Aims/hypothesis We investigated whether there was evidence of attempted beta cell regeneration in the pancreas obtained from a patient with recent-onset type 1 diabetes, and if so by what mechanism this occurred. Subjects, materials and methods We examined pancreas tissue from a lean 89-year-old patient (BMI 18.0 kg/m 2 ) with recent-onset type 1 diabetes who had had a distal pancreatectomy to remove a low-grade pancreatic intraepithelial neoplasia. Results In the tumour-free tissue, the fractional beta cell area was 0.54±0.2% of pancreas area (about one-third of that in non-diabetic humans). CD3-positive T lymphocytes and macrophages had infiltrated the majority of the islets. Subclassification of the T cell population revealed a predominance of CD8-positive cells over CD4-positive cells. Beta cell apoptosis (terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labelling [TUNEL] staining) was greatly increased, consistent with ongoing immune-mediated beta cell destruction. There was also a marked increase (more than ∼100-fold) in the frequency of beta cell replication (0.69±0.15% Ki67-positive beta cells) in all blocks examined. Conclusions/interpretationThe present report provides direct evidence of attempted beta cell regeneration through the mechanism of beta cell replication in a case of newly diagnosed type 1 diabetes, and affirms that beta cell apoptosis is an important mechanism for beta cell loss in type 1 diabetes.

Most previous studies suggest that physical exercise, or physiological response to exercise such as cortisol and adrenaline secretion regulate parathyroid hormone (PTH) secretion in humans. To investigate the effects and possible interaction of exercise and excessive glucocorticoid on PTH secretion, we examined the serum of levels of intact-PTH, cortisol, adrenocorticotrophic hormone (ACTH), calcium, magnesium and phosphorus before and during one-hour of bicycle-ergometric exercise at 60% of maximal oxygen uptake. These exercise tests were performed on eight Chinese male volunteers aged between 20 and 25 years, once with and once without pretreatment with 0.5 mg of dexamethasone taken orally 9.5 hours in advance. The results showed that dexamethasone pretreatment significantly lowered basal levels of cortisol and ACTH, but intact PTH did not change. After 60 minutes of bicycling, intact PTH level increases by 50% of baseline both with and without dexamethasone pretreatment. Serum levels of calcium, corrected for changes in serum albumin concentration, phosphorus and magnesium also increased in both cases. This study demonstrated an increase of intact-PTH with exercise which was not associated with hypocalcemia or hypomagnesemia, and was not altered in the presence of mild exogenous glucocorticoid excess and suppressed endogenous cortisol secretion.

Background: Heart failure (HF) is the leading cause of hospitalizations and death in patients with adult congenital heart disease (ACHD). Sacubitril/valsartan is a new agent in the treatment of HF, but its effects have not been assessed in ACHD. Methods: We retrospectively studied all 15 patients with ACHD at our center who were prescribed sacubitril/valsartan between June 2017 and June 2018. We assessed baseline characteristics and clinical and laboratory changes after initiation of sacubitril/valsartan. Adverse events, including renal function, medication intolerance, and worsening HF were documented. Results: The median age was 53.2 (27.6-83.6) years, with a median follow-up duration of 69 (8-419) days. At baseline, all patients had refractory HF despite guideline-directed medical therapy, with ten (67%) patients as New York Heart Association (NYHA) class II, and five (33%) patients NYHA class III. The medication was discontinued in one (7%) patient secondary to worsening kidney function. No patients reported clinical deterioration; four NYHA class III patients with complex CHD, pulmonary hypertension, and cyanosis reported significant improvement to NYHA class II. Baseline creatinine was 1.1 (0.9-1.7) and two weeks after starting sacubitril/valsartan it was 1.3 (0.8-2.5, P ¼ .22). Conclusions: Sacubitril/valsartan seems to be well tolerated in patients with ACHD who present with refractory HF symptoms. Patients with complex CHD associated with cyanosis and pulmonary hypertension could benefit the most, but larger studies are needed to assess the safety as well as the effectiveness of sacubitril/valsartan in this patient population.

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