Insulin and Sarcopenia in the Elderly

NCT00690534 | Completed Phase 1

• 2 other identifiers: 05-0905R01AG018311
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 1

Brief Summary

Muscle loss with aging is a significant contributor to disability in older people. Our general hypothesis is that loss of muscle with aging, known as sarcopenia, may be due to inability of muscle to grow in response to insulin. Our goal is to determine the mechanisms underlying this age-related insulin resistance of muscle proteins, which will allow us to define in the future specific interventions to target this defect and provide the scientific basis for the prevention and treatment of sarcopenia.

Conditions

Sarcopenia

Keywords

sarcopenia; aging; muscle metabolism

Outcome Measures

Primary Outcomes (1)

• muscle protein synthesis

  5 and 8 hours

Secondary Outcomes (1)

• blood flow

  5 and 8 hours

Study Arms (11)

CMAY

ACTIVE COMPARATOR

Insulin in young

Drug: Insulin Regular

IMAY

EXPERIMENTAL

L-NMMA + insulin in young

Drug: Insulin Regular; Drug: L-NMMA

SNPY

EXPERIMENTAL

SNP in young

Drug: Sodium Nitroprusside

CSNP

ACTIVE COMPARATOR

Insulin in elderly

Drug: Insulin Regular

ISNP

EXPERIMENTAL

SNP in elderly

Drug: Insulin Regular; Drug: Sodium Nitroprusside

SNPE

EXPERIMENTAL

SNP in elderly

Drug: Sodium Nitroprusside

CMealO

ACTIVE COMPARATOR

Meal in elderly

Other: mixed meal

SMealO

EXPERIMENTAL

SNP+meal in elderly

Drug: Sodium Nitroprusside; Other: mixed meal

MealY

ACTIVE COMPARATOR

meal in young

Other: mixed meal

ExIns

EXPERIMENTAL

insulin+exercise in elderly

Drug: Insulin Regular

ExMeal

EXPERIMENTAL

meal+exercise in elderly

Other: mixed meal

Interventions

Insulin Regular DRUG

insulin, 0.2 mU/kg/min for 3 hours

CMAY; CSNP; ExIns; IMAY; ISNP

L-NMMA DRUG

variable rate for 3 hours

IMAY

Sodium Nitroprusside DRUG

variable rate for 3 hours

ISNP; SMealO; SNPE; SNPY

mixed meal OTHER

mixed meal

CMealO; ExMeal; MealY; SMealO

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-40 yrs, and 65-85 yrs.
• Ability to sign consent form (score \>23 on the 30-item Mini Mental State Examination, MMSE)
• Stable body weight for at least 3 months

You may not qualify if:

• Physical dependence or frailty (impairment in any of the Activities of Daily Living (ADL), history of falls (\>2/year) or significant weight loss in the past year)
• Exercise training (\>2 weekly sessions of moderate to high intensity aerobic or resistance exercise)
• Pregnancy or nursing women.
• Significant heart, liver, kidney, blood or respiratory disease
• Peripheral vascular disease
• Diabetes mellitus or other untreated endocrine disease
• Active cancer
• Recent (within 6 months) treatment with anabolic steroids, or corticosteroids.
• Alcohol or drug abuse
• Severe depression (\>5 on the 15-item Geriatric Depression Scale, GDS)
• Potential subjects who have recently donated blood in the past 60 days will be excluded from participating in the study.

Sponsors & Collaborators

• The University of Texas Medical Branch, Galveston: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

Sealy Center on Aging, University of Texas Medical Branch

Galveston, Texas, 77555-0460, United States

Location

Related Publications (21)

• Rasmussen BB, Fujita S, Wolfe RR, Mittendorfer B, Roy M, Rowe VL, Volpi E. Insulin resistance of muscle protein metabolism in aging. FASEB J. 2006 Apr;20(6):768-9. doi: 10.1096/fj.05-4607fje. Epub 2006 Feb 7.

  PMID: 16464955 RESULT

• Bell JA, Volpi E, Fujita S, Cadenas JG, Sheffield-Moore M, Rasmussen BB. Skeletal muscle protein anabolic response to increased energy and insulin is preserved in poorly controlled type 2 diabetes. J Nutr. 2006 May;136(5):1249-55. doi: 10.1093/jn/136.5.1249.

  PMID: 16614412 RESULT

• Bell JA, Volpi E, Fujita S, Cadenas JG, Rasmussen BB. Dysregulation of muscle fatty acid metabolism in type 2 diabetes is independent of malonyl-CoA. Diabetologia. 2006 Sep;49(9):2144-52. doi: 10.1007/s00125-006-0362-9. Epub 2006 Jul 26.

  PMID: 16868746 RESULT

• Timmerman KL, Volpi E. Amino acid metabolism and regulatory effects in aging. Curr Opin Clin Nutr Metab Care. 2008 Jan;11(1):45-9. doi: 10.1097/MCO.0b013e3282f2a592.

  PMID: 18090658 RESULT

• Fujita S, Volpi E. Amino acids and muscle loss with aging. J Nutr. 2006 Jan;136(1 Suppl):277S-80S. doi: 10.1093/jn/136.1.277S.

  PMID: 16365098 RESULT

• Dreyer HC, Volpi E. Role of protein and amino acids in the pathophysiology and treatment of sarcopenia. J Am Coll Nutr. 2005 Apr;24(2):140S-145S. doi: 10.1080/07315724.2005.10719455.

  PMID: 15798081 RESULT

• Drummond MJ, Bell JA, Fujita S, Dreyer HC, Glynn EL, Volpi E, Rasmussen BB. Amino acids are necessary for the insulin-induced activation of mTOR/S6K1 signaling and protein synthesis in healthy and insulin resistant human skeletal muscle. Clin Nutr. 2008 Jun;27(3):447-56. doi: 10.1016/j.clnu.2008.01.012. Epub 2008 Mar 14.

  PMID: 18342407 RESULT

• Drummond MJ, Dreyer HC, Pennings B, Fry CS, Dhanani S, Dillon EL, Sheffield-Moore M, Volpi E, Rasmussen BB. Skeletal muscle protein anabolic response to resistance exercise and essential amino acids is delayed with aging. J Appl Physiol (1985). 2008 May;104(5):1452-61. doi: 10.1152/japplphysiol.00021.2008. Epub 2008 Mar 6.

  PMID: 18323467 RESULT

• Fujita S, Rasmussen BB, Cadenas JG, Drummond MJ, Glynn EL, Sattler FR, Volpi E. Aerobic exercise overcomes the age-related insulin resistance of muscle protein metabolism by improving endothelial function and Akt/mammalian target of rapamycin signaling. Diabetes. 2007 Jun;56(6):1615-22. doi: 10.2337/db06-1566. Epub 2007 Mar 9.

  PMID: 17351147 RESULT

• Fujita S, Rasmussen BB, Bell JA, Cadenas JG, Volpi E. Basal muscle intracellular amino acid kinetics in women and men. Am J Physiol Endocrinol Metab. 2007 Jan;292(1):E77-83. doi: 10.1152/ajpendo.00173.2006. Epub 2006 Aug 8.

  PMID: 16896165 RESULT

• Fujita S, Rasmussen BB, Cadenas JG, Grady JJ, Volpi E. Effect of insulin on human skeletal muscle protein synthesis is modulated by insulin-induced changes in muscle blood flow and amino acid availability. Am J Physiol Endocrinol Metab. 2006 Oct;291(4):E745-54. doi: 10.1152/ajpendo.00271.2005. Epub 2006 May 16.

  PMID: 16705054 RESULT

• Bell JA, Fujita S, Volpi E, Cadenas JG, Rasmussen BB. Short-term insulin and nutritional energy provision do not stimulate muscle protein synthesis if blood amino acid availability decreases. Am J Physiol Endocrinol Metab. 2005 Dec;289(6):E999-1006. doi: 10.1152/ajpendo.00170.2005. Epub 2005 Jul 19.

  PMID: 16030064 RESULT

• Volpi E, Chinkes DL, Rasmussen BB. Sequential muscle biopsies during a 6-h tracer infusion do not affect human mixed muscle protein synthesis and muscle phenylalanine kinetics. Am J Physiol Endocrinol Metab. 2008 Oct;295(4):E959-63. doi: 10.1152/ajpendo.00671.2007. Epub 2008 Aug 19.

  PMID: 18713956 RESULT

• Drummond MJ, Miyazaki M, Dreyer HC, Pennings B, Dhanani S, Volpi E, Esser KA, Rasmussen BB. Expression of growth-related genes in young and older human skeletal muscle following an acute stimulation of protein synthesis. J Appl Physiol (1985). 2009 Apr;106(4):1403-11. doi: 10.1152/japplphysiol.90842.2008. Epub 2008 Sep 11.

  PMID: 18787087 RESULT

• Fujita S, Glynn EL, Timmerman KL, Rasmussen BB, Volpi E. Supraphysiological hyperinsulinaemia is necessary to stimulate skeletal muscle protein anabolism in older adults: evidence of a true age-related insulin resistance of muscle protein metabolism. Diabetologia. 2009 Sep;52(9):1889-98. doi: 10.1007/s00125-009-1430-8. Epub 2009 Jul 9.

  PMID: 19588121 RESULT

• Timmerman KL, Lee JL, Dreyer HC, Dhanani S, Glynn EL, Fry CS, Drummond MJ, Sheffield-Moore M, Rasmussen BB, Volpi E. Insulin stimulates human skeletal muscle protein synthesis via an indirect mechanism involving endothelial-dependent vasodilation and mammalian target of rapamycin complex 1 signaling. J Clin Endocrinol Metab. 2010 Aug;95(8):3848-57. doi: 10.1210/jc.2009-2696. Epub 2010 May 19.

  PMID: 20484484 RESULT

• Timmerman KL, Lee JL, Fujita S, Dhanani S, Dreyer HC, Fry CS, Drummond MJ, Sheffield-Moore M, Rasmussen BB, Volpi E. Pharmacological vasodilation improves insulin-stimulated muscle protein anabolism but not glucose utilization in older adults. Diabetes. 2010 Nov;59(11):2764-71. doi: 10.2337/db10-0415. Epub 2010 Aug 19.

  PMID: 20724580 RESULT

• Drummond MJ, McCarthy JJ, Sinha M, Spratt HM, Volpi E, Esser KA, Rasmussen BB. Aging and microRNA expression in human skeletal muscle: a microarray and bioinformatics analysis. Physiol Genomics. 2011 May 1;43(10):595-603. doi: 10.1152/physiolgenomics.00148.2010. Epub 2010 Sep 28.

  PMID: 20876843 RESULT

• Timmerman KL, Dhanani S, Glynn EL, Fry CS, Drummond MJ, Jennings K, Rasmussen BB, Volpi E. A moderate acute increase in physical activity enhances nutritive flow and the muscle protein anabolic response to mixed nutrient intake in older adults. Am J Clin Nutr. 2012 Jun;95(6):1403-12. doi: 10.3945/ajcn.111.020800. Epub 2012 May 9.

  PMID: 22572647 RESULT

• Drummond MJ, Dickinson JM, Fry CS, Walker DK, Gundermann DM, Reidy PT, Timmerman KL, Markofski MM, Paddon-Jones D, Rasmussen BB, Volpi E. Bed rest impairs skeletal muscle amino acid transporter expression, mTORC1 signaling, and protein synthesis in response to essential amino acids in older adults. Am J Physiol Endocrinol Metab. 2012 May 15;302(9):E1113-22. doi: 10.1152/ajpendo.00603.2011. Epub 2012 Feb 14.

  PMID: 22338078 RESULT

• Drummond MJ, Timmerman KL, Markofski MM, Walker DK, Dickinson JM, Jamaluddin M, Brasier AR, Rasmussen BB, Volpi E. Short-term bed rest increases TLR4 and IL-6 expression in skeletal muscle of older adults. Am J Physiol Regul Integr Comp Physiol. 2013 Aug 1;305(3):R216-23. doi: 10.1152/ajpregu.00072.2013. Epub 2013 Jun 12.

  PMID: 23761639 RESULT

MeSH Terms

Conditions

Sarcopenia

Interventions

Insulin; omega-N-Methylarginine; Nitroprusside

Condition Hierarchy (Ancestors)

Muscular Atrophy; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Arginine; Amino Acids, Basic; Amino Acids; Amino Acids, Diamino; Amino Acids, Essential; Ferricyanides; Cyanides; Anions; Ions; Electrolytes; Inorganic Chemicals; Ferric Compounds; Iron Compounds; Hydrogen Cyanide; Nitrogen Compounds

Study Officials

• Elena Volpi, MD, PhD

  The University of Texas Medical Branch at Galveston

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 27, 2008
• First Posted: June 4, 2008
• Study Start: September 1, 2005
• Primary Completion: August 1, 2012
• Study Completion: August 1, 2012
• Last Updated: December 12, 2016

Record last verified: 2015-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)