bluuebunny/crossref_metadata_2025_split huggingface dataset:
212-OR: Five-Year Follow-Up of Lipid, Inflammatory, Hepatic, and Renal Markers in People with T2 Diabetes on a Very-Low-Carbohydrate Intervention Including Nutritional Ketosis (VLCI) via Continuous Remote Care (CRC)
Authors: ROBERTS CAROLINE G.P. , ATHINARAYANAN SHAMINIE J. , VANTIEGHEM MICHELLE , MCKENZIE AMY L. , VOLK BRITTANIE M. , ADAMS REBECCA N. , FELL BRANDON , RATNER ROBERT E. , VOLEK JEFF , PHINNEY STEPHEN , HALLBERG SARAH 
Published: May 2022

Objective: To address the long-term effectiveness of VLCI for T2D, we report changes in lipids, inflammatory, hepatic, and renal markers at 5y.
Research Design and Methods: Of the 200 subjects with T2D reaching 2-years in a non-randomized, controlled trial of CRC emphasizing VLCI, 169 (84.5%) consented to 3-year extension and 122 (61%) completed 5y. Metabolic changes from baseline (BL) to 5y were assessed with linear mixed effect models as an intent-to-treat analysis (n=169) . Holm-Bonferroni adjusted p-values are &lt;0.05 unless otherwise noted.
Results: At 5y, there were significant changes in HDLc from 43.0 mg/dl to 50.6 mg/dl (+17.7%) , apoA-I from 146.9 mg/dl to 153.5 mg/dl (+4.5%) , and no changes in Total Cholesterol, LDLc, apoB. There were marginal improvements in non-HDLc from 139.2 mg/dl to 128.9 mg/dl (-7.4%, unadjusted p-value &lt;0.01) , and triglycerides from 202.3 mg/dl to 165.1 mg/dl (-18.4%, unadjusted p-value &lt;0.01) . Inflammatory markers significantly improved: hs-CRP from 7.8 nmol/L to 4.4 nmol/L (-43.6%) , white blood cell count from 7.2 k/mm3 to 6.4 k/mm3 (-11.1%) . At all time points, liver markers have been in the normal range. There were no changes in renal biomarkers. eGFR was stable at CKD2. Subcohort completers’ analysis of those with eGFR&lt;60 ml/min/1.73m2 (n=10) showed an increase from 47.8 to 57.1 ml/min/1.73m2 (p=0.01). Six of the subjects (60%) with BL CKD3 who completed 5y rose to CKD2. Of the 107 subjects with BL CKD2, 7 (6.5%) progressed to CKD3.
Conclusions: People with T2D following VLCI for 5y show improvements in diabetic dyslipidemia and inflammation. Notably, there is no change in LDLc. There is no significant deterioration in liver and renal labs, although regression from CKD3 to 2 is possible with a VLCI and warrants further investigation.

Disclosure
C.G.Roberts: Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. S.Phinney: Employee; Virta Health Corp. S.Hallberg: Advisory Panel; Atkins Nutritionals Inc., Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. S.J.Athinarayanan: Employee; Virta Health Corp. M.Vantieghem: Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. A.L.Mckenzie: Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. B.M.Volk: Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. R.N.Adams: Employee; Virta Health Corp. B.Fell: Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. R.E.Ratner: Employee; Virta Health Corp. J.Volek: Advisory Panel; Abbott Diagnostics, Simply Good Foods, Stock/Shareholder; Virta Health Corp.
213-OR: Antidiabetic Potential of Novel, Long-Acting Amylin Analogue ZP8396 in ZDF Rats
Authors: SKARBALIENE JOLANTA , BAADER-PAGLER TAMARA , ERIKSSON PER-OLOF 
Published: May 2022

Amylin improves glucose homeostasis through at least three distinct mechanisms of action, including prevention of the postprandial rise in plasma glucagon, slowing of gastric emptying, and increased satiety, leading to decreased caloric intake and potential weight loss. Clinical efficacy has been demonstrated with short-acting amylin analogue pramlintide. ZP8396, currently in phase 1 clinical testing, is a long-acting, amylin analogue designed to improve solubility, stability and allow for co-formulation with other relevant peptides. We previously reported that ZP8396 provides body weight reduction in DIO rats alone and in combination with semaglutide, a once-weekly GLP-1 agonist (Skarbaliene et al, Obesity Week 2021) . Here we investigated the antidiabetes potential of ZP8396 in Zucker Diabetic Fatty (ZDF) rats. The antidiabetes potential after a single subcutaneous (s.c.) injection of ZP8396 (nmol/kg) or vehicle was measured in ZDF rats (aged 12-13 weeks, n=10) , an animal model of type 2 diabetes, and continuously monitored for 168 h after dosing.ZP8396 induced a significant body weight loss in ZDF rats vs. vehicle group. A significant decrease in body weight was observed in rats treated with ZP8396 from initiation of the dosing and up to 96 h post-dose. In addition, single s.c. injection of ZP8396 showed a significant reduction in blood glucose levels at 24 h post-dose, reaching a 20 % difference in blood glucose levels vs. vehicle group (14,97±0,39 and 18,60±1,18 mmol/L, respectively; p &lt;0.05) . Also, ZP8396 significantly reduced plasma glucagon levels, reaching a 55% difference in ZP8396-treated diabetic rats vs. vehicle group at 24 h post-dose (p &lt;0.05) .
In conclusion, in diabetic rat ZP8396 improved glycaemic status, supporting that long-acting amylin analogues may provide future valuable therapeutic options to manage diabetes. Further preclinical characterization of the antidiabetes effects of long-term treatment with ZP8396 is ongoing.

Disclosure
J.Skarbaliene: Employee; Zealand Pharma A/S, Stock/Shareholder; Zealand Pharma A/S. T.Baader-pagler: Employee; Boehringer Ingelheim International GmbH. P.Eriksson: Employee; Zealand Pharma A/S.
215-LB: Silencing of Fructose 1,6-Bisphosphatase (FBP1) in Liver Improves Glucose Homeostasis in Insulin-Resistant Rodent and Human Models
Authors: FLEDELIUS CHRISTIAN , IVERSEN HELLE , INGVORSEN RIKKE S. , ERIKSEN LISBETH B. , BLOIS ANNA , MONTAUBAN YVENET , RIJNBRAND RENE , HAN WEN , JEPPESEN JACOB F. , DEMOZAY DAMIEN 
Published: May 2022

Insulin resistant individuals display elevated fasting and post-prandial glucose levels which are mainly driven by inadequate inhibition of gluconeogenesis (GNG) and are rarely normalized. The aim of this study was to investigate whether direct inhibition of GNG could be a new therapeutical approach to improve glucose homeostasis using in vitro and in vivo models of insulin resistance. Fructose 1,6-bisphosphatase (FBP1) is key in controlling GNG in liver and kidney and loss of function patients display hypoglycaemia episodes and lactate acidosis. Systemic FBP1 inhibition using small molecules has shown to improve glucose homeostasis. To assess the clinical efficacy and safety potential of silencing FBP1 selectively in the liver we dosed insulin resistant DIO rats with a hepatocyte specific GalXC-FBP1 siRNA entity. GalXC-FBP1 siRNA markedly reduced FBP1 mRNA level in the liver by over 90%. This was associated with a complete lack of glucose excursion following a pyruvate challenge indicating inhibition of GNG. Blood glucose level decreased similarly in rats treated with GalXC-FBP1 siRNA or vehicle during an insulin challenge or a prolonged fast suggesting that hepatic FBP1 silencing is not inducing hypoglycaemia. Insulin sensitivity and hyperinsulinemia were improved. Plasma lactate and liver enzymes were not elevated, but a significant 2-fold increase in liver triglycerides was observed in the GalXC-FBP1 siRNA group. Using human hepatocytes in a Liver-on-Chip in vitro model FBP1 silencing reduced glucose production by 30% supporting the relevance of this approach in humans. Collectively these data suggest that liver specific FBP1 silencing has the potential to improve insulin sensitivity in DIO rats without inducing hypoglycaemia but may be associated with a risk of liver steatosis overtime. This concept highlights the difficulty of blocking liver GNG without re-directing the metabolic intermediates fluxes toward triglycerides accumulation in liver.

Disclosure
C. Fledelius: Employee; Novo Nordisk A/S. D. Demozay: Employee; Novo Nordisk A/S. H. Iversen: None. R. S. Ingvorsen: None. L. B. Eriksen: None. A. Blois: Employee; Novo Nordisk. Y. Montauban: None. R. Rijnbrand: Employee; Novo Nordisk. W. Han: None. J. F. Jeppesen: Employee; Novo Nordisk A/S.
216-OR: Hypoglycemia Frequency and Physiological Response to Double or Triple Doses of Once-Weekly Insulin Icodec vs. Once-Daily Insulin Glargine in T2D
Authors: SVEHLIKOVA EVA , ARFELT KRISTINE NISS , CAILLETEAU ROMAN , DELLER SIGRID , THOMSEN KAREN MARGRETE , HART MARLIES , MURSIC INES , PIEBER THOMAS , HAAHR HANNE 
Published: May 2022

Insulin icodec is a basal insulin in development for once-weekly (OW) dosing. The aim of this study was to compare the hypoglycemia frequency and response after icodec vs. insulin glargine U100 (IGlar) overdosing. In a randomized, open-label, two-period crossover trial, 43 individuals with T2D on basal insulin±metformin (mean±SD age 56±9 yrs, HbA1c 7.2±0.7%) received OW icodec for 6 weeks and once-daily IGlar for 12 days at equimolar total weekly doses based on the individual daily run-in IGlar dose (mean 30±14 U) titrated to a fasting SMPG target of 80-130 mg/dL. Once at steady state, double (DD) and triple (TD) doses of icodec and IGlar were followed by hypoglycemia induction 44 h (icodec) or 7 h (IGlar) post-dose (expected time of maximum glucose-lowering effect) : First, euglycemia was maintained at 100 mg/dL by variable i.v. glucose. Then, PG was allowed to decrease to a nadir of no less than 45 mg/dL maintained for 15 min. Euglycemia was restored by constant i.v. glucose. Hypoglycemic symptom score (HSS) and counterregulatory hormones were assessed at PG 100 mg/dL and at predefined PG levels until nadir PG. For DD, clinically significant hypoglycemia (PG&lt;54 mg/dL) occurred in 40 vs. 36% of subjects for icodec vs. IGlar (odds ratio 1.28; p=0.63) . For TD, clinically significant hypoglycemia occurred in 53 vs. 70% of subjects (odds ratio 0.48; p=0.14) , mean nadir PG was 56 vs. 52 mg/dL (treatment ratio 1.07; p&lt;0.001) , change in HSS at nadir PG was comparable for icodec vs. IGlar (treatment difference 0.46; p=0.77) , responses in adrenaline, noradrenaline and cortisol during hypoglycemia development were greater for icodec vs. IGlar, while glucagon and growth hormone levels increased similarly.
In conclusion, a DD or TD of once-weekly insulin icodec does not lead to increased risk of hypoglycemia compared to once-daily IGlar. During hypoglycemia, a comparable symptomatic response and a moderately greater endocrine response were seen for icodec vs. IGlar.

Disclosure
E.Svehlikova: n/a. K.Niss arfelt: Employee; Novo Nordisk. R.Cailleteau: Employee; Novo Nordisk A/S, Stock/Shareholder; Novo Nordisk A/S. S.Deller: None. K.Thomsen: Employee; Novo Nordisk. M.Hart: None. I.Mursic: None. T.Pieber: Advisory Panel; Arecor, Novo Nordisk A/S, Research Support; AstraZeneca, European Union, JDRF, Novo Nordisk Foundation, Sanofi, Speaker's Bureau; Novo Nordisk A/S, Roche Diagnostics. H.Haahr: Employee; Novo Nordisk A/S, Stock/Shareholder; Novo Nordisk A/S.

Funding
Novo Nordisk
217-OR: A Randomized Controlled Trial Comparing the Safety and Efficacy of IDegLira vs. Basal Bolus in Patients with Poorly Controlled Type 2 Diabetes and Very High HbA1c (&gt;9%–15%) : IDegLira HIGH Trial
Authors: GALINDO RODOLFO J. , MOAZZAMI BOBAK , SCIOSCIA MARIA F. , VELLANKI PRIYATHAMA , DAVIS GEORGIA M. , PASQUEL FRANCISCO J. , FAYFMAN MAYA , MIGDAL ALEXANDRA L. , SALING JARROD , UMPIERREZ GUILLERMO E. 
Published: May 2022

IDegLira-HIGH trial was a non-inferiority, prospective, randomized clinical trial, comparing the efficacy and safety of insulin degludec/liraglutide combination (IDegLira) and a regimen of multiple daily injections (MDI) with basal-bolus insulin (BB) in adults (&gt;18-80 years of age) , with type 2 diabetes (T2D) , and very high HbA1c (&gt;9%-15%) , previously treated with basal insulin or multiple oral agents. Primary endpoint was change in HbA1c from baseline to week 26. Secondary endpoints included incidence of hypoglycemia, changes on weight and glycemic variability (% coefficient of variation [%CV]) . Treatment with IDegLira and BB insulin resulted in similar improvement in glycemic control: 7.7±1.7% and 7.7±1.5%, (p=0.76) , with a reduction from baseline of -3.2±2.3% and -3.0±1.8%, (p=0.39) at 26-weeks. IDegLira resulted in lower rates of hypoglycemia &lt;70 mg/dl (22% vs. 36%, p=0.05) , similar glycemic variability (CGM %CV 30.4±9.1% vs. 33.2±7.3%, p=0.08) , and greater weight loss (-3.7±4.1 kg vs. +8.4±5.4 kg, p&lt;0.01) compared to BB. IDegLira was associated with higher rates of nausea (Table 1) . Conclusions: In patients with T2D and very high HbA1c (≥9%-15%) , a regimen of daily IDegLira injection is non-inferior to MDI with BB insulin on HbA1c reduction and was associated with weight loss and less hypoglycemia.

Disclosure
R.J.Galindo: Advisory Panel; Sanofi, WW International, Inc., Research Support; Dexcom, Inc., Eli Lilly and Company, Novo Nordisk. G.E.Umpierrez: Research Support; AstraZeneca, Dexcom, Inc., Novo Nordisk. B.Moazzami: None. M.F.Scioscia: None. P.Vellanki: n/a. G.M.Davis: Consultant; Medscape, Research Support; Insulet Corporation. F.J.Pasquel: Consultant; AI Health LLC, Boehringer Ingelheim International GmbH, Dexcom, Inc., Research Support; Dexcom, Inc., Insulet Corporation, Merck & Co., Inc. M.Fayfman: None. A.L.Migdal: None. J.Saling: None.

Funding
Investigator-initiated study to Emory University (PI. Dr. Rodolfo J. Galindo) from Novo Nordisk.
218-OR: The Effect of Insulin Degludec vs. Insulin Glargine U100 on Continuous Glucose Monitoring (CGM) Recorded Glycemic Metrics in People with Type 1 Diabetes and Recurrent Nocturnal Severe Hypoglycemia
Authors: BRØSEN JULIE M. , AGESEN RIKKE , ALIBEGOVIC AMRA CIRIC , ANDERSEN HENRIK U. , GUSTENHOFF PETER , HANSEN TROELS K. , HEDETOFT CHRISTOFFER , STOLBERG CHARLOTTE R. , JUHL CLAUS B. , LERCHE SUSANNE , NØRGAARD KIRSTEN , TARNOW LISE , THORSTEINSSON BIRGER , PEDERSEN-BJERGAARD ULRIK 
Published: May 2022

Background and Aims: Insulin Degludec (IDeg) , in comparison with Insulin Glargine U100 (IGla) , reduces the risk of hypoglycemic events in people with type 1 diabetes (T1D) . The impact on CGM assessed glycemic metrics: the coefficient of variation (CV) , time in range (TIR) , time below range (TBR) , and time-above range (TAR) is less known. We present CGM results from the HypoDeg trial comparing treatment with IDeg and IGla in people with T1D and recurrent nocturnal severe hypoglycemia.
Materials and Methods: This is a pre-defined optional substudy of the HypoDeg trial: a 2-year investigator-initiated, randomized, cross-over trial comparing treatment with IDeg or IGla in 149 participants with T1D and at least one nocturnal severe hypoglycemic event within the last two years. Participants underwent 2 x 6 days of blinded CGM (Medtronic iPro) in each treatment arm after 6 and 12 months of treatment. Seventy-four participants completed at least one CGM period in each treatment arm. The endpoints were CV, TIR (3.9 - 10.0 mmol/L) , TBR at level 2 (&lt; 3.0 mmol/L) and TAR (&gt;10.0mmol/L, &gt;13.9mmol/L) . Time spent in, below, or above range provided as percentage of readings.
Results: We collected 261 CGM traces with a mean (SD) observation period of 5.9 (0.7) days. The all-day CV was lower with IDeg than IGla, with a mean (SE) CV of 40.5% (0.9) and 42.5% (0.9) , respectively (p=0.009) . A difference in CV during the night (23:00h to 07:00h) drove this, with a mean CV of 35.7% (1.1) for IDeg versus 39.6% (1.1) for IGla (p=0.001) . The all-day level 2 TBR was lower with IDeg than IGla, with a mean TBR of 1.8% (0.4) and 3.1% (0.4) , respectively (p=0.001) . The percentages of TIR and TAR were not different between treatments.
Conclusion: In people with T1D prone to nocturnal severe hypoglycemia, treatment with IDeg results in a lower mean CV, reaching the definition of stable glucose levels during the night and a lower all-day TBR than IGla.

Disclosure
J.M.Brøsen: None. S.Lerche: None. K.Nørgaard: Advisory Panel; Medtronic, Novo Nordisk A/S, Consultant; Novo Nordisk A/S, Research Support; Dexcom, Inc., Medtronic, Novo Nordisk A/S, Zealand Pharma A/S, Speaker's Bureau; Medtronic, Stock/Shareholder; Novo Nordisk A/S. L.Tarnow: None. B.Thorsteinsson: None. U.Pedersen-bjergaard: Advisory Panel; Novo Nordisk A/S, Sanofi. R.Agesen: Employee; Novo Nordisk A/S. A.Alibegovic: Employee; Novo Nordisk A/S, Novo Nordisk A/S. H.U.Andersen: Advisory Panel; Abbott Diabetes, Stock/Shareholder; Novo Nordisk A/S. P.Gustenhoff: Advisory Panel; Abbott Diagnostics. T.K.Hansen: None. C.Hedetoft: None. C.R.Stolberg: None. C.B.Juhl: None.

Funding
Novo Nordisk
219-LB: The Mitochondrial Calcium Uniporter Regulates Hepatic Lipid Accumulation and Mitochondrial Oxidation
Authors: LAMOIA TRACI E. , HUBBARD BRANDON T. , GUERRA MATEUS , GOODMAN RUSSELL , NATHANSON MICHAEL H. , MOOTHA VAMSI , SHULMAN GERALD I. 
Published: May 2022

The mitochondrial calcium uniporter (MCU) facilitates mitochondrial calcium influx, and several enzymes that catalyze key steps of the tricarboxylic acid (TCA) cycle require calcium for their activation. As such, it is generally accepted that rates of mitochondrial oxidation correlate with mitochondrial calcium activity. Decreased rates of hepatic mitochondrial oxidation are associated with metabolic dysfunction and ectopic lipid accumulation as seen with type 2 diabetes and nonalcoholic fatty liver disease. Despite this, a role for MCU and mitochondrial calcium in regulating hepatic mitochondrial oxidation is still unclear. To address this question, we generated a liver-specific MCU knockout (MCU KO) mouse model which displayed significantly reduced mitochondrial calcium ([Ca2+]mt, p&lt;0.05) and increased cytosolic calcium ([Ca2+]cyt, p&lt;0.01) in isolated hepatocytes. Despite decreased [Ca2+]mt, we found that deletion of hepatic MCU resulted in increased rates of isocitrate dehydrogenase flux (VIDH, p&lt;0.01) , α-ketoglutarate dehydrogenase flux (VOGDH, p&lt;0.01) , and succinate dehydrogenase flux (VSDH, p&lt;0.05) , using a novel in vivo [13C5]glutamine tracer technique. Further, we report that rates of [14C16]palmitate oxidation (p&lt;0.01) and intrahepatic lipolysis (p&lt;0.05) were significantly increased in precision-cut liver slices collected from MCU KO mice compared to WT, consistent with [Ca2+]cyt activation of CAMKII (p&lt;0.01) and ATGL (p&lt;0.001) in MCU KO mice, and were associated with reductions in hepatic triacylglycerol content in vivo (p&lt;0.01) . Taken together, these data demonstrate that hepatic mitochondrial activity can be dissociated from mitochondrial calcium concentrations and reveal a key role for cytosolic calcium and mitochondrial anaplerosis in the regulation of hepatic mitochondrial fat oxidation.

Disclosure
T. E. Lamoia: n/a. B. T. Hubbard: None. M. Guerra: None. R. Goodman: None. M. H. Nathanson: None. V. Mootha: Advisory Panel; 5AM Ventures, LLC, Janssen Research & Development, LLC. G. I. Shulman: Advisory Panel; 89bio, Inc., AstraZeneca, Equator Therapeutics, Inc., Janssen Research & Development, LLC, Merck & Co., Inc., Consultant; DiCerna Pharmaceuticals, Inc. , Novo Nordisk, Other Relationship; Generian Pharmaceuticals, iMetabolic Biopharma Corporation, Maze Therapeutics, The Liver Company, Stock/Shareholder; Levels Health, Inc. .

Funding
F31 DK126362/DK/NIDDK NIH HHST32 GM007324/GM/NIGMS NIH HHS
222-LB: Switching Palmitoyl and Oleoyl Position in Sn-2 and Sn-3 of a Triacylglycerol Led to Differential Body Weight Gain Rates and Hepatic Gene Expressions in Mice Fed a High-Fat Diet
Authors: HU XINGE , WANG TIANNAN , CHEN GUOXUN 
Published: May 2022

Alterations of fatty acid metabolism have been associated with diabetes. Triacylglycerol (TAG) can be obtained from dietary sources and synthesized de novo. The composition and location of the fatty acyl groups in a TAG can affect its physicochemical features such as melting temperature, and physiological characteristics such as digestion, absorption, and lipid metabolism. We hypothesize that the TAG fatty acyl position affects the body weight gain and lipid metabolism of mice in a high-fat diet (HFD) setting. Twenty-seven 6-week-old male C57/BL6J mice were randomly assigned to 3 dietary treatment groups, 1,2-dipalmitoyl-3-oleoylglycerol (PPO, 36 % w/w diet) , 1,3-dipalmitoyl-2-oleoylglycerol (POP, 36% w/w diet) , and the chow diet control groups. Mice in each group were fed their respective diet for 6 weeks, and food intake and body weight were measured daily. Mice fed the PPO diet had significantly higher food intake, calories intake and body wight gain rate, and lower liver to body weight ratio than those fed the POP diet. Mice fed the chow diet had significantly higher total grams of food intake, but lower calories intake, liver and epididymal fat weight, and body weight gain rate than those fed the PPO, but not the POP, diet. Mice in the PPO group had significantly higher serum glucose than that in other two groups, whereas mice fed the chow diet had significantly lower plasma cholesterol level than those HFD groups. The plasma TAG levels were not different among them. The hepatic levels of insulin receptor substrate 1, and fatty acid synthase, and phosphorylated acetyl CoA carboxylase in mice fed the chow diet are significantly higher than those fed the PPO or POP diet, whereas the hepatic expression level of stearoyl CoA desaturase 1 in mice fed the POP diet was lower than those fed the PPO or chow diet. We conclude that feeding a HFD affects the expression levels of hepatic proteins for lipid metabolism in mice. In addition, the position of fatty acyl group in a TAG affects the food intake, the body weight gain rate and lipid homeostasis in mice.

Disclosure
X. Hu: None. T. Wang: None. G. Chen: None.
224-LB: Mitochondrial Capacity of Skeletal Muscle in Older Adults with Diabetes
Authors: RAMOS SOFHIA V. , DISTEFANO GIOVANNA , CAWTHON PEGGY , MARSHALL STEPHANIE M. , KRAMER PHILIP , MOLINA ANTHONY , JURCZAK MICHAEL J. , TOLEDO FREDERICO , GOODPASTER BRET H. , COEN PAUL M. 
Published: May 2022

Skeletal muscle mitochondrial capacity is reduced in both aging and diabetes. Whether diabetes further impairs mitochondrial capacity in older adults and how this relates to cardiorespiratory fitness (VO2peak) and glycemic control (HbA1c) remains uncertain. We examined muscle mitochondrial capacity of those with diabetes (self-reported, including Type 1 and 2) and without diabetes in the Study of Muscle Mobility and Aging (SOMMA) (273 men, 194 women; mean±SD age: 76.8±5.3 years) . Mitochondrial capacity was assessed by 31P magnetic resonance spectroscopy (ATPmax) and respirometry of vastus lateralis biopsy specimens. ATPmax (diabetes; 0.48 ± 0.1, nondiabetes; 0.54 ± 0.1 mM/sec, p=0.07) and fatty acid oxidation (FAO) supported OXPHOS (FAO: diabetes; 11.5 ± 4.5, nondiabetes; 12.5 ± 4.4 pmol/min/mg, p=0.01) were lower in those with diabetes compared to those without. VO2peak, assessed by a graded exercise test, was lower in those with diabetes (diabetes; 1478.8± 399.9, nondiabetes; 1495.5 ± 431.3 mL/min, p=0.01) . In all participants, ATPmax (r2=0.07, p=&lt;0.01) and FAO (r2=0.04, p=0.14) explained a small proportion of variance in HbA1c. VO2peak significantly related to mitochondrial capacity (ATPmax: r2=0.66, p=&lt;0.01, FAO: r2=0.64, p&lt;0.01) , but the relationships do not vary by diabetes status.
In summary, older adults with diabetes have marginally lower fitness and mitochondrial capacity. Mitochondrial capacity is related to both glycemic control and cardiorespiratory fitness regardless of diabetes status.

Disclosure
S. V. Ramos: None. P. M. Coen: None. G. Distefano: None. P. Cawthon: None. S. M. Marshall: None. P. Kramer: None. A. Molina: None. M. J. Jurczak: None. F. Toledo: None. B. H. Goodpaster: None.

Funding
Study of Muscle, Mobility and Aging (SOMMA) RO1 AG059416