Effect of dapagliflozin on 24-hour glycemic variables in Japanese patients with type 2 diabetes mellitus receiving basal insulin supported oral therapy (DBOT): a multicenter, randomized, open-label, parallel-group study.

INTRODUCTION: This study aimed to evaluate the impacts of dapagliflozin on 24-hour glucose variability and diabetes-related biochemical variables in Japanese patients with type 2 diabetes who had received basal insulin supported oral therapy (BOT). RESEARCH DESIGN AND METHODS: Changes in mean daily blood glucose level before and after 48-72 hours of add-on or no add-on of dapagliflozin (primary end point) and diabetes-related biochemical variables and major safety variables during the 12 weeks (secondary end point) were evaluated in the multicenter, randomized, two-arm, open-label, parallel-group comparison study. RESULTS: Among 36 participants, 18 were included in the no add-on group and 18 were included in the dapagliflozin add-on group. Age, gender, and body mass index were comparable between the groups. There were no changes in continuous glucose monitoring metrics in the no add-on group. In the dapagliflozin add-on group, mean glucose (183-156 mg/dL, p=0.001), maximum glucose (300-253, p<0.01), and SD glucose (57-45, p<0.05) decreased. Time in range increased (p<0.05), while time above the range decreased in the dapagliflozin add-on group but not in the no add-on group. After 12-week treatment with dapagliflozin add-on, 8-hydroxy-2'-deoxyguanosine (8OHdG), as well as hemoglobin A1c (HbA1c), decreased. CONCLUSIONS: This study showed that the mean daily blood glucose and other daily glucose profiles were amended after 48-72 hours of dapagliflozin add-on in Japanese patients with type 2 diabetes who received BOT. The diabetes-related biochemical variables such as HbA1c and urinary 8OHdG were also obtained during the 12 weeks of dapagliflozin add-on without major adverse events. A preferable 24-hour glucose profile in 'time in ranges' and an improvement in reactive oxygen species by dapagliflozin warrant us to evaluate these benefits in larger clinical studies. TRIAL REGISTRATION NUMBER: UMIN000019457.

Development of Graves' hyperthyroidism caused an adrenal crisis in a patient with previously unrecognized non-classical 21-hydroxylase deficiency.

A 75-year-old woman was found to be unconscious in hospital. She was febrile with a temperature of 38.4 degrees C. She had hypotension (blood pressure 80/40 mmHg) with serum Na 132 mEq/L and K 5.7 mEq/L (serum Na/K = 23.2), and serum cortisol 0.91 microg/dL, indicative of adrenal failure. She was admitted for the treatment of Graves' hyperthyroidism, and was found to be unconscious in hospital. We encountered a patient with unrecognized adrenocortical disease, in whom development of Graves' hyperthyroidism caused an adrenal crisis. The ACTH stimulation test indicated that she had 21-hydroxylase deficiency (21OHD); after ACTH stimulation, 17-OH-progesterone increased from 0.6 to 10.4 ng/mL (17.3 times), and 17-OH-progesterone/cortisol from 0.0049 to 0.045 (9.2 times). She did not have clinical signs of classical 21OHD. She had non-classical 21OHD (NC21OHD). Development of Graves' hyperthyroidism caused an adrenal crisis in a patient with previously unrecognized NC21OHD. A patient with unrecognized adrenocortical disease developed Graves' hyperthyroidism, which induced an adrenal crisis. She had NC21OHD.

Epitopes recognised by tissue transglutaminase antibodies in coeliac disease.

The interaction between IgA tissue transglutaminase (tTG) antibodies (Abs) and 35S-labelled tTG produced in a transcription/translation (TnT) system with various amino acid (aa) deletions has been studied. These experiments showed that the tTG N-terminal aa 1-89 were important for tTG Ab binding in all 15 coeliac disease sera studied and the central residues (aa 401-491) were important for binding of tTG Abs in all but one sera. The contribution of C-terminal residues to tTG Ab binding varied in different coeliac sera but overall was less than the contributions of the N terminal and central regions. Mouse monoclonal antibodies (MAbs) to tTG were produced and the tTG aa sequences recognised by the MAbs determined using modified 35S-labelled tTG proteins. Analysis of the inhibiting effects of patient sera tTG Ab on binding of tTG MAbs to tTG confirmed the importance of the N-terminal and central regions of tTG in forming serum tTG Ab binding sites. Recombinant human tTG was expressed in yeast and purified to better than 95% homogeneity using MAb affinity chromatography as a final purification step. This material was highly suitable for use in an ELISA for tTGAb.