Improvement In Glycemic Control Research Articles

217-OR: A Randomized Controlled Trial Comparing the Safety and Efficacy of IDegLira vs. Basal Bolus in Patients with Poorly Controlled Type 2 Diabetes and Very High HbA1c (>9%–15%) : IDegLira HIGH Trial

IDegLira-HIGH trial was a non-inferiority, prospective, randomized clinical trial, comparing the efficacy and safety of insulin degludec/liraglutide combination (IDegLira) and a regimen of multiple daily injections (MDI) with basal-bolus insulin (BB) in adults (>18-80 years of age) , with type 2 diabetes (T2D) , and very high HbA1c (>9%-15%) , previously treated with basal insulin or multiple oral agents. Primary endpoint was change in HbA1c from baseline to week 26. Secondary endpoints included incidence of hypoglycemia, changes on weight and glycemic variability (% coefficient of variation [%CV]) . Treatment with IDegLira and BB insulin resulted in similar improvement in glycemic control: 7.7±1.7% and 7.7±1.5%, (p=0.76) , with a reduction from baseline of -3.2±2.3% and -3.0±1.8%, (p=0.39) at 26-weeks. IDegLira resulted in lower rates of hypoglycemia <70 mg/dl (22% vs. 36%, p=0.05) , similar glycemic variability (CGM %CV 30.4±9.1% vs. 33.2±7.3%, p=0.08) , and greater weight loss (-3.7±4.1 kg vs. +8.4±5.4 kg, p<0.01) compared to BB. IDegLira was associated with higher rates of nausea (Table 1) . Conclusions: In patients with T2D and very high HbA1c (≥9%-15%) , a regimen of daily IDegLira injection is non-inferior to MDI with BB insulin on HbA1c reduction and was associated with weight loss and less hypoglycemia. Disclosure R.J.Galindo: Advisory Panel; Sanofi, WW International, Inc., Research Support; Dexcom, Inc., Eli Lilly and Company, Novo Nordisk. G.E.Umpierrez: Research Support; AstraZeneca, Dexcom, Inc., Novo Nordisk. B.Moazzami: None. M.F.Scioscia: None. P.Vellanki: n/a. G.M.Davis: Consultant; Medscape, Research Support; Insulet Corporation. F.J.Pasquel: Consultant; AI Health LLC, Boehringer Ingelheim International GmbH, Dexcom, Inc., Research Support; Dexcom, Inc., Insulet Corporation, Merck & Co., Inc. M.Fayfman: None. A.L.Migdal: None. J.Saling: None. Funding Investigator-initiated study to Emory University (PI. Dr. Rodolfo J. Galindo) from Novo Nordisk.

719-P: Tirzepatide Induces Weight Loss in Patients with Type 2 Diabetes Regardless of Baseline BMI: A Post Hoc Analysis of SURPASS-1 through -5 Studies

Tirzepatide (TZP) is a novel once-weekly dual GIP and GLP-1 receptor agonist evaluated in patients with type 2 diabetes (T2D) . Five Phase 3 SURPASS (S) trials have demonstrated safety and shown robust efficacy of TZP in improvement of glycaemic control and body weight (BW) in adults with T2D. To understand whether the weight-lowering effects of TZP are dependent on baseline BMI, we conducted subgroup analyses of S-1 through -5. BW change in the BMI subgroups (Subgroup 1 [<27 or ≥27 kg/m2] and Subgroup 2 [<30; ≥30 to <35; ≥35 kg/m2]) at primary endpoint was assessed in patients while on treatment without rescue medication (efficacy estimand) in the modified intention-to-treat (mITT) population, defined as all randomized patients who received at least one dose of study drug. All TZP doses (5, 10, 15 mg) lowered BW in patients with T2D irrespective of baseline BMI in both subgroups (p<0.001) . The weight reductions were generally dose-dependent and absolute weight change was generally greater in higher BMI categories. TZP-treated patients with T2D experienced weight loss across a spectrum of mean baseline BMI values in S-1 through -5 studies. The most frequent adverse events were GI-related events that were mild to moderate in severity and occurred during the dose-escalation period. Disclosure A.Kwan: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. J.M.Maldonado: Employee; Eli Lilly and Company. H.Wang: None. N.Rasouli: Advisory Panel; Eli Lilly and Company, Novo Nordisk, Sanofi, Research Support; Allergan, Eli Lilly and Company, Novo Nordisk. J.Wilding: Advisory Panel; Alnylam Pharmaceuticals, Inc., AstraZeneca, Eli Lilly and Company, Mundipharma, Novo Nordisk A/S, Rhythm Pharmaceuticals, Inc., Sanofi, Research Support; AstraZeneca, Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly Diabetes, Novo Nordisk A/S, Takeda Pharmaceutical Company Limited. Funding Eli Lilly and Company

708-P: Hypertension Control among People with Diabetes Using a Self-Management Multicondition Digital Platform

Introduction: Digital multicondition platforms seek to assist persons with diabetes in management of their diabetes and comorbidities. Hypertension is reported in over two-thirds of patients with type 2 diabetes. Both are major risk factors for cardiac, stroke, and kidney disorders. Dario’s digital therapeutics platform for chronic conditions supports self-management of diabetes and high blood pressure. The platform enables digital evaluation of blood glucose and blood pressure levels in real time and supports interventions based on clinical indicators. Method: A retrospective data evaluation was performed on the Dario data base since 2019. A population of active users who started with hypertension stage 1 as baseline was identified. Blood glucose and blood pressure readings were assessed at first month and 6th month of use. A subgroup of users who started at hypertension stage 2 was evaluated as well. Systolic, diastolic pressures and average blood glucose were evaluated along of the study. Results: For the 2554 users identified with diabetes and hypertension, more than two thirds improved their systolic blood pressure by 13 mmHg (P<0.001; 144±14 to 131±13) . A group of 38.7% (N=990) moved to a lower hypertensive stage (P<0.001) . The subset of 1367 users with stage 2 hypertension improved their systolic blood pressure from 150±12.4 to 141±15.2 mmHg on average and 43.9% (N=600) improved their blood pressure by more than mmHg over six months (P<0.001) . A subgroup of 3users who started at high-risk blood glucose levels significantly reduced their blood glucose average by 15% over 6 months (232.4±46 to 198±65 mg/dL) (P<0.001) . Conclusion: A multicondition digital therapeutic platform may promote behavioral modifications and result in sustainable improvements in both glycemic control and blood pressure levels. The study demonstrates an improvement in multiple chronic conditions (diabetes and Hypertension) for people using one digital platform. Disclosure Y.Hershcovitz: None. M.Tamir: None. O.Manejwala: Employee; DarioHealth Corp., Stock/Shareholder; DarioHealth Corp.

785-P: Comparison of Six Months Experience on Hybrid Closed Loop MiniMed 670G System and Advanced Hybrid Closed Loop MiniMed 780G System Using a Structured Initiation Protocol in Children and Adolescents with Type 1 Diabetes

Background: The objective of this study was to evaluate glycemic outcomes using a structured initiation protocol for Hybrid Closed Loop (HCL) MiniMed 670G and Advanced Hybrid Closed Loop (AHCL) Minimed 780G system in children and adolescents with Type 1 Diabetes (T1D) previously treated with Multiple Daily Injections. Methods: The data from two separate (HCL and AHCL system) investigations were analyzed in individuals (aged 7-18 years) with T1D on MDI therapy, both followed a structured initiation protocol. Time in Ranges, HbA1c and system characteristics were analyzed between two systems at 3 and 6 months of Automated Insulin Delivery (AID) . Results: 30 children (age 10.24 ± 2.6 years, HbA1c 8.2±1.4% (66±15.3 mmol/mol)) with HCL system and 34 children (12.5 ± 3.7 years, 8.6±1.7% (70±18.6 mmol/mol)) with AHCL system completed the planned 12 weeks of AID. TIR (70-180mg/dl) of 73.4±8.9% with HCL and 78.2±4.3% with AHCL (p=0.01) was achieved at 6 months of AID. No episodes of severe hypoglycemia or DKA were reported using both systems. Conclusion: Individuals using AHCL MiniMed 780G system had more stringent system settings, spent more time in AID with less exits, which possibly lead to further improvements of glycemic control compared to HCL MiniMed 670G system using the same structured protocol. Disclosure G.Petrovski: None. J.Campbell: Advisory Panel; Medtronic. F.Alkhalaf: None. K.Hussain: None.

Examining the evidence for weight management in individuals with type 2 diabetes.

The obesity epidemic has been linked to the worsening diabetes epidemic. Despite this, weight reduction for individuals with obesity is seen as a secondary, or even tertiary, consideration in the treatment of type 2 diabetes (T2D). The aim of this review is to examine the benefits of weight management in individuals with T2D. A literature review of current available published data on the benefits of weight reduction in individuals with T2D was conducted. In individuals with T2D who have obesity or overweight, modest and sustained weight reduction results in improvement in glycaemic control and decreased utilization of glucose-lowering medication. A total body weight loss of 5% or higher reduces HbA1c levels and contributes to mitigating risk factors of cardiovascular disease, such as hyperlipidaemia and hypertension, as well as other disease-related complications of obesity. Progressive improvements in glycaemic control and cardiometabolic risk factors can occur when the total body weight loss increases to 10% or more. In the approach to treating patients with T2D and obesity, prioritizing weight management and the use of therapeutics that offer glycaemic control as well as the additional weight loss should be emphasized given their potential to attenuate the progression and severity of T2D.

Pancreatic islet transplantation in type 1 diabetes: 20-year experience from a single-centre cohort in Canada

Islet transplantation offers an effective treatment for selected people with type 1 diabetes and intractable hypoglycaemia. Long-term experience, however, remains limited. We report outcomes from a single-centre cohort up to 20 years after islet transplantation. This cohort study included patients older than 18 years with type 1 diabetes undergoing allogeneic islet transplantation between March 11, 1999, and Oct 1, 2019, at the University of Alberta Hospital (Edmonton, AB, Canada). Patients who underwent islet-after-kidney transplantation and islet transplantation alone or islet transplantation before whole-pancreas transplantation (follow-up was censored at the time of whole-pancreas transplantation) were included. Patient survival, graft survival (fasting plasma C-peptide >0·1 nmol/L), insulin independence, glycaemic control, and adverse events are reported. To identify factors associated with prolonged graft survival, recipients with sustained graft survival (≥90% of patient follow-up duration) were compared with those who had non-sustained graft survival (<90% of follow-up duration). Multivariate binary logistic regression analyses were done to determine predictors of sustained graft survival. Between March 11, 1999, and Oct 1, 2019, 255 patients underwent islet transplantation and were included in the analyses (149 [58%] were female and 218 [85%] were White). Over a median follow-up of 7·4 years (IQR 4·4-12·2), 230 (90%) patients survived. Median graft survival was 5·9 years (IQR 3·0-9·5), and graft failure occurred in 91 (36%) patients. 178 (70%) recipients had sustained graft survival, and 77 (30%) had non-sustained graft survival. At baseline, compared with patients with non-sustained graft survival, those with sustained graft survival had longer median type 1 diabetes duration (33·5 years [IQR 24·3-41·7] vs 26·2 years [17·0-35·5]; p=0·0003), median older age (49·4 years [43·5-56·1] vs 44·2 years [35·4-54·2]; p=0·0011), and lower median insulin requirements (0·53 units/kg per day [0·45-0·67] vs 0·59 units/kg per day [0·48-0·70]; p=0·032), but median HbA1c concentrations were similar (8·2% [7·5-9·0] vs 8·5% [7·8-9·2]; p=0·23). 201 (79%) recipients had insulin independence, with a Kaplan-Meier estimate of 61% (95% CI 54-67) at 1 year, 32% (25-39) at 5 years, 20% (14-27) at 10 years, 11% (6-18) at 15 years, and 8% (2-17) at 20 years. Patients with sustained graft survival had significantly higher rates of insulin independence (160 [90%] of 178 vs 41 [53%] of 77; p<0·0001) and sustained improvements in glycaemic control mixed-main-effects model group effect, p<0·0001) compared with those with non-sustained graft survival. Multivariate analyses identified the combined use of anakinra plus etanercept (adjusted odds ratio 7·5 [95% CI 2·7-21·0], p<0·0001) and the BETA-2 score of 15 or higher (4·1 [1·5-11·4], p=0·0066) as factors associated with sustained graft survival. In recipients with sustained graft survival, the incidence of procedural complications was lower (23 [5%] of 443 infusions vs 17 [10%] of 167 infusions; p=0·027), whereas the incidence of cancer was higher (29 of [16%] of 178 vs four [5%] of 77; p=0·015) than in those with non-sustained graft survival; most were skin cancers (22 [67%] of 33). End-stage renal disease and severe infections were similar between groups. We present the largest single-centre cohort study of long-term outcomes following islet transplantation. Although some limitations with our study remain, such as the retrospective component, a relatively small sample size, and the absence of non-transplant controls, we found that the combined use of anakinra plus etanercept and the BETA-2 score were associated with improved outcomes, and therefore these factors could inform clinical practice. None.

Addition of intermittently scanned continuous glucose monitoring to standard care in a cohort of pregnant women with type 1 diabetes: effect on glycaemic control and pregnancy outcomes.

The aim of this study was to assess whether the addition of intermittently scanned continuous glucose monitoring (isCGM) to standard care (self-monitoring of blood glucose [SMBG] alone) improves glycaemic control and pregnancy outcomes in women with type 1 diabetes and multiple daily injections. This was a multicentre observational cohort study of 300 pregnant women with type 1 diabetes in Spain, including 168 women using SMBG (standard care) and 132 women using isCGM in addition to standard care. In addition to HbA1c, the time in range (TIR), time below range (TBR) and time above range (TAR) with regard to the pregnancy glucose target range (3.5-7.8mmol/l) were also evaluated in women using isCGM. Logistic regression models were performed for adverse pregnancy outcomes adjusted for baseline maternal characteristics and centre. The isCGM group had a lower median HbA1c in the second trimester than the SMBG group (41.0 [IQR 35.5-46.4] vs 43.2 [IQR 37.7-47.5] mmol/mol, 5.9% [IQR 5.4-6.4%] vs 6.1% [IQR 5.6-6.5%]; p=0.034), with no differences between the groups in the other trimesters (SMBG vs isCGM: first trimester 47.5 [IQR 42.1-54.1] vs 45.9 [IQR 39.9-51.9] mmol/mol, 6.5% [IQR 6.0-7.1%] vs 6.4% [IQR 5.8-6.9%]; third trimester 43.2 [IQR 39.9-47.5] vs 43.2 [IQR 39.9-47.5] mmol/mol, 6.1% [IQR 5.8-6.5%] vs 6.1% [IQR 5.7-6.5%]). The whole cohort showed a slight increase in HbA1c from the second to the third trimester, with a significantly higher rise in the isCGM group than in the SMBG group (median difference 2.2 vs 1.1mmol/mol [0.2% vs 0.1%]; p=0.033). Regarding neonatal outcomes, newborns of women using isCGM were more likely to have neonatal hypoglycaemia than newborns of non-sensor users (27.4% vs 19.1%; ORadjusted 2.20 [95% CI 1.14, 4.30]), whereas there were no differences between the groups in large-for-gestational-age (LGA) infants (40.6% vs 45.1%; ORadjusted 0.73 [95% CI 0.42, 1.25]), Caesarean section (57.6% vs 48.8%; ORadjusted 1.33 [95% CI 0.78, 2.27]) or prematurity (27.3% vs 24.8%; ORadjusted 1.05 [95% CI 0.55, 1.99]) in the adjusted models. A sensitivity analysis in pregnancies without LGA infants or prematurity also showed that the use of isCGM was associated with a higher risk of neonatal hypoglycaemia (non-LGA: ORadjusted 2.63 [95% CI 1.01, 6.91]; non-prematurity: ORadjusted 2.52 [95% CI 1.12, 5.67]). For isCGM users, the risk of delivering an LGA infant was associated with TIR, TAR and TBR in the second trimester in the logistic regression analysis. isCGM use provided an initial improvement in glycaemic control that was not sustained. Furthermore, offspring of isCGM users were more likely to have neonatal hypoglycaemia, with similar rates of macrosomia and prematurity to those of women receiving standard care.

Participation in Diabefly® digital therapeutics program leads to significant improvement in glycemic control and reduction in weight and BMI among people with T2D

Participation in Diabefly® digital therapeutics program leads to significant improvement in glycemic control and reduction in weight and BMI among people with T2D

Effectiveness of Roux-en-Y Gastric Bypass vs Sleeve Gastrectomy on Lipid Levels in Type 2 Diabetes: a Meta-analysis

IntroductionObesity and its co-morbidities, including type 2 diabetes (T2DM) and dyslipidemia, are accompanied by excess cardiovascular morbi-mortality. Aside from excess low density lipoprotein-cholesterol (LDL-C), atherogenic dyslipidemia (AD), mainly characterized by elevated triglycerides and decreased high density lipoprotein-cholesterol (HDL-C) levels, is often present in T2DM obese patients. Bariatric surgery, such as Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), has become a reference treatment in that population. However, the respective effects of RYGB vs SG on lipid metabolism in T2DM patients have been rarely studied. MethodsA meta-analysis of randomized controlled trials, comparing the effects of RGYBG vs SG on lipid metabolism 12 months after surgery in T2DM patients, was performed. ResultsFour studies including a total of 298 patients (151 patients in the RYGB and 147 patients in the SG group) were examined. Despite a greater decrease in body mass index and greater improvement in glycemic control in RYGB compared to SG. RYGB vs SG was more effective in reducing total cholesterol, LDL-C, and non-HDL-C levels (mean difference [MD] −26.10 mg/dL, 95 % CI −38.88 to −13.50, p<0.00001; [MD] −20.10 mg/dL, 95 % CI −27.90 to −12.20, p<0.00001 and MD 31.90 mg/dl, 95 % CI −46.90 to −16.80, p<0.00001, respectively). ConclusionsThe superiority of RYGB vs SG in reducing LDL-C, with an effect comparable to a moderate-intensity statin, suggests RYBG should be favored in hypercholesterolemic T2DM patients in order to further reduce cardiovascular risk.

FC 116: SGLT2 Inhibitors in Kidney Transplantation: A Multicenter Study

Abstract BACKGROUND AND AIMS SGLT2 inhibitors (SGLT2i) are the first-line therapy in patients with type 2 diabetes mellitus (DM2) and CKD, together with metformin according to most recent published guidelines. They are related to better renal and cardiovascular outcomes. SGLT2i could be potentially benefitial in terms of renal function preservation and cardiovascular outcomes in kidney transplantion (KT). Despite published data about SGLT2i in KT patients with DM2 or new-onset diabetes after transplantation are limited, their use seems to be common in everyday clinical practice. Our aim is to investigate if SGLT2i are safe and well tolerated in a cohort of KT recipients, as well as to analyze clinical and laboratory data at 6 months after SGLT2i initiation. METHOD Multicentre observational study in KT recipients with diabetes under SGLT2i treatment. RESULTS A total of 323 patients were included, and 284 completed a 6-month follow-up. Mean age was 61.2 ± 10.3 years old, 74.4% were men and 41% presented DM2. Previous antidiabetic therapies: insulin (48.1%), DPP4 inhibitors (36.1%) and metformin (33.1%). Empagliflozine was started in 55.8%, dapagliflozine in 23.2% and canagliflozin in 20.6%. After SGLT2i initiation, body weight reduction, an improvement in blood pressure and glycaemic control, higher haemoglobin levels and a decrease in cholesterol levels were observed. Also, a mild decrease in eGFR was detected while albuminuria was lower. These differences were statistically significant (Table 1). In 34 patients (10.5%), SGLT2i was stopped: 2.78% presented urinary tract infection (UTI), 1.5% balanitis and 1.2% important eGFR decreasing slope. During the study period, six patients presented a graft loss (one related to SLGT2) and six patients died (deaths not related to SGLT2i). CONCLUSION SGLT2i have a safe security profile in KT, and are related to a better glycaemic and blood pressure control, as well as to a decrease in albuminuria, and to an improvement in cardiovascular risk factors. Thus, SGLT2i should be prescribed in KT recipients with DM2 or NODAT with adequate eGFR. UTI surveillance is essential in these patients.

Prevention and management of type 2 diabetes mellitus in Uganda and South Africa: Findings from the SMART2D pragmatic implementation trial.

Health systems in many low- and middle-income countries are struggling to manage type 2 diabetes (T2D). Management of glycaemia via well-organized care can reduce T2D incidence, and associated morbidity and mortality. The primary aim of this study was to evaluate the effectiveness of facility plus community care interventions (integrated care), compared to facility only care interventions (facility care) towards improvement of T2D outcomes in Uganda and South Africa. A pragmatic cluster randomized trial design was used to compare outcomes among participants with T2D and those at high risk. The trial had two study arms; the integrated care arm, and the facility care arm; and in Uganda only, an additional usual care arm. Participants were enrolled at nine primary health facilities in Uganda, and two in South Africa. Participants were adults aged 30 to 75 years, and followed for up to 12 months. Primary outcomes were glycaemic control among participants with T2D, and reduction in HbA1c > = 3 mmol/mol among participants at high risk. Secondary outcomes were retention into care and incident T2D. Adjusted analysis revealed significantly higher retention into care comparing integrated care and facility care versus usual care in Uganda and integrated care versus facility care in South Africa. The effect was particularly high among participants at high risk in Uganda with an incident rate ratio of 2.46 [1.33-4.53] for the facility care arm and 3.52 [2.13-5.80] for the integrated care arm. No improvement in glycaemic control or reduction in HbA1c was found in either country. However, considerable and unbalanced loss to follow-up compromised assessment of the intervention effect on HbA1c. Study interventions significantly improved retention into care, especially compared to usual care in Uganda. This highlights the need for adequate primary care for T2D and suggest a role for the community in T2D prevention. Trial registration number: ISRCTN11913581.

Abstract #1184056: Tirzepatide Improves Glucose Levels from Baseline Irrespective of Gender: A Post Hoc Analysis of the SURPASS-1 to -5 Studies

Tirzepatide is a once-weekly dual GIP and GLP-1 receptor agonist developed as an adjunct to diet and exercise to improve glycaemic control in patients with type 2 diabetes (T2D). The SURPASS (S) program spanning the T2D disease progression from no background therapy to multiple background combinations and comparators led to robust improvements in glycaemic control by tirzepatide as shown by a reduction in HbA1c and fasting serum glucose (FSG) at 40 and/or 52 weeks. This post-hoc analysis from the 5 SURPASS studies (S-1 to S-5) assessed the effect of tirzepatide on glycaemic control and safety, according to patient gender.

Effect of a chromium‐fructooligosaccharide complex on glycemic parameters in obese and obese‐NIDDM rats

The incidence and odds ratio of obesity and Type 2 diabetes, a common sequela of obesity, are increasing in incidence to the point of becoming epidemic in Western society. To determine the potential beneficial effects of a chromium‐fructooligosaccharide complex (FCC) on glycemic responses of male obese and obese NIDDM rats, groups of 3 ‐ 4 month old lean and obese LA/Ntul//‐cp and SHR/Ntul//‐cp rats (NIDDM‐rats, n= 6 rats/group) reared normally on Purina #5012 chow from the time of weaning, were subjected to an oral glucose tolerance (OGT) after a brief 4‐hour fast. A second group of NIDDM rats (n=5) aged one year were also administered the OGT and FCC challenges. NIDDM rats develop IGT by adolescence and renal disease, cataracts, and impaired nerve conduction velocity typical of DM by adulthood. Animals were administered a glucose solution equivalent to 2.5 grams/kg BW via intragastric gavage, or the same glucose plus the FCC (2.5 g/kg BW, containing 200µg Cr and 2.25 mg/serving) or the FCC alone over a brief (1‐2 minute) duration. Measures of blood glucose (BG) were determined at 30‐minute intervals from zero to +120 minutes post gavage via tail bleeding, and the area under the curve (AUC) of each group determined. Final body weights (BW) of obese were greater than lean (p=0.05), and obese‐NIDDM &gt; Obese rats (p=&lt;0.05) and increased in NIDDM rats with older age. OGT of lean rats remained normal throughout, and FCC resulted in minor decreases in AUC and in BG concentrations at all time points (p= n.s.) The OGT of obese rats demonstrated significant increases in BG at +60, +90‐, and +120‐minutes post gavage but remained non‐diabetic, and FCC decreased the glycemic increase and AUC by ~50%, similar to the glycemic response off lean littermates. The OGT of young NIDDM was significantly impaired and FCC resulted in a 32% reduction in the AUC. The OGT and AUC of OLD NIDDM rats was greater than in young rats and was decreased by 25% with FCC. OGT and OGG+FCC were similar at both ages in NIDDM rats. These results are consistent with an FCC‐mediated improvement in glycemic control in congenic animal models for obesity and obesity+NIDDM and suggest that the FCC complex may be a useful nutraceutical adjunct in the dietary treatment of obesity and other glucose intolerant states as they occur in man and animals.

Thrice daily consumption of a novel, premeal shot containing a low dose of whey protein increases time in euglycemia during 7 days of free-living in individuals with type 2 diabetes

IntroductionDuring acute feeding trials, consuming a large dose of whey protein (WP) before meals improves postprandial glucose regulation in people with type 2 diabetes. It is unclear if the reported...

Canagliflozin Regulates Human Endothelial Cell Function: Role of Heme Oxygenase‐1

Sodium‐glucose cotransporter‐2 (SGLT2) inhibitors are the newest class of glucose lowering drugs that act by inhibiting glucose reabsorption in the proximal tubule of the kidney. Recent clinical trials found that SGLT2 inhibitors reduce cardiovascular disease and mortality in patients with diabetes. The mechanism underlying the salutary actions of these drugs is not completely clear; however, it does not involve differential improvements in glycemic control. Given the critical role that endothelial cells (ECs) play in maintaining vascular homeostasis, the present study investigated the effect of the SGLT2 inhibitor canagliflozin on EC function. It also determined if the vasoprotective protein heme oxygenase‐1 (HO‐1) contributes to the cellular actions of the drug. Treatment of human umbilical vein ECs with clinically relevant concentrations of canagliflozin blocked cell proliferation, and this was associated with a pronounced decline in DNA synthesis. Canagliflozin also inhibited the migration of ECs following scrape injury in a concentration‐dependent manner. Incubation of ECs with a high concentration of glucose (25mM) and oxidized low‐density lipoprotein (oxLDL;50mg/L), which mimics the diabetic milieu, stimulated the adhesion of monocytes to ECs. However, treatment of ECs with canagliflozin markedly reduced the binding of monocytes to these cells. In addition, canagliflozin increased the expression of HO‐1 in a time and concentration‐dependent fashion, leading to a significant rise in endothelial HO‐1 activity. Finally, inhibition of HO‐1 activity or expression increased the adhesion of monocytes to glucose/oxLDL‐challenged ECs exposed to canagliflozin but had no effect on the proliferative or migratory response of canagliflozin‐treated ECs. In conclusion, the present study identifies canagliflozin as a key regulator of EC function. Moreover, it demonstrates that the induction of HO‐1 by canagliflozin contributes to the anti‐inflammatory action the drug. Thus, canagliflozin may exert some of its favorable effects in diabetes by limiting endothelial inflammation via the upregulation of HO‐1.

Effects of the original Gymnastics for Pregnant Women program on glycaemic control and delivery outcomes in women with gestational diabetes mellitus: A randomized controlled trial

BackgroundGestational diabetes mellitus affects millions of pregnant women. Lifestyle intervention is recommended as the first-line treatment, in which exercise plays an important role. Effective and safe exercise is required to facilitate glycaemic control and improve delivery outcomes. ObjectiveTo investigate the efficacy and safety of the original Gymnastics for Pregnant Women program for glycaemic control and delivery outcomes improvement in gestational diabetes mellitus women. DesignThe study was a two-arm parallel randomized controlled clinical trial. SettingThe study was conducted in a tertiary specialized maternity hospital in Hangzhou, China. ParticipantsTotally 131 eligible pregnant women were enrolled from June to December 2020. MethodsParticipants were randomly allocated to the control group (conventional intervention) or experimental group that engaged in the original Gymnastics for Pregnant Women program. The primary outcomes included glycaemic control during pregnancy and postpartum. Secondary outcomes included adverse events, maternal and neonatal outcomes. ResultsParticipants showed a significant improvement in glycaemic control after engaging in the intervention for 2 weeks; the improvement was most significant in terms of the 2-h postprandial plasma glucose (P < 0.05). The fasting blood glucose and 2-h postprandial plasma glucose data indicated a higher glycaemic control rate in the experimental than control group (86.16% vs. 66.67%, P = 0.008; and 84.62% vs. 36.36% [6.09 ± 0.79 vs. 6.96 ± 1.06 mmol/L], P < 0.001, respectively). After delivery, the 2-h oral glucose tolerance test results indicated better glycaemic control in the experimental than control group (75.44% vs. 57.41% [6.93 ± 1.44 vs. 7.79 ± 2.03 mmol/L], P = 0.047). Additionally, the 2-h oral glucose tolerance test in the experimental group with reasonable exercise frequency (≥10 times per week) had the best glucose level (6.81 ± 1.30 mmol/L), followed by the experimental group with a lower exercise frequency (<10 times per week) (7.35 ± 1.83 mmol/L) and the control group (7.79 ± 2.03 mmol/L). No statistical differences in maternal or neonatal outcomes were observed between the control and experimental groups (P > 0.05). In addition, there were no adverse events in the experimental group; however, in the control group, two cases experienced at least one hypoglycaemic episode and two cases received insulin during the study period. ConclusionsThe original Gymnastics for Pregnant Women was associated with greater improvements in blood glucose levels during pregnancy and postpartum compared with a conventional intervention for women with gestational diabetes mellitus. RegistrationChiCTR2000033963 (2020-06-22). Tweetable abstractThe original Gymnastics for Pregnant Women program improves glycaemic control in GDM women but does not affect delivery outcomes.

ENDOCRINOLOGY IN PREGNANCY: Targeting metabolic health promotion to optimise maternal and offspring health.

There is an increase in maternal metabolic burden due to the rise in pregnancies complicated by obesity, gestational diabetes, type 2 diabetes and polycystic ovary syndrome. Metabolic dysfunction during pregnancy is associated with increased risks of long-term morbidity and mortality for women and their offspring. Lifestyle interventions in pregnancy in women at risk of metabolic dysfunction have demonstrated short-term improvements such as reduced gestational weight gain and lowered risk of gestational diabetes. It is not known whether these interventions lead to sustained improvements in the metabolic health of the mother and baby. Pharmacological interventions have also shown benefits for the mother and baby in pregnancy, including improvements in glycaemic control, reduction in gestational weight gain and reduction in large for gestational age infants; however, there remains uncertainty over long-term outcomes for mother and child. Existing studies on interventions targeting metabolic health are limited to selected populations in the preconception and postpartum periods and lack follow-up beyond delivery of the intervention. The COVID-19 pandemic has refocused our attention on the effects of maternal metabolic ill-health that play a role in contributing to premature morbidity and mortality. There is an urgent need for strategies to accurately identify the growing number of women and offspring at risk of long-term adverse metabolic health. Strategies which focus on early identification and risk stratification using individualised risk scores in the pre and inter-conception periods must take priority if we are to target and improve the metabolic health of women and their offspring who are at highest risk.

IDF21-0062 Improved glycemic control during chronic phase after Stroke

Background: Hyperglycemia is common in the early acute stroke phase especially in patients with diabetes and possible benefits are obtained from proper control of it. However, the course of hyperglycemia in patients with diabetes after stroke during the chronic phase or rehabilitation is not clear and to the best of our knowledge, there is no study evaluating this issue. Aim: The purpose of this study was to extend our understanding of glycemic control among patients with diabetes after the acute phase of stroke and especially during the rehabilitation period. Method: It was a case-series study, conducted in Tabassom Rehabilitation Center for Stroke Patients in Tehran from May 2018 and February 2021. Forty-seven consecutive patients with diabetes and stroke were enrolled in this study. Patients were included only if it has passed from their stroke at least three months. Any change in glycemic control of the patients before and after stroke was ascertained by monitoring any change in drugs used for control of diabetes, and laboratory results (Hb A1c & FBS). Results: The mean age was 63.6 ± 6.9 years and 22 patients (47%) were women. The median of time from the occurrence of a stroke to the first visit was 5 months and 6 days. Glycemic control was improved among patients with diabetes during the chronic phase of stroke. There was a significant decrease of 0.7 ± 1.3 % in HbA1c (P=0.001). Despite a decrease or no change in HbA1c and FPG, also the dose and the number of drugs used for treating diabetes were usually decreased. Interestingly, despite a significant weight loss, no significant correlation could be found between changes in HbA1c and weight. Discussion: We could not find any study that how stroke in patients with diabetes can affect these pathways but regarding our findings, interesting studies in this field can be expected. Our study is the first study representing that during the chronic phase of stroke, usually it is necessary to decrease ant diabetic drugs due to improvement in glycemic control; however, our study has several limitations that should be mentioned. First, this was a small study to test our hypothesis derived from our observation and follow-up of patients with diabetes after stroke and certainly, this needs to be reproduced in larger studies. Second, because of study design, we could not eliminate confounding factors and studies with a more powerful design should be performed. We cannot explain the cause of this improvement in glycemic control observed in patients with diabetes during the chronic phase of stroke but whatever the cause is, it has important implications for patients regarding their safety and to the caring physicians and institutions regarding a proper pharmacologic plan to reduce the risk of hypoglycemia and its disadvantageous subsequences.

IDF21-0445 Telehealth utilization in Diabetes Centre during COVID Pandemic in South-Western Sydney: An evolving model of care

Background: The coronavirus (COVID-19) pandemic posed significant challenges in the delivery of healthcare necessitating adoption of telehealth in many outpatient services including diabetes services. There were concerns about telehealth including: inability to conduct physical examinations ,difficulty establishing good rapport ,challenges with providing a review to those not proficient in English. Studies demonstrated telehealth can cause behavioral changes with improvement in glycaemic control whereas other studies have demonstrated that stressors associated with COVID-19 pandemic could affect adherence to therapy. Aim: To examine the impact of telehealth model of care on diabetic management in the COVID-19 pandemic. Method: We conducted a retrospective review of patients with diabetes who were reviewed via telehealth with endocrinologists in 2 metropolitan Sydney Hospitals (Liverpool and Fairfield Hospital) between April to September in 2020 in comparison to the same 5 months in 2019 where patients were assessed face-to-face. Their demographics, attendance rate, glycaemic control and unplanned admissions were evaluated. Results: Attendance rate improved with telehealth consultations (884 out of 994 [88.9%] in 2020 vs. 818 out of 959 [85.2%] in 2019, p = 0.016).Amongst the 629 patients who had been with the clinic service for at least 12 months, adjustments to diabetic therapy were made less frequently in telehealth consultations than during face-to-face consultations (55.6% in 2020 vs 71.5% in 2019, p < 0.001).Glycaemic control improved during the pandemic (HbA1c 7.8±1.4% [62 ± 15mmol/mol]) compared to 12 months prior (8.2±1.7% [66 ± 19mmol/mol], p < 0.001), however patients were less likely to have HbA1c results available at time of review (83% during pandemic vs 96% 12 months prior, p<0.001).There was no significant difference in unplanned admissions (58 [9.2%] in 2020 vs 75 [11.9%] in 2019, p = 0.100). Discussion: This study demonstrated that attendance and glycaemic control improved, and unplanned admission rates did not change in patients who received care via telehealth during the COVID-19 pandemic in comparison to the pre-COVID-19 period. Telehealth thus was an important and viable option for healthcare delivery during the COVID-19 pandemic. Its role in outpatient consultations in the post-COVID-19 era is yet to be defined, with emerging evidence telehealth should be considered to compliment face-to-face consultations.

IDF21-0186 Real-world effectiveness of Diabefly digital therapeutics program for glycemic control during COVID-19 pandemic in India

Background: The COVID-19 pandemic led to significant changes in everyday life through lockdowns and home confinement, leading to substantial indirect risk for people with diabetes. The resulting disruptions in the management of diabetes have been attributed to factors like limitations on physical activity, changes in dietary habits, anxiety, and limited access to health care facilities. Clinically validated digital therapeutics platforms have potential towards enabling continuity-of-care during the pandemic. Aim: The study is aimed at examining the effectiveness of Diabefly digital therapeutics program for people with type 2 diabetes (T2D) during the COVID-19 pandemic in India. Method: De-identified data was analyzed for 72 participants with T2D who had completed 90 days on the Diabefly digital therapeutics program during the COVID-19 pandemic since April 2020. The Diabefly program provided personalized glycemic response-based lifestyle management support, educational and motivational content, personalized nutrition plan by nutritionist, and remote health coaching. The program offered access to mobile application-based logging of meals while providing details of calorie intake as well as macro- and micro-nutrient compositions. The program also facilitated logging of clinical and anthropometric parameters like HbA1c, body weight and body mass index (BMI). In this work, the variation in these parameters was analyzed at the beginning (first 7 days) and at the end of the program. Paired t-test was used for statistical comparison between two groups, while Kruskal-Wallis test and Dunn’s multiple comparison test was used for assessing the difference between more than two groups. P<0.05 was considered as statistically significant. Results: The participants had a mean age of 44.44 ± 14.35 years with 32 females (44.44%). The average duration of diabetes was 4.24 ± 6.59 years with the most common comorbidities being hypertension in 20 participants (27.77%) and dyslipidemia in 14 participants (19.44%). After completion of the program, a significant mean reduction in HbA1c of 1.96 ± 2.06% was observed (P<0.0001). Similarly, weight and BMI of participants showed a mean reduction of 2.62 ± 3.33 kg (P<0.0001) and 0.88 ± 1.10 kg/m2 respectively (P<0.0001). After 90 days on the program, 68 participants (94.44%) showed reduction in HbA1c while 55 (76.38%) reduced their body weight when compared to baseline. The group with lesser than median interactions, median interactions, and higher than median interactions showed a median (IQR) reduction of HbA1c by 0.50 (0.95) %, 1.70 (3.47) %, and 1.75 (2.37) %. A significant variation in the HbA1c reduction was observed with different level of interactions with the platform (P=0.03). Group with higher than median interactions showed significantly higher reduction in HbA1c as compared to the group with lower than median interactions (P<0.05). Discussion: There was a significant reduction in HbA1c, body weight, and BMI in participants who completed 90 days on the Diabefly program. Higher interaction with the platform showed higher reduction in HbA1c suggesting the potential of the program for overall improvement in glycemic control. Thus, Diabefly program was used as an effective tool for diabetes self-management, education and support during the COVID-19 pandemic while ensuring continuity-of-care in times of limited access to health care resources.