Rimei Nishimura

Diabetes is a growing public health burden across the Asia-Pacific (APAC) region. The increasing use of continuous glucose monitoring (CGM) holds significant potential to improve glycemic control and safety outcomes in individuals with diabetes. However, CGM devices in APAC vary widely in technical performance, clinical validation, and regulatory oversight, posing risks of inaccurate readings and treatment errors, especially for nonadjunctive integrated CGM (iCGM) systems. This review synthesizes the literature and regional insights on CGM regulatory frameworks, accuracy standards, and unmet needs. The authors highlight the U.S. Food and Drug Administration (FDA) iCGM standards as the most stringent global standards. Adopting FDA iCGM criteria alongside the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) reporting recommendations, with contextual modifications for diverse epidemiological, infrastructural, and socioeconomic settings in APAC, is explored. A phased, regionally coordinated approach is proposed, incorporating voluntary benchmarks, capacity-building for lower-resourced regulators, regulatory reliance mechanisms, and shared postmarketing surveillance platforms. Emphasis is placed on multistakeholder collaboration and region-specific validation studies. Harmonizing iCGM regulatory standards in APAC is anticipated to enhance device accuracy, safety, and interoperability, improve diabetes care, and streamline regulatory processes, serving as a model for regulatory excellence for other emerging medical technologies.

Background: This post hoc analysis assessed continuous glucose monitoring (CGM)-based metrics with basal insulin icodec (icodec) versus once-daily (OD) comparators in insulin-naive and insulin-experienced Japanese individuals from the global, phase 3a ONWARDS 1, 2, and 4 trials. Methods: Double-blinded CGM data were collected from Japanese adults (aged ≥20 years) with type 2 diabetes (T2D) during prespecified assessment periods (weeks 0–4 [ONWARDS 1, 2, and 4], weeks 22–26 [ONWARDS 1, 2, and 4], weeks 48–52 [ONWARDS 1], and weeks 74–78 [ONWARDS 1]). For all assessment periods, percentages of time in range (TIR; sensor glucose [SG] 70–180 mg/dL), time above range (TAR; SG >180 mg/dL and >250 mg/dL), and time below range (TBR; SG <70 mg/dL and <54 mg/dL) were analyzed. Proportions of participants achieving internationally recommended CGM targets were calculated for all assessment periods except weeks 0–4. Duration of overall hypoglycemic episodes (SG 70% TIR was numerically higher with icodec versus OD comparator during all assessment periods; the opposite was observed in ONWARDS 2 and 4. TBR (SG <70 mg/dL and <54 mg/dL) remained below the recommended targets (<4% and <1%). Across trials, in both arms, the median duration of overall hypoglycemic episodes was ≤45 min; most hypoglycemic episodes included no level 2 hypoglycemic periods (SG <54 mg/dL for ≥15 min). Conclusions: In Japanese individuals with T2D, CGM-based metrics were similar for icodec and OD comparators. Overall duration of hypoglycemic episodes was ≤45 min for icodec and OD comparators and most hypoglycemic episodes included no or <15 min with SG <54 mg/dL. These data support icodec use across the spectrum of T2D in Japan.

Aims: Many guidelines recommend increases in potassium intake. However, the relationship of dietary potassium intake with incident cardiovascular disease (CVD) has not been examined in those with type 2 diabetes (T2DM), including sodium acting antagonistically with potassium. We investigated these relationships in Japanese patients with T2DM. Materials and Methods: The investigation was part of the JDCP study, a nationwide prospective study begun in 2007. Analysed were 1477 persons with T2DM, 40–75 years of age, who completed a brief‐type, self‐administered Diet History Questionnaire at baseline. Primary outcome was a CVD event during the follow‐up median 7 years (3.9–8.1 years). Hazard ratios (HRs) for CVD were estimated by Cox regression adjusted for confounders of daily potassium intake categorized by tertiles. Tertiles of sodium intake were also analysed. Results: Mean daily potassium intake in tertiles was 1877, 2627 and 3532 mg, respectively, and significant associations were not shown between potassium intake and incidence of CVD. When HRs for CVD were stratified for potassium intake in tertiles (reference group, bottom tertile) and sodium intake (reference group, bottom tertile), potassium intake in the bottom tertile and sodium intake in the second and top tertiles were associated with significantly elevated HR for CVD (2.79 [1.02–7.63] and 3.92 [1.30–11.79], respectively). Conclusions: Low potassium intake in conjunction with high sodium intake was significantly associated with increased incident CVD in persons with T2DM. However, CVD incidence was not related to high potassium intake, regardless of sodium intake.

The pathophysiology of type 2 diabetes involves insulin and glucagon. Protein kinase C (Pkc)-δ, a serine–threonine kinase, is ubiquitously expressed and involved in regulating cell death and proliferation. However, the role of Pkcδ in regulating glucagon secretion in pancreatic α-cells remains unclear. Therefore, this study aimed to elucidate the physiological role of Pkcδ in glucagon secretion from pancreatic α-cells. Glucagon secretions were investigated in Pkcδ-knockdown InR1G9 cells and pancreatic α-cell-specific Pkcδ-knockout (αPkcδKO) mice. Knockdown of Pkcδ in the glucagon-secreting cell line InR1G9 cells reduced glucagon secretion. The basic amino acid arginine enhances glucagon secretion via voltage-dependent calcium channels (VDCC). Furthermore, we showed that arginine increased Pkcδ phosphorylation at Thr⁵⁰⁵, which is critical for Pkcδ activation. Interestingly, the knockdown of Pkcδ in InR1G9 cells reduced arginine-induced glucagon secretion. Moreover, arginine-induced glucagon secretions were decreased in αPkcδKO mice and islets from αPkcδKO mice. Pkcδ is essential for arginine-induced glucagon secretion in pancreatic α-cells. Therefore, this study may contribute to the elucidation of the molecular mechanism of amino acid-induced glucagon secretion and the development of novel antidiabetic drugs targeting Pkcδ and glucagon.

Aims To investigate the changes in patient background and treatment lines between 2016–2019 and contributing factors when sodium-glucose co-transporter 2 inhibitors (SGLT2i) are newly prescribed for type 2 diabetes mellitus patients. Methods The subjects comprised patients who had attended outpatient clinics at the four Jikei University School of Medicine-affiliated hospitals. One-way analysis of variance was used to evaluate annual changes in patients’ characteristics. Logistic regression analysis was also used to explore factors contributing to the treatment lines. Results The age of the 1951 subjects [mean ± SD] was 59.1 ± 12.8 years; BMI 27.5 ± 4.9 kg/m²; HbA1c 8.15 ± 1.24%; eGFR 74.2 ± 25.3 ml/min/1.73m². SGLT2i was the 2.86th (± 1.22) new prescription among antidiabetic drugs, and at increasingly earlier treatment lines between 2016 and 2019 (3.28 ± 1.16 to 2.59 ± 1.19; P < 0.001). The age of initial SGLT2i prescription significantly increased over time (P < 0.001). In contrast, the patients’ BMI and eGFR values decreased over time. Again, the proportions of patients with chronic kidney disease (CKD) and cardiovascular disease-heart failure disease (CVD-HF) tended to increase over time. The patients for whom SGLT2i had been prescribed in the first line were more likely to have obesity and HF (1.64 [1.15–2.34] and 1.84 [1.12–3.02], respectively). Conclusions SGLT2i was more likely to be newly prescribed to patients with CVD-HF and CKD, older patients, and to be prescribed in earlier treatment lines in recent years. Obesity and HF were predictor of SGLT2i prescriptions in the first line.