Shuhei Nakanishi

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.

Durability of protective effect of dulaglutide on pancreatic β-cells in diabetic mice: GLP-1 receptor expression is not reduced despite long-term dulaglutide exposure

AIMS It is well-known that chronic exposure to large amounts of ligand leads to downregulation of its receptor. It is not known, however, whether a GLP-1R agonist downregulates its receptor. For this reason, our study examined whether GLP-1R expression is reduced after long-term exposure to dulaglutide (Dula) in non-diabetic and diabetic mice. METHODS Seven-week-old male db/db and db/m mice were given either Dula (0.6mg/kg×2/week) or a control vehicle (CTL) for 17 weeks. Various metabolic parameters, such as glucose-stimulated insulin secretion (GSIS), insulin and TG content in islets, were evaluated after the intervention. β-cell-related gene expression was also analyzed by real-time RT-PCR. RESULTS In db/m mice, GLP-1R expression in β-cells did not decrease, not even after long-term administration of Dula, compared with control mice, while GLP-1R expression in 24-week-old db/db mice treated with Dula was augmented, rather than downregulated, compared with 24-week-old CTL db/db mice. This was probably due to improved glycaemic control. In db/db mice treated with Dula, food intake and blood glucose levels were significantly decreased up to 24 weeks of age compared with CTL db/db mice, and their expression levels of various β-cell-related genes, insulin content and GSIS were also enhanced. In contrast, oxidative and endoplasmic reticulum stress, inflammation, fibrosis and apoptosis were suppressed with Dula treatment. CONCLUSION Dula exerts beneficial effects on glycaemic control and has long-lasting protective effects on pancreatic β-cells. GLP-1R expression levels were not reduced at all in non-diabetic as well as diabetic mice despite long-term dulaglutide exposure.

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.

Body composition and development of diabetes: a 15-year follow-up study in a Japanese population

Background/objectivesFew longitudinal studies have examined the association between diabetes risk and body composition in Asians. The aim of this prospective cohort study was to determine the role of body composition, estimated by whole-body dual-energy X-ray absorptiometry, in the development of diabetes and to examine the impact of body composition on diabetes risk in normal weight (body mass index (BMI) <23 kg/m2) and overweight/obese groups (≥23 kg/m2).Subjects/methodsWe measured the body composition for 1532 diabetes-free subjects (463 men and 1069 women), aged 48–79 years, at the baseline examination period from 1994–96 and followed-up to detect new cases of diabetes over the next 15 years (median 13.4 years).ResultsAfter being adjusted for BMI and other potential confounding factors, body fat distribution was associated with diabetes risk. Percentage of trunk fat was positively associated with the development of diabetes (hazards ratio (HR) per 1 SD (95% confidential interval (CI)), 1.58 (1.10–2.28) in men, and 1.34 (0.99–1.83) in women), and percentage of leg fat was negatively associated with the development of diabetes (HR per 1 SD (95% CI), 0.68 (0.50–0.91) in men and 0.68 (0.55–0.85) in women). The estimated HRs of % trunk and leg fat on the development of diabetes differed little between normal weight and overweight/obese subjects. Appendicular lean mass was also negatively associated with diabetes risk only in normal weight men.ConclusionsOpposite associations of trunk fat and leg fat with diabetes risk were observed. Assessment of body composition might help in the evaluation of diabetes risk.

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.

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.

Protective effects of the SGLT2 inhibitor luseogliflozin on pancreatic β-cells in db/db mice: The earlier and longer, the better

We compared the protective effects of sodium glucose co‐transporter (SGLT) 2 inhibitor luseogliflozin on pancreatic β‐cells between early and advanced stages of diabetes and between short‐ and long‐term use.

There is a Close Association Between the Recovery of Liver Injury and Glycemic Control after SGLT2 Inhibitor Treatment in Japanese Subjects with Type 2 Diabetes: A Retrospective Clinical Study

IntroductionSodium-glucose co-transporter 2 (SGLT2) inhibitors function not only to reduce hyperglycemia but also to ameliorate liver injury and reduce body weight. The aim of this study was to examine in which subjects SGLT2 inhibitors are more effective for glycemic control, liver injury, and obesity in Japanese subjects with type 2 diabetes mellitus.MethodsWe enrolled a total of 156 subjects with type 2 diabetes who initiated SGLT2 inhibitor treatment after September 1, 2014 in Kawasaki Medical School (Protocol No. 2375). We evaluated the alteration of glycemic control, liver injury, body mass composition, and various clinical parameters.ResultsSGLT2 inhibitors significantly ameliorated glycemic control and improved liver injury in Japanese subjects with type 2 diabetes. SGLT2 inhibitors were more effective for liver injury when glycemic control was improved with SGLT2 inhibitors. In multivariate analyses, the amelioration of glycemic control was an independent determinant factor for the improvement of liver damage in Japanese subjects with type 2 diabetes. The reverse was also correct; the improvement of liver damage was an independent determinant factor for the amelioration of glycemic control.ConclusionRecovery of liver injury with SGLT2 inhibitor treatment was closely associated with their effects on glycemic control in Japanese subjects with type 2 diabetes.