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It is very important to explore how we can reduce urinary albumin excretion which is an independent risk factor for ischemic heart disease. In this study, we retrospectively evaluated the effects of RAS inhibitor therapy on diabetic nephropathy in Japanese subjects whose urinary albumin levels were within normal range. We enrolled 100 subjects with type 2 diabetes who did not take any renin-angiotensin system (RAS) inhibitor. We defined the subjects taking RAS inhibitor for more than 3 years as RAS inhibitor group. RAS inhibitor exerted protective effect on the progression of urinary albumin excretion in subjects with type 2 diabetes without diabetic nephropathy. In addition, RAS inhibitor exerted more protective effects on renal function especially in subjects with poor glycemic control. In conclusion, RAS inhibitor could protect renal function against the deleterious effect of chronic hyperglycemia in Japanese subjects with type 2 diabetes even before the onset of diabetic nephropathy. [ABSTRACT FROM AUTHOR]

Sodium-glucose cotransporter 2 inhibitor tofogliflozin is a new type of antidiabetic drug for individuals with type 2 diabetes mellitus (T2DM). The aim of this study was to examine in which type of individuals and/or under which conditions tofogliflozin could exert more beneficial effects on body composition and/or glycemic control in Japanese individuals with T2DM. We retrospectively evaluated the effects of tofogliflozin on body composition and/or glycemic control in individuals with T2DM who newly started taking tofogliflozin. After tofogliflozin treatment, body weight was significantly reduced and HbA1c levels were significantly decreased. Body fat mass, skeletal muscle mass, and skeletal muscle index, a marker for sarcopenia, were also reduced after the treatment. In univariate analyses, there was a statistically significant association between the decrease of HbA1c level after tofogliflozin treatment (Δ HbA1c) and the following parameters such as HbA1c levels at baseline, visceral fat area (VFA) at baseline, and reduction of VFA after the treatment (Δ VFA). Furthermore, in multivariate analyses, HbA1c levels at baseline and duration of diabetes were independently associated with Δ HbA1c. These results suggest that tofogliflozin would be more suitable for relatively obese individuals whose duration of diabetes is relatively short. [ABSTRACT FROM AUTHOR]

Introduction: It is known that chylomicronemia is caused by several pathologies and is classified as primary and secondary chylomicronemia. Since hypertriglycemia is associated with an increased risk of cardiovascular disease and severe pancreatitis, it is very important to make a proper diagnosis of the cause of hypertriglycemia. Case description: We herein present the case of a 40-year-old male who developed severe hypertriglycemia accompanied with acute exacerbation of type 2 diabetes mellitus. On admission, his blood glucose level was 306 mg/dl and HbA1c was 12.5 %. Moreover, serum triglyceride level was elevated up to 5661 mg/dl. When blood was drawn, it presented strawberry milk-like color. After receiving insulin treatment, he obtained good glycemic control and the serum became back to normal transparent color. Discussion and Evaluation: Insulin resistance reduces triglyceride clearance and also increases triglyceride release from adipocyte. It is known that glucose toxicity and strong insulin resistance induce inactivation of LPL, which results in chylomicronemia. Conclusion: This case report suggests that when serum triglyceride level is markedly elevated due to diabetic lipemia, it is extremely important to obtain good glycemic control. [ABSTRACT FROM AUTHOR]

Diabetic neuropathy is the most common diabetic complication. Duloxetine, a serotonin noradrenaline reuptake inhibitor ( SNRI), is widely used for the treatment of diabetic painful neuropathy ( DPN) because of the efficacy and safety profile. Syndrome of inappropriate antidiuretic hormone secretion, which is strongly associated duloxetine, is a rare but occasionally life-threatening adverse effect. Here, we report a case of syndrome of inappropriate antidiuretic hormone secretion that rapidly developed after starting duloxetine in an elderly Japanese female type 2 diabetes mellitus patient. Furthermore, we discuss the possible relationship between the onset of syndrome of inappropriate antidiuretic hormone secretion and the gene polymorphism of cytochrome P450 isoform 1A2 and 2D6, both of which are responsible for duloxetine metabolism. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which discusses the onset of type 1 diabetes mellitus with diabetic ketoacidosis as risk factor for Hamman's syndrome or spontaneous pneumomediastinum.

A letter to the editor is presented about the case of an 80-year-old woman with insulin autoimmune syndrome (IAS).

A letter to the editor is presented which discusses a case study of a 40-year-old Japanese man presented with onset type 1 diabetes following the administration of highly active antiretroviral therapy (HAART) against human immunodeficiency virus (HIV) infection.

Aim: To compare the clinical usefulness of once‐weekly glucagon‐like peptide‐1 receptor agonists dulaglutide and semaglutide at the doses approved for use in Japanese patients with type 2 diabetes. Methods: In total, 120 patients with glycated haemoglobin (HbA1c) ≥7% were randomly assigned to dulaglutide (n = 59) or semaglutide group (n = 61), and 107 participants (dulaglutide/semaglutide = 53/54) completed the 24‐week trial. The primary endpoint was the difference of HbA1c level between the two groups at 24 weeks. Results: HbA1c level at 24 weeks was significantly lower in the semaglutide group (7.9 ± 0.5%‐6.7 ± 0.5%) compared with the dulaglutide group (8.1 ± 0.6%‐7.4 ± 0.8%) (p <.0001). Reduction in body mass index and visceral fat area were also more significant in the semaglutide group (p <.05, respectively). The achievement rate of HbA1c <7% was higher in the semaglutide group (p <.0001). The parameters such as low‐density lipoprotein cholesterol, alanine aminotransferase and γ‐glutamyl transpeptidase were decreased in the semaglutide group. Surprisingly, only semaglutide group significantly improved the apolipoprotein B/A1 ratio, which is considered a useful myocardial infarction risk index. Using computed tomography, the liver to spleen ratio was significantly elevated only in the semaglutide group. In contrast, gastrointestinal symptoms were observed in 13.2% of dulaglutide and 46.3% of semaglutide group (p <.01). The Diabetes Treatment‐Related Quality of Life scores related to pain and gastrointestinal symptoms were also superior in the dulaglutide group. Conclusions: This prospective trial showed that semaglutide has more pronounced glucose‐ and body mass index‐lowering effects and reduces liver fat percentage and visceral fat area and that dulaglutide has less gastrointestinal symptoms and superior Diabetes Treatment‐Related Quality of Life scores related to pain and gastrointestinal symptoms. [ABSTRACT FROM AUTHOR]

Primary pyomyositis is a pyogenic and uncommon infection of skeletal muscle, which is mainly observed in tropical areas and/or human immunodeficiency virus patients. In non-human immunodeficiency virus infected patients, the most common cause is diabetes mellitus. Because of its rarity, the accurate diagnosis is often challenging. Staphylococcus aureus is the most common causative bacteria. According to the severity, pyomyositis is divided into three stages, and the late stage is occasionally lethal. The present case was compatible with the most advanced stage. Therefore, it was very difficult to save her life without precise and timely diagnosis. Furthermore, in the invasive stage, surgical drainage and broad-spectrum antibiotics should be given for a long enough period. Here, we report a case of a Japanese woman who developed disseminated abscesses under poorly controlled diabetic conditions accompanied by ketoacidosis, but was successfully treated without any sequelae. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the effect of canagliflozin, a sodium‐glucose co‐transporter‐2 (SGLT2) inhibitor, on albuminuria and the decline of estimated glomerular filtration rate (eGFR) in participants with type 2 diabetes and microalbuminuria. Methods: The CANPIONE study is a multicentre, randomized, parallel‐group and open‐labelled study consisting of a unique 24‐week preintervention period, during which the rate of eGFR decline before intervention is estimated, followed by a 52‐week intervention and a 4‐week washout period. Participants with a geometric mean urinary albumin‐to‐creatinine ratio (UACR) of 50 and higher and less than 300 mg/g in two consecutive first‐morning voids at two different time points, and an eGFR of 45 ml/min/1.73m2 or higher, are randomly assigned to receive canagliflozin 100 mg daily or to continue guideline‐recommended treatment, except for SGLT2 inhibitors. The first primary outcome is the change in UACR, and the second primary outcome is the change in eGFR slope. Results: A total of 258 participants were screened and 98 were randomized at 21 sites in Japan from August 2018 to May 2021. The mean baseline age was 61.4 years and 25.8% were female. The mean HbA1c was 7.9%, mean eGFR was 74.1 ml/min/1.73m2 and median UACR was 104.2 mg/g. Conclusions: The CANPIONE study will determine whether the SGLT2 inhibitor canagliflozin can reduce albuminuria and slow eGFR decline in participants with type 2 diabetes and microalbuminuria. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Sodium-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.Methods: We 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.Results: SGLT2 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.Conclusion: Recovery of liver injury with SGLT2 inhibitor treatment was closely associated with their effects on glycemic control in Japanese subjects with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Abstract: Aims/Introduction: 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. Materials and Methods: A total of 31 participants were enrolled in the present study. We switched from thiazide diuretics to an SGLT2 inhibitor, ipragliflozin, in participants with type 2 diabetes and hypertension whose blood pressure was controlled with thiazide diuretics. Three months after the switch, we evaluated the effects of such switching on blood pressure, various metabolic parameters and body mass composition. Results: There was no significant difference in blood pressure from baseline to 3 months later. However, glycated hemoglobin, fasting plasma glucose and uric acid were significantly decreased after the switch. Body mass index and visceral fat area were also significantly reduced after the switch. Furthermore, urinary albumin excretion was also significantly decreased after the switch. Conclusions: Switching from thiazide diuretic to an SGLT2 inhibitor, ipragliflozin, markedly improved various metabolic parameters and body mass composition without affecting blood pressure in participants with type 2 diabetes and hypertension. [ABSTRACT FROM AUTHOR]

Dipeptidyl peptidase-4 (DPP-4) inhibitors are often used all over the world and exert various beneficial effects including glucose-lowering effect in many subjects with type 2 diabetes. It is poorly understood, however, which factors are closely related with the durability of glucose-lowering effect by DPP-4 inhibitor. In this study, we examined retrospectively which factors could mainly influence the durability of DPP-4 inhibitor. We enrolled 212 participants with type 2 diabetes to whom DPP-4 inhibitor was administered for over 1 year without an addition or increase of other hypoglycemic agents. Age and baseline HbA1c level were significantly higher in the effective group than those in the ineffective group. The effective group had a tendency of smaller amounts of weight change, average total cholesterol, and average triglyceride compared with the ineffective group. Multiple logistic regression analysis showed that average triglyceride and baseline HbA1c were independent predictors associated with the durability of DPP-4 inhibitor. Moreover, an average triglyceride level contributed to the durability of DPP-4 inhibitor in the obese group (BMI ≥ 25 kg/m2) but not in the nonobese group (BMI < 25 kg/m2). These results suggest the importance of strict triglyceride management to maintain the durability of glucose-lowering effect by DPP-4 inhibitor, especially in obese subjects with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Introduction: Fibroblast growth factor 23 (FGF23) is secreted from bone and suppresses the absorption of phosphorus in renal proximal tubule and in intestinal tract. Therefore, the increase of serum FGF23 levels leads to hypophosphatemic situations. Tumor-induced osteomalacia is often induced by various tumors, but it is often difficult to identify the localization of tumor, because most of the FGF23-producing tumors are small and could be observed in any part of the body. Case description: Here we report a case of elderly female subject with FGF23-related hypophosphatemic osteomalacia who repeatedly experienced severe bone pain and fragility fracture in various parts of the body. Although we failed to identify the localization of tumor in this subject even with various examination, after starting phosphorus replacement therapy with relatively small amounts of calcium phosphate (1.5 g/day) (phosphorus content: 270 mg), hypophosphatemia was ameliorated and repeated bone pain was dramatically mitigated without any surgical operation. Discussion and Evaluation: Even when we fail to identify the localization of tumor in subjects with FGF23-related hypophosphatemic osteomalacia, phosphorus replacement therapy for hypophosphatemia could reduce the bone pain. Conclusions: We should be aware of the possibility that phosphorus replacement therapy exert marked beneficial effects for the reduction of bone pain in subjects with FGF23-related hypophosphatemic osteomalacia even when we fail to identify tumor localization. [ABSTRACT FROM AUTHOR]

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 (≥ 65 years 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. [ABSTRACT FROM AUTHOR]

Aims/Introduction Increased levels of high-sensitivity C-reactive protein (hs- CRP) likely leads to the development of atherosclerosis. Therefore, it is very important to know which factors largely influence hs- CRP levels. In the present study, we examined the influence of various atherosclerosis-related factors on hs- CRP levels in patients with type 2 diabetes. Materials and Methods A total of 275 patients (176 men, 99 women) were enrolled in this study. We tested the relationship between the number of risk factors reaching a desired value and hs- CRP levels. The Mann-Whitney U-test was used to compare two groups. The Kruskal-Wallis test was used to carry out overall group comparisons, and the Steel-Dwass test was used to carry out between-group comparisons. Spearman's rank correlation was carried out to study the correlation between hs- CRP levels and clinical parameters. Multivariate regression method was used to analyze the factors independently contributing to hs- CRP levels. Results Hs- CRP levels were lower in patients with a larger number of risk factors reaching a desired value. In particular, triglyceride and body mass index ( BMI) were independent risk factors determining hs- CRP levels in a multivariate regression analysis. Furthermore, we compared the influence of various factors on hs- CRP levels in both obese ( BMI ≥25 kg/m2) and non-obese patients with type 2 diabetes ( BMI <25 kg/m2). In obese groups, BMI and urinary albumin were independent risk factors determining hs- CRP levels, whereas triglyceride and statin were independent risk factors in non-obese patients. Conclusions There is some difference in the factors responsible for hs- CRP levels in obese and non-obese patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Pancreatic β-cells secrete insulin when blood glucose levels become high; however, when β-cells are chronically exposed to hyperglycemia, β-cell function gradually deteriorates, which is known as β-cell glucose toxicity. In the diabetic state, nuclear expression of the pancreatic transcription factors pancreatic and duodenal homeobox 1 (PDX-1) and v-Maf musculoaponeurotic fibrosarcoma oncogene family, protein A (MafA) is decreased. In addition, incretin receptor expression in β-cells is decreased, which is likely involved in the impairment of incretin effects in diabetes. Clinically, it is important to select appropriate therapy for type 2 diabetes mellitus (T2DM) so that β-cell function can be preserved. In addition, when appropriate pharmacological interventions against β-cell glucose toxicity are started at the early stages of diabetes, β-cell function is substantially restored, which is not observed if treatment is started at advanced stages. These observations indicate that it is likely that downregulation of pancreatic transcription factors and/or incretin receptors is involved in β-cell dysfunction observed in T2DM and it is very important to start appropriate pharmacological intervention against β-cell glucose toxicity in the early stages of diabetes. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 28-year-old pregnant woman who was presented at the hospital due to positive urinary glucose. The patient has no previous history of epilepsy. She underwent several tests including magnetic resonance imaging, electroencephalography and other laboratory tests. The need for physicians to pay attention on the patients' neurological symptoms, particularly those with high titer glutamic acid decarboxylase (GAD) antibody, is also emphasized.

The aim of this study was to investigate the effect of apolipoprotein (apo)E4 allele on plasma LDL cholesterol response to calorie-restricted diet therapy in type 2 diabetic patients. There were no significant differences in baseline FPG levels, HbA1c levels, BMI, and plasma levels of total cholesterol, triglyceride, and HDL cholesterol between the two apoE genotype groups, but baseline plasma levels of LDL cholesterol were significantly higher in the apoE4/3 group than in the apoE3/3 group. Body weight decreased slightly and FPG levels decreased significantly after diet therapy in both apoE genotype groups. In the apoE3/3 group, only plasma levels of triglyceride decreased significantly after diet therapy, whereas in the apoE4/3 group, plasma levels of triglyceride, total cholesterol, and LDL cholesterol decreased significantly after diet therapy. The decrease (percentage of change) in total cholesterol (-16.3 vs. -6.6%) and LDL cholesterol (-15.6 vs. -0.7%) after diet therapy was significantly greater in the apoE4/3 group than in the apoE3/3 group. Calorie-restricted diet therapy is more effective in reducing plasma LDL cholesterol in type 2 diabetic patients with the apoE4 allele. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The article describes the case of a 71 year old woman with type 2 diabetes referred to the hospital due to severe lipoatrophy throughout the whole abdomen induced by insulin therapy. The patient was diagnosed with insulin-induced lipoatrophy since it appeared after the introduction of insulin therapy and started spreading from the site of insulin injection. Insulin therapy was stopped and she was started on an oral antidiabetes drug.