Diabetes and Cardiovascular Disease in Older Adults: Current Status and Future Directions

The prevalence of diabetes increases with age, driven in part by an absolute increase in incidence among adults aged 65 years and older. Individuals with diabetes are at higher risk for cardiovascular disease, and age strongly predicts cardiovascular complications. Inflammation and oxidative stress appear to play some role in the mechanisms underlying aging, diabetes, cardiovascular disease, and other complications of diabetes. However, the mechanisms underlying the age-associated increase in risk for diabetes and diabetes-related cardiovascular disease remain poorly understood. Moreover, because of the heterogeneity of the older population, a lack of understanding of the biology of aging, and inadequate study of the effects of treatments on traditional complications and geriatric conditions associated with diabetes, no consensus exists on the optimal interventions for older diabetic adults. The Association of Specialty Professors, along with the National Institute on Aging, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Heart, Lung, and Blood Institute, and the American Diabetes Association, held a workshop, summarized in this Perspective, to discuss current knowledge regarding diabetes and cardiovascular disease in older adults, identify gaps, and propose questions to guide future research.

[1]  A. Chang,et al.  Aging and insulin secretion. , 2003, American journal of physiology. Endocrinology and metabolism.

[2]  Suzanne Craft,et al.  The role of metabolic disorders in Alzheimer disease and vascular dementia: two roads converged. , 2009, Archives of neurology.

[3]  Mark A. Smith,et al.  Faculty of 1000 evaluation for Protection of synapses against Alzheimer's-linked toxins: insulin signaling prevents the pathogenic binding of Abeta oligomers. , 2012 .

[4]  Jeffrey B Halter,et al.  Diabetes and cardiovascular disease prevention in older adults. , 2009, Clinics in geriatric medicine.

[5]  F. Ovalle 10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study , 2010 .

[6]  K. Bornfeldt,et al.  Insulin resistance, hyperglycemia, and atherosclerosis. , 2011, Cell metabolism.

[7]  K. Langa,et al.  Clinical Complexity in Middle-Aged and Older Adults With Diabetes: The Health and Retirement Study , 2010, Medical care.

[8]  C. Blaum,et al.  Geriatric Conditions Develop in Middle-Aged Adults with Diabetes , 2010, Journal of General Internal Medicine.

[9]  S. Beske,et al.  Weight Loss Alone Improves Conduit and Resistance Artery Endothelial Function in Young and Older Overweight/Obese Adults , 2008, Hypertension.

[10]  B. Spiegelman,et al.  A PGC-1α Isoform Induced by Resistance Training Regulates Skeletal Muscle Hypertrophy , 2012, Cell.

[11]  Eric E. Smith,et al.  Race/Ethnicity, Quality of Care, and Outcomes in Ischemic Stroke , 2010, Circulation.

[12]  Clifford Qualls,et al.  Weight loss, exercise, or both and physical function in obese older adults. , 2011, The New England journal of medicine.

[13]  D. Lloyd‐Jones,et al.  Racial Differences in Risks for First Cardiovascular Events and Noncardiovascular Death: The Atherosclerosis Risk in Communities Study, the Cardiovascular Health Study, and the Multi-Ethnic Study of Atherosclerosis , 2012, Circulation.

[14]  Jennifer G. Robinson,et al.  Racial and Ethnic Differences in Incident Hospitalized Heart Failure in Postmenopausal Women: The Women's Health Initiative , 2012, Circulation.

[15]  Paola Sebastiani,et al.  Health span approximates life span among many supercentenarians: compression of morbidity at the approximate limit of life span. , 2012, The journals of gerontology. Series A, Biological sciences and medical sciences.

[16]  S. Minoshima,et al.  Insulin resistance and Alzheimer-like reductions in regional cerebral glucose metabolism for cognitively normal adults with prediabetes or early type 2 diabetes. , 2011, Archives of neurology.

[17]  M. Hayden,et al.  HDL and LDL cholesterol significantly influence β-cell function in type 2 diabetes mellitus , 2010, Current opinion in lipidology.

[18]  Mark D. Huffman,et al.  Heart disease and stroke statistics--2013 update: a report from the American Heart Association. , 2013, Circulation.

[19]  William H. Herman,et al.  The Economic Costs of Diabetes: Is It Time for a New Treatment Paradigm? , 2013, Diabetes Care.

[20]  Mark Woodward,et al.  Severe hypoglycemia and risks of vascular events and death. , 2010, The New England journal of medicine.

[21]  Nathaniel Clark,et al.  Diabetes in Older Adults , 2012, Diabetes Care.

[22]  David R. Sinacore,et al.  Weight Loss, Exercise, or Both and Cardiometabolic Risk Factors in Obese Older Adults: Results of a Randomized Controlled Trial , 2013, International Journal of Obesity.

[23]  P. Cryer Mechanisms of sympathoadrenal failure and hypoglycemia in diabetes. , 2006, The Journal of clinical investigation.

[24]  David A Sinclair,et al.  The intersection between aging and cardiovascular disease. , 2012, Circulation research.

[25]  Haiying Chen,et al.  Association of an intensive lifestyle intervention with remission of type 2 diabetes. , 2012, JAMA.

[26]  Ryuichi Morishita,et al.  Diabetes-accelerated memory dysfunction via cerebrovascular inflammation and Aβ deposition in an Alzheimer mouse model with diabetes , 2010, Proceedings of the National Academy of Sciences.

[27]  C. Talchai,et al.  Pancreatic β Cell Dedifferentiation as a Mechanism of Diabetic β Cell Failure , 2012, Cell.

[28]  Patrick J Heagerty,et al.  Temporal trends in the prevalence of diabetic kidney disease in the United States. , 2011, JAMA.

[29]  Peter H Whincup,et al.  Impact of diabetes on cardiovascular disease risk and all-cause mortality in older men: influence of age at onset, diabetes duration, and established and novel risk factors. , 2011, Archives of internal medicine.

[30]  Akshay S. Desai,et al.  Strategies for multivessel revascularization in patients with diabetes. , 2012, The New England journal of medicine.

[31]  J. Regensteiner,et al.  Exercise attenuates the premature cardiovascular aging effects of type 2 diabetes mellitus , 2011, Vascular medicine.

[32]  Yisrael Parmet,et al.  Skin cancer awareness, attitude, and sun protection behavior among medical students at the University of Miami Miller School of Medicine. , 2010, Archives of dermatology.

[33]  C. Scott,et al.  Changes in diastolic dysfunction in diabetes mellitus over time. , 2009, The American journal of cardiology.

[34]  T. Montine,et al.  Intranasal Insulin Therapy for Alzheimer Disease and Amnestic Mild Cognitive Impairment A Pilot Clinical Trial , 2011 .

[35]  M. Shishehbor,et al.  Strategies for multivessel revascularization in patients with diabetes , 2013 .

[36]  Michael Brownlee,et al.  The pathobiology of diabetic complications: a unifying mechanism. , 2005, Diabetes.

[37]  S. Fowler,et al.  The influence of age on the effects of lifestyle modification and metformin in prevention of diabetes. , 2006, The journals of gerontology. Series A, Biological sciences and medical sciences.

[38]  B. Kestenbaum,et al.  Kidney disease and increased mortality risk in type 2 diabetes. , 2013, Journal of the American Society of Nephrology : JASN.

[39]  Edward H Ip,et al.  Lifestyle change and mobility in obese adults with type 2 diabetes. , 2012, The New England journal of medicine.

[40]  D. Reda,et al.  Percutaneous coronary intervention versus coronary bypass surgery in United States veterans with diabetes. , 2013, Journal of the American College of Cardiology.

[41]  The Emerging Risk Factors Collaboration Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies , 2010, The Lancet.

[42]  Maria Mori Brooks,et al.  A randomized trial of therapies for type 2 diabetes and coronary artery disease. , 2009, The New England journal of medicine.

[43]  P. Rabinovitch,et al.  Mitochondria and cardiovascular aging. , 2012, Circulation research.

[44]  Ralph A. DeFronzo,et al.  From the Triumvirate to the Ominous Octet: A New Paradigm for the Treatment of Type 2 Diabetes Mellitus , 2009, Diabetes.

[45]  N. Adler,et al.  Elevated Rates of Diabetes in Pacific Islanders and Asian Subgroups , 2013, Diabetes Care.

[46]  L. Ferrucci,et al.  Insulin resistance and aging: a cause or a protective response? , 2012, The journals of gerontology. Series A, Biological sciences and medical sciences.

[47]  M. Chin,et al.  The Effect of Comorbid Illness and Functional Status on the Expected Benefits of Intensive Glucose Control in Older Patients with Type 2 Diabetes: A Decision Analysis , 2008, Annals of Internal Medicine.

[48]  J. Danesh,et al.  Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. , 2010, Lancet.

[49]  D. Munoz,et al.  An anti-diabetes agent protects the mouse brain from defective insulin signaling caused by Alzheimer's disease- associated Aβ oligomers. , 2012, The Journal of clinical investigation.

[50]  Edward L. Schneider,et al.  Handbook of the Biology of Aging , 1990 .

[51]  L. Kuller,et al.  10-year follow-up of subclinical cardiovascular disease and risk of coronary heart disease in the Cardiovascular Health Study. , 2006, Archives of internal medicine.

[52]  W. Rosamond,et al.  The population burden of heart failure attributable to modifiable risk factors: the ARIC (Atherosclerosis Risk in Communities) study. , 2012, Journal of the American College of Cardiology.

[53]  D. Seals,et al.  Vascular health in the ageing athlete , 2012, Experimental physiology.

[54]  W. Klein,et al.  Protection of synapses against Alzheimer's-linked toxins: Insulin signaling prevents the pathogenic binding of Aβ oligomers , 2009, Proceedings of the National Academy of Sciences.

[55]  David M Nathan,et al.  10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study. , 2009, Lancet.

[56]  R. Rizza,et al.  Forearm vascular control during acute hyperglycemia in healthy humans. , 2004, American journal of physiology. Endocrinology and metabolism.

[57]  R. DeFronzo,et al.  Reduction in Reactive Oxygen Species Production by Mitochondria From Elderly Subjects With Normal and Impaired Glucose Tolerance , 2011, Diabetes.

[58]  F. Inserra,et al.  Angiotensin II blockade: a strategy to slow ageing by protecting mitochondria? , 2011, Cardiovascular research.