In the present randomized study, we assessed the efficacy of ipragliflozin compared with sitagliptin in 124 Japanese patients with type 2 diabetes. Sodium‐glucose co‐transporter‐2 inhibitor‐naïve and incretin‐related agent‐naïve patients were randomly assigned to receive additional 50 mg ipragliflozin or sitagliptin. The primary endpoint was the proportion of participants with >0.5% decrease in glycated haemoglobin (HbA1c) without body weight gain at 12 weeks. For secondary endpoints, we measured several biomarkers related to metabolic changes. After 12 weeks, 53.9% of participants in the ipragliflozin and 42.9% in the sitagliptin group reached the primary endpoint ( P = 0.32). Decreases in homeostatic model assessment of insulin resistance, body fat percentage and skeletal muscle mass index, and increases in free fatty acids, ketone body concentration and HDL cholesterol levels were greater in the ipragliflozin group. Increases in homeostatic model assessment of β‐cell function and decreases in proinsulin‐to‐insulin ratio were greater in the sitagliptin group. No serious adverse events occurred in either group. In conclusion, ipragliflozin had beneficial effects on fat reduction, insulin resistance and lipid metabolism, while sitagliptin had beneficial effects on β‐cell function.

Objective To clarify the associations between serum omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acid (PUFA) levels and obesity-related metabolic abnormalities in patients with type 2 diabetes. Methods and Materials Data from 225 Japanese patients with type 2 diabetes were cross-sectionally analyzed. The serum levels of n-6 PUFAs [dihomo-γ-linolenic acid (DGLA) and arachidonic acid (AA)] and n-3 PUFAs (eicosapentaenoic acid and docosahexaenoic acid) were measured, and the estimated Δ-5 desaturase (D5D) activity was calculated based on the AA to DGLA ratio. The associations between the composition of PUFAs and obesity-related parameters, including the body mass index (BMI), waist circumference, alanine amino transferase (ALT) level, homeostatic model assessment of insulin resistance (HOMA-IR), and body fat percentage, as measured by a bioelectrical impedance analysis, were analyzed. Results Among the PUFAs, the DGLA level had the strongest correlations with BMI (p<0.001), waist circumference (p<0.001), ALT level (p<0.001), HOMA-IR (p<0.001), and body fat percentage (p<0.01). AA was positively correlated and D5D was negatively correlated with several obesity-related parameters, while n-3 PUFAs did not have a constant correlation. A multivariate regression analysis revealed that the DGLA level was an independent determinant for HOMA-IR (β=0.195, p=0.0066) after adjusting for sex, age, BMI, and the ALT, triglyceride, and HbA1c levels. Conclusion A high serum DGLA level was associated with obesity, body fat accumulation, a high ALT level, and insulin resistance in patients with type 2 diabetes. The measurement of the serum PUFA levels may be useful for evaluating metabolic abnormalities and estimating the dietary habits of patients.

BACKGROUND: Renin suppression in primary aldosteronism indicates mineralocorticoid receptor activation via excessive aldosterone secretion, inducing renal damage. We investigated whether the reversal of renin suppression after the initiation of mineralocorticoid receptor antagonist therapy was associated with long-term renal outcomes in medically treated patients with primary aldosteronism. METHODS: This retrospective cohort study included 318 patients with primary aldosteronism treated with mineralocorticoid receptor antagonist between 2008 and 2020 at the Yokohama Rosai Hospital in Japan. The posttreatment renin status was defined as unsuppressed (ie, reversal of renin suppression) when individual plasma renin activity after the initiation of mineralocorticoid receptor antagonist (post-plasma renin activity) was ≥1.0 ng/mL per hour; otherwise, it was defined as suppressed. We analyzed the association of posttreatment renin status with subsequent longitudinal estimated glomerular filtration rate changes using linear mixed-effects models for repeated measurements, adjusting for potential confounders. RESULTS: The posttreatment renin status of 119 patients was unsuppressed (median post-plasma renin activity, 1.7 ng/mL per hour) and that of 199 patients was suppressed (median post-PRA, 0.5 ng/mL per hour). Through the median follow-up period of 3.1 years, the decline in estimated glomerular filtration rate was milder among patients with the unsuppressed posttreatment renin (−0.46 [95% CI, −0.63 to −0.28] mL/min per 1.73 m ² per year) than those with suppressed posttreatment renin (−1.41 [95% CI, −1.56 to −1.27] mL/min per 1.73 m ² per year; difference, 0.96 [95% CI, 0.72–1.20] mL/min per 1.73 m ² per year). CONCLUSIONS: Our findings may highlight the importance of reversing renin suppression with optimal mineralocorticoid receptor antagonist titration in medically treated primary aldosteronism, which could mitigate adverse renal outcomes.

Background: Primary aldosteronism can cause cardiac dysfunction, including left ventricular hypertrophy, left ventricular diastolic dysfunction, and left atrial enlargement. A few studies have compared the cardioprotective effects between surgery and medication for primary aldosteronism, although most have not adjusted for baseline disease status. In this study, we investigated the difference in cardiovascular outcomes between surgery and medication treatment for primary aldosteronism after adjusting for baseline clinical characteristics, including aldosterone level and pretreatment echocardiographic information. Methods and Results: We retrospectively analyzed 220 patients diagnosed with primary aldosteronism who underwent adrenalectomy (n=144) or medication treatment (n=76) between 2009 and 2019. Echocardiographic changes were evaluated pretreatment and 1 year posttreatment. The surgery group had lower potassium, lower plasma renin activity, and higher plasma aldosterone concentration than the medication group, indicating a severe primary aldosteronism phenotype in the former. The decrease in left ventricular mass index after treatment was significantly greater in the surgery group than in the medication group ( P =0.047). However, this relationship was not noted after multivariable regression analysis (standard β=−0.08, P =0.17). Additionally, decreased parameter values related to left ventricular diastolic dysfunction and left atrial enlargement were not different between the groups. Pretreatment echocardiographic values were most associated with changes in all echocardiographic parameters. The findings were consistent in the propensity score‐matched analysis. Conclusions: This study's findings suggest that there is no difference in cardioprotective efficacy between surgical and medication treatment under similar disease severity; however, it should be considered that several study participants with severe hyperaldosteronism were managed surgically.

Background: Diabetic kidney disease (DKD) is one of the main complications of type 2 diabetes mellitus (T2DM). DKD is a known risk factor for end-stage renal disease, cardiovascular disease, and all-cause death. Effective intervention for early-stage DKD is vital to slowing down the progression of kidney disease and improve prognoses. Mobile health (mHealth) is reportedly effective in supporting patients’ self-care and improving glycemic control, but the impact of mHealth on DKD has yet to be shown. Objective: The purpose of this study is to evaluate the efficacy of standard therapy with the addition of a self-management support system, DialBetesPlus, in patients with DKD and microalbuminuria. Methods: This study is a prospective, randomized, open-label, multicenter clinical trial. The target population consists of 160 patients diagnosed with T2DM accompanied by microalbuminuria. We randomly assigned the patients to 2 groups—the intervention group using DialBetesPlus in addition to conventional therapy and the control group using conventional therapy alone. DialBetesPlus is a smartphone application that supports patients’ self-management of T2DM. The study period was 12 months, with a follow-up survey at 18 months. The primary outcome was a change in albuminuria levels at 12 months. Secondary outcomes included changes in physical parameters, blood test results (glycemic control, renal function, and lipid metabolism), lifestyle habits, self-management scores, medication therapy, and quality of life. Results: The study was approved in April 2018. We began recruiting patients in July 2018 and completed recruiting in August 2019. The final 18-month follow-up was conducted in March 2021. We recruited 159 patients and randomly allocated 70 into the intervention group and 61 into the control group, with 28 exclusions due to withdrawal of consent, refusal to continue, or ineligibility. The first results are expected to be available in 2021. Conclusions: This is the first randomized controlled trial assessing the efficacy of mHealth on early-stage DKD. We expect that albuminuria levels will decrease significantly in the intervention group due to improved glycemic control with ameliorated self-care behaviors. Trial Registration: UMIN-CTR UMIN000033261; https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000037924 International Registered Report Identifier (IRRID): DERR1-10.2196/31061

Primary aldosteronism (PA) usually accompanies suppressed plasma renin activity (PRA) through a negative feedback mechanism. While some cases of PA with unsuppressed PRA were reported, there have been no studies about the characteristics of PA with unsuppressed PRA; thus, these characteristics were examined herein. Nine patients with unsuppressed PRA and 86 patients with suppressed PRA were examined. All patients underwent segmental adrenal venous sampling (sAVS) and adrenalectomy, and were pathologically confirmed to have cytochrome P450 11B2 (CYP11B2)-positive aldosterone-producing adenoma according to international histopathology consensus criteria. Unsuppressed and suppressed PRA were defined as PRA levels of > 1.0 and ≤ 1.0 ng/mL/hr, respectively, in multiple blood samples obtained in the resting position. The unsuppressed PRA group had higher morning cortisol levels (12.6 [8.5, 13.5] vs. 8.5 [7.1, 11.0] μg/dL, P = 0.03) and higher cortisol levels after a 1 mg dexamethasone suppression test (DST) (2.2 [1.6, 2.5] vs. 1.3 [1.0, 1.9] μ g/dL, P = 0.004) than the suppressed PRA group. The unsuppressed PRA group also showed higher aldosterone levels on the non-surgical side during sAVS (P = 0.02 before adrenocorticotropic hormone (ACTH) stimulation, P = 0.002 after ACTH stimulation), a higher intensity of CYP17 expression in the resected adrenal gland (P = 0.02), and a lower clinical complete success rate 1 year after surgery (P = 0.04) compared with those in the suppressed PRA group. These findings suggest that PA should not be ruled out by unsuppressed PRA among patients with hypertension, particularly when their cortisol levels remain unsuppressed in the 1 mg DST. Meanwhile, it should be acknowledged that patients with unsuppressed PRA have higher aldosterone levels on the non-surgical side, and a lower likelihood of postoperative complete clinical success is to be expected.