Titration of Long-Acting Insulin Using Continuous Glucose Monitoring and Smart Insulin Pens in Type 1 Diabetes: A Model-Based Carbohydrate-Free Approach

ObjectiveMultiple daily injections (MDI) therapy is the most common treatment for type 1 diabetes (T1D), consisting of long-acting insulin to cover fasting conditions and rapid-acting insulin to cover meals. Titration of long-acting insulin is needed to achieve satisfactory glycemia but is challenging due to inter-and intra-individual metabolic variability. In this work, a novel titration algorithm for long-acting insulin leveraging continuous glucose monitoring (CGM) and smart insulin pens (SIP) data is proposed.MethodsThe algorithm is based on a glucoregulatory model that describes insulin and meal effects on blood glucose fluctuations. The model is individualized on patient’s data and used to extract the theoretical glucose curve in fasting conditions; the individualization step does not require any carbohydrate records. A cost function is employed to search for the optimal long-acting insulin dose to achieve the desired glycemic target in the fasting state. The algorithm was tested in two virtual studies performed within a validated T1D simulation platform, deploying different levels of metabolic variability (nominal and variance). The performance of the method was compared to that achieved with two published titration algorithms based on self-measured blood glucose (SMBG) records. The sensitivity of the algorithm to carbohydrate records was also analyzed.ResultsThe proposed method outperformed SMBG-based methods in terms of reduction of exposure to hypoglycemia, especially during the night period (0 am–6 am). In the variance scenario, during the night, an improvement in the time in the target glycemic range (70–180 mg/dL) from 69.0% to 86.4% and a decrease in the time in hypoglycemia (<70 mg/dL) from 10.7% to 2.6% was observed. Robustness analysis showed that the method performance is non-sensitive to carbohydrate records.ConclusionThe use of CGM and SIP in people with T1D using MDI therapy has the potential to inform smart insulin titration algorithms that improve glycemic control. Clinical studies in real-world settings are warranted to further test the proposed titration algorithm.SignificanceThis algorithm is a step towards a decision support system that improves glycemic control and potentially the quality of life, in a population of individuals with T1D who cannot benefit from the artificial pancreas system.

Rhabdomyolysis: An evidence-based approach

A 76-year-old lady was found on the floor following a fall at home. She was uninjured, but unable to get up, and had been lying on the floor for roughly 18 hours before her son arrived. She had been unwell for the past 3 days with a cough and shortness of breath. She had a past medical history of diabetes, hypertension, hypercholesterolaemia and atrial fibrillation (AF). On examination, she was alert but distressed, clinically dehydrated, febrile and tachycardic. She was treated for community acquired pneumonia with co-amoxiclav and was fluid resuscitated with Hartmann’s solution. Her hyperkalaemia was treated with 50 mL of 50% glucose containing 10 units of rapid-acting insulin. Her creatinine kinase (CK) on admission was 200,000, and she had an acute kidney injury (AKI). Urine dipstick was positive for blood. However, her renal function continued to deteriorate over the succeeding 48 h, when she required renal replacement therapy (RRT) due to fluid overload and anuria.

Diabetic Ketoacidosis Updates: Titratable Insulin Infusions and Long-Acting Insulin Early

Background. To compare a titratable insulin infusion order set (vs. nontitratable) and early administration of long-acting insulin in adult patients with diabetic ketoacidosis (DKA). Methods. Single health system, retrospective study of adult patients admitted to the intensive care unit (ICU) for DKA. The primary outcomes were insulin infusion duration and ICU/hospital length of stays (LoS). Secondary outcomes included ICU/hospital survival, hypoglycemia, and hypokalemia. Results. 151 patients were included in the titratable versus nontitratable insulin infusion comparison. Patients treated with the titratable insulin had shorter hospitalization (6.4 vs. 10.4 days, p = 0.03 ) and reduced the number hypoglycemic events by over half (20.6% vs. 46.0%, p < 0.01 ). 110 patients were identified to compare overlapping a long-acting insulin for more than 4 h with the insulin infusion versus the standard 1-2 h overlap. Patients who received the insulin early spent over 18 h longer on the infusion ( p < 0.01 ). Conclusions. A titratable insulin infusion added to the institutional DKA order set was associated with fewer days in the hospital and a significant reduction in hypoglycemic events. Furthermore, overlapping the long-acting insulin earlier with the insulin infusion early showed no benefit and could potentially be worse than the standard overlap.

Changes in diabetes prescription patterns following Affordable Care Act Medicaid expansion

IntroductionMost patients with diabetes mellitus are prescribed medications to control their blood glucose. The implementation of the Affordable Care Act (ACA) led to improved access to healthcare for patients with diabetes. However, impact of the ACA on prescribing trends by diabetes drug category is less clear. This study aims to assess if long-acting insulin and novel agents were prescribed more frequently following the ACA in states that expanded Medicaid compared with non-expansion states.Research design and methodsIn this analysis of a natural experiment, prescriptions reimbursed by Medicaid (US public insurance) for long-acting insulins, metformin, and novel agent medications (DPP4 inhibitors, sodium/glucose cotransporter 2 inhibitor antagonists, and glucagon-like peptide-1 receptor agonists) from 2012 to 2017 were obtained from public records. For each medication category, we performed difference-in-differences (DID) analysis modeling change in rate level from pre-ACA to post-ACA in Medicaid expansion states relative to Medicaid non-expansion states.ResultsExpansion and non-expansion states saw a decline in both metformin and long-acting insulin prescriptions per 100 enrollees from pre-ACA to post-ACA. These decreases were larger in non-expansion states relative to expansion states (metformin: absolute DID = +0.33, 95% CI=0.323 to 0.344) and long-acting insulin (absolute DID: +0.11; 95% CI=0.098 to 0.113). Novel agent prescriptions in expansion states (+0.08 per 100 enrollees) saw a higher absolute increase per 100 Medicaid enrollees than in non-expansion states (absolute DID= +0.08, 95% CI=0.079 to 0.086).ConclusionsThere was a greater absolute increase for prescriptions of novel agents in expansion states relative to non-expansion states after accounting for number of enrollees. Reducing administrative barriers and improving the ability of providers to prescribe such newer therapies will be critical for caring for patients with diabetes—particularly in Medicaid non-expansion states.

Utilisation Trend of Long-Acting Insulin Analogues including Biosimilars across Europe: Findings and Implications

Background. Diabetes mellitus rates and associated costs continue to rise across Europe enhancing health authority focus on its management. The risk of complications is enhanced by poor glycaemic control, with long-acting insulin analogues developed to reduce hypoglycaemia and improve patient convenience. There are concerns though with their considerably higher costs, but moderated by reductions in complications and associated costs. Biosimilars can help further reduce costs. However, to date, price reductions for biosimilar insulin glargine appear limited. In addition, the originator company has switched promotional efforts to more concentrated patented formulations to reduce the impact of biosimilars. There are also concerns with different devices between the manufacturers. As a result, there is a need to assess current utilisation rates for insulins, especially long-acting insulin analogues and biosimilars, and the rationale for patterns seen, among multiple European countries to provide future direction. Methodology. Health authority databases are examined to assess utilisation and expenditure patterns for insulins, including biosimilar insulin glargine. Explanations for patterns seen were provided by senior-level personnel. Results. Typically increasing use of long-acting insulin analogues across Europe including both Western and Central and Eastern European countries reflects perceived patient benefits despite higher prices. However, activities by the originator company to switch patients to more concentrated insulin glargine coupled with lowering prices towards biosimilars have limited biosimilar uptake, with biosimilars not currently launched in a minority of European countries. A number of activities were identified to address this. Enhancing the attractiveness of the biosimilar insulin market is essential to encourage other biosimilar manufacturers to enter the market as more long-acting insulin analogues lose their patents to benefit all key stakeholder groups. Conclusions. There are concerns with the availability and use of insulin glargine biosimilars among European countries despite lower costs. This can be addressed.

EP.TU.200Improving variable rate insulin infusion compliance in general surgery

Aims 1. Audit the current variable rate insulin infusion (VRII) practice per local guidelines. 2. Understand barriers to good VRII practice to create an intervention. 3. Re-Audit the VRII practice following intervention. Methods Junior doctors were surveyed using Likert scales (1 to 5: not at all confident to very confident) as well as closed and open questions. Chain action reaction (CAR) theory was used. Six domains were identified against a local proforma. Initial audit and questionnaire were collected from November 2019 to January 2020 and analysed using Microsoft Excel. Intervention consisted of a condensed one-page algorithm with group teaching. Re-audit data was collected between June 2020 to August 2020 for comparison. Results Questionnaire – 53.6% (15/28) of juniors responded. Challenges included conversion oral hypoglycaemics and complexity of the guidance. Group teaching and a condensed portable format were the most popular modalities for delivery of further education. Initial Audit – 12 VRII charts were audited. 33.3% (4/12) were completed correctly. Areas of significant need for improvement were as follows: ensuring long-acting insulin is prescribed, transferring from a VRII back to oral medications and appropriate fluid prescribing. Re-Audit – 18 charts were audited following intervention. Of these, 66.7% (12/18) were completed correctly. There was a significant improvement in appropriate fluid prescribing and long-acting insulin prescriptions. Conclusions Understanding the factors involved throughout the chain of how VRIIs are prescribed has helped to implement a positive intervention in our department. The improvement has been significant (100% better) however there is still further work required to improve compliance.

Faster Aspart: a fast-acting insulin analog for an optimal glycemic control

The basal-bolus insulin regimen in the management of diabetes is essential to achieve the recommended glycosylated hemoglobin (HbA1c) to reduce the incidence or the progression of chronic complications. HbA1c is influenced by either fasting plasma glucose and post-prandial hyperglycemia. Faster Aspart is an insulin Aspart with two additional excipients, L-arginine and niacinamide, which provide a faster subcutaneous absorption, the earlier onset of appearance, and consequently the optimization of post-prandial glucose control. Faster Aspart has been widely investigated in the ‘‘onset’’ clinical trials, which show better post-prandial glycemic excursions and noninferiority compared to insulin Aspart with HbA1c reduction. Clinical evidence demonstrates that faster Aspart is a therapeutic option able to provide clinical benefits over the current rapid-acting insulin analogs in terms of improved meal-related glycaemic control in subjects with diabetes. KEY WORDS post-prandial hyperglycemia; cardiovascular disease; insulin treatment; faster-acting insulin; faster aspart.