Comprehensive efficacy of ipragliflozin on various conditioned type 2 diabetes compared with dipeptidyl peptidase-4 inhibitors and with both agents, based on a real-world multicenter trial.

AIMS: The effects of ipragliflozin, the first sodium-glucose co-transporter 2 inhibitors (SGLT2i) launched in Japan in 2014, and with dipeptidyl peptidase-4 inhibitors (DPP-4i) on glycemic control and metabolic changes were investigated comprehensively on various conditioned type 2 diabetes (T2DM) by evaluating various clinical parameters in a real-world setting. MATERIALS AND METHODS: A total of 101 patients with T2DM aged 20-80 years with 7.0% ≤ HbA1c < 10.0% were followed in this 52-week, open-label, prospective, real-world, multicenter study. RESULTS: HbA1c decreased significantly in all groups. In ipragliflozin using groups, body weight, waist circumference, blood pressure, HOMA-IR, AST, ALT, γ-GTP, uric acid and leptin levels decreased, in contrast, HDL-cholesterol, total ketone bodies, blood urea nitrogen, creatinine, RBC, hemoglobin and hematocrit levels increased, however, in DPP-4i sole group, no significant trends were observed in these parameters. Change in leptin positively correlated with insulin, while change in total ketone bodies inversely correlated with ALT in ipragliflozin using groups. Fasting active gastric inhibitory polypeptide levels decreased in ipragliflozin sole group. Glucagon showed no changes. No significant safety concerns were observed in this study. CONCLUSIONS: Ipragliflozin is useful and safe, showing some contrastive effects on several clinical parameters which are not shown with DPP-4i, resulting several clinical benefits. The co-administration of ipragliflozin and a DPP-4i has a better clinical outcome than either single-agent therapy.

Association between aerobic capacity and the improvement in glycemic control after the exercise training in type 2 diabetes.

BACKGROUND: We investigated the influence of aerobic capacity on the improvement in glycemic control achieved by long-term aerobic exercise in type 2 diabetes. METHODS: Fifty-three male patients with type 2 diabetes, recruited from outpatient clinics, wore multiple-memory accelerometers and were instructed to exercise at moderate intensity for ≥30 min on ≥3 days per week over 12 months. Peak oxygen uptake (peak [Formula: see text]) and serum glycated albumin (GA) were measured at baseline and after 3, 6, 12 months. Peak [Formula: see text] data were expressed as percentages of predicted values. RESULTS: According to the number of bouts of exercise (intensity, ≥4 METs; duration, ≥15 min), the subjects were divided into inactive (<3 times per week) or active (≥3 times per week) groups. Serum GA decreased significantly after 3, 6, 12 months only in the active group. When the subjects were assigned to four groups according to initial peak [Formula: see text] (%pred) (low-fitness or high-fitness) and the number of bouts of exercise (active or inactive), serum GA decreased significantly after 3, 6, 12 months only in the high-fitness/active group. When the subjects were also assigned to four groups according to the change in peak [Formula: see text] (%pred) (improved or unimproved) and the number of bouts of exercise (active or inactive), serum GA decreased significantly after 3 and 12 months only in the improved/active group. CONCLUSION: The improvement in glycemic control achieved by aerobic exercise was associated with both the initial and the increase in peak [Formula: see text] during aerobic exercise.

Effect of aerobic exercise training on oxidative stress in patients with type 2 diabetes mellitus.

The purpose of this study was to determine whether moderate-intensity exercise training reduces oxidative stress in patients with type 2 diabetes mellitus over 12 months. The patients were divided into 3 groups: aerobic training combined with the use of a fitness center (group A, n = 43), aerobic training only (group B, n = 44), or controls (group C, n = 16). The subjects in groups A and B were instructed to exercise at 50% of peak oxygen uptake for more than 30 minutes on at least 3 days per week over a 12 month period. In addition, the subjects in group A were instructed to use a fitness center and were taught how to perform aerobic training in the indicated manner by certified fitness instructors. We measured the levels of urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) as a parameter of oxidative stress. Serum glycated albumin levels were reduced significantly after 6 and 12 months in groups A and B and after 12 months in group C. Urinary 8-OHdG levels decreased after 12 months in groups A and B, but remained unchanged in group C. There was a significant positive linear association between percentage changes in urinary 8-OHdG and glycated albumin levels over the 12 months. In conclusion, aerobic exercise training improved glycemic control and reduced oxidative stress in patients with type 2 diabetes mellitus. Furthermore, improvement in glycemic control was associated with a reduction in oxidative stress.

A case of Addison's disease confirmed with low dose cosyntropin stimulation test.

An eighty-year-old man who had complained of skin pigmentation and weight loss was referred to our hospital. Upon physical examination, marked hyperpigmentation was found on the whole body including oral mucosa, tongue and fingernails. Endocrinological findings showed increased ACTH (126 pg/ml) and normal serum cortisol (15.4 microg/dl). First, we used a 250 microg cosyntropin stimulation test which is valid to diagnose Addison's disease, resulting in an adequate cortisol response. Second, we performed 1 microg cosyntropin stimulation test, and the cortisol response was blunted. Since the diagnosis of Addison's disease was fairly certain, he was treated with hydrocortisone 15 mg/day, and improvement of his skin pigmentation and an increase in body weight were observed. To our knowledge, this is the first report that 1 mug cosyntropin stimulation test was helpful to make diagnosis as having Addison's disease rather than the 250 microg cosyntropin stimulation test, although it is established that the 1 mug cosyntropin stimulation test is useful in secondary or relative adrenal insufficiency.

Circulating visfatin level is correlated with inflammation, but not with insulin resistance.

OBJECTIVE: Recent studies, both in vitro and in vivo, have indicated that visfatin is one of the inflammatory cytokines, although the relationship between visfatin and insulin resistance remains inconclusive. Accordingly, we assessed the association between visfatin concentrations in serum and those of interleukin-6 (IL-6) and C-reactive protein (CRP), known as markers of systemic inflammation, and also investigated the relationship between these serum concentrations and insulin resistance. DESIGN AND METHOD: A total of 295 Japanese Americans living in Hawaii (126 men and 169 women, mean age 68.7 +/- 14.9 years) were enrolled. The serum levels of visfatin, IL-6 and CRP levels were measured, and homeostasis model assessment for insulin resistance (HOMA-IR) was calculated as a marker of insulin resistance. RESULTS: Significant positive correlations were found between serum levels of visfatin and IL-6 or CRP (r = 0.271, P < 0.001; r = 0.118, P < 0.05, respectively). Multiple regression analysis revealed that correlations between serum levels of visfatin and IL-6 or CRP remained significant after adjustments for age, sex, body mass index, per cent body fat and waist girth. There was no significant trend of the HOMA-IR for the tertiles of serum concentrations of visfatin. On the other hand, a significant trend towards increase of HOMA-IR with increasing tertile of serum concentrations, from the lowest to the highest, was observed for both IL-6 and CRP. The HOMA-IR in subjects with serum concentration of IL-6 or CRP in the highest or intermediate tertiles of IL-6 or CRP were significantly higher than that in subjects in the lowest tertile, even after adjustment for age and sex (IL-6: P < 0.001 and P < 0.001, respectively; CRP: P < 0.001 and P < 0.01, respectively). CONCLUSION: Serum visfatin levels were positively correlated with the serum levels of IL-6 and slightly related with serum levels of CRP, but not with HOMA-IR, in Japanese Americans. Our results indicate that circulating visfatin may reflect inflammation status.

A protective effect of adiponectin against oxidative stress in Japanese Americans: the association between adiponectin or leptin and urinary isoprostane.

Adiponectin, which is produced by adipose tissue, is thought to play an important role in inflammation. On the other hand, adiposity, or the hypertrophy of adipose tissue, has been reported to increase oxidative stress. Accordingly, the possibility exists that adiponectin, as well as leptin, influences oxidative stress, resulting in a proinflammatory state. However, the relationship between adiponectin and oxidative stress is unclear. We examined 259 Japanese Americans living in Hawaii who were diagnosed as having normal glucose tolerance (NGT), impaired glucose tolerance, or diabetes by a 75-g oral glucose tolerance test. First, we measured their serum adiponectin, leptin, and high-sensitivity C-reactive protein levels as markers of inflammation, and urinary 8-iso-protaglandin F(2 alpha) (isoprostane) as a relevant marker of oxidative stress. We investigated the relationship between adiponectin or leptin and isoprostane among these subjects. In the diabetic subjects, the adiponectin and leptin levels were significantly lower and higher, respectively, than among the NGT subjects. Urinary isoprostane levels tended to decrease significantly after a rise in adiponectin levels (P = .014) among the NGT subjects. Next, we investigated the association between the 2 adipocytokines and isoprostane by regression models. Adiponectin was negatively but significantly associated with urinary isoprostane levels adjusted for age, gender, and smoking status, whereas leptin was positively and significantly correlated with urinary isoprostane levels (P = .014 and .004, respectively). With respect to adiponectin, this association was attenuated but still significant when further adjustments were made for waist-to-hip ratio, body mass index, percent body fat, C-reactive protein levels, glucose tolerance status, or homeostasis model assessment. In conclusion, this study suggests that adiponectin and leptin might be associated with oxidative stress levels. These results also suggest the possibility that adiponectin might modulate oxidative stress, leading to antidiabetic and anti-arteriosclerotic effects.