A 66-year-old Japanese man was referred to Sapporo Medical University Hospital for treatment of newly developed TBIR. He had suffered from discoid lupus with leucopenia, hypocomplementemia, positive anti-nuclear antibody and anti-Smith antibody. He was diagnosed with SLE at the age of 48 years and had been stable on only topical therapy for discoid lupus. At the age of 65 years, his regular medical checkup did not reveal any glucose intolerance. However, six months later, he developed both polyuria and thirst and visited his local doctor. He was diagnosed as having diabetes mellitus with blood glucose of 300 mg/dl and HbA1c of 9.1%, and he was admitted to his local hospital. He was initially treated with metformin and multiple daily injections of insulin, but his hyperglycemia did not improve even with a total insulin dose of 120 units/day (insulin degludec of 30 units and insulin aspart of 30 units per each meal). Addition of sulfonylureas and dulaglutide, a weekly glucagon-like peptide 1 (GLP-1) receptor agonist, at 0.75 mg/week also did not improve his hyperglycemia. In addition to marked elevation in fasting serum insulin and C-peptide levels, serum anti-insulin receptor antibody test was positive, leading to the diagnosis of TBIR. He was transferred to our hospital for further treatment of TBIR.
On admission, his body weight was 70.0 kg, body mass index (BMI) was 24.2 kg/m2, blood pressure was 85/64 mmHg, pulse rate was 107 bpm, and body temperature was 36.1 C. Since he was suffering from hyperglycemia and anorexia, decreased blood pressure with tachycardia on admission was considered to be due to intravascular dehydration caused by osmotic diuresis. There was no skin rash including melanosis nigricans, erythema spheroids or discoid lupus. Achilles tendon reflex was not decreased, but bilateral lower extremity vibratory sensation was decreased. Results of laboratory tests on admission revealed severe insulin resistance and ketosis: fasting blood glucose level was 225 mg/dl, fasting serum insulin level was 455 muIU/ml, fasting serum C-peptide level was 5.45 ng/ml, and beta-hydroxybutyrate level was 1.8 mM ( Table 1 ). The activity of SLE was assessed by Systemic Lupus Erythematosus Disease Activity Index-2K (SLEDAI-2K) and it was 4 points for hypocomplementemia (2 points), thrombocytopenia (1 point), and leukopenia (1 point). In addition, serum anti-Sjogren's-syndrome-related antigen A (anti-SS-A) and B (anti-SS-B) antibodies were positive and the Schirmer test was positive (right 3 mm/5 min, left 1 mm/5 min) together with positive ocular surface staining by fluorescein, indicating a new diagnosis of Sjogren's syndrome. There was no diabetic retinopathy on his eyes. Since pancytopenia was observed, bone marrow aspirations and biopsies were performed and revealed fatty marrow, resulting in a diagnosis of pancytopenia secondary to autoimmune diseases. No malignancy was found in his body.
His clinical course after admission is shown in  Figure 1A . Results of intermittently-scanned CGM (isCGM, FreeStyle Libre, Abbott Diabetes Care Inc., CA, U.S.A.) revealed severe hyperglycemia throughout the day without evidence of hypoglycemia ( Figure 2A ). In addition to persistent ketosis, his body weight was progressively reduced, suggesting catabolic state. Therefore, we decided to perform combination therapy with DFPP (twice a week) and infusion of the anti-CD20 antibody rituximab (375 mg/m2, once weekly for 4 weeks) as previously reported, followed by administration of hydroxychloroquine for reducing SLE activity. Furthermore, an SAP (MiniMed 640G system, Medtronic, Dublin, Ireland), which can detect rapid decline in interstitial glucose levels, was introduced instead of isCGM ( Figure 2B ) due to early detection of hypoglycemic event. Following these combined treatment strategies, hyperglycemia and ketosis improved, and he was discharged on his 71st admission day. Thereafter, his HbA1c gradually improved and no severe hypoglycemia occurred due to glycemic monitoring and fine-tuning of insulin dosage using an SAP. Additional rituximab administration (375 mg/m2/week, 1 time) was performed six months after initial infusion. Anti-insulin receptor antibodies became negative after seven months of initiation of the therapy. Representative glucose profiling nine months after these treatments is shown in  Figure 2C . Soft lean mass evaluated by bioelectrical impedance analysis was increased from 46.5 kg at baseline to 50.7 kg after his anti-insulin receptor antibodies became negative, suggesting an improvement in the catabolic state ( Figure 1B ). Platelets counts and hypocomplementemia were also recovered with an improvement of glycemic control and SLEDAI-2K became 1 point seven months after the initiation of therapy ( Figure 1B ). There were no remarkable adverse events including infusion reaction, opportunistic infections, severe infections, gastrointestinal symptoms, retinopathy and hemorrhagic events throughout his clinical course.