Conventional Insulin Research Articles

5040 Leveraging Continuous Glucose Monitoring Data as an Additional Source for Glucagon Prescription Behavior

Abstract Disclosure: J. Ambalavanan: None. J. Rusticelli: None. D. Isaacs: Consulting Fee; Self; Medtronic Diabetes, Lilly USA, LLC, Novo Nordisk, Insulet Corporation, Abbott Laboratories, Dexcom. H. Xiao: None. J. Bena: None. Z. Jin: None. C. Babiuch: None. M. Lansang: Consulting Fee; Self; Glooko. Research Investigator; Self; Abbott Laboratories, Dexcom, Xeris. Background: Hypoglycemia is a major source of anxiety in, and can be life-threatening for, patients with diabetes (DM). Even though the American Diabetes Association (ADA) recommends glucagon be made available to all individuals taking insulin or at high risk for hypoglycemia (level E evidence), few patients have access to this life-saving medication. Given the rapid adoption of continuous glucose monitoring (CGM) in the management of DM, we aimed to 1) evaluate glucagon prescription by identifying patients with hypoglycemia on CGM reports, and 2) deliver an educational letter to the providers. Methods: Our study had a retrospective chart review and a quality improvement (QI) component. From Mar-Oct 2023, we identified adult patients in the Cleveland Clinic Ohio health system with type 1 or type 2 DM on insulin (including insulin pumps), sulfonylurea, or meglitinide, and hypoglycemia defined as time below range (TBR) ≥4% on CGM reports. We evaluated the percentages of pre-existing and incident glucagon prescription among those patients. For the QI component, we contacted providers individually via letter if the patients did not have a glucagon prescription and shared with them the ADA Standards of Care on hypoglycemia along with information about various forms of glucagon. Whether to prescribe glucagon was left to the clinical judgement of the providers. Information was collected 4 weeks later to see whether there was any change in the prescription practice. Results: Patients numbered 1543, with170 patients having TBR ≥4%. Among patients with hypoglycemia, 37% had pre-existing prescription and 14% incident glucagon prescription, compared with patients without hypoglycemia (p<0.001). Significant (p<0.001) risk factors for hypoglycemia included type 1 DM, insulin-only therapy, use of conventional insulin pumps, and lower A1c. Among patients with TBR ≥4%, 66 (39%) had level 1 hypoglycemia (54 to <70 mg/dl), 88 (52%) had level 2, and 16 (9%) had level 3 (hospitalization or ER admission for hypoglycemia). Pre-existing or incident glucagon prescription was seen in 28% without hypoglycemia, 38% with level 1 hypoglycemia, 49% with level 2, and 63% with level 3 (p<0.001 level 1 vs level 3; level 2 vs no hypoglycemia; level 3 vs no hypoglycemia). Among 70 patients whose providers received education letters, 27 (39%) prescribed glucagon after education. Glucagon emergency kit, glucagon autoinjector, and inhaled glucagon were the top prescription choices. A greater proportion of advanced practice providers responded to our education than physicians (p=0.021). Conclusion: Glucagon prescription remains suboptimal though better than in other studies even among patients with documented hypoglycemia on CGM reports. Effective provider education and communication can increase glucagon prescription. Provider and patient factors should be studied next to determine steps for further improvement. Presentation: 6/1/2024

Assessment of growth status in children and adolescents with type 1 diabetes mellitus in Baghdad: a case-control study.

To assess growth parameters in adolescents and children with type 1 diabetes mellitus, and the factors influencing their growth. The case-control study was conducted from February to December 2020 at the Endocrine Outpatient Clinic of the Central Child Teaching Hospital of Paediatrics, Baghdad, Iraq, and comprised patients aged 2-16 years who had type 1 diabetes for at least a year. The patients formed group A, while healthy controls matched for age and gender from different schools and kindergartens formed group B. Weight, height and body mass index of all the subjects in both groups were measured and worked out, and the values were compared. Data was analysed using SPSS 25. Of the 192 subjects, 96(50%) were in each of the 2 groups; 50(52.1%) girls and 46(47.9%) boys in group A, and 58(60.4%) girls and 38(39.6%) boys in group B. The overall mean age was 9.66±3.26 years. Group A children had significantly lower mean height, weight and body mass index Z scores compared to group B (p=0.001). The height Z score of group A children was significantly inversely associated with age, duration of disease, and glycated haemoglobin level (p=0.001), while the weight Z score was significantly inversely correlated with age and glycated haemoglobin (p=0.001). The body mass index Z score of group A was significantly inversely associated with age and glycated haemoglobin level (p<0.05). Children with type 1 diabetes mellitus had significantly lower mean height, weight and body mass index Z scores compared to their counterparts in the control group. Pubertal age group, poor glycaemic control, longer disease duration, and using conventional insulin regimen were the factors affecting growth parameters.

Crinophagic granules in pancreatic β cells contribute to mouse autoimmune diabetes by diversifying pathogenic epitope repertoire

Autoimmune attack toward pancreatic β cells causes permanent loss of glucose homeostasis in type 1 diabetes (T1D). Insulin secretory granules store and secrete insulin but are also thought to be tissue messengers for T1D. Here, we show that the crinophagic granules (crinosome), a minor set of vesicles formed by fusing lysosomes with the conventional insulin dense-core granules (DCG), are pathogenic in T1D development in mouse models. Pharmacological inhibition of crinosome formation in β cells delays T1D progression without affecting the dominant DCGs. Mechanistically, crinophagy inhibition diminishes the epitope repertoire in pancreatic islets, including cryptic, modified and disease-relevant epitopes derived from insulin. These unconventional insulin epitopes are largely undetectable in the MHC-II epitope repertoire of the thymus, where only canonical insulin epitopes are presented. CD4+ T cells targeting unconventional insulin epitopes display autoreactive phenotypes, unlike tolerized T cells recognizing epitopes presented in the thymus. Thus, the crinophagic pathway emerges as a tissue-intrinsic mechanism that transforms insulin from a signature thymic self-protein to a critical autoantigen by creating a peripheral-thymic mismatch in the epitope repertoire.

A homeostatic gut-to-brain insulin antagonist restrains neuronally stimulated fat loss

In C. elegans mechanisms by which peripheral organs relay internal state information to the nervous system remain unknown, although strong evidence suggests that such signals do exist. Here we report the discovery of a peptide of the ancestral insulin superfamily called INS-7 that functions as an enteroendocrine peptide and is secreted from specialized cells of the intestine. INS-7 secretion is stimulated by food withdrawal, increases during fasting and acts as a bona fide gut-to-brain peptide that attenuates the release of a neuropeptide that drives fat loss in the periphery. Thus, INS-7 functions as a homeostatic signal from the intestine that gates the neuronal drive to stimulate fat loss during food shortage. Mechanistically, INS-7 functions as an antagonist at the canonical DAF-2 receptor and functions via FOXO and AMPK signaling in ASI neurons. Phylogenetic analysis suggests that INS-7 bears greater resemblance to members of the broad insulin/relaxin superfamily than to conventional mammalian insulin and IGF peptides. The discovery of an endogenous insulin antagonist secreted by specialized intestinal cells with enteroendocrine functions suggests unexpected and important properties of the intestine and its role in directing neuronal functions.

Pancreas transplantation: review.

Pancreas transplant (PTx) is the only treatment that establishes normal glucose levels for patients diagnosed with diabetes types 1 and 2. The paper aims to review and analyze graft survival, patient survival, and the impact on diabetic complications. We describe that the graft survival was 82-98% at 1 year, 90% at 5 years, and 75-54% at 10 years for simultaneous pancreas-kidney recipient; 71% pancreas after kidney (PAK), and 62% PTx alone at 1 year. Patient survival: At 1 year for recipients was 96.9% simultaneous pancreas-kidney transplantation (SPK); for PAK transplantation recipients, 96.3%; and for PTx alone recipients, 98.3%. In general, the pancreas transplantation improves and reverses diabetic complications. Finally, the pancreatic transplant is a morbid procedure and emerges as a significant alternative in diabetes management, directly competing with conventional insulin therapies. Results so far suggest that the most effective transplant model is the SPK. While more patients could benefit from this procedure, surgical complications and the need for immunosuppression pose significant challenges.

Real-world glycaemic outcomes of automated insulin delivery in type 1 diabetes: A meta-analysis.

To evaluate the real-world effectiveness of automated insulin delivery (AID) systems in patients with type 1 diabetes (T1D). PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov were searched for studies published up until 2 March 2024. We included pragmatic randomized controlled trials (RCTs), cohort studies, and before-after studies that compared AID systems with conventional insulin therapy in real-world settings and reported continuous glucose monitoring outcomes. Percent time in range (TIR; 3.9-10 mmol/L), time below range (TBR; <3.9 mmol/L), time above range (TAR; >10 mmol/L), and glycated haemoglobin (HbA1c) level were extracted. Data were summarized as mean differences (MDs) with 95% confidence interval. A total of 23 before-after studies (101 704 participants) were included in the meta-analysis. AID systems were associated with an increased percentage of TIR (11.61%, 10.47 to 12.76; p < 0.001). The favourable effect of AID systems was consistently observed when used continuously for 6 (11.76%) or 12 months (11.33%), and in both children (12.16%) and adults (11.04%). AID systems also showed favourable effects on TBR (-0.53%, -0.63 to -0.42), TAR (-9.65%, -10.63 to -8.67) and HbA1c level (-0.42%, -0.47 to -0.37) when compared with previous treatments. Similar improvements in glycaemic parameters were observed in real-world settings in RCTs using AID systems in T1D. AID systems benefit both children and adults by increasing TIR for both short- and long-term interventions.

Real-World Effectiveness of the Gla-300 + Cap + App Program in Adult Users Living with Type2 Diabetes in Taiwan.

Health2Sync (H2S) is a digital health technology platform that provides coaching and titration support to patients with diabetes. The Mallya cap converts a conventional insulin pen into a smart connected device that can automatically synchronize dose values and associated timestamps (upon injection) to the H2S platform. This single-arm real-world study evaluated the effectiveness of insulin glargine 300U/mL (Gla-300) combined with H2S and Mallya cap (Gla-300 + Cap + App program) on clinical outcomes among users with type 2 diabetes (T2D) in Taiwan. Adults (aged ≥ 20years) with T2D who were registered H2S users and initiated Mallya cap for a new/existing Gla-300 regimen (identification period May1, 2021-May31, 2022) were included in this retrospective cohort study. Follow-up data from H2S were collected for 90days. Glycated hemoglobin (HbA1c) change (baseline to follow-up) and HbA1c goal attainment were primary outcomes. Hypoglycemia incidence and usage metrics of Mallya cap were secondary outcomes. Of 83 participants, 38.6% were new Gla-300 users. HbA1c was reduced in both new (- 2.4 [2.7] %, - 26.2 [29.5] mmol/mol) and previous Gla-300 users (- 0.5 [1.6] %, - 5.5 [17.5] mmol/mol). Reduction in HbA1c was significant (p < 0.05) in both groups. At follow-up, 43.4% of users had a reduction of > 0.5%. Mean HbA1c reductions increased numerically with higher baseline HbA1c and with longer duration of Mallya cap usage. Use of digital technology within a connected ecosystem such as Gla-300 + Cap + App program could help people with type2 diabetes to improve their glycemic condition.

Are New Ultra-Rapid-Acting Insulins Associated with Improved Glycemic Control and Reduced Hypoglycemia in Comparison to Conventional Rapid-Acting Insulins for Individuals with Type 1 and Type 2 Diabetes? A Systematic Review and Meta-Analysis.

Introduction: This study aimed to compare efficacy and safety of ultra-rapid-acting insulin analogs (URAIs; faster aspart [FAsp], ultra-rapid lispro [URLi], and technosphere insulin [TI]) with rapid-acting insulin analogs (RAI) in individuals with type 1 (T1D) or type 2 diabetes (T2D). Methods: Searching for randomized control trial comparing the effects of URAI versus RAI that lasted at least 12 weeks, we initially selected 15 studies for analysis. Three studies involving TI were excluded due to a high degree of heterogeneity. The final meta-analysis included only 12 studies with either FAsp or URLi. Results: Mealtime URAI significantly reduced overall early 1 h postprandial glycemia in individuals with T1D (-20.230 mg/dL [95% confidence interval, 95% CI -24.040 to -16.421]; P < 0.001; I2 = 33.42%) and those with T2D (-9.138 mg/dL [95% CI -12.612 to -5.663]; P < 0.001; I2 = 0%). However, the significant reduction in 2 h postprandial glucose remained only in individuals with T1D (-17.620 mg/dL [95% CI -26.047 to -9.193]; P < 0.001; I2 = 65.88%). These benefits were lost when URAI was administered postmeal. At 24-26 weeks, there was no significant difference in HbA1c between groups, but at 52 weeks, a slight reduction in HbA1c with mealtime URAI was observed (-0.080% [95% CI -0.147 to -0.013]; P = 0.019; I2 = 0%). No difference in weight or the rate of severe or confirmed hypoglycemia was observed. Only individuals with T1D showed a small, but significant increase in early 1-h hypoglycemia with URAI (1.468 [95% CI 1.235 to 1.747]; P < 0.001; I2 = 0%). Conclusion: Mealtime URAI improves 1 and 2 h postprandial glycemic control compared to RAI without increasing hypoglycemia or weight gain.

Effect of Intensive Insulin Therapy on Prognosis in Patients With Acute Myocardial Infarction

Objective To evaluate the clinical efficacy and safety of intensive insulin therapy in the patients with acute myocardial infarction and provide guidance for improving the prognosis. Methods The articles involving the randomized controlled trials(RCT)focusing on the effects of intensive versus conventional insulin therapy on the clinical outcomes of the patients with acute myocardial infarction were retrieved from Cochrane,Embase,PubMed,CNKI,Wanfang Data,VIP,and CBM with the time interval from inception to October 2022.The data of each RCT were extracted and used for meta-analysis in RevMan5.4. Results A total of 8 articles were included in this study,involving 726 patients(372 in the intensive insulin group and 354 in the normal insulin group).The meta-analysis results showed that the intensive insulin group had lower incidence of major cardiovascular adverse events (RR=0.53, 95%CI=0.44-0.64, P<0.001), lower all-cause mortality (RR=0.51, 95%CI=0.33-0.78, P=0.002),lower high-sensitivity C-reactive protein level on day 7(WMD=-2.00,95%CI=-2.17- -1.83,P<0.001),higher left ventricular ejection fraction on day 30 (WMD=3.94, 95%CI=2.45-5.43,P<0.001), and higher incidence of hypoglycemia events (RR=2.96, 95%CI=1.12-7.83,P=0.030) than the normal insulin group.There was no significant difference between the two groups in terms of no-reflow event after percutaneous coronary intervention(RR=0.39,95%CI=0.14-1.13,P=0.080). Conclusion Intensive insulin therapy might be associated with more clinical benefits in the patients with acute myocardial infarction,while the conclusion remains to be confirmed by more studies.

Novel Automated Self-adjusting Subcutaneous Insulin Algorithm Improves Glycemic Control and Physician Efficiency in Hospitalized Patients.

Hyperglycemia occurs in 22% to 46% of hospitalized patients, negatively affecting patient outcomes, including mortality, inpatient complications, length of stay, and hospital costs. Achieving inpatient glycemic control is challenging due to inconsistent caloric intake, changes from home medications, a catabolic state in the setting of acute illness, consequences of acute inflammation, intercurrent infection, and limitations in labor-intensive glucose monitoring and insulin administration. We conducted a retrospective cross-sectional analysis at the University of California San Francisco hospitals between September 3, 2020 and September 2, 2021, comparing point-of-care glucose measurements in patients on nil per os (NPO), continuous total parenteral nutrition, or continuous tube feeding assigned to our novel automated self-adjusting subcutaneous insulin algorithm (SQIA) or conventional, physician-driven insulin dosing. We also evaluated physician efficiency by tracking the number of insulin orders placed or modified. The proportion of glucose in range (70-180 mg/dL) was higher in the SQIA group than in the conventional group (71.0% vs 69.0%, P = .153). The SQIA led to a lower proportion of severe hyperglycemia (>250 mg/dL; 5.8% vs 7.2%, P = .017), hypoglycemia (54-69 mg/dL; 0.8% vs 1.2%, P = .029), and severe hypoglycemia (<54 mg/dL; 0.3% vs 0.5%, P = .076) events. The number of orders a physician had to place while a patient was on the SQIA was reduced by a factor of more than 12, when compared with while a patient was on conventional insulin dosing. The SQIA reduced severe hyperglycemia, hypoglycemia, and severe hypoglycemia compared with conventional insulin dosing. It also improved physician efficiency by reducing the number of order modifications a physician had to place.

Treatment Satisfaction With Omnipod DASH in Adults With Type 1 Diabetes: A Nonblinded 1:1 Randomized Controlled Trial.

Omnipod DASH Insulin Management System is a tubeless insulin pump that overcomes the physical inconveniences of conventional tubed insulin pump therapy (IPT). We compared treatment satisfaction with Omnipod DASH System to usual care (multiple daily injections [MDIs] or tubed IPT) in adults with type 1 diabetes using self-monitoring blood glucose (SMBG). Adults with type 1 diabetes on MDI (n = 40) or IPT (n = 25) from 4 diabetes centers in Australia were randomly assigned in a 1:1 nonblinded manner to Omnipod DASH System (Omnipod group) or continue usual care (Usual Care group) for 12 weeks, followed by a further 12-week extension during which all participants used the device. The primary outcome was treatment satisfaction assessed by change in Diabetes Technology Questionnaire "current" (ΔDTQ-current) score at 12 weeks (study end). Secondary outcomes included ΔDTQ-current following extension and other participant-reported outcomes (PROs) measuring quality of life, burden of disease treatment, and glycemic and device-related outcomes at 12 weeks (study end) and 24 weeks (end extension). Treatment satisfaction improved more in the Omnipod group vs the Usual Care group (ΔDTQ-current score of 16.4 [21.2] vs 0.0 [12.8]; P < .001) at study end. Significantly greater improvements in other PROs and glycated hemoglobin A1c were also observed. Improvements in DTQ-current and other PROs comparing study end and end extension were similar. While percentage in time in range change from baseline did not differ at study end (-2.0 [12.7] %), it was significantly greater at end extension (5.6 [10.9] %; P = .016). The Omnipod DASH System resulted in greater treatment satisfaction at 12 weeks in adults with type 1 diabetes using SMBG that was sustained after 24 weeks of device use without compromising sleep quality and fear of hypoglycemia. Improvements in glycemia were also observed.

The Conclusion of Diabetes Mellitus on Endodontic Treatment Result: A New Appraisal

Background- The writers used a custom-built electronic utmost agreement to examine endodontic analytical and management consequence measurements in patients with and without diabetes. Methods- The medical histories and endodontic management statistics for nonsurgical endodontic patients treated in predoctoral and postgraduate specialty clinics were entered into an electronic record system. A entire of 5,134 cases (including 284 cases in patients with diabetes) were treated, and 150 cases (including 63 cases in patients with diabetes) had follow-up data two years or additional postoperatively. The writers applied and multivariate evaluates to control significant issues touching endodontic analysis and treatment. Results- Patients with diabetes had enlarged periodontal infection of teeth with endodontic connection associated with patients who did not have diabetes. There was a movement near enlarged suggestive peri-radicular illness in patients with diabetes who conventional insulin, as well as flare ups in all patients with diabetes. Two years or longer post-operatively, 58 percent of cases surveyed were effective. Older age, the absence of preoperative lesions, the presence of permanent restorations and longer postoperative evaluation phases all were supplementary with an effective outcome. A multivariate examination displayed that in cases with preoperative peri-radicular lesions, a history of diabetes was supplementary with a meaningfully complete successful outcome. Conclusions- Patients with diabetes have enlarged periodontal disease in teeth involved endodontically and have a reduced likelihood of success of endodontic treatment in cases with preoperative peri-radicular lesions. Clinical Implications- Patients with diabetes who are preserved endodonticaly should be evaluated carefully and be preserved with operative antimicrobial root canal regimens, mainly in cases with preoperative lesions.

A Nutritional Approach to Optimizing Pump Therapy in Type 1 Diabetes Mellitus

Achieving optimal glucose control in individuals with type 1 diabetes (T1DM) continues to pose a significant challenge. While continuous insulin infusion systems have shown promise as an alternative to conventional insulin therapy, there remains a crucial need for greater awareness regarding the necessary adaptations for various special circumstances. Nutritional choices play an essential role in the efficacy of diabetes management and overall health status for patients with T1DM. Factors such as effective carbohydrate counting, assessment of the macronutrient composition of meals, and comprehending the concept of the glycemic index of foods are paramount in making informed pre-meal adjustments when utilizing insulin pumps. Furthermore, the ability to handle such situations as physical exercise, illness, pregnancy, and lactation by making appropriate adjustments in nutrition and pump settings should be cultivated within the patient–practitioner relationship. This review aims to provide healthcare practitioners with practical guidance on optimizing care for individuals living with T1DM. It includes recommendations on carbohydrate counting, managing mixed meals and the glycemic index, addressing exercise-related challenges, coping with illness, and managing nutritional needs during pregnancy and lactation. Additionally, considerations relating to closed-loop systems with regard to nutrition are addressed. By implementing these strategies, healthcare providers can better equip themselves to support individuals with T1DM in achieving improved diabetes management and enhanced quality of life.

The Role of Ultra-Rapid-Acting Insulin Analogs in Diabetes: An Expert Consensus.

Ultra-rapid-acting insulin analogs (URAA) are a further development and refinement of rapid-acting insulin analogs. Because of their adapted formulation, URAA provide an even faster pharmacokinetics and thus an accelerated onset of insulin action than conventional rapid-acting insulin analogs, allowing for a more physiologic delivery of exogenously applied insulin. Clinical trials have confirmed the superiority of URAA in controlling postprandial glucose excursions, with a safety profile that is comparable to the rapid-acting insulins. Consequently, many individuals with diabetes mellitus may benefit from URAA in terms of prandial glycemic control. Unfortunately, there are only few available recommendations from authoritative sources for use of URAA in clinical practice. Therefore, this expert consensus report aims to define populations of people with diabetes mellitus for whom URAA may be beneficial and to provide health care professionals with concrete, practical recommendations on how best to use URAA in this context.

Does fully closed-loop automated insulin delivery improve glycaemic control in patients with type 2 diabetes? A meta-analysis of randomized controlled trials.

This meta-analysis investigated the efficacy and safety of fully closed-loop automated insulin delivery (AID) in patients with type 2 diabetes. We systemically searched PubMed, Scopus, Web of Science, and Cochrane Central from inception until April 26, 2023. We included randomized controlled trials (RCTs) comparing fully closed-loop AID versus conventional insulin therapy. The outcomes were pooled as the mean difference (MD) and risk ratio with 95% confidence interval (CI) in the random effect model. Our primary outcome was the proportion of time in the target glucose range (5.6-10 mmol/L, 3.9-10 mmol/L, or 3.9-8 mmol/L, depending on the study). Key secondary outcomes included the proportion of time spent in hyperglycaemia or hypoglycaemia. We included seven RCTs (three crossover and four parallel design), compromising 390 patients. Our analysis showed that compared to the control group, fully closed-loop AID increased the proportion of time spent within the target glucose range by additional 337 min per 24 h (MD = 23.39%, 95% CI [16.64%, 30.14%], p < 0.01), additional 108 min overnight (MD = 22.40%, 95% CI [12.88%, 31.91%], p < 0.01), and additional 258 min during the daytime period (MD = 26.85%, 95% CI [21.06%, 32.63%], p < 0.01). Compared to the control group, the overall time in hyperglycaemia was shortened by 326 min per 24 h (MD = -22.67%, 95% CI [-30.87%, -14.46%], p < 0.01). There was no significant difference between the two groups in terms of overall, overnight, and daytime periods spent in hypoglycaemia. Our meta-analysis suggests that fully closed-loop AID may improve glycaemic control in patients with type 2 diabetes, particularly for those with more challenging diabetes management. Further research is required to establish the feasibility of implementing these systems in clinical practice. [Correction added on 26 August 2023 after first online publication: Under Results, the first sentence "We included seven RCTs (three crossover and one parallel designs)" has been changed to "We included seven RCTs (three crossover and four parallel designs)".].

413-P: Intensive Insulin Therapy Delays the “Breakpoint” to Progressive Kidney Function Decline—New Findings and Implications of eGFR Trajectory Analysis in DCCT/EDIC Data

Patterns of kidney function decline vary among those with T1D. End-stage kidney disease (ESKD) develops after progressive kidney function decline that begins when kidney function is normal, regardless of albuminuria. We aimed to determine if these findings were observed in the DCCT/EDIC cohort, which enrolled 1,441 individuals and randomly assigned them to intensive insulin therapy (n=711) or conventional insulin therapy (n=730). Baseline mean eGFR and AER were 125 ml/min/1.73m2 and 12 mg/24 hours, respectively. During 27 years of follow-up 129 individuals reached reduced eGFR &amp;lt;60ml/min/1.73m2 or ESKD. For these individuals we applied latent class trajectory analysis minimizing sum of squares of linear spline models with varying knot placement to identify patterns of eGFR decline. We identified two patterns: i) slow decline without eGFR breakpoint (n=56) and ii) fast decline with clear breakpoint (n=73). Slow decliners reached reduced eGFR but rarely ESKD (2%), while many fast decliners progressed to ESKD (35%) within 5-15 years after the breakpoint. Fast decline was less frequent in intensive compared to conventional insulin therapy [26 (3.7%) vs 47 (6.4%), respectively, p=0.022] and had longer median time from enrollment to breakpoint (18 vs 13 years, respectively, p=0.0004). However, the slope of annual loss of eGFR after breakpoint did not differ. In conclusion, we identified a unique phenotype - the “breakpoint” to fast decline in eGFR - as the main predictor of ESKD in T1D. This breakpoint started while eGFR was normal, subsequent decline was linear, and the onset of the breakpoint was substantially delayed by intensive insulin therapy rather than the slope of decline itself. Research on biomarkers that predict the onset of the eGFR ‘breakpoint’ is needed. Disclosure K.Ihara: None. J.K.Skupien: None. E.Satake: None. B.A.Perkins: Advisory Panel; Dexcom, Inc., Insulet Corporation, Novo Nordisk, Sanofi, Vertex Pharmaceuticals Incorporated, Other Relationship; Abbott, Medtronic, Sanofi, Research Support; Novo Nordisk, Bank of Montreal (BMO). A.Krolewski: None.

917-P: Treatment Satisfaction with Omnipod DASH System vs. Usual Care in Adults with Type 1 Diabetes in Australia

Background: Conventional insulin pumps can be inconvenient and increase diabetes distress in people with type 1 diabetes (T1D). A tubeless insulin pump discreetly controlled by a handheld device, may be more acceptable. This is the first randomized controlled trial on patient-reported outcomes with tubeless insulin pumps. Aim: To compare treatment satisfaction with Omnipod DASH® Insulin Management System (Insulet, Acton MA) vs. usual care (MDI or conventional IPT) in T1D adults self-monitoring with fingerstick blood glucose. Methods: T1D adults were randomized to 12-weeks of Omnipod DASH System (intervention) or usual care (control). At study-end, treatment satisfaction was assessed by the difference in Diabetes Technology Questionnaire current score (DTQ-current). Secondary outcomes included patient-reported measures assessed through six other questionnaires and HbA1c. Results: Baseline characteristics were similar between both groups. Those on Omnipod DASH System expressed significantly higher treatment satisfaction, better sleep quality, reduced fear of hypoglycemia and diabetes distress than those on usual care. HbA1c reduction was clinically relevant in the intervention group. Conclusion: This study demonstrated that Omnipod DASH System is associated with better treatment satisfaction and patient-reported outcomes whilst maintaining glycemia in T1D adults. Disclosure Y.W.Kong: None. E.I.Ekinci: Advisory Panel; Eli Lilly Australia Pty Limited, Research Support; Eli Lilly Australia Pty Limited, Novo Nordisk, Boehringer Ingelheim and Eli Lilly Alliance, Insulet Corporation, Medtronic. D.N.O'neal: None. C.Yuan: None. K.V.Kiburg: None. K.Brown: None. S.Trawley: Research Support; Insulet Corporation, Juvenile Diabetes Research Foundation (JDRF). A.Partovi: None. K.L.Roem: None. N.Harrison: None. S.Fourlanos: Advisory Panel; Viatris Inc., Pfizer Inc., Speaker's Bureau; Novo Nordisk, AstraZeneca, Boehringer Ingelheim and Eli Lilly Alliance. Funding Insulet Corporation

Real-World Diabetes Technology: Overcoming Barriers and Disparities.

Real-World Diabetes Technology: Overcoming Barriers and Disparities.

Low risk for diabetic complications in type 1 diabetes patients carrying a protective insulin gene variant.

Type 1 diabetes patients carrying a 'protective' insulin gene (INS) variant present a disease endotype with reduced insulin antibody titers, preserved beta cell function and improved glycemic control. We tested whether this protective INS variant associated with lowered risk for development of proliferative diabetic retinopathy (PDR) and diabetic kidney disease (DKD) as long-term diabetic complications. Insulin gene polymorphisms were evaluated in 1,363 type 1 diabetes patients participating in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study that compared intensive versus conventional insulin therapy in relation with development of PDR and DKD with a follow-up of over two decades. PDR and DKD were absent in type 1 diabetes patients carrying the protective INS variant and receiving intensive insulin therapy (the current standard of clinical care) 1-5 years from their diagnosis (n = 67; mean post-diagnosis follow up of 20.4 ± 1.6 years), versus 11 of 258 patients (4.3%) lacking this variant (20.4 ± 1.8 years follow up). In the secondary intervention group of the intensive therapy arm (1-15 years of disease), PDR was significantly less frequent in carriers of the protective INS variant than those without it (4 of 83 [4.8%] vs. 31 of 260 [11.9%]; p = 0.032; 26.1 ± 3.9 and 26.3 ± 4.1 years follow-up, respectively), whereas DKD frequencies were no different between those with or without this variant (5 of 83 [6.0%] vs. 11 of 260 [4.2%]). Carrying a copy of this protective INS variant further reduces the risk of diabetic complications achieved by intensive insulin therapy and marks a disease endotype with superior glycemic control, increased and extended beta cell function, and prevention of DKD and PDR.

Congenital malformations among offspring of women with type 1 diabetes who use insulin pumps: a prospective cohort study.

Continuous subcutaneous insulin infusion by insulin pump is often superior in improving glycaemic control compared with conventional multiple daily insulin injection (MDI). However, whether pump treatment leads to improved pregnancy outcomes in terms of congenital malformations and perinatal death remains unknown. The present aim was to evaluate the risk of malformations and perinatal and neonatal death in pregnant women with type 1 diabetes treated with pump or MDI. We performed a secondary analysis of a prospective multinational cohort of 2088 pregnant women with type 1 diabetes in a real-world setting who were treated by pump (n=750) or MDI (n=1338). ORs for offspring with congenital malformations or perinatal or neonatal death were calculated using crude data and by logistic regression on propensity score-matched data. At enrolment (gestational week 8; 95% CI 4, 14), pump users had a higher educational level (university degree: 37.3% vs 25.1%; p<0.001) and better glycaemic control (mean HbA1c: 51±10 mmol/mol [6.8±0.9%] vs 54±14 mmol/mol [7.1±1.3%], p<0.001) compared with MDI users. Moreover, a greater proportion of pump users had an HbA1c level below 75 mmol/mol (9%) (97.6% vs 91.9%, p<0.001), and more often reported taking folic acid supplementation (86.3% vs 74.8%; p<0.001) compared with MDI users. All clinically important potential confounders were balanced after propensity score matching, and HbA1c remained lower in pump users. The proportion of fetuses with at least one malformation was 13.5% in pump users vs 11.2% in MDI users (crude OR 1.23; 95% CI 0.94, 1.61; p=0.13; propensity score-matched (adjusted) OR 1.11; 95% CI 0.81, 1.52; p=0.52). The proportion of fetuses with at least one major malformation was 2.8% in pump users vs 3.1% in MDI users (crude OR 0.89; 95% CI 0.52, 1.51; p=0.66; adjusted OR 0.78; 95% CI 0.42, 1.45; p=0.43), and the proportions of fetuses carrying one or more minor malformations (but no major malformations) were 10.7% vs 8.1% (crude OR 1.36; 95% CI 1.00, 1.84; p=0.05; adjusted OR 1.23; 95% CI 0.87, 1.75; p=0.25). The proportions of perinatal and neonatal death were 1.6% vs 1.3% (crude OR 1.23; 95% CI 0.57, 2.67; p=0.59; adjusted OR 2.02; 95% CI 0.69, 5.93; p=0.20) and 0.3% vs 0.3% (n=2 vs n=4, p=not applicable), respectively. Insulin pump treatment was not associated with a lower risk of congenital malformations, despite better glycaemic control in early pregnancy compared with MDI. Further studies exploring the efficacy and safety of pump treatment during pregnancy are needed.