Aims/Introduction: The slope of estimated glomerular filtration rate (eGFR) decline (eGFR slope) in early‐stage type 2 diabetes patients might predict the future risk of end‐stage renal disease. Type 2 diabetes patients who show rapid progressive eGFR decline are termed rapid decliners. Several studies of rapid decliners have investigated the efficacy of sodium–glucose cotransporter 2 inhibitors (SGLT2i) in patients with advanced renal dysfunction; however, no studies, to our knowledge, have focused on patients with preserved renal function. Therefore, we investigated the efficacy of SGLT2i in rapid decliners with preserved renal function.Materials and Methods: This study enrolled type 2 diabetes patients with baseline eGFR ≥60 mL/min/1.73 m² who had been treated with SGLT2i for ≥3 years. Among these individuals, we defined those with annual eGFR declines ≥5 mL/min/1.73 m² per year before SGLT2i administration as rapid decliners. The primary end‐point was the change in eGFR slope after SGLT2i administration.Results: Among 165 patients treated with SGLT2i for ≥3 years, 21 patients were rapid decliners with preserved renal function. The mean age and eGFR at SGLT2i administration were 58.6 years and 87.1 mL/min/1.73 m², respectively. The mean annual eGFR slope improved significantly in those administered SGLT2i compared with the control group (−1.00 and −4.36 mL/min/1.73 m² per year, respectively; P < 0.001). Notably, the steeper the eGFR slope before starting SGLT2i administration, the larger the improvement of eGFR slope, which was independent of the reduction of albuminuria.Conclusions: Early intervention with SGLT2i may have renoprotective effects in type 2 diabetes patients with rapid decline and preserved renal function.

Aims/Introduction: Although several studies have shown the association between continuous glucose monitoring (CGM)‐derived glycemic variability (GV) and diabetic peripheral neuropathy, no studies have focused on outpatients or used NC‐stat®/DPNCheck™, a new point‐of‐care device for nerve conduction study (NCS). We investigated the association between CGM‐derived GV and NCS using DPNCheck™ in outpatients with type 2 diabetes, and further analyzed the difference in results between patients with and without well‐controlled HbA1c levels.Materials and Methods: All outpatients with type 2 diabetes using the CGM device (FreeStyle Libre Pro®) between 2017 and 2022 were investigated. Sural nerve conduction was evaluated by sensory nerve action potential (SNAP) amplitude and sensory conduction velocity (SCV) using DPNCheck™. Associations of CGM‐derived GV metrics with SNAP amplitude and SCV were investigated.Results: In total, 304 outpatients with type 2 diabetes were included. In a linear regression model, most CGM‐derived GV metrics except for the mean amplitude of glucose excursion and low blood glucose index were significantly associated with SCV, but not with SNAP amplitude. The significant associations of most CGM‐derived GV metrics with SCV remained after adjustment for possible confounding factors, but not after adjustment for glycated hemoglobin (HbA1c). Most CGM‐derived GV metrics were significantly associated with SCV after adjustment for HbA1c in patients with a HbA1c ≤ 6.9%, but not in those with a HbA1c ≥ 7.0%.Conclusions: In outpatients with type 2 diabetes, multiple CGM‐derived GV metrics were significantly associated with SCV obtained by DPNCheck™. GV may have independent impacts on peripheral nerve function, particularly in patients with well‐controlled HbA1c levels.

Objective To explore causes for diabetic retinopathy (DR), the relationships of 24-hour ambulatory blood pressure (BP) and hormone levels with the severity of DR were investigated. Methods The diabetic patients were classified as having no DR, simple DR, or severe DR (pre-proliferative DR plus proliferative DR) based on funduscopic examination, and 24-hour BP, plasma active renin (ARC), aldosterone (PAC), adrenocorticotropic hormone, and cortisol levels were measured in each group. Results Compared to no or simple DR patients, severe DR patients showed significantly higher 24-hour BPs, including daytime and nighttime systolic and diastolic BP levels, independent of diabetic duration and HbA1c levels. The variability of nighttime systolic BP was greater in patients with severe DR than in those with non-severe DR, although nocturnal BP reduction was similar between the groups. The ambulatory BPs were significantly inversely associated with ARC. ARC was significantly lower in severe DR patients than in no or simple DR patients (3.2 [1.5–13.6] vs. 9.8 [4.6–18.0] pg/mL, P < 0.05), but there were no differences in PAC in patients taking Ca channel blockers and/or α-blockers. No associations were found between DR severity and other hormone levels. Conclusion Severe DR was associated with higher 24-hour BPs and suppressed ARC. These findings suggest that mineralocorticoid receptor overactivation may play a role in the higher BP levels and severe DR in diabetic patients.

Background/Objectives: Sleeve gastrectomy (SG) is the most commonly performed bariatric surgery worldwide. It results in significant weight loss and improves metabolic disorders such as hypertension. Weight loss is thought to be the main factor contributing to blood pressure (BP) reduction after SG. Small-intestinal hormones may also mediate the antihypertensive effects of SG. We aimed to investigate the mechanisms underlying the antihypertensive effects of SG through small-intestinal hormones independently of weight loss. Methods: This study involved male Sprague–Dawley rats that underwent a sham operation or SG, followed by a dietary intervention involving a standard diet, a high-fat and high-salt diet, or pair-feeding with SG. Results: Three weeks postoperatively, SG significantly reduced systolic blood pressure (SBP) and increased urinary sodium excretion. RNA sequencing of the small intestine revealed upregulation of the gene encoding prouroguanylin (proUGN). proUGN is a small-intestinal hormone that inhibits renal sodium reabsorption by converting sodium/hydrogen ion exchanger type 3 (NHE3) in the proximal tubules into the inactive phosphorylated form at Ser552 (pS552-NHE3). Furthermore, SG significantly increased proUGN levels in the ileum and plasma, as well as the levels of pS552-NHE3 in the renal cortex. The administration of exogenous uroguanylin, which is converted from proUGN, resulted in increased renal pS552-NHE3, increased urinary sodium excretion, and decreased SBP without body weight reduction. These effects were similar to those observed with SG. Conclusions: SG increases proUGN secretion from the small intestine, leading to increased blood concentration. This inhibits NHE3 activity in the proximal tubules, promotes natriuresis and reduces BP.