bluuebunny/crossref_metadata_2025_split huggingface dataset:
1179-P: Deletion of IER3IP1 in ß-Cells Causes Glucose Intolerance via Disruption of IRE1α-XBP1 Signaling
Authors: MEN LILI , QIAO LU , DU JIANLING , REN DECHENG 
Published: June 2024

Background: Mutations in the gene for immediate early response 3 interacting protein 1 (IER3IP1) caused permanent neonatal diabetes in human. In previous report, we showed IER3IP1 KD induced cell death and decreased proliferation in MIN6 cells. In this study, we define the role of IER3IP1 in β-cells in vivo, and identify the mechanism of diabetes induced by IER3IP1 deficiency in mice.
Methods: In order to determine the role of IER3IP1 in β-cells and molecular mechanism by which IER3IP1 deficiency cause diabetes, IER3IP1 specific β-cell knockout mice lines were generated using RIP-Cre transgenic mice (βKO).
Results: There was no significant difference in the body weight between Βko mice and WT (IER3IP1+/+Cre+) mice. βKO mice develop glucose intolerance and decreased insulin secretion response to glucose in vivo as well as in isolated islets compared to WT mice. Moreover, βKO mice showed a decrease in β-cell mass due to the increase in β-cell death. Furthermore, deletion of IER3IP1 in β-cells causes ER stress. Both mRNA and protein levels of IRE1α were increased while spliced XBP1 (sXBP1), a downstream target of IRE1α, was decreased in the two animal models.
Conclusion: IER3IP1 deficiency in β-cells induces diabetes via disruption IRE1α-XBP1 signaling pathway.

Disclosure
L. Men: None. L. Qiao: None. J. Du: None. D. Ren: None.
1209-P: The Influence of Chronic Metformin Exposure for Gestational Diabetes on Infant Mesenchymal Stem Cell Response
Authors: BIAGIONI ERICKA M. , ROWE JOHN C. , YENDAMURI SRIPALLAVI , ZHENG DONGHAI , WISSEMAN BREANNA L. , FISHER-WELLMAN KELSEY H. , DARRELL NEUFER P. , MAY LINDA , BROSKEY NICHOLAS T. 
Published: June 2024

Introduction & Objectives: Offspring exposed to metformin treatment for gestational diabetes (GDM) experience altered growth patterns, increasing the risk of cardiometabolic diseases later in life. The adaptive cellular mechanisms underlying these altered growth patterns in offspring remain unclear. Therefore, the objective of this study was to determine if chronic metformin exposure from GDM treatment elicits infant cellular metabolic adaptations.
Methods: In a cross-sectional design, 22 pregnant women with GDM treated solely with metformin (Met; n=12) were compared to those treated exclusively by diet (A1DM; n=10). GDM was diagnosed between 24-28 weeks gestation by 2-hr 75g oral glucose tolerance test. Women were matched for age, race, BMI, and infant sex. Umbilical cord derived mesenchymal stem cells (MSCs) were used to study infant metabolism in vitro. Content of mitochondrial respiratory complexes were assessed by Western blot and intracellular lipid content was measured by Oil Red O staining. Substrate oxidation and insulin action were measured with 14C radiolabeled glucose, palmitate, and oleate at baseline and following a 24-hr lipid challenge. ANOVAs and t-tests were used to examine differences between groups.
Results: No differences in gestational age at delivery (p=0.55), infant blood glucose at delivery (p=0.52), birth weight (p=0.88), ponderal index (p=0.23), or infant circumferences of abdominal (p=0.38), chest (p=0.88), or head (p=0.46) were observed between groups. MSC outcomes revealed no differences in substrate metabolism except for lower rates of oleate oxidation among Met-MSCs at baseline (p=0.03). No differences in mitochondrial content or lipid content were detected.
Conclusions: Met-MSCs had no differences in substrate oxidation (albeit oleate), lipid storage, or mitochondrial content compared to A1DM. These cellular outcomes may not explain the altered growth patterns in infants exposed to metformin in utero.

Disclosure
E.M. Biagioni: None. J.C. Rowe: None. S. Yendamuri: None. D. Zheng: None. B.L. Wisseman: None. K.H. Fisher-Wellman: None. P. Neufer: None. L. May: None. N.T. Broskey: None.

Funding
National Institutes of Health (R01DK120296)
1227-P: Observational Study on Subclinical Inflammation and Lymphocyte Distribution in Adipose Tissue during Pregnancy and Gestational Diabetes Mellitus
Authors: SHANKAR ANAND , SINHA AJAY K. , DAS AMIT K. , GUHA SHAIBAL , KUMAR SUBHASH 
Published: June 2024

Introduction: Subclinical inflammation within adipose tissues is known to influence metabolic health, particularly during pregnancy and in conditions like Gestational Diabetes Mellitus (GDM). This study aims to investigate the patterns of inflammation and lymphocyte presence in subcutaneous and visceral adipose tissues during pregnancy, with a focus on the impact of GDM.
Methods: This observational study included 100 pregnant women, 50 with GDM and 50 without (controls), matched for age and BMI. Biopsies of subcutaneous and visceral adipose tissues were taken during cesarean sections. Histological examinations were performed to identify inflammatory markers and lymphocyte counts. The comparison between groups and tissue types was analyzed using independent t-tests and multivariate regression to adjust for potential confounders.
Results: Subclinical inflammation and lymphocyte counts were significantly higher in GDM patients' adipose tissues (inflammation: 2.5±0.8 GDM vs. 1.3±0.6 controls, p&lt;0.001; lymphocytes: 25±5 vs. 15±4, p&lt;0.001). Visceral tissue showed more inflammation (2.8±0.7) than subcutaneous (2.2±0.7) in GDM (p&lt;0.01). Inflammation severity correlated with HbA1c (r=0.62, p&lt;0.001) and gestational age at diagnosis (r=0.47, p&lt;0.01).
Conclusion: Subclinical inflammation, higher lymphocyte counts in adipose tissues, and GDM have been associated in the study. Visceral adipose tissue had more inflammation, suggesting a therapeutic attention. Understanding these patterns can help reduce GDM's inflammatory effects on mothers and children. Following these findings, additional study is needed to determine mechanisms and therapies.

Disclosure
A. Shankar: None. A.K. Sinha: None. A.K. Das: None. S. Guha: None. S. Kumar: None.
1228-P: Pregnancy Outcomes in Women with HNF4A and HNF1A-MODY
Authors: CROWLEY MAIREAD , BACON SIOBHAN , KINSLEY BRENDAN T. , HATUNIC MENSUD , KENNELLY MARIA , BYRNE MARIA M. 
Published: June 2024

Introduction & Objective: HNF4A-MODY is associated with macrosomia and neonatal hypoglycemia. Glycemic control is achieved during pregnancy with insulin or sulphonylurea therapy. We aim to determine pregnancy outcomes in women with HNF4A-MODY and HNF1A-MODY.
Methods: We performed a multi-center retrospective review of pregnancy outcomes (n=39) in 14 women with HNF4A-MODY and (n=145) in 46 women with HNF1A-MODY. Offspring genotype was known in 13 HNF4A-MODY and 36 HNF1A-MODY. Outcomes included offspring birth centile, gestational age, mode of delivery and incidence of neonatal hypoglycemia (NH).
Results: Miscarriage rates were 15% for HNF4A-MODY and 23% for HNF1A-MODY respectively (p=0.24). Overall median birthweight was 3.7±0.5 vs. 3.6±0.5kg (p = 0.11) and birthweight centiles were 85±17 vs. 70±29 (p=0.22). Incidence of LGA was 50% vs 32% (p=0.41). Cesarean section rate was 17% vs 26% respectively (p=0.3). NH was significantly greater in HNF4A-MODY (36% vs 14%, p value = 0.014). HNF4A-MODY genotype positive offspring (n=12) had a median birthweight of 4.78±1.2kg (83% LGA).
Diabetes was confirmed in 137 pregnancies (HNF4A:HNF1A = 26:111). Third trimester median insulin doses were 0.33unit/kg/day vs. 0.61±0.13unit/kg/day for HNF4A vs. HNF1A (p=0.85). HbA1c was similar(trimester one: 42±11 vs. 40±6 mmol/mol, p = 0.86, trimester 3: 37±7 vs. 34±4mmol/mol, p = 0.88). HNF4A-MODY offspring of diabetic mothers were significantly heavier than offspring of nondiabetic mothers (3.82±0.6 vs. 3.3±0.5kg, p=0.048) however HNF1A-MODY offspring were not (3.64±0.43 vs. 3.32±0.5kg, p=0.2).
Conclusion: Increased birthweight and neonatal hypoglycemia was observed in HNF4A-MODY positive offspring. Glycemic control was achieved with relatively low doses of insulin.

Disclosure
M. Crowley: None. S. Bacon: None. B.T. Kinsley: None. M. Hatunic: None. M. Kennelly: None. M.M. Byrne: Speaker's Bureau; Novo Nordisk A/S. Advisory Panel; Novo Nordisk A/S. Research Support; Novo Nordisk A/S.

Funding
Irish Endocrine Society Clinical Science Award 2022
1269-P: Cumulative Effect of Early-Onset Type 2 Diabetes on Cardiac Dysfunction—The Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: YOSHIDA YILIN , FERDINAND KEITH C. , AGUILAR DAVID , FONSECA VIVIAN 
Published: June 2024

Objective: Adults with early-onset type 2 diabetes (T2D, diagnosed
&lt;age 40)="" experience="" premature="" and="" more="" severe="" cardiovascular="" complications.="" we="" investigated="" cumulative="" hyperglycemia="" insulin="" resistance="" (ir)="" over="" 25="" years="" in="" patients="" with="" early-onset="" t2d="" related="" to="" cardiac="" dysfunction="" midlife.="" Methods: We used Coronary Artery Risk Development in Young Adults study (CARDIA, Year 0 to 25) data. Early-onset T2D was self-reported or by fasting glucose (FG)≥126 or oral glucose≥200 mg/dL at/before Year 10. Left ventricular systolic function was estimated by ejection fraction and global longitudinal strain (GLS); diastolic function by early peak diastolic mitral annular velocity, e’, and mitral E/e′. We used the area under the growth curve (AUC) derived from quadratic random-effects models of≥4 repeated measures of FG and HOMA-IR to estimate the cumulative burden of T2D. We performed linear regressions to examine the associations of the total AUC of FG or HOMA-IR with echocardiographic outcomes, accounting for sex, race, education, mid-life age, smoking, alcohol drinking, hypertension, hyperlipidemia, diabetic medication, and heart rate.
Results: We included 271 CVD-free patients with early-onset T2D and 514 sociodemographic-matched individuals with euglycemia. In adjusted models, an SD higher AUC of FG was significantly associated with the worsening of diastolic function (β coefficients for e’= - 0.18 and E/e’=0.27) and marginally associated with the worsening of GLS (β=0.13). However, these associations were not significant in the euglycemia group. One SD higher AUC of HOMA-IR was associated with the worsening of e’ and GLS irrespective of T2D status (e’ β= -0.2 and -0.16, and GLS β=0.13 and 0.19 in T2D and euglycemia, respectively).
Conclusion: Cumulative hyperglycemia alters midlife diastolic function in patients with early-onset T2D. Sustained IR negatively affects both systolic and diastolic function regardless of T2D status.

Disclosure
Y. Yoshida: None. K.C. Ferdinand: Consultant; Amgen Inc., Novartis Pharmaceuticals Corporation, Lilly Diabetes, Janssen Pharmaceuticals, Inc., Medtronic, Boehringer-Ingelheim. D. Aguilar: None. V. Fonseca: Consultant; Abbott, Bayer Inc. Stock/Shareholder; BRAVO4HEALTH, LLC. Consultant; Corcept Therapeutics. Speaker's Bureau; Eli Lilly and Company. Research Support; Fractyl Health, Inc. Consultant; Sun Pharmaceutical Industries Ltd. Stock/Shareholder; Amgen Inc.

Funding
American Diabetes Association (7-23-JDFWH-10)
1276-P: Insulin Resistance Is Associated with Salt Sensitivity and Endothelial Dysfunction
Authors: SANCHEZ RAMIRO A. , SANCHEZ MARIA J. , RAMIREZ AGUSTIN J. 
Published: June 2024

Aims: To evaluate in non-obese young normotensive salt sensitive (SS) or salt resistant (SR) offspring of hypertensive parents (offSS-HT or offSR-HT, respectively) 1) the possible association with insulin resistance and endothelial disfunction
Design and Methods: 41 offSS-HT (29±2 years; 20 female), and 36 offSR-HT (26±2 years; 16 female). Both groups were considered lean with a BMI 25kg/m2 and a waist circumference &lt;98cm in males or &lt;105cm in females. At baseline, creatinine clearance (CrCl), 24h urinary albumin excretion (UAE), glycemia and insulinemia, before and after 60 and 120 min a glucose overload (75 g) were measured. HOMA = fasting glucose (mg/dl × fasting insulin (μU/ml)/22.5 and the area under the curve of the Oral Glycemia Tolerance Test (OGTT) were calculated. Post ischemic minimun vascular resistance and forearm blood flow by pletismography was also assessed at baseline to determine endothelial function
Results: In offSS-HT, UAE (53±3μg.min) and CrCl (124±6ml/min) were significantly higher than in offSR-HT. (UAE: 12±4μg.min; p, 0.01 and CrCl 107±6ml.min; p, 0.01). An impaired vasodilatory post ischemic response was observed in offSS-HT (1.8±0.3 AU) compared to offSR-HT (2.8±0.6 AU; (p&lt;0.01)At 60 min and 120-min, glycemia and insulinemia, post OGTT, were higher in offSS-HT (140.1±18; 130±15mg.dl and 31.8±11; 31.8±11 IU, respectively) than in offSR-HT (116.5±5: 6.5±3mg.dl and 18.8±7; 21.3±4IU, respectively; p&lt;0.01).In a similar way, in SS-HT, glycemia AUC (258.80±25) and HOMA-IR (3.26±1.36 were greater compared to offSR-HT(AUC: 194.39±6, p&lt;0.0001; HOMA-IR: 1.52±0.27, p &lt; 0.002).
Conclusions: Insulin resistance, endothelial disfunction and glomerular hyperfiltration was found in offSS-HT suggesting a familiar aggregation and a higher cardio-reno-metabolic risk when compared with offSR-HT.

Disclosure
R.A. Sanchez: None. M.J. Sanchez: None. A.J. Ramirez: None.
1283-P: Association between Body Shape and the Risk of Cardiovascular Disease in People with Obesity
Authors: HWAN PARK JUNG 
Published: June 2024

Background: Although obesity is a significant risk factor of metabolic disorders, some people have metabolically healthy obesity (MHO). Many studies reported inconsistent results about the development of cardiovascular disease (CVD) in individuals with MHO. This study aimed to evaluate the effect of body shape on CVD outcomes in individuals with MHO.
Methods: We analyzed the data of 8,416 participants from the Korean Genome and Epidemiology Study, a 10-year follow-up population-based cohort study. To evaluate the participants’ body shape, we calculated the Z-score of log-transformed A Body Shape Index (LBSIZ) and divided the participants into the following groups: metabolically healthy normal weight (MHNW), MHO, metabolically unhealthy normal weight (MUNW), and metabolically unhealthy obesity (MUO). Then, each group was classified into four subgroups based on the LBSIZ quartile. A multivariate logistic regression analysis was performed to evaluate the effect of LBSIZ for CVD events according to obesity phenotypes. The graphical relationships between LBSIZ and CVD events were also evaluated with restricted cubic spline plots.
Results: During the 10-year study period, 696 CVD events occurred in the participants. In the multivariate Cox regression model, MHO individuals did not have an increased risk of CVD compared with MHNW individuals. However, the further analysis with LBSIZ showed that the MHO participants with 3rd and 4th LBSIZ quartiles had a significantly higher hazards ratio for CVD events, whereas those with 1st and 2nd LBSIZ quartiles did not have an elevated risk of CVD compared to the MHNW participants with 1st quartile. In the restricted cubic spline regression, LBISZ showed a linear relationship with CVD events regardless of obesity phenotypes.
Conclusion: The MHO individuals with a high quartile of LBSIZ have a significant increased risk for CVD events.

Disclosure
J. Park: None.
1329-P: Correlates of Diabetes Mellitus in Care-Seeking Populations at Commercial Eye-Care Centres in Kampala, Uganda
Authors: KAGANDA PASCHAL N. , ANGUZU RONALD , KICONCO ARTHUR , MUTYOBA JOAN N. 
Published: June 2024

Introduction & Objective: Incident diabetes mellitus (DM) cases are increasing in urban settings in Uganda. Commercial eye centers are potential options to improve DM detection in urban populations. This study aimed to determine the factors independently associated with DM in an eyecare seeking population in commercial eye centers in Kampala, Uganda.
Methods: This cross-sectional study surveyed 501 consecutively recruited clients attending four private ophthalmology centres in Kampala, Uganda in June 2022. Our outcome was presence of DM measured using random blood sugar tests ≥7 mmol/L (yes) vs &lt;7mmol/L (no). Modified Poisson regression assessed factors independently associated with DM in this study population. Adjusted prevalence rate ratios (PRR) and 95% confidence intervals (CI) were reported.
Results: Among 501 participants, 31.7% (n=159) had DM and 7.4% (n=37) had pre-DM. After adjusting for potential confounders, participants were more likely to be diabetic; (i) 37% times higher among those who have never taken an A1C compared to those who ever had A1C tests (adjusted PRR 0.63, 95%CI 0.48-0.83), (ii) 46% times higher among those who never tested for DM compared to those who had ever tested for DM (adjusted PRR 0.54, 95%CI 0.38-0.75), and (iii) 45% times higher among participants who were aware of DM than those aware of DM (adjusted PRR 0.54, 95%CI 0.38-0.75)
Conclusion: Increasing symptom awareness and testing for DM suggests improvement in DM detection among urban eyecare seeking populations in Kampala. DM awareness and early DM treatment initiation are potential opportunities for future research and practice.

Disclosure
P.N. Kaganda: None. R. Anguzu: None. A. Kiconco: None. J.N. Mutyoba: None.
1338-P: Low Birthweight Is Associated with Elevated Risk of Chronic Kidney Disease in Type 2 Diabetes—A Follow-up Study of Persons Diagnosed with Type 2 Diabetes in the DD2 Cohort
Authors: LÜHR HANSEN ALEKSANDER , FYNBO CHRISTIANSEN CHRISTIAN , BRØNS CHARLOTTE , ENGELHARD LEONIE M. , HANSEN TORBEN , NIELSEN JENS S. , VESTERGAARD PETER , HOJLUND KURT , JESSEN NIELS , HECHT OLSEN MICHAEL , SØRENSEN HENRIK T. , ROSSING PETER , THOMSEN REIMAR W. , VAAG ALLAN A. 
Published: June 2024

Introduction & Objective:&lt;u&gt;&lt;/u&gt; Low birthweight (BW), a proxy for an adverse intrauterine environment, has been associated with risk of type 2 diabetes (T2D) and chronic kidney disease (CKD) later in life. The extent to which lower birthweight among people with T2D increases risk of CKD is unknown.
Methods: Original midwife records were reviewed for 5979 people recently diagnosed with T2D in the Danish Center for Strategic Research in T2D (DD2) cohort. Individuals were followed for the incidence of CKD, defined by 1) two eGFR values &lt;60ml/min per 1.73m2, 90 to 365 days apart, or 2) two urine albumin/creatinine ratios &gt;30mg/g, 90 to 365 days apart. Ten-year standardized risks of CKD were estimated by the parametric G-formula using the Aalen-Johansen estimator, considering death as a competing risk. Adjusted hazard ratios (aHRs) were computed using Cox regression analysis. Continuous relations between BW and incident CKD were assessed with linear and restricted cubic spline regression. All models were standardized or adjusted for sex, age, calendar year at birth, family history of diabetes, and born-at-term status.
Results: A total of 1443 incident CKD outcomes occurred in people with T2D during median follow-up of 8.5 years. Spline models showed progressively increasing aHRs of CKD with successively lower BW. The 10-year standardized risk of CKD was 39.9% in people with low BW &lt;2500 g, compared with 33.5% in people with a BW of 2500-4500 g, yielding a CKD risk difference of 6.4% (95% CI: -0.3, 13.3) and an aHR of 1.25 (95% CI: 0.99, 1.58). People with T2D and a high BW &gt;4500 g, compared with a BW of 2500-4500 g, had similar 10-year standardized CKD risks of 31.7% vs. 33.5%, respectively, corresponding to an aHR of 0.93 (95% CI: 0.59, 1.47).
Conclusion: Lower birthweight is associated with elevated risk of CKD among people with type 2 diabetes.

Disclosure
A. Lühr Hansen: None. C. Christiansen: None. C. Brøns: Stock/Shareholder; Novo Nordisk A/S. L.M. Engelhard: None. T. Hansen: None. J.S. Nielsen: None. P. Vestergaard: None. K. Hojlund: None. N. Jessen: None. M. Olsen: Other Relationship; AstraZeneca, Novo Nordisk A/S. Advisory Panel; Novo Nordisk A/S. Other Relationship; Teva Pharmaceutical Industries Ltd. H.T. Sørensen: Other Relationship; See text. P. Rossing: Other Relationship; AstraZeneca, Bayer Inc., Boehringer-Ingelheim, Gilead Sciences, Inc., Novo Nordisk, Eli Lilly and Company, Novartis AG, Abbott Diagnostics. R.W. Thomsen: None. A.A. Vaag: None.

Funding
Danish Agency for Science (09-067009 and 09-075724); Novo Nordisk Foundation ( NNF17SA0030962-2, NNF20O0063292, NNF17SA0030364)
1354-P: Diabetes-Related Acute Complications during the COVID-19 Pandemic among Medicare Fee-for-Service Beneficiaries
Authors: ZHOU XILIN , ANDES LINDA J. , ROLKA DEBORAH B. 
Published: June 2024

Introduction & Objective: During the COVID-19 pandemic, health care utilization sharply declined, raising concerns about the impact on health outcomes. This study examined changes in diabetes-related acute complications (ACs) over the initial 3 years of the pandemic. ACs require immediate medical attention and may be caused by delaying or canceling essential diabetes care.
Methods: Using Medicare fee-for-service claims, we identified persons with diabetes (≥ 67 years old) and ACs with International Classification of Diseases diagnosis codes. Age- and sex-adjusted monthly AC prevalence, per 1,000 people, were estimated in total and by setting (inpatient and outpatient). We compared data during the pandemic months (03/2020-02/2023) and the corresponding pre-pandemic months (03/2019-02/2020).
Results: Total AC prevalence decreased by 14-30% in the initial 3 months of the pandemic (03/2020-05/2020) and remained 3-15% lower than pre-pandemic levels thereafter. Outpatient AC prevalence mirrored the overall trend. Inpatient AC prevalence had a larger reduction, declining by 14-33% initially and sustaining a 4-22% reduction subsequently.
Conclusion: The findings suggest a decrease in diabetes-related AC prevalence among Medicare beneficiaries during the pandemic. Further analyses may be needed to explore the underlying reasons behind these observed changes.

Disclosure
X. Zhou: None. L.J. Andes: None. D.B. Rolka: None.
1381-P: Beta-Cell Failure Is Frequently the Cause of Diabetes in Africans
Authors: SAYED MARIAM , THYPARAMBIL ARAVINDAKSHAN PRAMODKUMAR , WORTHY CHARLITA , HUEFNER ELIZA A. , HURSTON JAMAIICA , DUBOSE CHRISTOPHER , JAGANNATHAN RAM , SUMNER ANNE E. 
Published: June 2024

Emerging data suggests that type 2 diabetes (DM) incidence is rapidly rising in Africa. Beta-cell failure rather than insulin resistance (IR) may be the precipitator. As causative data allows for optimization of therapy, screening strategies to determine when beta-cell failure is the primary cause of DM are essential. OGTT were performed in 589 African-born Blacks (Male: 64% (374/589), Age: 39±11y (mean±SD), BMI: 27.1±4.5 kg/m2). Insulin resistance (IR) was defined by the threshold at the lowest quartile of the population distribution for Matsuda Insulin Sensitivity Index (MISI) (≤2.89) and upper quartile for HOMA-IR, Lipid Accumulation Product (LAP) and TG-Glucose Index (TyG) (Table). With the MISI as the standard, the ability to predict IR by each index was assessed by AUC-ROC. Beta-cell failure was defined by the presence of DM in the absence of IR. K-statistic was used for beta-cell failure detection by each index relative to the MISI. DM was identified in 7% (40/589). In Africans with DM, beta-cell failure occurred in 45% (18/40); IR in 55% (22/40). AUC-ROC for IR prediction was highest for HOMA-IR (Table). By k-statistic criteria, the ability of HOMA-IR to detect beta-cell failure was excellent, but only fair for LAP and TyG. Overall, nearly half of Africans with DM have beta-cell failure as the primary cause, denoting the critical need for determining DM pathophysiology, and HOMA-IR may be the most clinically relevant test to detect etiology.

Disclosure
M. Sayed: None. P. Thyparambil Aravindakshan: None. C. Worthy: None. E.A. Huefner: None. J. Hurston: None. C. DuBose: None. R. Jagannathan: None. A.E. Sumner: None.