Health Benefits of Aerobic and Resistance Training in Individuals With Type 2 Diabetes (HART-D)

• ClinicalTrials.gov Identifier: NCT00458133
• Recruitment Status: Completed
• First Posted: April 9, 2007
• Last Update Posted: September 15, 2022
• Sponsor: Pennington Biomedical Research Center
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Information provided by (Responsible Party): Pennington Biomedical Research Center

Study Description

Brief Summary:

The goal of the proposed study, Health Benefits of Aerobic and Resistance Training in individuals with type 2 diabetes (HART-D), is to compare the effect of resistance training alone (RT), resistance in combination with aerobic training (AT+RT), and aerobic training alone (AT) to standard care (SC) on hemoglobin A1C (HbA1C), in initially sedentary women and men with type 2 diabetes (T2D).

Condition or disease	Intervention/treatment	Phase
Type 2 Diabetes	Behavioral: exercise	Not Applicable

Detailed Description:

Although it is generally accepted that regular exercise provides substantial health benefits to individuals with T2D, the exact exercise prescription in terms of type (AT versus RT versus AT+RT) still remains an important research issue, particularly in regard to week-to-week glucose control as assessed by HbA1C.

There is a need for more adequately powered and well-controlled studies to examine the effects of RT, AT and AT+RT on HbA1C in individuals with T2D. With the incidence of T2D expected to increase dramatically in the coming years, it is essential to have a better understanding of the relative benefits of various exercise interventions. This information can help better formulate exercise recommendations for patients with T2D as well as potentially provide more exercise options, which is important given the small percentage of individuals with TD2 who regularly exercise. The study group was sedentary women and men with T2D, aged 30 to 75 years. We randomly assigned 262 individuals to an aerobic exercise training only group (AT; n=72), a resistance training only group (RT; n=73), a combination of aerobic plus resistance training (AT+RT; n=76), or a standard care group (SC; n=41). The AT individuals participated in 3 or 4 training sessions each week for 9 months progressing to a total energy expenditure of 12 kcal/kg/week (KKW), which is an exercise dose consistent with the current public health recommendations for physical activity for individuals with T2D. The target exercise intensity was 50%-80% of baseline VO2 max. The RT group participated in 3 sessions per week (9 exercises, 2-3 sets each), which focuses on large muscle groups. This RT regimen is based on the studies that most successfully improved HbA1C in individuals with T2D. Individuals in the AT+RT group completed 10 KKW of aerobic training and a reduced resistance-training regimen of 2 sessions per week (9 exercises, 1 set of each). The AT+RT regimen represents the exercise recommendations of the American College of Sports Medicine (ACSM) and the American Diabetes Association (ADA).

Simply stated, we compared the effect of resistance training alone, resistance in combination with aerobic training, and aerobic training alone to standard care on HbA1C, in initially sedentary women and men with T2D. The primary outcome measure was HbA1C, an integrated measure of blood glucose control over the past 8-12 weeks. Other outcomes of interest included resting blood pressure, C-reactive protein (CRP), total body fat, and lean muscle mass as measured by DEXA, cardiorespiratory fitness, muscular strength, and metabolic measures including serum cholesterol and triglycerides.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 262 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Health Benefits of Aerobic and Resistance Training in Individuals With Type 2 Diabetes
• Study Start Date: April 2007
• Actual Primary Completion Date: March 2010
• Actual Study Completion Date: June 2010

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1; We randomly assigned 72 individuals to an aerobic exercise training only group.	Behavioral: exercise; compared effects on HbA1C on aerobic only, resistance only, combination of aerobic and resistance, and a stretching & relaxing groups.
Experimental: 2; We randomly assigned 73 individuals to an resistance exercise training only group.	Behavioral: exercise; compared effects on HbA1C on aerobic only, resistance only, combination of aerobic and resistance, and a stretching & relaxing groups.
Experimental: 3; We randomly assigned 76 individuals to a combination of aerobic plus resistance training group.	Behavioral: exercise; compared effects on HbA1C on aerobic only, resistance only, combination of aerobic and resistance, and a stretching & relaxing groups.
Placebo Comparator: 4; We randomly assigned 41 individuals to a stretching and relaxation group.	Behavioral: exercise; compared effects on HbA1C on aerobic only, resistance only, combination of aerobic and resistance, and a stretching & relaxing groups.

Outcome Measures

Primary Outcome Measures :

1. Hemoglobin A1C [ Time Frame: at 9 months ]

Secondary Outcome Measures :

1. Fasting glucose [ Time Frame: at 9 months ]
2. Basal insulin [ Time Frame: at 9 months ]
3. Resting blood pressure [ Time Frame: at 9 months ]
4. C reactive protein [ Time Frame: at 9 months ]
5. Visceral adiposity [ Time Frame: at 9 months ]
6. Body Composition [ Time Frame: at 9 months ]
7. Cardiorespiratory fitness [ Time Frame: at 9 months ]
8. Muscular strength [ Time Frame: at 9 months ]
9. metabolic measures, including serum cholesterol and triglycerides [ Time Frame: at 9 months ]

Eligibility Criteria

• Ages Eligible for Study: 30 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Age 30-75 years
• type 2 diabetes determined by self-report with verification
• 6.5% < HbA1C < 11%
• sedentary lifestyle - not being physically active greater than or equal to 3 days per week for 20 minutes each time for the previous 6 months, and not performing regular resistance exercise

Exclusion Criteria:

• inadequate control of co-morbid conditions
• resting blood pressure greater than or equal to 160/100 mm Hg
• Triglycerides greater than or equal to 500 mg/dL
• BMI is greater than or equal to 48
• current use of an insulin pump or insulin injections other than Lantus
• metal object in the body that may interfere with MRI/MRS scans

• factors that may limit adherence to intervention or affect conduct of the trial

  1. unable or unwilling to communicate with staff, to provide written informed consent, or accept the randomized assignment
  2. failure to complete behavioral run-in and baseline testing
  3. hospitalization for depression in the last 6 months
  4. not physically capable of performing the exercise required for the study protocols
  5. consuming > 14 alcoholic beverages per week
  6. plans to be away > 4 weeks in the next 9 months
  7. lack of support from primary health care provider or family members
  8. significant weight loss in the past year (>20 lbs) or current use of weight loss medications
  9. current diagnosis of schizophrenia, other psychotic disorders, or bipolar disorder
  10. another member of household is a participant or staff member of HART-D
  11. bariatric surgery
  12. other temporary intervening event, such as sick spouse, bereavement, or recent move
  13. other medical, psychiatric, or behavioral limitations that, in the view of the principal investigator, may interfere with study participation or the ability to follow the intervention protocol

• underlying diseases or conditions likely to limit lifespan and/or affect the safety of the intervention

  1. pregnant or plan on becoming pregnant in the next 9 months
  2. cancers requiring treatment in the past 5 years, unless prognosis is excellent
  3. self-reported HIV or tuberculosis
  4. history or evidence of serious arrythmias, cardiomyopathy, congestive heart failure, aortic aneurysm, or heart transplantation
  5. renal disease: urine dipstick 4+ protein, serum creatinine is greater than or equal to 1.4 mg/dL (women) or is greater than or equal to 1.5 mg/dL (men) or currently receiving dialysis
  6. any other medical condition or disease that is life threatening or that can interfere with or be aggravated by exercise
  7. advanced neuropathy or retinopathy

Contacts and Locations

Locations

United States, Louisiana

Pennington Biomedical Research Center

Baton Rouge, Louisiana, United States, 70817

Sponsors and Collaborators

Pennington Biomedical Research Center

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

• Principal Investigator: Timothy S Church, MPH, MD, PhD; Pennington Biomedical Research Center

More Information

Publications of Results:

Church TS, Blair SN, Cocreham S, Johannsen N, Johnson W, Kramer K, Mikus CR, Myers V, Nauta M, Rodarte RQ, Sparks L, Thompson A, Earnest CP. Effects of aerobic and resistance training on hemoglobin A1c levels in patients with type 2 diabetes: a randomized controlled trial. JAMA. 2010 Nov 24;304(20):2253-62. doi: 10.1001/jama.2010.1710. Erratum In: JAMA. 2011 Mar 2;305(9):892.

Swift DL, Johannsen NM, Earnest CP, Blair SN, Church TS. Effect of exercise training modality on C-reactive protein in type 2 diabetes. Med Sci Sports Exerc. 2012 Jun;44(6):1028-34. doi: 10.1249/MSS.0b013e31824526cc.

Swift DL, Johannsen NM, Myers VH, Earnest CP, Smits JA, Blair SN, Church TS. The effect of exercise training modality on serum brain derived neurotrophic factor levels in individuals with type 2 diabetes. PLoS One. 2012;7(8):e42785. doi: 10.1371/journal.pone.0042785. Epub 2012 Aug 6.

Other Publications:

Zinman B, Ruderman N, Campaigne BN, Devlin JT, Schneider SH; American Diabetes Association. Physical activity/exercise and diabetes mellitus. Diabetes Care. 2003 Jan;26 Suppl 1:S73-7. doi: 10.2337/diacare.26.2007.s73. No abstract available.

Albright A, Franz M, Hornsby G, Kriska A, Marrero D, Ullrich I, Verity LS. American College of Sports Medicine position stand. Exercise and type 2 diabetes. Med Sci Sports Exerc. 2000 Jul;32(7):1345-60. doi: 10.1097/00005768-200007000-00024.

Hamdy O, Goodyear LJ, Horton ES. Diet and exercise in type 2 diabetes mellitus. Endocrinol Metab Clin North Am. 2001 Dec;30(4):883-907. doi: 10.1016/s0889-8529(05)70220-6.

Kelley DE, Goodpaster BH. Effects of exercise on glucose homeostasis in Type 2 diabetes mellitus. Med Sci Sports Exerc. 2001 Jun;33(6 Suppl):S495-501; discussion S528-9. doi: 10.1097/00005768-200106001-00020.

Nelson KM, Reiber G, Boyko EJ; NHANES III. Diet and exercise among adults with type 2 diabetes: findings from the third national health and nutrition examination survey (NHANES III). Diabetes Care. 2002 Oct;25(10):1722-8. doi: 10.2337/diacare.25.10.1722.

Khaw KT, Wareham N, Luben R, Bingham S, Oakes S, Welch A, Day N. Glycated haemoglobin, diabetes, and mortality in men in Norfolk cohort of european prospective investigation of cancer and nutrition (EPIC-Norfolk). BMJ. 2001 Jan 6;322(7277):15-8. doi: 10.1136/bmj.322.7277.15.

Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998 Sep 12;352(9131):837-53. Erratum In: Lancet 1999 Aug 14;354(9178):602.

Boule NG, Haddad E, Kenny GP, Wells GA, Sigal RJ. Effects of exercise on glycemic control and body mass in type 2 diabetes mellitus: a meta-analysis of controlled clinical trials. JAMA. 2001 Sep 12;286(10):1218-27. doi: 10.1001/jama.286.10.1218.

Ishii T, Yamakita T, Sato T, Tanaka S, Fujii S. Resistance training improves insulin sensitivity in NIDDM subjects without altering maximal oxygen uptake. Diabetes Care. 1998 Aug;21(8):1353-5. doi: 10.2337/diacare.21.8.1353.

Baldi JC, Snowling N. Resistance training improves glycaemic control in obese type 2 diabetic men. Int J Sports Med. 2003 Aug;24(6):419-23. doi: 10.1055/s-2003-41173.

Castaneda C, Layne JE, Munoz-Orians L, Gordon PL, Walsmith J, Foldvari M, Roubenoff R, Tucker KL, Nelson ME. A randomized controlled trial of resistance exercise training to improve glycemic control in older adults with type 2 diabetes. Diabetes Care. 2002 Dec;25(12):2335-41. doi: 10.2337/diacare.25.12.2335.

Dunstan DW, Daly RM, Owen N, Jolley D, De Courten M, Shaw J, Zimmet P. High-intensity resistance training improves glycemic control in older patients with type 2 diabetes. Diabetes Care. 2002 Oct;25(10):1729-36. doi: 10.2337/diacare.25.10.1729.

Kumar S, Boulton AJ, Beck-Nielsen H, Berthezene F, Muggeo M, Persson B, Spinas GA, Donoghue S, Lettis S, Stewart-Long P. Troglitazone, an insulin action enhancer, improves metabolic control in NIDDM patients. Troglitazone Study Group. Diabetologia. 1996 Jun;39(6):701-9. doi: 10.1007/BF00418542. Erratum In: Diabetologia 1996 Oct;39(10):1245.

Hanley AJ, Williams K, Stern MP, Haffner SM. Homeostasis model assessment of insulin resistance in relation to the incidence of cardiovascular disease: the San Antonio Heart Study. Diabetes Care. 2002 Jul;25(7):1177-84. doi: 10.2337/diacare.25.7.1177.

Katsuki A, Sumida Y, Gabazza EC, Murashima S, Furuta M, Araki-Sasaki R, Hori Y, Yano Y, Adachi Y. Homeostasis model assessment is a reliable indicator of insulin resistance during follow-up of patients with type 2 diabetes. Diabetes Care. 2001 Feb;24(2):362-5. doi: 10.2337/diacare.24.2.362.

Dumortier M, Brandou F, Perez-Martin A, Fedou C, Mercier J, Brun JF. Low intensity endurance exercise targeted for lipid oxidation improves body composition and insulin sensitivity in patients with the metabolic syndrome. Diabetes Metab. 2003 Nov;29(5):509-18. doi: 10.1016/s1262-3636(07)70065-4.

Helge JW. Prolonged adaptation to fat-rich diet and training; effects on body fat stores and insulin resistance in man. Int J Obes Relat Metab Disord. 2002 Aug;26(8):1118-24. doi: 10.1038/sj.ijo.0802058.

Miyatake N, Takahashi K, Wada J, Nishikawa H, Morishita A, Suzuki H, Kunitomi M, Makino H, Kira S, Fujii M. Daily exercise lowers blood pressure and reduces visceral adipose tissue areas in overweight Japanese men. Diabetes Res Clin Pract. 2003 Dec;62(3):149-57. doi: 10.1016/s0168-8227(03)00176-1.

Stewart KJ. Exercise training and the cardiovascular consequences of type 2 diabetes and hypertension: plausible mechanisms for improving cardiovascular health. JAMA. 2002 Oct 2;288(13):1622-31. doi: 10.1001/jama.288.13.1622.

Grossman E, Messerli FH, Goldbourt U. High blood pressure and diabetes mellitus: are all antihypertensive drugs created equal? Arch Intern Med. 2000 Sep 11;160(16):2447-52. doi: 10.1001/archinte.160.16.2447.

Kelley GA, Kelley KA, Tran ZV. Aerobic exercise and resting blood pressure: a meta-analytic review of randomized, controlled trials. Prev Cardiol. 2001 Spring;4(2):73-80. doi: 10.1111/j.1520-037x.2001.00529.x.

Leon AS, Sanchez OA. Response of blood lipids to exercise training alone or combined with dietary intervention. Med Sci Sports Exerc. 2001 Jun;33(6 Suppl):S502-15; discussion S528-9. doi: 10.1097/00005768-200106001-00021.

Taylor PA, Ward A. Women, high-density lipoprotein cholesterol, and exercise. Arch Intern Med. 1993 May 24;153(10):1178-84.

Durstine JL, Haskell WL. Effects of exercise training on plasma lipids and lipoproteins. Exerc Sport Sci Rev. 1994;22:477-521. No abstract available.

Maiorana A, O'Driscoll G, Goodman C, Taylor R, Green D. Combined aerobic and resistance exercise improves glycemic control and fitness in type 2 diabetes. Diabetes Res Clin Pract. 2002 May;56(2):115-23. doi: 10.1016/s0168-8227(01)00368-0.

Dunstan DW, Puddey IB, Beilin LJ, Burke V, Morton AR, Stanton KG. Effects of a short-term circuit weight training program on glycaemic control in NIDDM. Diabetes Res Clin Pract. 1998 Apr;40(1):53-61. doi: 10.1016/s0168-8227(98)00027-8.

Eriksson J, Taimela S, Eriksson K, Parviainen S, Peltonen J, Kujala U. Resistance training in the treatment of non-insulin-dependent diabetes mellitus. Int J Sports Med. 1997 May;18(4):242-6. doi: 10.1055/s-2007-972627.

Honkola A, Forsen T, Eriksson J. Resistance training improves the metabolic profile in individuals with type 2 diabetes. Acta Diabetol. 1997 Dec;34(4):245-8. doi: 10.1007/s005920050082.

Haffner SM. Insulin resistance, inflammation, and the prediabetic state. Am J Cardiol. 2003 Aug 18;92(4A):18J-26J. doi: 10.1016/s0002-9149(03)00612-x.

Ridker PM, Hennekens CH, Buring JE, Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med. 2000 Mar 23;342(12):836-43. doi: 10.1056/NEJM200003233421202.

Ridker PM. High-sensitivity C-reactive protein: potential adjunct for global risk assessment in the primary prevention of cardiovascular disease. Circulation. 2001 Apr 3;103(13):1813-8. doi: 10.1161/01.cir.103.13.1813.

Church TS, Barlow CE, Earnest CP, Kampert JB, Priest EL, Blair SN. Associations between cardiorespiratory fitness and C-reactive protein in men. Arterioscler Thromb Vasc Biol. 2002 Nov 1;22(11):1869-76. doi: 10.1161/01.atv.0000036611.77940.f8.

Nguyen-Duy TB, Nichaman MZ, Church TS, Blair SN, Ross R. Visceral fat and liver fat are independent predictors of metabolic risk factors in men. Am J Physiol Endocrinol Metab. 2003 Jun;284(6):E1065-71. doi: 10.1152/ajpendo.00442.2002. Epub 2003 Jan 28.

Mourier A, Gautier JF, De Kerviler E, Bigard AX, Villette JM, Garnier JP, Duvallet A, Guezennec CY, Cathelineau G. Mobilization of visceral adipose tissue related to the improvement in insulin sensitivity in response to physical training in NIDDM. Effects of branched-chain amino acid supplements. Diabetes Care. 1997 Mar;20(3):385-91. doi: 10.2337/diacare.20.3.385.

Kohl HW 3rd, Dunn AL, Marcus BH, Blair SN. A randomized trial of physical activity interventions: design and baseline data from project active. Med Sci Sports Exerc. 1998 Feb;30(2):275-83. doi: 10.1097/00005768-199802000-00016.

Blair SN, Applegate WB, Dunn AL, Ettinger WH, Haskell WL, King AC, Morgan TM, Shih JA, Simons-Morton DG. Activity Counseling Trial (ACT): rationale, design, and methods. Activity Counseling Trial Research Group. Med Sci Sports Exerc. 1998 Jul;30(7):1097-106. doi: 10.1097/00005768-199807000-00012.

Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985 Jul;28(7):412-9. doi: 10.1007/BF00280883.

Smutok MA, Reece C, Kokkinos PF, Farmer C, Dawson P, Shulman R, DeVane-Bell J, Patterson J, Charabogos C, Goldberg AP, et al. Aerobic versus strength training for risk factor intervention in middle-aged men at high risk for coronary heart disease. Metabolism. 1993 Feb;42(2):177-84. doi: 10.1016/0026-0495(93)90032-j.

Smutok MA, Reece C, Kokkinos PF, Farmer CM, Dawson PK, DeVane J, Patterson J, Goldberg AP, Hurley BF. Effects of exercise training modality on glucose tolerance in men with abnormal glucose regulation. Int J Sports Med. 1994 Aug;15(6):283-9. doi: 10.1055/s-2007-1021061.

Physical activity and cardiovascular health. NIH Consensus Development Panel on Physical Activity and Cardiovascular Health. JAMA. 1996 Jul 17;276(3):241-6.

Surgeon General's report on physical activity and health. From the Centers for Disease Control and Prevention. JAMA. 1996 Aug 21;276(7):522. No abstract available.

Snyder KA, Donnelly JE, Jabobsen DJ, Hertner G, Jakicic JM. The effects of long-term, moderate intensity, intermittent exercise on aerobic capacity, body composition, blood lipids, insulin and glucose in overweight females. Int J Obes Relat Metab Disord. 1997 Dec;21(12):1180-9. doi: 10.1038/sj.ijo.0800533.

Willey KA, Singh MA. Battling insulin resistance in elderly obese people with type 2 diabetes: bring on the heavy weights. Diabetes Care. 2003 May;26(5):1580-8. doi: 10.2337/diacare.26.5.1580.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Senechal M, Johannsen NM, Swift DL, Earnest CP, Lavie CJ, Blair SN, Church TS. Association between Changes in Muscle Quality with Exercise Training and Changes in Cardiorespiratory Fitness Measures in Individuals with Type 2 Diabetes Mellitus: Results from the HART-D Study. PLoS One. 2015 Aug 7;10(8):e0135057. doi: 10.1371/journal.pone.0135057. eCollection 2015.

Pandey A, Swift DL, McGuire DK, Ayers CR, Neeland IJ, Blair SN, Johannsen N, Earnest CP, Berry JD, Church TS. Metabolic Effects of Exercise Training Among Fitness-Nonresponsive Patients With Type 2 Diabetes: The HART-D Study. Diabetes Care. 2015 Aug;38(8):1494-501. doi: 10.2337/dc14-2378. Epub 2015 Jun 17.

Henagan TM, Stewart LK, Forney LA, Sparks LM, Johannsen N, Church TS. PGC1alpha -1 Nucleosome Position and Splice Variant Expression and Cardiovascular Disease Risk in Overweight and Obese Individuals. PPAR Res. 2014;2014:895734. doi: 10.1155/2014/895734. Epub 2014 Dec 28.

Johannsen NM, Swift DL, Lavie CJ, Earnest CP, Blair SN, Church TS. Categorical analysis of the impact of aerobic and resistance exercise training, alone and in combination, on cardiorespiratory fitness levels in patients with type 2 diabetes: results from the HART-D study. Diabetes Care. 2013 Oct;36(10):3305-12. doi: 10.2337/dc12-2194. Epub 2013 Jul 22.

Johannsen NM, Sparks LM, Zhang Z, Earnest CP, Smith SR, Church TS, Ravussin E. Determinants of the Changes in Glycemic Control with Exercise Training in Type 2 Diabetes: A Randomized Trial. PLoS One. 2013 Jun 21;8(6):e62973. doi: 10.1371/journal.pone.0062973. Print 2013.

Senechal M, Swift DL, Johannsen NM, Blair SN, Earnest CP, Lavie CJ, Church TS. Changes in body fat distribution and fitness are associated with changes in hemoglobin A1c after 9 months of exercise training: results from the HART-D study. Diabetes Care. 2013 Sep;36(9):2843-9. doi: 10.2337/dc12-2428. Epub 2013 May 13.

• Responsible Party: Pennington Biomedical Research Center
• ClinicalTrials.gov Identifier: NCT00458133
• Other Study ID Numbers: PBRC 26046; R01DK068298 ( U.S. NIH Grant/Contract )
• First Posted: April 9, 2007
• Last Update Posted: September 15, 2022
• Last Verified: September 2022

Keywords provided by Pennington Biomedical Research Center:

aerobic exercise; resistance exercise; type 2 diabetes; hemoglobin A1C; exercise

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 2; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases