Insulin Requirements Research Articles

Abstract #1184998: A Case of using U-500 During Pregnancy for Optimal Glycemic Control

Insulin resistance is a common and challenging complication faced by many women during pregnancy. Due to severe resistance, patients can have very high insulin requirements making its management challenging for physicians. This has been a well-established phenomenon due to the human placental lactogen which decreases insulin sensitivity in pregnant women. U-500 regular insulin is a concentrated insulin used in patients with high insulin requirements however its use during pregnancy has not been fully established. We present a case of a pregnant female who was insulin naive prior to pregnancy, who was successfully managed with U-500 to achieve optimal glycemic control. A 24 year old woman with history of Type 2 diabetes (controlled by diet alone) presented to her endocrinologist at 8 weeks gestation. Her last Hemoglobin A1c prior to pregnancy was 7.1%. Due to elevated fasting blood sugars, she was initially started on Metformin 1 gram twice a day along with Glargine 10 units daily. Due to persistently elevated fasting and post prandial blood sugars, meal time insulin was also initiated using Lispro. Patient’s insulin had to be gradually up titrated to 100 units daily in her first trimester using the traditional basal bolus regimen. She continued to have increasing insulin requirements, peaking at 300 units in the third trimester with the abovementioned basal bolus regimen. The decision was made to switch patient to U-500 to assist with glucose optimization. With the use of U-500, patient was able to maintain the required tight pregnancy blood glucose goals. For the remainder of her pregnancy, she stayed on U-500 100 units thrice daily. Patient eventually delivered a 6 pound healthy baby without any complications. Post-partum, patient’s insulin requirements improved significantly within the first two weeks and was taken off all insulin. She continues to remain well controlled on only Metformin 1g twice a day. The use of U-500 is typically for patients requiring more than 200 units of insulin daily. There have not been enough studies with the use of U-500 in the pregnant population. We present a case where U-500 was safely used in a pregnant woman in the setting of extreme insulin resistance for a safe and healthy pregnancy. Furthermore, to our knowledge there have been no cases showing the use of U-500 during pregnancy with complete resolution of insulin requirement post-partum. Our case demonstrates that U-500 can be considered in clinical trials for further assessment of its safety and efficacy in pregnant subjects with severe insulin resistance.

An Exercise‐Driven, Insulin‐Independent Glucose Uptake Pathway in Contracting Skeletal Muscle

Glucose uptake by skeletal muscles, which import and store up to 80% of circulating glucose, plays a major role in glucose homeostasis. Prior research has focused largely on the insulin regulated GLUT4 transporter, which mediates glucose uptake in quiescent (non‐contracting) muscles using a canonical insulin‐dependent translocation mechanism. An ongoing paradox in the field is that actively contracting muscles take up glucose at 50‐100x greater rates than quiescent muscles, despite declining insulin levels. For this reason, exercise is a potent treatment for disorders of insulin insufficiency and insulin resistance. However, despite more than 30 years of study, the mechanism by which contracting muscles take up glucose without a requirement for insulin remains incompletely understood. It is proposed that GLUT4‐translocation occurs using signaling pathways that bypass the insulin receptor. However, no GLUT4 models have accounted for all the glucose taken up by contracting muscles or the great discrepancy between measured GLUT4 translocation (2‐fold increase in membrane density) and glucose uptake rate (50‐100‐fold increase), suggesting the existence of additional mechanisms. The goals of this study were to:i) develop a technology based on Inductively Coupled Plasma‐Mass Spectroscopy (ICP‐MS) that allows simultaneous detection of multiple transported species, including 13C‐labeled hexoses; and ii) test the hypothesis that contraction‐stimulated glucose uptake may be linked to Na,K‐ATPase (NKA) transport, which is also dramatically stimulated during muscle contraction. We measured uptake of Rb (a congener for K+), and 13C‐[6C]‐D‐glucose or 13C‐[6C]‐2‐deoxy glucose in isolated mouse EDL muscles stimulated to contract ex vivo. Muscles were obtained from WT mice. Glucose uptake was measured for 5 min at 32 C in a physiological solution containing 200 mM tracer RbCl and 11mM 13C glucose. Following uptake, the Rb and 13C content of the muscle were measured by ICP‐MS. We achieved a Limit of Detection of 54uM for 13C glucose in mouse muscle. This detection power for 13C by ICP‐MS is entirely new and was achieved by combining technical approaches: i) introduction of 13C‐based hexose substrates; ii) modifications to sample preparation that reduce background carbon; iii) ratiometric monitoring of the 13C/12C signal; and iv) 13C‐optimized instrument conditions. Contracting skeletal muscle took up 13C‐[6C]‐labeled‐D‐glucose at a rate of 10.8 mM/g‐min, and Rb at a rate of 1.2 mM/g‐min. The ability to detect glucose and other carbon‐based organic compounds by ICP‐MS is expected to advance studies of coupled transport and other biological processes that require multi‐species detection.

Deprescribing in type 2 diabetes and cardiovascular disease: Recommendations for safe and effective initiation of glucagon-like peptide-1 receptor agonists in patients on insulin therapy

Select glucagon-like peptide-1 (GLP-1) receptor agonists have demonstrated cardiovascular benefits in both primary and secondary prevention populations and are recommended in multiple guidelines for cardiovascular risk reduction in people with type 2 diabetes (T2D). Despite this, uptake of GLP-1 receptor agonists in clinical practice has been lagging. While the etiology of their underuse is multifactorial, lack of comfortability in adding a GLP-1 receptor agonist to established insulin regimens is a common barrier. Adjustments to basal and bolus insulin doses upon initiation of GLP-1 receptor agonists in trials have varied. When recommending empiric dose adjustments during initiation of GLP-1 receptors agonists, the most recent A1C and the current blood glucose levels, if available, should be taken into consideration. When initiating in a person being managed with basal-only insulin regimens, an empiric 20 % dose reduction is recommended if the baseline A1C is ≤8 %. For individuals using intensive insulin regimens, empiric dose reductions of up to 25 % in basal and 50 % in bolus therapy were implemented and summarized further in this review. Overall, initiation of GLP-1 receptor agonists can decrease insulin requirements and may permit deintensification of antihyperglycemic therapy through the reduction or discontinuation of bolus insulin therapy. As a result, this simplified regimen promotes increased adherence, reduces glycemic variability and hypoglycemia, and improves overall glycemic management and quality of life. This review aims to serve as a guide for clinicians to facilitate the initiation of GLP-1 receptor agonists and deintensification of insulin by providing suggested dose adjustments based on available literature.

Heterogeneity in phenotype, disease progression and drug response in type 2 diabetes.

Type 2 diabetes (T2D) is a complex chronic disease characterized by considerable phenotypic heterogeneity. In this study, we applied a reverse graph embedding method to routinely collected data from 23,137 Scottish patients with newly diagnosed diabetes to visualize this heterogeneity and used partitioned diabetes polygenic risk scores to gain insight into the underlying biological processes. Overlaying risk of progression to outcomes of insulin requirement, chronic kidney disease, referable diabetic retinopathy and major adverse cardiovascular events, we show how these risks differ by patient phenotype. For example, patients at risk of retinopathy are phenotypically different from those at risk of cardiovascular events. We replicated our findings in the UK Biobank and the ADOPT clinical trial, also showing that the pattern of diabetes drug monotherapy response differs for different drugs. Overall, our analysis highlights how, in a European population, underlying phenotypic variation drives T2D onset and affects subsequent diabetes outcomes and drug response, demonstrating the need to incorporate these factors into personalized treatment approaches for the management of T2D.

Identifying the Risk Group for Insulin Therapy in Patients with Gestational Diabetes

Aim: This study aims to determine the predictors of antenatal insulin therapy (AIT) in patients with gestational diabetes mellitus (GDM) who applied to the outpatient endocrine clinic of a tertiary hospital. Material and Methods: The study included 619 patients with GDM.Oral glucose tolerance test (OGTT), HbA1c (%), lipid levels, and other biochemical measurements of two groups (patients with or without insulin use) were compared with Mann-Whitney U or Student t-test. Demographic characteristics, obesity, and diet adherence were compared with the Chi-Square test. OGTT-75 measurements between the three insulin groups (basal, bolus or both uses) were compared with ANOVA. Results: In this study, 27.0% of the GDM patients needed insulin therapy. The insulin group had a significantly higher rate of obese, morbidly obese, and poor diet adherence patients than the MNT group and had significantly higher values measured in the 75-g OGTT (OGTT-75) for 0-h glucose, 2-h glucose, HbA1C (%), and triglyceride. In OGTT-75, all three measurement values (0-h, 1-h, 2-h glucose) above the cut-off were associated with insulin requirement. In OGTT-75, 2-h glucose value > 151.5 mg/dL (68.4% sensitivity and 60.0% specificity) predicted general need for insulin, and 0-h glucose value > 95.0 mg/dL (72.0% sensitivity and 69.0% specificity) predicted the need for basal AIT. Conclusion: We suggest identifying the risky group for insulin therapy at the time of diagnosis in GDM. Closer follow-up is required for the patients found to be in the risk group for insulin therapy.

Short-Term Effectiveness and Reduction in Insulin Requirements in Patients With Type 2 Diabetes Treated With IdegLira in a Real-World Setting.

BackgroundType 2 diabetes mellitus (T2DM) is a chronic, highly prevalent disease with a significant impact on health. Appropriate treatment requires effective and timely escalation to achieve metabolic control. To evaluate the effectiveness and safety of IDegLira on adults with T2DM previously treated with oral antidiabetics and/or insulin in a real-life setting.MethodsAn observational study in a real-world setting was conducted. Patients were selected from the outpatient clinic of two centers dedicated to specialized diabetes care. Main outcomes were HbA1c, body weight, insulin dose changes, hypoglycemia, and other adverse events.Results67 T2DM patients treated with IDegLira were monitored between 3 and 7 months. At the end of foll ow-up, the median change in HbA1c was -1.05% (CI95% -1.45, -0.65), and a decrease in insulin requirement was also observed (mean difference -10 TDD units (CI95% - 17 to -2.5). No treatment discontinuation was reported, hypoglycemia events were reported in 3 patients at the end of follow-up versus 8 patients at baseline.ConclusionsThis real-life study shows the effectiveness in glycemic control of IDegLira use in T2DM patients who do not achieve goals with other therapies, with an adequate safety profile. The findings need to be confirmed with evaluation of therapeutic results in larger cohorts.

Insulin Requirement and Complications Associated With Serum C-Peptide Decline in Patients With Type 1 Diabetes Mellitus During 15 Years After Diagnosis

ObjectiveC-peptide is conventionally used in assessing pancreatic function in patients with diabetes mellitus. The clinical significance of this molecule during the course of type 1 diabetes mellitus (T1DM) has been recently revisited. This study aimed to investigate the natural course of C-peptide in T1DM patients over the period of 15 years and analyze the association between the residual C-peptide and diabetes complications.MethodsThis retrospective study included a total of 234 children and adolescents with T1DM. Patient data including sex, age at diagnosis, anthropometric measures, daily insulin dose, serum HbA1c, post-prandial serum C-peptide levels, lipid profiles, and diabetic complications at the time of diagnosis and 1, 3, 5, 10, and 15 years after diagnosis were retrospectively collected.ResultsAmong the 234 patients, 101 were men and 133 were women, and the mean patient age at initial diagnosis was 8.3 years. Serum C-peptide decreased constantly since the initial diagnosis, and showed a significant decline at 3 years after diagnosis. At 15 years after diagnosis, only 26.2% of patients had detectable serum C-peptide levels. The subgroup with older patients and patients with higher BMI standard deviation score showed higher mean serum C-peptide, but the group-by-time results were not significant, respectively. Patients with higher serum C-peptide required lower doses of insulin and had fewer events of diabetic ketoacidosis.ConclusionSerum C-peptide decreased consistently since diagnosis of T1DM, showing a significant decline after 3 years. Patients with residual C-peptide required a lower dose of insulin and had a lower risk for diabetic ketoacidosis.

Glycated hemoglobin at diagnosis of type 1 diabetes and at follow-up in children and adolescents during the COVID-19 pandemic in Germany.

BackgroundThis study investigated the diagnostic delay and the subsequent quality of care during the Covid‐19 pandemic among children with new‐onset type 1 diabetes.MethodsWe compared the HbA1c levels of 3111 children at diagnosis of type 1 diabetes and of 2825 children at a median follow‐up of 4.7 months (interquartile range, 4.1–5.4) together with their daily insulin requirement during the Covid‐19 pandemic with the two previous years via multivariable linear regression, using data from the German Diabetes Registry DPV.ResultsDuring the Covid‐19 pandemic, HbA1c levels were higher at diagnosis of type 1 diabetes (mean estimated difference, 0.33% [95% confidence interval, 0.23–0.43], p < 0.001), but not at follow‐up (mean estimated difference, 0.02% [−0.02–0.07]). Children with diabetes onset during the Covid‐19 pandemic had a significantly higher daily insulin requirement after initiation of therapy (mean estimated difference, 0.08 U/kg [0.06–0.10], p < 0.001). Both the increase in HbA1c and daily insulin requirement were evident only after the first wave of the pandemic.ConclusionsThis increase in HbA1c at diagnosis of type 1 diabetes during the Covid‐19 pandemic may indicate a delay in seeking medical care due to the pandemic. However, this did not affect short‐term glycemic control. The increased insulin requirement at follow‐up could suggest a more rapid autoimmune progression during the pandemic.

Effectiveness of Intraoperative Versus Dedicated Islet Cell Laboratory Isolation for Total Pancreatectomy With Islet Autotransplant.

Background.Total pancreatectomy with islet autotransplantation (TPIAT) requires a complex islet isolation process of the explanted pancreas. Islet isolation has historically required a specialized laboratory to perform islet isolation. We report our experience with a novel technique of intraoperative islet isolation that does not require a specialized islet laboratory, thereby making the isolation process simpler, more accessible, and less costly.Methods.We performed a retrospective, comparative effectiveness analysis of 50 adult patients who underwent TPIAT from 2012 to 2020 (TPIAT with remote isolation [n = 20] versus intraoperative isolation of islet cells [n = 30]). The primary outcome was islet equivalents per body weight (IEQ/kg) for patients in each group.Results.Mean IEQ/kg‘s (4294 remote group versus 3015 intraoperative group, P = 0.06) and 1-y postoperative C-peptide levels (1.51 ng/mL remote group versus 0.91 ng/mL intraoperative group, P = 0.10) were not different between groups. Mean 1-y HbA1c levels (7.7% in the remote group versus 7.1% intraoperative group, P = 0.67) and 1-y insulin requirements (P = 0.31) were not statistically different. Lower average cost of hospitalization was seen in the intraoperative group, although this was not statistically significant ($104 398 remote versus $78 986 intraoperative, P = 0.81).Conclusions.Intraoperative islet isolation has similar effectiveness in regard to glycemic outcomes compared with the use of a dedicated islet cell isolation laboratory at a lower cost.

Long-term efficacy and safety of porcine islet macrobeads in nonimmunosuppressed diabetic cynomolgus macaques.

Although human islet transplantation has proven to provide clinical benefits, especially the near complete amelioration of hypoglycemia, the supply of human islets is limited and insufficient to meet the needs of all people that could benefit from islet transplantation. Porcine islets, secreting insulin nearly identical to that of human insulin, have been proposed as a viable supply of unlimited islets. Further, encapsulation of the porcine islets has been shown to reduce or eliminate the use of immunosuppressive therapy that would be required to prevent rejection of the foreign islet tissue. The goal of the current study was to determine the long-term safety and efficacy of agarose encapsulated porcine islets (macrobeads) in diabetic cynomolgus macaques, in a study emulating a proposed IND trial in which daily exogenous insulin therapy would be reduced by 50% with no loss of glucose regulation. Four of six animals implanted with macrobeads demonstrated ≥ 30% reduction in insulin requirements in year 1 of follow-up. Animals were followed for 2, 3.5, and 7.4 years with no serious adverse events, mortality or evidence of pathogen transmission. This study supports the continued pursuit of encapsulated porcine islet therapy as a promising treatment option for diabetes mellitus.

Selection of parenchymal preserving or total pancreatectomy with/without islet cell autotransplantation surgery for patients with chronic pancreatitis

BackgroundThe selection of surgery between parenchymal preserving (PPS) and total pancreatectomy (TP) with/without islet cell autotransplantation (IAT) for chronic pancreatitis (CP) patients varies based on multiple factors with a scarcity in literature addressing both at the same time. The aim of this manuscript is to present an algorithm for the surgery selection based on dominant area of disease, ductal dilatation, and glycemic control and compare outcomes. MethodsFrom 2017 to 2021, CP patients offered surgery at a single institution were retrospectively evaluated. Results51 patients underwent surgery (20 [39.2%] TPIAT, 4 [7.8%] TP, and 27 [52.9%] PPS – 9 Whipple procedures, 15 distal pancreatectomies, and 3 duct drainage procedures). No significant difference was observed in baseline characteristics or perioperative outcomes except median length of stay (8 days [IQR 6–10] vs. 13 days [IQR 9–15.5], p < 0.001), attributed to insulin requirement and education for TPIAT group. No differences in postoperative complications, such as clinically significant leak and intrabdominal fluid collection (3 [11.1%] vs 2 [10%], p = 1.0), hemorrhage (0 vs. 2 [10.0%], p = 0.2), delayed feeding (1 [3.7%] vs. 5 [25.0%], p = 0.07), or wound infection (4 [14.8%] vs. 0, p = 0.1) between PPS and TPIAT groups, respectively, were observed nor requirement of long-acting insulin at discharge (2 [15.4%] vs. 7 [43.8%], p = 0.1) for pre-operatively non-diabetic patients. No significant difference in weaning off narcotics and no mortality observed. ConclusionThe most appropriate selection of surgery based on the algorithm yields good and comparable outcomes.

IDF21-0533 Diabetes Mellitus in hospitalized COVID-19 patients – a retrospective cohort study

Background: Pre-existing diabetes in COVID-19 patients is considered an important and independent factor in the clinical severity of the infection, impacting the duration of hospital stay and prognosis. Furthermore, infected patients typically have altered glucose metabolism, which is reflected in higher daily insulin needs or newly-onset diabetes. Aim: To identify the correlation between the insulin needs in COVID-19 patients and hospital stay and other related medical conditions. To identify the factors that would contribute to diabetes onset during COVID-19 infection. Method: This is a retrospective cohort study analysing data from 96 COVID patients hospitalized between December 2020-March 2021. The cohort was stratified in 3 groups: patients already diagnosed with diabetes, patients with newly-onset diabetes, patients with no diabetes. Maximum total daily doses of Insulin (TDD) for each patient, based on glycemic profile, was calculated. Baseline characteristics, comorbidities and clinical prognosis, including hospital stay were also examined. Results: The participants age ranged from 28 to 84 years old (mean 62.6 years old). 64.6% of them (62/96 patients) had comorbidities prior to hospitalisation, with a predominance of cardiovascular diseases, mostly hypertension (51%). TDD varied from 0-132 UI/day (mean 19.4 UI/day, SD ±35.3). Only 26/96 patients were previously diagnosed with diabetes (17 on oral hypoglycemics and 9 on insulin), with a mean HbA1c 8.3 %. Patients with higher Insulin requirement had longer hospital stay (p 0.03) and compared to those with no diabetes, significantly more coexisting cardiovascular disease (p 0.01), including hypertension (p.0.02). In the group with unknown diabetes, 41/70 developed newly onset diabetes, with maximum TDD ranging from 12 to 130 UI/day (mean 55 UI/day, SD ±26.8). Higher HbA1c values in the day of admission were statistically correlated with longer hospital stay (p 0.01). Patients with newly-onset diabetes had significantly more coexisting cardiovascular disease (53.6% vs 24.1%, p 0.012) including hypertension (53.6% vs 24.1%, p 0.012). Also, we noticed longer hospital stay (p 0.07) using independent samples test. Discussion: Within the limits of our small cohort study, there are several points of interest. High insulin requirement determine hospital stay in diabetic patients, in correlation with cardiovascular comorbidities. The development of newly-onset diabetes is an area that needs further exploration. We pointed out that the patients with borderline HbA1c and related medical conditions are more predisposed to develop newly onset diabetes. It remains to be determined whether insulin requirement is due to insulin resistance as part of the systemic inflammation and critical illness or as a result of direct pancreatic beta-cell damage.

IDF21-0097 Concomitant COVID-19 Infection and Ketosis Prone Diabetes. Coincidence or Relationship? A Case Report

Background: Since the beginning of COVID 19 pandemic, great evidence has emerged regarding higher risk of coronavirus disease, its severity and complications in patients with type 2 diabetes mellitus (DM). Otherwise, it had been postulated that SARS-CoV-2 could induce severe metabolic decompensation of pre-existing or new-onset diabetes. In this report, we explore the possibility of COVID 19 induced diabetes. Results: Case presentation: A 39-year-old man was admitted to a tertiary referral hospital with a 10-day history of thirst, polyuria and feeling generally unwell. He referred fever and cough, and he had lost 3 kg in weight over the past 2 weeks. He did not report dyspnoea, abdominal pain or dysuria. There was no significant past medical history of note. Family history included type 2 diabetes in his mother and uncle. On examination, he was tired, tachycardic at 105 beats/min, had a temperature of 37.6°C, blood pressure of 125/70 mmHg, body mass index (BMI) 28.77 kg/m2 and respiratory rate of 28/min, with otherwise normal chest examination. Cardiac auscultation and abdominal palpation were normal. Arterial blood gas revealed a pH of 7.34, bicarbonate 19 mmol/L, PaO2 of 96 mmHg, PaCO2 of 41 mmHg. Serum glucose was 27.53 mmol/L with strong positive uric ketones. A chest X-ray was performed and reported as normal. He was sent for testing for COVID-19 with a positive result. He was initially managed with insulin intravenous infusion at around 0.1 U/kg/h and fluid and potassium replacement. He received antipyretic and analgesic drugs but no other therapy for COVID-19 infection as he had not respiratory symptoms. The diabetes study was completed in the conventional hospital ward. Haemoglobin A1c was 14.3%. C peptide was at lower limit of normal values and autoantibodies were negative. Those findings were sufficient to establish a diagnosis of ketosis-prone diabetes mellitus (KPDM). He underwent a good evolution and could start during the remaining hospitalization a subcutaneous basal-bolus insulin therapy. His insulin requirement was approximately 1.5 U/kg/d. He was finally discharged with an insulin regimen. During the next weeks of follow-up the insulin requirements were progressively lower so that the prandial insulin was retired, basal insulin dose was decreased and metformin was introduced finally achieving an appropriate metabolic control. Discussion: KPMD is a clinical entity characterized by an acute onset with severe hyperglycemia and ketosis similar to the presenting form of type 1 DM, but without its autoimmune component. Subsequently, its evolution resembles that of type 2 DM. This situation is caused by an acute, reversible dysfunction of the beta cell in individuals with insulin resistance. In our case, KPDM onset is occurring in a patient at the same time he was infected by coronavirus disease. We hypothesize that SARS-CoV-2 could perform a role when triggering the diabetes onset, as coronavirus can induce beta cell damage due to either its direct lytic effects and the host inflammatory response induced. However, there is not enough evidence to say if it was a trigger or simply COVID-19 infection and diabetes onset concurred at the same time.

IDF21-0203 A1C Target Attainment Without Hypoglycemia According to BMI: Insulin Glargine 300 U/mL vs 1st-Generation Basal Insulin

Background: High BMI is associated with insulin resistance and greater basal insulin (BI) requirements, which can lead to increased risk of hypoglycemia. The real-life, pragmatic, randomized ACHIEVE Control study (NCT02451137) demonstrated that among insulin-naive adults with T2D ≥1 year and A1C 8–11%, those who received the 2nd-generation BI analog glargine 300 U/mL (Gla-300) were significantly more likely to achieve individualized A1C targets (<8% for participants ≥65 years or with defined comorbidities; <7% for all others) without documented symptomatic (≤70 mg/dL) and/or severe hypoglycemia versus first-generation BI analogs (insulin glargine 100 U/mL; insulin detemir) at 6 months, with the trend continuing at 12 months. Aim: This post-hoc analysis of ACHIEVE Control explored the correlation between A1C target attainment without hypoglycemia with daily insulin dose according to BMI. Method: Participants were categorized according to baseline BMI (<30, 30–<35, 35–<40, ≥40 kg/m2). Proportions of participants achieving individualized A1C targets without documented symptomatic (≤70 and <54 mg/dL) and/or severe hypoglycemia; mean daily insulin doses at 6 and 12 months were estimated. Results: The <30 kg/m2 BMI group comprised individuals who were predominantly male (61 vs 42–58%), were older (61.7 vs 55.1–59.7 years), and had longer duration of T2D (12.6 vs 9.8–11.2 years) versus those with higher BMIs. Mean A1C was 9.1–9.2% across all BMI subgroups. Background medication use was generally well balanced, except for higher GLP-1 RA use as BMI increased. The proportion of individuals with the more stringent A1C goal of <7% increased as BMI increased, likely related to their younger age. Insulin dose at 12 months (U/kg/day) was similar across all BMI categories (range: 0.351–0.395). At both 6 and 12 months, a numerically higher proportion of participants who received Gla-300 versus 1st-generation BIs achieved their individualized A1C target without documented symptomatic (at both ≤70mg/dL and <54 mg/dL) or severe hypoglycemia (except for the ≥40 kg/m2 group at 6 months) (Table). Discussion: The results of this post-hoc analysis were consistent with those of the primary endpoint of the overall ACHIEVE Control study. The trend for benefit of Gla-300 versus 1st-generation BI for achievement of individualized A1C target without documented symptomatic and/or severe hypoglycemia at 12 months was consistent regardless of BMI.

IDF21-0544 Artificial Intelligence in Diabetes Care

Background: Artificial intelligence (AI) is making a paradigm shift in traditional diabetes care in terms of target achieving efficacy, excellent safety, best quality care, effective monitoring and improved quality of life for both patients with Type-1 diabetes (T1D) and Type-2 diabetes (T2D). All guidelines for adult and pediatric T1D suggest that target Glycated hemoglobin (HbA1c) should be less than 53 mmol/mol (7%) but very less percent population with T1D can achieve this target due to many factors namely individual variability of insulin requirements, fear of hypoglycemia, errors in insulin dose calculations, etc. These lead to poor glycemic control, diabetes complications and a major source of stress for families and care givers especially in pediatric populations. All these affects quality of life (QoL), mental well-being and productivity of patients. So, the emergence of AI in diabetes care has revolutionized the management of diabetes care in optimizing the glycemic control by extending the ‘Target In Range’ (TIR), reducing ‘Target Above Range’ (TAR), ‘Target Below Range’ (TBR) and minimizing severe hypoglycemia. Glucose monitoring by Self Monitoring Blood Glucose (SMBG) using smart glucometer or Ambulatory glucose profile (AGP), Continuous Glucose Monitoring System (CGMS), to name a few. AI is being used in delivering insulin by smart pens, Continuous Subcutaneous Insulin Infusion (CSII), recently introduced Hybrid Artificial Pancreas and with prolonged CGMS. Smart insulin pens namely InPen, Novo Pen 6, Novo Pen Echo Plus, etc. can calculate the bolus dose considering current glucose reading, target, carb intake, probable exercise, etc. by algorithm. Furthermore, it can record the amount and timing of each insulin dose, display the last dose and insulin onboard, and wirelessly transmit the information via Bluetooth to a dedicated mobile application and transfers data automatically on the cloud for sharing with health care professionals as well. Novo Pen 6 and Novo Pen Echo Plus use near-field communication technology. CGMS uses sensor to monitor blood glucose continuously for 14 days and shows results in real-time without using a needle which made the life of young children much comfortable. It calculates TIR, TAR, TBR and probable HbA1c in a graphic presentation. Now new models are in pipeline for much longer duration. Smart glucometers are incorporated with bolus advisors to calculate insulin dosages, algorithm-driven message response to each glucose reading. The Hybrid Close Loop artificial pancreas is the new generation of CSII which automatically determines the basal rates, can determine the bolus dose as per CGMS but this feature is still under trial and having other old generation basic and advanced features. The ongoing trials results will guide further improvements and eventually will lead complete AI based diabetes management. Aim: To see the scope, feasibility and critical role of AI in diabetes care. Method: Contemporary literature is being searched to get the latest information on AI use in diabetes care. Results: PubMed, MEDLINE, CINAHL Plus, EMBASE, Cochrane and Google Scholar is being searched with search words 'Artificial Intelligence AND Diabetes', 'Artificial Pancreas', Close Loop system', 'Smart Insulin Pen'. 312 articles were found and finally 34 were selected.

IDF21-0439 Type 2 Diabetes Mellitus History in the Prognosis of Hospitalized COVID-19 Patients – A Prospective Observational Study

Background: COVID-19 is found to affect Type 2 Diabetes Patients drastically. Aim: To evaluate the association between a known history of diabetes mellitus (DM) and its clinical outcomes in hospitalized COVID-19 diabetic patients. Method: This prospective cohort study categorized COVID-19 positive patients admitted to a secondary care hospital in South India into DM patients and Non-DM patients. Data regarding the past medical and medication history was collected on the day of admission and the patients were regularly followed up till discharge or death. The outcome measures including duration of hospital stay, mortality, need for ICU care/mechanical ventilation were compared between the two groups. Data is extracted and statistically analyzed using Pearson correlation. Results: A total of 118 patients were observed, 53 patients were diabetic and 65 were non-diabetic. Out of the 53 hyperglycemic patients, 39 patients were on metformin therapy while 15 patients were on insulin before admission due to COVID-19. A higher mortality rate was observed in the DM group when compared with the Non-DM group [26.4% (14) vs 9.23% (6)]. An increased random blood glucose level at the time of admission had a positive correlation with mortality (p = 0.003). While insulin administration prior to admission had negative correlation with mortality [R value is -0.282 (p = 0.02)], increased insulin requirement during hospitalization is associated with poor outcomes [R value is 0.327 (p = 0.002)]. Discussion: People with diabetes when infected with COVID-19 are at a greater risk of morbidity and mortality. The study highlights the need of rational management of hyperglycemia in COVID patients with a history of diabetes mellitus.

IDF21-0444 Association Between Prior Antidiabetic Therapy and Outcome in Hospitalized COVID-19 Diabetic Subjects

Background: The death toll due to the COVID‐19 pandemic is linked to various comorbidities including diabetes. Data regarding the association between prior antidiabetic medications and prognosis in hospitalized COVID-19 subjects shows conflicting results. Prior evidences indicated that the risk of fatal complications from COVID-19 was up to 50% higher in patients with DM than in those without. Moreover, the presence of typical complications of DM (heart failure and chronic kidney disease) increased COVID-19 mortality. Aim: The main aim of this retrospective study is to assess the association between prior antidiabetic treatment and outcomes in hospitalized COVID‐19 diabetic subjects. Method: This retrospective observational study included 510 consecutive COVID‐19 positive patients with diabetes admitted to various hospitals in month of May to June 2021. Data was collected on the day of admission and regularly followed up till discharge or death and tabulated in Excel sheet. Statistical analysis was done using SPSS 25.0. Results: Out of 510 patients, 374 patients were on metformin therapy, 228 subjects were on DPP4i, 210 subjects were on SGLT2i, 54 subjects were on GLP-1Ra, 289 subjects were on hydroxychloroquine (HCQs), while 119 subjects were on insulin prior to admission. Out of 510 patients, 24 expired. Admission mean average glycated haemoglobin (HbA1c) levels was 9.2±1.8% mg/dl and had positive correlation with mortality (p = 0.001). Both metformin and hydroxychloroquine usage prior to admission had negative correlation with mortality; r = −0.289 (p = 0.03) and -0.436 (p = 0.01) respectively. SGLT2i, DPP4i, GLP-1Ra and Insulin usage prior to admission had no statistical correlation with mortality, while increased insulin requirement in hospital was associated with poor outcomes (r = 0.439; p = 0.002). Severe obesity (BMI ≥ 35 kg/m2), d-dimer level, increasing age, and male sex were independently associated with mortality. No deaths were occurred among the subjects who were on HCQs for more than 6 months and more likely to be discharged from the hospital within 10 days. No difference in the incidence of new major cardiac arrhythmia or increase of QTc greater than 500 ms among the patients who received HCQs. Discussion: The result of the study shows that mortality rate is reduced significantly in patients who were on hydroxychloroquine and metformin before exposure to COVID‐19 and significantly increased in patients who required higher insulin doses for in-hospital management.

The remission phase in adolescents and young adults with newly diagnosed type 1 diabetes mellitus: prevalence, predicting factors and glycemic control during follow-up.

There is little data about the remission phase in adolescents and young adults with newly diagnosed type 1 diabetes mellitus (T1D). The aims of this study were to determine the prevalence of remission and its predicting factors among adolescents and young adults with newly diagnosed T1D and to assess the association between remission and long-term glycemic control in this population. This is a longitudinal and retrospective study including 128 type 1 diabetic patients aged between 12 and 30 years at diabetes onset. Clinical, biological and therapeutic features were collected at diagnosis and for 5 years after diagnosis. Remission was defined by an HbA1c < 6.5% with a daily insulin dose < 0.5 IU/kg/day. Twenty-three patients (18%) experienced a remission. The peak of remission prevalence was at 6 months after diabetes diagnosis. An insulin dose at discharge <0.8 IU/kg/day was independently associated with remission (p=0.03, adjusted OR [CI 95%] = 0.2 [0.1-0.9]). A low socioeconomic level was independently associated with non remission (p=0.02, adjusted OR [CI 95%] = 4.3 [1.3-14.3]). HbA1c was significantly lower during the first five years of follow-up in remitters. The daily insulin dose was significantly lower during the first four years of follow-up in remitters. Occurrence of remission in adolescents and young adults with newly diagnosed T1D is associated with better glycemic control and lower insulin requirements during the first 5 years of follow-up. A lower initial dose of insulin was associated with a higher percentage of remission.

Zone-MPC Automated Insulin Delivery Algorithm Tuned for Pregnancy Complicated by Type 1 Diabetes.

Type 1 diabetes (T1D) increases the risk for pregnancy complications. Increased time in the pregnancy glucose target range (63-140 mg/dL as suggested by clinical guidelines) is associated with improved pregnancy outcomes that underscores the need for tight glycemic control. While closed-loop control is highly effective in regulating blood glucose levels in individuals with T1D, its use during pregnancy requires adjustments to meet the tight glycemic control and changing insulin requirements with advancing gestation. In this paper, we tailor a zone model predictive controller (zone-MPC), an optimization-based control strategy that uses model predictions, for use during pregnancy and verify its robustness in-silico through a broad range of scenarios. We customize the existing zone-MPC to satisfy pregnancy-specific glucose control objectives by having (i) lower target glycemic zones (i.e., 80-110 mg/dL daytime and 80-100 mg/dL overnight), (ii) more assertive correction bolus for hyperglycemia, and (iii) a control strategy that results in more aggressive postprandial insulin delivery to keep glucose within the target zone. The emphasis is on leveraging the flexible design of zone-MPC to obtain a controller that satisfies glycemic outcomes recommended for pregnancy based on clinical insight. To verify this pregnancy-specific zone-MPC design, we use the UVA/Padova simulator and conduct in-silico experiments on 10 subjects over 13 scenarios ranging from scenarios with ideal metabolic and treatment parameters for pregnancy to extreme scenarios with such parameters that are highly deviant from the ideal. All scenarios had three meals per day and each meal had 40 grams of carbohydrates. Across 13 scenarios, pregnancy-specific zone-MPC led to a 10.3 ± 5.3% increase in the time in pregnancy target range (baseline zone-MPC: 70.6 ± 15.0%, pregnancy-specific zone-MPC: 80.8 ± 11.3%, p < 0.001) and a 10.7 ± 4.8% reduction in the time above the target range (baseline zone-MPC: 29.0 ± 15.4%, pregnancy-specific zone-MPC: 18.3 ± 12.0, p < 0.001). There was no significant difference in the time below range between the controllers (baseline zone-MPC: 0.5 ± 1.2%, pregnancy-specific zone-MPC: 3.5 ± 1.9%, p = 0.1). The extensive simulation results show improved performance in the pregnancy target range with pregnancy-specific zone MPC, suggest robustness of the zone-MPC in tight glucose control scenarios, and emphasize the need for customized glucose control systems for pregnancy.

Falling Insulin Requirement in Pregnant Women With Diabetes Delivering Preterm: Prevalence, Predictors, and Consequences.

Falling insulin requirements often lead to considerations of whether a pregnancy can continue safely or if delivery is indicated. To evaluate prevalence and predictors of falling insulin requirements in pregnant women with preexisting diabetes delivering preterm and to explore the relationship to fetal asphyxia and neonatal morbidity. A prospective cohort study of 101 consecutive singleton pregnant women with preexisting diabetes delivering preterm < 37 weeks (68 type 1 and 33 type 2 diabetes) where the prevalence of falling insulin requirements (≥20%) before delivery was recorded. In total, 27% (27/101) experienced falling insulin requirements of median 30% (interquartile range 24-40) before delivery. In all women with type 1 diabetes, the prevalence was 37% (25/68), whereas it was 43% (24/56) in those with indicated preterm delivery and 6% (2/33) among women with type 2 diabetes. In women with type 1 diabetes and indicated preterm delivery, falling insulin requirements were first identified at 34 + 5 (33 + 6-35 + 4) weeks + days and delivery occurred 3 (1-9) days later. Gestational age at delivery, prevalence of suspected fetal asphyxia, and neonatal morbidity were similar in women with and without falling insulin requirements. Neither glycemic control, nausea, or preeclampsia was associated with falling insulin requirement. Falling insulin requirements often preceded preterm delivery in women with type 1 diabetes, foremost when preterm delivery was indicated, but was not related to fetal asphyxia or neonatal morbidity. Whether falling insulin requirements in late pregnancy are a warning sign of placental insufficiency or mainly reflects variations in normal physiology needs further investigation.