Introduction and Objective: In presymptomatic type 1 diabetes (T1D) the initial islet autoantibody (IAb) has been characterized as GADA-first with DR3 or IAA-first with DR4 in Caucasian population. Recently the PREP-T1D study, screening first-degree relatives in Japan for presymptomatic T1D, found ZnT8A-positivity was the most prevalent among IAb-positive cases. We aim to characterize the initial IAb patterns and their association with HLA haplotypes in the Japanese population. Methods: A cross-sectional analysis was conducted on 96 IAb-positive cases from PREP-T1D. Participants with single IAb positivity (SP) were extracted and HLA DRB1-DQB1 haplotypes were classified as disease-susceptible (*0405-*0401, *0802-*0302 and *0901- *0303) or protective (*1501-*0602, *1502-*0601 and *08:03-*06:01). Associations between IAb type and HLA haplotypes were analyzed. Results: The cohort comprised 26 GADA-only, 18 IA-2A-only, and 35 ZnT8A-only positive cases, with no significant age (P=0.893) or sex (P=0.631) differences. GADA-only group was strongly associated with the presence of two susceptible HLA haplotypes (13/20, P<0.01 vs. other SPs), while few cases carried protective HLA haplotypes (2/16, P=0.05 vs. other SPs). In contrast, the IA-2A-only and ZnT8A-only groups included a substantial proportion of protective HLA haplotypes (27.8% and 27.3%, respectively). ZnT8A-only group was significantly enriched in DRB1*08:03-DQB1*06:01 (7/8, P=0.01 vs other SPs), while IA-2A-only group was in DRB1*15:01-DQB1*06:02 (4/7, P=0.03 vs other SPs). Conclusion: GADA-only positivity with strong association of susceptible HLA may reflect the typical GADA-first progression of T1D pathogenesis. In contrast, ZnT8A/IA-2A-only positivity exhibits a “dual-layer structure” based on HLA background, where those with protective HLA may represent a “non-progressor” population. This unique immunogenetic architecture may partly explain the distinct Japanese T1D disease structure and its lower prevalence versus Caucasians. Disclosure Y. Oikawa: Other - Honoraria; Ended; Novo Nordisk, Eli Lilly and Company, Sanofi, Daiichi Sankyo, Kowa Company, Ltd., Astellas Pharma Inc., Medtronic, Bayer AG, AstraZeneca, Taiho Pharmaceutical Co. Ltd., Sumitomo Dainippon Pharma Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Dexcom, Inc., Abbott Japan Co., Ltd., Boehringer Ingelheim International GmbH, Sanwa Kagaku Kenkyusho. D. Chujo: Speaker's Bureau; Current; Sanofi K.K. A. Imagawa: Consultant; Current; Sanofi. T. Kawamura: Speaker's Bureau; Ended; Abbott Japan Co., Ltd., Sanofi, Novo Nordisk, Eli Lilly and Company, Medtronic, Terumo Corporation. T. Kikuchi: Advisory Panel; Current; Sanofi K.K. Other - Lecture fee; Current; Novo Nordisk A/S. Y. Shiraki: Employee; Current; Sanofi K.K. R. Koshiba: Employee; Current; Sanofi K.K. A. Shimada: Speaker's Bureau; Current; Sanofi. Funding Sanofi

AIMS:To identify individuals with a disease process comparable to presymptomatic stages of type 1 diabetes (T1D) and to evaluate their prevalence among first-degree relatives in Japan. METHODS:In this nationwide multicenter observational study conducted at 71 sites, 2,614 first-degree relatives of individuals with T1D underwent islet autoantibody (IAb) screening. Participants positive for ≥1 IAb received metabolic evaluation, including oral glucose tolerance testing, to classify presymptomatic stage. RESULTS:IAb positivity was identified in 95 participants (3.6%), including 16 (0.6%) with multiple-IAb positivity, with ZnT8A (49.5%, 47 of 95) and GADA (42.1%, 40) being the most frequent. 5 participants met stage 1 criteria, 9 were classified as stage 2, and 2 as stage 3. The most common HLA-A allele was A*24:02 (36.8%), with the predominant DRB1-DQB1 haplotypes being *09:01-*03:03 (24.2%) and *04:05-*04:01 (23.6%). CONCLUSIONS:From this first study describing the epidemiological characteristics of presymptomatic T1D in Japan and Asia, it was shown that the prevalence of IAbs in Japan was comparable to that in other countries, underscoring the importance of screening and monitoring for presymptomatic T1D in Japan as well. Further studies involving longitudinal observation of IAb-positive individuals are crucial for establishing an effective screening and monitoring system.

INTRODUCTION:Despite advances in insulin therapy, acute diabetic complications continue to pose a significant and potentially life-threatening risk in type 1 diabetes. Since there have been no nationwide studies regarding acute diabetic complications in individuals with type 1 diabetes in Japan, we investigated the incidence of those complications and examined the association between the incidence and clinical factors in the patients. MATERIALS AND METHODS:Registry-based cross-sectional analyses were conducted using data from patients with type 1 diabetes from 125 medical institutions across Japan. RESULTS:A total of 4,405 cases were registered in the database, of which 2,679 cases with confirmed diagnosis of type 1 diabetes subtypes were included in the analyses. Following insulin therapy, 18.8 and 7.8% of the patients experienced diabetic ketosis and diabetic ketoacidosis, respectively. Furthermore, 12.7 and 28.9% of the participants experienced severe hypoglycemia and hypoglycemic unawareness, respectively. C-peptide levels were significantly lower in patients with these complications than in those without the complications. Notably, the incidence of these complications in patients with slowly progressive type 1 diabetes "definite" was comparable with those in patients with acute-onset or fulminant type 1 diabetes. CONCLUSIONS:A substantial proportion of patients with type 1 diabetes in Japan experience potentially life-threatening acute diabetic complications despite receiving insulin replacement therapy. Advanced medical care for type 1 diabetes should be further developed in this country.

OBJECTIVE:This study aimed to investigate the progression of β-cell dysfunction and its predictors in Japanese patients with type 1 diabetes, using data from the nationwide, multicenter, prospective longitudinal Japanese Type 1 Diabetes Database Study (TIDE-J). RESEARCH DESIGN AND METHODS:TIDE-J enrolled 314 Japanese individuals with type 1 diabetes, including 165 with acute-onset, 105 with slowly progressive, and 44 with fulminant type 1 diabetes. Clinical data, including C-peptide levels, glycemic control, and autoantibody status, were collected annually for up to 14 years. HLA genotypes were analyzed at study entry. The time to insulin depletion was analyzed using survival curves and Cox proportional hazards models to determine predictive factors. RESULTS:The rate of undetectable C-peptide varied significantly among subtypes. At 5 years after onset, 43.1% (n = 55) of patients with acute-onset, 9.1% (n = 7) with slowly progressive, and 93.2% (n = 38) with fulminant type 1 diabetes reached undetectable C-peptide. Even within acute-onset type 1 diabetes, a marked interindividual variation was observed in the progression toward β-cell depletion. HLA genotypes influenced progression rates as follows: DRB1*04:05-DQB1*04:01/DRB1*04:05-DQB1*04:01 (DR4/DR4) carriers exhibited slower β-cell depletion, whereas DR4/DRB1*08:02-DQB1*03:02 (i.e., DR4/DR8) and DR4/DRB1*09:01-DQB1*03:03 (i.e., DR4/DR9) were associated with a rapid progression. For slowly progressive type 1 diabetes, low BMI, GAD antibody positivity, and absence of the DRB1*15:01-DQB1*06:02 or DRB1*15:02-DQB1*06:01 (i.e., DR2) haplotype were predictive of progression to insulin dependence. CONCLUSIONS:This study elucidates the heterogeneity in β-cell dysfunction among Japanese individuals with type 1 diabetes and identifies genetic and clinical predictors of disease progression. These findings provide insights for individualized management strategies and future therapeutic interventions.

BACKGROUND:Early diagnosis of left ventricular diastolic dysfunction (LVDD) is essential for preventing heart failure. B-type natriuretic peptide (BNP) is a viable marker for predicting LVDD, as elevated BNP levels have been associated with worsening LVDD in patients with diabetes over time. However, the utility of BNP as a diagnostic marker in diabetes is controversial, as BNP levels are often low in overweight individuals. AIM:To examine the effectiveness of BNP levels and fragmented QRS (fQRS) on electrocardiography for diagnosing LVDD in patients with type 2 diabetes. METHODS:This retrospective cohort study included 303 patients with type 2 diabetes (67.4 ± 12.3 years old) with preserved ejection fraction (EF) ≥ 50% admitted to Toyama University Hospital for glycemic management and comorbidity evaluation between November 2017 and April 2021. All participants underwent plasma BNP measurement, electrocardiography, and echocardiography. Cardiologists who were blinded to the BNP results assessed the electrocardiograms and echocardiograms. Subgroup analyses were conducted for overweight individuals. RESULTS:Receiver operating characteristic (ROC) curve analysis determined optimal BNP cut-off values of 34.8 pg/mL and 7.2 pg/mL for diagnosing LVDD in non-overweight [area under the ROC curve (AUC): 0.70] and overweight (AUC: 0.55) groups, respectively (P = 0.040). In the overweight subgroup, fQRS showed greater diagnostic accuracy for LVDD (AUC: 0.67), indicating moderate diagnostic utility compared with the low performance of the BNP cutoff of 35 pg/mL (AUC: 0.52) (P = 0.010). Multivariate analyses confirmed that fQRS was superior to BNP for LVDD diagnosis regardless of the patient's weight. CONCLUSION:A BNP level ≥ 35 pg/mL in non-overweight individuals may be a reliable LVDD marker. Additionally, fQRS was more effective than BNP in diagnosing LVDD irrespective of the patient's weight. fQRS can complement BNP in the early detection of LVDD, especially in overweight patients, potentially improving early detection and mitigating progression to heart failure with preserved EF in patients with type 2 diabetes.

AIMS/INTRODUCTION:Little is known about the effect of diabetologists on perioperative complication risk. Given that colorectal cancer surgery is known to carry a high complication risk among patients with diabetes, this study aimed to examine the association between the presence of diabetologists at the facility level and the risk of perioperative complications during colorectal cancer surgery. MATERIALS AND METHODS:In this retrospective cohort study, we sourced the number of board-certified diabetologists from the Japan Diabetes Society and combined it with Diagnosis Procedure Combination (DPC) data, encompassing receipt data from acute care facilities across Japan. We used a modified Poisson model to estimate the risk of perioperative complications associated with the presence of diabetologists by adjusting for potential confounding patient and facility factors. RESULTS:Analysis included 887 facilities, of which 299 (34%) had no diabetologists. A total of 24,714 patients with diabetes underwent colorectal cancer surgery between April 2018 and March 2019, with a median age of 73 years (interquartile range: 67-79 years) and 16,274 (66%) men. There were 3,165 (13%) perioperative complications. After adjustment, the risk of perioperative complications was 0.86 times (95% confidence interval: 0.77-0.96) lower in centers with at least one diabetologist than in those without a diabetologist. CONCLUSIONS:Our study suggests that the presence of a diabetologist may be important in reducing the risk of perioperative complications during colorectal cancer surgery in patients with diabetes. Future studies factoring in other facility factors and surgical types may be required to further validate our findings.

East Asians are known to develop diabetes mellitus at a lower body weight than Caucasians, potentially because of the different mechanisms underlying disease development. This study aimed to evaluate the variation in weight transition leading to diabetes onset in two subtypes of individuals (obese and non-obese) in a Japanese population. We conducted a retrospective, observational, longitudinal cohort study using health checkup data from 9, 260 participants in Japan. Individuals who developed diabetes within three years of the start of the observation period were excluded. Among the participants, 61.4% were men, and 259 developed diabetes. In the obesity group (body mass index [BMI] ≥25 kg/m2), the average BMI increased prior to the diabetes onset and subsequently decreased. Conversely, in the non-obesity group (BMI <25 kg/m2), the average BMI decreased and then stabilized before the onset of diabetes. Notably, a greater number of participants in the non-obesity group exhibited a BMI change of ≤-0.15 kg/m2 per year compared with those with a BMI change of ≥0.15 kg/m2 per year before diabetes onset (p = 0.003). Our findings indicate that body weight loss precedes the onset of diabetes in the non-obesity group. We recommend that non-obese individuals with elevated blood glucose levels who do not meet the criteria for diabetes should be considered a high-risk group for diabetes development. Therefore, it is imperative to identify these individuals and provide lifestyle guidance that does not focus on weight loss to prevent the onset of diabetes.

Aims:To clarify the pathways from a healthy state to the diabetes onset via pre-disease states, we applied energy landscape analysis (ELA) to Specific Health Checkup data in Japan. Methods:This retrospective and observational cohort study analyzed data from 4,928 males aged 56.0 ± 3.2 years, including 242 individuals with diabetes, over a period of 5.26 ± 3.21 years. A total of 22,326 records were examined using six features: hemoglobin A1c, plasma glucose, high-density lipoprotein-cholesterol, body mass index (BMI), uric acid, and alanine aminotransferase. ELA was also applied to subdata from the 242 individuals with diabetes. Results:ELA revealed three stable states: healthy, intermediate, and unhealthy (pre-diabetes) states. The intermediate state was characterized by obesity. Obese individuals with BMI ≥ 25 kg/m2 (n = 1,460) preferred a pathway via the intermediate state, whereas non-obese individuals with BMI < 25 kg/m2 (n = 3,468) preferred to transit directly to the unhealthy state. There was a significant difference between the preferences of the two groups (p = 0.0085, chi-squared test). Two distinct pathways were also observed for obese and non-obese individuals with diabetes. Conclusions:We demonstrated that ELA could indicate different pathways of diabetes development in obese and non-obese individuals in a data-driven manner. These insights could inform more targeted diabetes prevention measures, such as reducing visceral fat in obese individuals and protecting beta-cells in non-obese individuals.

The fourth heart sound (S4) is an auscultatory marker of left ventricular diastolic dysfunction (LVDD). Additionally, S4 correlates with atrial function, which is typically impaired in patients with Type 2 diabetes (T2D) but can improve with sodium-glucose co-transporter-2 inhibitor (SGLT2i) therapy. This case report highlights the dynamic changes in S4 associated with modification of SGLT2i therapy. An 83-year-old male with T2D and LVDD, confirmed via echocardiography, was treated with SGLT2i therapy for 4 years for glycemic control. The therapy was discontinued in December 2023 because of increased nocturnal urination. Two months after discontinuation, the patient developed pronounced S4, accompanied by mild chest discomfort and worsening of evening leg edema. Resumption of SGLT2i therapy led to a marked reduction in S4 along with a remarkable improvement in chest discomfort and edema within 1 month. These findings were confirmed by visual phonocardiography. This case underscores the potential utility of dynamic S4 changes as a noninvasive indicator of SGLT2i therapy adjustment. These findings highlight the novel clinical application of S4 monitoring in mitigating heart failure progression in patients with T2D.

Introduction This study aimed to identify factors associated with pancreatic abnormal findings on imaging (PAI) suggesting precancerous potential between slowly progressive type 1 diabetes and acute-onset type 1 diabetes.Research design and Methods The study was designed to identify factors associated with PAI using data from a nationwide cohort, the Japanese Type 1 Diabetes Database. Clinical factors, including sex, age, type of diabetes onset, diabetes duration, body mass index, and human leucocyte antigen genotypes associated with type 1 diabetes, were evaluated.Results Among 279 patients with type 1 diabetes, 95 patients who had not undergone imaging evaluations, two patients with pancreatic lipomatosis, and 15 patients with missing data were excluded. Finally, a total of 167 patients with type 1 diabetes were analyzed. Among 13 patients who were identified as PAI positive, female sex (92.3% vs 53.2%, p=0.007), slowly progressive type 1 diabetes (69.2% vs 36.4%, p=0.034), and older age were more common compared with PAI-negative cases. The multivariable logistic regression analysis revealed that female sex (OR 13.87; 95% CI 1.6 to 120.1; p=0.017), slowly progressive type 1 diabetes (OR 5.70; 95% CI 1.46 to 22.19; p=0.012), and age (OR 1.05; 95% CI 1.002 to 1.103; p=0.043) were independently associated with PAI positivity.Conclusions The findings indicate that slowly progressive type 1 diabetes and female sex are closely associated with PAI, along with age. These results suggest the need for increased clinical vigilance for pancreatic pathology in patients with slowly progressive type 1 diabetes.

Type 1 diabetes is often accompanied by autoimmune thyroid disease. We aimed to investigate the clinical characteristics of Japanese patients with acute-onset type 1 diabetes and thyroid autoantibodies, focusing on decreased endogenous insulin secretion. We examined 80 patients with acute-onset type 1 diabetes, classifying them into two groups with and without thyroid autoantibodies and compared the clinical characteristics of the two groups. A fasting serum C-peptide immunoreactivity (CPR) of less than 0.1 ng/mL was defined as insulin depletion. In patients with thyroid autoantibodies, the median fasting serum CPR levels at the fourth year after the onset of type 1 diabetes were significantly lower than in those without thyroid autoantibodies (p = 0.02). The cumulative incidence of insulin depletion at 5 years of duration after diagnosis of type 1 diabetes was significantly higher in thyroid autoantibody-positive group than in thyroid autoantibody-negative group (p = 0.01). In the Cox proportional models adjusted for selected baseline factors (age, sex, and BMI), the presence of thyroid autoantibodies did not increase the risk of insulin depletion within 5 years after the onset. However, in bivariate Cox proportional hazards models that investigated the association between thyroid autoantibodies and each baseline factor, the presence of thyroid autoantibodies significantly increased the risk of insulin depletion. Our study showed that Japanese patients with acute-onset type 1 diabetes and positive for thyroid autoantibodies had a higher risk of insulin deficiency within 5 years after the onset than those without thyroid autoantibodies.

Insulin treatment should be introduced in patients with slowly progressive type 1 diabetes (SPIDDM; definite), according to the revised diagnostic criteria of SPIDDM (2023). In contrast, SPIDDM (probable) patients are in a non-insulin-dependent state; therefore, a more flexible treatment can be considered, although sulfonylurea agents should be avoided. Insulin treatment has been shown to maintain endogenous insulin secretion capacity in SPIDDM (probable); however, this does not mean that all SPIDDM (probable) patients should use insulin from the early phase. Dipeptidyl peptidase-4 inhibitors and biguanides might be the treatment of choice for SPIDDM (probable), but no evidence exists for other hypoglycemic agents. In any case, careful monitoring of the endogenous insulin secretion capacity should be carried out, and if a decrease in insulin secretion capacity is suspected, a change in treatment should be considered to prevent progression to an insulin-dependent state.

Introduction & Objective: Autoreactive T cell responses in type 1 diabetes (T1D) may vary depending on race. In Japan, T1D is classified into three subtypes based on disease progression: acute onset (AT1D), slowly progressive (SP1D), and fulminant (FT1D). The aim of this study was to compare the features of islet antigen-specific CD4+ T cell (Th) responses among these subtypes and determine the Th epitope in Japanese AT1D patients. Methods: Blood mononuclear cells from 20 AT1D, 17 SP1D, and 18 FT1D patients, and 17 nondiabetics (NDs) were stimulated with GAD65, preproinsulin (PPI), IGRP, and ZnT8 peptide clusters (4-6 peptides/cluster) in the presence of IL-2. Subsequently, intracytoplasmic cytokine staining (ICS) was performed to analyze cytokine expression on specific T cells (cluster analysis). After identifying the feature of Th cell responses in each T1D subtype, another stimulation and ICS were performed using single peptides to identify Th cell epitopes (epitope analysis). Results: In the cluster analysis, the frequencies of GAD65- and PPI-specific Th1 cells were significantly higher in AT1D patients (P = 0.007 and P = 0.004, respectively) than in NDs, whereas GAD65- and IGRP-specific Th2 cells were more prevalent in SP1D patients (P = 0.010 and P = 0.030, respectively) than in NDs. Notably, FT1D patients displayed significantly less Tr1 cells specific for all four antigens. Epitope analysis, focusing on GAD65- and PPI-specific Th1 responses in AT1D patients, revealed that 3, 16, 3, and 3 out of 20 patients displayed positive Th1 responses (stimulation index > 3.0) under GAD65115-127, GAD65247-266, PPIC19-A3, and PPIC22-A5 stimulation, respectively. In addition, the frequencies of GAD65247-266-specific Th1 cells were significantly higher than those specific for other epitopes (P < 0.001). Conclusion: The phenotypes of islet antigen-specific Th cells were distinct among the three T1D subtypes. Furthermore, GAD65247-266 was identified as a major Th1 epitope in Japanese AT1D patients. Disclosure D. Chujo: Research Support; Kyowa Kirin Co., Ltd. K. Ajima: None. M. Matsushita: None. C. Tsutsumi: None. F. Haseda: None. A. Imagawa: None. T. Hanafusa: None. H. Kajio: None. M. Shimoda: None. K. Tobe: None. Funding Japan Society for the Promotion of Science (21K08525)

The diagnostic criteria for slowly progressive type 1 diabetes (slowly progressive insulin-dependent diabetes mellitus; SPIDDM) have been revised by the Committee on Type 1 Diabetes of the Japan Diabetes Society. All of the following three criteria must be met for “a definitive diagnosis of SPIDDM”: (1) presence of anti-islet autoantibodies at some point in time during the disease course; (2) absence of ketosis or ketoacidosis at the diagnosis of diabetes with no requirement of insulin treatment to correct hyperglycemia immediately after diagnosis in principle; and (3) gradual decrease of insulin secretion over time, with insulin treatment required at more than 3 months after diagnosis, and presence of severe endogenous insulin deficiency (fasting serum C-peptide immunoreactivity < 0.6 ng/mL) at the last observed point in time. When a patient fulfills the only (1) and (2), but not (3), he/she is diagnosed with “SPIDDM (probable)” because the diabetes is non-insulin-dependent state.

AbstractAims/IntroductionThis study aimed to identify risk factors that contribute to the progression of slowly‐progressive type 1 diabetes by evaluating the positive predictive value (PPV) of factors associated with the progression to an insulin‐dependent state.Materials and MethodsWe selected 60 slowly‐progressive type 1 diabetes patients who tested positive for glutamic acid decarboxylase autoantibodies (GADA) at diagnosis from the Japanese Type 1 Diabetes Database Study. GADA levels in these patients were concurrently measured using both radioimmunoassay (RIA) and enzyme‐linked immunosorbent assay (ELISA) techniques.ResultsCompared with the non‐progressor group (fasting C‐peptide [F‐CPR] levels maintained ≥0.6 ng/mL), the progressor group showed a younger age at diagnosis, lower body mass index (BMI), lower F‐CPR levels and a higher prevalence of insulinoma‐associated antigen‐2 autoantibodies (IA‐2A). The PPV of RIA‐GADA increased from 56.3 to 70.0% in the high titer group (≥10 U/mL), and further increased to 76.9, 84.2, 81.0 and 75.0% when combined with specific thresholds for age at diagnosis <47 years, BMI <22.6 kg/m2, F‐CPR <1.41 ng/mL and IA‐2A positivity, respectively. In contrast, the PPV of ELISA‐GADA (71.8%) remained the same at 73.1% in the high titer group (≥180 U/mL), but increased to 81.8, 82.4 and 79.0% when evaluated in conjunction with age at diagnosis, BMI and F‐CPR level, respectively.ConclusionsOur findings show that, unlike RIA‐GADA, ELISA‐GADA shows no association between GADA titers and the risk of progression to an insulin‐dependent state. The PPV improves when age at diagnosis, BMI and F‐CPR levels are considered in combination.

Introduction & Objective: Paradoxical increase of postprandial glucagon is considered to be a factor inducing hyperglycemia in type 2 diabetes (T2D). Although continuous glucose monitoring (CGM) is often used to evaluate glycemic control in T2D patients, no studies on the association between glycemic stability and functional balance of pancreatic alpha to beta cells have been reported. We aimed to investigate the association between CGM data and the ratio of glucagon to insulin secretion. Methods: We recruited 62 T2D patients who were admitted to our hospital, and patients with <45 ml/min/1.73 m2 of eGFR were excluded. We analyzed the data obtained from CGM, including time in range (TIR), time below range (TBR), time above range (TAR), average glucose (AVG), and standard deviation of glucose (SD), and the ratio of plasma glucagon level to C-peptide index (G-CPIR) before and after meal tolerance test or other metabolic factors. Results: Postprandial G-CPIR was inversely correlated with TIR (r = -0.230, P = 0.009), correlated with TAR (r = 0.234, P = 0.014), and AVG (r = 0.251, P = 0.006). Upon comparing the CGM data between the group with high postprandial G-CPIR (HG group) and low G-CPIR (LG group), divided using the median values, TIR was significantly lower (62.4±21.5 vs. 78.5±18.8, P = 0.0053), AVG (166.7±33.5 vs. 145.5±27.9, P = 0.0153) and SD (46.2±14.3 vs. 38.2±11.8, P = 0.0310) were higher than those in LG group. Body fat mass was inversely correlated with SD (r = -0.448, P = 0.014), and subcutaneous fat area (SFA) and visceral fat area (VFA) were correlated with TIR (SFA: r = 0.339, P = 0.006, VFA: r = 0.310, P = 0.032), inversely correlated with TAR (SFA: r = -0.326, P = 0.010, VFA: r = -0.298, P = 0.040) and SD (SFA: r = -0.411, P = 0.001, VFA: r = -0.454, P = 0.001). Conclusion: Our study suggests that CGM indicators, including TIR, are associated with the functional balance of pancreatic alpha to beta cells and body fat mass. Disclosure M. Kamigishi: None. D. Chujo: Research Support; Kyowa Kirin Co., Ltd. A. Takikawa: None. S. Inagawa: None. A. Enkaku: None. S. Ohgaku: None. A. Sato: None. S. Matsukoshi: None. H. Honoki: None. S. Fujisaka: None. K. Tobe: None.

Gut microbiota is an important driver of metabolic status. Recent studies have demonstrated that dysbiosis precedes the development of metabolic disorders. However, the bacterial species associated with metabolic syndrome and their physiological role in obesity and glucose metabolism have not been fully elucidated. In this study, we performed 16S rRNA sequencing analysis on fecal samples from 49 metabolically healthy volunteers, a detailed lifestyle questionnaire survey including diet, and an analysis on metabolic parameters. We also examined the metabolic effects of some microbes by transplantation into HFD-fed mice. The average age, BMI and HbA1c were 43.5±9.0, 23.9±3.9 and 5.5±0.3, respectively. A clear correlation was observed between lifestyle and metabolic parameters. Analysis of fecal microbial structure divided the participants into three enterotypes according to their predominant phylogenic pattern; 1) Prevotella copri group, 2) Bacteroides group, and 3) others. Enterotype 1 had higher random blood glucose (BG), and lower HDL-C, while enterotype 2 had lower random BG, BMI, and waist circumference. Eleven bacterial species were identified as being positively or negatively correlated with metabolic parameters. Relative abundances of the Family Fusobacteriaceae and Prevotella stercorea were positively correlated with BMI, fasting BG, and visceral fat mass. In contrast, the Family Rikenellaceae and Bacteroides uniformis (Bu) negatively correlated with metabolic parameters. Transplantation of Alistipes indistinctus (Ali), a major bacterium of the Family Rikenellaceae, or Bu into HFD-fed C57BL/6J mice suppressed body weight gain, improved glucose tolerance and histological findings without altering food intake. In summary, our results suggest that microbial community structure can be altered by lifestyle even in good health. Moreover, maintaining microbial species such as Ali and Bu may contribute to the prevention of metabolic disorders in Japanese adults. Disclosure H. Honoki: None. S. Fujisaka: None. Y. Watanabe: None. M. Oku: None. Y. Kondo: None. A. Nishimura: None. T. Kado: None. M. Bilal: None. A. Enkaku: None. A. Takikawa: None. D. Chujo: None. Y. Morinaga: None. K. Tobe: Other Relationship; MSD K.K., Novo Nordisk Pharma Ltd., Takeda Pharmaceutical Company Limited, Daiichi Sankyo, Mitsubishi Tanabe Pharma Corporation, Suntory Global Corporation, Ltd.,, Taiho Pharmaceutical Co. Ltd., Japan Diabetes Foundation, Japan Association for Diabetes Education and Care. Funding Japan Society for the Promotion of Science (20K10318); Japan Association for Diabetes Education and Care