Aging And Diabetes Research Paper

Abstract

Aging is a risk factor for impaired glucose tolerance and diabetes. Of the reported 25.8 million Americans estimated to have diabetes, 26.9% are over the age of 65. In certain ethnic groups, the proportion is even higher; almost 1 in 3 older Hispanics and African Americans and 3 out of 4 Pima Indian elders have diabetes. As per the NHANES III (Third National Health and Nutrition Examination) survey, the percentage of physician-diagnosed diabetes increased from 3.9% in middle-aged adults (40–49 years) to 13.2% in elderly adults (≥75 years). The higher incidence of diabetes is especially alarming considering that diabetes in itself increases the risk for multiple other age-related diseases such as cancer, stroke, cardiovascular diseases,

Diabetes and its complications remain major causes of morbidity and mortality in the USA [1]. It has been reported that the prevalence of T2D increases with age and peaks at 60–74 [2–4]. Almost one third of the elderly have diabetes and three quarters have diabetes or prediabetes [5]. The higher incidence of diabetes is especially alarming considering that diabetes in itself increases the risk for multiple other age-related diseases such as cardiovascular disease (CVD), atherosclerosis, stroke, Alzheimer disease (AD), Parkinson's disease, nonalcoholic fatty liver disease (NAFLD), and cancer [6]. The pathogenesis of T2D in aging is characterized by two major features: peripheral insulin resistance and impaired insulin secretion from β cells [7]. Here, we review how aging predisposes to diabetes and impaired glucose tolerance through effects on insulin secretion and insulin

Glucose and amino acid are major stimuli for insulin release from the pancreatic β cell. With aging, there is a decrease in insulin secretion following stimulation with glucose as well as amino acid arginine [8]. Decrease in glucose-stimulated insulin secretion (GSIS) in vivo has been shown in rodents using the state-of-the-art hyperglycemic clamps [9]. In humans, disorderly insulin release, a decrease in insulin pulse amplitudes, and decreased response to glucose oscillations as well as alterations in insulin clearance have all been demonstrated [10]. When the insulin secretory defects are superimposed over an increased need for insulin as in old age, impaired glucose homeostasis, glucose intolerance, and diabetes can result. We have demonstrated in rodent models that older rodents are unable to increase insulin secretion in proportion to the increased demands imposed by insulin resistance [9], thus contributing to impaired glucose tolerance. Similarly, studies in humans have demonstrated a secretory defect that is consistently observed even after controlling for insulin action. Many factors contribute to the decrease in insulin secretion in aging, including the age-associated loss of Sirt1-mediated GSIS [11], decreased β-cell sensitivity to circulating incretins [10], age-associated decrease in mitochondrial function, as well as increased oxidative stress [12]. In this section of