Glycemic Measures Research Articles

Efficacy and safety of the glucagon receptor antagonist volagidemab in type-1 diabetes: A systematic review and meta-analysis.

The glucagon receptor antagonist (GRA) volagidemab is the first-in-class fully human monoclonal antibody that inhibits glucagon receptor. GRA can improve glycemia by reducing endogenous glucose production and reduce risks of diabetic ketoacidosis by suppressing ketogenesis. This systematic review and meta-analysis analyzed the efficacy and safety of volagidemab in type-1 diabetes (T1D). Electronic databases were searched for randomized controlled trials (RCTs) involving T1D patients receiving volagidemab. The primary outcome was to evaluate changes in total daily dose (TDD) of insulin. The secondary outcomes were to evaluate changes in measures of glycemia, hypoglycemia, and adverse events. Data from 3 RCTs (98 patients) were analyzed. Volagidemab (70mg/week) was associated with a significant reduction in TDD of insulin requirement (mean difference [MD]: -8.45 units/day (95% confidence interval [CI]: [-12.09, -4.81]); I2=83%; p<0.01) and average blood glucose (MD: -21.42mg/dL (95% CI: [-37.10, -5.74]); I2=88%; p<0.01), compared to placebo. Volagidemab use was associated with a significant increase in time in range (blood glucose: 70-180mg/dL) (MD: 10.93% (95% CI: [6.69, 15.17]); I2=55%; p<0.01) and significant reduction in time above range (blood glucose >180mg/dL) (MD: -11.93% (95% CI: [-14.71, -9.15]); I2=6%; p<0.01) without any impact on time below range (blood glucose <70mg/dL) (MD: 0.14% (95% CI: [-0.56, 0.84]); I2=0%; p=0.70), compared to placebo. Occurrence of treatment-emergent adverse events (odds ratio [OR]: 0.96 (95% CI: [0.36, 2.56]); I2=8%; p=0.94) and hypoglycemia (OR: 0.56 (95% CI: [0.11, 2.89]); I2=0%; p=0.49) were similar among volagidemab users as compared to placebo. Short-term volagidemab use was associated with significant reduction in insulin requirement along with improvement in glycemia.

Use of Sliding Scale Insulin: Investigating the use of sliding scale insulin (SSI) in managing hyperglycemia in emergency cases in the hospital, and comparing it with evidence-based approaches like basal-bolus insulin regimens

Objective: This clinical audit focuses on identifying and describing the pattern of Sliding Scale Insulin in the management of hyperglycemia in emergencies in Lady Reading Hospital, Peshawar. This study matches SSI to EB-BBI to determine which of the two produces more favorable patient outcomes such as glycaemic control, incidence of hypoglycaemia, hospital stay, and mortality. Pre-intervention and post-intervention were audited to determine the best practice to embrace after the cycling accord. Methods: A total of 456 patients who developed hyperglycemia during their admission were part of the audit. A pilot survey during the first audit cycle (from 1 Dec 2023 to 29 Feb 2024) assessed the implementation of SSI versus basal-bolus insulin regimens. After applying the intervention strategies to enhance the use of basal-bolus insulin among the patients a second audit (from March 1 2024 to June 15, 2024) was conducted. Information from patient characteristics such as age, sex, insulin treatment and dose, glycemic control measures, complications, hospitalization length and mortality rate of patients were gathered and analyzed between the two cycles. Results: In the first audit cycle, 68% of patients were managed with SSI to increased risk of hypoglycemia 28% and longer hospital stay of 6.2 days compared to patients with basal bolus insulin who experienced 12% of hypoglycemia and 4.5 days of hospital stay. Interventions were used to decrease the use of SSI down to 45 %; this was accompanied by better results; for instance, incidences of hypoglycaemia were recorded at 19 % while the average length of stay in hospital was 5.4 days. The results in basal-bolus insulin regimens were more favorable, though all compared regimens had similar or slightly reduced mortality rates. Conclusion: The audit showed that basal-bolus insulin management regimens provided better and superior glycemic control and better patient outcomes than SSI in emergency hyperglycemia situations. In the first instance, implementing basal-bolus insulin posed lessons in staff development and had limited sources; nonetheless, the study established enhanced patient safety and shortened length of stay. Specifically, this audit assists to validate basal-bolus regimens as the best approach of treating hyperglycemia in emergencies.

Cross-sectional and longitudinal associations between glycaemic measures and grip strength in people without diabetes in the UK Biobank cohort study.

To investigate associations between glycaemic measures (HbA1c, random glucose), and grip strength (GS) in adults without prevalent diabetes. We included 381,715 UK Biobank participants aged 38-73years without diabetes (any type) with complete baseline measures for GS and HbA1c (main analyses), and glucose (supplementary analyses). Cross-sectional sex- and age-stratified associations between each glycaemic measure, GS, and probable sarcopenia (low GS) were examined with regression analyses. Changes in GS over 8.9years were classified into four groups (decline, stable low, stable high, or reference (increase or maintained within the normal range)) in 36,228 participants and associations with baseline glycaemic measures explored using multinomial regression. Higher HbA1c (mmol/mol) was associated with weaker mean GS (kg) (regression coefficient and 95% confidence intervals (CI): -0.08 (-0.09, -0.07)), and increased odds of probable sarcopenia (odds ratio (OR) and 95% CIs: 1.02 (95% CI: 1.01, 1.02)) in males and across the age groups. In females, higher HbA1c was associated with weaker mean GS only in mid-life (e.g., 50-59years: -0.06 (-0.07, -0.05)). In males, but not in females with repeated GS, higher HbA1c was associated with decreased odds of stable high (0.97 (0.96, 0.99) and increased odds of stable low (1.03 (1.01, 1.04)) GS pattern (0.98 (0.97, 0.980)) over the follow-up. The results for glucose in supplementary analyses were mixed, especially in females. The associations between HbA1c and GS in people without diabetes warrant replication and consideration of the effect on muscle strength when interventions to promote normoglycaemia are trialled.

Improvement of Glycemia Risk Index and Continuous Glucose Monitoring Metrics During Ramadan Fasting in Type 1 Diabetes: A Real-World Observational Study.

Managing glycemia during Ramadan is challenging for individuals with type 1 diabetes (T1D) due to prolonged fasting and altered eating patterns. While many are exempt from fasting, some choose to fast, necessitating careful monitoring. The glycemia risk index (GRI) is valuable for assessing glycemic quality and interpreting continuous glucose monitoring (CGM) data to identify individuals needing closer clinical attention. This study investigates the effects of Ramadan fasting on glycemic control in T1D, focusing on GRI and its components for hypoglycemia (CHypo) and hyperglycemia (CHyper). An ambispective study involved 186 individuals with T1D using intermittent scanning CGM (isCGM). Data were retrospectively collected for one month before Ramadan and prospectively during and one month after Ramadan. Clinical, metabolic, and glycemic data were collected, with GRI calculated alongside its components. During Ramadan, GRI improved by 54.6% (from 56.4 to 25.6), CHypo decreased by 60% (from 6 to 2.4), and CHyper dropped by 40.5% (from 21 to 12.5). However, these benefits were temporary, as glycemic measures increased after Ramadan, reflecting a return to pre-Ramadan patterns once normal routines resumed. No participants were admitted for diabetes emergencies during Ramadan. Adolescents and patients on insulin pumps had more favorable outcomes. GRI and its components significantly correlated with other CGM metrics, with these relationships maintained during and after Ramadan. Ramadan fasting significantly improved GRI and its components in individuals with T1D. Incorporating GRI as a novel metric alongside classical CGM metrics could enhance glycemic control, highlighting the need for personalized diabetes management strategies.

The impact of insulin resistance and glycaemic control on insulin-like growth factor-1 in patients with type 2 diabetes: a cross-sectional study

BackgroundType 2 diabetes mellitus (T2DM) is a multifaceted metabolic disorder. Over the past decade, the potential role of Growth Hormone (GH) and Insulin-like Growth Factor-1 (IGF-1) in the pathogenesis and progression of T2DM has garnered scientific interest. These hormones, while interrelated, exert differential effects on glucose homeostasis; GH elevates blood glucose levels, whereas IGF-1 sustains insulin secretion and augments insulin sensitivity.ObjectiveThe study aimed to investigate the impact of insulin resistance and glycaemic control on IGF-1 levels and to assess other risk factors influencing IGF-1 in T2DM.MethodsA cross-sectional study was conducted at the National Diabetes Centre, Baghdad, Iraq, from May 2020 to May 2021. Sixty patients with T2DM were evaluated for fasting plasma glucose (FPG), GH, IGF-1, HbA1c, HOMA-IR, HOMA-B, and anthropometric measures following a comprehensive history and physical examination, focusing on any variables that could influence their metabolic profile. Patients with Type 1 diabetes mellitus, thyroid disease, pituitary disease, chronic kidney disease, hepatic disease, and pregnancy were excluded from the study.ResultsPatients with poorly controlled diabetes (HbA1c > 8) exhibited significantly elevated IGF-1 levels compared to those with HbA1c < 8 (166 vs. 134, P = 0.016). The mean IGF-1 was significantly lower in patients with insulin resistance (IR) compared to those without IR (143 vs. 192, P = 0.001), with a significant negative correlation with Body Mass Index (BMI) and a significant positive correlation with HbA1c and Quantitative Insulin Sensitivity Index (QUICKI). Elevated IGF-1 levels were observed with increasing age, duration of T2DM, higher HbA1c, higher QUICKI, and lower BMI. No significant difference was found in IGF-1 values with regards to HOMA-B, fasting insulin, and waist-hip ratio.ConclusionPatients with poorly controlled T2DM exhibit higher IGF-1 levels, while those with obesity and high insulin resistance demonstrate lower IGF-1 levels. Further prospective studies are warranted to evaluate the potential of using IGF-1 to reduce insulin resistance and improve metabolic and glycaemic measures in individuals with T2DM and obesity or insulin resistance.

Continuous glucose monitoring in adults with short bowel syndrome receiving overnight infusions of home parenteral nutrition.

Consumers of home parenteral nutrition (HPN) are susceptible to dysglycemia. The aim was to characterize 24-h glucose profiles of HPN consumers using continuous glucose monitors (CGM) and to identify factors that influence glucose. Glucose profiles of 20 adults with short bowel syndrome (SBS) without diabetes were assessed using the Freestyle Libre Pro CGM. Measures included mean 24-h glucose, coefficient of variation (%), % time in range (TIR 70-140 mg/dL), among others. HPN parameters and lifestyle behaviors were obtained from self-reports and validated surveys. Linear mixed-effects models were used to test associations with glycemic measures adjusted for age, sex, and BMI. Significance was considered at P < 0.05. Participants (77% female, age = 52 years, BMI = 21.4 kg/m², 95% white) had a 24-h mean and CV for glucose of 94.69 (8.96) mg/dL and 20.27%, respectively, and a mean TIR of 87.73%. Among non-daily HPN-dependent patients, the mean glucose and TIR were higher on days receiving HPN. Tapering HPN was associated with -6.882 (95% confidence interval = -12.436, -1.329) % lower CV, and higher HPN dextrose content per gram was associated with 0.039 (95% confidence interval = 0.008, 0.07) % higher CV. Smoking, more depressive symptoms, and higher insomnia severity showed associations with glucose levels and variability. Metabolically stable HPN adult consumers have 24-h glucose measures comparable to healthy adults yet are notable for more time spent below range. The glucose profiles are influenced by HPN parameters such as tapering and dextrose and behaviors including smoking, depressive symptoms, and insomnia.

Effectiveness of flaxseed consumption and fasting mimicking diet on anthropometric measures, biochemical parameters, and hepatic features in patients with Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): a randomized controlled clinical trial.

Although benefits of flaxseed and fasting mimicking diet (FMD), each alone, have been shown in the management of metabolic dysfunction-associated steatotic liver disease (MASLD), the benefit of combining the two is not clear. This study aimed to investigate the effect of the combination of FMD and flaxseed supplementation on surrogate measures of MASLD. The present study was conducted as a randomized, parallel, open-label controlled clinical trial on a hundred patients with MASLD for 12 weeks. Eligible participants were assigned to four groups including control group (lifestyle modification recommendations); flaxseed group (30 g/day of flaxseed powder consumption); FMD group (16 h of fasting per day), and combination of FMD with flaxseed. Changes in anthropometric parameters, serum levels of lipids, glycemic measures, High-sensitivity C-reactive protein (hs-CRP), and liver enzymes, and hepatic steatosis and fibrosis by transient elastography were assessed. Serum triglycerides, total cholesterol, fasting blood glucose and insulin, hs-CRP and liver enzymes decreased in all intervention groups. Hepatic steatosis score decreased in the intervention groups, but not significantly in comparison to the control group. Hepatic fibrosis score decreased significantly in the intervention groups compared to control. Our data indicate that the combination of FMD with flaxseed consumption is not superior to either of the interventions alone in the management of MASLD.

Diabetes Device Satisfaction Among Adolescents Living With Type 1 Diabetes and Their Parents.

Diabetes technologies are valuable tools to reduce burden and enhance glycemic control, especially during adolescence. The current study sought to understand the factors associated with parent and adolescent diabetes device satisfaction. This study used cross-sectional data from 175 adolescents living with type 1 diabetes and 176 parents. Adolescent ages ranged from 12 to 19 (Mage=14.7, SD=1.89) and were balanced by gender (48% male). Kendall's W examined concordance between parent and adolescent satisfaction and bivariate correlations and paired t-tests identified correlates of satisfaction. There was low concordance (Kendall's W = 0.13) between parent and adolescent device satisfaction. Automated insulin delivery (AID) use (vs non-use) was related to higher satisfaction for adolescents (4.52 [0.71] vs 4.20 [0.87], P = .008) and parents (4.25 [0.82] vs 3.71 [0.90], P < .001). Pump use was not significantly related. Parent satisfaction was correlated with hemoglobin A1c (HbA1c; R = -0.301, P < .001), percent time-in-range (R = 0.214, P = .007), and percent time-above-range (R = -0.193, P = .015). Adolescent satisfaction was unrelated to glycemic measures. Adolescent and parent satisfaction were both related to better psychosocial functioning. Significant associations between AID use, psychosocial functioning, and glycemic control and device satisfaction remained after accounting for one another. Demographic correlates were non-significant. Adolescents and their parents have discrepant levels of satisfaction with devices. Although both adolescent and parent satisfaction are linked to use of automated technology and better psychosocial functioning, only parent satisfaction is associated with glycemia. This pattern suggests adolescents and parents hold varying priorities when it comes to device use. Acknowledging and addressing these differences may enhance the uptake and continued use of devices.

Survodutide for treatment of obesity: rationale and design of two randomized phase 3 clinical trials (SYNCHRONIZE™-1 and -2).

The objective of this study was to describe the rationale and design of two multinational phase 3 clinical trials of survodutide, an investigational glucagon and glucagon-like peptide-1 receptor dual agonist for the treatment of obesity with or without type 2 diabetes (T2D; SYNCHRONIZE-1 and -2). In these ongoing double-blind trials, participants were randomized to once-weekly subcutaneous injections of survodutide or placebo added to lifestyle modification. Survodutide doses are uptitrated to 3.6 or 6.0 mg, and dose flexibility is permitted. Participants (n = 726) in SYNCHRONIZE-1 (NCT06066515) have a baseline BMI ≥ 30 kg/m2 or ≥27 kg/m2 with at least one obesity-related complication but without T2D; participants (n = 755) in SYNCHRONIZE-2 (NCT06066528) have a baseline BMI ≥ 27 kg/m2 and T2D. The primary endpoints are percentage change in body weight and proportion of participants achieving ≥5% body weight reduction from baseline to week 76. Secondary endpoints include change in systolic blood pressure and measures of glycemia. A SYNCHRONIZE-1 substudy is evaluating changes in body composition and liver fat content using magnetic resonance imaging. These trials are designed to provide robust evaluation of the efficacy, safety, and tolerability of survodutide for the treatment of obesity in the presence or absence of T2D.

Real-Life Achievements of MiniMed 780G Advanced Closed-Loop System in Youth with Type 1 Diabetes: AWeSoMe Study Group Multicenter Prospective Trial.

Background: We assessed real-life glycemic outcomes and predictors of composite measures of optimal glycemic control in children and adolescents with type 1 diabetes (T1D) during their initial 12 months of the MiniMed™ 780G use. Methods: This prospective observational multicenter study collected demographic, clinical, and 2-week 780G system data at five time points. Optimal glycemic control was defined as a composite glycemic control (CGC) score requiring the attainment of four recommended continuous glucose monitoring (CGM) targets, as well as the glycemia risk index (GRI) of hypoglycemia and hyperglycemia and composite CGM index (COGI). Outcome measures included longitudinal changes in multiple glycemic parameters and CGC, GRI, and COGI scores, as well as predictors of these optimal measures. Results: The cohort included 93 children, 43% girls, with a median age of 15.1 years (interquartile range [IQR] 12.9,17.0). A longitudinal analysis adjusted for age and socioeconomic index yielded a significant improvement in glycemic control for the entire cohort (ptime < 0.001) after the transition to 780G. The mean hemoglobin A1c (HbA1c) (SE) was 8.65% (0.12) at baseline and dropped by >1% after 1 year to 7.54% (0.14) (ptime < 0.001). Optimal glycemic control measures improved at 12 months post 780G; CGC improved by 5.6-fold (P < 0.001) and was attained by 24% of the participants, the GRI score improved by 10-fold (P = 0.009) and was achieved by 10% of them, and the COGI improved by 7.6-fold (P < 0.001) and was attained by 20% of them. Lower baseline HbA1c levels and increased adherence to Advanced Hybrid Closed-Loop (AHCL) usage were predictors of achieving optimal glycemic control. Conclusions: The AHCL 780G system enhances glycemic control in children and adolescents with T1D, demonstrating improvements in HbA1c and CGM metrics, albeit most participants did not achieve optimal glycemic control. This highlights yet ongoing challenges in diabetes management, emphasizing the need for continued proactive efforts on the part of health care professionals, youth, and caregivers.

Plasma lipids and glycaemic indices in Australians following plant-based diets versus a meat-eating diet

BackgroundVegan and vegetarian dietary patterns are known to beneficially modulate risk factors for cardiovascular disease; however, the current literature does not differentiate between various plant-based diets. This study aimed to examine the association between various plant-based diets and plasma lipids and glycaemic indices compared to a regular meat-eating diet.MethodsA cross-sectional study of Australian adults (n = 230) aged 30-75yrs habitually consuming the following were recruited: vegan, lacto-vegetarian, pesco-vegetarian, semi-vegetarian, or regular meat-eater. Multivariable regression analysis was used to adjust for covariates.ResultsCompared to regular meat-eaters, vegans had significantly lower total cholesterol (-0.77mmol/L,95% CI -1.15, -0.39, P < 0.001), low-density lipoprotein cholesterol (LDL-C, -0.71mmol/L, 95% CI -1.05, -0.38, P < 0.001), non-high-density lipoprotein cholesterol (non-HDL-C, -0.75mmol/L, 95% CI -1.11, -0.39, P < 0.001), total cholesterol/HDL-C-ratio (-0.49mmol/L, 95% CI -0.87, -0.11, P = 0.012), fasting blood glucose (FBG, -0.29mmol/L, 95% CI -0.53, -0.06, P = 0.014), haemoglobin A1C (-1.85mmol/mol, 95% CI -3.00, -0.71, P = 0.002) and insulin (-1.76mU/L, 95% CI -3.26, -0.26, P = 0.021) concentrations. Semi-vegetarians had significantly lower LDL-C (-0.41mmol/L, 95% CI -0.74, -0.08, P = 0.041) and non-HDL-C (-0.40mmol/L, 95% CI -0.76, -0.05, P = 0.026) and lacto-ovo vegetarians had significantly lower FBG (-0.34mmol/L, 95% CI -0.56, -0.11, P = 0.003) compared to regular meat-eaters. There were no differences in HDL-C and triglycerides between plant-based and regular-meat diets.ConclusionsPlasma lipaemic and glycaemic measures as a collective were more favourable among vegans, whereas among lacto-ovo vegetarians and semi-vegetarians, only some measures were favourable.Trial registrationACTRN12621000743864. Date 6/11/2021.

Glycaemic outcomes in adults with type 2 diabetes over 34 weeks with the Omnipod® 5 Automated Insulin Delivery System.

The aim was to evaluate the effect of extended use of the Omnipod® 5 Automated Insulin Delivery (AID) System in adults with type 2 diabetes and suboptimal glycaemic control. Following an 8-week single-arm, multicentre, outpatient trial of AID in adults with type 2 diabetes and baseline HbA1c ≥ 8% (≥ 64 mmol/mol), participants were given the opportunity to continue use of the AID system in a 26-week (~6 month) extension phase. The primary safety endpoints were percentage of time with sensor glucose ≥ 250 mg/dL and < 54 mg/dL. Additional glycaemic measures, including percentage of time in range (TIR) (70-180 mg/dL) and HbA1c, were evaluated. The use of non-insulin anti-hyperglycaemic medications was permitted throughout the entire study. During the initial 8-week study, participants (N = 22) achieved a decrease in percentage of time ≥ 250 mg/dL from 27.4% ± 21.0% to 10.5% ± 8.8% (p < 0.0001), which further decreased to 9.7% ± 9.2% during the extension phase (p = 0.0002 vs. standard therapy). Percentage of time < 54 mg/dL remained low from standard therapy through extension (median [interquartile range] 0.00% [0.00%, 0.06%] vs. 0.02% [0.00%, 0.05%], p > 0.05). HbA1c decreased by 1.6% ± 1.2% (15.5 ± 13.1 mmol/mol, p < 0.0001) and TIR increased by 22.4% ± 19.2% (p < 0.0001) from standard therapy through extension with no significant change in body mass index and without an observed increase in total daily insulin requirements. These longer-term findings of Omnipod 5 AID System use demonstrate the potential value of AID in helping people with type 2 diabetes reach glycaemic targets.

6547 Glycated Hemoglobin is a Better Glycemic Indicator than Glycated Albumin in Mothers with Pregestational Diabetes: Preliminary Results of a CGM study in the 2nd and 3rd Trimesters

Abstract Disclosure: M. Md Amin: None. J. Ratnasingam: None. S.S. Paramasivam: None. L. Ibrahim: None. L. Lim: None. Q. Lim: None. N. Hee Ken Yoong: None. M. Hamdan: None. S. Ganapathy: None. P. Sthaneshwar: None. S.R. Vethakkan: None. Glycemic control is strongly associated with maternofetal outcomes in mothers with pregestational diabetes. Glycated Hemoglobin (HbA1c) is most accurate in the first trimester. The use of HbA1c to monitor glycemia in pregnancy however is controversial, as altered red-cell kinetics and iron deficiency render it less accurate than in the nongravid state, especially in the 2nd or 3rd trimester. Glycated albumin (GA) is an alternative measure of intermediate-term glycemia (2-3 weeks) which is unaffected by red-cell survival that has been used to monitor glycemia in CKD and pregnancy. However, the accuracy of HbA1c as opposed to GA is unclear, especially in later pregnancy and there are no published data comparing it with CGM (Continuous Glucose Monitoring) metrics in pregnancy. We compared the accuracy of HbA1c and GA as a glycemic indicator in later pregnancy using mean glucose from a 6-day CGM as reference, hypothesizing that GA would correlate more strongly with CGM metrics.Twelve pregnant Malaysian mothers with pregestational Type 1 (n=2) and Type 2 DM(n=10) were enrolled in this prospective observational study. Mothers with known hemoglobinopathy, nephrotic syndrome and liver cirrhosis were excluded. Patients underwent blinded 6-day CGM (Medtronic iPro2) followed by blood sampling for GA, HbA1c, albumin and hemoglobin on Day 7 at standardized timepoints in the 2nd and 3rd trimester (20-28 weeks, 30-36 weeks). Mean pre-pregnancy BMI was 28kg/m2(±5). Mean Hb was 12.3g/dL (±1.5), 16.7% of mothers had anemia, while 62.5% had serum albumin &amp;lt; 35g/L. GA did not correlate with mean CGM glucose (2nd trimester: r=0.180 [n=10], 3rd trimester r=0.493 [n=8], p=NS). After excluding obese women (pre-pregnancy BMI&amp;gt;30kg/m2) however, GA correlated well with mean CGM glucose in the 3rd trimester (r=0.870, p&amp;lt;0.05). HbA1c correlated significantly and strongly with mean CGM glucose in later pregnancy (2nd trimester: r=0.621 [n=11], 3rd trimester r=0.718[n=8], p&amp;lt;0.05) and correlated with estimated A1c from CGM (r=0.548, p=0.01). Unexpectedly, our data indicate that HbA1c correlates well with gold standard mean CGM glucose with a strength approximating that observed in the nongravid population with diabetes, thus validating its use as a complementary secondary measure of glycemia to fingerstick-glucose for therapeutic decision-making in later, as well as early pregnancy. Obesity is a known confounder of accuracy of GA, our findings corroborate this. Therefore, utility of GA as an alternative glycemic measure in pregnancy is potentially limited by the increasing prevalence of obesity worldwide and impact of gestational weight gain. A larger sample is needed to confirm these preliminary findings. Presentation: 6/2/2024

8026 Growth Hormone Receptor (GHR) is Independently Associated with Body Composition and Glycemic Measures in Youth with Type 2 Diabetes (T2D)

Abstract Disclosure: C. Lu: None. D. Wolfs: None. L. El ghormli: None. L.M. Laffel: None. M. Patti: Advisory Board Member; Self; Fractyl Health. Consulting Fee; Self; AstraZeneca, Hamni, MBX Biosciences. Grant Recipient; Self; Dexcom. E. Isganaitis: None. Background: T2D is more severe in youth than in adults, with growth and puberty as potential drivers. Growth hormone (GH) action, which peaks during puberty, also regulates carbohydrate metabolism. We previously showed that higher plasma levels of GHR are associated with hyperglycemia, insulin resistance, and decreased insulin secretion in youth with T2D. Plasma GHR is higher in obesity, and reductions in GHR after bariatric surgery may mediate improvements in glycemia. The association of GHR with body composition in youth with T2D has not been previously studied. Hypothesis: We hypothesize that the association of GHR with glycemic outcomes in youth with T2D is mediated by differences in body composition, and that associations between GHR and body composition differ by sex. Methods: Utilizing plasma samples from Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study (N=398), we examined association of plasma GHR (ELISA; ng/mL) with a) body composition measures including zBMI, absolute lean mass (kg), percent body fat (dual-energy x-ray absorptiometry), and b) glycemic outcomes including hemoglobin A1c (HbA1c), fasting glucose (mg/dL), 1/fasting C-peptide (mL/ng), C-peptide index (ng/mL per mg/dL), and C-peptide oral disposition index (CODI; mL/uU x ng/mL per mg/dL), stratified by sex. Linear regressions were adjusted for age, race/ethnicity, and Tanner stage in the base models, with additional adjustments for HbA1c, zBMI, lean mass, or percent fat. Results: This subcohort of youth with T2D from the TODAY study included 150 males and 248 females, mean age 13.9 ± 2.0 years. Females had lower zBMI (+2.2 ± 0.4 vs. +2.3 ± 0.5, p=0.005), lower lean mass (51 ± 10 vs. 59 ± 14, p&amp;lt;0.001), and higher percent body fat (39 ± 5 vs. 34 ± 6, p&amp;lt;0.001). Higher log2 GHR was associated with higher zBMI (B=0.44, SE=0.04, p&amp;lt;0.001), higher lean mass (B=4.3, SE=1.2, p&amp;lt;0.001), and higher percent fat (B=4.4, SE=0.7, p&amp;lt;0.001), even after adjustment for HbA1c, and without sex-specific differences. Higher log2 GHR was associated with higher HbA1c (B=0.35, SE=0.08, p&amp;lt;0.001), higher fasting glucose (B=9.0, SE=2.6, p&amp;lt;0.001), lower 1/fasting C-peptide (B=-0.17, SE=0.01, p&amp;lt;0.001), and lower CODI (B=-0.001, SE=0.001, p=0.02). These associations did not change with further adjustments for zBMI, lean mass, or percent fat, suggesting that associations between GHR and glycemia are independent of obesity or body composition. In analyses stratified by sex, the effect of GHR on CODI was attenuated after adjustment for lean mass in males only. Conclusion: Plasma GHR is independently associated with body composition and glycemia in youth with T2D. There were no sex differences in associations of GHR with HbA1c and insulin resistance. However, the association of GHR with beta cell function may be mediated by lean mass in boys but not in girls, although power was more limited in the sex-stratified analyses. Presentation: 6/3/2024

8765 Assessment of the Social Vulnerability Index of a 10-Year Retrospective Cohort of Youth with Prediabetes

Abstract Disclosure: D. Somerville: None. R.H. Kolagani, MHS: None. C.E. McCrory: None. S. Budakoti: None. V.M. Chinchilli, PhD: None. J. Joseph: None. D.E. Hale: None. N. Raja-Khan: None. L.P. Huerta Saenz: None. Background: The incidence of prediabetes (preD) is rising among youth in the US. While there are known metabolic risk factors linked to preD development, we were interested in exploring the role of social determinants of health (SDoH) in the development of pediatric preD. The social vulnerability index (SVI) is a tool developed by the CDC to stratify SDoH risk for communities based on 14 factors such socioeconomic status (SES), household composition, race and transportation access. By understanding the role of SVI in the development of preD in youth, we may be able to plan interventions to prevent progression to Type 2 Diabetes (T2D). Objective: Our study goal was to determine the relationship between SVI and preD in youth receiving care at our institution, a large pediatric referral center in Central Pennsylvania. Methods: We conducted a 10-year retrospective chart review of electronic medical records (EMRs) to identify children/youth aged 6-17 years old diagnosed with preD at our pediatric health system between 01/2010 and 01/2020. We used the American Diabetes Association definitions of preD (one or more sub-type): 1) Impaired fasting glucose (IFG), 2) Impaired glucose tolerance (IGT), and 3) Elevated hemoglobin A1c (HA1C). ICD10 codes were used for initial chart identification (R73.01, R73.02, R73.03 and R73.09). The second phase of identification of youth with preD included the review of biological measures of glycemia of the initial identified charts to support the reported ICD10 diagnosis (either isolated subtypes or combinations). Social, demographic characteristics, and residence setting (urban vs. rural) were also investigated. SVI was assessed on a 0-1 scale, with high SVI (0.5-1) indicating greater social vulnerability and low SVI (0-0.49) indicating lower social vulnerability. Rurality was determined per the Health Resources and Services Administration Tool (HRSA). SAS frequencies were calculated. Fisher’s exact tests were applied to compare the frequencies of the aforementioned groups with respect to IFG, IGT, and HA1C. Results: We identified 2700 charts of youth with preD per ICD10 codes search, but only 552 had confirmed preD diagnosis supported by biological data registered in EMRs. The most common preD isolated subtype was HA1C (87.3%), while 12% and 4% had isolated IFG and IGT, respectively. Most youth had high SVI (66.9%) and only 5.8% were rural (p &amp;gt; 0.05). Neither SVI or rurality were associated with isolated preD subtypes, but 8.2% of low-SVI youth had composite [IFG +HA1C] subtypes compared to 3.5% of high-SVI youth (p=0.02). Conclusions: SVI was not significantly associated with any isolated preD subtype. However, youth with the combined preD subtypes [IFG + HA1C] had lower SVI. As T2D is more prevalent in youth from low SES, addressing SDoH at earlier stages of T2D (preD phase) is needed in the effort to prevent the progression of the disease. Presentation: 6/1/2024

Perioperative Glycemic Variability Influences Infection Rates Differently Following Revision Hip and Knee Arthroplasty

BackgroundRecent investigations have determined that abnormal postoperative glycemia following primary total joint arthroplasty is associated with adverse events. Our study aimed to determine if hyperglycemia and glycemic variability following aseptic revision total joint arthroplasty were associated with periprosthetic joint infection (PJI) within two years postoperatively. MethodsA retrospective review was performed of 2,208 patients within a single institution undergoing aseptic revision total joint arthroplasty from 2012 to 2019. Postoperative glucose values were recorded. Glycemic variability was measured via three parameters: coefficient of variation, mean amplitude of glycemic excursions, and J-index. Logistic regression analyses were performed to examine associations with PJI at 90-day, 1-, and 2-year follow-up. ResultsIn revision hips, all glycemic measures were not associated with PJI at any time point in logistic regression analyses, except for the mean amplitude of glycemic excursions, which predicted PJI at one year (P = 0.045); body mass index was the only factor associated with PJI at all timepoints in all models. In revision knees, all glycemic measures were not associated with PJI at any timepoint in logistic regression analyses; however, PJI rates differed between diabetics and nondiabetics at all time points (P < 0.05). ConclusionsOur findings illustrate that decreasing preoperative body mass index and postoperative glycemic variability may be critical in reducing PJI rates in revision hips. Furthermore, patients who have diabetes should be counseled that they remain at higher risk of PJI regardless of perioperative glucose control after revision knee surgery.

Preoperative Laparoscopic Sleeve Gastrectomy Improves Weight Loss Potential in Morbidly Obese Voluntary Kidney Donors

This was a retrospective study aimed at evaluating the efficacy of laparoscopic sleeve gastrectomy (LSG) as a strategy for weight loss in obese prospective voluntary kidney donors who were unable to achieve weight reduction through lifestyle changes. This retrospective study included living kidney donors who underwent LSG as a strategy for weight loss in obese prospective voluntary kidney donors between 2012 and 2022. Prospective donors who were initially rejected due to obesity underwent LSG after pretransplantation evaluation. Changes in weight, body mass index (BMI), and laboratory parameters (hemogram, kidney function tests, liver function tests, fasting and postprandial glycemia, HbA1c, and lipid profile measurements) were recorded before bariatric surgery and before nephrectomy. Of the 16 candidates who underwent LSG, one did not proceed with donor nephrectomy due to the intended recipient's death. Among the remaining 15 subjects, the average interval between bariatric surgery and donor nephrectomy was 165.95 ± 48.86 days. There was a significant decrease in BMI following bariatric surgery (P < .0001); the mean BMI before bariatric surgery was 40.94 ± 4.53 kg/m², and before nephrectomy, it was 30.91 ± 3.87 kg/m2. The mean weight loss was 22.64 ± 5.75 kg. This study supports LSG as an effective approach for obese individuals who are potential kidney donors to achieve weight loss, mitigate obesity-associated risks, and become successful kidney donors.

Study protocol for Early Tracking of Childhood Health determinants (ETCHED): A longitudinal observational life course study

BackgroundThe prevalence of childhood obesity and diabetes continues to rise in the United States (US), especially among minority populations. The objective of the Early Tracking of Childhood Health Determinants (ETCHED) study is to investigate the role of adverse fetal and early-life risk exposures that contribute to the development of childhood obesity and metabolic risk.MethodsETCHED is a longitudinal observational study of American Indian/Alaska Native (AI/AN) and Hispanic pregnant woman and their offspring. Pregnant mothers ≥ 18 years old are enrolled at a large public hospital system in the southwestern US. Enrolled mothers are followed through pregnancy, delivery, and the maternal/offspring dyad will be followed until the child’s 18th birthday. At each maternal visit, questionnaires assessing medical history, diet, physical activity, sleep, perceived stress, and socioeconomic and sociocultural information are obtained. Standard laboratory tests during maternal visits include glycemic measures, lipids, and renal function. Additional bio samples obtained include venous blood samples and cord blood for obesity/metabolic biomarkers and genetic/epigenetic testing, urinalysis, placental tissue for examining functional pathways, breast milk for metabolomics, and stool for metabolites and microbiome analysis. The offspring will have 6 infant/toddler visits at 6–12 weeks, 4 months, 6 months, 18 months, 2 and 3 years respectively. Thereafter, they will undergo comprehensive research visits (major visits) at 4–5 years, 6–9 years, 10–13 years, and 14–17 years. The major visits in children include detailed medical history, anthropometry, developmental assessment, socioeconomic and environmental assessments (food insecurity, family structure, and childcare), feeding and activity, biochemical tests, genetics/epigenetic testing, and ultrasound elastography. Electronic health records will be reviewed for additional clinical information. The primary analysis will constitute estimation of correlation coefficients between continuous variables. The planned study duration in this ongoing study is 23-years.DiscussionThis is a life course study that that will examine biological and environmental risk factors for obesity and cardiometabolic risk from the intrauterine period to early childhood and adolescence in a population with high-risk of obesity and type 2 diabetes in the United States. The ETCHED study would also provide a unique opportunity to combine multi-omics and clinical data to create novel integrative models to predict the cardiometabolic risk associated with childhood obesity and possibly identify etiopathogenetic mechanisms and future targets of intervention.Trial registration numberClinicalTrials.gov identifier: NCT03481829. Updated July 19, 2024, https://clinicaltrials.gov/study/NCT03481829?cond=ETCHED&rank=1.

Continuous measurement of interstitial glycaemia in professional female UCI world tour cyclists undertaking a 9-day cycle training camp.

Nine cyclists (age: 26±5years, height: 168±5cm and mass 58.5±4.5kg) were observed using continuous glucose monitoring devices throughout a training camp. Interstitial glucose [iG] data were captured via the Abbott libre sense biosensor (Abbott Laboratories) and paired with the Supersapiens software (TT1 Products Inc.). [iG] data were split into time ranges, that is, overall (24-hourly), day-time (06:00-23:59), night-time (00:00-05:59) and exercise. [iG] data were stratified into percentage of time, below range ([TBR]<70mg/dl), in range ([TIR] 70-140mg/dl) and above range ([TAR]≥141mg/dl). Differences in diurnal and nocturnal data were analysed via repeated measures analysis of variance and paired t-tests where appropriate. p-value of ≤0.05 was accepted as significant. Riders spent an average of 3±1% TAR, 93±2% TIR and 8±3% TBR. Mean 24h [iG] was 93±2mg/dl with a coefficient of variation (CV) of 18±1%. Mean (day: 95±3 vs. night: 86±3mg/dl and p<0.001) and CV (day: 18±1 vs. night: 9±1% and p<0.001) in [iG] were higher during the day-time hours. TAR was greater during the day (day: 3±1 vs. night: 0±0% and p<0.001) but TBR and TIR were similar. Glucose levels below the clinical range may have implications for those without diabetes and warrants further investigation.

A randomized feasibility trial of time-restricted eating during pregnancy in people with increased risk of gestational diabetes

Time-restricted eating (TRE) is a nutritional intervention that confines the daily time-window for energy intake. TRE reduces fasting glucose concentrations in non-pregnant individuals, but whether this eating protocol is feasible and effective for glycemic control in pregnancy is unknown. The aim of this randomized controlled trial was to investigate the adherence to and effect of a 5-week TRE intervention (maximum 10 h daily eating window) among pregnant individuals at risk of gestational diabetes mellitus (GDM), compared with a usual-care control group. Participants underwent 2-h oral glucose tolerance tests and estimation of body composition, before and after the intervention. Interstitial glucose levels were continuously measured, and adherence rates and ratings of hunger were recorded daily. Thirty of 32 participants completed the trial. Participants allocated to TRE reduced their daily eating window from 12.3 (SD 1.3) to 9.9 (SD 1.0) h, but TRE did not affect glycemic measures, blood pressure, or body composition, compared with the control group. TRE increased hunger levels in the evening, but not in the morning, and induced only small changes in dietary intake. Adhering to a 5-week TRE intervention was feasible for pregnant individuals with increased risk of GDM but had no effect on cardiometabolic outcomes.