious side-effect of heparin, and is observed in a small percentage of patients treated with heparin. HIT leads to the development of thromboembolism and is a lifethreating disease without appropriate therapy, such as stopping heparin. AntiHIT antibody is an antibody against the complex of platelet factor 4 and heparin, which is thought to lead to the onset of *Corresponding author. Hideaki Kaneto Tel.: +81-86-464-1111 Fax: +81-86-464-1046 E-mail address: kaneto@med.kawasaki-m.ac.jp Received 9 October 2017; revised 10 November 2017; accepted 11 January 2018

Verification of Kumamoto Declaration 2013 and Glycemic Targets for Elderly Patients with Diabetes in Japan for prevention of diabetic complications: A retrospective longitudinal study using outpatient clinical data

The present study examined the association between the onset of micro‐ and macroangiopathy in type 2 diabetes mellitus patients and levels of glycated hemoglobin (HbA1c) described in the Evidence‐based Practice Guideline for the Treatment for Diabetes in Japan 2013 or those indicated in the Japan Diabetes Society and the Japan Geriatrics Society Joint Committee on Improving Care for Elderly Patients with Diabetes.

Switching from low-dose thiazide diuretics to sodium–glucose cotransporter 2 inhibitor improves various metabolic parameters without affecting blood pressure in patients with type 2 diabetes and hypertension

Sodium–glucose cotransporter 2 (SGLT2) inhibitors function to increase urinary glucose excretion and improve glycemic control in individuals with type 2 diabetes mellitus. SGLT2 inhibitors, as well as diuretics, increase urinary volume, which leads to the reduction of blood pressure. The aim of the present study was to compare the effects of SGLT2 inhibitor and thiazide diuretic on blood pressure, metabolic parameters and body mass composition.

Efficacy and Safety of Switching from Insulin Glargine 100 U/mL to the Same Dose of Glargine 300 U/mL in Japanese Type 1 and 2 Diabetes Patients: A Retrospective Analysis

Objective Insulin glargine [300 U/mL (Gla-300)] achieved better glycemic control and reduced the risk of hypoglycemia in comparison to glargine [100 U/mL; (Gla-100)] in phase 3 trials. This is the first study to retrospectively evaluate the efficacy and safety of Gla-300 in Japanese type 1 and 2 diabetes patients in a routine clinical setting. Methods We analyzed 20 type 1 diabetes patients and 62 type 2 diabetes patients who switched from Gla-100 to the same dose of Gla-300. Sixty type 2 diabetes patients who continued the use of Gla-100 during the study were included as controls. Results At three months after switching, the HbA1c levels were decreased in the patients with type 1 diabetes, but not to a significant extent. In the type 2 diabetes patients, the HbA1c levels were significantly decreased after switching (p<0.01). In contrast, there was no change in the HbA1c levels of the type 2 diabetes patients who continued the use of Gla-100 over the same period. The BMI values of the type 1 diabetes patients tended to decrease (p=0.06) and there was a significant decrease in the BMI values of the type 2 diabetes patients (p<0.05). There was no change in the BMI values of the type 2 diabetes patients who continued the use of Gla-100. The rates of hypoglycemia and adverse events did not change during the follow-up period. Conclusion In the clinical setting, switching from Gla-100 to the same dose of Gla-300 had a favorable effect on glycemic control and body weight control in Japanese type 1 and type 2 diabetes patients, without any increase in adverse events; however, a prospective study should be performed to confirm these findings.

Fulminant Type 1 Diabetes Mellitus Complicated with a Life-threatening Electrolyte Abnormality and Abnormal Electrocardiogram Findings

Fulminant type 1 diabetes mellitus (T1DM) is idiopathic T1DM with the rapid destruction of pancreatic β-cells. We herein report a 48-year-old man who developed fulminant T1DM complicated with a life-threatening electrolyte abnormality and abnormal electrocardiogram findings. He had no remarkable medical history, but one day, he developed general fatigue. His blood glucose level and HbA1c were 806 mg/dL and 6.3%, and his insulin secretion was markedly suppressed. He had ketoacidosis, hyponatremia and hyperkalemia. Furthermore, a life-threatening abnormality was noted on electrocardiogram. After fluid infusion and insulin therapy, the abnormality disappeared. In conclusion, we should bear in mind the possibility of fulminant T1DM in patients complaining of general malaise.