Effects of SGLT2 Inhibitors and DPP-4 Inhibitors on Advanced Glycation End Products.

Clinical trials have revealed that sodium glucose cotransporter 2 (SGLT2) inhibitors suppress the onset of heart failure and cardiovascular death in diabetic patients. On the other hand, few reports have been published concerning such effects of dipeptidyl peptidase-4 (DPP-4) inhibitors. We undertook the present study to evaluate the effects of SGLT2 inhibitors and DPP-4 inhibitors on the advanced glycation end products (AGEs), well known as a risk factor for the development of cardiovascular disorders.

Effects of SGLT2 inhibitors on the intestinal bacterial flora in Japanese patients with type 2 diabetes mellitus.

Selective inhibitors of sodium glucose co-transporter-2 (SGLT2) suppress renal glucose reabsorption and promote urinary glucose excretion, thereby lowering blood glucose. SGLT2 inhibitors have been reported to reduce body weight. However, the mechanism underlying the reduction in the body weight induced by SGLT2 inhibitor treatment remains to be elucidated.

Effects of Dapagliflozin on Adipose and Liver Fatty Acid Composition and mRNA Expression Involved in Lipid Metabolism in High-Fat-Fed Rats.

Background: SGLT2 inhibitor enhances not only glucose excretion but also fatty acid utilization. Those facts suggest that SGLT2 inhibitor affects fat accumulation and lipid storage.

Objective: In the present study, we evaluated the effects of dapagliflozin on fatty acid composition and gene expression involved in fatty acid metabolism in rat adipose and liver tissues.

Effect of Treatment With Sodium-Glucose Cotransporter 2 Inhibitor on the Initiation of Continuous Positive Airway Pressure Therapy in Type 2 Diabetic Patients With Obstructive Sleep Apnea Syndrome.

Background: Obese patients with type 2 diabetes mellitus often develop obstructive sleep apnea syndrome (OSAS). In this study, continuous positive airway pressure (CPAP) was initiated in Japanese patients with type 2 diabetes mellitus who developed OSAS during treatment with a sodium-glucose cotransporter 2 (SGLT2) inhibitor, and the effect of the SGLT2 inhibitor therapy on the patients was investigated.

Methods: The study was conducted in outpatients with type 2 diabetes mellitus with serum hemoglobin A1c (HbA1c) values of ≥ 6.

Effects of dapagliflozin on peripheral sympathetic nerve activity in standard chow- and high-fat-fed rats after a glucose load.

To clarify the effects of long-term administration of SGLT2 inhibitor, a hypoglycemic agent, on basal sympathetic nerve activity (SNA) and on SNA under development of insulin resistance, we measured peripheral SNA in response to a glucose load in standard chow- (SCF) and high-fat-fed (HFF) rats treated with or without dapagliflozin for 7 weeks. We conducted an intravenous glucose administration (IVGA), and evaluated SNA microneurographically recorded in the unilateral sciatic nerve. Dapagliflozin did not affect the steady state action potential (AP) rate just before the IVGA (baseline) in both the SCF and HFF rats.

Influence of Luseogliflozin on Vaginal Bacterial and Fungal Populations in Japanese Patients With Type 2 Diabetes.

Background: Selective sodium-glucose cotransporter 2 inhibitors, known to lower the blood glucose levels by promoting the urinary glucose excretion, can predispose to genitourinary infections. This prospective study investigated the influence of selective sodium-glucose cotransporter 2 inhibitors luseogliflozin on the vaginal flora of the pre- and postmenopausal women with type 2 diabetes mellitus.

Methods: Twelve premenopausal and 24 postmenopausal female Japanese patients with type 2 diabetes mellitus took luseogliflozin 2.

The Effects of Pemafibrate in Japanese Patients with Type 2 Diabetes Receiving HMG-CoA Reductase Inhibitors.

Objective: The combination therapy of HMG-CoA reductase inhibitors (statins), which are anti-hyperlipidemic agents, and fibrates may increase the risk of hepatic dysfunction and myopathy, therefore, this combination required careful administration for patients. In the present study, the effects of combination therapy of pemafibrate, a novel fibrate, and statins, was evaluated.

Methods: Pemafibrate was administered for 6 months as an add-on to statin therapy in 27 type 2 diabetes patients with dyslipidemia already receiving statins for 6 months (combination group), and the efficacy and safety of the combination therapy in comparison with a pemafibrate monotherapy group was examined.

Effects of Additional Administration of a Selective Inhibitor of Sodium Glucose co-transporter-2 Inhibitor on the Glycemic Control in Japanese Type 2 Diabetes Mellitus Patients Receiving Treatment with a Dipeptidyl Peptidase-4 Inhibitor.

We conducted this study to determine whether additional administration sodium-glucose co-transporter 2 (SGLT2) inhibitor might provide further improvement of glycemic control and also to explore any advantages in Japanese type 2 diabetes patients showing relatively good glycemic control under treatment dipeptidyl peptidase-4 (DPP-4) inhibitors. We divided the patients in two groups, MT group and CT group. The MT group were continued on the DPP-4 inhibitor treatment for 6-months, and CT group were additionally administered an SGLT2 inhibitor treatment for 6-months.

Effects of Concomitant Administration of Sodium Glucose Co-transporter 2 Inhibitor with Insulin on Hemoglobin A1c, Body Mass Index and Serum Lipid Profile in Japanese Type 2 Diabetic Patients.

In patients with type 2 diabetes mellitus who show suboptimal blood glucose control under insulin therapy alone, concomitant treatment with an additional hypoglycemic agent that differs in its mechanism of action from insulin may be considered. We conducted this clinical trial to explore whether further control of increased blood glucose level can be achieved with concomitant use of sodium glucose co-transporter 2 (SGLT2) inhibitor as concomitant with other hypoglycemic therapy, as compared to SGLT2 inhibitor monotherapy, in patients with type 2 diabetes mellitus showing decrease in blood glucose level but less than the effect of insulin monotherapy and there was no significant differences. In the SGLT2 inhibitor monotherapy group, decreases of the serum hemoglobin A1c (HbA1c) level, body weight, body mass index (BMI) and serum triglyceride, and elevation of the serum high density lipoprotein cholesterol concentration were observed as compared to the baseline values.

Effects of Concomitant Administration of a Dipeptidyl Peptidase-4 Inhibitor in Japanese Patients with Type 2 Diabetes Showing Relatively Good Glycemic Control Under Treatment with a Sodium Glucose Co-Transporter 2 Inhibitor.

We conducted this study to determine whether additional administration of a dipeptidyl peptidase-4 (DPP-4) inhibitor might provide further improvement of the glycemic control in Japanese type 2 diabetes patients showing relatively good glycemic control under treatment with a sodium glucose co-transporter 2 (SGLT2) inhibitor. Five SGLT2 inhibitor (luseogliflozin, dapagliflozin, tofogliflozin, empagliflozin and canagliflozin) preparations and five DPP-4 inhibitor (sitagliptin, vildagliptin, alogliptin, anagliptin and linagliptin) preparations were used. The results showed that monotherapy with SGLT2 inhibitor produced significant decreases of the body weight and BMI, hemoglobin A1c (HbA1c) also decreased, but not to a significant extent.

PPARγ activation alters fatty acid composition in adipose triglyceride, in addition to proliferation of small adipocytes, in insulin resistant high-fat fed rats.

It was reported that adipocyte size is potentially correlated in part to amount of long chain polyunsaturated fatty acids (PUFAs) and insulin resistance because several long chain PUFAs can be ligands of peroxisome proliferator-activated receptors (PPARs). In our previous study, marked reduction of PUFAs was observed in insulin-resistant high-fat fed rats, which may indicate that PUFAs are consumed to improve insulin resistance. Although PPARγ agonist, well known as an insulin sensitizer, proliferates small adipocytes, the effects of PPARγ agonist on FA composition in adipose tissue have not been clarified yet.

Gender differences in the perception of difficulty of self-management in patients with diabetes mellitus: a mixed-methods approach.

Aim: The aim of this study was to examine the challenges of self-management of diabetes comparing gender.

Methods: Sixty-four women and 129 men (mean age 63 vs. 60 years) with diabetes mellitus (DM) were interviewed using 12 categories (classification codes b1300, d240, d570, d620, d845, d920, e410 + e414, e420, e425, e465, e560) related to self-care management selected from 99 categories of the International Classification of Functioning, Disability and Health (ICF) Core Set for DM.

Effects of aldose reductase inhibitor on microneurographically assessed peripheral sympathetic nerve activity in rats.

Autonomic neuropathy, one of the serious complications of diabetes, decreases quality of life. Aldose reductase inhibitor (ARI) blocks sorbitol production, and results in prevention of damage of nerve fibers. Beneficial effects of ARI have usually been confirmed through nerve conduction velocity tests in motor and sensory nerves.

Identification of physical and psychosocial problems associated with diabetic nephropathy using the International Classification of Functioning, Disability and Health Core Set for Diabetes Mellitus.

Background: We previously demonstrated validation of the Comprehensive International Classification of Functioning, Disability and Health Core Set for Diabetes Mellitus (ICF-CS for DM) in patients with diabetic nephropathy (DMN). The objective of the present study was to identify differences in experience of physical and psychosocial problems between DMN patients with and without hemodialysis (HD), and diabetes patients without nephropathy using the ICF-CS for DM.

Methods: A total of 302 diabetes outpatients (men, 68 %; mean age, 62 years) were interviewed using four components of the ICF-CS for DM including "Body functions", "Body structures", "Activities and participation", and "Environmental factors".

Black soybean extract reduces fatty acid contents in subcutaneous, but not in visceral adipose triglyceride in high-fat fed rats.

It is known that black soybean (BS) extract, rich in polyphenols, has beneficial effects against obesity, inflammation and insulin resistance. However, detailed effects of BS on lipid metabolism have not been documented well. In the present study, we compared fatty acid composition in visceral and subcutaneous adipose tissues of high-fat fed (HFF) rats and BS administered HFF rats.

Black soybean extract improves lipid profiles in fenofibrate-treated type 2 diabetics with postprandial hyperlipidemia.

Black soybeans (Glycine max (L.) Merr.) are known to be rich in polyphenols, including anthocyanins, and they have been consumed since ancient times for their beneficial effects on health.

Validation of the Comprehensive International Classification of Functioning, Disability and Health (ICF) Core Set for Diabetes Mellitus in patients with diabetic nephropathy.

Background: Diabetic nephropathy (DMN) is the most common cause of end-stage renal disease. Progression of DMN leads to impairment of physical activity, restriction of daily activities, and diminished social participation. Therefore, the precise assessment of the physical and psychosocial problems of DMN patients is important.

Characteristics of sympathetic nerve activity in the rat sciatic nerve in response to microstimulation in a sympathetic fascicle in the contralateral side.

Microneurography is used for the monitor of various peripheral nerve activities. We recently reported that the electrical stimulation of peripheral sympathetic nerve fascicle via the microelectrode, i.e.

Fatty acid composition in fetal, neonatal, and cultured cardiomyocytes in rats.

Reconstructed myocardial tissue still does not have enough pulsatile contraction. It is well known that fetal and mature neonatal cardiomyocytes utilize glucose and lipid, respectively, as their energy substrates, and that cultured ones mainly use glucose in spite of their age comparable to neonate ones, probably due to insufficient supply of lipids from culture medium. In the present study, we compared 7 saturated, 6 monounsaturated, and 11 polyunsaturated fatty acid contents in cultured cardiomyocytes (Cul group) with those in fetal (Fet group, approximately 17 d after impregnation) and neonatal (Neo group, 9 d old) rats, where the age of the Cul cells were set nearly equal to the Neo ones.

Characteristics of spike rate of peripheral sympathetic nervous signal in streptozotocin-induced diabetic rats.

Although streptozotocin-administered (STZ) rats were widely used as an experimental diabetic neuropathy model, sympathetic nerve activity (SNA) in STZ rats has not been microneurographically evaluated so far. In the present study, we investigated the multi-unit, compound sympathetic signal from the sciatic nerve of rats 3 weeks after the administration of streptozotocin, and compared the signal with that of normal (control) rats. After obtaining the sympathetic signal, glucose was intravenously administered to make a transient increase in the blood glucose level to cause SNA change.

Effects of electrical microstimulation of peripheral sympathetic nervous fascicle on glucose uptake in rats.

Artificial pancreas systems control insulin-mediated glucose uptake. Although these systems are widely used in the clinical setting, they are still fraught with structural and biological problems. The non-insulin mediated glucose uptake (NIMGU) mechanism could be an alternative candidate as a target system for the artificial control of peripheral glucose uptake.

Pioglitazone-induced body weight gain is prevented by combined administration with the lipoprotein lipase activator NO-1886.

Pioglitazone improves insulin resistance in diabetics but often causes body weight gain. The lipoprotein lipase activator NO-1886 has been shown to exert both anti-obesity and anti-insulin-resistance effects. In this study, we investigated the effect of the combined administration of pioglitazone with NO-1886 (pioglitazone+NO-1886) in preventing body weight gain in insulin-resistant, high-fat fed rats.

Activation of lipoprotein lipase increases serum high density lipoprotein 2 cholesterol and enlarges high density lipoprotein 2 particles in rats.

It is known that postheparin plasma lipoprotein lipase (LPL) activity correlates with serum high density lipoprotein cholesterol (HDL-C) levels in humans and animals. Furthermore, LPL has been reported to cause enlargement of HDL particle size in vitro. However, these effects have not yet been experimentally proven.

Site dependency of fatty acid composition in adipose triacylglycerol in rats and its absence as a result of high-fat feeding.

It is currently believed that metabolic syndrome, in general, and type 2 diabetes mellitus, in particular, depend more on visceral than on subcutaneous adipose tissue. However, the relationship between insulin resistance and fatty acid composition in visceral and subcutaneous adipose tissues remains to be clarified. In the present study, we extracted the triacylglycerol from visceral (epididymis and mesentery) and subcutaneous adipose tissues in normal and insulin-resistant, high-fat-fed (HFF) rats and determined the composition of each fatty acid.