The performance of a simple single-leg balance test as well as that of a grip strength test were negatively associated with the risk of T2DM among Japanese.

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Context Although calorie loss from increased urinary glucose excretion continues after long-term treatment with sodium-glucose cotransporter 2 inhibitors (SGLT2is), the mechanisms of the attenuated weight loss due to SGLT2is are not well known. Objective To examine the mechanism of the attenuated weight loss during long-term treatment with an SGLT2i, tofogliflozin, focusing on the antilipolytic effect of insulin on adipose tissue. Design and Participants An integrated analysis was performed using data from two phase 3 studies of 52 weeks of tofogliflozin administration. The antilipolytic effect was evaluated using adipose tissue insulin resistance (Adipo-IR) calculated from the product of the levels of fasting insulin (f-IRI) and fasting free fatty acids (f-FFAs). Results Data from 774 patients with type 2 diabetes (mean age, 58.5 years; glycosylated hemoglobin, 8.1%; body mass index, 25.6 kg/m2; estimated glomerular filtration rate, 83.9 mL/min/1.73m2; 66% men) were analyzed. Weight loss plateaued between weeks 24 and 52 after decreasing significantly. f-IRI levels decreased significantly from baseline to week 24, and the decrease was maintained until Week 52. f-FFA levels significantly increased, peaked at week 24, then declined from weeks 24 to 52. Adipo-IR levels declined progressively throughout the 52 weeks (−3.6 mmol/L·pmol/L and −6.2 mmol/L·pmol/L at weeks 24 and 52, respectively; P < 0.001 baseline vs weeks 24 and 52 and week 24 vs week 52). Higher baseline Adipo-IR levels were independently associated with greater weight loss at week 52. Conclusion The improved antilipolytic effect in adipose tissue may attenuate progressive lipolysis, leading to attenuating future weight loss induced by an SGLT2i in patients with type 2 diabetes.

Citation: Yamamoto M, Fujihara K, Ishizawa M, et al. Overt proteinuria, moderately reduced eGFR and their combination are predictive of severe diabetic retinopathy or diabetic macular edema in diabetes. Invest Ophthalmol Vis Sci. 2019;60:2685-2689. https://doi.org/10.1167 PURPOSE. Since the combined effects of proteinuria and a moderately decreased eGFR on incident severe eye complications in patients with diabetes are still largely unknown, these associations were determined in a large historical cohort of Japanese patients with diabetes mellitus. METHODS.We evaluated the effects of overt proteinuria (OP) (dipstick 1þ and over) and/or moderately reduced estimated glomerular filtration rate (eGFR) (MG) (baseline eGFR 30.0-54.9 mL/min/1.73 m 2 ) on the incidence of treatment-required diabetic eye diseases (TRDED). We divided 7709 patients into four groups according to the presence or absence of OP and MG: no OP without MG (NP[MGÀ]), OP without MG (OP[MGÀ]), no OP with MG (NP[MGþ]), and OP with MG (OP[MGþ]). Multivariate Cox analyses were performed to calculate hazard ratios (HRs) with 95% confidence intervals for combinations of the presence and/or absence of OP and MG on the risk of developing TRDED. RESULTS.During the median follow-up period of 5.6 years, 168 patients developed TRDED. HRs for OP and MG for incident TRDED were 1.91 (95% confidence interval, 1.27-2.87) and 1.90 (1.11-3.23), respectively. HRs for incident TRDED were 1.73 (1.11-2.69) and 5.57 (2.40-12.94) for OP(MGÀ) and OP(MGþ), respectively, in comparison with NP(MGÀ). CONCLUSIONS.In Japanese patients with diabetes, OP and MG were separately as well as additionally associated with higher risks of TRDED. Results indicate the necessity of the simultaneous assessment of proteinuria and eGFR for appropriate evaluation of risks of severe eye complications in patients with diabetes.

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Abstract. Ghrelin has a stimulating effect on arginine vasopressin (AVp). however, it is not known whether GhRp-2, a synthetic ghrelin receptor agonist, also has a stimulating effect on AVp release in men. to determine whether the GhRp-2 test is useful for assessing AVp secretion, blood Acth, Gh, FSh, Lh, pRL, tSh and AVp levels, as well as glucose, osmolality, sodium and hematocrit, were measured before and 15, 30, 45 and 60 min after an intravenous bolus of 100 µg GhRp-2 in 10 healthy men with and without fasting. blood pressure was measured at 15-min intervals. AVp secretion was not stimulated by the GHRP-2 test with and without fasting. There were no significant differences in hematocrit, blood pressure and plasma osmolality before and after GFRP-2 injection, although significant (p<0.001) peak blood Gh, and Acth and pRL levels were observed 30 and 15 min after GhRp-2 injection with and without fasting, respectively, and the maximal peaks were significantly (p<0.05) higher with fasting than without fasting. these results suggest that AVp secretion is not stimulated by the GhRp-2 test both with and without fasting, though Gh, Acth and pRL levels were higher with than without fasting.

Background Evidence of the role of systolic blood pressure ( SBP ) in development of severe diabetic retinopathy is not strong, although the adverse effect of low diastolic blood pressure has been a partial explanation. We assessed the predictive ability of incident severe diabetic retinopathy between pulse pressure ( PP ) which considers both SBP and diastolic blood pressure, compared with SBP . Methods and Results Eligible patients (12 242, 83% men) aged 19 to 72 years from a nationwide claims database were analyzed for a median observational 4.8‐year period. Severe diabetic retinopathy was defined as vision‐threatening treatment‐required diabetic eye diseases. Multivariate Cox regression analysis revealed that hazard ratios (95% CI ) of treatment‐required diabetic eye diseases for 1 increment of standard deviation and the top tertile compared with the bottom tertile were 1.39 (1.21–1.60) and 1.72 (1.17–2.51), respectively, for PP and 1.22 (1.05–1.41) and 1.43 (0.97–2.11), respectively, for SBP adjusted for age, sex, body mass index, hemoglobin A1c, fasting plasma glucose, lipids, and smoking status. In a model with SBP and PP simultaneously as covariates, the hazard ratios of only PP (hazard ratios [95% CI ], 1.57 [1.26–1.96]) but not SBP (0.85 [0.68–1.07]) were statistically significant. Delong test revealed a significant difference in the area under the receiver operating characteristic curve between PP and SBP (area under the receiver operating characteristic curve [95% CI ], 0.58 [0.54–0.63] versus 0.54 [0.50–0.59]; P =0.03). The strongest predictor remained as hemoglobin A1c (area under the receiver operating characteristic curve [95% CI ], 0.80 [0.77–0.84]). Conclusions After excluding the significant impact of glycemic control, PP in comparison with SBP is a better predictor of severe diabetic retinopathy, suggesting a role of diastolic blood pressure and arterial stiffness in pathology.