The purpose of this cross-sectional study was to examine the effects of circadian rhythm on glucose and lipid metabolism via a questionnaire survey. We compared 91 subjects under 75 years of age with type 2 diabetes and impaired glucose tolerance. The subjects were separated into three groups (the H, M, and L groups) based on their phase score on a three-dimensional sleep scale. Higher phase scores indicate better circadian rhythm. The subjects in the L group had significantly higher BMI values in comparison to the H group (28.7±5.1 vs. 24.6±4.3 kg/m², p = 0.007). In addition, the M group had significant higher triglyceride levels in comparison to the H group (145±84 vs. 105±60 mg/dL, p = 0.027). However, there were no differences among the three groups with respect to energy intake and energy consumption. With respect to type 2 diabetes and impaired glucose tolerance, better circadian rhythms, as indicated by higher phase scores, have been shown to be associated with low BMI and TG values.

It is important to prevent the development of sarcopenia and frailty in elderly diabetic patients. We conducted nutrition education using a food diversity score and an exercise program to improve muscle strength for 16 weeks, and evaluated the effects on the food intake and exercise function in 17 elderly diabetic patients. In these patients, the muscle quality score (p< 0.01), peak reaction force per body weight (p=0.04), maximal rate force development per body weight (p< 0.01), and balance deviation value (p< 0.01) were significantly improved, while the muscle quantity, body weight and basal metabolism were not changed. Their intake of protein (p=0.01), vitamin B₁ (p=0.03), niacin equivalent (p=0.04) and protein-energy ratio (p=0.01) were significantly increased. In addition, their HDL-cholesterol levels were also significantly increased. We found that combination of nutrition and exercise education for 16 weeks was able to improve the food intake diversity and exercise function in elderly diabetic patients. These improvements may lead to the prevention of sarcopenia and frailty over the long term.

We investigated the time-dependent changes in anti-GADA titers and fasting serum C-peptide (FSC) levels after GADA seroconversion in 12 patients with SPIDDM initially regarded as having type 2 diabetes at the diagnosis and became GADA-positive after the initiation of insulin therapy at our hospital between 1998 and 2015. Twelve patients were classified into 3 groups according to the time-dependent changes in the titers: 1) antibody titer ≥2000 U/mL on an enzyme-linked immunosorbent assay (ELISA) after sustained positivity on a radioimmunoassay (RIA) (n=3); 2) antibody titer 100-300 U/mL on an ELISA or ELISA conversion after sustained positivity on a radioimmunoassay (n=2); and 3) negativity on an RIA or ELISA (n=7). The FSC levels were preserved in groups 2 and 3, but exhausted (< 0.6 ng/mL) in 1.

The patient was a 74-year-old Japanese woman. She had been diagnosed with lung adenocarcinoma in the left upper lobe at 69 years of age, and had undergone thoracoscopic left upper lobectomy. At three months after lobectomy, multiple lung metastases and rib metastases were detected. Chemotherapy was initiated at 5 months after surgery. The patient was initially treated with gefitinib; however, due to progressive tumor growth, the regimen was changed to osimertinib. This was followed by the combination of carboplatin, pemetrexed and bevacizumab, monotherapy by atezolizumab and monotherapy by docetaxel therapy. At 23 weeks after the first administration of atezolizumab, she was diagnosed with immune acute onset type 1 diabetes mellitus associated with diabetic ketoacidosis based on the results of laboratory tests, including anti-GAD antibody positivity. Tests for islet cell cytoplasmic antibodies, anti-IA-2 antibodies, anti-insulin antibodies and anti-zinc transporter 8 antibodies were negative. This is the first case of acute onset type 1 diabetes secondary to the administration of atezolizumab in a subject with HLA DRB1*04:05 and DQB1*04:01 alleles. These are some of the genotypes that increase susceptibility to Japanese acute onset type 1 diabetes. We believe that this is the first reported case of autoimmune acute onset type 1 diabetes mellitus induced by atezolizumab, an immune checkpoint inhibitor.

We herein report the case of a 57-year-old man with hyperglycemic hyperosmolar syndrome resulting in hemolytic anemia, who was diagnosed with hereditary spherocytosis during treatment. He was referred to our hospital with disturbance of consciousness. His plasma glucose concentration was very high (1617 mg/dL) with an HbA1c concentration of 12.4 %, suggesting hyperglycemic hyperosmolar syndrome. He was therefore admitted to our hospital. His plasma glucose concentration was gradually decreased with fluid replacement and continuous intravenous insulin infusion. As his dehydration and hyperglycemia improved, his hemoglobin level showed an extreme decrease, declining to 6 g/dL, and blood transfusion was performed. He was diagnosed with hemolytic anemia because his indirect bilirubin level was high, and his haptoglobin was very low with negative direct and indirect Coombs tests and no hemorrhagic lesion. Microscopy revealed some spherocytes in his peripheral blood. He had a swollen spleen with a family history of hemolytic anemia. A red blood cell resistance test showed that his red blood cells were weaker than normal. Thus, he was diagnosed with hereditary spherocytosis. Hemolytic anemia rarely occurs in patients with hereditary spherocytosis when they are in a normal condition. The drastic change of osmolarity induced by treatment for hyperglycemic hyperosmolar syndrome was suggested to have induced the hemolyzation of the weak membrane of the red blood cells in the present case.

Recently conducted glucagon research suggests that glucagon abnormalities are associated with the pathophysiology of diabetes. However, the measurement system for glucagon has an issue with accuracy due to the cross-reactivity with glucagon-related peptides in the plasma. Thus, the Japan Diabetes Society established the "Research Committee on Validation of Glucagon Assay Methods" in order to identify the most accurate glucagon immunoassay and clarify the glucagon abnormalities in diabetes patients. Comparisons between glucagon immunoassays and liquid chromatography with tandem mass spectrometry findings demonstrated that sandwich enzyme-linked immunosorbent assays (ELISAs) can measure plasma glucagon levels more accurately than conventional competitive RIAs. Three notable findings were obtained when plasma glucagon levels were measured with a sandwich ELISA in type 2 diabetic patients (T2DM) and healthy subjects (CONT) during a glucose tolerance test and a meal tolerance test: (1) T2DM showed higher fasted plasma glucagon levels than CONT; (2) Plasma glucagon levels decreased 30 minutes after glucose loading in CONT but did not decrease in T2DM; and (3) Plasma glucagon levels moderately increased 30 minutes after meal loading in CONT but increased more markedly in T2DM. It was also revealed that the difference in plasma glucagon levels 30 minutes before and after meal loading correlated well with glucose intolerance in T2DM. A sandwich ELISA has the potential to be used for glucagon measurements as a clinical test for the diagnosis of the pathology in diabetic patients.