Standard Insulin Research Articles

Effect of metformin adjunct therapy on cardiometabolic parameters in Indian adolescents with type 1 diabetes: a randomized controlled trial.

Insulin resistance is being increasingly reported in type-1 Diabetes (T1D) and is known to accelerate microvascular complications. The Asian Indian population has a higher risk of double diabetes development compared to Caucasians. Hence, we studied the effect of adding Metformin to standard insulin therapy on glycemic control, insulin sensitivity (IS), cardiometabolic parameters and body composition in Indian adolescents with T1D. A Randomized controlled trial was conducted spanning 9 months (Registration number:CTRI/2019/11/022126). Inclusion: Age 10-19 years, T1D duration>1year, HbA1c>8% Exclusion: Uncontrolled vascular complications/comorbidities, Metformin intolerance, concomitant drugs affecting insulin sensitivity. Participants were randomized to Metformin/Placebo (n=41 each) groups and age, sex, duration-matched. Assessments were performed at baseline, 3 and 9 months. 82 participants aged 14.7 ± 3years (40 females) were enrolled, with a mean diabetes duration of 5.2 ± 2.3 years. Over 9 months, HbA1c decreased significantly by 0.8 (95% confidence interval: -1.2 to -0.3) from 9.8 ± 1.8% to 9.1 ± 1.7% on Metformin but remained largely unchanged (difference of 0.2, 95% confidence interval: -0.7 to 0.2) i.e. 9.9 ± 1.6% and 9.7 ± 2.2% on placebo. HbA1c improvement correlated negatively with baseline IS (EGDR:r= -0.3;SEARCH:r = -0.24, p<0.05) implying better HbA1c-lowering in those with decreased initial IS. CGM-based glycemic variability (standard deviation) reduced by 6.3 mg/dL (95% confidence interval: -12.9 to 0.2) from 100.2 ± 19.1 mg/dL to 93.7 ± 19.9 mg/dL in those on Metformin (p=0.05) but not placebo (94.0 ± 20.5; 90.0 ± 22.6 mg/dL). Insulin sensitivity: CACTIexa & SEARCH scores demonstrated no change with Metformin but significant worsening on placebo. Significant increase in LDL-C(42%), total cholesterol(133.6 to 151.1 mg/dL), triglyceride (60.0 to 88.0 mg/dL) and carotid intima-media thickness was noted on placebo but not Metformin. Weight, BMI, fat Z-scores increased significantly on placebo but not Metformin. Adverse events (AE) were minor; AE, compliance and safety parameters were similar between the two groups. Metformin as an adjunct to insulin in Asian Indian adolescents with T1D demonstrated beneficial effect on glycemic control, glycemic variability, IS, lipid profile, vascular function, weight and body fat, with a good safety profile when administered for 9 months.

Automated Insulin Delivery in Women with Pregnancy Complicated by Type 1 Diabetes

BackgroundHybrid closed-loop insulin therapy has shown promise for management of type 1 diabetes during pregnancy; however, its efficacy is unclear.MethodsIn this multicenter, controlled trial, we randomly assigned pregnant women with type 1 diabetes and a glycated hemoglobin level of at least 6.5% at nine sites in the United Kingdom to receive standard insulin therapy or hybrid closed-loop therapy, with both groups using continuous glucose monitoring. The primary outcome was the percentage of time in the pregnancy-specific target glucose range (63 to 140 mg per deciliter [3.5 to 7.8 mmol per liter]) as measured by continuous glucose monitoring from 16 weeks’ gestation until delivery. Analyses were performed according to the intention-to-treat principle. Key secondary outcomes were the percentage of time spent in a hyperglycemic state (glucose level >140 mg per deciliter), overnight time in the target range, the glycated hemoglobin level, and safety events.ResultsA total of 124 participants with a mean (±SD) age of 31.1±5.3 years and a mean baseline glycated hemoglobin level of 7.7±1.2% underwent randomization. The mean percentage of time that the maternal glucose level was in the target range was 68.2±10.5% in the closed-loop group and 55.6±12.5% in the standard-care group (mean adjusted difference, 10.5 percentage points; 95% confidence interval [CI], 7.0 to 14.0; P<0.001). Results for the secondary outcomes were consistent with those of the primary outcome; participants in the closed-loop group spent less time in a hyperglycemic state than those in the standard-care group (difference, −10.2 percentage points; 95% CI, −13.8 to −6.6); had more overnight time in the target range (difference, 12.3 percentage points; 95% CI, 8.3 to 16.2), and had lower glycated hemoglobin levels (difference, −0.31 percentage points; 95% CI, −0.50 to −0.12). Little time was spent in a hypoglycemic state. No unanticipated safety problems associated with the use of closed-loop therapy during pregnancy occurred (6 instances of severe hypoglycemia, vs. 5 in the standard-care group; 1 instance of diabetic ketoacidosis in each group; and 12 device-related adverse events in the closed-loop group, 7 related to closed-loop therapy).ConclusionsHybrid closed-loop therapy significantly improved maternal glycemic control during pregnancy complicated by type 1 diabetes. (Funded by the Efficacy and Mechanism Evaluation Program; AiDAPT ISRCTN Registry number, ISRCTN56898625.)

Efficacy of the MiniMed™ 670G hybrid closed loop system in managing postprandial glucose excursion with high protein high fat foods in children and adolescents under free-living conditions

Objectives: High protein high fat (HPHF) meals are considered “difficult” foods because they can cause prolonged hyperglycemia after ingestion. The potential of hybrid closed loop therapy in managing postprandial glucose excursions with these difficult foods remains unknown. This pilot study aimed to explore the impact of manual mode in standard insulin pump therapy and auto mode with hybrid closed loop pump therapy in managing glucose excursions caused by HPHF foods and to obtain feedback from families about each mode. Material and Methods: Children and adolescents (8–18 years) with type 1 diabetes and using the MiniMed™ 670G were recruited to a free-living randomized cross-over study. Participants consumed a standardized lasagne or pizza meal two nights a week for 4 weeks while in auto mode and manual mode. Postprandial continuous glucose monitoring data were collected for 7 h post-meal. The primary outcomes were mean postprandial net incremental area under the glucose × time curve. User experiences were collected during end-of-study interviews administered to parents. Results: Postprandial excursions from 38 meals in seven participants were analyzed. There were no significant differences between auto mode and manual mode for the mean net incremental area under the glucose × time curve, irrespective of meal type. Semi-structured end-of-study interviews revealed that five of seven families felt more confident eating HPHF meals in auto mode. Conclusion: Although most families felt confident with auto mode for postprandial HPHF excursions, this was not reflected in the postprandial glucose levels.

Bionic pancreas reduces HbA1c compared with standard insulin delivery

Bionic pancreas reduces HbA1c compared with standard insulin delivery

MODY6 with NEUROD1 Mutation an Unusual Presentation in Adolescent: A Case Report

MODY( Maturity onset diabetes of young) is a rare monogenic type of diabetes and which comprises 1-5 % of all diabetes cases [1]. It is often misdiagnosed as either type 1 or type 2 diabetes mellitus in children and adolescents due to common clinical signs and symptoms. With the availability of genetic testing, an increasing number of cases of MODY are being reported. We are reporting a case of 15 years old male child who presented with hyperglycemia without metabolic acidosis. He started on standard insulin regimen in view of suspected type1 diabetes. Later he was detected with NEUROD1 mutation, which is associated with MODY6, and the child was put on oral hypoglycemic drug, Metformin. At present the child is not on medication and is euglycemic. NEUROD1 is one of the least reported mutations in MODY6, only 5-6 cases are reported from India, and we report the youngest case.

Ameliorative effect of montelukast against STZ induced diabetic nephropathy: targeting HMGB1, TLR4, NF-κB, NLRP3 inflammasome, and autophagy pathways

Diabetic nephropathy (DN) is reported as one of the most serious microvascular diabetic complications and the trigger of end-stage renal disease (ESRD), underscoring the concern of any therapeutic intervention directed at ameliorating the development and progression of DN. The current study explored the renoprotective impact of montelukast (Mon) against streptozotocin (STZ)-induced DN in rats compared to a standard anti-hyperglycemic insulin (Ins) treatment. Diabetes was induced by a single dose of STZ (55 mg/kg). Diabetic rats were treated with Mon (10 and 20 mg/kg, oral gavage) for eight weeks. Mon administration for 8 weeks after induction of diabetes conferred significant dose-dependent renoprotection, independent of blood glucose levels (unlike Ins), as evidenced by the improvement in serum creatinine, and blood urea nitrogen (BUN), and ameliorated STZ-induced renal necrotic, inflammatory alterations, and renal fibrosis. Additionally, Mon treatment in diabetic rats significantly restored redox hemostasis as evidenced by malondialdehyde (MDA) and total antioxidant capacity (TAC) levels; significantly reduced the renal expression of high mobility group box (HMGB) 1, toll-like receptor (TLR) 4, nuclear factor kappa B (NF-κB) (in the nucleus), NOD-like receptor family pyrin domain containing (NLRP) 3, and interleukin (IL)-1β. Moreover, Mon administration ameliorated the dysregulation in autophagy as evidenced by p62 and microtubule-associated protein 1A/1B-light chain 3 (LC3)-II levels. In conclusion, the renoprotective effect of Mon is potentially associated with its modulatory effect on inflammatory cytokines, antioxidant properties, and autophagy.Graphical Renoprotective effect of montelukast and its underlying pathway: Hyperglycemia and advanced glycation end products (AGEs) stimulate the release of high mobility group box (HMGB) 1 from necrotic and inflammatory cells. HMGB1 is considered as one of the endogenous ligands of toll-like receptor (TLR) 4, and the interaction of HMGB1 with TLR4 results in a subsequent translocation of nuclear factor kappa B (NF-κB) from the cytoplasm into the nucleus inducing an inflammatory response. NF-κB is a key mediator of the priming signal responsible for the activation of NOD-like receptor family pyrin domain containing (NLRP) 3 inflammasome by stimulating the expression of both NLRP3 and pro- interleukin (IL)-1β, which is then converted to IL-1β by to mediate inflammation. NLRP3 can induce reactive oxygen species production, while autophagy inhibits AGEs and NLRP3 accumulation. Montelukast show an inhibitory effect on HMGB1, TLR4, NF-κB, NLRP3, and IL-1β and has autophagy stimulating characteristics indicating its potential renoprotective effect.

A Comparison of Faster Insulin Aspart with Standard Insulin Aspart Using Hybrid Automated Insulin Delivery System in Active Children and Adolescents with Type 1 Diabetes: A Randomized Double-Blind Crossover Trial.

Objective: To evaluate the use of faster acting (FIA) and standard insulin aspart (SIA) with hybrid automated insulin delivery (AID) in active youth with type 1 diabetes. Research Design and Methods: In this double-blind multinational randomized crossover trial, 30 children and adolescents with type 1 diabetes (16 females; aged 15.0 ± 1.7 years; baseline HbA1c 7.5% ± 0.9% [58 ± 9.8 mmol/mol]) underwent two unrestricted 4-week periods using hybrid AID with either FIA or SIA in random order. During both interventions, participants were using the hybrid AID (investigational version of MiniMed™ 780G; Medtronic). Participants were encouraged to exercise as frequently as possible, capturing physical activity with an activity monitor. The primary outcome was the percentage of sensor glucose time above range (180 mg/dL [10.0 mmol/L]) measured by continuous glucose monitoring. Results: In an intention-to-treat analysis, mean time above range was 31% ± 15% at baseline, 19% ± 6% during FIA use, and 20% ± 6% during SIA use with no difference between treatments: mean difference = -0.9%; 95% CI: -2.4% to 0.6%; P = 0.23. Similarly, there was no difference in mean time in range (TIR) (78% and 77%) or median time below range (2.5% and 2.8%). Glycemic outcomes during exercise or postprandial periods were comparable for the two treatment arms. No severe hypoglycemia or diabetic ketoacidosis events occurred. Conclusions: FIA was not superior to SIA with hybrid AID system use in physically active children and adolescents with type 1 diabetes. Nonetheless, both insulin formulations enabled high overall TIR and low time above and below ranges, even during and after documented exercise. Trial Registration Clinicaltrials.gov: NCT04853030.

Adipose Tissue-Derived Stromal/Stem Cells Transplantation with Cholecalciferol Supplementation in Recent-Onset Type 1 Diabetes Patients: Twelve Months Follow-Up.

To evaluate safety and therapeutic effect along 12 months of allogenic adipose tissue-derived stromal/stem cells (ASCs) transplantation with cholecalciferol (VITD) in patients with recent-onset type 1 diabetes (T1D). Prospective, phase II, open trial, pilot study in which patients with recent onset T1D received ASCs (1xKgx106 cells) and VITD 2000UI/day for 12 months (group 1) and were compared to controls with standard insulin therapy (group 2). Adverse events, C-peptide area under the curve (CPAUC), insulin dose, HbA1c and frequency of FoxP3+ in CD4+ or CD8+ T-cells(flow cytometry) were evaluated at baseline(T0), after 3(T3), 6(T6) and 12 months(T12). Eleven patients completed follow up (7:group 1;4:group 2). Group 1 had lower insulin requirement at T3(0.24±0.18vs0.53±0.23UI/kg,p=0.04), T6(0.24±0.15vs0.66±0.33 UI/kg,p=0.04) and T12(0.39±0.15vs0.74±0.29 UI/Kg,p=0.04).HbA1c was lower at T6 (50.57±8.56vs72.25±10.34 mmol/mol,p=0.01), without differences at T12 (57.14±11.98 in group 1 vs. 73.5±14.57 mmol/min in group 2, p=0.16). CPAUC was not significantly different between groups at T0(p=0.07), higher in group 1 at T3(p=0.04) and T6(p=0.006), but similar at T12(p=0.23). IDAA1c was significantly lower in group 1 than group 2 at T3,T6 and T12 (p=0.006, 0.006 and 0.042, respectively). IDDA1c was inversely correlated to FoxP3 expression in CD4 and CD8+ T cells at T6 (p<0.001 and p=0.01, respectively). In group 1, one patient had recurrence of a benign teratoma that was surgically removed, not associated to the intervention. ASCs with VITD without immunosuppression were safe and associated lower insulin requirements, better glycemic control, and transient better pancreatic function in recent onset T1D, but the potential benefits were not sustained.

924-P: Glycemic Outcomes Improved and Maintained Regardless of Demographic Characteristics of Young Children with Type 1 Diabetes Using Closed-Loop System

Automated insulin delivery improves glycemic control in young children with type 1 diabetes (T1D). We investigated the potential impact of baseline participant characteristics on glycemic improvements when using the Tandem t:slim X2 insulin pump with Control-IQ technology (CIQ). After a 13 wk randomized, multi-center, controlled trial comparing CIQ (CLC) to standard care insulin delivery plus CGM (SC) in 102 children with T1D age 2 to &amp;lt;6 years, 95 continued CLC for 13 wks (CLC-CLC, N=62) or transitioned to CLC (SC-CLC, N=33). We compared glycemic outcomes from the RCT to the extension phase in subgroups based on baseline characteristics. At baseline, participants were 3.9 ± 1.2 years old with 25% minority race/ethnicity; 48% household income &amp;lt;$100,000; 57% parents with bachelor’s degree or less; 21% public insurance; 69% baseline HbA1c ≥7%; and 34% used multiple daily injections. In the SC-CLC group, time 70-180 mg/dL (TIR) improved in all subgroups regardless of race/ethnicity, family income, education, health insurance type, baseline HbA1c, and experience with devices (Table 1). In the CLC-CLC group, TIR improvement with CLC during the RCT was maintained regardless of subgroup. Our results support the findings that young children with T1D benefit from using CIQ regardless of their baseline characteristics. The benefit is maintained over a 26-week period. Disclosure L.Ekhlaspour: Consultant; Ypsomed AG, Tandem Diabetes Care, Inc., Other Relationship; NIH - National Institutes of Health, Research Support; MannKind Corporation, Tandem Diabetes Care, Inc., JDRF, Speaker's Bureau; Insulet Corporation. C.Kollman: Research Support; Insulet Corporation, Dexcom, Inc., Tandem Diabetes Care, Inc. R.Beck: Consultant; Eli Lilly and Company, Novo Nordisk, Diasome, Insulet Corporation, Research Support; Tandem Diabetes Care, Inc., Beta Bionics, Inc., Dexcom, Inc., Bigfoot Biomedical, Inc., Medtronic, Ascensia Diabetes Care, Roche Diabetes Care, Eli Lilly and Company, Novo Nordisk. M.D.Breton: Consultant; Dexcom, Inc., Tandem Diabetes Care, Inc., Roche Diabetes Care, Sanofi, Arecor, Research Support; Dexcom, Inc., Tandem Diabetes Care, Inc., Novo Nordisk. Pedap trial study group: n/a. Z.Reed: None. B.A.Buckingham: Advisory Panel; Medtronic, Novo Nordisk, Consultant; Lilly, Research Support; Medtronic, Insulet Corporation, Tandem Diabetes Care, Inc. M.D.Deboer: Research Support; Dexcom, Inc., Tandem Diabetes Care, Inc. G.P.Forlenza: Advisory Panel; Medtronic, Consultant; Dexcom, Inc., Insulet Corporation, Tandem Diabetes Care, Inc., Lilly Diabetes, Research Support; Medtronic, Abbott, Dexcom, Inc., Insulet Corporation, Tandem Diabetes Care, Inc. R.S.Kingman: None. M.Schoelwer: Research Support; Tandem Diabetes Care, Inc., Insulet Corporation. R.Wadwa: Consultant; Eli Lilly and Company, Other Relationship; Dexcom, Inc., Eli Lilly and Company, Research Support; Dexcom, Inc., Eli Lilly and Company, Beta Bionics, Inc., Tandem Diabetes Care, Inc. J.W.Lum: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (U01DK127551); Tandem Diabetes Care, Inc; Dexcom, Inc.

925-P: Postprandial Glucose Control Using an Extended Bolus for High Fat High Protein (HFHP) Meals during Closed-Loop (CL) in Patients with Type 1 Diabetes (T1D)

We investigated the impact of an extended bolus (EB) for a HFHP breakfast on postprandial glycemia in adolescents with T1D using the Control IQ (CIQ) system. In a randomized cross-over trial, following optimization, the participants with CIQ were asked to have identical standardized HFHP breakfasts (carbohydrate:51 g, fat:40 g, protein:54 g). Meal insulin bolus infusion began within 0.25 hrs of meal consumption (time 0). Eight adolescents (mean age 15.2 ± 1.7 yrs) were randomly assigned in blocks of two to the order in which they received the extended and standard insulin bolus (SB). Postprandial sensor glucose (SG) was measured for 5 hrs. The 5-hr incremental area under the curves (AUC) for SG was comparable for EB and SB (8913 and 10305 mg/dl/min, respectively). Peak SG value, time to peak SG, time in range SG (69.75% for SB vs. 71.7% for EB) and percent time &amp;gt;180 mg/dl were similar in both groups; however, the AUC for SG 2 hrs post meal onset and the rise in SG was significantly higher with EB (p= 0.02 and 0.03 respectively). Insulin use was not significantly different between arms. CL cannot fully compensate for a HFHP meal. However, SB appears to achieve better glycemic control than EB during the two hour postprandial period. Further studies with a larger sample size and larger and longer extended meal boluses may be needed to optimize pre-meal bolus dosing for HFHP meals. Disclosure L.Ekhlaspour: Consultant; Ypsomed AG, Tandem Diabetes Care, Inc., Other Relationship; NIH - National Institutes of Health, Research Support; MannKind Corporation, Tandem Diabetes Care, Inc., JDRF, Speaker's Bureau; Insulet Corporation. Y.J.Hosseinipour: None. B.A.Buckingham: Advisory Panel; Medtronic, Novo Nordisk, Consultant; Lilly, Research Support; Medtronic, Insulet Corporation, Tandem Diabetes Care, Inc. E.Cengiz: Advisory Panel; Eli Lilly and Company, Adocia, Novo Nordisk, Arecor. Funding National Institutes of Health (1K23DK121942)

923-P: CamAPS FX Hybrid Closed-Loop with Ultra-Rapid Insulin Lispro Increases Time in Range Compared with Standard Insulin Lispro in Adults with Type 1 Diabetes—A Double-Blind, Randomized, Crossover Study

Aim: To evaluate hybrid closed-loop with ultra-rapid insulin lispro (Lyumjev) in adults with type 1 diabetes (T1D). Methods: In a double-blind, randomized, crossover study, 28 adults with T1D (mean±SD; age 44.5±10.7 years, HbA1c 7.1±0.9% [54±10mmol/mol]) underwent two 8-week periods comparing hybrid closed-loop with Lyumjev and hybrid closed-loop with standard insulin lispro in random order. CamAPS FX closed-loop system was used in both periods. Results: In an intention-to-treat analysis, proportion of time sensor glucose was in target range (70 to 180mg/dL; primary endpoint) was greater with Lyumjev compared with standard insulin lispro (mean±SD; 78.7±9.8% vs. 76.2±9.6%; mean difference 2.5 percentage points [95%CI 0.8 to 4.2]; p=0.005). Mean sensor glucose was lower with Lyumjev compared with standard insulin lispro (142±14mg/dL vs. 146±16mg/dL; p=0.048). Proportion of time with sensor glucose &amp;lt;70mg/dL was similar between interventions (median[IQR] Lyumjev 2.3% [1.3-2.7%] vs. standard insulin lispro 2.1% [1.4-3.3%]; p=0.33). No severe hypoglycemia or ketoacidosis occurred. Conclusions: The use of Lyumjev with CamAPS FX hybrid closed-loop increases time in range and reduces mean glucose with no difference in hypoglycemia compared with standard insulin lispro in adults with T1D. Disclosure M.Nwokolo: None. R.Lakshman: None. C.K.Boughton: Consultant; CamDiab Ltd., Speaker's Bureau; Ypsomed AG. J.Ware: Other Relationship; Ypsomed AG. J.M.Allen: Research Support; CamDiab Ltd. M.E.Wilinska: Consultant; CamDiab Ltd. H.Alwan: None. M.Evans: Advisory Panel; Zucara Therapeutics, Pila Pharma, Dexcom, Inc., Other Relationship; Novo Nordisk, AstraZeneca, Abbott Diabetes, Speaker's Bureau; Eli Lilly and Company. R.Hovorka: Advisory Panel; Ypsomed AG, Consultant; Abbott Diabetes, B.Braun, Speaker's Bureau; Eli Lilly and Company, Stock/Shareholder; CamDiab Ltd. Funding National Institute for Health and Care Research; Cambridge Biomedical Research Centre (BRC-1215-20014)

108-LB: Randomized Trial of Automated Insulin Delivery in Pregnant Women with Type 1 Diabetes

Objective: To examine the clinical efficacy of automated insulin delivery (AID) during type 1 diabetes (T1D) pregnancy. Methods and Outcomes: We randomized pregnant women with T1D from nine UK clinical sites to hybrid closed-loop (CamAPS FX) or standard insulin therapy with continuous glucose monitoring. The primary outcome was the between-group difference in percentage time in the pregnancy-specific target glucose range (63-140mg/dl) from 16-weeks’ gestation until delivery. Analyses were performed according to intention-to-treat principles. Key secondary outcomes included overnight time-in-range (TIR), time spent hyperglycaemic (time-above-range, TAR &amp;gt;140mg/dl), HbA1c and safety events. Results: 124 participants (aged 31.1 ± 5.3yrs, HbA1c 7.7 ± 1.2%, T1D duration 2-31yrs, weight 49.0-138.0kg, total daily insulin doses 0.3-1.4units/kg) were randomized. The percentage of time that maternal glucose levels were within target was higher during AID than standard insulin therapy; mean between-group treatment difference 10%; 95% CI 7 to 10%; p &amp;lt; 0.001. Participants randomized to AID had larger reductions in hyperglycemia (AID vs control -11%; 95% CI -14 to - 7%; p&amp;lt;0.001), higher overnight time-in-range; (13%; 95% CI 9 to 17%; p&amp;lt;0.001), and lower HbA1c (-0.34%; 95%CI -0.52 to -0.15%; p&amp;lt;0.001), without additional insulin, weight gain or hypoglycemia. The treatment effect was apparent from early pregnancy, consistent across clinical sites, maternal HbA1c categories and previous insulin pump or injections. A significantly higher percent of AID participants reached CGM targets (TIR &amp;gt;70%: 46% vs 10%; p&amp;lt;0.001 and TAR &amp;lt;25%: 37% vs 11%; p=0.007 [AID vs. control]). One neonatal death that was unrelated to standard insulin therapy occurred. Conclusions: AID significantly improved maternal glycemia throughout T1D pregnancy. Our results support proposed NICE guideline recommendations that hybrid closed-loop therapy should be offered to all pregnant women with T1D. Disclosure H. R. Murphy: Advisory Panel; Medtronic, Research Support; Dexcom, Inc. L. Shepstone: None. M. E. Wilinska: Consultant; CamDiab Ltd. S. Bergford: None. J. Sibayan: None. C. Kollman: Research Support; Insulet Corporation, Dexcom, Inc., Tandem Diabetes Care, Inc. R. Beck: Consultant; Eli Lilly and Company, Novo Nordisk, Diasome, Insulet Corporation, Research Support; Tandem Diabetes Care, Inc., Beta Bionics, Inc., Dexcom, Inc., Bigfoot Biomedical, Inc., Medtronic, Ascensia Diabetes Care, Roche Diabetes Care, Eli Lilly and Company, Novo Nordisk. R. Hovorka: Advisory Panel; Ypsomed AG, Consultant; Abbott Diabetes, B. Braun, Speaker's Bureau; Eli Lilly and Company, Stock/Shareholder; CamDiab Ltd. T. T. M. Lee: None. C. Collett: None. S. Hartnell: Advisory Panel; Dexcom, Inc., Medtronic, Consultant; CamDiab Ltd., Other Relationship; AskDiabetes Ltd, Speaker's Bureau; Abbott Diabetes, Ypsomed AG. E. M. Scott: Research Support; Abbott Diabetes, Speaker's Bureau; Abbott Diabetes. R. S. Lindsay: None. K. F. Hunt: None. D. R. Mccance: None. M. Hammond: None. Funding National Institute for Health Research (16/35/01); JDRF (22-2013-266, 2-RSC-2019-828-M-N); Diabetes Research and Wellness Foundation (SECF/21 to T.T.M.L.)

Metabolic Memory of Type 1 Diabetes Revisited

In 2021, there were 8.4 million cases of type 1 diabetes mellitus (T1DM) worldwide which projected to reach 17.4 million cases in 2040. Patients diagnosed with T1DM are on life-long insulin injections in order to regulate their blood glucose levels. The standard insulin therapy and subsequent monitoring HbA1c is no longer sufficient for T1DM patients management. Instead, postprandial hyperglycemia as well as glycemic variations should be minimized to reach near normoglycemic state. To do so, intensive insulin therapy should be introduced so as to restore homeostatic glycemic control.

The diabetes insulin self-management education (DIME) intervention for people with type 2 diabetes starting insulin: a pilot feasibility randomised controlled trial

ObjectiveTo determine the feasibility and acceptability of a diabetes insulin self-management education (DIME) group intervention for people with type 2 diabetes starting insulin.DesignSingle-centre parallel randomised pilot trial.SettingPrimary care, South London, UK.SubjectsAdults with type 2 diabetes, requiring insulin treatment, on maximum tolerated dose of 2 or more oral antidiabetic drugs with HbA1c > / = 7.5% (58 mmol/mol) on 2 occasions. We excluded people who were non-fluent in English; morbid obesity (BMI > / = 35 kg/m2); in employment that contraindicates insulin treatment; and those with severe depression, anxiety disorders, psychotic disorders, personality disorders, or cognitive impairment.MethodsParticipants were randomised using blocks of 2 or 4 to 3, 2-h group, face-to-face, DIME sessions or standard insulin group education sessions (control). We assessed feasibility according to consent to randomisation and attendance at intervention (DIME) and standard group insulin education sessions. Acceptability of the interventions was determined using exit interviews. We additionally measured change in self-reported insulin beliefs, diabetes distress and depressive symptoms between baseline and 6-month post-randomisation.ResultsThere were 28 potentially eligible participants, of which 17 consented to randomisation, 9 were allocated to the DIME group intervention and 8 were allocated to the standard group insulin education. Three people withdrew from the study (1 from DIME and 2 from standard insulin education) before the start of the first session and did not complete baseline questionnaires. Of the remaining participants (n = 14), all DIME participants (n = 8) completed all 3 sessions, and all standard insulin education participants (n = 6) completed at least 1 standard insulin education session. The median group size was 2, the mean age of participants was 57.57 (SD 6.45) years, and 64% were female (n = 9). Exit interviews demonstrated that all participants (n = 7) found the group sessions acceptable, and thematic analysis of interview transcripts indicated social support, the content of group sessions and post-group experiences were positive, especially amongst DIME participants. There was improvement on self-report questionnaires.ConclusionsThe DIME intervention was acceptable and feasible to deliver to participants with type 2 diabetes starting insulin in South London, UK.Trial registrationInternational Study Registration Clinical Trial Network (ISRCTN registration number 13339678).

Lipid Profile Normalization Effect of Hunteria Umbellata Aqueous Fruit Extract in Wistar Rats Induced with Aloxan Monohydrate

The present study investigated the potential effect of Hunteria Umbellata fruit extract on lipid profile reduction administered at different daily doses ie 200mg/kg, 400mg/kg compared with control (1) and group5 treated at 0.3ml standard drug insulin following aloxan monohydrate induction. The lipid profile- HDL,LDL,vLDL,Triglycerides and Total cholesterol were determine using precipitant (mmol), enzymatic hydrolysis, enzymatic and point methods. Results from this study indicate that the lipid profile reduction potential of H.U fruit extract was most effective in group2 administered 200mg/kg body weight with no aloxan induction. This was closely followed by group3 treated at 400mg/kg and group5 treated with the standard drug insulin after aloxan induction compared with the control. However, goup4 induced with aloxan and treated at 200mg/kg body weight has an elevated lipid profile compared with the control and other groups studied. Findings from this study have shown that moderate dose intake of Hunteria umbellata fruit extract by subjects with hyperlipidaemia can be beneficial in the reduction of lipid profile but the rapidity of its reduction rate is dose dependent.

Time requirements for perioperative glucose management using fully closed-loop versus standard insulin therapy: A proof-of-concept time-motion study.

To compare the time required for perioperative glucose management using fully automated closed-loop versus standard insulin therapy. We performed a time-motion study to quantify the time requirements for perioperative glucose management with fully closed-loop (FCL) and standard insulin therapy applied to theoretical scenarios. Following an analysis of workflows in different periods of perioperative care in elective surgery patients receiving FCL or standard insulin therapy upon hospital admission (pre- and intra-operatively, at the intermediate care unit and general wards), the time of process-specific tasks was measured by shadowing hospital staff. Each task was measured 20 times and its average duration in combination with its frequency according to guidelines was used to calculate the cumulative staff time required for blood glucose management. Cumulative time was calculated for theoretical scenarios consisting of elective minor and major abdominal surgeries (pancreatic surgery and sleeve gastrectomy, respectively) to account for the different care settings and lengths of stay. The FCL insulin therapy reduced the time required for perioperative glucose management compared to standard insulin therapy, across all assessed care periods and for both perioperative pathways (range 2.1-4.5). For a major abdominal surgery, total time required was 248.5 min using FCL versus 753.9 min using standard insulin therapy. For a minor abdominal surgery, total time required was 68.6 min and 133.2 min for FCL and standard insulin therapy, respectively. The use of fully automated closed-loop insulin delivery for inpatient glucose management has the potential to alleviate the workload of diabetes management in an environment with adequately trained staff.

Implementation of fully closed-loop insulin delivery for inpatients with diabetes: real-world outcomes.

Fully closed-loop insulin delivery has been shown in clinical trials to be safe and improve glucose control compared with standard insulin therapy in the inpatient setting. We investigated the feasibility of implementing the approved CamAPS HX fully closed-loop system in a hospital setting. This implementation project was conducted in a large teaching hospital in Cambridge, UK. Healthcare professional training was multimodal including face-to-face workshops, online learning modules and supported by standard operating procedures. Set-up and maintenance of closed-loop devices was undertaken by the inpatient diabetes team. Selection of suitable patients was multidisciplinary and prioritised those with more challenging diabetes management. Demographic and clinical data were collected from electronic health records and diabetes data management platforms. In the 12 months since the closed-loop system was implemented, 32 inpatients (mean±SD age 61±16 years, 8 females, 24 males) used closed-loop insulin delivery during their admission, across medical and surgical wards in the hospital with a total of 555 days of closed-loop glucose control (median[IQR]: 14[6, 22] days per inpatient). The time spent in target glucose range 3.9-10.0mmol/L was 53.3±18.3%. Mean glucose was 10.7±1.9mmol/L with 46.0±18.2% of time spent with glucose >10.0mmol/L. Time spent with sensor glucose below 3.9mmol/L was low (median[IQR]: 0.38[0.00, 0.85]). There were no episodes of severe hypoglycaemia or diabetic ketoacidosis during closed-loop use. We have demonstrated that the fully closed-loop system can be safely and effectively implemented by a diabetes outreach team in complex medical and surgical inpatients with challenging glycaemic control.

Patient perceptions of insulin therapy in diabetes self-management with insulin injection devices

AimsSeveral insulin delivery systems are available to control glycemia in patients with diabetes. Recently introduced devices feature connectivity enabling data transfer to smartphone applications to provide decision support and reduce errors in dosing and timing, while reducing the cognitive burden.MethodsWe conducted an online survey in Italian patients with a self-reported diagnosis of diabetes to assess patient perceptions of insulin therapy management, and their impressions of connection-enabled insulin pens compared to standard insulin pens. The Morisky Medication Adherence Scale-8 was used to assess adherence to insulin therapy.ResultsAmong 223 respondents (108 with type 1 diabetes; 115 with type 2 diabetes), the most prominent unmet need was the necessity to overcome the cognitive burden of care associated with measuring, calculating, timing, and recording therapy. Only 25% of respondents had high adherence; 28% had low adherence.ConclusionsWhen asked to compare the attributes of a non-connected insulin pen with those of a new connected device, 71% of patients rated the new proposal “very useful”. The cognitive burden associated with self-management of diabetes therapy may influence preferences for advanced insulin delivery systems.

Effect of glucagon-like peptide-1 receptor agonists administration during coronary artery bypass grafting: a systematic review and meta-analysis of randomized control trials.

Aim: To determine if glucagon-like peptide-1 receptor agonists (GLP-1 RAs) can benefit patients receiving coronary artery bypass graft (CABG), GLP-1 RAs administration alongside standard insulin was compared with perioperative insulin alone. Materials & methods: All articles from Pubmed and Scopus databases that compared GLP-1 RA administration to insulin alone during CABG were included for meta-analysis. Short-term postoperative outcomes were analyzed between groups. Results: Average postoperative blood glucose levels significantly favored GLP-1 RA with a mean difference of -0.72 (p<0.001). No other variables were significantly different between GLP-1 RA and insulin alone. Conclusion: GLP-1 RA is a safe option for perioperative care of CABG patients that can potentially improve postoperative outcomes of CABG patients by improving glycemic control and reducing hyperglycemic episodes.

CHoKI-based MPC for blood glucose regulation in artificial Pancreas

This work presents a Model Predictive Control (MPC) algorithm for the artificial pancreas able to autonomously manage basal insulin injections in type 1 diabetic patients. The MPC goal is to maintain the blood glucose inside the safe range (70-180 mg/dL) acting on the insulin amount, using a model to make predictions of the system behavior and satisfying operational constraints. The complexity of diabetes complicates the identification of a general physiological model, so a data-driven learning method is proposed, the Componentwise Hölder Kinky Inference (CHoKI), leading to customized controllers. For the data collection phase and also to test the proposed controller, the FDA-accepted UVA/Padova simulator is exploited. The final results are promising since the proposed controller reduces the time in hypoglycemia if compared to the standard constant basal insulin therapy, satisfying also the time in range requirements.