Insulin resistance: A risk marker for disease and disability in the older person

Diabetic Medicine

Volumn 30, Issue 5, 2013, Pages 535-548

  Krentz, A J ^a,b   Viljoen, A ^a,c   Sinclair, A ^a  

^a UNIVERSITY OF BEDFORDSHIRE   (United Kingdom)

^b Profil Institute for Clinical Research   (United States)

^c LISTER HOSPITAL   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

2,4 THIAZOLIDINEDIONE DERIVATIVE; ADIPOCYTOKINE; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; BIGUANIDE DERIVATIVE; CORTICOSTEROID; GHRELIN; HUMAN INSULIN; IMMUNOSUPPRESSIVE AGENT; INSULIN; INSULIN GLARGINE; INSULIN SENSITIZING AGENT; MELATONIN; METFORMIN; MURAGLITAZAR; PIOGLITAZONE; RAPAMYCIN; RESVERATROL; SEX HORMONE;

AGED; AGING; ATHEROSCLEROSIS; BLADDER CANCER; BODY COMPOSITION; BONE DISEASE; BROWN ADIPOSE TISSUE; CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; CARDIOVASCULAR SYMPTOM; COGNITION; DEMENTIA; DISABILITY; DRUG EFFECT; EYE DISEASE; HUMAN; HYPERINSULINEMIA; INSULIN RESISTANCE; INSULIN SENSITIVITY; LIFE EXPECTANCY; LIFESTYLE; LONGEVITY; MALIGNANT NEOPLASTIC DISEASE; MITOCHONDRION; MUSCLE ATROPHY; NEOPLASM; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OBESITY; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; RISK FACTOR; SIDE EFFECT; THROMBOSIS; WEIGHT GAIN;

AGED; AGING; BIOLOGICAL MARKERS; CORONARY ARTERY DISEASE; DIABETES MELLITUS, TYPE 2; DIABETIC ANGIOPATHIES; DISABILITY EVALUATION; DISEASE PROGRESSION; FEMALE; HUMANS; INSULIN RESISTANCE; MALE; OBESITY; PREDICTIVE VALUE OF TESTS; RISK FACTORS; SENTINEL SURVEILLANCE; THIAZOLIDINEDIONES;

EID: 84876361745     PISSN: 07423071     EISSN: 14645491     Source Type: Journal    
DOI: 10.1111/dme.12063     Document Type: Review

References (132)

1. Facchini FS, Hua N, Abbasi F, Reaven GM. Insulin resistance as a predictor of age-related diseases. J Clin Endocrinol Metab 2001; 86: 3574-3578.
2. Nigro J, Osman N, Dart AM, Little PJ. Insulin resistance and atherosclerosis. Endocr Rev 2006; 27: 242-259.
3. Draznin B. Mitogenic action of insulin: friend, foe or 'frenemy'? Diabetologia 2010; 53: 229-233.
4. Kinsella Kevin, Wan He U.S. Census Bureau, International Population Reports, P95/09-1, An Aging World: 2008, U.S. Government Printing Office, Washington, DC, 2009.
5. Kim SH, Reaven G. Obesity and insulin resistance: an ongoing saga. Diabetes 2010; 59: 2105-2106.
6. Kohrt WM, Kirwan JP, Staten MA, Bourey RE, King DS, Holloszy JO. Insulin resistance is related to abdominal obesity. Diabetes 1993; 42: 273-281.
7. Eckel RH, Alberti KG, Grundy SM, Zimmet PZ. The metabolic syndrome. Lancet 2010; 375: 181-183.
8. Hardy OT, Czech MP, Corvera S. What causes the insulin resistance underlying obesity? Curr Opin Endocrinol Diabetes Obes 2012; 19: 81-87.
9. Kim SH, Reaven GM. Insulin resistance and hyperinsulinemia. Diabetes Care 2008; 31: 1433-1438.
10. Barzilay JI, Stein PK. Association of the metabolic syndrome with age-related, non-atherosclerotic, chronic medical conditions. Metab Syndr Relat Disord 2011; 9: 327-335.
11. Fadini GP, Ceolotto G, Pagnin E, de Kreutzenberg S, Avogaro A. At the crossroads of longevity and metabolism: the metabolic syndrome and lifespan determinant pathways. Aging Cell 2011; 10: 10-17.
12. Bourdel-Marchasson I, Helmer C, Fagot-Campagna A, Dehail P, Joseph PA. Disability and quality of life in elderly people with diabetes. Diabetes Metab 2007; 33: S66-74.
13. Cowie CC, Rust KF, Byrd-Holt DD, Eberhardt MS, Flegal KM, Engelgau MM et al. Prevalence of diabetes and impaired fasting glucose in adults in the US population: National Health And Nutrition Examination Survey 1999-2002. Diabetes Care 2006; 29: 1263-1268.
14. Centers for Disease Control and Prevention. Percentage of Civilian, Noninstitutionalized Population with Diagnosed Diabetes, by Age, United States, 1980-2010. Available at http://www.cdc.gov/diabetes/statistics/prev/national/figbyage.htm Last accessed 18 October 2012.
15. Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 2004; 27: 1047-1053.
16. Fagot-Campagna A, Bourdel-Marchasson I, Simon D. Burden of diabetes in an aging population: prevalence, incidence, mortality, characteristics and quality of care. Diabetes Metab 2005; 31: 5S35-5S52.
17. Scheen AJ. Diabetes mellitus in the elderly: insulin resistance and/or impaired insulin secretion? Diabetes Metab 2005; 31: 5S27-5S34.
18. Muller DC, Elahi D, Tobin JD, Andres R. Insulin response during the oral glucose tolerance test: the role of age, sex, body fat and the pattern of fat distribution. Aging (Milano) 1996; 8: 13-21.
19. Chen M, Bergman RN, Pacini G, Porte D Jr. Pathogenesis of age-related glucose intolerance in man: insulin resistance and decreased beta-cell function. J Clin Endocrinol Metab 1985; 60: 13-20.
20. Chang A, Halter JB. Aging and insulin secretion. Am J Physiol Endocrinol Metab 2003; 284: E7-E12.
21. Fink RI, Kolterman OG, Griffin J, Olefsky JM. Mechanisms of insulin resistance in aging. J Clin Invest 1983; 71: 1523-1535.
22. Ferrannini E, Vichi S, Beck-Nielsen H, Laakso M, Paolisso G, Smith U. Insulin action and age. European Group for the Study of Insulin Resistance (EGIR). Diabetes 1996; 45: 947-953.
23. Petersen KF, Befroy D, Dufour S, Dziura J, Ariyan C, Rothman DL et al. Mitochondrial dysfunction in the elderly: possible role in insulin resistance. Science 2003; 300: 1140-1142.
24. Phielix E, Szendroedi J, Roden M. Mitochondrial function and insulin resistance during aging - a mini-review. Gerontology 2011; 57: 387-396.
25. Lee HC, Wie YH. Mitochondria and aging. Adv Exp Med Biol 2012; 942: 311-327.
26. Puddu P, Puddu G, Cravero E, De Pascalis S, Muscari A. The emerging role of cardiovascular risk factor-induced mitochondrial dysfunction in athogenesis. J Biomed Sci 2009; 16: 112.
27. Nishigaki Y, Fuku N, Tanaka M. Mitochondrial haplotypes associated with lifestyle-related diseases and longevity in the Japanese population. Geriatr Gerontol Int 2010; 10: S221-235.
28. Waters DL, Baumgartner RN. Sarcopenia and obesity. Clin Geriatr Med 2011; 27: 401-421.
29. Narici MV, Maffulli N. Sarcopenia: characteristics, mechanisms and functional significance. Br Med Bull 2010; 95: 139-159.
30. Amati F, Dube JJ, Coen PM, Stafanovi-Racic M, Toledo FGS, Goodpaster BH. Physical inactivity and obesity underlie the insulin resistance of aging. Diabetes Care 2009; 32: 1547-1549.
31. Basu R, Breda E, Oberg AL, Powell CC, Dalla Man C, Basu A et al. Mechanisms of the age-associated deterioration in glucose tolerance: contribution of alterations in insulin secretion, action, and clearance. Diabetes. 2003; 52: 1738-48.
32. Coon PJ, Rogus EM, Drinkwater D, Muller DC, Goldberg AP. Role of body fat distribution in the decline in insulin sensitivity and glucose tolerance with age. J Clin Endocrinol Metab 1992; 75: 1125-1132.
33. Szendroedi J, Roden M. Ectopic lipids and organ function. Curr Opin Lipidol 2009; 20: 50-56.
34. Cusi K. Role of insulin resistance and lipotoxicity in non-alcoholic steatohepatitis. Clin Liver Dis 2009; 13: 545-563.
35. Gastaldelli A, Basta G. Ectopic fat and cardiovascular disease: what is the link? Nutr Metab Cardiovasc Dis 2010; 20: 481-490.
36. Lazo M, Clark JM. The epidemiology of nonalcoholic fatty liver disease: a global perspective. Semin Liver Dis 2008; 28: 339-350.
37. Blüher M. The distinction of metabolically 'healthy' from 'unhealthy' obese individuals. Curr Opin Lipidol 2010; 21: 38-43.
38. Gustafson B. Adipose tissue, inflammation and atherosclerosis. J Atheroscler Thromb 2010; 17: 332-341.
39. Arai Y, Takayama M, Abe Y, Hirose N. Adipokines and aging. J Atheroscler Thromb 2011; 18: 545-550.
40. Taube A, Schlich R, Sell H, Eckardt K, Eckel J. Inflammation and metabolic dysfunction: links to cardiovascular diseases. Am J Physiol Heart Circ Physiol 2012; 302: H2148-2165.
41. Virtanen KA, Nuutila P. Brown adipose tissue in humans. Curr Opin Lipidol 2011; 22: 49-54.
42. Orava J, Nuutila P, Lidell ME, Oikonen V, Noponen T, Viljanen T et al. Different metabolic responses of human brown adipose tissue to activation by cold and insulin. Cell Metab 2011; 14: 272-279.
43. Mattson MP. Perspective: does brown fat protect against diseases of aging? Ageing Res Rev 2010; 9: 69-76.
44. Boss O, Farmer SR. Recruitment of brown adipose tissue as a therapy for obesity-associated disease. Front Endocrinol 2012; 3: 14.
45. Abellan van Kan G, Rolland Y, Bergman H, Morley JE, Kritchevsky SB, Vellas B. The I.A.N.A. Task Force on frailty assessment of older people in clinical practice. J Nutr Health Aging 2008; 12: 29-37.
46. Wang C, Bai L. Sarcopenia in the elderly: basic and clinical issues. Geriatr Gerontol Int 2012; 12: 388-396.
47. Sakuma K, Yamaguchi A. Sarcopenia and age-related endocrine function. Int J Endocrinol 2012; 2012: 127362.
48. Abbatecola AM, Paolisso G. Is there a relationship between insulin resistance and frailty syndrome? Curr Pharm Des 2008; 14: 405-410.
49. Johannsen DL, Conley KE, Bajpeyi S, Punyanitya M, Gallagher D, Zhang Z et al. Ectopic lipid accumulation and reduced glucose tolerance in elderly adults are accompanied by altered skeletal muscle mitochondrial activity. J Clin Endocrinol Metab 2012; 97: 242-250.
50. Pedersen BK, Febbraio MA. Muscles, exercise and obesity: muscle as a secretory organ. Nat Rev Endocrinol 2012; 8: 457-652012.
51. Castillo-Quan JI. From white to brown fat through the PCG-1α-dependent myokine irisin. Dis Model Mech 2012; 5: 293-295.
52. Aagard P, Suetta C, Caserotti P, Magnusson SP, Kjaer M. Role of the nervous system in sarcopenia and muscle atrophy with aging: strength training as a countermeasure. Scand J Sci Sports 2010; 20: 49-64.
53. Adamo ML, Farrar RP. Resistance training, and IGF involvement in the maintenance of muscle mass during the aging process. Ageing Res Rev 2006; 5: 310-331.
54. Kim JS, Wilson JM, Lee SR. Dietary implications on mechanisms of sarcopenia: role of proteins, amino acids and antioxidants. J Nutr Biochem 2010; 21: 1-13.
55. Wilson GJ, Wilson JM, Manninen AH. Effects of beta-hydroxy-beta-methylbutyrate (HMB) on exercise performance and body composition across varying levels of age, sex, and training experience: a review. Nutr Metab 2008; 3; 5:1.
56. Rothwell PM, Coull AJ, Silver LE, Fairhead JF, Giles MF, Lovelock CE et al. Population-based study of event-rate, incidence, case fatality, and mortality for all acute vascular events in all arterial territories (Oxford Vascular Study). Lancet 2005; 366: 1773-1783.
57. DeFronzo RA. Insulin resistance, lipotoxicity, type 2 diabetes and atherosclerosis: the missing links. The Claude Bernard Lecture 2009. Diabetologia 2010; 53: 1270-1287.
58. Laakso M. Cardiovascular disease in type 2 diabetes from population to man to mechanisms: the Kelly West Award Lecture 2008. Diabetes Care 2010; 33: 442-449.
59. Beckman JA, Creager MA, Libby P. Diabetes and atherosclerosis: epidemiology, pathophysiology, and management. J Am Med Assoc 2002; 287: 2570-2581.
60. Viljoen A, Sinclair AJ. Diabetes and insulin resistance in older people. Med Clin North Am 2011; 95: 615-629.
61. 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; 25: 1177-1184.
62. Kahn R, Buse J, Ferrannini E, Stern M, American Diabetes Association; European Association for the Study of Diabetes. The metabolic syndrome: time for a critical appraisal: joint statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2005; 28: 2289-2304.
63. Meigs JB. Epidemiology of type 2 diabetes and cardiovascular disease: translation from population to prevention. Diabetes Care 2010; 33: 1865-1871.
64. Bechtold M, Palmer J, Valtos J, Iasiello C, Sowers J. Metabolic syndrome in the elderly. Curr Diab Rep 2006; 6: 64-71.
65. Maggi S, Noale M, Gallina P, Bianchi D, Marzari C, Limongi F, Crepaldi G, ILSA Working Group. Metabolic syndrome, diabetes, and cardiovascular disease in an elderly Caucasian cohort: the Italian Longitudinal Study on Aging. J Gerontol A Biol Sci Med Sci 2006; 61: 505-510.
66. Sattar N, McConnachie A, Shaper AG, Blauw GJ, Buckley BM, de Craen AJ et al. Can metabolic syndrome usefully predict cardiovascular disease and diabetes: outcomes data from two prospective studies. Lancet 2008; 371: 1927-193.
67. Manzato E, Romanato G, Zambon S, Corti MC, Baggio G, Sartori L et al. Metabolic syndrome and cardiovascular disease in the elderly: the Progetto Veneto Anziani (Pro.V.A.) study. Aging Clin Exp Res 2008; 20: 47-52.
68. Polotsky HN, Polotsky AJ. Metabolic implications of menopause. Semin Reprod Med 2010; 28: 426-434.
69. Guarner-Lans V, Rubio-Ruiz ME, Pérez-Torres I, Baños de MacCarthy G. Relation of aging and sex hormones to metabolic syndrome and cardiovascular disease. Exp Gerontol 2011; 46: 517-523.
70. Tajar A, Huhtaniemi IT, O'Neill TW, Finn JD, Pye SR, Lee DM et al., EMAS Group Characteristics of androgen deficiency in late-onset hypogonadism: results from the European Male Aging Study (EMAS). J Clin Endocrinol Metab 2012; 97: 1508-1516.
71. Sam S, Dunaif A. Polycystic ovary syndrome: syndrome XX? Trends Endocrinol Metab 2003; 14: 365-370.
72. Krentz AJ, von Mühlen D, Barrett-Connor E. Searching for polycystic ovary syndrome in postmenopausal women: evidence for a dose-effects association with prevalent cardiovascular disease. Menopause 2007; 14: 284-292.
73. Schmidt J, Landin-Wilhelmsen K, Brännström M, Dahlgren E. Cardiovascular disease and risk factors in PCOS women of postmenopausal age: a 21-year controlled follow-up study. J Clin Endocrinol Metab 2011; 96: 3794-3803.
74. Arai Y, Kojima T, Takayama M, Hirose N. The metabolic syndrome, IGF-1, and insulin action. Mol Cell Endocrinol 2009; 299: 124-128.
75. Hardeland R. Melatonin in aging and disease - multiple conseqeunces of reduced secretion, options and limits of treatment. Aging Dis 2012; 3: 194-225.
76. Van Cauter E. Sleep disturbances and insulin resistance. Diabet Med 2011; 28: 1455-1462.
77. Cardinali DP, Cano P, Jiménez-Ortega V, Esquifino AI. Melatonin and the metabolic syndrome: physiopathologic and therapeutical implications. Neuroendocrinology 2011; 93: 133-142.
78. Beccuti G, Pannain S. Sleep and obesity. Curr Opin Clin Nutr Metab Care 2011; 14: 402-412.
79. Castañeda TR, Tong J, Datta R, Culler M, Tschöp MH. Ghrelin in the regulation of body weight and metabolism. Front Neuroendocrinol 2010; 31: 44-60.
80. Ariyasu H, Iwakura H, Yamada G, Nakao K, Kangawa K, Akamizu T. Efficacy of ghrelin as a therapeutic approach for age-related physiological changes. Endocrinology 2008; 149: 3722-3728.
81. North BJ, Sinclair Da. The intersection between aging and cardiovascular disease. Circ Res 2012; 110: 1097-1098.
82. Chung WH, Dao RL, Chen LK, Hung SI. The role of genetic variants in human longevity. Ageing Res Rev 2010; 9: S67-78.
83. Murabito JM, Yuan R, Lunetta KL. The search for longevity and healthy aging genes: insights form epidemiological studies and samples of long-lived individuals. J Gerontol A Biol Sci Med Sci 2012; 67: 470-479.
84. Nolan CJ, Damm P, Prentki M. Type 2 diabetes across generations: from pathophysiology to prevention and management. Lancet 2011; 378: 169-181.
85. Terry DF, Nolan VG, Andersen SL, Peris TT, Cawthon R. Association of longer telomeres with better health in centenarians. J Gerontol A Biol Sci Med Sci 2008; 63: 809-812.
86. Zhu H, Belcher M, van der Harst P. Healthy aging and disease: role for telomere biology? Clin Sci 2011; 120: 427-440.
87. Demissie S, Levy D, Benjamin EJ, Cupples LA, Gardner JP, Herbert A et al. Insulin resistance, oxidative stress, hypertension, and leukocyte telomere length in men from the Framingham Heart Study. Aging Cell 2006; 5: 325-330.
88. Barnes SK, Ozanne SE. Pathways linking the early environment to long-term health and lifespan. Prog Biophys Mol Biol 2011; 106: 323-336.
89. Ludlow AT, Roth SM. Physical activity and telomere biology: exploring the link with aging-related disease prevention. J Aging Res 2011; 2011: 790378.
90. Kim JH, Ko JH, Lee DC, Lim I, Bang H. Habitual physical exercise has beneficial effects telomere length in postmenopausal women. Menopause 2012; 19: 1109-15.
91. Epel ES. Psychological and metabolic stress: a recipe for accelerated cellular aging? Hormones 2009; 8: 7-22.
92. Cholerton B, Baker LD, Craft S. Insulin resistance and pathological brain ageing. Diabet Med 2011; 28: 1463-1475.
93. Bosco D, Fava A, Plastino M, Montalcini T, Pujia A. Possible implications of insulin resistance and glucose metabolism in Alzheimer's disease pathogenesis. J Cell Mol Med 2011; 15: 1807-1821.
94. Levine ME, Crimmins EM. Sarcopenic obesity and cognitive functioning: the mediating roles of insulin resistance and inflammation? Curr Gerontol Geriatr Res 2012: 826398.
95. Norman D, Loredo JS. Obstructive sleep apnea in older adults. Clin Geriatr Med 2008; 24: 151-165.
96. Cherniack EP, Cherniack NS. Obstructive sleep apnea, metabolic syndrome, and age: will geriatricians be caught asleep on the job? Aging Clin Exp Res 2010; 22: 1-7.
97. Uranga RM, Bruce-Keller AJ, Morrison CD, Fernandez-Kim SO, Ebenezer PJ, Zhang L et al. Intersection between metabolic dysfunction, high fat diet consumption, and brain aging. J Neurochem 2010; 114: 344-361.
98. Perez-Lopez FR, Chedraui CP, Haya J, Cuadros JL. Effects of the Mediterranean diet on longevity and age-related morbid conditions. Maturitas 2009; 64: 67-79.
99. Zhang W, Li P, Hu X, Zhang F, Chen J, Gao Y. Omega-3 polyunsaturated fatty acids in the brain: metabolism and neuroprotection. Front Biosci 2011; 17: 2653-2670.
100. Luevano-Contreras C, Chapman-Novakofski K. Dietary advanced glycation end-products and agin. Nutrients 2010; 2: 1247-1265.
101. Krentz AJ, Bailey CJ. Drug treatment of type 2 diabetes. Drugs 2005; 65: 385-411.
102. Li J, Deng J, Sheng W, Zuo Z. Metformin attenuates Alzheimer's disease-like neuropathology in obese, leptin-resistant mice. Pharmacol Biochem Behav 2012; 101: 564-574.
103. Wang J, Gallagher D, DeVito LM, Cancino GI, Tsui D, He L et al. Metformin activates an atypical PKC-CBP pathway to promote neurogenesis and enhance spatial memory formation. Cell Stem Cell. 2012; 11: 23-35.
104. Chen Y, Zhou K, Wang R, Liu Y, Kwak YD, Ma T et al. Antidiabetic drug metformin (GlucophageR) increases biogenesis of Alzheimer's amyloid peptides via up-regulating BACE1 transcription. Proc Natl Acad Sci U S A 2009; 106: 3907-3912.
105. Arcidiacono B, Iiritano S, Nocera A, Possidente K, Nevolo MT, Ventura V et al. Insulin resistance and cancer risk: an overview of the pathogenetic mechanisms. Exp Diabetes Res 2012; 2012: 789174.
106. Braun S, Bitton-Worms K, LeRoith D. The link between metabolic syndrome and cancer. Int J Biol 2011; 7: 1003-1015.
107. Shehzad A, Iqbal W, Shehzad O, Lee YS. Adiponectin: regulation of its production and its role in human diseases. Hormones 2012; 11: 8-20.
108. Currie CJ, Poole CD, Jenkins-Jones S, Gale EA, Johnson JA, Morgan CL. Mortality after incident cancer in people with and without type 2 diabetes: impact of metformin on survival. Diabetes Care 2012; 35: 299-304.
109. Gallagher EJ, LeRoith D. Diabetes, cancer, and metformin: connections of metabolism and cell proliferation. Ann N Y Acad Sci 2011; 1243: 54-68.
110. Dowling RJ, Goodwin PJ, Stambolic V. Understanding the benefit of metformin use in cancer treatment. BMC Med 2011; 9: 33.
111. Azoulay L, Yin H, Filion KB, Assayag J, Majdan A, Pollak MN et al. The use of pioglitazone and the risk of bladder cancer in people with type 2 diabetes: nested case-control study. Br Med J 2012; 344: e3645.
112. Viljoen A, Sinclair A. Safety and efficacy of rosiglitazone in the elderly diabetic patient. Vasc Health Risk Manag 2009; 5: 389-395.
113. Johnson JA, Gale EAM. Diabetes, insulin use, and cancer risk: are observational studies part of the solution-or part of the problem? Diabetes 2010; 59: 1129-1131.
114. The ORIGIN Trial Investigators. Basal insulin and cardiovascular and other outcomes in dysglycemia. N Engl J Med 2012; 367: 319-328.
115. Currie CJ, Johnson JA. The safety profile of exogenous insulin in people with type 2 diabetes: justification for concern. Diabetes Obes Metab 2012; 14: 1-4.
116. Christensen K, Johnson TW, Vaupel JW. The quest for genetic determinants of longevity: challenges and insights. Nat Rev Genet 2006; 7: 436-448.
117. Lanza IR, Nair KS. Muscle mitochondrial changes with aging and exercise. Am J Clin Nutr 2009; 89: 467S-471S.
118. Vendelbo MH, Nair KS. Mitochondrial longevity pathways. Biochim Biophys Acta 2011; 1813: 634-644.
119. Gremese E, Ferraccioli G. The metabolic syndrome: the crossroads between rheumatoid arthritis and cardiovascular risk. Autoimmun Rev 2011; 10: 582-589.
120. Colman RJ, Anderson RM, Johnson SC, Kastman EK, Kosmatka KJ, Beasley TM et al. Caloric restriction delays disease onset and mortality in rhesus monkeys. Science. 2009; 325: 201-4.
121. Corbi G, Conti V, Scapagnini G, Filippelli A, Ferrara N. Role of sirtuins, calorie restriction and physical activity in aging. Front Biosci 2012; 1: 768-778.
122. Mattison JA, Roth GS, Beasley TM, Tilmont EM, Handy AM, Herbert RL et al. Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study. Nature 2012; 489: 318-321.
123. UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet. 1998; 352: 854-65.
124. Yoshino J, Conte C, Fontana L, Mittendorfer B, Imai S, Schechtman KB, et al. Samuel Klein. Resveratrol supplementation does not improve metabolic function in nonobese women with normal glucose tolerance. Cell Metab, 2012; 16: 658-664.
125. Crandall JP, Oram V, Trandafirescu G, Reid M, Kishore P, Hawkins M, et al. Pilot study of resveratrol in older adults with impaired glucose tolerance. J Gerontol A Biol Sci Med Sci 2012; 67: 1307-1312.
126. Blagosklonny MV. Validation of anti-aging drugs by treating age-related diseases. Aging 2009; 1: 281-288.
127. Atienzar P, Abizanda P, Guppy A, Sinclair AJ. Diabetes and frailty: an emerging issue. Part 1: Sarcopaenia and factors affecting lower limb function. Br J Diab Vasc Dis 2012; 12: 110-116.
128. Krentz AJ, Patel M, Bailey CJ. New therapies for type 2 diabetes - What is their place in therapy? Drugs 2008; 68: 2131-2162.
129. Sakuma K, Yamaguchi A. Novel intriguing strategies attenuating to sarcopenia. J Aging Res 2012; 2012: 251217.
130. Blagosklonny MV. Prospective treatment of age-related disease by slowing down aging. Am J Pathol 2012; 181: 1142-1146.
131. Lee CG, Boyko EJ, Barrett-Connor E, Miljkovic I, Hoffman AR, Everson-Rose SA et al. Insulin sensitizers may attenuate lean mass loss in older men with diabetes. Diabetes Care 2011; 34: 2381-2386.
132. Himsworth HP. Diabetes mellitus: its differentiation into insulin-sensitive and insulin-insensitive types. Lancet 1936; 1: 127-130.