Bihormonal fully closed-loop system for the treatment of type 1 diabetes: a real-world multicentre, prospective, single-arm trial in the Netherlands.

BACKGROUND: Management of insulin administration for intake of carbohydrates and physical activity can be burdensome for people with type 1 diabetes on hybrid closed-loop systems. Bihormonal fully closed-loop (FCL) systems could help reduce this burden. In this trial, we assessed the long-term performance and safety of a bihormonal FCL system. METHODS: The FCL system (Inreda AP; Inreda Diabetic, Goor, Netherlands) that uses two hormones (insulin and glucagon) was assessed in a 1 year, multicentre, prospective, single-arm intervention trial in adults with type 1 diabetes. Participants were recruited in eight outpatient clinics in the Netherlands. We included adults with type 1 diabetes aged 18-75 years who had been using flash glucose monitoring or continuous glucose monitors for at least 3 months. Study visits were integrated into standard care, usually every three months, to evaluate glycaemic control, adverse events, and person-reported outcomes. The primary endpoint was time in range (TIR; glucose concentration 3·9-10·0 mmol/L) after 1 year. The study is registered in the Dutch Trial Register, NL9578. FINDINGS: Between June 1, 2021, and March 2, 2022, we screened 90 individuals and enrolled 82 participants; 78 were included in the analyses. 79 started the intervention and 71 were included in the 12 month analysis. Mean age was 47.7 (SD 12·4) years and 38 (49%) were female participants. The mean preintervention TIR of participants was 55·5% (SD 17·2). After 1 year of FCL treatment, mean TIR was 80·3% (SD 5·4) and median time below range was 1·36% (IQR 0·80-2·11). Questionnaire scores improved on Problem Areas in Diabetes (PAID) from 30·0 (IQR 18·8-41·3) preintervention to 10·0 (IQR 3·8-21·3; p<0·0001) at 12 months and on World Health Organization-Five Well-Being Index (WHO-5) from 60·0 (IQR 44·0-72·0) preintervention to 76·0 (IQR 60·0-80·0; p<0·0001) at 12 months. Five serious adverse events were reported (one cerebellar stroke, two severe hypoglycaemic, and two hyperglycaemic events). INTERPRETATION: Real-world data obtained in this trial demonstrate that use of the bihormonal FCL system was associated with good glycaemic control in patients who completed 1 year of treatment, and could help relieve these individuals with type 1 diabetes from making treatment decisions and the burden of carbohydrate counting. FUNDING: Inreda Diabetic.

[A woman with oedema of the lower legs]. / Een vrouw met oedeem van de onderbenen.

We present a 46-year-old female with hyperthyroidism, orbitopathy and dermopathy who we diagnosed with Grave's disease. Myxoedema is a rare extrathyroidal symptom and is associated with orbitopathy. TSH-receptor expressing fibroblasts lead to by accumulation of subcutaneous glycosaminoglycans, causing the oedema. Often it is self-limiting, but corticosteroid therapy may be required.

Performance and safety of an integrated bihormonal artificial pancreas for fully automated glucose control at home.

AIMS: To assess the performance and safety of an integrated bihormonal artificial pancreas system consisting of one wearable device and two wireless glucose sensor transmitters during short-term daily use at home. METHODS: Adult patients with type 1 diabetes using an insulin pump were invited to enrol in this randomized crossover study. Treatment with the artificial pancreas started with a day and night in the clinical research centre, followed by 3 days at home. The control period consisted of 4 days of insulin pump therapy at home with blinded continuous glucose monitoring for data collection. Days 2-4 were predefined as the analysis period, with median glucose as the primary outcome. RESULTS: A total of 10 patients completed the study. The median [interquartile range (IQR)] glucose level was similar for the two treatments [7.3 (7.0-7.6) mmol/l for the artificial pancreas vs. 7.7 (7.0-9.0) mmol/l for the control; p = 0.123]. The median (IQR) percentage of time spent in euglycaemia (3.9-10 mmol/l) was longer during use of the artificial pancreas [84.7 (82.2-87.8)% for the artificial pancreas vs. 68.5 (57.9-83.6)% for the control; p = 0.007]. Time in hypoglycaemia was 1.3 (0.2-3.2)% for the artificial pancreas and 2.4 (0.4-10.3)% for the control treatment (p = 0.139). Separate analysis of daytime and night-time showed that the improvements were mainly achieved during the night. CONCLUSIONS: The results of this pilot study suggest that our integrated artificial pancreas provides better glucose control than insulin pump therapy in patients with type 1 diabetes at home and that the treatment is safe.

An exercise programme for patients with diabetic complications: a study on feasibility and preliminary effectiveness.

AIMS: To investigate the feasibility and preliminary effectiveness of an exercise programme for patients with diabetic complications. METHODS: In this pre-post design study, 22 patients from a diabetic foot outpatient clinic participated in a 12-week individualized exercise programme, consisting of aerobic and resistance exercise, with specific safety precautions. Feasibility was assessed on the basis of programme adherence, adverse events, achievement of the target training intensity and patient satisfaction. Preliminary effectiveness was evaluated with pre-post-changes in blood glucose regulation (HbA(1c) ), muscle strength (isometric peak torque) and perceived limitations in functioning (Patient Specific Function Scale with visual analogue scale). RESULTS: Twenty patients completed the exercise programme with a high mean attendance (85%). No training-related severe adverse events occurred. The target training intensity was achieved by 70% of the participants. Patient satisfaction was high. HbA(1c) decreased from 8.2% before to 7.8% after the programme (P=0.005), muscle strength increased from 136.4 to 150.4 Nm (P = 0.046) and perceived limitations in functioning decreased from 7.2 to 5.8 mm (P=0.003). CONCLUSIONS: The prescribed exercise programme had a potentially positive effect on blood glucose regulation, muscle strength and perceived limitations in functioning in patients with diabetic complications.

Evaluation of endocrine tests. D: the prolonged fasting test for insulinoma.

OBJECTIVE: To establish the diagnostic performance of the prolonged fasting test in patients suspected of insulinoma. METHODS: We included all patients who were referred to our department between August 1995 and August 2006 with a clinical suspicion of insulinoma. Insulinoma was diagnosed by a positive Whipple's triad during the prolonged fast in combination with an insulin/C-peptide ratio below 1. The presence of insulinoma was confirmed by histopathological data, which was considered the golden standard. If the prolonged fast was negative, long-term follow-up was obtained. RESULTS: Ten patients had a positive Whipple's triad during the prolonged fast: eight had a histologically proven insulinoma, and two had factitious hypoglycaemia (insulin/C-peptide ratio >1.0) One additional patient likely had an insulinoma, but the Whipple's triad remained absent at up to 56 hours of fasting. Follow-up (median 53 months (3 to 142) in 76% of patients with a negative fasting test revealed no missed cases of insulinoma. During the prolonged fast the glucose, insulin and C-peptide concentrations overlapped in patients with and without insulinoma. CONCLUSION: In our centre, the prolonged fasting test defined as a positive Whipple's triad in combination with an insulin/C-peptide ratio <1 had a sensitivity of 88.9% and a specificity of 100% for the diagnosis of insulinoma.

[Pain in the throat due to acute suppurative thyroiditis caused by Salmonella]. / Een pijnlijke hals door acute suppuratieve thyreoïditis veroorzaakt door Salmonella.

A 53-year-old woman presented with fever accompanied by chills and an extremely painful swelling of her right thyroid lobe. She was initially diagnosed as having subacute thyroiditis, but after 14 days her disease appeared to be caused by a destructive suppurative thyroiditis due to Salmonella group C. A pre-existing hyperplastic nodule in the right thyroid lobe was the predisposing factor. Antibiotics were given for several weeks and surgical drainage was performed. Finally a hemithyroidectomy was done to eliminate the predisposing factor.

Goserelin-induced transient thyrotoxicosis in a hypothyroid woman on L-thyroxine replacement.

An increase in free thyroxine (fT4) and a decrease in thyroid-stimulating hormone (TSH) was observed in a hypothyroid woman on levothyroxine treatment after implantation of goserelin, a gonadotropin-releasing hormone (GnRH) analogue. In the literature no data are available that describe a drug interaction between GnRH analogues and thyroid hormone replacement. Our hypothesis to explain this observation is that goserelin decreased serum thyroxine-binding-globulin (TBG), resulting in an increase in fT4 and thereby a decrease in serum TSH.