Type 1 Diabetes Participants Research Articles

Attenuated kidney oxidative metabolism in young adults with type 1 diabetes.

In type 1 diabetes (T1D), impaired insulin sensitivity may contribute to the development of diabetic kidney disease (DKD) through alterations in kidney oxidative metabolism. Young adults with T1D (n = 30) and healthy controls (HC, n = 20) underwent hyperinsulinemic-euglycemic clamp studies, MRI, 11C-acetate PET, kidney biopsies, single-cell RNA sequencing, and spatial metabolomics to assess this relationship. Participants with T1D had significantly higher glomerular basement membrane thickness compared to HC. T1D participants exhibited lower insulin sensitivity and cortical oxidative metabolism, correlating with higher insulin sensitivity. Proximal tubular transcripts of TCA cycle and oxidative phosphorylation enzymes were lower in T1D. Spatial metabolomics showed reductions in tubular TCA cycle intermediates, indicating mitochondrial dysfunction. The Slingshot algorithm identified a lineage of proximal tubular cells progressing from stable to adaptive/maladaptive subtypes, using pseudotime trajectory analysis, which computationally orders cells along a continuum of states. This analysis revealed distinct distribution patterns between T1D and HC, with attenuated oxidative metabolism in T1D attributed to a greater proportion of adaptive/maladaptive subtypes with low expression of TCA cycle and oxidative phosphorylation transcripts. Pseudotime progression associated with higher HbA1c, BMI, GBM, and lower insulin sensitivity and cortical oxidative metabolism. These early structural and metabolic changes in T1D kidneys may precede clinical DKD. gov NCT04074668.

Clinical importance of cytokine (IL-6, IL-8, and IL-10) and vitamin D levels among patients with Type-1 diabetes

Type-1 diabetes (T1D) is an autoimmune disorder characterized by impaired insulin release by islet β cells. It has been shown that proinflammatory cytokines released during the disease can exacerbate the condition, while anti-inflammatory cytokines offer protection. This study analyzed the clinical role of interleukin (IL)-6, -8, -10, and vitamin D levels in T1D patients compared to healthy controls. The levels of IL-6, IL-8, IL-10, and vitamin D in the participants’ serum samples were analyzed using ELISA. The findings showed that T1D patients had significantly increased levels (p < 0.0001) of fasting blood glucose, HbA1c, systolic blood pressure, low-density lipoprotein, triglycerides, cholesterol, and very low-density lipoprotein and decreased levels of high-density lipoprotein and vitamin D (p < 0.0001) compared to healthy controls. Moreover, the levels of IL-6, IL-8, and IL-10 were also significantly greater (p < 0.0001) in T1D patients. The study also determined the significance of these cytokines among T1D patients and healthy controls using ROC curves. Furthermore, we found that smokers had significantly higher levels of IL-6 (p = 0.01) and IL-8 (p = 0.003) than non-smokers. These results showed that elevated levels of IL-6, IL-8, and IL-10, decreased vitamin D levels, and smoking among T1D participants could contribute to the worsening of T1D disease and could serve as predictive indicators.

7892 Longitudinal Changes in Bone Microarchitecture and Strength in Girls with Type 1 Diabetes

Abstract Disclosure: R. Dhaliwal: None. R.K. Saunders: None. M. Misra: None. M.L. Bouxsein: None. D.M. Mitchell: None. Introduction: Type 1 diabetes (T1D) confers an increased fracture risk, only partly explained by low areal bone mineral density (aBMD). We have previously shown in a cross-sectional study that bone microarchitecture is altered early in the course of T1D. The goal of this study is to evaluate how T1D influences longitudinal changes in volumetric BMD (vBMD) and microarchitecture. Methods: This is a 2-year prospective study of girls ages 10-16 years (62 with T1D and 59 controls). We used dual-energy x-ray absorptiometry (DXA) to measure aBMD, and high-resolution peripheral quantitative computed tomography (HR-pQCT) at the distal radius (7% site) and tibia (8% site) to measure vBMD and microarchitecture. We used linear mixed models to assess the effects of T1D on change in bone parameters over time, adjusting for bone age as an index of skeletal maturity, height, lean mass index (LMI), and fat mass index (FMI). Results: At baseline, mean duration of disease in T1D was 4.8 ± 3.2 years, and mean HbA1c was 8.6 ± 1.4%. The groups did not differ by age, bone age, and height, while T1D participants had higher LMI (p&amp;lt;0.001) and borderline higher FMI (p=0.107). Linear growth, weight gain, and changes in body composition over time did not differ between groups. Growth-mediated aBMD gains were observed in both groups at the subtotal body, total hip, femoral neck, and spine. While adjusted aBMD as well as trabecular bone score were lower in T1D, we did not observe between-group differences in changes in these endpoints over time. In both groups, at the distal radius, we observed significant increases over time in total and cortical vBMD, cortical thickness, trabecular (Tb) thickness, and estimated failure load, while cortical porosity decreased. While several microarchitectural parameters were altered in T1D participants, we did not observe significant between-group differences in changes in these measures over time. Of note, trabecular development was subtly altered, with T1D participants demonstrating a borderline significant decrease in Tb vBMD (-14.3 ± 9.0 mg HA/cm3, p=0.112) and Tb number (-0.14 ± 0.07 mm-[1], p=0.057), while control participants had no change in Tb vBMD or number, but a significant increase in Tb thickness (5.8 ± 2.5 µm, p=0.018). At the distal tibia, we observed similar overall detrimental effects of T1D at baseline. However, we did not observe between-group differences in microarchitectural change over time. Glycemic control as measured by HbA1c was not associated with changes in skeletal parameters among T1D participants. Conclusions: T1D leads to substantially altered areal and volumetric BMD as well as microarchitectural parameters in girls. While our data suggest that much of this deficit appears to occur early in the course of disease as prospective change is similar in T1D and controls, subtle changes in trabecular bone development at the radius may indicate ongoing impairment of bone accrual. Presentation: 6/3/2024

Early feasibility study with an implantable near-infrared spectroscopy sensor for glucose, ketones, lactate and ethanol.

To evaluate the safety and performance of an implantable near-infrared (NIR) spectroscopy sensor for multi-metabolite monitoring of glucose, ketones, lactate, and ethanol. This is an early feasibility study (GLOW, NCT04782934) including 7 participants (4 with type 1 diabetes (T1D), 3 healthy volunteers) in whom the YANG NIR spectroscopy sensor (Indigo) was implanted for 28 days. Metabolic challenges were used to vary glucose levels (40-400 mg/dL, 2.2-22.2 mmol/L) and/or induce increases in ketones (ketone drink, up to 3.5 mM), lactate (exercise bike, up to 13 mM) and ethanol (4-8 alcoholic beverages, 40-80g). NIR spectra for glucose, ketones, lactate, and ethanol levels analyzed with partial least squares regression were compared with blood values for glucose (Biosen EKF), ketones and lactate (GlucoMen LX Plus), and breath ethanol levels (ACE II Breathalyzer). The effect of potential confounders on glucose measurements (paracetamol, aspartame, acetylsalicylic acid, ibuprofen, sorbitol, caffeine, fructose, vitamin C) was investigated in T1D participants. The implanted YANG sensor was safe and well tolerated and did not cause any infectious or wound healing complications. Six out 7 sensors remained fully operational over the entire study period. Glucose measurements were sufficiently accurate (overall mean absolute (relative) difference MARD of 7.4%, MAD 8.8 mg/dl) without significant impact of confounders. MAD values were 0.12 mM for ketones, 0.16 mM for lactate, and 0.18 mM for ethanol. The first implantable multi-biomarker sensor was shown to be well tolerated and produce accurate measurements of glucose, ketones, lactate, and ethanol. Clinical trial identifier: NCT04782934.

Retinal artery to vein ratio is associated with cerebral microbleeds in individuals with type 1 diabetes.

A third of asymptomatic individuals with type 1 diabetes (T1D) show signs of cerebrovascular disease in brain MRI. These signs associate with advanced stages of diabetic retinal disease, but not in mild or moderate retinopathy. We aimed to evaluate a wider spectrum of retinal changes by exploring the relationship between quantitative measures of retinal vessel parameters (RVP) and cerebrovascular changes in T1D. We included 146 neurologically asymptomatic individuals with T1D [51% women, median age 40 (33.0-45.1) years] and 24 healthy, sex-matched and age-matched controls. All individuals underwent a clinical and biochemical work-up and brain MRI, which was evaluated for cerebral microbleeds (CMBs), white matter hyperintensities, and lacunar infarcts. RVPs, including central retinal arteriole (CRAE) and central retinal vein (CRVE) equivalents and the ratio of the two variables (arteriovenous ratio, AVR) were assessed quantitatively by a computer-assisted method (IVAN software, version 3.2.6) from fundus images. Among T1D participants, those with CMBs had a lower arteriovenous ratio (AVR) compared with those without CMBs ( P = 0.023). AVR was inversely associated with the amount of CMBs ( r = -0.063, P = 0.035). CMB prevalence was higher in those with AVR below the median (31%) compared with above the median (16%, P < 0.001), and this difference was significant also after individuals with only no-to-mild retinopathy were included (28 vs. 16%, P = 0.005). A correlation between blood pressure and CRAE ( r = -0.19, P = 0.025) appeared among those with T1D. Regardless of the severity of diabetic retinopathy, AVR is associated with the existence of CMBs in T1D.

Hyperglycemia Suppresses Lactate Clearance During Exercise in Type 1 Diabetes.

Circulating lactate concentration is an important determinant of exercise tolerance. This work aimed to determine the role of hyperglycemia on lactate metabolism during exercise in individuals with type 1 diabetes (T1D). The protocol at the University of Virginia compared 7 T1D participants and 7 participants without diabetes (ND) at euglycemia (5.5 mM) or hyperglycemia (9.2 mM) in random order in T1D and at euglycemia in ND. Intervention included [1-13C] lactate infusion, exercise at 65% maximal oxygen uptake (VO2max), euglycemia, and hyperglycemia visits. The main outcome measure was lactate turnover before, during, and after 60 minutes of exercise at 65% VO2max. A 2-compartment model with loss only from the peripheral compartment described lactate kinetics. Volume of distribution of the accessible compartment was similar between T1D and ND individuals (P = .76) and concordant with plasma volume (∼40 mL/kg). Circulating lactate concentrations were higher (P < .001) in T1D participants during exercise at hyperglycemia than euglycemia. Exercise-induced lactate appearance did not differ (P = .13) between hyperglycemia and euglycemia. However, lactate clearance (CL) was lower (P = .03) during hyperglycemia than euglycemia in T1D participants. There were no differences in any of the aforementioned parameters between T1D and ND participants during euglycemia. Hyperglycemia modulates lactate metabolism during exercise by lowering CL, leading to higher circulating lactate concentrations in T1D individuals. This novel observation implies that exercise during hyperglycemia can lead to higher circulating lactate concentrations thus increasing the likelihood of reaching the lactate threshold sooner in T1D, and has high translational relevance both for providers and recreationally active people with T1D.

Multi-Horizon Glucose Prediction Across Populations with Deep Domain Generalization.

Real-time continuous glucose monitoring (CGM), augmented with accurate glucose prediction, offers an effective strategy for maintaining blood glucose levels within a therapeutically appropriate range. This is particularly crucial for individuals with type 1 diabetes (T1D) who require long-term self-management. However, with extensive glycemic variability, developing a prediction algorithm applicable across diverse populations remains a significant challenge. Leveraging meta-learning for domain generalization, we propose GPFormer, a Transformer-based zero-shot learning method designed for multi-horizon glucose prediction. We developed GPFormer on the REPLACE-BG dataset, comprising 226 participants with T1D, and proceeded to evaluate its performance using three external clinical datasets with CGM data. These included the OhioT1DM dataset, a publicly available dataset including 12 T1D participants, as well as two proprietary datasets. The first proprietary dataset included 22 participants, while the second contained 45 participants, encompassing a diverse group with T1D, type 2 diabetes, and those without diabetes, including patients admitted to hospitals. These four datasets include both outpatient and inpatient settings, various intervention strategies, and demographic variability, which effectively reflect real-world scenarios of CGM usage. When compared with a group of machine learning baseline methods, GPFormer consistently demonstrated superior performance and achieved the lowest root mean square error for all the evaluated datasets up to a prediction horizon of two hours. These experimental results highlight the effectiveness and generalizability of the proposed model across a variety of populations, demonstrating its substantial potential to enhance glucose management in a wide range of practical clinical settings.

Fasted C-Peptide Distribution and Associated Clinical Factors in Adults With Longstanding Type 1 Diabetes: Analysis of the Canadian Study of Longevity in Type 1 Diabetes

ObjectiveAlthough insulin production is reportedly retained in many people with longstanding type 1 diabetes (T1D), the magnitude and relevance of connecting peptide (C-peptide) production are uncertain. In this study, we aimed to define fasted C-peptide distributions and associated clinical factors. MethodsIn a cross-sectional analysis of the Canadian Study of Longevity, fasted serum and urinary C-peptide was measured in 74 patients with longstanding T1D (duration ≥50 years) and 75 age- and sex-matched controls. Extensive phenotyping for complications was performed and patient-reported variables were included. C-peptide distributions were analyzed, and multivariable logistic regression was used to assess the variable association in participants with T1D. ResultsThe 74 participants with T1D had a mean age of 66±8 years, a disease duration of 54 (interquartile range 52 to 58) years, and a glycated hemoglobin (A1C) of 7.4%±0.8% (56.8±9.15 mmol/mol). The 75 controls had a mean age of 65±8 years and an A1C of 5.7%±0.4% (38.4±4.05 mmol/mol). Participants with T1D had lower fasted serum C-peptide than controls (0.013±0.022 vs 1.595±1.099 nmol/L, p<0.001). Of the participants with T1D, C-peptide was detectable in 30 of 73 (41%) serum samples, 32 of 74 (43%) urine samples, and 48 of 74 (65%) for either serum or urine. The variables independently associated with detectable serum or urinary C-peptide were lower total daily insulin requirement (odds ratio 2.351 [for 1 lower unit/kg], p=0.013) and lower hypoglycemia worry score (odds ratio 1.059 [for 1 point lower on the worry subscore of the Hypoglycemia Fear Survey], p=0.030). ConclusionsAlthough detectable C-peptide in longstanding diabetes was common, the magnitude of concentration was extremely low when compared with age- and sex-matched controls. Despite minimal detectability, its presence is validated by lower insulin requirements and strongly associated with lower hypoglycemia worry.

Investigating polymorphisms in genes encoding TGF-β1, IL-10, and IL-6 and their associations with type 1 diabetes mellitus

Many cytokines play a role in the pathogenesis of Type 1 Diabetes (T1D), and gene polymorphisms could possibly contribute to the disease’s genetic predisposition because they can affect cytokine production or function. The purpose of this study was to investigate the role of the gene polymorphisms TGF-β1 (+869T/C), (+915G/C), IL-10 {-1082 G/A), (-819 C/T), and (-592 A/C), and IL-6 (-174 G/C) in hereditary vulnerability to T1D. The Polymerase Chain Reaction with Sequence-Specific Primers (PCR-SSP) was used to analyze the polymorphisms. According to their genotypes, individuals were divided into the low-, high-, or intermediate-producer phenotypes predicted for these cytokines polymorphisms. Our findings revealed that the production of TGF-β1 was significantly higher in control than in T1D participants whereas the IL-6 genotype with low IL-6 production was significantly increased in the cases compared to the control. A significant association was evident between TGF-β1 and IL-6 low production and the incidence of T1D, thereby confirming the importance of TGF-β1 and IL-6 polymorphism as a genetic factor contributing to the incidence of T1D. By contrast, the involvement of IL-10 in the incidence of T1D was not as clear. Although some evidence supports a relationship, no statistically significant association has been verified between IL-10 and T1D. This type of measurement could be beneficial in determining the susceptibility and severity of the T1D condition while also taking into consideration the prediction of T1D incidence.

SAT041 18F-FDG PET/CT Mapping Of Functional Microbial Niches To Understand Host Glucose Regulation After BCG Vaccinations

Abstract Disclosure: H. Dias: None. J.F. Fu: None. T.G. Luck: None. G.E. Wolfe: None. E. Hostetter: None. N.C. Ng: None. H. Zheng: None. W. Kühtreiber: None. J.C. Price: None. C. Catana: None. D.L. Faustman: None. Diverse microbiomes in humans are known to change host energy metabolism. When the bacillus Calmette-Guérin (BCG) vaccine, which consists of live but avirulent Mycobacterium bovis, is introduced as experimental therapy into human hosts with underlying type 1 diabetes (T1D), the BCG bacillus has been shown to gradually shift energy metabolism in host blood lymphoid cells from oxidative phosphorylation to aerobic glycolysis. Aerobic glycolysis draws more glucose out of the blood to fuel intracellular metabolism, and it may underlie the BCG bacillus’ therapeutic benefit: the systemic and long-term reduction of excess glucose from the blood of TID patients. The organ-specific niches where the BCG bacillus similarly alters metabolism and establishes persistent residence are not known. In a human clinical trial, we mapped the organ(s) niches for BCG-induced shift to aerobic glycolysis using fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) and x-ray computed tomography (CT). This technique allowed us to reveal quantitatively, by Standardized Uptake Value Ratios, the organs with heightened glucose uptake in T1D participants (n=6) over a 2-year time-period after BCG vaccination versus before vaccination, as well as confirm earlier work that BCG vaccination gradually lowers blood sugar levels without any contribution from endogenous insulin. We also tested BALB/c mice (n=17) for the direct presence of BCG colonies in particular organ niches before and after vaccination. Results from both human and murine studies of the BCG microorganism concurred that the major anatomic site of functional metabolic change and residence is the spleen. The BCG bacillus also transiently mapped to the bone marrow, liver, circulating lymphocytes as in the descending aorta, and the lungs. Findings from human and murine studies support the spleen as the niche for the BCG vaccine’s functional improvement of metabolism. The spleen is significant because it is a lymphoid organ massive enough to explain BCG’s systemic benefit of lowering blood sugar to near normal levels in T1D. Presentation: Saturday, June 17, 2023

Total Calcium Intake Is Associated With Trabecular Bone Density in Adolescent Girls With Type 1 Diabetes.

Type 1 diabetes (T1D) confers an increased risk of fracture and is associated with lower bone mineral density (BMD) and altered microarchitecture compared with controls. Adequate calcium (Ca) intake promotes bone mineralization, thereby increasing BMD. The objective of this analysis was to evaluate the associations of total daily Ca intake with bone outcomes among youth with T1D. This was a cross-sectional analysis of girls ages 10-16 years with (n = 62) and without (n = 60) T1D. We measured Ca intake with a validated food-frequency questionnaire and BMD, microarchitecture, and strength estimates with dual-energy X-ray absorptiometry and high-resolution peripheral quantitative computed tomography. Total daily Ca intake did not differ between groups (950 ± 488 in T1D versus 862 ± 461 mg/d in controls, p = 0.306). Serum 25OHD was lower in T1D (26.3 ± 7.6 versus 32.6 ± 9.0 ng/mL, p = <0.001), and parathyroid hormone (PTH) was higher in T1D (38.9 ± 11 versus 33.4 ± 9.7 pg/mL, p = 0.004). Trabecular volumetric BMD and thickness at the tibia were lower in T1D (p = 0.013, p = 0.030). Ca intake correlated with trabecular BMD at the radius and tibia among T1D participants (β = 0.27, p = 0.047, and β = 0.28, p = 0.027, β = 0.28, respectively) but not among controls (pinteraction = 0.009 at the radius, pinteraction = 0.010 at the tibia). Similarly, Ca intake was associated with estimated failure load at the tibia in T1D but not control participants (p = 0.038, β = 0.18; pinteraction = 0.051). We observed the expected negative association of Ca intake with parathyroid hormone in controls (p = 0.022, β = -0.29) but not in T1D participants (pinteraction = 0.022). Average glycemia as measured by hemoglobin A1c did not influence the relationship of Ca and PTH among participants with T1D (pinteraction = 0.138). These data suggest that youth with T1D may be particularly vulnerable to dietary Ca insufficiency. Increasing Ca intake may be an effective strategy to optimize bone health in this population. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

Assessment of selected muscle damage markers and zonulin concentration after maximum-intensity exercise in men with type 1 diabetes treated with a personal insulin pump

AimExercise-induced muscle damage depends on exercise intensity and duration and on individual susceptibility. Mechanical and metabolic stress may disturb the intestinal microflora. The study evaluated selected muscle damage markers and zonulin concentration after maximum-intensity exercise in type 1 diabetes (T1D) men compared with healthy controls.MethodsThe study involved 16 T1D participants and 28 controls matched by age (22.7 [21.3–25.1] vs. 22.6 [20.9–26.3] years), body mass index (24.2 ± 1.6 vs. 24.2 ± 1.9 kg/m2), and body fat percentage (16.1 ± 5.2 vs. 14.9 ± 4.6%). The T1D group had 11.3 ± 5.1 years of diabetes duration and a suboptimal mean glycated haemoglobin level of 7.2 ± 1.1%. The subjects underwent a graded running treadmill test until exhaustion. Lactate concentration was assessed in arterialized blood at baseline and 3 and 20 min after the test. Cortisol, testosterone, tumour necrosis factor α, myoglobin, lactate dehydrogenase, zonulin, and vitamin D levels were evaluated in cubital fossa vein blood before and 60 min after the test.ResultsT1D patients presented higher baseline zonulin, myoglobin concentration, testosterone/cortisol ratio, and lower maximal oxygen uptake. On adjusting for the baseline values, the groups differed in zonulin, lactate dehydrogenase, and myoglobin levels, testosterone/cortisol ratio, and lactate concentration determined 20 min after exercise (P < 0.05).ConclusionMaximum-intensity exercise increased muscle and intestinal damage in T1D participants. In patients with lower physical activity, very-high-intensity exercise should be recommended with caution. Observing the anabolic-catabolic index may help individualize effort intensity in T1D individuals.

702-P: Similarities and Differences in Type 1 and Type 2 Diabetes Diagnosis Stories

Background: Research on the diagnosis of diabetes portrays it as a functional process of adapting to the condition. People experience variations in physical and psychosocial responses to their diagnosis. No known research has compared diagnosis experiences between people with type 1 diabetes (T1D) and type 2 diabetes (T2D). The purpose of this study was to identify similarities and differences in T1D and T2D diagnosis stories. Methods: We conducted in-depth interviews with adults with T1D and T2D. Two researchers coded the interviews, met to resolve discrepancies, and agreed on themes using NVivo software. Results: A purposive sample of 48 adults participated (mean A1C=7.7±1.8%; mean duration=13.4±12.9 years, mean age=45.8±21.7 years). Nineteen (39.6%) reported a diagnosis of T1D and 29 (60.4%) reported a diagnosis of T2D. Qualitative analysis revealed three themes: 1) Similar Emotional Reactions to Diagnosis: Both participants with T1D and T2D expressed feelings of frustration, depression, fear, and denial in their diagnosis experiences. Interestingly, only T2D participants expressed worry for long-term complications, with some individuals equating their diagnosis to a “death sentence.” 2) Similar Experiences with Diagnosis as a Major Life Event: Both T1D and T2D participants described their diagnosis as a significant life event, with several noting that their life will never be the same. 3) Different Perceptions of Diagnosis as a Surprise: Participants with T1D described their diagnosis as a surprise, whereas participants with T2D did not. Those with T1D expressed initial feelings of denial, while those with T2D referred to their diabetes as inevitable. Conclusion: T1D and T2D participants shared similar emotional reactions, and both described their diagnosis as a major life event. Differently, T1D participants perceived their diagnosis as a surprise, while T2D participants expected their diagnosis. This information may assist clinicians in supporting people with diabetes at diagnosis. Disclosure A.M.Pugh: None. E.A.Beverly: None.

337-OR: Hyperglycemia Lowers Lactate Clearance during Exercise in Type 1 Diabetes

To determine the role of hyperglycemia on lactate metabolism during exercise in type 1 diabetes (T1D), we studied 7 T1D participants during two visits (EuLoI; euglycemia, low insulin; HyLoI: hyperglycemia, low insulin) in random order. 7 nondiabetic (ND) subjects were studied on one occasion (EuLoI). Lactate turnover was measured using [1-13C] lactate before, during and after 60 min of exercise at 65% VO2 max. While lactate clearance was lower (p=0.031) during exercise at HyLoI than EuLoI in T1D, it was not different between T1D and ND subjects at EuLoI (p=0.707). In contrast, rate of lactate appearance during exercise was not different between EuLoI vs. HyLoI in T1D (p=0.129), demonstrating that higher plasma lactate concentration during exercise in HyLoI (p&amp;lt;0.001) was due to reduced lactate clearance in T1D. The results from this pilot study indicates that hyperglycemia modulates lactate metabolism during exercise by lowering lactate clearance in T1D individuals. This novel observation implies that exercise during hyperglycemia can lead to higher circulating lactate concentrations thus increasing the likelihood of reaching the lactate threshold sooner, in type 1 diabetes. Disclosure D.Romeres: None. Y.Yadav: None. F.Ruchi: None. R.Carter: None. C.Cobelli: None. R.Basu: Consultant; Sparrow Pharmaceuticals Inc, Research Support; Abbott Diabetes, AstraZeneca. A.Basu: None. Funding National Institutes of Health (DK29953 to R.B.), (DK85516 to A.B.)

414-P: Multiomic Plasma Markers of Diabetic Kidney Disease in Type 1 Diabetes

Diabetic kidney disease (DKD) is a major complication of type 1 diabetes (T1D). We investigated whether metabolomic, lipidomic and proteomic plasma markers were associated with albuminuria in the Coronary Artery Calcification in Type 1 Diabetes cohort. Two timed overnight urine collections were performed, and albumin excretion rates (AER) were averaged. If overnight samples were unable to be obtained, a spot urine sample was collected and albumin/creatinine ratio (ACR) was used to determine albuminuria status. Albuminuria was defined as an AER ≥ 20 ug/min or an ACR ≥ 30mg/g. Plasma samples from the baseline examination were assayed by LC-MS for multiple omics markers in 225 participants with T1D. Moderated t-tests using false discovery rate (FDR) adjustment for multiple comparisons were used to examine the markers associated with albuminuria presence. An FDR adjusted p-value &amp;lt;0.05 was considered to be statistically significant. Average ± SD for age was 36 ± 9 years and for diabetes duration was 23 ± 9 years, and 58% [n = 120] were female. The prevalence of albuminuria at baseline was 20.4% (n = 46). There were 15 metabolite markers (3 metabolites of symmetric dimethylarginine, 2 of glycyl-glycine, and one each of aspartyl-glycine, glycyl-aspartate and 1-methylhistidine, 7 uncertain) with higher expression in participants with DKD than in those without DKD. There were 7 lipid markers in the acylcarnitine family that were elevated in participants with DKD compared to those without DKD, and 19 glycated peptides (16 in fibrinogen, 1 in kininogen and 1 in hemopexin) showed higher expression in participants with DKD than in those without DKD. None of the unmodified proteins differed by DKD status. Multiple omics markers were higher in T1D participants with albuminuria than in people without any sign of DKD. These findings may suggest changes in lipids, metabolites and glycated proteins early in the course of DKD, and these markers should be explored as potential predictors of worsening DKD. Disclosure J.K.Snell-bergeon: None. R.K.Johnson: None. L.Pyle: None. G.Chen: None. M.M.Weldemariam: None. Q.Zhang: None.

1452-P: Type 1 Diabetes Subphenotypes—A Cluster Analysis

Adult-onset type 1 diabetes (T1D) is a chronic disease with progressive beta-cell destruction. However, individuals with adult-onset T1D are metabolically dissimilar. We aimed to identify metabolically distinct groups in a comprehensively phenotyped cohort of individuals with recent-onset T1D. Participants with T1D (n=550) were split by presence of glutamic-acid decarboxylase antibody (GADA) into a GADA- (n=95) and GADA+ groups (n=455). GADA+ was clustered using partitioning around medoids based on fasting C-peptide, glucose, triglycerides and HDL resulting in 2 distinguished GADA+ clusters. All 3 clusters were compared at baseline (first year of diabetes diagnosis) and after five years of follow-up using ANOVA, chi-squared test and logistic regression adjusted for age and sex. The larger GADA+ cluster (n=285) with younger age, lower BMI and lower C-peptide was termed “classic T1D”. The other GADA+ cluster (n=170) combined features of type 1 and type 2 diabetes and was named “mixed T1D”. Patients of the “mixed T1D” cluster did not gain weight over 5 years (p=0.29), which was not the case for “classic T1D” cluster (p&amp;lt;0.001, increased BMI with an effect size 0.07) and GADA-cluster (p=0.01, effect size 0.04) participants. The “classic T1D” cluster had the highest insulin sensitivity at baseline (p&amp;lt;0.001) that sharply decreased during five years of follow-up. At five years, there was no difference in insulin sensitivity across the 3 clusters (p=0.78). There were no differences in HbA1c levels across clusters neither at baseline (p=0.48) nor after 5 years (p=0.64). Classic T1D participants reported a higher incidence of hypoglycemia (OR 4.92, 95% CI 1.9-13.5, p=0.001). The incidence of both distal peripheral sensory (OR 2.89, 95%CI1.05-8.29, p= 0.041) and cardiac autonomic neuropathy (OR 9.61, 95%CI 2.35-49.8, p= 0.003), was higher in “mixed T1D”. Based on rapidly available laboratory variables, individuals with recent-onset adult type 1 diabetes can be stratified into clusters with different clinical course and complication risk Disclosure K.Prystupa: Other Relationship; Berlin-Chemie AG. S.M.Meyhöfer: Speaker's Bureau; Novo Nordisk, AstraZeneca, Lilly, Amgen Inc., Boehringer-Ingelheim, Novartis. O.P.Zaharia: None. N.Saatmann: None. M.Huttasch: None. K.Strassburger: None. V.Burkart: None. M.Roden: Advisory Panel; Eli Lilly and Company, Consultant; TARGET PharmaSolutions, Inc., Research Support; Boehringer-Ingelheim, Novo Nordisk, Novartis, Sanofi. R.Wagner: Advisory Panel; Daiichi Sankyo, Speaker's Bureau; Novo Nordisk, Sanofi. A.Fritsche: Advisory Panel; Novo Nordisk, Lilly, Sanofi, Boehringer-Ingelheim, Speaker's Bureau; AstraZeneca, SYNLAB Holding Deutschland GmbH. G.J.Bönhof: None. A.Strom: None. M.Heni: Advisory Panel; Boehringer-Ingelheim, Sanofi, Research Support; Boehringer Ingelheim Inc., Speaker's Bureau; Lilly, Bayer Inc., Sanofi, Boehringer-Ingelheim, Novo Nordisk, Amryt Pharma Plc. J.Seissler: None. J.Szendroedi: None. A.F.Pfeiffer: Advisory Panel; Abbott Diabetes, Speaker's Bureau; Novo Nordisk, Sanofi-Aventis Deutschland GmbH. M.W.Stumvoll: None.

The psychological and health benefits of using a continuous glucose monitor for a person with type 1 diabetes: A South African higher education context

Background: There has been an increasing focus on the unique health needs and experiences of people with chronic health problems, given health disparities between these groups and the wider population. The focus of this study is on understanding the psychological and health benefits of using continuous glucose monitoring (CGM) by people with type 1 diabetes (T1D) and to present findings from interviews on their experiences. All interviewees were subsequently invited for intervention at an Open Distance Learning institution in South Africa. Methods: Data were collected using an online semi-structured questionnaire to gather information influencing the study participant’s decision to use CGM during the context of COVID-19. An invitation was sent via Facebook group ‘Type 1 Diabetics South Africa’ and attracted 30 responses. The final study comprised of 10 respondents whose returned questionnaires met the inclusion criteria and took part in the in-depth interviews for analysis using Atlas.ti9 software. Results: The results suggest that T1D participants benefited from using CGM in combating chronic medical and psychological (psychosocial) conditions. Many reported improvements in health and psychological factors; in time monitoring of glucose levels, low events of hypoglycaemia, improved self-confidence, improved concentration span, diminished numbers of hospitalization. Some reported improved socialization, relief from finger pricking pains and better control of life. Graphical representations of the different results will be depicted in tables and figures. Conclusions: The 4th industrial revolution is technology-based and continuous glucose monitoring is a form of artificial intelligence enabling people living with T1 diabetes to make smarter choices more often and at a faster pace with more information. If people with diabetes are unable to access this intelligent technology, they will be at increased risk of complications, hypoglycaemia, reducing their quality of life. The use of CGM by T1D, with complementary psychotherapy, indicated improved health related quality of life.

Disordered Eating Behaviors and Insulin Restriction in Saudi Adolescents and Young Adults with Type 1 Diabetes

Background and Objectives: The prevalence of disordered eating behaviors (DEBs) in type 1 diabetes (T1D) has been studied globally; however, data from Saudi Arabia and Arab-speaking countries are scarce. This study aimed to measure the prevalence of DEBs and associated clinical characteristics in adolescents and young adults with T1D, and the impact of DEBs on glycemic parameters. Materials and Methods: A total of 265 adolescents and young adults with T1D (aged 12-25 years) were recruited randomly from the registry at the Jazan Endocrinology and Diabetes Center, Saudi Arabia. Participants completed the Diabetes Eating Problem Survey-Revised (DEPS-R) questionnaire. Other measures included hemoglobin A1c (HbA1c) in addition to sociodemographic, anthropometric, and clinical data. Results: The prevalence of DEBs among T1D was 27.2%. Females (32.5%) had a higher proportion of DEBs than males (18.6%) (p = 0.01). About 27% of the participants reported insulin restriction. A history of hospital admission in the previous 6 months due to DKA and frequent hypoglycemia was more frequently reported in T1D participants with DEBs compared to those without (p = 0.03). Participants with DEBs had higher HbA1c and higher BMI compared to those without DEBs. Conclusions: Adolescents and young adults with T1D with disordered eating and insulin restriction have higher glycated hemoglobin, and are at higher risk of DKA. Routine screening for DEBs should be an essential element in diabetes care, especially among highly vulnerable groups.

Defining and Phenotyping Gastric Abnormalities in Long-Term Type 1 Diabetes Using a Novel Body Surface Gastric Mapping Device

Diabetic gastroenteropathy is associated with poor glycemic control and morbidity in people with type 1 diabetes (T1D). There is a lack of noninvasive techniques to assess and monitor gastric abnormalities. We aimed to define phenotypes of gastric myoelectrical abnormalities in people with longstanding T1D with and without symptoms using a novel noninvasive body surface gastric mapping (BSGM) device. BSGM was performed on people with T1D of >10 years duration and matched controls, employing Gastric Alimetry (Alimetry, New Zealand), comprising of a high-resolution 64-channel array, validated symptom-logging App, and wearable reader. Thirty-two people with T1D were recruited (15 with a high symptom burden), and 32 controls. Those with symptoms showed more unstable gastric myoelectrical activity (Gastric Alimetry Rhythm Index 0.39 vs 0.51, P= .017; and lower average spatial covariance 0.48 vs 0.51, P= .009) compared with controls. Symptomatic patients also had a higher prevalence of peripheral neuropathy (67% vs 6%, P= .001), anxiety/depression diagnoses (27% vs 0%, P= .001), and higher mean hemoglobin A1C levels (76 vs 56 mmol/mol, P < .001). BSGM defined distinct phenotypes in T1D participants including those with markedly unstable gastric rhythms (4/32, 12.5%) and abnormally high gastric frequencies (9/32, 28%). Deviation in gastric frequency was positively correlated with symptoms of bloating, upper gut pain, nausea and vomiting, and fullness (R > 0.35, P < .05). Gastric symptoms in people with longstanding T1D correlate with myoelectrical abnormalities on BSGM evaluation, in addition to glycemic control, psychological comorbidities, and peripheral neuropathy. BSGM using Gastric Alimetry identified a range of myoelectrical phenotypes, presenting targets for diagnosis, monitoring, and therapy.

Dietary Intake and Physical Activity of Thai Children and Adolescents with Type 1 Diabetes Mellitus.

Appropriate dietary intake and physical activity (PA) are essential for glycemic control and optimal growth in youth with type 1 diabetes (T1D). Thus, this study aimed to compare dietary intake and PA between youth with T1D and healthy controls. One hundred Thai youth with T1D and 100 age-matched healthy participants were recruited. A 3-day food record was completed and converted into nutrient intake data. PA data were collected via interview. Participants with T1D had a significantly higher mean ± SD carbohydrate (50.8 ± 6.8% vs. 46.2 ± 7.5%, p < 0.01), lower fat (32.4 ± 5.9% vs. 35.9 ± 6.4%, p < 0.01), and lower protein (16.8 ± 2.6% vs. 17.9 ± 3.5%, p = 0.01) intake compared to controls. Fifty percent of T1D participants and 41% of control participants consumed saturated fat more than recommendations (p = 0.20). Participants with T1D had a higher median (IQR) calcium intake compared to controls (474 (297−700) vs. 328 (167−447) mg/day, p < 0.01). Both groups consumed less fiber and more sodium compared to recommendations. Both groups had inadequate PA. Participants with T1D had significantly less PA compared to controls (25 (13−48) vs. 34 (14−77) minutes/day, p = 0.04). In addition to the need for counseling that promotes consumption of more dietary fiber and calcium and less saturated fat and sodium, the benefits of performing regular exercise need to be emphasized among youth with T1D.