{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T14:58:04Z","timestamp":1791212284320,"version":"4.1.0"},"reference-count":32,"publisher":"American Diabetes Association","issue":"11","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2003,11,1]]},"abstract":"<jats:p>OBJECTIVE\u2014We investigated whether autonomic nervous system dysfunction, estimated by slow heart rate recovery (HRR) following cessation of an exercise treadmill test, was associated with increases in insulin and glucose over time and the development of type 2 diabetes.<\/jats:p>\n               <jats:p>RESEARCH DESIGN AND METHODS\u2014Maximal exercise tests were performed by 3,295 healthy adults aged 18\u201330 years in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Repeat measurements of insulin and glucose collected at 7-, 10-, and 15-year examinations were compared by quartiles of HRR (maximum heart rate minus heart rate 2 min after cessation of the test). Incident diabetes was identified at any follow-up examination as glucose \u22657 mmol\/l or the use of diabetes control medication.<\/jats:p>\n               <jats:p>RESULTS\u2014Among participants who did not develop diabetes, fasting insulin concentrations increased from baseline to year 15. Following adjustment (for age, race, sex, smoking status, and BMI), participants with the slowest HRR (quartile 1) had higher fasting insulin at each examination than participants with faster HRR (e.g., year 15 examination: 88.1 vs. 81.3 pmol\/l for quartile 1 vs. quartile 4, respectively, P = 0.05). Glucose did not differ by quartile of HRR at any examination. Among participants with poor fitness, the risk of developing diabetes (n = 98) was 3.4-fold greater (95% CI 1.5\u20138.0) when HRR was &amp;lt;42 vs. &amp;gt;42 bpm. This persisted following adjustment for baseline insulin.<\/jats:p>\n               <jats:p>CONCLUSIONS\u2014Autonomic dysfunction, in combination with poor physical fitness, may be a mechanism associated with early glucose dysmetabolism and the development of diabetes.<\/jats:p>","DOI":"10.2337\/diacare.26.11.3035","type":"journal-article","created":{"date-parts":[[2007,3,5]],"date-time":"2007-03-05T22:51:27Z","timestamp":1173135087000},"page":"3035-3041","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":144,"title":["Influence of Autonomic Nervous System Dysfunction on the Development of Type 2 Diabetes"],"prefix":"10.2337","volume":"26","author":[{"given":"Mercedes R.","family":"Carnethon","sequence":"first","affiliation":[{"name":"Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"David R.","family":"Jacobs","sequence":"additional","affiliation":[{"name":"Division of Epidemiology, School of Public Health, University of Minnesota, Minneapolis, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Sidney","sequence":"additional","affiliation":[{"name":"Division of Research, Kaiser Permanente Medical Care Program, Oakland, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","reference":[{"key":"2022031214271759800_R1","doi-asserted-by":"crossref","unstructured":"Toyry J, Niskanen L, Mantysaari M, Lansimies E, Uusitupa M: Occurrence, predictors, and clinical significance of autonomic neuropathy in NIDDM: ten-year follow-up from the diagnosis. Diabetes\u200845:308\u2013315, 1996","DOI":"10.2337\/diabetes.45.3.308"},{"key":"2022031214271759800_R2","doi-asserted-by":"crossref","unstructured":"Pfeifer MA, Weinberg CR, Cook DL, Reenan A, Halter JB, Ensinck JW, Porte D Jr: Autonomic neural dysfunction in recently diagnosed diabetic subjects. Diabetes Care\u20087: 447\u2013453, 1984","DOI":"10.2337\/diacare.7.5.447"},{"key":"2022031214271759800_R3","doi-asserted-by":"crossref","unstructured":"Lehtinen JM, Uusitupa M, Siitonen O, Pyo\u0308ra\u0308la\u0308 K: Prevalence of neuropathy in newly diagnosed NIDDM and nondiabetic control subjects. Diabetes\u200838: 1307\u20131313, 1989","DOI":"10.2337\/diabetes.38.10.1307"},{"key":"2022031214271759800_R4","doi-asserted-by":"crossref","unstructured":"Panzer C, Lauer MS, Brieke A, Blackstone E, Hoogwerf B: Association of fasting plasma glucose with heart rate recovery in healthy adults: a population-based study. Diabetes\u200851: 803\u2013807, 2002","DOI":"10.2337\/diabetes.51.3.803"},{"key":"2022031214271759800_R5","doi-asserted-by":"crossref","unstructured":"Singh JP, Larson MG, O\u2019Donnell CJ, Wilson PF, Tsuji H, Lloyd-Jones DM, Levy D: Association of hyperglycemia with reduced heart rate variability (the Framingham Heart Study). Am J Cardiol\u200886: 309\u2013312, 2000","DOI":"10.1016\/S0002-9149(00)00920-6"},{"key":"2022031214271759800_R6","doi-asserted-by":"crossref","unstructured":"Seshadri N, Acharya N, Lauer MS: Association of diabetes mellitus with abnormal heart rate recovery in patients without known coronary artery disease. Am J Cardiol\u200891: 108\u2013111, 2003","DOI":"10.1016\/S0002-9149(02)03014-X"},{"key":"2022031214271759800_R7","doi-asserted-by":"crossref","unstructured":"Watkins L, Surwit R, Grossman P, Sherwood A: Is there a glycemic threshold for impaired autonomic control? Diabetes Care\u200823: 826\u2013830, 2000","DOI":"10.2337\/diacare.23.6.826"},{"key":"2022031214271759800_R8","doi-asserted-by":"crossref","unstructured":"Liao D, Cai J, Brancati FL, Folsom A, Barnes RW, Tyroler HA, Heiss G: Association of vagal tone with serum insulin, glucose, and diabetes mellitus: the ARIC study. Diabetes Res Clin Pract\u200830: 211\u2013221, 1995","DOI":"10.1016\/0168-8227(95)01190-0"},{"key":"2022031214271759800_R9","doi-asserted-by":"crossref","unstructured":"Carnethon MR, Golden SH, Folsom AR, Haskell W, Liao D: Prospective investigation of autonomic nervous system function and the development of type 2 diabetes: the Atherosclerosis Risk in Communities study, 1987\u20131998. Circulation\u2008107: 2190\u20132195, 2003","DOI":"10.1161\/01.CIR.0000066324.74807.95"},{"key":"2022031214271759800_R10","doi-asserted-by":"crossref","unstructured":"Van De Borne P, Hausberg M, Hoffman RP, Mark AL, Anderson EA: Hyperinsulinemia produces cardiac vagal withdrawal and nonuniform sympathetic activation in normal subjects. Am J Physiol\u2008276: R178\u2013R183, 1999","DOI":"10.1152\/ajpregu.1999.276.1.R178"},{"key":"2022031214271759800_R11","doi-asserted-by":"crossref","unstructured":"Nonogaki K: New insights into sympathetic regulation of glucose and fat metabolism. Diabetologia\u200843: 533\u2013549, 2000","DOI":"10.1007\/s001250051341"},{"key":"2022031214271759800_R12","doi-asserted-by":"crossref","unstructured":"Shimazu T: Innervation of the liver and glucoregulation: the role of the hypothalamus and autonomic nerves. Nutrition\u200812: 65\u201366 1996","DOI":"10.1016\/0899-9007(96)00060-3"},{"key":"2022031214271759800_R13","doi-asserted-by":"crossref","unstructured":"Reaven GM, Lithell H, Landsberg L: Hypertension and associated metabolic abnormalities: the role of insulin resistance and the sympathoadrenal system. N Engl J Med\u2008334: 374\u2013382, 1996","DOI":"10.1056\/NEJM199602083340607"},{"key":"2022031214271759800_R14","doi-asserted-by":"crossref","unstructured":"Cole CR, Blackstone EH, Pashkow FJ, Snader CE, Lauer MS: Heart-rate recovery immediately after exercise as a predictor of mortality. N Engl J Med\u2008341: 1351\u20131357, 1999","DOI":"10.1056\/NEJM199910283411804"},{"key":"2022031214271759800_R15","doi-asserted-by":"crossref","unstructured":"Cole CR, Foody JM, Blackstone EH, Lauer MS: Heart rate recovery after submaximal exercise testing as a predictor of mortality in a cardiovascularly healthy cohort. Ann Intern Med\u2008132: 552\u2013555, 2000","DOI":"10.7326\/0003-4819-132-7-200004040-00007"},{"key":"2022031214271759800_R16","doi-asserted-by":"crossref","unstructured":"Imai K, Sato H, Hori M, Kusuoka H, Ozaki H, Yokoyama H, Takeda H, Inoue M, Kamada T: Vagally mediated heart rate recovery after exercise is accelerated in athletes but blunted in patients with chronic heart failure. J Am Coll Cardiol\u200824: 1529\u20131535, 1994","DOI":"10.1016\/0735-1097(94)90150-3"},{"key":"2022031214271759800_R17","doi-asserted-by":"crossref","unstructured":"Arai Y, Saul JP, Albrecht P, Hartley LH, Lilly LS, Cohen RJ, Colucci WS: Modulation of cardiac autonomic activity during and immediately after exercise. Am J Physiol\u2008256: H132\u2013H141, 1989","DOI":"10.1152\/ajpheart.1989.256.1.H132"},{"key":"2022031214271759800_R18","doi-asserted-by":"crossref","unstructured":"Friedman GD, Cutter GR, Donahue RP, Hughes GH, Hulley SB, Jacobs DR, Liu K, Savage P: CARDIA: study design, recruitment, and some characteristics of the examined subjects. J Clin Epidemiol\u200841: 1105\u20131116, 1988","DOI":"10.1016\/0895-4356(88)90080-7"},{"key":"2022031214271759800_R19","doi-asserted-by":"crossref","unstructured":"Wilkoff BL, Miller RE: Exercise testing for chronotropic assessment. Cardiol Clin\u200810: 705\u2013717, 1992","DOI":"10.1016\/S0733-8651(18)30211-X"},{"key":"2022031214271759800_R20","doi-asserted-by":"crossref","unstructured":"Sidney S, Haskell WL, Crow R, Sternfeld B, Oberman A, Armstrong MA, Cutter GR, Jacobs DR, Savage PJ, Van Horn L: Symptom-limited graded treadmill exercise testing in young adults in the CARDIA study. Med Sci Sports Exerc\u200824: 177\u2013183, 1992","DOI":"10.1249\/00005768-199202000-00004"},{"key":"2022031214271759800_R21","doi-asserted-by":"crossref","unstructured":"Lauer MS, Francis GS, Okin PM, Pashkow FJ, Snader CE, Marwick TH: Impaired chronotropic response to exercise stress testing as a predictor of mortality. JAMA\u2008281: 524\u2013529, 1999","DOI":"10.1001\/jama.281.6.524"},{"key":"2022031214271759800_R22","doi-asserted-by":"crossref","unstructured":"Ekelund LG, Haskell WL, Johnson JL, Whaley FS, Criqui MH, Sheps DS: Physical fitness as a predictor of cardiovascular mortality in asymptomatic North American men: the Lipid Research Clinics Mortality Follow-up Study. N Engl J Med\u2008319: 1379\u20131384, 1988","DOI":"10.1056\/NEJM198811243192104"},{"key":"2022031214271759800_R23","doi-asserted-by":"crossref","unstructured":"Haffner SM, Bowsher RR, Mykkanen L, Hazuda HP, Mitchell BD, Valdez RA, Gingerich R, Monterrosa A: Proinsulin and specific insulin concentration in high- and low-risk populations for NIDDM. Diabetes\u200843: 1490\u20131493, 1994","DOI":"10.2337\/diabetes.43.12.1490"},{"key":"2022031214271759800_R24","doi-asserted-by":"crossref","unstructured":"Folsom AR, Jacobs DR, Wagenknecht LE, Winkhart SP, Yunis C, Hilner JE, Savage PJ, Smith DE, Flack JM: Increase in fasting insulin and glucose over seven years with increasing weight and inactivity of young adults: the CARDIA study: Coronary Artery Risk Development in Young Adults. Am J Epidemiol\u2008144: 235\u2013246, 1996","DOI":"10.1093\/oxfordjournals.aje.a008918"},{"key":"2022031214271759800_R25","doi-asserted-by":"crossref","unstructured":"Jacobs DR, Hahn L, Haskell WL, Pirie P, Sidney S: Validity and reliability of short physical activity history: CARDIA study and the Minnesota Heart Health Program. J Cardiopulm Rehabil\u20089: 448\u2013459, 1989","DOI":"10.1097\/00008483-198911000-00003"},{"key":"2022031214271759800_R26","unstructured":"Landsberg L: Diet, obesity and hypertension: an hypothesis involving insulin, the sympathetic nervous system, and adaptive thermogenesis. Q J Med\u200861: 1081\u20131090, 1986"},{"key":"2022031214271759800_R27","doi-asserted-by":"crossref","unstructured":"Emdin M, Gastaldelli A, Muscelli E, Macerata A, Natali A, Camastra S, Ferrannini E: Hyperinsulinemia and autonomic nervous system dysfunction in obesity: effects of weight loss. Circulation\u2008103: 513\u2013519, 2001","DOI":"10.1161\/01.CIR.103.4.513"},{"key":"2022031214271759800_R28","doi-asserted-by":"crossref","unstructured":"Vanninen E, Uusitupa M, Lansimies E, Siitonen O, Laitinen J: Effect of metabolic control on autonomic function in obese patients with newly diagnosed type 2 diabetes. Diabet Med\u200810: 66\u201373, 1993","DOI":"10.1111\/j.1464-5491.1993.tb01999.x"},{"key":"2022031214271759800_R29","doi-asserted-by":"crossref","unstructured":"Wei M, Gibbons LW, Mitchell TL, Kampert JB, Lee CD, Blair SN: The association between cardiorespiratory fitness and impaired fasting glucose and type 2 diabetes mellitus in men. Ann Intern Med\u2008130: 89\u201396, 1999","DOI":"10.7326\/0003-4819-130-2-199901190-00002"},{"key":"2022031214271759800_R30","doi-asserted-by":"crossref","unstructured":"Lee CD, Blair SN: Cardiorespiratory fitness and smoking-related and total cancer mortality in men. Med Sci Sports Exerc\u200834: 735\u2013739, 2002","DOI":"10.1097\/00005768-200205000-00001"},{"key":"2022031214271759800_R31","doi-asserted-by":"crossref","unstructured":"Iellamo F, Legramante JM, Pigozzi F, Spataro A, Norbiato G, Lucini D, Pagani M: Conversion from vagal to sympathetic predominance with strenuous training in high-performance world class athletes. Circulation\u2008105: 2719\u20132724, 2002","DOI":"10.1161\/01.CIR.0000018124.01299.AE"},{"key":"2022031214271759800_R32","doi-asserted-by":"crossref","unstructured":"Howard G, Bergman R, Wagenknecht LE, Haffner SM, Savage PJ, Saad MF, Laws A, D\u2019Agostino RB Jr: Ability of alternative indices of insulin sensitivity to predict cardiovascular risk: comparison with the \u201cminimal model\u201d: Insulin Resistance Atherosclerosis Study (IRAS) Investigators. Ann Epidemiol\u20088: 358\u2013369, 1998","DOI":"10.1016\/S1047-2797(98)00002-7"}],"container-title":["Diabetes Care"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/26\/11\/3035\/590356\/dc1103003035.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/26\/11\/3035\/590356\/dc1103003035.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,12]],"date-time":"2022-03-12T14:27:30Z","timestamp":1647095250000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/care\/article\/26\/11\/3035\/22251\/Influence-of-Autonomic-Nervous-System-Dysfunction"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,11,1]]},"references-count":32,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2003,11,1]]}},"URL":"https:\/\/doi.org\/10.2337\/diacare.26.11.3035","relation":{},"ISSN":["0149-5992","1935-5548"],"issn-type":[{"value":"0149-5992","type":"print"},{"value":"1935-5548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,11,1]]}}}