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Aim: To conduct a post hoc subgroup analysis of patients with type 2 diabetes (T2D) from the RECAP study, who were treated with sodium‐glucose cotransporter‐2 (SGLT2) inhibitor and glucagon‐like peptide 1 receptor agonist (GLP‐1RA) combination therapy, focusing only on those patients who had chronic kidney disease (CKD), to examine whether the composite renal outcome differed between those who received SGLT2 inhibitor treatment first and those who received a GLP‐1RA first. Methods: We included 438 patients with CKD (GLP‐1RA‐first group, n = 223; SGLT2 inhibitor‐first group, n = 215) from the 643 T2D patients in the RECAP study. The incidence of the composite renal outcome, defined as progression to macroalbuminuria and/or a ≥50% decrease in estimated glomerular filtration rate (eGFR), was analysed using a propensity score (PS)‐matched model. Furthermore, we calculated the win ratio for these composite renal outcomes, which were weighted in the following order: (1) both a ≥50% decrease in eGFR and progression to macroalbuminuria; (2) a decrease in eGFR of ≥50% only; and (3) progression to macroalbuminuria only. Results: Using the PS‐matched model, 132 patients from each group were paired. The incidence of renal composite outcomes did not differ between the two groups (GLP‐1RA‐first group, 10%; SGLT2 inhibitor‐first group, 17%; odds ratio 1.80; 95% confidence interval [CI] 0.85 to 4.26; p = 0.12). The win ratio of the GLP‐1RA‐first group versus the SGLT2 inhibitor‐first group was 1.83 (95% CI 1.71 to 1.95; p < 0.001). Conclusion: Although the renal composite outcome did not differ between the two groups, the win ratio of the GLP‐1RA‐first group versus the SGLT2 inhibitor‐first group was significant. These results suggest that, in GLP‐1RA and SGLT2 inhibitor combination therapy, the addition of an SGLT2 inhibitor to baseline GLP‐1RA treatment may lead to more favourable renal outcomes. [ABSTRACT FROM AUTHOR]

Objective: Because quantifying glycans with complex structures is technically challenging, little is known about the association of glycosylation profiles with the renal prognosis in diabetic kidney disease (DKD).Research Design and Methods: In 675 patients with type 2 diabetes, we assessed the baseline urinary glycan signals binding to 45 lectins with different specificities. The end point was a decrease of estimated glomerular filtration rate (eGFR) by ≥30% from baseline or dialysis for end-stage renal disease.Results: During a median follow-up of 4.0 years, 63 patients reached the end point. Cox proportional hazards analysis revealed that urinary levels of glycans binding to six lectins were significantly associated with the outcome after adjustment for known indicators of DKD, although these urinary glycans, except that for DBA, were highly correlated with baseline albuminuria and eGFR. Hazard ratios for these lectins were (+1 SD for the glycan index) as follows: SNA (recognizing glycan Siaα2-6Gal/GalNAc), 1.42 (95% CI 1.14-1.76); RCA120 (Galβ4GlcNAc), 1.28 (1.01-1.64); DBA (GalNAcα3GalNAc), 0.80 (0.64-0.997); ABA (Galβ3GalNAc), 1.29 (1.02-1.64); Jacalin (Galβ3GalNAc), 1.30 (1.02-1.67); and ACA (Galβ3GalNAc), 1.32 (1.04-1.67). Adding these glycan indexes to a model containing known indicators of progression improved prediction of the outcome (net reclassification improvement increased by 0.51 [0.22-0.80], relative integrated discrimination improvement increased by 0.18 [0.01-0.35], and the Akaike information criterion decreased from 296 to 287).Conclusions: The urinary glycan profile identified in this study may be useful for predicting renal prognosis in patients with type 2 diabetes. Additional investigation of glycosylation changes and urinary glycan excretion in DKD is needed. [ABSTRACT FROM AUTHOR]

Introduction: ACE cleaves angiotensin I (Ang I) to angiotensin II (Ang II) inducing vasoconstriction via Ang II type 1 (AT1) receptor, while ACE2 cleaves Ang II to Ang (1-7) causing vasodilatation by acting on the Mas receptor. In diabetic kidney disease (DKD), it is still unclear whether plasma or urine ACE2 levels predict renal outcomes or not., Research Design and Methods: Among 777 participants with diabetes enrolled in the Urinary biomarker for Continuous And Rapid progression of diabetic nEphropathy study, the 296 patients followed up for 9 years were investigated. Plasma and urinary ACE2 levels were measured by the ELISA. The primary end point was a composite of a decrease of estimated glomerular filtration rate (eGFR) by at least 30% from baseline or initiation of hemodialysis or peritoneal dialysis. The secondary end points were a 30% increase or a 30% decrease in albumin-to-creatinine ratio from baseline to 1 year., Results: The cumulative incidence of the renal composite outcome was significantly higher in group 1 with lowest tertile of plasma ACE2 (p=0.040). Group 2 with middle and highest tertile was associated with better renal outcomes in the crude Cox regression model adjusted by age and sex (HR 0.56, 95% CI 0.31 to 0.99, p=0.047). Plasma ACE2 levels demonstrated a significant association with 30% decrease in ACR (OR 1.46, 95% CI 1.044 to 2.035, p=0.027) after adjusting for age, sex, systolic blood pressure, hemoglobin A1c, and eGFR., Conclusions: Higher baseline plasma ACE2 levels in DKD were protective for development and progression of albuminuria and associated with fewer renal end points, suggesting plasma ACE2 may be used as a prognosis marker of DKD., Trial Registration Number: UMIN000011525., Competing Interests: Competing interests: JW receives speaker honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Kyowa Kirin, Novo Nordisk, and Mitsubishi Tanabe, and receives grant support from Bayer, Chugai, Kyowa Kirin, Otsuka, Shionogi, Sumitomo, and Mitsubishi Tanabe., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: We previously reported the mean average relative difference (MARD) of the sensor glucose (SG) of the first-generation FreeStyle Libre with the original algorithm, an intermittent scanning continuous glucose monitoring (isCGM) device, was 15.6% in the Effect of Intermittent-Scanning Continuous Glucose Monitoring to Glycemic Control Including Hypoglycemia and Quality of Life of Patients with Type 1 Diabetes Mellitus Study (ISCHIA Study). In the present study, we aimed to further analyze its accuracy in detail by conducting a post-hoc analysis of the study., Methods: The ISCHIA Study was a multicenter, randomized, cross-over trial to assess the efficacy of isCGM. The SG levels of isCGM and the measured capillary blood glucose (BG) levels of 91 participants were used for the analysis., Results: Bland-Altman analysis showed bias of -13.0 mg/dl when the SG levels were compared to the BG levels, however no proportional bias was observed ( r = 0.085). MARD of the participants without and with contact dermatitis were 15.0 ± 6.0% and 27.4 ± 21.4% ( P = 0.001), respectively., Conclusion: There was negative bias in the SG levels of isCGM compared to the BG levels. There is a possibility that the complication of the contact dermatitis during isCGM use may be related with deteriorated accuracy of the SG levels.

Background: Information about factors related to better adherence to continuous glucose monitoring (CGM) sensor adherence is quite limited., Materials and Methods: Forty-six participants with type 1 diabetes using continuous subcutaneous insulin infusion (CSII) without CGM were recruited. The participants' characteristics and diabetes-related quality of life (QOL) were evaluated at baseline and one year after starting to use CGM. Participants wearing the sensor for ≥60% of the time were considered as adherent., Results: The mean age of the 46 participants was 44.1 ± 15.0 years old and the mean glycohemoglobin (HbA1c) was 7.7 ± 1.0%; 60.9% of the participants were classified as adherent. The duration of using CSII was longer in the adherent group, and the degree of diabetic retinopathy was significantly different. There were no significant differences in age, frequency of self-monitoring of blood glucose, or Hypoglycemia Fear Survey (HFS-B for behavior, HFS-W for worry) score at baseline between the adherent and nonadherent groups. The Problem Areas in Diabetes (PAID) score at baseline was significantly higher and the total CSII-QOL score at baseline was significantly lower in the adherent group. The usage of dual-wave bolus was significantly increased in the adherent group (34.6%-61.5%, P  = .016), but not in the nonadherent group (33.3%-33.3%, P  > .999). The HbA1c level showed a significant improvement in the adherent group (7.8%-7.3%, P  < .001), but not in the nonadherent group (7.5%-7.2%, P  = .102)., Conclusions: Higher adherence to CGM sensors may be associated with a heavier emotional burden of diabetes and a worse QOL in relation to CSII at baseline.

Objective: Intermittent-scanning continuous glucose monitoring (isCGM) is widely used in type 1 diabetes (T1D) patients; however, the education required to prevent hypoglycemia by using isCGM is not established. This study examines the combined effect of isCGM device usage and the education to reduce the time in hypoglycemia in comparison to conventional self-monitoring of blood glucose (SMBG)., Methods: The Effect of Intermittent-Scanning Continuous Glucose Monitoring to Glycemic Control Including Hypoglycemia and Quality of Life of Patients with Type 1 Diabetes Mellitus Study (ISCHIA Study), a randomized, crossover trial, enrolls 104 T1D patients (age, 20-74 years) with T1D. Participants are randomized to use isCGM combined with structured education (Intervention period) or SMBG (Control period) for 84 days, followed by the other for a further 84 days. During the Intervention period, participants have access to the sensor glucose levels and trend arrow of the device. During the Control period, participants conduct SMBG at least three times a day, and retrospective CGM is used to record the blinded sensor glucose levels. The primary endpoint is the decrease of time in hypoglycemia ( < 70 mg/dL) per day (hour/day) during the Intervention period compared with the Control period. The secondary endpoints include other indices of glycemic control, glycoalbumin, accuracy of isCGM, diabetes-related quality of life (QOL), adherence, and cost-effectiveness. The study protocol has received Certified Review Board (CRB) approval from National Hospital Organization Osaka National Hospital (N2018002, Feb 14, 2019). This study is carried out in accordance with the Declaration of Helsinki and the Clinical Trials Act. The findings will be published in peer-reviewed journals., Conclusion: The ISCHIA study will contribute to the standardization of patient education regarding the prevention of hypoglycemia by using isCGM.

A 43-year-old male with type 2 diabetes, under treatment with 5 mg/day of dapagliflozin, was referred to our hospital with upper left abdominal pain and marked hypertriglyceridemia (triglycerides [TGs], 5,960 mg/dl). He was also on a low-carbohydrate diet that promoted ketosis under sodium glucose cotransporter 2 (SGLT2) inhibitor administration. Polyacrylamide gel electrophoresis revealed a remarkable increase in very-low-den-sity lipoprotein, a TG-rich lipoprotein particle synthesized in the liver using free fatty acids derived from adi-pose tissue. Although SGLT2 inhibitors generally improve the lipid profile, under certain conditions such as a low-carbohydrate diet, they may adversely exacerbate the lipid profile via ketosis., Competing Interests: No potential conflict of interest relevant to this article was reported.

Objective We compared the pain accompanying the injection of high-concentration (300 units/mL) insulin glargine (U300G) with that accompanying the injection of conventional (100 units/mL) insulin glargine (U100G). Methods U100G was switched to U300G at basically the same dosage. Visual analog scales were used to assess the quality of life (QOL). The primary outcome was the change in the pain accompanying injections in those using ≥30 units of U100G compared with those using <30 units at baseline. Standardized mean differences (Cohen's d) were used to measure the effect size. Patients Adult patients with type 2 diabetes mellitus using U100G. Results One hundred and eight patients were recruited. The numbers of patients who used U100G at ≥30 units, 20 to <30 units, 10 to <20 units, and <10 units were 13, 14, 34, and 47, respectively. The improvement in the pain score was not significant for ≥30 units compared with <30 units (-50.3±24.0 vs. -40.4±28.5, p=0.25, d=0.38), but a significant difference was observed for ≥20 units compared with <20 units (-50.8±22.7 vs. -38.4±29.1, p=0.03, d=0.48), as well as for ≥10 units compared with <10 units (-48.1±25.0 vs. -33.0±29.7, p<0.01, d=0.56). When all patients were analyzed together, significant improvements in the pain score (-41.5±28.0, p<0.01), ease of use score (-37.5±32.2, p<0.01), force needed to inject score (-46.5±28.6, p<0.01), and preference for U300G compared with U100G score (-45.8±33.1, p<0.01) were observed. Conclusion There is possibility that switching from U100G to U300G might be associated with better QOL for patients who require insulin glargine injections. To prove this hypothesis, a randomized controlled trial (preferably double-blinded) will be required in the future.