Mealtime Insulin Research Articles

ADO09, a co-formulation of pramlintide and insulin A21G, lowers body weight versus insulin lispro in type 1 diabetes.

To study safety, efficacy and weight loss with ADO09, a co-formulation of insulin A21G and pramlintide, in type 1 diabetes. A randomized, two-arm ambulatory 16-week study compared ADO09 with insulin lispro in 80 participants with type 1 diabetes. We compared changes of weight, glycated haemoglobin, glycaemic patterns during continuous glucose monitoring, and insulin doses at baseline and at the end of treatment. A significant and continuing weight loss, the primary endpoint, was observed with ADO09 compared with lispro as prandial insulin. In the whole group, the weight loss with ADO09 relative to lispro was 2.1 kg. Glycaemic control was relatively good (7.7% mean glycated haemoglobin) in both groups and did not change during treatment. Prandial insulin doses were reduced by 21% in the ADO09 group, whereas basal insulin dosage was not modified. Gastrointestinal symptoms were more frequent with ADO09, but no clear difference in hypoglycaemia was observed. These results extend previous observations on the efficacy and safety of this insulin/pramlintide co-formulation. They show a beneficial effect on weight, using less mealtime insulin and without increased hypoglycaemia.

EBM BLS: Adding tirzepatide to long-acting insulin is superior to adding mealtime insulin for type 2 diabetes mellitus.

EBM BLS: Adding tirzepatide to long-acting insulin is superior to adding mealtime insulin for type 2 diabetes mellitus.

Carbohydrate Estimation Accuracy of Two Commercially Available Smartphone Applications vs Estimation by Individuals With Type 1 Diabetes: A Comparative Study.

Despite remarkable progress in diabetes technology, most systems still require estimating meal carbohydrate (CHO) content for meal-time insulin delivery. Emerging smartphone applications may obviate this need, but performance data in relation to patient estimates remain scarce. The objective is to assess the accuracy of two commercial CHO estimation applications, SNAQ and Calorie Mama, and compare their performance with the estimation accuracy of people with type 1 diabetes (T1D). Carbohydrate estimates of 53 individuals with T1D (aged ≥16 years) were compared with those of SNAQ (food recognition + quantification) and Calorie Mama (food recognition + adjustable standard portion size). Twenty-six cooked meals were prepared at the hospital kitchen. Each participant estimated the CHO content of two meals in three different sizes without assistance. Participants then used SNAQ for CHO quantification in one meal and Calorie Mama for the other (all three sizes). Accuracy was the estimate's deviation from ground-truth CHO content (weight multiplied by nutritional facts from recipe database). Furthermore, the applications were rated using the Mars-G questionnaire. Participants' mean ± standard deviation (SD) absolute error was 21 ± 21.5 g (71 ± 72.7%). Calorie Mama had a mean absolute error of 24 ± 36.5 g (81.2 ± 123.4%). With a mean absolute error of 13.1 ± 11.3 g (44.3 ± 38.2%), SNAQ outperformed the estimation accuracy of patients and Calorie Mama (both P > .05). Error consistency (quantified by the within-participant SD) did not significantly differ between the methods. SNAQ may provide effective CHO estimation support for people with T1D, particularly those with large or inconsistent CHO estimation errors. Its impact on glucose control remains to be evaluated.

Expert Panel Recommendations for a Standardized Ambulatory Glucose Profile Report for Connected Insulin Pens.

Connected insulin pens capture data on insulin dosing/timing and can integrate with continuous glucose monitoring (CGM) devices with essential insulin and glucose metrics into a single platform. Standardization of connected insulin pen reports is desirable to enhance clinical utility with a single report. An international expert panel was convened to develop a standardized connected insulin pen report incorporating insulin and glucose metrics into a single, clinically useful report. An extensive literature review and identification of examples of current connected insulin pen reports was performed serving as the basis for creation of a draft of a standardized connected insulin pen report. The expert panel participated in three virtual standardization meetings and online surveys. The AGP Report: Connected Insulin Pen brings all clinically relevant CGM-derived glucose and connected insulin pen metrics into a single simplified two-page report. The first page contains the time in ranges bar, summary of key insulin and glucose metrics, the ambulatory glucose profile (AGP) curve, and detailed basal (long-acting) insulin assessment. The second page contains the bolus (mealtime and correction) insulin assessment periods with information on meal timing, insulin-to-carbohydrate ratio (ICR), average bolus insulin dose and number of days with bolus doses recorded. The report's second page contains daily glucose profiles with an overlay of the timing and amount of basal and bolus insulin administered. The AGP Report: Connected Insulin Pen is a standardized clinically useful report that should be considered by companies developing connected pen technology as part of their system reporting/output.

Improving glycemic control by transitioning from the MiniMedTM 640G to 770G in Japanese adults with type 1 diabetes mellitus: a prospective, single-center, observational study.

The effectiveness of a hybrid closed-loop (HCL) system in improving glycemic control is unclear in Japanese individuals. Therefore, we assessed the effect impact of the MiniMed 770G HCL system on glycemic control in this population. This prospective, single-center, 24-week observational study (registration number: UMIN000047394) enrolled 23 individuals with type 1 diabetes mellitus using the Medtronic MiniMed 640G system. The primary endpoint was the improvement in time in the range of 70-180 mg/dL after transitioning to the MiniMed 770G HCL system. We observed an increase in time in range (from 64.1 [55.8-69.5] to 70.9 [67.1-74.4] %, interquartile range 25-75%, p < 0.001) and a decrease in glycated hemoglobin level (from 7.4 [7.0-7.9] to 7.1 [6.8-7.4] %, p = 0.003). There was a significant reduction in time above the range (181-250 mg/dL: 25.8 [20.9-28.6] to 19.5 [17.1-22.1] %, p < 0.001; >251 mg/dL: 8.7 [4.0-13.0] to 4.7 [3.6-9.1] %, p < 0.001). Time below the range remained unchanged (54-69 mg/dL: 1.8 [0.4-2.4] to 2.1 [0.4-3.9] %, p = 0.24; <54 mg/dL: 0.2 [0.0-1.0] to 0.5 [0.1-1.3] %, p = 0.14). In a subgroup of 12 patients with a high HCL implementation rate, the basal insulin infusion decreased immediately after mealtime insulin administration and increased after approximately 120 minutes. The ratings from questionnaires assessing treatment burden, satisfaction, and quality of life remained unchanged. The MiniMed 770G HCL system improved glycemic control and optimized insulin delivery, particularly in patients with high implementation rates.

Advanced decision support system for individuals with diabetes on multiple daily injections therapy using reinforcement learning and nearest-neighbors: In-silico and clinical results

Many individuals with diabetes on multiple daily insulin injections therapy use carbohydrate ratios (CRs) and correction factors (CFs) to determine mealtime and correction insulin boluses. The CRs and CFs vary over time due to physiological changes in individuals' response to insulin. Errors in insulin dosing can lead to life-threatening abnormal glucose levels, increasing the risk of retinopathy, neuropathy, and nephropathy. Here, we present a novel learning algorithm that uses Q-learning to track optimal CRs and uses nearest-neighbors based Q-learning to track optimal CFs. The learning algorithm was compared with the run-to-run algorithm A and the run-to-run algorithm B, both proposed in the literature, over an 8-week period using a validated simulator with a realistic scenario created with suboptimal CRs and CFs values, carbohydrate counting errors, and random meals sizes at random ingestion times. From Week 1 to Week 8, the learning algorithm increased the percentage of time spent in target glucose range (4.0 to 10.0 mmol/L) from 51 % to 64 % compared to 61 % and 58 % with the run-to-run algorithm A and the run-to-run algorithm B, respectively. The learning algorithm decreased the percentage of time spent below 4.0 mmol/L from 9 % to 1.9 % compared to 3.4 % and 2.3 % with the run-to-run algorithm A and the run-to-run algorithm B, respectively. The algorithm was also assessed by comparing its recommendations with (i) the endocrinologist's recommendations on two type 1 diabetes individuals over a 16-week period and (ii) real-world individuals' therapy settings changes of 23 individuals (19 type 2 and 4 type 1) over an 8-week period using the commercial Bigfoot Unity Diabetes Management System. The full agreements (i) were 89 % and 76 % for CRs and CFs for the type 1 diabetes individuals and (ii) was 62 % for mealtime doses for the individuals on the commercial Bigfoot system. Therefore, the proposed algorithm has the potential to improve glucose control in individuals with type 1 and type 2 diabetes.

Splitting Mealtime Insulin Doses for Mixed Fat and Protein Meals in Children and Adolescents with Type 1 Diabetes Using Multiple Daily Injection Regimen: A Randomized Cross-Over Trial

Aims. Assessment of the glycemic outcomes of increasing and splitting mealtime insulin doses for mixed fat and protein meals in pediatric patients with type 1 diabetes mellitus (T1DM) using multiple daily injection regimen and comparing the effects of regular insulin and fast-acting insulin on glycemic outcomes following those meals. Methods. This single-center, randomized, cross-over trial included 43 children and adolescents with T1DM randomly assigned to receive three interventional insulin doses for lunch meals over 3 consecutive days; Intervention A (100% insulin-to-carbohydrate ratio (ICR) dose given as premeal insulin lispro with an additional insulin sensitivity factor-calculated correction dose after 3 hr), Intervention B (130% ICR dose split into 60% premeal insulin lispro and 40% postmeal insulin lispro after 30 min), and Intervention C (130% ICR dose split into 60% premeal insulin lispro and 40% postmeal regular insulin after 30 min). The test meal consisted of two slices of pizza (weight: 150 g, carbohydrates: 40 g, fat: 15 g, protein: 20 g, and calories: 380 kcal). Postprandial blood glucose levels were monitored for 6 hr. Results. There were no significant differences in postprandial blood glucose excursions following the three interventions. However, Intervention C had a significantly lower late (3–6 hr) blood glucose area under the curve ( p = 0.01 ). Postprandial hypoglycemia developed in 12 participants (27.9%) following Interventions A and B and in 17 participants (39.5%) following Intervention C ( p = 0.32 ). Conclusions. Using regular insulin as a postmeal portion of increased and split insulin doses provided better late postprandial glycemic outcomes following mixed fat and protein meals. However, the amount of additional insulin used needs optimization to reduce the frequency of postprandial hypoglycemia. This trial is registered with NCT04783376.

THU366 Type 1 Diabetes Complicated By Multiple Episodes Of Diabetic Ketoacidosis Secondary To Flares Of Hidradenitis Suppurativa

Abstract Disclosure: S.R. Vasavada: None. K.A. Chopra: None. L. Philipson: Grant Recipient; Self; Novo Nordisk. Background: Hidradenitis suppurativa (HS) is an inflammatory skin condition of the pilosebaceous unit characterized by subcutaneous nodules that if untreated can form purulent abscesses, fistulae, and sinus tracts. HS may result from dysregulated autoimmune response to skin flora with overexpression of inflammatory cytokines, such as IL-17A, TNF-a, IL-1B (Shah et al 2017). Although HS and type 1 diabetes both share underlying autoimmune etiologies, and autoimmune diseases have been reported in higher frequencies in HS than controls, co-incidence with type 1 diabetes is extremely rare (Straalen et al 2022). Herein, we describe a case of a patient with type 1 diabetes with recurrent admissions for diabetic ketoacidosis (DKA) secondary to HS flares. Clinical Case: 37-year-old female with medical history of type 1 diabetes, hypogammaglobulinemia, and HS presented with rectal pain and hematochezia. Previously, she had several hospitalizations due to HS flares complicated by episodes of DKA and 20+ corrective surgeries for infected HS lesions. Prior to admission, patient was treated with clindamycin lotion, spironolactone, and weekly adalimumab for HS. Patient’s initial labs showed DKA with glucose 494 mg/dL (RR 60-99 mg/dL), bicarbonate 21 mmol/L (RR 23-30 mmol/L), anion gap 16 mmol/L (RR 6-15 mmol/L), and beta hydroxybutyrate level 1.44 mmol/L (N &amp;lt;0.3 mmol/L). Hemoglobin A1c was 10.4% (RR &amp;lt;5.7%). Physical exam showed Hurley Stage 2 HS with multiple atrophic scars, boils, and double comedones on bilateral axillae. She was treated with insulin infusion and IV fluids. After anion gap closed and bicarbonate improved to 24 mmol/L (RR 23-30 mmol/L), she transitioned to regimen of insulin glargine 38 units and started mealtime insulin lispro using a ratio of 1 unit of lispro for 6 grams of carbs. Subsequent glucose values stabilized, ranging 120-200 mg/dL (RR 60-99 mg/dL) during hospitalization. She underwent colonoscopy due to concern for colonic involvement of HS, however pathology was normal. After multidisciplinary discussion with endocrinology and dermatology specialists, HS treatment with prednisone was avoided due to concern of worsening patient’s glycemic control. Patient started infliximab treatment and reported mild symptom improvement. Conclusion: This case showing a patient with multiple episodes of DKA triggered by flares of HS has demonstrated the importance of further study to improve our current understanding of the potential overlap of these two conditions to help guide future treatment decisions and improve patients’ overall quality of life. Reference: Shah A, Alhusayen R, Amini-Nik S. The critical role of macrophages in the pathogenesis of hidradenitis suppurativa. Inflamm Res. 2017;66(11):931-945. Straalen KR van, Prens EP, Gudjonsson JE (2022) Insights into hidradenitis suppurativa. J Allergy Clin Immun 149(4):1150–1161. Presentation: Thursday, June 15, 2023

Mealtime Insulin BOLUS Score More Strongly Predicts HbA1c Than the Self-Care Inventory in Youth With Type 1 Diabetes.

To meet their glycated hemoglobin (HbA1c) goals, youth with type 1 diabetes (T1D) need to engage with their daily T1D treatment. The mealtime insulin Bolus score (BOLUS) is an objective measure of youth's T1D engagement which we have previously shown to be superior to other objective engagement measures in predicting youth's HbA1c. Here, to further assess the BOLUS score's validity, we compared the strengths of the associations between youth's HbA1c with their mean insulin BOLUS score and a valid, self-report measure of T1D engagement, the Self-Care Inventory (SCI). One-hundred and five youth with T1D self-reported their T1D engagement using the SCI. We also collected two weeks of insulin pump data and a concurrent HbA1c level. We scored youth's SCI and calculated their mean insulin BOLUS score using standardized methods. For the analyses, we performed simple correlations, partial correlations, and multiple regression models. Youth had a mean age of 15.03 ± 1.97 years, mean time since diagnosis of 8.11 ± 3.26 years, and a mean HbA1c of 8.78 ± 1.49%. The sample included n = 58 boys (55%) and n = 96 families (91%) self-identified as white. Simple correlations between youth's age, HbA1c, SCI total score, and BOLUS score were all significant. Partial correlation and regression models revealed that youth's insulin BOLUS score was more strongly associated with HbA1c than the SCI. Youths' BOLUS score has better concurrent validity with HbA1c than the SCI. We should consider reporting the BOLUS score as an outcome metric in insulin pump data reports.

804-P: Similar Hypoglycemia Duration with Once-Weekly Icodec vs. Degludec or Glargine U100 in Insulin-Treated T2D—A Post Hoc CGM Analysis from ONWARDS 2 and 4

Once weekly (OW) icodec is a basal insulin in development. Hypoglycemia duration during the switch (weeks 0-4) and steady state (weeks 22-26) periods from two phase 3, randomized, treat-to-target trials in T2D was investigated, using double-blinded Dexcom G6 CGM. Insulin-treated individuals were randomized to OW icodec or once-daily (OD) degludec (ONWARDS 2), or OW icodec or OD glargine U100 with mealtime insulin aspart (ONWARDS 4). When switching, a one-time only additional 50% icodec dose was administered. Basal insulins were titrated weekly. Median hypoglycemia &amp;lt;70 mg/dL duration for episodes lasting ≥ 15 minutes and the proportion of such episodes spent &amp;lt;54 mg/dL were assessed. Median duration of hypoglycemia &amp;lt;70 mg/dL was similar between icodec and comparators during switch and at steady state (Figure), with no apparent clustering in either time-period. At steady state (icodec/degludec and icodec/glargine U100), of the episodes &amp;lt;70 mg/dL, 66.6/63.9% and 60.4/60.0% spent no time &amp;lt;54 mg/dL; 23.2/26.6% and 29.2/28.8% included episodes &amp;lt;54 mg/dL for ≥15 minutes; and 10.2/9.5% and 10.4/11.2% included episodes &amp;lt;54 mg/dL for &amp;lt;15 minutes, respectively. In insulin-treated T2D, the duration of hypoglycemic episodes &amp;lt;70 mg/dL was similar, with no apparent clustering, during switch and at steady state for OW icodec versus OD degludec or glargine U100. Disclosure H.S.Bajaj: Research Support; Amgen Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Anji Pharmaceuticals, Eli Lilly and Company, Kowa Company, Ltd., Novo Nordisk, Pfizer Inc., Sanofi, Tricida, Inc. B.Ásbjörnsdóttir: Employee; Novo Nordisk. L.Carstensen: Employee; Novo Nordisk A/S, Stock/Shareholder; Novo Nordisk A/S. L.Lang lehrskov: Employee; Novo Nordisk A/S, Stock/Shareholder; Novo Nordisk A/S. C.Mathieu: Advisory Panel; Novo Nordisk A/S, Boehringer Ingelheim Inc., Eli Lilly and Company, Medtronic, Vertex Pharmaceuticals Incorporated, Roche Diabetes Care, Imcyse, Speaker's Bureau; Novo Nordisk A/S, AstraZeneca, Boehringer Ingelheim Inc., Eli Lilly and Company, Medtronic, Vertex Pharmaceuticals Incorporated. A.Philis-tsimikas: Advisory Panel; Dexcom, Inc., Novo Nordisk A/S, Sanofi, Other Relationship; Medtronic, Research Support; Novo Nordisk A/S, Lilly, Viking Therapeutics, NIH - National Institutes of Health. T.Battelino: Advisory Panel; Eli Lilly and Company, Novo Nordisk, Sanofi, Medtronic, Abbott Diabetes, Consultant; Indigo Diabetes, Research Support; Novo Nordisk, Sanofi, Medtronic, Novartis, Speaker's Bureau; Eli Lilly and Company, Novo Nordisk, Sanofi, Medtronic, Abbott Diabetes, Dexcom, Inc. Funding Novo Nordisk A/S

819-P: Impact of Meal Bolus Timing and Bedtime Snacking on Glycemic Control in Hospitalized Patients

Background: Basal-bolus insulin is the standard of care to treat hyperglycemia in hospitalized patients in the non-ICU setting. Matching insulin with food is a barrier to achieving blood glucose (BG) goals. The glycemic impact of a snack at bedtime without prandial insulin and delayed meal-time bolus in the hospital has not been previously explored. Methods: The InFi study is an ongoing randomized controlled open-label trial comparing Fiasp vs aspart in hospitalized patients using the Dexcom G6 PRO CGM to assess postmeal glycemic outcomes. We performed an interim analysis of 100 subjects to assess the impact of bedtime snacks on fasting POC glucose (FG) and the impact of delayed meal bolus on postprandial sensor glucose (PPSG) time in range (TIR) 70-180 mg/dL. Meal intake was determined by a CGM heuristic, insulin bolus time by barcoded EMR. Results: Four hour post-meal TIR was 54% for on-time boluses (n=119) vs 25% with bolus delay of &amp;gt;5 minutes (n=86), p &amp;lt;0.001. Evening snacking (9pm-12am) was associated with higher FG levels, 201 vs 158 mg/dL (N=30, 50), p = 0.03. Conclusion: Delayed meal-time insulin bolusing is common in hospitalized patients and results in a significant reduction in post-meal TIR. Evening snacking is a significant cause of overnight hyperglycemia. Given the importance of BG control, hospitals should work to optimize meal insulin delivery and develop strategies to address bedtime food intake. Disclosure S.Alexanian: Research Support; Novo Nordisk. M.C.Cheney: None. J.Bello ramos: None. N.L.Spartano: Research Support; Novo Nordisk. H.Wolpert: Consultant; Abbott Diabetes, Employee; Eli Lilly and Company. D.W.Steenkamp: Research Support; Abbott Diabetes, Novo Nordisk. Funding Novo Nordisk (ISS-001295)

The Burden and Impacts of Mealtime Insulin from the Perspective of People with Diabetes

While there have been continued advances in insulin treatment for diabetes since the discovery of insulin 100years ago, some unmet needs still remain, including those related to mealtime insulin (MTI). The objective of this study was to explore the impacts related to MTI and the relative burden of the impacts on people with diabetes. This study was conducted across two phases, namely, a qualitative and quantitative phase. People with type 1 and 2 diabetes using MTI in the USA and UK were recruited for the study. The qualitative phase involved 30 interviews to explore the impacts associated with MTI. Based on the results of the qualitative phase, a list of impacts was developed to evaluate the importance of MTI impacts using best-worst scaling. A total of 30 participants completed interviews, and 336 completed the quantitative phase. Participants described a range of impacts associated with MTI, including psychological (72.0%), social (63.0%), work/school (53.8%), and sleep (51.7%). Impacts for the quantitative phase were categorized under the following domains: diabetes distress, diabetes management, work productivity, and social. The three most burdensome impacts were related to diabetes distress, but the diabetes management domain contributed more than diabetes distress to the relative burden. There were minor differences in the relative importance of impacts by diabetes type, diabetes duration, and experience with continuous glucose monitoring. This study confirms that people with diabetes using MTI still have an array of unmet needs, including those related to the management of their diabetes and the emotional distress of having diabetes. These findings may be useful for healthcare provider (HCP)-patient interactions to ensure HCPs are allowing patients an opportunity to discuss their experiences with MTI.

A Personalized and Adaptive Insulin Bolus Calculator Based on Double Deep Q- Learning to Improve Type 1 Diabetes Management.

Mealtime insulin dosing is a major challenge for people living with type 1 diabetes (T1D). This task is typically performed using a standard formula that, despite containing some patient-specific parameters, often leads to sub-optimal glucose control due to lack of personalization and adaptation. To overcome the previous limitations here we propose an individualized and adaptive mealtime insulin bolus calculator based on double deep Q-learning (DDQ), which is tailored to the patient thanks to a personalization procedure relying on a two-step learning framework. The DDQ-learning bolus calculator was developed and tested using the UVA/Padova T1D simulator modified to reliably mimic real-world scenarios by introducing multiple variability sources impacting glucose metabolism and technology. The learning phase included a long-term training of eight sub-population models, one for each representative subject, selected thanks to a clustering procedure applied to the training set. Then, for each subject of the testing set, a personalization procedure was performed, by initializing the models based on the cluster to which the patient belongs. We evaluated the effectiveness of the proposed bolus calculator on a 60-day simulation, using several metrics representing the goodness of glycemic control, and comparing the results with the standard guidelines for mealtime insulin dosing. The proposed method improved the time in target range from 68.35% to 70.08% and significantly reduced the time in hypoglycemia (from 8.78% to 4.17%). The overall glycemic risk index decreased from 8.2 to 7.3, indicating the benefit of our method when applied for insulin dosing compared to standard guidelines.

Gaps Remain for Achieving HbA1c Targets for People with Type 1 or Type 2 Diabetes Using Insulin: Results from NHANES 2009-2020.

Glycated hemoglobin A1c (HbA1c) is an important measure to assess glycemic control and predict diabetes complications. However, there is limited information on trends in HbA1c among people with diabetes (PwDs) who use insulin. The aim of this study was to describe trends in HbA1c among PwDs who use insulin by diabetes type and insulin regimen. A retrospective analysis was conducted using data from the National Health and Nutrition Examination Survey (NHANES, 2009-2020). PwDs were classified into three cohorts: type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus using mealtime insulin (T2DM-MTI), and type 2 diabetes mellitus (T2DM) using basal-only insulin (T2DM basal-only). Trends in HbA1c over time were assessed using regression analysis after adjusting for age, gender, and race/ethnicity. Mean HbA1c values aggregated over 2009-2020 were 8.0% (T1DM), 8.6% (T2DM-MTI), and 8.6% (T2DM basal-only). The American Diabetes Association-recommended target of HbA1c of < 7% was achieved by 25.2% of people in the T1DM and T2DM-MTI groups each and by 12.3% of people in the T2DM basal-only group. Over time, an upward trend was observed in the percentage of people achieving HbA1c < 7% in the T2DM basal-only group. The percentage of PwDs achieving individualized HbA1c targets was 27.0%, 12.4%, and 16.1% for the T1DM, T2DM-MTI, and T2DM basal-only groups, respectively. Our study using NHANES data suggests that approximately 25% of PwDs achieve glycemic targets. This study highlights the need for improved therapies to better manage glycemic targets in PwDs.

Effects of postprandial exercise on blood glucose levels in adults with type 1 diabetes: a review.

People with type 1 diabetes experience challenges in managing blood glucose around exercise. Previous studies have examined glycaemic responses to different exercise modalities but paid little attention to participants' prandial state, although this is an important consideration and will enhance our understanding of the effects of exercise in order to improve blood glucose management around activity. This review summarises available data on the glycaemic effects of postprandial exercise (i.e. exercise within 2 h after a meal) in people with type 1 diabetes. Using a search strategy on electronic databases, literature was screened until November 2022 to identify clinical trials evaluating acute (during exercise), subacute (≤2 h after exercise) and late (>2 h to ≤24 h after exercise) effects of postprandial exercise in adults with type 1 diabetes. Studies were systematically organised and assessed by exercise modality: (1) walking exercise (WALK); (2) continuous exercise of moderate intensity (CONT MOD); (3) continuous exercise of high intensity (CONT HIGH); and (4) interval training (intermittent high-intensity exercise [IHE] or high-intensity interval training [HIIT]). Primary outcomes were blood glucose change and hypoglycaemia occurrence during and after exercise. All study details and results per outcome were listed in an evidence table. Twenty eligible articles were included: two included WALK sessions, eight included CONT MOD, seven included CONT HIGH, three included IHE and two included HIIT. All exercise modalities caused consistent acute glycaemic declines, with the largest effect size for CONT HIGH and the smallest for HIIT, depending on the duration and intensity of the exercise bout. Pre-exercise mealtime insulin reductions created higher starting blood glucose levels, thereby protecting against hypoglycaemia, in spite of similar declines in blood glucose during activity between the different insulin reduction strategies. Nocturnal hypoglycaemia occurred after higher intensity postprandial exercise, a risk that could be diminished by a post-exercise snack with concomitant bolus insulin reduction. Research on the optimal timing of postprandial exercise is inconclusive. In summary, individuals with type 1 diabetes exercising postprandially should substantially reduce insulin with the pre-exercise meal to avoid exercise-induced hypoglycaemia, with the magnitude of the reduction depending on the exercise duration and intensity. Importantly, pre-exercise blood glucose and timing of exercise should be considered to avoid hyperglycaemia around exercise. To protect against late-onset hypoglycaemia, a post-exercise meal with insulin adjustments might be advisable, especially for exercise in the evening or with a high-intensity component.

Insulin-to-carbohydrate ratios: An overview for nurses.

Carbohydrate counting is an efficacious technique to safely achieve glycemic targets and improve outcomes for patients using meal-time insulin. This article provides nurses with the knowledge and skills to assist and support their patients. It also reviews how to evaluate glycemic control and provides guidelines for referral to diabetes education programs.

A Head-to-Head Comparison of Two Algorithms for Adjusting Mealtime Insulin Doses Based on CGM Trend Arrows in Adult Patients with Type 1 Diabetes: Results from an Exploratory Study.

Continuous glucose monitoring (CGM) users are encouraged to consider trend arrows before injecting a meal bolus. We evaluated the efficacy and safety of two different algorithms for trend-informed bolus adjustments, the Diabetes Research in Children Network/Juvenile Diabetes Research Foundation (DirectNet/JDRF) and the Ziegler algorithm, in type 1 diabetes. We conducted a cross-over study of type 1 diabetes patients using Dexcom G6. Participants were randomly assigned to either the DirectNet/JDRF or the Ziegler algorithm for two weeks. After a 7-day wash-out period with no trend-informed bolus adjustments, they crossed to the alternative algorithm. Twenty patients, with an average age of 36 ± 10 years, completed this study. Compared to the baseline and the DirectNet/JDRF algorithm, the Ziegler algorithm was associated with a significantly higher time in range (TIR) and lower time above range and mean glucose. A separate analysis of patients on CSII and MDI revealed that the Ziegler algorithm provides better glucose control and variability than DirectNet/JDRF in CSII-treated patients. The two algorithms were equally effective in increasing TIR in MDI-treated patients. No severe hypoglycemic or hyperglycemic episode occurred during the study. The Ziegler algorithm is safe and may provide better glucose control and variability than the DirectNet/JDRF over a two-week period, especially in patients treated with CSII.

Making sense of weekly insulins

The current issue of The Lancet Diabetes & Endocrinology sees publication of a phase 2 study of the weekly insulin under development from Eli Lilly. 1 Frias J Chien J Zhang Q et al. Safety and efficacy of once-weekly basal insulin Fc in people with type 2 diabetes previously treated with basal insulin: a multicentre, open-label, randomised, phase 2 study. Lancet Diabetes Endocrinol. 2023; (published online Feb 6.)https://doi.org/10.1016/S2213-8587(22)00388-6 Google Scholar Phase 2 studies have also been published from Novo Nordisk, who have further announced top-line results of a series of phase 3 studies to investors. 2 Rosenstock J Bajaj HS Janež A et al. Once-weekly insulin for type 2 diabetes without previous insulin treatment. N Engl J Med. 2020; 383: 2107-2116 Crossref PubMed Scopus (77) Google Scholar Once-daily basal insulin is the standard starter regimen in people with type 2 diabetes, 3 Davies MJ Aroda VR Collins BS et al. Management of hyperglycaemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia. 2022; 65: 1925-1966 Crossref PubMed Scopus (20) Google Scholar and experience with other once-weekly injectables in people with type 2 diabetes, notably of GLP-1 receptor agonists, 4 Holleman C Hopcroft A Close K 3Q22 GLP-1 industry roundup. www.closeconcerns.com/knowledgebase/r/db4d2bb8Date: Nov 15, 2022 Date accessed: December 2, 2022 Google Scholar is of market preference over once-daily preparations; it is probable that clinical practice will adopt licensed weekly insulins very quickly. Weekly basal insulin might be of less relevance to people with type 1 diabetes, for whom multiple meal-time insulin doses will still be needed. Safety and efficacy of once-weekly basal insulin Fc in people with type 2 diabetes previously treated with basal insulin: a multicentre, open-label, randomised, phase 2 studyWeekly BIF achieved a similar efficacy compared with degludec despite higher fasting glucose targets in the BIF groups. Higher fasting glucose targets and lower glucose variability might have contributed to lower hypoglycaemia rates for BIF compared with degludec. These findings support continued development of BIF as a once-weekly insulin treatment for people with diabetes. Full-Text PDF

Fast-acting insulin aspart in pediatric type 1 diabetes mellitus patients in a tertiary care center: Indian experience

Background: The objective of this retrospective study was to evaluate the effectiveness and safety of fast-acting insulin aspart with additional drug excipients (L-arginine and niacinamide) in the Indian pediatric population. Methods: Data of pediatric type 1 diabetes mellitus (T1DM) outpatients in the age group of 1 to 18 years on treatment with injection degludec as long-acting Insulin OD and faster aspart as rapid-acting mealtime insulin 5-minutes before the meal for 20-weeks, was collected from the medical records of subjects. The primary endpoint was the mean change in glycated hemoglobin (HbA1c) and the secondary endpoints were mean changes in fasting plasma glucose (FPG) and 1 and 2-hour postprandial glucose (PPG), from baseline to 20-weeks post-treatment. The safety of treatment was also evaluated. Results: Data of 30 pediatric patients (Male: Female-14:16) with a mean age of 7.98 years was considered for this retrospective data analysis. Compared to baseline, there was a significant decline (p&lt;0.001) in mean HbA1c levels by -0.72, in FPG by -32.87 mg/dl, in 1-hour PPG levels by -8.57 mg/dl, and 2-hour PPG levels by -11.3 mg/dl, after 20-weeks of treatment. Three and two patients reported symptomatic undocumented hypoglycemia and symptomatic documented hypoglycemia respectively, and one patient each reported local site reaction, and lipodystrophy. No episodes of nocturnal hypoglycemia were reported. Conclusions: In Indian pediatric T1DM patients 20-weeks mealtime faster aspart along with insulin degludec provided effective glycemic control, and treatment resulted in lower HbA1c, FPG, and 1 and 2-hour PPG levels. Conclusions: In Indian pediatric T1DM patients 20-weeks mealtime faster aspart along with insulin degludec provided effective glycemic control, and treatment resulted in lower HbA1c, FPG, and 1 and 2-hour PPG levels.

Prolonged remission in latent autoimmune diabetes of adults (LADA): Is insulin resistance a major influence?

Abstract Introduction Type 1 diabetes mellitus (T1DM) is a chronic inflammatory disease that courses with high serum glucose levels as a result of pancreatic beta cell destruction and subsequent insulinopenia. LADA is a type of autoimmune diabetes where damage to the beta cell occurs much slower. The natural history of type 1 diabetes is very heterogeneous and variable. This is especially true for LADA with several possible different clinical courses due to a wider variety of pancreatic cell destruction and insulin resistance. Clinically overt diabetes ensues when more than 80% of pancreatic cell mass is loss. After treatment initiation partial disease remission is common, especially in children. However complete remission is rare, and remission lasting for over a year is even rarer, with few reports published in literature. Some agents such as vitamin D and DPP4 inhibitors have been presented has having potential immunomodulatory effects. Clinical Case A 36-year-old man with grade 1 obesity (BMI 33 kg/m2) presented at the emergency department with symptoms of insulinopenia (polyuria and polydipsia in the previous 3 months) and hyperglycemia (capillary blood glucose &amp;gt;500mg/dL). Ketonemia was negative and pH was normal on blood gas analysis The diagnosis of diabetes mellitus was made and insulin therapy was instituted on a basal-bolus regimen. At the first follow-up appointment, due to his morphotype and familiar history of type 2 diabetes (mother diagnosed at 52 years of age), he stopped short-acting insulin and was started on metformin and SGLT2 inhibitor. A week later he was admitted in the hospital in euglycemic ketoacidosis. Initial workup revealed positive anti-GAD 41.8 U/mL, HbA1C 9.8%, C-peptide 1.83 ng/mL, serum insuline 17.4 uU/mL. Consequently, metformin and SGLT2 inhibitor therapy was stopped, and the patient resumed basal bolus insulin regimen. He then remained under a basal insulin without need of meal-time insulin bolus, progressively lowering the basal insulin dose until suspension four months later. Simultaneously, lifestyle changes were implemented with significant weigh loss (BMI 33 &amp;gt; 26.4 kg/m2 at the time of insulin suspension). After 3 years of follow-up the patient remains without need of antidiabetic therapy, with normal Hba1c 5.3%. Anti-GAD antibodies remain positive (39.4 U/mL) but C-peptide and serum insulin are within the reference range (1.69 ng/mL [1.1–4–4], 6.9uU/mL [2.6–25], respectively). Conclusion Prolonged disease remission in type 1 diabetes is rare. This case highlights an especially long “honeymoon” period in a patient with LADA. Obesity and insulin resistance probably played a role in the initial patient presentation, and its improvement probably helps to justify this prolonged remission. In spite of the family history of diabetes, other types of diabetes seem unlikely due to positive antibodies and SGLT2 inhibitor associated euglycemic ketoacidosis.