bluuebunny/crossref_metadata_2025_split huggingface dataset:
175-OR: The Mitochondrial Life Cycle Determines ß-Cell Maturity through Activation of the Integrated Stress Response
Authors: PEARSON GEMMA , LAWLOR NATHAN , ZHU JIE , WALKER EMILY M. , RECK EMMA C. , STITZEL MICHAEL L. , SOLEIMANPOUR SCOTT 
Published: June 2021

Mitochondrial function is pivotal to β-cell competence. The mitochondrial life cycle balances mitochondrial biogenesis and turnover (mitophagy) to ensure optimal metabolic function. Human type 2 diabetic (T2D) β-cells are known to develop mitochondrial structural/functional defects, suggestive of a defective mitochondrial life cycle. However, it is unclear if these defects are a cause or consequence of T2D. Here, we observed that human T2D β-cells had reduced mitophagic flux, mtDNA content, and expression of mitochondrially encoded genes. To test the importance of the mitochondrial life cycle to drive β-cell failure in T2D, we developed 2 distinct β-cell specific mouse models: βTfamKO (to deplete mtDNA) and βClec16aΚΟ (to impair mitophagy). We observed age dependent loss of glucose tolerance, glucose stimulated insulin secretion and β-cell mass in both models, which was exacerbated by obesity in βClec16aΚΟ mice. Loss of β-cell mass was largely independent of changes in proliferation or apoptosis but rather, due to an induction of β-cell immaturity. Using lineage tracing approaches, we confirmed that βClec16aKO and βTfamKO mice induce formation of both insulin-negative immature β-cells and β-to-α cell transdifferentiation. Further, high-throughput gene expression profiling, biochemical, and metabolic assays highlighted that either Clec16a or Tfam deficiency induces an aberrant retrograde signaling program, manifested by reductions in cellular ATP and activation of the integrated stress response (ISR). Importantly, inhibition of the ISR in vivo ameliorated glucose intolerance, defective insulin secretion, β-cell immaturity, and loss of β-cell mass, suggesting that aberrant retrograde signaling may directly lead to loss of β-cell identity. Taken together, our studies illustrate that a unified mitochondrial lifecycle is necessary to maintain β-cell mass and identity and may be targeted to prevent β-cell failure in T2D.

Disclosure
G. Pearson: None. N. Lawlor: None. J. Zhu: None. E. M. Walker: None. E. C. Reck: None. M. L. Stitzel: None. S. Soleimanpour: None.

Funding
American Diabetes Association (1-19-PDF-063 to G.P.)
179-OR: Defining Circadian Clock Dependency of Pancreatic Islet Transcriptional and Epigenetic Identity
Authors: BROWN MATTHEW , MATVEYENKO ALEKSEY 
Published: June 2021

The circadian regulation of pancreatic β-cell function and identity is critical for the maintenance of glucose homeostasis. The circadian clock is entrained by rhythmic environment cues (e.g., light/dark and feeding/fasting cycles) that coordinate expression of the molecular circadian machinery. Nevertheless, the relative contribution of the aforementioned components in maintaining circadian β-cell identity remains unclear. Therefore, we set out to test the hypothesis that the molecular clockwork is required for the circadian regulation of β-cell transcriptional and epigenetic identity. To address this question, we performed diurnal RNA sequencing (RNA-seq) and assay for transposase-accessible chromatin using sequencing (ATAC-seq) in pancreatic islets isolated from adult wild type (WT) and β-cell-specific Bmal1 (requisite circadian clock transcription factor) deficient (β-Bmal1-/-) mice. Time-dependent RNA-seq of β-Bmal1-/- islets revealed &gt;95% decrease in the number of rhythmic transcripts compared to WT islets. Of the remaining rhythmic genes in β-Bmal1-/- islets, they predominately encoded for GO pathways regulating protein folding (FDR&lt;.05). Correspondingly, ATAC-seq analysis found that there was &gt;50% decrease in rhythmic chromatin accessibility in β-Bmal1-/- islets compared to WT. In line with transcriptomic findings, the remaining rhythmically accessible regions in β-Bmal1-/- islets annotated to regions regulating protein folding and insulin processing (FDR&lt;.05). Interestingly, these regions were enriched for transcription factor motifs critical for insulin processing and biosynthesis including RFX and FOXA1. This study suggests that although the circadian clockwork is critical for entrainment of circadian β-cell identity, environmental stimuli (e.g., feeding) may maintain rhythmicity of insulin biosynthesis and protein folding in lieu of the circadian clock.

Disclosure
M. Brown: None. A. Matveyenko: None.

Funding
National Institutes of Health (DK098468 to A.M.), (DK123834 to M.B.)
180-OR: Single-Cell RNA Sequencing Reveals a Role for ROS Signaling in Nutrient-Induced ß-Cell Proliferation
Authors: VIVOLI ALEXIS , GHISLAIN JULIEN , CASTELL ANNE-LAURE , FILALI ALI , SLADEK ROBERT M. , POITOUT VINCENT 
Published: June 2021

In nondiabetic obese individuals, β-cell mass accretion maintains glucose homeostasis by balancing levels of circulating insulin and insulin resistance. Type 2 diabetes appears when these compensatory mechanisms fail. Deciphering the pathways controlling β-cell proliferation may help to identify therapeutic targets to expand β-cell mass and prevent or delay the onset of diabetes. Previously we demonstrated that the monounsaturated fatty-acid oleate potentiates glucose-induced rat β-cell proliferation.
Aim: To identify the transcriptional mechanisms underlying oleate-induced rat β-cell proliferation.
Methods: Rat islets were exposed to 16.7mM glucose (Glu) with or without 0.5 mM oleate (Glu+Ol) or palmitate (Glu+Pal) for 48h. Proliferation was assessed by flow cytometry (C-peptide staining and EdU incorporation). Single-cell cDNA libraries were generated using 10X Genomics technology and sequenced on the Illumina platform. Bioinformatic analyses were performed using Seurat package.
Results: β-cell proliferation was potentiated by Ol, but not Pal. Following single-cell RNA sequencing, UMAP plots revealed several β-cell sub-populations, including proliferating β-cells. A number of differences in gene expression were identified between groups in non-proliferating sub-populations. Among these, gene sets involved in ER-stress and β-cell differentiation were significantly up- and down-regulated, respectively, in response to Pal, but not Ol. Gene set enrichment analyses comparing proliferative vs. non-proliferative β-cells revealed an up-regulation of reactive oxygen species (ROS) and oxidoreductase activity-related pathways in both Glu and Glu+Ol groups. The antioxidant N-acetyl cysteine or the peroxiredoxin inhibitor Conoidin A inhibited Glu+Ol-induced β-cell proliferation.
Conclusion: Our results suggest the involvement of ROS signaling through a redox relay via peroxiredoxin activation in nutrient-induced β-cell proliferation.

Disclosure
A. Vivoli: None. J. Ghislain: None. A. Castell: None. A. Filali: None. R. M. Sladek: None. V. Poitout: None.
184-LB: Lipid and HbA1c Profiles among People with Lean and Overweight Type 2 Diabetes in the Peruvian Amazon
Authors: ROBBINS DAVID C. , DEAN BARTHOLOMEW C. , GERHOLD CHAD , MOSHER M J , CAMARGO JULIANA 
Published: June 2021

Type 2 DM in patients with BMIs &gt; 25 is well defined. Gaps exist in understanding lean diabetes (LD), those with BMI &lt; 25. In the US, LD presents in &lt; 12% of patients and most prevalent in minorities. Childhood malnutrition, low socioeconomic status, and early age of onset contribute to this disease variant in developing countries. In Peru, diabetes is estimated to be prevalent in 7% of the population and may be, contrary to some publications, more widespread in remote Amazonian communities where poverty is common and access to health care is lacking. This study identifies characteristics in LD in comparison to individuals with overweight/obese (OOD) type 2 diabetes in Peru. A subsample of individuals with diabetes from a larger pilot study were profiled [F/M = 42/24, age ≥ 18 yrs] in the Amazonian town of Yurimaguas, Peru. We collected glycated hemoglobin (HbA1c), fasting blood lipids panels, height and weight from participants. Diabetes was determined using American Diabetes Association guidelines for HbA1c. In our sample (n = 64), 31.3% of individuals (n = 20) had BMI &lt; 25. HbA1c percentages were significantly higher for LD compared to OOD (11.51%, 9.97% res, p = 0.034). We found no mean difference in age and lipid biomarkers for LD and OOD; for age (54.50 yrs, 53.89 yrs res, p = 0.841), triglycerides (223.56 mg/dL, 218.58 mg/dL res, p = 0.886), LDL (111.97 mg/dL, 114.85 mg/dL res, p = 0.731), HDL (48.12 mg/dL, 48.25 mg/dL res, p = 0.954). The proportion of LD with triglyceride levels &gt; 150mg/dL was less than expected compared to OOD (χ2 = 4.30, df = 1, p = 0.038). We found a larger than expected portion of LD. Consistent with other studies, LD had higher HbA1c levels and less incidences of elevated triglycerides. Elevated blood lipids may be more important when screening OOD. For LD the focus should center on controlling HbA1c levels. Cause for concern is the high number of LD concealed in this study, in a population with a low prevalence of diabetes, and regional physicians could overlook screening in this population.

Disclosure
D. C. Robbins: None. B. C. Dean: None. C. Gerhold: None. M. Mosher: None. J. Camargo: None.

Funding
KU Diabetes Institute
19-LB: Statin Use as a Primary Prevention in Patients with Type 1 Diabetes: Where Do We Stand?
Authors: ALI DALAL S.A. , GRIFFIN TOMAS P. , CROWLEY RACHEL , CANAVAN RONAN 
Published: June 2021

Type 1 diabetes (T1D) carries a high cardiovascular risk (CVD). Statins reduce risk of non-fatal myocardial infarction when used as primary prevention in selected patients[1]. We reviewed 205 electronic records of patients with T1D at our center from July 2019 to September 2019. We followed 2018 NICE guidelines for statin use as a primary prevention for our analysis (1)age ≥40 years (2)diabetes duration ≥10 years (3)established nephropathy (4)established other CVD risks.
Our cohort consisted of 119 males (58%) with a mean BMI of 25.5±4.4 kg/m2 and mean age of 43±16 years. The median duration of diabetes was 16 [IQR 8 - 27] years. More than 50% of our patients had attended “Dose Adjustment For Normal Eating, DAFNE” course. Approximately 71% had T1D for ≥10 years and 56% were ≥40 years. Mean systolic and diastolic blood pressures were 128 (±15.3) mmHg and 77 (±10) mmHg, respectively. Mean LDL was 2.4 (±0.74) mmol/L. In total 24.8% were on statin therapy, 2.4% on fibrates and 4.4% declined statin. Of the patients reviewed, 180 (87.8%) met the criteria for primary prevention; however, of those 51/180 (28.3%) were on statin, 44/146 (30.1%) with diabetes ≥10 years, 46/115 (40.0%) ≥40, 34/93 (36.6%) with established retinopathy. Regarding macro and microvascular complications, 3.4% had CAD, 6.8% chronic kidney disease (eGFR&lt;60) and 47.8% retinopathy. Patients with T1D have higher CVD risk, for which statin therapy is advised[2, 3]. Our patients are undertreated with statins as primary prevention.
References: 1.Cholesterol Treatment Trialists’, C., et al., Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet (London, England), 2010. 376(9753): p. 1670-1681.2.De Ferranti, S.D., et al., Type 1 Diabetes Mellitus and Cardiovascular Disease. Circulation, 2014. 130(13): p. 1110-1130.3.Sharma, H., et al., Cardiovascular disease in type 1 diabetes. Cardiovascular endocrinology & metabolism, 2019. 8(1): p. 28-34.

Disclosure
D. S. A. Ali: None. T. P. Griffin: None. R. Crowley: None. R. Canavan: None.
192-LB: Human CD4+CD25+CD226- Regulatory T Cells Demonstrate High Purity and Lineage Stability following In Vitro Expansion for Adoptive Cell Therapy
Authors: BROWN MATTHEW E. , HANBALI SEIF R. , RODRIGUEZ LUZ MARINA GOMEZ , ARNOLETTI JUAN M. , CARPENTER EMMA B. , BRUSKO TODD M. 
Published: June 2021

Human regulatory T cells (Tregs) are essential for the suppression of autoimmunity and adoptive cell therapy has been proposed as a means for restoring durable immune tolerance in T1D. The rare nature of this subset requires the isolation and in vitro expansion of thymic-derived Tregs (tTregs) for adoptive cell therapies to attenuate autoimmunity or islet transplant rejection. Current approaches involve the isolation of a subset with the marker profile of CD4+CD25+CD127-/lo. This strategy yields a population of Tregs that contains both naïve and peripheral Tregs (pTregs), with peripheral Tregs tending to lose lineage stability over time. Here, a novel gating strategy is presented for obtaining tTregs with high purity and extended lineage stability involving the elimination of the effector costimulatory molecule CD226. Tregs were obtained by fluorescence-activated cell sorting (FACS). This allows for the isolation of CD4+CD25+CD226- Tregs for comparison to classically sorted CD4+CD25+CD127-/lo Tregs over a 28-day culture period. Throughout the expansion, assessment of the lineage’s canonical transcription factors (FOXP3 and Helios), along with functional characteristics and epigenetic markers of the lineage occurred. Isolation of CD226- Tregs as compared to CD127- Tregs yields a Treg population with a higher proportion of tTregs (9.35%, p=0.0016), increased expression of CD25 (1.13-fold, p=0.0023), Helios (1.21-fold, p=0.0419), and CD45RA (1.24-fold, p=0.0017), equally low expression of CD127, and decreased expression of CD226 (2.27-fold, p=0.0001). Overall, this study suggests CD226- Tregs possess an increased therapeutic potential for adoptive transfer immunotherapies, including a more naïve phenotype and increased suppressive capabilities - both of which are critical factors for suppressing autoimmune destruction in vivo.

Disclosure
M. E. Brown: None. S. R. Hanbali: None. L. Gomez rodriguez: None. J. M. Arnoletti: None. E. B. Carpenter: None. T. M. Brusko: Consultant; Self; OneVax, LLC.

Funding
National Institutes of Health (1R01DK106191-01A1, UG3DK122638)
193-LB: A Puzzling Case of Hypoglycemia in a Patient with Type 1 Diabetes Mellitus and Cushing Syndrome
Authors: AMINI MEHDIA , KHINE AYE H. , LAMBA SIMARJEET S. , MISHRA SHREELA , NAING SOE , BABU VARSHA 
Published: June 2021

Introduction: Exogenous insulin antibodies are common in patients with type 1 diabetes mellitus (T1DM) on insulin. However, they are clinically irrelevant as a cause of hypoglycemia. We report a unique case of exogenous insulin antibody-mediated severe hypoglycemia in a patient with T1DM and Cushing syndrome.
Case Report: A 55-year-old woman with T1DM on insulin pump presented with proximal muscle weakness and myalgia. She was diagnosed with Cushing syndrome due to an adrenal adenoma. Despite high serum cortisol, she had severe symptomatic episodic hypoglycemia with glucose levels &lt;10 mg/dL requiring intermittent prolonged suspension of insulin pump. Surprisingly, she did not develop hyperglycemia or ketosis when off the insulin pump. During a witnessed hypoglycemic episode, serum insulin was 20.8 uIU/mL (NRR &lt;19.7 uIU/mL), C-peptide &lt;0.10 ng/mL (NRR 0.80-2.85 ng/mL), glucagon 11 pg/nl (NRR 8-57 pg/nl), and insulin antibody 4.1 U/mL (NRR &lt;0.4/U/mL). She eventually underwent right adrenalectomy and was started on prednisone post-operatively resulting in a marked decrease in frequency of hypoglycemia. She was discharged on prednisone with plan for outpatient taper.
Discussion: Our case highlights the complex nature of glycemic dysregulation in insulin antibody-mediated hypoglycemia. Literature review suggests that binding capacity and affinity to insulin, rather than the quantity of insulin antibodies, determines the severity of hypoglycemia. We hypothesize that high binding capacities in our patient resulted in rapid sequestration of exogenous insulin through formation of immunoglobulin-insulin complexes. The low affinity allowed for subsequent rapid release of insulin in a physiologically dyssynchronous manner resulting in hyperinsulinemic hypoglycemia. A distinctive aspect of our patient is the presence of severe hypoglycemia despite endogenous hypercortisolism, although she responded to prednisone. This finding may have implications for future research.

Disclosure
M. Amini: None. A. H. Khine: None. S. S. Lamba: None. S. Mishra: None. S. Naing: None. V. Babu: None.
193-OR: Memory Advancement with Intranasal Insulin in Type 2 Diabetes: Randomized Control Trial
Authors: NOVAK VERA , MANTZOROS CHRISTOS , NOVAK PETER , MCGLINCHEY REGINA , DAI WEIYING , LIOUTAS VASILEIOS , BUSS STEPHANIE , FORTIER CATHERINE B. , KHAN FAIZAN , BECERRA LAURA APONTE , NGO LONG H. 
Published: June 2021

Type 2 diabetes mellitus (T2DM) increases the risk of dementia. Intranasal insulin (INI) has emerged as treatment for T2DM-related cognitive impairment. This randomized, doubled blind trial consisted of 24-week treatment with 40 IU of intranasal insulin (Novolin® R) or placebo (sterile saline) once daily and 24-week follow-up period. T2DM and control participants &gt; 50 years old and able to walk for 6 minutes, were enrolled. The primary outcomes were INI effect on cognition and normal and dual task walking. A total of 244 participants (122 women; 65.8 ± 9.1 years old) were randomized in the four groups (57 DM-INI, 58 DM-Placebo, 65 Control-INI, 64 Control-Placebo). Of 223 at baseline, 174 completed treatment (84 DM [70% of planned enrollment] and 90 controls [100%]), and 156 (69 DM) completed the follow-up. In T2DM, INI did not improve cognitive outcomes or depression as compared to placebo. In controls, INI improved verbal learning during on-treatment (p=0.03) and post-treatment (p=0.03) periods (Mixed Models). DM-INI group had faster normal walking at baseline and on-treatment (p&lt;0.05), and dual task walking at baseline, on-treatment and post-treatment (p&lt;0.05), as compared to DM-placebo. In T2DM, INI treatment increased perfusion in medio-prefrontal cortex (n=8) (p&lt;0.001) measured using pseudo-continuous arterial spin labeling on 3T MRI. There were no clinically significant adverse events related to treatment. This was the Phase 2 Trial, thus the research design was not sufficiently powered to determine efficacy. On-INI improvement of normal and dual-task walking of ~ 5cm/s in T2DM participants and improvement of cognitive function in INI-treated controls are clinically significant and warrant further investigation (NCT02415556).

Disclosure
V. Novak: Advisory Panel; Spouse/Partner; Endonovo Therapeutics, Inc., Consultant; Spouse/Partner; Dysimmune Foundtation, Other Relationship; Spouse/Partner; Oxford University Press. L. Aponte becerra: None. L. H. Ngo: Consultant; Self; Five Islands Consulting, Other Relationship; Self; Radiological Society of America. C. Mantzoros: Advisory Panel; Self; Amgen Inc., GENFIT, Intercept Pharmaceuticals, Inc., Novo Nordisk, Regeneron Pharmaceuticals Inc. P. Novak: Other Relationship; Self; Dysimmune Foundation, Endonovo Therapeutics, Oxford Press. R. Mcglinchey: None. W. Dai: None. V. Lioutas: Consultant; Self; QMetis. S. Buss: Consultant; Self; Kinto Care. C. B. Fortier: None. F. Khan: None.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases (1R01DK103902); U.S. Food and Drug Administration (IND107690); Novo Nordisk (ISS-001063), Medtronic (NERP15-0310); World Health Organization (UTN-U111-1175-1588)
198-LB: A Novel Heterozygous Mutation in Peroxisome Proliferator-Activated Receptor Gamma (PPAR-γ) Gene in a Woman with Familial Partial Lipodystrophy
Authors: WANDERLEY PATRÍCIA V. , DIAS JOAO C. , VIEIRA MARTA W. , GARCIA GIANE , FILHO ITUO T. , CHAMMA RAYSSA F. , GUGONI LILIAN S. , GIORGI RAFAEL B. , BARCELLOS CRISTIANO R.G. 
Published: June 2021

Background: The nuclear peroxisome proliferator-activated receptor gamma (PPAR-γ) plays a role in the regulation of glucose and lipid metabolism in adipocytes by regulating their differentiation, distribution and function. Heterogeneous mutations of PPAR-γ can cause loss of gene function or reduce its expression leading to a clinical variety of phenotypes that characterize type 3 familial partial lipodystrophy syndrome. The most common features of this syndrome are abnormal body fat accumulation, muscle hypertrophy, insulin resistance, hypertriglyceridemia, polycystic ovary syndrome and hepatic steatosis.
Case report: A 32-year-old-woman was referred to the Endocrinology Division of PUC-SP for treatment of a severe hypertriglyceridemia diagnosed 4 years ago with recurrent episodes of acute pancreatitis and eruptive xanthomas since then. Also, diabetes mellitus (DM) was diagnosed 1 year ago with poor glycemic control. Her sister also had severe hypertriglyceridemia, recurrent episodes of acute pancreatitis and died in 2016. No DM was reported in her family. On physical examination, we found the presence of lipodystrophy, acanthosis nigricans on the neck and eruptive xanthomas on trunk, upper limbs, and thighs. BMI=24.9kg/m2; waist circumference=96cm. Abdominal CT scan revealed splenomegaly and fatty liver disease. Genetic sequencing showed a heterozygous (autosomal dominant inheritance) in the PPAR-γ of a Chr3 variant: 12.416.957 T&gt; C (or alternatively c.1073T&gt; C - ENST000002287820), promoting the substitution of leucine in codon 358 by proline (p.Leu358Pro).
Conclusion: The substitution of the amino acid leucine in codon 358 for proline is highly conserved in several species, and computer programs for predicting in silico of pathogenicity, suggesting that this new heterozygous mutation in the PPAR-γ gene is probably related to the type 3 familial partial lipodystrophy syndrome.

Disclosure
P. V. Wanderley: None. J. C. Dias: None. M. W. Vieira: None. G. Garcia: None. I. T. Filho: None. R. F. Chamma: None. L. S. Gugoni: None. R. B. Giorgi: None. C. R. G. Barcellos: None.
201-OR: Remission of Type 2 Diabetes and Decreased Inflammatory Markers with a High-Protein Diet
Authors: STENTZ FRANKIE B. , AMMONS ANN , CHRISTMAN JOHN V. 
Published: June 2021

The purpose of this study was to determine if remission of type 2 diabetes(T2D) and a decrease in inflammatory cytokines (IC) can be achieved by macronutrients dietary changes without diabetes medications. High Protein (HP)(30% protein, 30% fat, 40% carbohydrates) or High Carbohydrate (HC)(15% protein, 30% fat, 55% carbohydrates) diets were used to study remission of type 2 diabetes(T2D) to Normal Glucose Tolerance(NGT), inflammatory cytokines, weight loss, body composition, and metabolic parameters in this randomized controlled clinical trial feeding study for 6 month(mo). Obese, age 20-65 years subjects withT2D were randomized to a HP or HC diet for 6 mo with all food provided. Caloric need for weight loss was determined by Resting Metabolic Rate-500 calories/day. Oral Glucose Tolerance Tests (OGTT) were performed at Baseline (BL) and 6 mo to determine T2D/NGT status. Glucose BL≥126 mg/dl and HbA1c≥6.5% and 2 hr glucose &gt;199mg/dl was considered T2D and remission at 6 mo was glucose BL&lt;126 mg/ml and HbA1c&lt;6.5% and 2 hr glucose &lt;140 mg/dl. DXA was done at BL and 6 mo. Food pick up and weight checks were weekly.T2D subjects on HP diet had 100% remission to NGT while HC diet subjects had 16% remission. IC were significantly decreased in HP compared to HC subjects at 6 mo for TNFa pg/ml (p=0.001) [HP 3.9±0.7 vs. HC 12.6±1.9] and IL-6 pg/ml (p=0.005) [HP 4.7±0.5 vs. HC 9.1±0.9]. Both diet groups had improvement in insulin sensitivity: HOMA IR [HP(BL 5.3±0.29; 6 mo 2.1±0.13)], [HC(BL 5.2±0.27; 6 mo 4.4±0.26)] and decrease in HbA1c [HP(BL 7.7±.05; 6 mo 5.6±.02)], [HC(BL 7.8±.04; 6 mo 6.6±.06)]. While both HP and HC groups has similar weight loss (HP =15.4±5 lb, HC=19.9±5 lb), HP group had a 2.7± 0.4% increase in lean body mass(LM) and 2.9± 0.4% decrease in fat mass(FM) while the HC group had a 1.9±0.3% LM and 3.3±0.9 % FM decrease respectively. The HP diet demonstrated improvement in glucose tolerance and insulin sensitivity with 100% remission of T2D to NGT and a significant decrease in inflammatory cytokines.

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

Funding
AD Baskin (R073316012)