bluuebunny/crossref_metadata_2025_split huggingface dataset:
246-LB: Smad3 Deficiency Promotes Beta-Cell Proliferation by Augmenting Glucose-Stimulated UPR
Authors: WANG HONGLIAN , HE HUIJUN , HUANG XR , WANG LI , MA RONALD C. , LAN HY 
Published: June 2020

Understanding the mechanism governing β cell proliferation is essential for the in vitro expansion of β cells and the replacement therapy for patients with diabetes. We recently found that deletion of Smad3, a downstream effector of TGF-β signaling, promoted β cell proliferation, while the underlying mechanisms remain elusive. It’s reported that high glucose stimulates β cell proliferation through unfold protein response (UPR). In this study, we tested the hypothesis that whether deficiency of Smad3 promotes β cell proliferation by regulating UPR. As a result, we found that knockout of Smad3 promoted β cell proliferation in diabetic db/db mice, but not in healthy db/m mice. Interestingly, islets from db/db mice of Smad3 knockout presented increased UPR compared with db/m mice of Smad3 knockout. In cultured islet cells, deletion of Smad3 increased β cell proliferation under high glucose (20mM) conditions, which was associated with up-regulated and non-decompensated UPR. Further studies showed that inhibition of UPR with an inhibitor 4-PBA abolished the pro-proliferative effect of Smad3 deficiency in β cells.
In conclusion, Smad3 deficiency increases β cell proliferation by augmenting UPR. Therefore, targeting Smad3 may be an effective therapy for diabetes.

Disclosure
H. Wang: None. H. He: None. X. Huang: None. L. Wang: None. R.C. Ma: Advisory Panel; Self; AstraZeneca. Stock/Shareholder; Self; GemVCare. Other Relationship; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Merck & Co., Inc., Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis, Tricida Inc. H. Lan: None.

Funding
Research Grants Council of Hong Kong (C7018-16G, R4012-18); Health and Medical Research Fund of Hong Kong (14152321, 05161326, 06173986)
257-OR: Profiling Transcriptional Maturation of Human Pluripotent Stem Cell–Derived Islets after Transplantation
Authors: AUGSORNWORAWAT PUNN , MAXWELL KRISTINA G. , MILLMAN JEFFREY R. 
Published: June 2020

Differentiation of human pluripotent stem cells to islet organoids (SC-islets) containing functional β cells is a promising source of replacement cells for diabetes cellular therapy. While there has been significant successes in recent years generating these cells in vitro, stem cell-derived β (SC-β) cells are still functionally and transcriptionally immature when compared to donor primary β cells. Here, we identify and characterize the transcriptional changes that occur after transplantation of SC-islets derived from human embryonic stem (hESC) and induced pluripotent stem cell (hiPSC) lines. This was accomplished by developing methodologies to generate SC-β cells capable of undergoing dynamic glucose-stimulated insulin secretion in vitro along with the successful retrieval of high purity and viable transplanted cells. Using single-cell RNA sequencing of SC-islets before and after transplantation into diabetic mice, we identified 5,867 genes that were differentially expressed in SC-β cells. Genes and gene sets associated with β cell maturation were much more highly expressed after SC-β cell transplantation, including INS, MAFA, G6PC2, and UCN3 now matching primary β cells. SC-β cells had substantially reduced expression of the non-β cell hormone genes GCG and SST along with other off-target or immaturity genes, including ALDH1A1 and CRYBA2. Overall, the transcriptome of transplanted SC-β cells matured to closely resemble that of primary β cells from 3 donors. Single-cell analysis revealed that not only SC-β cells but also SC-α cells underwent drastic transcriptional changes to more closely resemble primary α cells. Similar results were observed with hESC- and hiPSC-derived islet organoids. This study provides an extensive indexing of transcriptional maturation of SC-islets through transplantation and serves as an important resource to understanding maturation of differentiated cell types to enable improved protocols for generating replacement cells.

Disclosure
P. Augsornworawat: None. K.G. Maxwell: None. J.R. Millman: Employee; Spouse/Partner; Acera Surgical, Inc. Other Relationship; Self; Harvard University, Washington University.

Funding
National Institutes of Health (R01DK114233, T32DK108742); JDRF (5-CDA-2017-391-A-N); Washington University in St. Louis
259-OR: Epigenetic Coregulation of Beta-Cell Function and Survival in Postnatal Life
Authors: DHAWAN SANGEETA , GURLO TATYANA , WANG JEAN K. 
Published: June 2020

Both type 1 and type 2 diabetes are caused by inadequate functional beta-cells. Loss of beta-cells in diabetes is preceded by progressive beta-cell failure due to impaired beta-cell function and adaptive capacity, driven by cellular stress. While plenty of evidence suggests that beta-cell function and mass are co-regulated to dictate adaptive capacity, the molecular mechanisms that direct such co-regulation and are disrupted by cellular stress remain unclear. In the present study, we show that the CCCTC binding factor, CTCF is a novel epigenetic regulator of beta-cell functional maturity and mass. CTCF is a zinc finger protein that regulates 3D chromatin architecture and epigenetic stability towards transcriptional regulation, and plays an important role in cell differentiation, self-renewal, and survival. In addition, the levels of CTCF are sensitive to cellular-stress. Our data show that the beta-cell specific CTCF knockout mice (CTCF-BKO) become diabetic by 4-5 months of age, due to a progressive loss of beta-cell maturity and viability that mirrors evolving T2D. The CTCF-BKO mice have impaired glucose stimulated insulin secretion (GSIS), with metabolic, epigenetic, and gene expression profiles that resemble functionally immature neonatal beta-cells, around 1-2 months of age. This is followed by progressive loss of beta-cell mass due to p53 dependent apoptosis. In addition, mice with haplo-insufficiency of CTCF in their beta-cells display impaired GSIS and a deficit in the adaptive beta-cell expansion in response to high-fat diet challenge. Finally, we show that the CTCF program is disrupted in islets of diabetic mice. Taken together, these studies provide a novel insight into the epigenetic regulation of functional beta-cell mass and adaptive capacity in postnatal life.

Disclosure
S. Dhawan: None. T. Gurlo: None. J.K. Wang: None.
264-OR: Characterizing the Distinct Glycemic Patterns Of Postbariatric Hypoglycemia (PBH)
Authors: LEE DANIEL , DREYFUSS JONATHAN , MULLA CHRISTOPHER M. ,   MARY-ELIZABETH PATTI
Published: June 2020

While bariatric surgery can promote remission of type 2 diabetes (T2D), it can also result in severe hypoglycemia, termed post-bariatric hypoglycemia (PBH). Hypoglycemia is most often recognized after meals, but also can occur after activity or during mid-nocturnal hours and can yield unawareness and disabling neuroglycopenia.
We used blinded CGM (Dexcom G4) to characterize glycemia, glycemic variability (GV), and severity and length of hypoglycemia in patients with PBH with prior roux-en-Y gastric bypass (PBH, n=40). We compared results to those of individuals with reactive hypoglycemia with no prior GI surgery (Hypo, no-GS, n=20) and to publicly available Dexcom G4 data from 3 additional groups: healthy controls (HC, n=38), prediabetes (Pre-DM, n=14), and T2D (n=5). Metrics were assessed over 24 hours as well as during daytime (6 AM to midnight) and nighttime (midnight to 6 AM) independently.
Mean and median sensor glucose (SG) were similar for PBH and HC (mean: 99.8±18.6 vs. 96.9±10.2 mg/dL; median: 93.0±14.8 vs. 94.5±7.4 mg/dL, p&gt;0.05 for both). By contrast, PBH had higher coefficient of variation (27.3±6.8 vs. 17.9±2.4%, p&lt;0.0001) and a wider range and IQR of SG values (range: 154.5±50.4 vs. 112.0±26.7 mg/dL; IQR: 28.0±7.4 vs. 20.0±4.4, p&lt;0.0001 for both). Nadir SG was lowest in PBH (42.5± 3.7 mg/dL vs. other groups, p&lt;0.0001) with statistical significance vs. HC (49.0±11.9 mg/dL, p=0.0046). PBH had greater percentage of time with SG&lt;70 mg/dL vs. HC (7.7±8.4 vs. 3.2±4.1%, p&lt;0.002); these differences were greater at night (12.6±16.9 vs. 1.0±1.5%, p&lt;0.0001). Also, the frequency of severe hypoglycemic episodes (&lt;54 mg/dL, duration ≥ 15 minutes) per day was higher for PBH group vs. HC (0.5 vs. 0.1, p&lt;0.002).
In summary, patients with PBH experience higher GV and greater severity and frequency of hypoglycemia compared to HC, especially at night. Future studies should explore the potential of CGM technology in assisting PBH patients to recognize early hypoglycemia and prevent severe hypoglycemia.

Disclosure
D. Lee: None. J. Dreyfuss: None. C.M. Mulla: None. M. Patti: Consultant; Self; Fractyl Laboratories, Inc. Research Support; Self; Dexcom, Inc., Xeris Pharmaceuticals, Inc. Other Relationship; Self; Academy of Nutrition and Dietetics, American Diabetes Association, American Society of Metabolic and Bariatric Surgery, Endocrine Society, Insulet Corporation, King Abdullah International Medical Research Center, SUNY Downstate.

Funding
National Institutes of Health (R01DK121995); National Institute of Diabetes and Digestive and Kidney Diseases (T32DK007260)
266-OR: Rebound Hyperglycemia in Real-World Data and Its Mitigation with a CGM-Based Predictive Alert
Authors: ACCIAROLI GIADA , PARKER ANDREW , WELSH JOHN , PUHR SARAH , WALKER TOMAS C. , AKTURK HALIS K. 
Published: June 2020

Symptomatic hypoglycemia is an incentive for carbohydrate intake which, in excess, can lead to rebound hyperglycemia (RH) and contribute to high glycemic variability. We examined whether an optional "urgent low soon" (ULS) alert triggered by impending hypoglycemia could mitigate RH in the real world. Sensor glucose values (SGVs) were from the G5 and G6 continuous glucose monitoring (CGM) systems (Dexcom). G5 does not offer the ULS feature; all G6 usage was with the ULS alert enabled. An RH event was defined as any series of SGVs &gt;180 mg/dL preceded within 2 hours by a low SGV (&lt;70 or &lt;55 mg/dL). Event severity was defined as the area under the curve (AUC) for consecutive SGVs &gt;180 mg/dL. Data from a convenience sample of 24,518 anonymized G5 users who transitioned to G6 and uploaded ≥30 days of data from each system in 2018 were analyzed. RH events preceded by an SGV &lt;70 mg/dL and those preceded by an SGV &lt;55 mg/dL were analyzed separately. For both types of RH events, the transition from G5 to G6 and its predictive alert was associated with favorable and statistically significant reductions in the mean (SD) frequency, severity, and duration RH events (Table). The ULS alert in the G6 CGM system, intended to reduce hypoglycemia, mitigates RH events in users who transition from a system without predictive alerts and may contribute to other metrics of improved glycemic control.

Disclosure
G. Acciaroli: Employee; Self; Dexcom, Inc. A. Parker: Employee; Self; Dexcom, Inc. Stock/Shareholder; Self; Dexcom, Inc. J. Welsh: Employee; Self; CSL Behring. S. Puhr: Employee; Self; Dexcom, Inc. T.C. Walker: Employee; Self; Dexcom, Inc. H.K. Akturk: Advisory Panel; Self; Sanofi US. Research Support; Self; Eli Lilly and Company, REMD Biotherapeutics, Senseonics.
270-OR: Nocturnal Hypoglycemia with Insulin Degludec and Glargine U100 in Patients with Type 1 Diabetes Prone to Severe Nocturnal Hypoglycemia (HypoDeg): A CGM Substudy
Authors: BRØSEN JULIE M. , AGESEN RIKKE M. , ALIBEGOVIC AMRA CIRIC , ANDERSEN HENRIK U. , GUSTENHOFF PETER , HANSEN TROELS K. , JENSEN TONNY , JUHL CLAUS B. , LERCHE SUSANNE , NØRGAARD KIRSTEN , PARVING HANS-HENRIK D. , TARNOW LISE , THORSTEINSSON BIRGER , PEDERSEN-BJERGAARD ULRIK 
Published: June 2020

Background and Aims: Nocturnal hypoglycemia is a major source of concern of people with type 1 diabetes (T1D) and may result in suboptimal glycemic control due to avoidance behavior. Optimal basal insulin therapy may reduce nocturnal hypoglycemia. Insulin degludec is associated with lower risk of nocturnal hypoglycemia in T1D. However, it has not been studied in people specifically prone to severe nocturnal hypoglycemia. We report frequencies of CGM-recorded nocturnal non-severe hypoglycemia (NSH) from the HypoDeg trial, which compared insulin degludec with insulin glargine in people with T1D and previous severe nocturnal hypoglycemia.
Materials and Methods: Seventy-four people completed 4 x 6 days of blinded CGM (Medtronic iPro) during a 2-year randomized cross-over study. CGM traces were reviewed for clinically important hypoglycemic events ≤ 3.0 mmol/L according to current international consensus.
Results: When defining night-time from 23-06:59 a total of 193 episodes of nocturnal NSH were found at the glucose threshold ≤ 3.0 mmol/L. A 53% (95% confidence interval [CI] 35%-64%; p&lt;0.001) relative risk reduction (RRR) in nocturnal NSH during treatment with insulin degludec (0.6 episodes/person-week) was observed as compared to insulin glargine (1.3 episodes/person-week). The reduction in nocturnal NSH was mainly due to a 52% (95%[CI]:32-70%; p&lt;0.001) RRR in nocturnal asymptomatic hypoglycemia with insulin degludec (0.4 episodes/person-week) as compared to insulin glargine (0.9 episodes/person-week). Similar results were found when defining night-time from 00-05:59.
Conclusion: People with T1D prone to nocturnal severe hypoglycemia have lower rates of CGM-recorded nocturnal hypoglycemia with insulin degludec as compared to insulin glargine.

Disclosure
J.M. Brøsen: None. R.M. Agesen: Employee; Self; Novo Nordisk A/S. A. Alibegovic: Employee; Self; Novo Nordisk A/S. H.U. Andersen: Advisory Panel; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. P. Gustenhoff: Advisory Panel; Self; Abbott Laboratories, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk A/S, Sanofi-Aventis. T.K. Hansen: None. T. Jensen: Stock/Shareholder; Self; Novo Nordisk A/S. C.B. Juhl: None. S. Lerche: None. K. Nørgaard: Advisory Panel; Self; Abbott, Medtronic. Research Support; Self; Novo Nordisk A/S. Speaker’s Bureau; Self; Medtronic, Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk Inc. H.D. Parving: None. L. Tarnow: None. B. Thorsteinsson: None. U. Pedersen-Bjergaard: Advisory Panel; Self; Novo Nordisk A/S, Sanofi. Research Support; Self; Novo Nordisk A/S.
28-LB: Improved Time in Glucose Range over One Year Is Associated with Reduced Albuminuria in Sensor-Augmented Insulin Pump–Treated Type 1 Diabetes
Authors: RANJAN AJENTHEN , ROSENLUND SIGNE , HANSEN TINE W. , ROSSING PETER , ANDERSEN STEEN , NØRGAARD KIRSTEN 
Published: June 2020

Objective: To investigate the association between treatment induced change in continuous glucose monitored (CGM) time in range (TIR) and microalbuminuria in persons with type 1 diabetes (T1D) treated with sensor-augmented pumps (SAP).
Methods: In an open labelled controlled trial, 60 participants with T1D treated with multiple daily injections (MDI) and history of albuminuria were randomised to MDI- or SAP-therapy for 1 year. During the study, the SAP group wore a CGM (Enlite®, Medtronic). The MDI group wore blinded CGMs (Ipro2®, Medtronic) for 6 days at baseline and study end. Anthropometrics, CGM data, blood and urine samples were collected at 0, 1, 3, 6, 9, and 12-month visits. Based on CGM data collected between each visit, the percentage of time spent within 3.9-10.0 mmol/l (%TIR) was calculated. Urine albumin creatinine ratio (UACR) was measured in 3 samples at all visits. Only CGM data for the SAP group were included in the analysis. A linear mixed model with a participant-specific random intercept was used to analyse the effect of %TIR during 1 year after start of SAP on UACR, adjusting for changes in mean arterial pressure (MAP), HbA1c and body mass index.
Results: Twenty-six participants were assigned to the SAP group and had a baseline median (interquartile range) age of 51.5 (45.9; 62.1) years, HbA1c of 66 (58; 77) mmol/mol, UACR of 78.8 (37; 205) mg/g and 51Cr-EDTA-GFR 85.0 (73.0; 96.5) ml/min/1.73m2. From baseline to study end, the mean improvement (95% CI) in %TIR was 11.3 (6.0; 16.6) %, HbA1C was -14.4 (-17.5; -11.2) mmol/mol and UACR was -13 (-33; -22) %; all p&lt;0.001. HbA1c decreased with 4.7 mmol/mol per 10% increase in %TIR (p&lt;0.001). The UACR decreased with 13% per 10% increase in %TIR (p=0.038), with 15% per 10 mmol/mol decrease in HbA1c (p=0.071), and with 31 % per 10 mmHg decrease in MAP (p&lt;0.001).
Conclusion: In this longitudinal study, treatment induced increase in CGM-derived %TIR were significantly associated with decrease in albuminuria in T1D.

Disclosure
A. Ranjan: None. S. Rosenlund: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. T.W. Hansen: None. P. Rossing: Advisory Panel; Self; Sanofi. Consultant; Self; Astellas Pharma Inc., AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Boehringer Ingelheim International GmbH, Gilead Sciences, Inc., Novo Nordisk A/S. Research Support; Self; Novo Nordisk A/S. Speaker’s Bureau; Self; Eli Lilly and Company. Stock/Shareholder; Self; Novo Nordisk A/S. S. Andersen: None. K. Nørgaard: Advisory Panel; Self; Abbott, Medtronic. Research Support; Self; Novo Nordisk A/S. Speaker’s Bureau; Self; Medtronic, Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk Inc.

Funding
Novo Nordisk Foundation (NNF17SA0031406); Medtronic A/S
285-OR: Long-Term HbA1c Trajectories and Mortality and Major Atherosclerotic Cardiovascular Events (MACE) in Type 1 Diabetes (T1D)
Authors: MILLER RACHEL G. , COSTACOU TINA , ORCHARD TREVOR J. 
Published: June 2020

While poor glycemic control is a well-established risk factor for mortality and MACE in T1D, specific patterns of control over time have not been well-studied. Thus, we sought to identify long-term trajectories of HbA1c and examine associated participant characteristics, mortality, and MACE incidence in the Pittsburgh Epidemiology of Diabetes Complications (EDC) study, a prospective observational cohort with childhood-onset (&lt;17 years) T1D. These data were analyzed as part of a DNA methylation sub-study (currently in progress), where n=422 (baseline mean T1D duration 21 yrs, 53% male) have been followed for outcomes, including 28-year mortality and MACE. Beginning in 1988, HbA1c was measured at baseline, 2, 4, 6, 8, 15, and 22 yrs. HbA1c trajectories were identified using latent class growth modeling. Five HbA1c trajectories were identified (Figure). There were no significant differences in age, T1D duration, age at T1D onset, sex, education, or insulin dose between groups. Both mortality and MACE were significantly increased in IMPROVED (p&lt;0.02) and even more so in HIGH (p&lt;.0001) compared to LOW. MODERATE and WORSENED did not have increased risk of either outcome compared to LOW. These results demonstrate that, despite improvement, past high HbA1c remains associated with increased long-term mortality and MACE risk in this T1D cohort.

Disclosure
R.G. Miller: None. T. Costacou: None. T.J. Orchard: None.

Funding
American Diabetes Association (1-19-JDF-109 to R.G.M.)
29-OR: Comparison of Empagliflozin and Sitagliptin on Ectopic Fat Accumulation and Tissue-Specific Insulin Sensitivity
Authors: HIRUMA SHIGENORI , SHIGIYAMA FUMIKA , HISATAKE SHINJI , MIZUMURA SUNAO , SHIRAGA NOBUYUKI , HORI MASAAKI , IKEDA TAKANORI , HIROSE TAKAHISA , KUMASHIRO NAOKI 
Published: June 2020

Background: Ectopic fat accumulation is the major pathogenesis of insulin resistance, type 2 diabetes mellitus (T2DM), and cardiovascular diseases. To date, no prospective study compared the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) and dipeptidyl peptidase-4 inhibitors on ectopic fat accumulation and tissue-specific insulin sensitivity.
Methods: This is the prospective, randomized, open-label, and blind-endpoint study in 44 Japanese patients with T2DM. Patients (HbA1c: 7.2±0.9%, known duration: 3.9±4.0 years, BMI: 29.1±4.8 kg/m2) were randomized to empagliflozin (Empa) add-on group or sitagliptin (Sita) add-on group, and treated for 12 weeks. The primary endpoint was the change of pericardial fat content estimated by magnetic resonance imaging. The secondary endpoints were the changes in the amount of intrahepatic, intra- and extra-myocellular lipid content estimated by proton magnetic resonance spectroscopy, and tissue-specific insulin sensitivity assessed by hyperinsulinemic-euglycemic clamp tests using stable isotope.
Results: There was no difference in pericardial fat content between the groups. Interestingly, intrahepatic lipid content (IHL) was reduced significantly from baseline in Empa group compared to Sita (-23.0±26.3 vs. -3.9±19.8%, respectively, p&lt;0.05). However, the change in clamped % suppression of endogenous glucose production was comparable between the groups. On the other hand, rate of glucose disappearance was significantly increased in Empa group compared to Sita (+18.5±55.2 vs. -8.6±20.2%, p&lt;0.05), while the amount of intra- and extra-myocellular lipid content remained similar between the groups.
Conclusion: This is the first study that compared Empa and Sita on ectopic fat content and tissue-specific insulin sensitivity. Empa significantly reduced IHL and increased insulin sensitivity in muscle compared to Sita. SGLT2i might be preferable in treatment of T2DM with hepatic steatosis.

Disclosure
S. Hiruma: None. F. Shigiyama: None. S. Hisatake: None. S. Mizumura: None. N. Shiraga: None. M. Hori: None. T. Ikeda: None. T. Hirose: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo, Mitsubishi Tanabe Pharma Corporation, Ono Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited. Speaker’s Bureau; Self; AstraZeneca, Lilly Diabetes, Novo Nordisk Inc., Sanofi, Sumitomo Dainippon Pharma Co., Ltd. N. Kumashiro: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc. Speaker’s Bureau; Self; Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited.

Funding
Nippon Boehringer Ingelheim Co., Ltd. (1245-0162)
292-OR: Treg Cells Control Systemic Lipid and Iron Metabolism via the OGT-STAT5 Axis
Authors: SALGADO BARRERO OSCAR C. , RUAN HAI-BIN 
Published: June 2020

Adipose tissue-resident regulatory T (Treg) cells have been proposed to exert metabolic roles in controlling inflammation, insulin sensitivity and thermogenesis. However, it is still largely unclear how Treg cells integrate immunological and metabolic signals to maintain systemic energy balance. Here we show that the glucose-sensitive O-linked N-Acetylglucosamine (O-GlcNAc) post-translational modification in Treg cells is activated by T cell receptor signaling. Through modifying the STAT5 protein and IL-2 signaling, protein O-GlcNAcylation supports the lineage stability and effector function of Treg cells, while loss of O-GlcNAc transferase (OGT) in Treg cells leads to systemic inflammation in mice. When fed with high fat diet, heterozygous Foxp3-OGT knockout females gain more fat mass as a result of reduced energy expenditure. On the other hand, constitutively active STAT5-mediated Treg-cell expansion and activation protect mice from diet-induced obesity and glucose intolerance. Mechanistically, Treg cells inhibit fatty acid uptake and regulate iron cycling in the adipose tissue. Taken together, we propose that the OGT-STAT5 axis enables Treg cells to maintain systemic lipid and iron homeostasis.

Disclosure
O.C. Salgado Barrero: None. H. Ruan: None.

Funding
American Diabetes Association (1-18-IBS-167 to H-B.R.); National Institutes of Health (R01AI139420)