bluuebunny/crossref_metadata_2025 huggingface dataset:
126-OR: Long-Term Consequences of Diabetic Foot Infection: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: FANG MICHAEL , HU JIAQI , MATSUSHITA KUNIHIRO , SELVIN ELIZABETH , HICKS CAITLIN W.
Published: May 2022

Introduction: Foot infections are a common complication of type 2 diabetes. However, the clinical sequelae of diabetic foot infection (DFI) in the general population remain poorly characterized.

Methods: We conducted a prospective cohort analysis of 1,451 participants with diabetes (mean age, 63 years [SD: 5.6]; 33% black; 47% female) in the ARIC study (visit 4: 1996-1998) . DFI was ascertained using ICD-9/codes from Medicare claims and hospital discharge records. We used Kaplan-Meier analyses to estimate the 5-year cumulative incidence of nontraumatic lower-extremity amputation (NLEA) , major fall, cardiovascular disease (CVD) [coronary heart disease, stroke, or heart failure], and death following incident DFI. We evaluated the association between incident DFI (modeled as a time-varying exposure) and the subsequent risk of clinical outcomes with Cox models.

Results: During over two decades of follow-up (1996-1998 to 2017) , there were 328 incident DFIs, 72 NLEAs, 502 major falls, 748 CVD events, and 915 deaths. Following incident DFI, the five-year cumulative incidence of major clinical outcomes ranged from 14.7% (NLEA) to 38.6% (death) (Fig 1a) . Incident DFI was significantly associated with all clinical outcomes after multivariable adjustment (Fig 1b) .

Conclusion: DFI is a high-risk marker for major morbidity and mortality in the general population of adults with diabetes.

Disclosure

M.Fang: n/a. J.Hu: None. K.Matsushita: Consultant; Akebia Therapeutics, Inc., Mitsubishi Tanabe Pharma Corporation, Other Relationship; Fukuda Denshi, Research Support; Kyowa Kirin Co., Ltd. E.Selvin: Other Relationship; Wolters Kluwer. C.W.Hicks: None.

Funding

HHS (N268201700001I) , HHS (N268201700002I) , HHS (N268201700003I) , HHS (N268201700005I) , HHS (N268201700004I) , NHLBI (K24HL152440)
1262-P: Developing a Computable Phenotype Algorithm for Identification of Children and Adolescents with Diabetes Using Electronic Health Records
Authors: LI PIAOPIAO , SPECTOR ELIOT , ALKHUZAM KHALID , PATEL RAHUL S. , DONAHOO WILLIAM T. , BOST SARAH , LYU TIANCHEN , WU YONGHUI , HOGAN WILLIAM , PROSPERI MATTIA , DIXON BRIAN E. , DABELEA DANA , UTIDJIAN LEVON H. , CRUME TESSA L. , THORPE LORNA , LIESE ANGELA D. , SCHATZ DESMOND , ATKINSON MARK A. , HALLER MICHAEL J. , SHENKMAN ELIZABETH , BIAN JIANG , GUO YI , SHAO HUI , ATKINSON MARK A.
Published: May 2022

The Assessing the Burden of Diabetes by Type in Children, Adolescents, and Young Adults (DiCAYA) Network, a CDC/NIDDK-funded collaborative, aims to create a multi-site electronic health record (EHR) -based diabetes surveillance system. Foundational to the network's efforts is the development of a computable phenotype (CP) algorithm that can identify cases of diabetes. To advance the mission of the DiCAYA network, University of Florida (UF) Health system researchers developed a pilot CP algorithm for identifying diabetes cases in youth. The CP algorithm was iteratively derived based on structured data from EHRs (UF Health system 2012-2020) . We randomly selected 500 presumed cases among individuals < 18 years old who has (1) HbA1c ≥ 6.5%; or (2) fasting glucose ≥ 126 mg/dL; or (3) random plasma glucose ≥ 200 mg/dL; or (4) diabetes-related diagnosis code from an inpatient or outpatient encounter; or (5) prescribed, administered, or dispensed diabetes-related medication. Four reviewers independently reviewed the patient charts to determine diabetes status and type. Presumed cases without type 1 (T1D) or type 2 (T2D) diabetes diagnosis codes were categorized as nondiabetes or other types. The rest were categorized as T1D if the ratio of T1D codes to the sum of T1D and T2D codes was ≥ 0.5, or otherwise categorized as T2D. Next, we applied a list of diagnoses and procedures that can determine diabetes type (e.g., steroid use suggests induced diabetes) to correct misclassifications from step 1. Among the 500 reviewed cases, 159 and 64 had T1D and T2D. The sensitivity, specificity, and positive predictive values of the CP algorithm were 94%, 98%, and 96% for T1D; 95%, 95%, and 73% for T2D. We developed a highly accurate EHR-based CP for diabetes in youth based on EHR data from UF Health. Consistent with prior studies, T2D was more difficult to identify using these methods. A DiCAYA-wide validation and algorithm refinement process will be conducted.

Disclosure

P.Li: None. M.Prosperi: None. B.E.Dixon: Advisory Panel; Merck Sharp & Dohme Corp. D.Dabelea: None. L.H.Utidjian: None. T.L.Crume: None. L.Thorpe: None. A.D.Liese: None. D.Schatz: Advisory Panel; Abbott Diabetes, Medtronic. M.A.Atkinson: None. M.J.Haller: Advisory Panel; SAB Biotherapeutics , Consultant; MannKind Corporation, Sanofi. E.Spector: None. E.Shenkman: None. J.Bian: None. Y.Guo: None. H.Shao: Board Member; BRAVO4HEALTH, LLC. M.A.Atkinson: None. K.Alkhuzam: None. R.S.Patel: None. W.T.Donahoo: None. S.Bost: None. T.Lyu: None. Y.Wu: None. W.Hogan: None.

Funding

CDC/NIDDK U18DP006512
1285-P: Differentiating between Diabetic and Idiopathic Gastroparesis: A Genetic Perspective
Authors: SMIESZEK SANDRA P.
Published: May 2022

Gastroparesis is a serious medical condition characterized by delayed gastric emptying and symptoms of nausea, vomiting, bloating, fullness after meals, and abdominal pain. An innate immune dysregulation and injury to the interstitial cells of Cajal and other components of the enteric nervous system is likely central to the pathogenesis of gastroparesis. Most common etiologies include diabetes, post-surgical but most cases are idiopathic. Thus far, little is known about the underlying genetic risk factors for gastroparesis. We have done a genome-wide association study comparing idiopathic and diabetic cases with controls as well as contrasting idiopathic versus diabetic cases. We report a novel genetic association of SLC15A4 locus with idiopathic gastroparesis. This signal is driven by multiple variants with top missense variant SLC15A4:NM145648:exon2:c.T716C:p.V239A, rs33990080. Altogether, among EUR cohort we report 69 carriers out of 214 versus controls 165 out of 896 (MAF: cases 0.18; MAF: controls 0.09) and OR: 1.9 (p-value<10^-6) . We furthermore differentiate idiopathic from diabetic gastroparesis with an established diabetes genetic risk score, - result that is statistically significant (p-value<0.0004) . We also delineate a number of significant loci implicated in diabetes risk including (HLA-DQB1,HLA-DQA2, EXOC6B) in the idiopathic versus diabetic gastroparesis analysis. Of particular interest are the Exocyst complex component, 6 (EXOC6/6B) with lead variant rs41420. previously identified to play a role in insulin signaling through its interaction with the glucose transporter GLUT4. Current genetic findings suggest that a mechanism directly connected to macrophage polarization may be implicated in the etiology gastroparesis. The GWAS picture that is emerging implicates novels loci implicated in the pathophysiology of gastroparesis differentiating those of diabetic versus idiopathic etiology.

Disclosure

S.P.Smieszek: None.
1363-P: Remission of Type 2 Diabetes and Improvement in Incretins, Cardiovascular Risk Factors, and Weight Loss with a High-Protein Diet
Authors: STENTZ FRANKIE B. , AMMONS ANN , CHRISTMAN JOHN V.
Published: May 2022

The incretins GLP-1 and GIP have important roles in insulin sensitivity and have been shown to be effective in pharmacological treatment of type 2 diabetes (T2D) . Therefore, we studied these incretin level changes with remission of T2D and weight loss using a high protein (HP) diet in 12 obese women and men with T2D. Our studies have shown that subjects with T2D on a 6 month HP diet (30%protein,30%fat, 40%CHO) had 100% remission of T2D compared to only 33% on a HC diet (15%protein,30%fat, 55%CHO) . Effects of HP and HC diets on ghrelin levels were determined since HP subjects had increased satiety compared to HC diet. GLP-1, GIP, and Ghrelin levels were determined with a Meal Tolerance Test (MTT) at baseline and after 6 mo on HP and HC diets where all food was provided. Since cardiovascular risk factors (CVRF) decreased more in the HP than the HC diet, we determined if the B-Type Natriuretic Peptide (BNP) released from the heart was affected by either diet. As shown in Table, HP diet had a greater increase in GLP-1 and GIP than the HC diet. BNP decrease demonstrates improvement in heart tissue with the HP diet having a greater effect than the HC diet. Weight loss was similar (9.8% in HP vs. 11.3% in HC, p=0.692) . this study demonstrates that the HP diet increases GLP-1 and GIP which may be responsible in part for the improved insulin sensitivity and decreased BNP with greater improvement in CVRF with remission of T2D

Disclosure

F.B.Stentz: None. A.Ammons: None. J.V.Christman: None.

Funding

AD Baskin Research Grant
1377-P: Pramlintide Lowers Postprandial Glucagon Concentrations by Inhibiting Glucagon Secretion without Altering Clearance in Type 1 Diabetes: A [13C15N]-Glucagon Study
Authors: RUCHI FNU , ROMERES DAVIDE , SCHIAVON MICHELE , RENUSE SANTOSH , PANDEY AKHILESH , MAN CHIARA DALLA , COBELLI CLAUDIO , BASU RITA , BASU ANANDA
Published: May 2022

To determine the underlying mechanism of pramlintide effects on postprandial (PP) glucagon concentrations, we studied thirteen C-peptide negative T1D subjects (Age 35±yrs, BMI 27.6±2.2 kg/m2, fasting plasma glucose 9.4±4 mM, HbA1c 7.1±1%) on two occasions in random order, with and without 30 μg of sc pramlintide at the onset of a mixed meal (75 gm carb, 15% fat and 35% protein; 8 kcal/kg) . Subjects administered insulin bolus at meal onset. 13C15N glucagon tracer was infused intravenously to estimate PP glucagon turnover. Arterialized venous samples were drawn periodically for measurements of glucose (YSI) , 13C15N-glucagon (LC-MS/MS) and glucagon (Mercodia) concentrations. Systemic glucagon turnover was calculated using non-steady state Steele's equation after determining glucagon volume of distribution. Integrated PP glucagon concentrations were lower (p<0.01) in pramlintide (Pram) than without pramlintide (No Pram) . Integrated rates of glucagon appearance and glucagon disappearance were lower (p<0.01) in Pram vs. No Pram. When adjusted for plasma glucagon concentrations, glucagon clearance was not different (p=0.7) between Pram vs. No Pram. These data demonstrate that pramlintide lowers postprandial glucagon concentrations by lowering glucagon secretion without altering clearance in subjects with T1D.

Disclosure

F.Ruchi: None. D.Romeres: None. M.Schiavon: None. S.Renuse: None. A.Pandey: None. C.Dalla man: Research Support; Becton, Dickinson and Company, Sanofi-Aventis Deutschland GmbH. C.Cobelli: None. R.Basu: Consultant; Sparrow Pharmaceuticals Inc, Research Support; Abbott Diabetes, AstraZeneca. A.Basu: Speaker's Bureau; Zealand Pharma A/S.

Funding

National Institute of Health (DK 085516, DK 029953)
1400-P: Endothelial Cell Autophagy Contributes to HFD-Induced Obesity and Insulin Resistance in Mice
Authors: REN GUANG , KIM JEONGA
Published: May 2022

Autophagy is a catabolic process and plays crucial roles in cellular physiology, including energy homeostasis, cell survival, and inflammation. Autophagy-related gene 7 (ATG7) is an essential regulator of autophagosome formation. Although endothelial cell ATG7 (EC-ATG7) plays a critical role in atherosclerosis, thrombosis, and injuries from ischemia/reperfusion, the role of EC-ATG7 in obesity and insulin resistance is not known. Because endothelial function contributes to insulin resistance by regulating blood flow and delivery of nutrients and hormones to metabolic tissues, EC autophagy may affect metabolism and insulin resistance. Thus, we hypothesize that EC-ATG7 contributes to high-fat diet (HFD) -induced obesity and insulin resistance. To examine the role of EC-ATG7 in obesity and insulin resistance, we generated an EC-specific ATG7 knockout mouse (ATG7Δ EC) by breeding Cdh5-CRE mouse with ATG7flox/flox mouse. ATG7Δ EC mice were fed a normal chow diet (NCD) or HFD for twelve weeks. HFD-fed ATG7Δ EC mice gained less body weight compared with HFD-fed wild-type (WT) mice, while body weight was not different when the mice were fed NCD. HFD-fed ATG7Δ EC mice demonstrated lower food intake. Interestingly, intraperitoneal injection of low dose 2-arachidonoyl glycerol (2AG) , a cannabinoid receptor agonist, restored the food intake in ATG7Δ EC mice but not in WT mice. This indicates that the EC-ATG7 affects food intake by stimulating endogenous cannabinoid receptor (s) in the brain. Furthermore, HFD-fed ATG7Δ EC mice were more insulin sensitive than HFD-fed WT mice.

In conclusion, our findings demonstrate a novel function of EC-ATG7 in regulating food intake and insulin resistance.

Disclosure

G.Ren: None. J.Kim: None.

Funding

National Institutes of Health (R01-HL128695, R03-AG058078, P30-DK079626)
1411-P: Increased 24-Hour Plasma Free Fatty Acids in People with Obesity and Prediabetes
Authors: PETERSEN MAX C. , FARABI SARAH S. , SMITH GORDON , KLEIN SAMUEL
Published: May 2022

The importance of increased plasma free fatty acids (FFAs) in the pathogenesis of insulin resistance in people with prediabetes is unclear. It has been proposed that the increase in plasma insulin associated with obesity should be adequate to suppress adipose tissue lipolytic rates and maintain normal plasma FFA levels. We evaluated serial plasma FFA concentrations for 24 h in 20 adults with obesity and normal fasting glucose and glucose tolerance (metabolically healthy obesity [MHO]) and 20 adults with prediabetes, matched on age, sex, BMI and percent body fat with the MHO group. Insulin sensitivity, assessed as the glucose infusion rate during an insulin clamp, was greater in the MHO than the prediabetes group (48.1 ± 3.0 vs. 23.5 ± 1.3 μmol/kg fat-free mass/min, respectively, P < 0.0001) . Plasma FFA were greater throughout 24 h in the prediabetes group than the MHO group (Figure) . The 24-h areas under the curve were greater for plasma FFA (5.59 ± 0.37 vs. 4.58 ± 0.30 mmol/L x hour, P = 0.04) and plasma insulin (13,5± 1720 vs. 6,541 ± 558 pmol/L x hour, P = 0.0004) in the prediabetes group than the MHO group. We conclude that plasma FFA concentrations are greater throughout the day in people with prediabetes than those with MHO, despite a marked increase in plasma insulin concentration in those with prediabetes. These data support the notion that increased 24-h plasma FFAs contribute to insulin resistance associated with obesity.

Disclosure

M.C.Petersen: None. S.S.Farabi: n/a. G.Smith: None. S.Klein: Advisory Panel; Altimmune, Consultant; Janssen Research & Development, LLC, ProSciento, Research Support; Janssen Research & Development, LLC.

Funding

NIH T32DK007120Endocrine Fellows Foundation
1430-P: Association of Obesity and Diabetes with SARS-Cov-2 Infection and Symptoms
Authors: MONGRAW-CHAFFIN MORGANA , TJADEN ASHLEY H. , SEALS AUSTIN , MILLER KRISTEN , AHMED NAHEED , ESPELAND MARK , GIBBS MICHAEL A. , USCHNER DIANE , WEINTRAUB WILLIAM S. , EDELSTEIN SHARON
Published: May 2022

Background: Obesity and T2D are risk factors for SARS-CoV-2 outcomes, but less is known about non-hospitalized cases. We hypothesized that those with obesity or T2D are more likely to have a positive Covid test, and among those with a positive test, to have symptoms.

Methods: Among 31,117 North Carolina Covid Community Research Partnership participants with EHR data, we evaluated the association of self-reported and EHR obesity and T2D with a self-reported positive Covid test at any time. Among 2,418 participants with a positive test during the study, we evaluated the association of obesity and T2D with self-report of symptoms. Logistic regression models were adjusted for age, sex, race/ethnicity, socioeconomic status, and healthcare worker status.

Results: We found a positive graded association between BMI category and positive Covid test, and a similar but weaker association with Covid symptoms among those with a positive test (Table) . T2D was associated with Covid infection but not symptoms.

Conclusions: While the limitations of this health system convenience sample include generalizability and test seeking selection bias, the strong graded association of BMI and T2D with self-reported Covid infection suggests that obesity and T2D may play a role in risk for symptomatic SARS-CoV-2 beyond co-occurrence with socioeconomic risk factors.

Disclosure

M.Mongraw-chaffin: None. S.Edelstein: None. A.H.Tjaden: None. A.Seals: None. K.Miller: None. N.Ahmed: None. M.Espeland: None. M.A.Gibbs: None. D.Uschner: None. W.S.Weintraub: None.

Funding

The CARES Act of the U.S. Department of Health and Human Services (HHS) [Contract # NC DHHS GTS #49927].
1453-P: Possible Delta- to Beta-Cell Transdifferentiation in Aged Diabetic Mutant CRY1 Transgenic Mice
Authors: OKANO SATOSHI , YASUI AKIRA , SATOH KENNICHI , KANNO SHIN-ICHIRO , IGARASHI MASAHIKO , NAKAJIMA OSAMU
Published: May 2022

Cysteine414 (zinc-binding site of mCRY1) -alanine mutant mCRY1 transgenic mice (TG) show diabetes characterized by the reduction of β-cell proliferation due to the characters of senescence-associated secretory phenotype (SASP) in β-cells as we have reported at ADA Scientific Sessions in 2015. We also showed that various structural remodeling progresses in the islets of TG age-dependently: the increase of the population ratios of α-cell to β-cell and of ∂-cell to β-cell as well as fibrillation, angiogenesis and also the generation of mucin-producing atypical intra-islet ducts. Also, we revealed that trefoil factor family 2 (TFF2) is up-regulated in the β-cell of aged TG (Okano S. et al., ADA Scientific Sessions in 2020). To explore the mechanisms of keeping of the amount of β-cells under hyperglycemia for prolonged period in TG, we further conducted detailed double immune-staining experiments in the pancreatic sections of various ages (approximately 1, 10, and 19 months) of TG. The results demonstrated that, somatostatin and insulin double-positive cells were observed exclusively in aged TG (19 months of age). In wild-type mice (WT) of all stages, the double-positive cells were not observed. No glucagon and insulin double-positive cell was observed in islets of both TG and WT of all stages. In addition, scrutinized analyses demonstrated that not only β-cells but also small portion of somatostatin-positive cells express TFF2 in islets of aged TG. Taken together, these results suggest the possible ∂-cell to β-cell transdifferentiation in aged TG, that is, ∂-cells may play some role as the source for β-cells to supply new β-cells for islets in TG.

Disclosure

S.Okano: None. A.Yasui: None. K.Satoh: None. S.Kanno: None. M.Igarashi: None. O.Nakajima: None.

Funding

Grants-in-Aid for Scientific Research (19K07498). The Joint Research Program of IDAC, Tohoku University (38).
1457-P: Cholesterol Accumulation in Islets Increases Steroidogenic Acute Regulatory (StAR) Protein Expression and Decreases Islet Cell Viability and ß-Cell Function
Authors: AKTER REHANA , HOGAN MEGHAN F. , ESSER NATHALIE , CASTILLO JOSEPH J. , HULL-MEICHLE REBECCA L. , ZRAIKA SAKENEH , KAHN STEVEN E.
Published: May 2022

Diabetes is associated with elevated plasma cholesterol (Chol) , with its intracellular accumulation resulting in β-cell dysfunction. In steroidogenic tissues, StAR facilitates Chol transport from the outer to inner mitochondrial membrane for subsequent metabolism. We have shown that StAR is expressed in β cells and its upregulation increases mitochondrial Chol content and decreases mitochondrial function. To determine whether excess Chol per se increases StAR expression and reduces islet viability, we cultured mouse islets for 24 hours in Chol and quantified mRNA levels of Star and genes involved in Chol synthesis (Hmgcr) , uptake (Ldlr) and efflux (Abca1) , cell viability and glucose stimulated insulin secretion (GSIS) . Islet Chol content increased with increasing Chol concentrations (27.1±1.7, 55.3±0.5 and 72.7±5.2 µg/mg protein for 0, 0.25 and 0.5 mM respectively; n=3, p<0.0by ANOVA) , with mitochondrial Chol increasing 2.4-fold in 0.5 mM (9.1±0.2 to 22.4±1.9 µg/mg protein; n=3, p<0.005) . This was associated with increased Star mRNA expression (1.0±0.1, 3.0±0.9 and 7.0±1.5; n=3, p=0.014) . Further, mRNA expression of Hmgcr tended to decrease (1.0±0.2, 0.8±0.3 and 0.3±0.0; n=3, p=0.088) , whereas expression of Ldlr and Abca1 did not change (Ldlr: 1.7±0.8, 1.1±0.7 and 0.5±0.3; n=3, p=0.508; Abca1: 1.1±0.3, 1.9±0.7 and 1.1±0.1; n=3, p=0.413) . These changes were associated with reductions in cell viability (100±15.7%, 68.0±12.6% and 57.3±9.6%; n=2, p=0.025) and GSIS in response to 20 mM glucose (fold increase over 2.8 mM: 0 mM Chol 28.5±0.6, 0.25 mM Chol 8.9±0.5, 0.5 mM Chol 10.8±0.9; n=2, p<0.0001) .

In summary, islet cholesterol accumulation is associated with increased StAR expression, decreased cell viability and reduced β-cell function. These data suggest that elevated cholesterol in diabetes may contribute to β-cell dysfunction by increasing StAR expression and mitochondrial cholesterol accumulation.

Disclosure

R.Akter: None. M.F.Hogan: Employee; NanoString. N.Esser: None. J.J.Castillo: None. R.L.Hull-meichle: Research Support; Casma Therapeutics. S.Zraika: None. S.E.Kahn: Advisory Panel; Bayer AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Intarcia Therapeutics, Inc., Merck & Co., Inc., Novo Nordisk, Pfizer Inc.

Funding

VA (I01BX001060) ,VA (IBX004063) ,NIDDK (P30 DK017047) ,NIDDK (T32 DK007247)
148-LB: Glomerular Filtration Rate Trajectories in Children with Type 1 Diabetes
Authors: FAVEL KRISTEN , MAMMEN CHERRY , PANAGIOTOPOULOS CONSTADINA
Published: May 2022

Background: While children with type 1 diabetes (T1D) may be at risk for chronic kidney disease (CKD) , data describing changes in kidney function from diagnosis is lacking. Currently, Canadian guidelines do not recommend routine monitoring of serum creatinine in these children. As part of a quality improvement initiative, we implemented routine serum creatinine monitoring. In this study, we describe estimated glomerular filtration rate (eGFR) trajectories in children with T1D.

Methods: This longitudinal cohort study involved children with T1D followed in the Diabetes Clinic, who had ≥2 eGFR measurements. Data was collected from health records from 2016 to 2021. Annualized change in eGFR was calculated using the Bedside Schwartz equation, and a declining trajectory was defined a priori as <-3 ml/min/1.73m2 per year. Latent class mixed models were used to categorize eGFR trajectories, and patient characteristics were compared between trajectories.

Results: Of the 307 participants, 46% were male; the median age at diagnosis and duration of T1D was 6.2 years and 6.9 years, respectively. Three eGFR trajectories were identified: stable-declining from normal baseline (93.8%) , rapidly declining from high baseline (4.5%) , and rapidly inclining from normal baseline (1.6%) . During their follow-up, 68 (22%) patients had an eGFR <90 ml/min/1.73 m2. Increasing BMI and blood pressure were observed in patients with a declining trajectory (46.9% of all patients) .

Conclusion: Nearly half of children with T1D in this cohort had a declining eGFR trajectory. Notably, 22% of these children are at risk for CKD (eGFR <90 ml/min/1.73 m2) early in their T1D course. These findings, along with the steady rise in blood pressure, are concerning given the increased risk of CKD and end-stage renal disease in adults with T1D. These data suggest that careful monitoring of serum creatinine and blood pressure at baseline and regular intervals is warranted in children with T1D.

Disclosure

K. Favel: None. C. Mammen: None. C. Panagiotopoulos: Speaker's Bureau; Eli Lilly and Company.

Funding

BC Children's Hospital Research Institute, Canucks for Kids Fund Diabetes Legacy Grant (FAS #: F21-02506)
149-OR: Genetic Modulation of HNF1A Activity via SGLT2 Deficiency Leads to Transient Intermittent Hyperglycemia: Consequences for HNF1A-MODY
Authors: ACOSTA-MONTALVO ANA , SAPONARO CHIARA , THEVENET JULIEN , CHIRAL MAGALI , PIRON ANTHONY , DELALLEAU NATHALIE , PASQUETTI GIANNI , CODDEVILLE ANAÏS , MORENO MARIA , GMYR VALERY , CNOP MIRIAM , KERR-CONTE JULIE A. , PATTOU FRANCOIS , PONTOGLIO MARCO , LISTON ADRIAN , BONNER CAROLINE
Published: May 2022

Hepatocyte Nuclear Factor-1A (HNF1A) is a master regulator of key glucose-responsive genes in metabolic organs such as the intestine, liver, kidney, and pancreas. Heterozygous mutations in HNF1A cause Maturity-Onset-Diabetes-of-the-Young (HNF1A-MODY) . Mutant carriers are normoglycemic in childhood, but with age, they develop hyperglycemia. Although insulin secretory defects have been extensively studied, it is unclear whether HNF1A deficiency contributes to a progressive decline in alpha cell function. HNF1A-MODY patients display glycosuria and endogenous glucose production linked to reduced renal SGLT2 expression. Since SGLT2 is also expressed in alpha cells and is required for glucagon regulation, we hypothesized that HNF1A coordinates renal and alpha cell SGLT2 activity to maintain glucose homeostasis. Here, we studied Hnf1a regulation of renal Sglt2, Sglt1, and Glut2 in Hnf1a-/- mutant mice, glucagon expression and secretion in siHNF1A transfected human islets and we developed a novel Hnf1a mutant mouse model (Hnf1a+/Δe4-10) . Sglt2 protein was significantly reduced in the kidney of Hnf1a-/- mice, with no changes in Sglt1 or Glut2 protein expression. We observed that HNF1A is heterogeneously expressed in alpha, beta, and delta cells. siHNF1A islets displayed reduced insulin secretion and content, which was rescued by GLP1 treatment. HNF1A deficiency reduced SGLT2 levels, correlating with increased glucagon content and secretion. The Hnf1a+/Δe4-mice were born normoglycemic but became glucose intolerant at 12 weeks of age, mimicking the clinical characteristics of HNF1A-MODY patients. Collectively, these findings indicate that HNF1A deficiency downregulates renal and alpha cell SGLT2 expression, which is associated with an alteration in glucagon secretion in response to glucose stimulation. The new Hnf1a+/Δe4-mouse model may be a useful tool to study the progression of MODY with and without chronic drug treatment.

Disclosure

A.Acosta-montalvo: None. V.Gmyr: None. M.Cnop: None. J.A.Kerr-conte: None. F.Pattou: None. M.Pontoglio: None. A.Liston: None. C.Bonner: None. C.Saponaro: None. J.Thevenet: None. M.Chiral: None. A.Piron: None. N.Delalleau: None. G.Pasquetti: None. A.Coddeville: None. M.Moreno: None.

Funding

EFSD/Lilly (2017) awarded to Caroline Bonner, I-SITE ULNE awarded to Caroline Bonner, the European Genomic Institute for Diabetes (ANR-10-LABX-46) , the European Consortium for Islet Transplantation funded by the Juvenile Diabetes Research Foundation. TIGER was developed within the European Union’s Horizon 2020 research and innovation program project T2DSystems, under grant agreement 667191 (to Miriam Cnop) .
152-OR: Evidence Linking Loss of Hypothalamic Perineuronal Nets to Obesity Pathogenesis
Authors: ALONGE KIMBERLY M. , DORFMAN MAURICIO D. , SCARLETT JARRAD M. , MELHORN SUSAN J. , YE YUANCHAO , HU SHANNON J.W. , FRANCIS KENDRA L. , HENDRICKSON AARUN , CUI KATHERINE , MORTON GREGORY J. , SCHUR ELLEN , THALER JOSHUA , SCHWARTZ MICHAEL W.
Published: May 2022

Defective neurocircuit activity within the hypothalamic arcuate nucleus (ARC) , a crucial brain area for the regulation of metabolism, is implicated in obesity pathogenesis. Perineuronal nets (PNNs) are extracellular matrix structures that regulate neurocircuit activity, and PNN loss can adversely influence the activity of the enmeshed neurons. To determine if defective ARC PNNs might contribute to obesity, we first quantified PNN abundance in obese mice induced by consuming a high-fat high-sucrose diet (HFHS; Bio-Serv #F4997) 12 wk. We found that compared to chow-fed controls, HFHS diet feeding caused an 84.3% decrease (p<0.0001) in the abundance of PNNs enmeshing ARC neurons. This loss was also associated with increases of ARC microgliosis (1.5-fold; p=0.004) and astrogliosis (2.9-fold; p=0.006) , suggesting a link between ARC PNN loss and glial activation. To translate these findings to humans, we analyzed postmortem hypothalamic samples from 9 subjects (Sex, 7M/2F; Age, 22-71y) that had previously undergone quantitative T2 magnetic resonance imaging (MRI) to assess obesity-associated hypothalamic gliosis. Consistent with our findings in mice, ARC PNN content was strongly and inversely correlated with the hypothalamic gliosis score measured by T2-weighted MRI imaging (R2=0.63, p=0.01) . To assess whether this depletion of ARC PNNs might contribute to obesity, we microinjected either the PNN-digesting enzyme, ChABC, or heat-inactivated ChABC control, into the rat ARC at the onset of a 4 wk HFHS dietary intervention. We found that compared to controls, the magnitude of diet-induced hyperphagia (17%; p<0.0001) , weight gain (41%; p<0.0001) , and excess body fat accumulation (28%; p=0.01) increased following PNN digestion, driven largely by increased dark cycle food intake (24%; p=0.006) . These findings collectively identify ARC PNNs as novel participants in the central control of energy homeostasis, and implicate their loss as a potential contributor to obesity pathogenesis.

Disclosure

K.M.Alonge: None. G.J.Morton: Research Support; Novo Nordisk A/S. E.Schur: None. J.Thaler: None. M.W.Schwartz: None. M.D.Dorfman: None. J.M.Scarlett: None. S.J.Melhorn: None. Y.Ye: None. S.J.W.Hu: None. K.L.Francis: None. A.Hendrickson: None. K.Cui: None.

Funding

AG066509DK017047AG074152DK101997DK720269
154-OR: The Site Specific Role of GDF15 in Metformin Action
Authors: ZHANG SONG-YANG , LI ROSA J.W. , DANAEI ZAHRA , LIM YUMI , LAM TONY K.
Published: May 2022

Metformin lowers glucose levels, appetite and body weight in rodents and humans, but the mechanisms on energy balance regulation have been rarely studied. Metformin increases plasma growth/differentiation factor 15 (GDF15) levels in humans and rodents, while elevating GDF15 via GDF15 infusion in rodents lowers food intake and body weight via its receptor GDNF family receptor α-like (GFRAL) , which is expressed in the hindbrain nucleus area postrema (AP) . However, whether the GDF15-GFRAL axis in the AP mediates metformin effect is unknown. In this study, metformin (200 mg/kg) was infused into the upper small intestine (USI) of rats, while fasting-refeeding study or intravenous glucose tolerance test was performed. USI metformin infusion elevated plasma GDF15 levels (met 138 ± 25 vs. veh 59 ± 7 pg/ml, n = 8, p < 0.01) in parallel to a lowering of food intake (met 30 ± 2 vs. veh 40 ± 2 kcal, n = 16, p < 0.01) and an increase in glucose tolerance (AUC met 5243 ± 75 vs. veh 5674 ± 153, n = 7, p < 0.05) . Further, metformin lowered not only food intake but also body weight gain by 12 h (met 14 ± 1 vs. veh 23 ± 3 g, n = 8, p < 0.01) . Importantly, a knockdown of GFRAL achieved via an injection of lentivirus expressing shRNA GFRAL vs. mismatch into the AP by ∼40% (p < 0.05) negated the ability of metformin to not only lower food intake and body weight, but also increase glucose tolerance independent of body weight. Finally, acute AP GDF15 infusion (2 pmol) decreased food intake (GDF15-25 ± 2 vs. veh-36 ± 3 kcal, n = 10, p < 0.01) and weight gain (as early at 6 h, GDF15 3.6 ± 1.2 vs. vehicle 8.7 ± 1.6 g, n = 10, p < 0.05) , and increased glucose tolerance independently from body weight (AUC, GDF15-5322 ± 94 vs. veh-5722 ± 169, n = 6, p < 0.05) , and these metabolic effects of AP GDF15 infusion were prevented by GFRAL knockdown in the AP.

In summary, our findings indicate that the AP GDF15-GFRAL axis is sufficient and necessary for metformin to regulate energy and glucose homeostasis in rodents.

Disclosure

S.Zhang: None. R.Li: None. Z.Danaei: None. Y.Lim: None. T.K.Lam: None.

Funding

Canadian Institutes of Health Research (FDN-143204)
174-LB: Diabetes as a Risk Factor for Long-COVID-19—A Scoping Review
Authors: HARDING JESSICA L. , ALI MOHAMMED K. , GANDER JENNIFER C. , PATZER RACHEL E.
Published: May 2022

Background: Diabetes is a key risk factor for severe COVID-19 (i.e., hospitalization, mortality) . Whether diabetes is also a risk factor for post-acute sequelae of COVID-19 (PASC) , also known as long COVID, is unknown.

Methods: We conducted a scoping literature review on January 27, 2022 using the keyword terms ‘long hauler’, ‘long COVID-19’, ‘post-acute sequalae’, and ‘persistent COVID-19’ combined with the operator OR, with AND ‘diabetes’, AND ‘COVID-19 [MeSH Term]’. We included all peer-reviewed full-text observational research studies published in English between January 1, 2020 and January 27, 2022 that reported on the risk of PASC in people with and without diabetes with a minimum of 4-weeks follow-up after COVID-19 diagnosis, and narratively synthesized results.

Results: Among 39 studies identified, seven were included in the review and are summarized in Table 1. Overall, we found that 43% of studies identified diabetes as a potent risk factor for PASC (all odds ratios were >4) . However, this conclusion is limited by the heterogeneity of studies with regard to PASC definitions (e.g., ongoing symptoms of fatigue, cough, dyspnea etc.) , populations at risk (hospitalized vs. non-hospitalized populations) , and follow-up times (range 4 weeks to 7 months) .

Conclusions: More high-quality studies across multiple populations and settings are needed to determine if diabetes is indeed a risk factor for PASC. In the meantime, careful monitoring of people with diabetes for development of PASC may be advised.

Disclosure

J. L. Harding: None. M. K. Ali: Advisory Panel; Bayer AG, Research Support; Merck & Co., Inc. J. C. Gander: None. R. E. Patzer: None.
178-LB: Prevalence of Vitamin D Deficiency among Patients with Type 2 Diabetes in Qingdao, China
Authors: ZHANG LEI , WANG JUN , YANG YUXIU , DONG YANHU
Published: May 2022

The aim of the current study is to investigate the prevalence of vitamin D deficiency among patients with type 2 diabetes (T2DM) in a Chinese cohort. We enrolled 3025 patients with T2DM (aged 30-91 yrs) who were hospitalized in Qingdao Endocrine and Diabetes Hospital from Jan 2018 to Jan 2019. The exclusion criteria were as follows: (1) with other types of diabetes; (2) pregnant or lactating females; (3) with acute complications of diabetes or other stress states, such as surgery and trauma; (4) with rheumatologic, serious hepatic, cardiac, renal failure, malignancy, and endocrine diseases that affect the metabolism of vitamin D. Serum level of 25-OH-vitamin D ≥ 30 ng/mL was defined as normal, 20 ng/mL ≤ 25-OH-vitamin D < 30 ng/mL as vitamin D insufficiency (VDI) , and serum 25-OH-vitamin D < 20 ng/mL as vitamin D deficiency (VDD) . The chi-square test was used for group comparison of VDD or VDI prevalence. In all subjects, the prevalence of VDI was 35%. Male patients had higher prevalence of VDI than female patients (40.0% vs. 28.9%, P<0.05) . The prevalence of VDD was 48.8% in total while female had higher prevalence than male patients (57.2% vs. 41.8%, P<0.001) . We found a clear trend toward decreasing serum vitamin D concentration with rising HbA1c levels (P<0.001 in male and P<0.003 in female) . Dividing the HbA1c into deciles showed a linear association.

In conclusion, VDI and VDD is prevalent in patients with type 2 diabetes. Poor glucose control is related to lower serum level of vitamin D. Future studies are required to verify if vitamin D supplementation could be beneficial in patients with diabetes.

Disclosure

L. Zhang: n/a. J. Wang: None. Y. Yang: None. Y. Dong: None.
189-OR: Immune-Profiling of Pancreatic Tissue Affected by Immune Checkpoint Inhibitor–Induced Diabetes (CPI-D)
Authors: QUANDT ZOE , YOUNG ARABELLA , BARLOW GRAHAM , DONG SHEN , SMITH JENNIFER , KUSMARTSEVA IRINA , BRUSKO TODD M. , COOPER STEWART , ANDERSON MARK S.
Published: May 2022

Intro: CPI-D is a rare but morbid side effect of cancer immunotherapy. Limited availability of affected pancreatic tissue is a critical barrier to understanding its molecular and cellular underpinnings.

Methods: We procured pancreatic tissue and blood from a 68-year-old man who had developed CPI-D during immunotherapy for metastatic melanoma and was then diagnosed with pancreatic cancer, leading to partial pancreatectomy. Tumor-uninvolved pancreatic tissue was examined using H&E, IHC (including an advanced form of IHC, CODEX) , and single cell RNA sequencing (scRNAseq) .

Results: The pancreatic tissue harbored few islets, which were identified by the presence of glucagon given lack of insulin production. The islets were surrounded by immune cells that were composed primarily of B cells, CD4+ T and CD8+ T cells, some of which expressed PD-1, as demonstrated by scRNAseq and CODEX, which also identified FOXP3+ regulatory T cells that highly expressed OX40. Discussion: We report the first analysis of CPI-D-affected pancreatic tissue at single cell resolution, combining scRNAseq and spatial imaging to provide evidence for an autoimmune etiology for CPI-D. The pancreatic immune composition shared similarities with tertiary lymphoid organs (TLOs) , as previously observed in the pancreas of T1D patients. The presence of PD-1 was further notable, given the specific association of CPI-D with PD-1 inhibitor therapy. Despite the presence of B cells, this patient was negative for typical T1D autoantibodies (GAD65, insulin, IC512, zinc transporter 8) , which occur in approximately half of CPI-D cases.

Conclusion: Profiling the pancreatic histology and immune composition in a patient with CPI-D offered a rare opportunity to explore pathogenesis. This portion of CPI-D affected pancreas was significantly depleted of insulin expressing islets and displayed an immune cell infiltrate reminiscent of T1D in composition and topology, supporting that CPI-D is an autoimmune state.

Disclosure

Z.Quandt: Advisory Panel; Novartis AG, Consultant; Novartis AG. A.Young: None. G.Barlow: None. S.Dong: None. J.Smith: None. I.Kusmartseva: None. T.M.Brusko: None. S.Cooper: None. M.S.Anderson: Advisory Panel; Imcyse, Consultant; Provention Bio, Inc., Sana Biotechnology Inc., Stock/Shareholder; Medtronic, Merck & Co., Inc.

Funding

American Diabetes Association (1-19-PDF-131) ; Parker Institute for Cancer Immunotherapy
2-LB: Semaglutide 2.4 mg Reduces the 10-Year T2D Risk in People with Overweight/Obesity
Authors: TIMOTHY GARVEY W. , HOLST-HANSEN THOMAS , LAURSEN PETER N. , RINNOV ANDERS R. , WILKINSON LUA J.
Published: May 2022

The effect of once-weekly s.c. semaglutide 2.4 mg (sema) on the risk of developing T2D in people with obesity is unknown. Weight management with sema vs. PBO plus diet/exercise was assessed in participants (pts) with overweight/obesity in STEP 1 (68 wks) and STEP 4 (20-wk run-in on sema, 48-wk randomized withdrawal) . The 10-yr T2D risk was calculated post hoc using Cardiometabolic Disease Staging (CMDS) , a validated Bayesian logistic regression of T2D risk factors. Risk scores decreased after 68 wks from 18% to 7% with sema, and 18% to 16% with PBO (61% vs. 13% reduction [p<0.01]; STEP 1; Figure) . Most of the risk score reduction with sema occurred during wks 0-20, from 21% to 11%; risk score decreased further to 8% with continued sema during wks 20-68, but increased to 15% with switch to PBO (32% reduction vs. 41% increase [p<0.01]; STEP 4; Figure) . Wk 0 risk scores were higher in pts with prediabetes vs. normoglycemia (Figure) , but treatment effects were comparable at wk 68 (p=0.45 for interaction [STEP 1]) . Risk score changes mirrored weight loss, which was 17% with sema vs. 3% with PBO in STEP 1, and in STEP 4 was ‍11% for wks 0-20 with sema, and a further 9% with continued sema vs. a 6% regain with switch to PBO for wks 20-68.

In summary, treatment with sema reduces the 10-yr risk of T2D by ∼60% regardless of initial glycemic status, with sustained treatment required to maintain this benefit. These data suggest sema could help prevent T2D in people with obesity.

Disclosure

W. Garvey: Other Relationship; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Epitomee, JAZZ Pharmaceuticals, Novo Nordisk, Novo Nordisk, Pfizer Inc., Pfizer Inc. T. Holst-hansen: Employee; Novo Nordisk A/S, Stock/Shareholder; Novo Nordisk A/S. P. N. Laursen: Employee; Novo Nordisk A/S. A. R. Rinnov: Employee; Novo Nordisk. L. J. Wilkinson: Employee; Novo Nordisk.

Funding

Novo Nordisk A/S
215-OR: Once Weekly (QW) Basal Insulin Fc (BIF) Demonstrated Similar Glycemic Control to Once Daily (QD) Insulin Degludec (DEG) in Insulin-Naïve Patients with Type 2 Diabetes (T2D)
Authors: BUE-VALLESKEY JULIANA M. , KAZDA CHRISTOF M. , MA CHENCHEN , CHIEN JENNY , ZHANG QIANYI , CHIGUTSA EMMANUEL , LANDSCHULZ WILLIAM , SWAN JENNIFER , HAUPT AXEL , FRIAS JUAN PABLO
Published: May 2022

Basal Insulin Fc (BIF; LY3209590) , a fusion protein combining a novel single-chain insulin variant with a human IgG Fc domain, is designed for QW administration. This randomized, parallel, open-label Ph2 study assessed safety and efficacy of BIF vs. DEG in insulin-naïve patients with T2D previously treated with oral antihyperglycemic medication. BIF was injected QW, and DEG was injected QD. Both groups were titrated to fasting blood glucose (FBG) ≤100 mg/dL. The primary endpoint was HbA1c change from baseline (CFBL) to Wk 26 (non-inferiority margin=0.4%) . Patients randomized to BIF (N=129) and DEG (N=135) had a mean age of 58.4 yrs and baseline HbA1c of 8.0%. After 26 wks, BIF showed non-inferiority vs. DEG for HbA1c CFBL with a treatment difference of 0.06% (90% CI = -0.11, 0.24; p = .56) , and both groups had >75% time in range (70-180 mg/dL) on average at Wk 26 (Figure) . BIF and DEG significantly reduced FBG from baseline (treatment difference BIF vs. DEG = 4.7 mg/dL [90% CI = 0.1, 9.3]; p = .09) . Rate of Level 2 hypoglycemia was low and not significantly different (BIF = 0.22; DEG = 0.15 events/pt/yr; p = 0.64) . Occurrence of treatment-emergent adverse events was similar between BIF and DEG. QW BIF achieved excellent glycemic control similar to DEG with no concerning hypoglycemia or other safety findings, supporting continued development of BIF in Ph3.

Disclosure

J.M. Bue-Valleskey: None. C.M. Kazda: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. C. Ma: None. J. Chien: Employee; Eli Lilly and Company. Q. Zhang: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. E. Chigutsa: Employee; Eli Lilly and Company. W. Landschulz: Employee; Eli Lilly and Company. J. Swan: Employee; Eli Lilly and Company. A. Haupt: Employee; Lilly. Stock/Shareholder; Lilly. J. Frias: Advisory Panel; Altimmune, Becton, Dickinson and Company, Eli Lilly and Company, Gilead Sciences, Inc., Intercept Pharmaceuticals, Inc., Merck & Co., Inc., Sanofi. Consultant; 89bio, Inc., Akero Therapeutics, Inc., Altimmune, Becton, Dickinson and Company, Carmot Therapeutics, Inc., Eli Lilly and Company, Novo Nordisk, Pfizer Inc., Sanofi. Research Support; Afimmune Limited, Akero Therapeutics, Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, Carmot Therapeutics, Inc., Eli Lilly and Company, Intercept Pharmaceuticals, Inc., Ionis Pharmaceuticals, Janssen Pharmaceuticals, Inc., Madrigal Pharmaceuticals, Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk, Pfizer Inc., Poxel SA, Sanofi. Speaker's Bureau; Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk, Sanofi.

Funding

Funded by Eli Lilly and Company.
243-LB: Glucometabolism Benefited Differently from Bariatric Surgery within Four Artificial Intelligence–Assisted Metabolic (AIM) Subtypes of Obesity
Authors: LIU YAO , SHENG CHUNJUN , LIN ZIWEI , QU SHEN
Published: May 2022

Objectives: The purpose of this study was to look into the benefit of a bariatric surgery in four artificial intelligence-assisted metabolic (AIM) subtypes of obesity with respect to the improvement of glucometabolism, as well as the remission of diabetes and hyperinsulinemia.

Methods: This multicenter retrospective study prospectively collected data from 5 hospitals in China from 2010 to 2021. A total of 1008 patients who underwent a bariatric surgery were enrolled (median age 31 years; median BMI 38.1kg/m2; 57.40% women) and grouped into four AIM subtypes of obesity. Data at baseline, 3- and 12-months post-surgery were collected for the longitudinal effect analysis.

Results: At baseline, the hypermetabolic obesity-hyperinsulinemia (HMO-I) group was characterized by severe insulin resistance and high incidence of hyperinsulinemia (87.8%) . After surgery, HMO-I with hyperinsulinemia had achieved remission, yet the prevalence of hypoglycemia was still high (42.9%) . Hypometabolic obesity (LMO) group showed decompensated insulin secretion and high incidence of diabetes (99.2%) at baseline. After surgery, 62.1% of LMO patients with diabetes achieved remission, lower than the other three groups. Still, the bariatric surgery significantly reduced their blood glucose (median HbA1c decreased by 27.2%) . For both metabolic healthy obesity (MHO) and hypermetabolic obesity-hyperuricemia (HMO-U) groups, who showed a relatively healthy glucometabolism at baseline, prevalence of glucometabolic comorbidities improved moderately after surgery.

Conclusion: This multicenter study found that the four AIM subtypes of obesity benefited differently from a bariatric surgery in terms of glucometabolism. Bariatric surgery significantly relieves hyperinsulinemia and hyperglycemia for HMO-I and LMO, respectively. As a result, patients of the two subtypes should be motivated for a bariatric surgery for the improvement of glucometabolism.

Disclosure

Y. Liu: None. C. Sheng: None. Z. Lin: None. S. Qu: n/a.

Funding

Clinical Research Plan of SHDC (No.SHDC2020CR1017B) , National Natural Science Foundation of China (82170861,81970677) , Shanghai Medicine and Health Development Foundation (DMRFP_I_07) , Shanghai Commission of Science and Technology (19DZ1910200)
243-OR: Effect of Menstrual Cycle on Glycemic Responses to Exercise in Female Participants with Type 1 Diabetes
Authors: MOMENI ZEINAB , YARDLEY JANE E.
Published: May 2022

Fear of hypoglycemia is a major barrier to exercise in people with type 1 diabetes (T1D) . Females with T1D tend to be less active than males with T1D, which might be due to significant knowledge gaps around blood glucose responses to exercise, especially with regards to the menstrual cycle. We compared the effect of a moderate aerobic exercise (cycling at 50% of pre-determined VO2peak for 45 min) on glycemic responses between the early follicular and late luteal phases of the menstrual cycle in 9 female participants with T1D (mean±SD: age 30.2±9 years, A1C 7.4±0.7%, VO2peak 32.5±4.2 mL/kg/min) with regular menstrual cycles not using oral contraceptives. In both phases, serum glucose decreased from pre to post exercise and increased throughout the 60-min recovery (effect of time p<0.05) but was not significantly different between the two phases (effect of phase p>0.05) . Serum insulin (log transformed) decreased from pre to post exercise in both phases (effect of time p<0.05) but was not significantly different between the two phases (effect of phase p>0.05) . The number of participants needing glucose supplementation (Dex4) to prevent hypoglycemia before and during exercise and recovery was significantly higher in the luteal versus the follicular phase (6/9 vs. 1/9, Fisher’s p=0.049) . Continuous glucose monitoring, however, showed no increase in the number of hypoglycemic episodes post exercise during the luteal phase. There were more post-exercise hyperglycemic episodes in the follicular versus the luteal phase (3±0.5 vs. 1.3±0.3, p=0.029) . These data suggest that females with T1D may be more prone to post-exercise hyperglycemia during the follicular phase, while needing more glucose supplementation to prevent hypoglycemia during the luteal phase of the menstrual cycle. These data should help guide recommendations for carbohydrate and insulin adjustment.

Disclosure

Z.Momeni: None. J.E.Yardley: Research Support; Abbott, Dexcom, Inc., LifeScan, Speaker's Bureau; Abbott Diabetes.