Background: Impaired endogenous insulin secretion was related to instability of glucose variability (GV) in patients with type 2 diabetes (T2DM) in our previous studies. However, some patients, including those with fasting serum C-peptide (CPR) ≤2 ng/mL, did not show this relationship. Given these findings, the present study aimed to identify other factors that affect GV in T2DM patients with impaired endogenous insulin secretion. Methods: Data were obtained from our prospective observational study, comprising 2Japanese outpatients with T2DM who underwent continuous glucose monitoring (CGM) , fasting blood sample collection, and a computed tomography scan of their abdominal visceral and subcutaneous fat. Fasting CPR was used as a marker of endogenous insulin secretion and the coefficient of variation (CV) for the CGM data was used as a measure of GV. Background characteristics related to unstable GV were identified by multivariate logistic regression analysis after we extracted the data for patients with T2DM and CPR ≤2 ng/mL. All tests were two-sided. P<0.was considered to indicate statistical significance. Results: In the total cohort, mean age was 67.0 (IQR 58.0, 74.8) years, mean HbA1c 7.1% (IQR 6.6%, 7.7%) , and mean body mass index (BMI) 25.0 (IQR 23.0, 28.4) kg/m2. In patients with low CPR (≤2 ng/mL; n=119) , small visceral fat area (VFA) was an independent risk factor for CV above the median CV (OR 0.98, 95% CI 0.97-0.99, P=0.0443) , while subcutaneous fat area (SFA) and BMI were equally distributed. In patients with high CPR (>2 ng/mL; n=85) , VFA, SFA, and BMI were equally distributed between patients with CV above or below the median CV. Conclusions: GV is unstable in T2DM patients with impaired endogenous insulin secretion, particularly in patients with small VFA. The present findings suggest that visceral fat is related to the stability of GV. Disclosure A.Miya: None. A.Nakamura: Research Support; Kissei Pharmaceutical Co., Ltd., MSD, Nippon Boehringer Ingelheim, Taisho Pharmaceutical Holdings Co., Ltd. H.Nomoto: None. H.Kameda: None. K.Cho: None. S.Nagai: Other Relationship; Eli Lilly and Company. Y.M.Ito: None. H.Miyoshi: Research Support; Abbott Japan Co., Ltd., Boehringer Ingelheim International GmbH, Daiichi Sankyo, Kowa Company, Ltd., LifeScan, Mitsubishi Tanabe Pharma Corporation, Novo Nordisk, Ono Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., Speaker’s Bureau; Astellas Pharma Inc., Boehringer Ingelheim International GmbH, Eli Lilly and Company, Kowa Company, Ltd., Merck & Co., Inc., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk, Ono Pharmaceutical Co., Ltd., Sanofi K.K., Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd. T.Atsumi: Consultant; AbbVie Inc., AstraZeneca, MEDICAL & BIOLOGICAL LABORATORIES CO., Nippon Boehringer Ingelheim Co. Ltd., Novartis Pharma K.K., Ono Pharmaceutical Co., Ltd., Pfizer Inc., Research Support; AbbVie Inc., Alexion Pharmaceuticals, Inc., Astellas Pharma Inc., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo, Mitsubishi Tanabe Pharma Corporation, Nippon Boehringer Ingelheim Co. Ltd., Otsuka Pharmaceutical Co., Ltd., Pfizer Inc., Taiho Pharmaceutical Co. Ltd., Takeda Pharmaceutical Company Limited, Teijin Pharma Limited, Speaker’s Bureau; AbbVie Inc., Astellas Pharma Inc., Bristol-Myers Squibb Company, Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo, Eisai Co., Ltd., Eli Lilly and Company, Kyowa Kirin Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Novartis Pharma K.K., Pfizer Inc., Taiho Pharmaceutical Co. Ltd., Takeda Pharmaceutical Company Limited, UCB, Inc.