Eruptive xanthomas as a marker for metabolic disorders: A specific form of xanthoma that reflects hypertriglyceridemia.

Eruptive xanthomas are skin manifestations associated with hypertriglyceridemia. Accordingly, the improvement of hypertriglyceridemia can ameliorate this condition. We report a case of a patient with type 2 diabetes mellitus who was diagnosed with this skin lesion. Clinicians should be aware that eruptive xanthomas could indicate metabolic disorders associated with atherosclerosis.

Case Report: Metreleptin and SGLT2 Inhibitor Combination Therapy Is Effective for Acquired Incomplete Lipodystrophy.

Childhood cancer survivors (CCSs) who have undergone bone marrow transplantation with systemic chemotherapy and whole-body irradiation often experience impaired glucose tolerance with marked insulin resistance. Incomplete acquired diabetic lipodystrophy should be considered as a late complication of bone marrow transplantation. A 24-year-old Japanese female patient with incomplete acquired lipodystrophy, a CCS of acute lymphocytic leukemia at the age of 3 years, was treated for diabetes mellitus and dyslipidemia at our hospital. Administration of multiple daily insulin injections (70 units/day), and oral administration of 500 mg/day metformin, 15 mg/day pioglitazone, and 200 mg/day bezafibrate had proven ineffective for her metabolic disorders. Subcutaneous administration of metreleptin improved her insulin resistance and hypertriglyceridemia within a month; however, it failed to maintain adequate plasma glucose levels in the long term. When oral administration of 10 mg/day empagliflozin was added to the metreleptin supplementation, her HbA1c value (National Glycohemoglobin Standardization Program) improved from 11% to 8%, which was maintained for an additional 18 months. This is the first case report of incomplete lipodystrophy that shows efficacy of a combination therapy with metreleptin and a sodium glucose cotransporter 2 (SGLT2) inhibitor for the treatment of diabetes and dyslipidemia. An SGLT2 inhibitor attenuates hyperglycemia through urinary glucose excretion and has been suggested to enhance lipid catabolism in the extra-adipose tissues, especially in the liver and skeletal muscles. Furthermore, metreleptin supplementation could enhance the action of the SGLT2 inhibitor by promoting satiety and lipolysis through the central nervous system. Combination therapy with metreleptin and an SGLT2 inhibitor was suggested to recover the volume of adipose tissue, possibly through improvement of insulin resistance in the adipose tissue. This report highlights the pathophysiological mechanism of an SGLT2 inhibitor in the improvement of glucose metabolism in non-healthy lean CCSs with insulin resistance. Administration of SGLT2 inhibitor, along with metreleptin supplementation, could be a good alternative therapy for diabetic lipodystrophy observed in CCSs.

Human Leukocyte Antigen (HLA) Subtype-Dependent Development of Myasthenia Gravis, Type-1 Diabetes Mellitus, and Hashimoto Disease: A Case Report of Autoimmune Polyendocrine Syndrome Type 3.

BACKGROUND Patients with type 1 diabetes mellitus, myasthenia gravis (MG), and Hashimoto disease are diagnosed as having autoimmune polyendocrine syndrome type 3 (APS3). APS3 is rare, and its pathogenesis is unclear. We describe a female patient with APS3 whose human leukocyte antigen (HLA) type could provide a clue to the pathogenesis of APS3. CASE REPORT A 40-year-old Japanese female patient who had been diagnosed with MG at 5 years of age, and which had been treated with cholinesterase inhibitors, was referred to our hospital with thirst, polydipsia, polyuria, weight loss, and hyperglycemia. She was found to have type 1 diabetes mellitus based on laboratory tests. She was also positive for anti-thyroid peroxidase antibody and was thus diagnosed with Hashimoto disease. This combination of type 1 diabetes mellitus, myasthenia gravis, and Hashimoto disease led to a diagnosis of APS3. Her HLA serotype was A24; B46/54; DR4/9; DQ8/9, and genotype was A*24: 02; B*46: 01: 01/54: 01: 01; C*01: 02; DRB1*04: 06/09: 01: 02; DQB1*03: 02: 01/03: 03: 02; and DQA1*03: 01/03: 02: 01. We subsequently reviewed 10 cases of APS3 combined with MG, including the present case and cases reported in Japanese. This review revealed that HLA-DR9/DQ9 might be a specific HLA subtype associated with APS3 with MG. Four of the 10 cases had MG diagnosed before diabetes mellitus and autoimmune thyroid disease. CONCLUSIONS The present case showed that, in people with HLA-B46 and -DR9, antibody-negative MG can precede the development of APS3 by many years. Physicians should consider the possibility of APS3 when evaluating patients with ocular-type myasthenia gravis, and screen them for type 1 diabetes.

Prevalence and clinical characteristics of unremembered nocturnal eating in diabetic subjects: Kurume sleep trouble in obesity and metabolic disorders (KUSTOMED) study.

Nighttime food intake is associated with weight gain and higher HbA1c levels. We experienced night eaters who have no memory of their nocturnal eating in the morning. In this study, the curious night eating behavior was designated as "unremembered nocturnal eating syndrome (UNES)". We screened 1,169 patients with diabetes for sleep quality and abnormal eating behavior at night using the Pittsburgh Sleep Quality Index questionnaire with an additional question regarding UNES. When abnormal nocturnal eating behavior was noted, detailed clinical information was extracted from interviews with the patients. We identified 9 patients who experienced UNES. They had a higher BMI compared with subjects who reported no such episodes. Among them, 6 patients who consumed food at night without memory 2-5 times per month or more had significantly higher HbA1c levels. Continuous glucose monitoring in a patient with type 1 diabetes revealed an abrupt elevation of glucose levels from midnight when some foods were consumed. Eight of the 9 patients were taking benzodiazepine and/or non-benzodiazepine hypnotic agents when they experienced the episodes. The prevalence of UNES was 0.8% in all subjects and 4% in those taking hypnotic drugs. The ratio of hypnotic drug use in subjects with UNES was significantly higher than for individuals without UNES (89% vs. 17%, p<0.0001). Although UNES seems to be etiologically heterogeneous, hypnotics-induced parasomnia and/or anterograde amnesia may be associated with the behavior. UNES is not rare in diabetic patients on hypnotic medicine and may be a hidden cause of unexpected morning hyperglycemia.