Seigo Sugiyama

Background: Despite the widespread use of sodium-glucose cotransporter 2 inhibitors (SGLT2i), many patients with diabetic kidney disease continue to exhibit persistent proteinuria, highlighting an unmet clinical need for effective add-on therapies. Non-steroidal mineralocorticoid receptor antagonists (MRA) such as finerenone have recently shown benefits; however, the role of classical steroidal agents like spironolactone in this setting remains unclear.

Background: Patients with type 2 diabetes mellitus (T2DM) have a high-risk condition of developing cardiovascular disease, and therefore, therapeutic strategies should consider cardiovascular risk reduction. Previously, we demonstrated that circulating glucagon-like peptide-1 (GLP-1) levels are significantly lower in Japanese patients with coronary artery disease (CAD) compared with non-CAD subjects. Once-weekly semaglutide, a GLP-1 receptor agonist, has demonstrated clinical cardiometabolic benefits; however, its effect on vascular endothelial function in Japanese patients with T2DM remains unclear.

Purpose of Review Insulin resistance is a key component of the metabolic syndrome, type 2 diabetes mellitus (T2DM), and related cardiovascular complications. However, despite its clinical relevance, a simple and reliable surrogate marker of insulin resistance is lacking. The body muscle-to-fat ratio (BMFR) is a novel anthropometric index, and particularly in treatment-naïve patients with T2DM, BMFR correlates more closely with insulin sensitivity, assessed using the hyperinsulinemic–euglycemic clamp, than conventional indices, such as the Matsuda Index and the Quantitative Insulin Sensitivity Check Index. In this review, we critically evaluate the current evidence regarding the BMFR as an index of insulin resistance and metabolic disease risk, highlight its strengths and limitations versus conventional measures, and discuss future directions. Recent Findings Several recent studies have demonstrated the importance of body composition metrics for the evaluation of metabolic health, including those by Guan et al. (Adv Nutr), Oliver et al. (J Cachexia Sarcopenia Muscle), and Vieira et al. (Rev Endocr Metab Disord). The findings have resulted in a growing recognition of the need for reliable, accessible markers of muscle quality and metabolic risk. Summary BMFR offers advantages over the fat-to-muscle ratio and conventional anthropometric indices as an intuitive and clinically relevant marker of insulin resistance. It represents a promising method of screening for obesity-related complications, evaluating treatment responses, and guiding personalized care, including in patients with high-risk phenotypes, such as sarcopenic obesity. With further validation, BMFR could become a standard tool for the evaluation of metabolic health and risk in clinical practice.

BackgroundDecreased blood insulin concentrations resulting from reduced pancreatic β-cell insulin secretion and elevated insulin clearance (IC) could be involved in impaired glucose metabol... Elevated Insulin Clearance in Type 2 Diabetes MellitusT2DM in Western populations has been attributed to insulin resistance. Of 100 patients in a cohort from Japan with newly diagnosed T2DM, 44 had...

Background: Insulin resistance (IR) assessment is important in treating type 2 diabetes mellitus (T2DM). We thus compared body muscle-to-fat ratio (BMFR) and fat-to-muscle ratio (FMR) values against M/I values as clinical index of IR. Methods: Subject included 118 untreated T2DM patients. Hyperinsulinemic-euglycemic clamp examination was performed to calculate the M/I as index of IR. Body composition was measured by impedance analysis using InBody770. Results: Simple linear regression analyses confirmed correlations between M/I and BMFR (B: 0.756 (P < 0.01), coefficients of determination (R²): 0.572, mean absolute error (MAE): 3.19, and root mean squared error (RMSE): 4.14), and between M/I and FMR (B: -0.601 (P < 0.01), R²: 0.362, MAE: 3.97, and RMSE: 5.05). Against the M/I values, BMFR also showed better goodness-of-fit than did FMR. In comparing correlation coefficients, the BMFR absolute B value was significantly larger than that of FMR (P = 0.027). Conclusions: BMFR is more useful than FMR in quantifying IR in patients with T2DM because the correlation between BMFR and the insulin sensitivity index M/I is significantly greater than that between FMR and M/I. J Clin Med Res. 2021;13(7):387-391 doi: https://doi.org/10.14740/jocmr4401

Diabetes mellitus is a heterogeneous and complex metabolic disorder characterized by hyperglycemia secondary to either resistance to insulin actions on the liver and peripheral tissues, insufficient insulin secretion from pancreatic β-cells, or both. An integrated balance between blood insulin levels and whole-body insulin sensitivity could theoretically provide the clinical effectiveness of insulin action. Peripheral blood insulin concentrations might be determined by the capacity of endogenous pancreatic β-cell insulin secretion and the degree of the whole body insulin clearance. Here, we report a non-obese normoinsulinemic Japanese diabetic patient with elevated insulin clearance assessed by a hyperinsulinemic-euglycemic clamp examination and increased insulin secretion measured by daily urinary excretion of C-peptide immunoreactivity. We propose this unique pathogenic condition of diabetes with normoinsulinemia and elevated insulin clearance as “type 2 Japanese diabetes mellitus (T2JDM).”

The overall goal in the treatment of type 2 diabetes mellitus (T2DM) is remission. However, the effects of a sodium-glucose cotransporter 2 inhibitor (SGLT2i) on remission of T2DM are unknown. We herein report a case involving an overweight 43-year-old man who completely recovered from T2DM after SGLT2i therapy (dapagliflozin at 5 mg/day). In the pretreatment period, he had a body mass index (BMI) of 26.0 kg/m², hemoglobin A1c (HbA1c) concentration of 10.3%, advanced insulin resistance, pancreatic β-cell dysfunction, and fatty liver. Eighteen months after comprehensive therapy, including the administration of an SGLT2i and metformin, his BMI had decreased to 21.3 kg/m² and his glycemic control was almost normal (HbA1c of 5.3%) despite discontinuation of all hypoglycemic medications. This report is the first to propose the usefulness of the combination therapy of SGLT2i and metformin for achieving normal body weight and remission of newly diagnosed T2DM in a real-world clinical situation.

New/worsening cognitive and physical impairments following critical care pose significant problems. Multidisciplinary cardiac rehabilitation (CR) can improve physical function after cardiac intensive care (CIC). This observational study aimed to evaluate cognitive function in patients participating in multidisciplinary CR and to identify correlates of impaired cognitive function after CIC. We analyzed 111 consecutive patients admitted to our comprehensive care ward at least 7 days after CIC and assessed factors associated with cognitive function using the Functional Independence Measure (FIM). Patients were stratified into two groups based on the median FIM-Cognitive scores: impaired (n = 56) and preserved cognition (n = 55) groups. Multiple logistic regression analysis identified age [odds ratio (OR) 1.06; 95% confidence interval (CI) 1.00–1.13; p = 0.042], Mini-Nutrition Assessment-Short Form (MNA-SF; OR 0.73; 95% CI 0.56–0.95; p = 0.017), and FIM-Physical scores (OR: 0.94; 95% CI 0.90–0.99; p = 0.012) as significant and independent factors associated with impaired cognition. The median length of hospital stay was 28 (interquartile range: 18, 43) days. The FIM-Cognitive and FIM-Physical scores significantly increased from admission to discharge [32.0 (27.0, 35.0) vs. 34.0 (29.0, 35.0) points; p < 0.001; 67.0 (53.0, 75.0) vs. 85.0 (73.5, 89.0) points; p < 0.001, respectively]. On subgroup analysis within the impaired cognition group, increased FIM-Cognitive scores positively and significantly correlated with increased FIM-Physical scores (ρ = 0.450; p = 0.001). Multiple linear regression analysis identified atrial fibrillation (AF; β = − 0.29; p = 0.016), ln(glycated hemoglobin; HbA1c) (β = 0.29; p = 0.018), and ln(high-sensitivity C-reactive protein; hs-CRP) (β = − 0.26; p = 0.034) as significant and independent factors correlated with increased FIM-Cognitive scores. In conclusion, advanced age, low MNA-SF score, and FIM-Physical score were independent factors associated with impaired cognition in post-CIC patients. Multidisciplinary CR improved both physical and cognitive functions, and AF, HbA1c, and hs-CRP were independent factors correlated with increased FIM-Cognitive score.

Background: Renal function deterioration accompanied by an acute decrease in estimated glomerular filtration rate (eGFR) was observed early after starting sodium-glucose cotransporter-2 inhibitor (SGLT2i) therapy. It is unclear how much and how frequently the initial acute decline in eGFR (IAD-eGFR) would occur after SGLT2i administration, and the effects of IAD-eGFR on subsequent renal function are unknown in type 2 diabetes mellitus (T2DM) patients with chronic kidney disease (CKD). Methods: We retrospectively recruited T2DM patients with CKD (stage 3b; 30 ≤ eGFR < 45 mL/min/1.73 m²) and who were newly treated with add-on SGLT2i. We further investigated the effects of SGLT2i therapy on eGFR early after starting treatment (1 - 3 months) and after 6 months of treatment. We examined the factors associated with a large IAD-eGFR (≥ 10%) using logistic regression analyses. Results: Eighty-seven patients (male, 74.7%; mean age, 69.8 years; median hemoglobin A1c, 7.3%; mean eGFR, 37.8 mL/min/1.73 m²) were analyzed. The mean minimum eGFR early after SGLT2i administration was 34.9 mL/min/1.73 m², which was significantly lower than before treatment (mean, -7.7%). Seventy patients (80.5%) had IAD-eGFR, and 36 patients (41.4%) had a large IAD-eGFR (≥ 10%). Overall, the mean eGFR was 38.2 at 6 months after starting SGLT2i administration. In patients with a large IAD-eGFR (≥ 10%), the eGFR decreased by 72.2% at 6 months to 35.5 mL/min/1.73 m², showing a significant decline from the pretreatment value. In patients without a large IAD-eGFR, eGFR increased by 66.7% at 6 months to 40.0 mL/min/1.73 m². Multiple logistic regression analysis showed that patients with a large IAD-eGFR had a significant association with a high estimated daily salt intake. Conclusions: SGLT2i treatment frequently induced a significant decrease in eGFR early after starting therapy, but eGFR tended to recover after 6 months in T2DM patients with CKD stage 3b. A large IAD-eGFR (≥ 10%) caused by SGLT2i may lead to subsequent deterioration in renal function, and it was significantly associated with a higher estimated daily salt intake. These results suggest that a more effective renoprotective therapeutic strategy using SGLT2i may be implemented by avoiding the occurrence of a large IAD-eGFR. Further prospective studies are warranted. J Clin Med Res. 2020;12(11):724-733 doi: https://doi.org/10.14740/jocmr4351

Renoprotective Effects of Additional SGLT2 inhibitor Therapy in Patients With Type 2 Diabetes Mellitus and Chronic Kidney Disease Stages 3b-4: A Real World Report From A Japanese Specialized Diabetes Care Center