Real-time continuous glucose monitoring immediately after severe hypoglycaemia requiring emergency medical services: A randomised controlled trial.

AIMS: Severe hypoglycaemia requiring emergency medical services remains prevalent despite advances in all aspects of diabetes self-management. Real-time continuous glucose monitoring (RTCGM) technologies can reduce the risk of severe hypoglycaemia for adults with type 1 diabetes, but the impact of these devices has not been assessed in the acute phase after an episode of severe hypoglycaemia. METHODS: We recruited and randomised 35 adults with type 1 diabetes in the acute period after an episode of severe hypoglycaemia requiring emergency medical services and randomised participants to RTCGM with alerts and alarms, or usual care with self-monitored blood glucose for 12 weeks with intermittent blinded CGM. The primary outcome was the difference between groups in percentage time spent in hypoglycaemia (≤3.0 mmol/L, 55 mg/dL). RESULTS: Thirty participants completed the study (median (IQR) age, duration of diabetes, and BMI was 43 (36-56) years, 26 (19-37) years, and 24.9 (21.9-29.0) kg/m2 , respectively). Sufficient CGM data was available for 15 participants in RT-CGM group and 8 in SMBG group for the primary outcome analysis. The RTCGM group had a significantly larger reduction in exposure to glucose below 3.0 mmol/L (RTCGM -0.16 [-1.23 to 0.01] vs. SMBG 1.58 [0.41 to 3.48], p = 0.03) and episodes of nocturnal hypoglycaemia (RT-CGM -0.03 [-0.15 to 0.02] vs. SMBG 0.05 [-0.03 to 0.40], p = 0.02). Episodes of severe hypoglycaemia were significantly lower in the RTCGM group (RTCGM 0.0 vs. SMBG 4.0, p 0.04). CONCLUSIONS: RTCGM implemented acutely after an episode of severe hypoglycaemia is feasible and clinically effective with important implications for hypoglycaemia management pathways and self-monitoring cost effectiveness.

Cross-sectional analysis of emergency hypoglycaemia and outcome predictors among people with diabetes in an urban population.

AIMS/HYPOTHESIS: Out-of-hospital hypoglycaemia is a common complication for individuals with diabetes mellitus and represents a significant burden to emergency medical services (EMS). We aim to identify the factors associated with receiving parenteral treatment and hospital conveyance. METHODS: We retrospectively analysed a 6-month data set of all London EMS hypoglycaemia. Individuals with a known diabetes diagnosis were included in our analysis and stratified as either having type 1 diabetes or type 2 diabetes. RESULTS: A total of 2862 incidents occurred within the area served by London Ambulance Service between January and June 2018. Fifty percent of incidents required parenteral treatment (intravenous glucose or intramuscular glucagon) and were conveyed to hospital. A higher arrival of blood glucose, intact consciousness and receiving oral glucose treatment were all negative predictors for requiring parenteral therapy. Forty-three percent of incidents were labelled as 'hypoglycaemia' by the EMS call handler, and greater odds of hospitalisation were observed among incidents that received parenteral treatment (OR 2.52 [95% CI 1.46, 4.33] p < 0.01) and individuals with type 2 diabetes (OR 2.67 [95% CI 1.52, 4.71] p < 0.01). Repeated callouts from 2% (n = 50) of individuals accounted for 10% (286) of all incidents attended, and 56.4% of individuals attended by EMS on more than one occasion had type 1 diabetes. CONCLUSIONS/INTERPRETATION: Severe hypoglycaemia requiring emergency service attendance remains common, as does the requirement for parenteral therapy and conveyance to hospital. Early intervention, education and improved accessibility to risk prevention strategies may reduce the necessity for emergency parenteral treatment and hospitalisation, especially among individuals suffering from recurrent hypoglycaemia and high-risk individuals with type 2 diabetes.

Primary Hypothyroidism Unleashing Severe Pericardial Effusion: Lessons Learnt From an Atypical Presentation of a Common Endocrine Condition.

Primary hypothyroidism is a commonly encountered endocrine disorder and can be associated with pericardial effusion and cardiac tamponade in severe cases. Early detection of hypothyroidism is key since it is a potentially treatable and reversible cause of pericardial effusions. A 53-year-old female was admitted following a fall. The clinical history was remarkable, with symptoms of persistent tiredness and fatigue for six months. She had no known medical conditions and was not taking any regular medications. Vital signs were stable. Physical examination revealed bilateral pitting pedal oedema and a tense abdomen with shifting dullness. Cardiovascular and respiratory examinations were normal. Notably, the patient exhibited delayed relaxation of deep-tendon reflexes bilaterally at the patellar and ankle sites. Pertinent laboratory findings showed an elevated thyroid-stimulating hormone (TSH) level of 151.69 milliunits/L, a low free thyroxine (fT4) level of <5.4 pmol/L, a haemoglobin level of 85 g/L, and a markedly high anti-thyroid peroxidase antibody level of 957.35 IU/mL. An electrocardiogram revealed a normal sinus rhythm with a low-voltage QRS complex. Chest X-ray findings indicated cardiomegaly suggestive of left heart failure. An emergent transthoracic echocardiography (TTE) demonstrated a large pericardial effusion measuring 5.4 cm posterior to the left ventricle. The most likely aetiology in this case was severe primary hypothyroidism. She initially received intravenous liothyronine 10 micrograms every four hours, followed by oral liothyronine 5 micrograms twice a day in conjunction with levothyroxine 100 micrograms once a day. The adrenal reserve assessment was satisfactory. An urgent pericardiocentesis was performed, draining a total of 900 mL of serosanguinous fluid. Serial echocardiograms demonstrated the absence of residual effusion. Hypothyroidism is a relatively uncommon cause of pericardial effusion. By ensuring early detection and appropriate treatment, we can optimise patient outcomes and prevent potential complications associated with untreated hypothyroidism.

Enhancing self-management in type 1 diabetes with wearables and deep learning.

People living with type 1 diabetes (T1D) require lifelong self-management to maintain glucose levels in a safe range. Failure to do so can lead to adverse glycemic events with short and long-term complications. Continuous glucose monitoring (CGM) is widely used in T1D self-management for real-time glucose measurements, while smartphone apps are adopted as basic electronic diaries, data visualization tools, and simple decision support tools for insulin dosing. Applying a mixed effects logistic regression analysis to the outcomes of a six-week longitudinal study in 12 T1D adults using CGM and a clinically validated wearable sensor wristband (NCT ID: NCT03643692), we identified several significant associations between physiological measurements and hypo- and hyperglycemic events measured an hour later. We proceeded to develop a new smartphone-based platform, ARISES (Adaptive, Real-time, and Intelligent System to Enhance Self-care), with an embedded deep learning algorithm utilizing multi-modal data from CGM, daily entries of meal and bolus insulin, and the sensor wristband to predict glucose levels and hypo- and hyperglycemia. For a 60-minute prediction horizon, the proposed algorithm achieved the average root mean square error (RMSE) of 35.28 ± 5.77 mg/dL with the Matthews correlation coefficients for detecting hypoglycemia and hyperglycemia of 0.56 ± 0.07 and 0.70 ± 0.05, respectively. The use of wristband data significantly reduced the RMSE by 2.25 mg/dL (p < 0.01). The well-trained model is implemented on the ARISES app to provide real-time decision support. These results indicate that the ARISES has great potential to mitigate the risk of severe complications and enhance self-management for people with T1D.

Improved glycaemia during the Covid-19 pandemic lockdown is sustained post-lockdown and during the "Eat Out to Help Out" Government Scheme, in adults with Type 1 diabetes in the United Kingdom.

AIMS: The majority of studies report that the Covid-19 pandemic lockdown did not have a detrimental effect on glycaemia. We sought to explore the impact of lockdown on glycaemia and whether this is sustained following easing of restrictions. METHODS: Retrospective, observational analysis in adults and children with type 1 diabetes attending a UK specialist centre, using real-time or intermittently scanned continuous glucose monitoring. Data from the following 28-day time periods were collected: (i) pre-lockdown; (ii) during lockdown; (iii) immediately after lockdown; and (iv) a month following relaxation of restrictions (coinciding with Government-subsidised restaurant food). Data were analysed for times in glycaemic ranges and are expressed as median (IQR). RESULTS: 145 adults aged 35.5 (25.8-51.3) years with diabetes duration of 19.0 (7.0-29.0) years on multiple daily injections of insulin (60%) and continuous insulin infusion (40%) were included. In adults, % time in range (70-180mg/dL) increased during lockdown (60.2 (45.2-69.3)%) compared to pre-lockdown (56.7 (43.5-65.3)%; p<0.001). This was maintained in the post-lockdown time periods. Similarly, % time above range (>180mg/dL) reduced in lockdown compared to pre-lockdown (p = 0.01), which was sustained thereafter. In children, no significant changes to glycaemia were observed during lockdown. In multivariable analysis, a greater increase in %TIR 3.9-10mmol/L (70-180mg/dL) during lockdown was associated with higher levels of deprivation (coefficient: 4.208, 95% CI 0.588 to 7.828; p = 0.02). CONCLUSIONS: Glycaemia in adults improved during lockdown, with people from more deprived areas most likely to benefit. This effect was sustained after easing of restrictions, with government-subsidised restaurant eating having no adverse impact on glycaemia.

Double jeopardy: a patient's tale of two concurrent hypercalcaemic syndromes.

Primary hyperparathyroidism (PHPT) is the most common cause of parathyroid hormone (PTH) dependent hypercalcaemia, however there are few reported cases of its co-occurrence in patients with familial hypocalciuric hypercalcaemia (FHH). This case highlights the challenges in managing a rare case of dual pathology. A 49-year-old Caucasian woman with symptoms of hypercalcaemia presented with an adjusted serum calcium of 2.77 mmol/L and PTH of 11.5 pmol/L. Neck ultrasound and sestamibi scan were concordant with a left lower parathyroid adenoma, and a preoperative dual-energy X-ray absorptiometry scan confirmed osteopenia. Parathyroidectomy resulted in a PTH reduction from 11.5 pmol/L to 2.7 pmol/L. Interestingly, her lowest pre-operative adjusted serum calcium of 2.67 mmol/L remained unchanged 14 months post-parathyroidectomy. Twenty-four hours urine calcium:creatinine clearance ratio performed postoperatively was low and sequencing analysis of the calcium-sensing receptor gene confirmed the coexistence of FHH. Although surgery is not indicated in FHH, parathyroidectomy may help reduce hypercalcaemia and its associated complications if there is coexistent PHPT.

Differences for Percentage Times in Glycemic Range Between Continuous Glucose Monitoring and Capillary Blood Glucose Monitoring in Adults with Type 1 Diabetes: Analysis of the REPLACE-BG Dataset.

Background: Self-monitored blood glucose (SMBG) and real-time continuous glucose monitoring (rtCGM) are used by people living with type 1 diabetes (T1D) to assess glucose and inform decision-making. Percentage time in range (%TIR) between 3.9 and 10 mmol/L has been associated with incident microvascular complications using historical SMBG data. However, the association between %TIR calculated from rtCGM data has not been identified. This study investigates whether %TIR values generated from rtCGM and SMBG data significantly differ from each other in adults with T1D. Materials and Methods: rtCGM and SMBG data from the REPLACE-BG study were obtained and analyzed. The dataset contained rtCGM (Dexcom G4 Platinum) and SMBG (Contour Next) values for 226 participants during a run-in phase lasting up to 10 weeks, followed by the 26-week trial. Percentages times in hypoglycemic, euglycemia and hyperglycemic ranges were generated from rtCGM and SMBG data using last observation carry forward method (zero-order hold) and linear interpolation (first-order hold). Results: Participants had a median (interquartile range [IQR]) age of 43.0 (31.0-55.0) years, and hemoglobin A1C of 53 (49-57) mmol/mol [7.0 (6.6-7.4)%]. The median (IQR) %TIR was significantly higher with rtCGM than with SMBG; 63.0 (55.9-71.0)% versus 54.6 (45.6-63.0)%, respectively, P < 0.001. Median %times in hypoglycemia and hyperglycemia were significantly different with SMBG than rtCGM (P < 0.001). SMBG-derived data using linear interpolation significantly differed from the carry forward method (P < 0.001 for all glycemic ranges). Differences reported were greater at night than during the day (P < 0.001 for all glycemic ranges). Conclusion: The %time in all glycemic ranges reported by SMBG and rtCGM differ significantly, suggesting relationships between times in ranges, and complication status may be different between monitoring modalities. In addition, varying methods of calculating %TIR from SMBG-derived data provide significantly differing results. %TIR targets may therefore vary by monitoring choice and methods of calculation and harmonization of TIR standards may be challenging.

The Bio-inspired Artificial Pancreas for Type 1 Diabetes Control in the Home: System Architecture and Preliminary Results.

BACKGROUND: Artificial pancreas (AP) technology has been proven to improve glucose and patient-centered outcomes for people with type 1 diabetes (T1D). Several approaches to implement the AP have been described, clinically evaluated, and in one case, commercialized. However, none of these approaches has shown a clear superiority with respect to others. In addition, several challenges still need to be solved before achieving a fully automated AP that fulfills the users' expectations. We have introduced the Bio-inspired Artificial Pancreas (BiAP), a hybrid adaptive closed-loop control system based on beta-cell physiology and implemented directly in hardware to provide an embedded low-power solution in a dedicated handheld device. In coordination with the closed-loop controller, the BiAP system incorporates a novel adaptive bolus calculator which aims at improving postprandial glycemic control. This paper focuses on the latest developments of the BiAP system for its utilization in the home environment. METHODS: The hardware and software architectures of the BiAP system designed to be used in the home environment are described. Then, the clinical trial design proposed to evaluate the BiAP system in an ambulatory setting is introduced. Finally, preliminary results corresponding to two participants enrolled in the trial are presented. RESULTS: Apart from minor technical issues, mainly due to wireless communications between devices, the BiAP system performed well (~88% of the time in closed-loop) during the clinical trials conducted so far. Preliminary results show that the BiAP system might achieve comparable glycemic outcomes to the existing AP systems (~73% time in target range 70-180 mg/dL). CONCLUSION: The BiAP system is a viable platform to conduct ambulatory clinical trials and a potential solution for people with T1D to control their glucose control in a home environment.

Pharmacological aspects of closed loop insulin delivery for type 1 diabetes.

Insulin deficiency and impaired glucose homeostasis are hallmarks of type 1 diabetes. Since the discovery of insulin, pharmacological and clinical developments have endeavoured to replicate its endogenous pharmacokinetics (PK) and pharmacodynamics (PD). Closed loop insulin delivery systems operate as an artificial pancreas by making automated insulin dose adjustments based on real time continuous glucose monitoring. The increasing adoption of continuous insulin pump therapy and evolving technological advances have seen significant progress in the development of closed loop insulin delivery systems. This article reviews the current landscape of closed loop insulin delivery systems and pharmacological advances that could overcome current barriers.