Table 3.

A Summary of Human Studies Examining Role of Advanced Glycation End Products in Noncommunicable Diseases.

Type of Study	Purpose of the Study	Duration of Intervention or Follow-up	Study Population Characteristics	Key Findings	Reference
Population-based prospective cohort study	To evaluate role of AGE in risk of all-cause and CVD mortality	6 Years	N = 1013; age: ≥65 years	• Older adults with high plasma AGEs are at higher risk of all-cause and CVD mortality	25
Longitudinal study	To evaluate role of AGE in CKD and eGFR	6 Years	N = 750; men and women, aged 26-93 years	• Elevated AGE is independently associated with CKD • Elevated AGE is independently associated with eGFR	43
Cross-sectional study	To evaluate role of AGE in memory decline in aged	1.25-7 Years	71.0 Years ± 8.1 SD	• AGEs are associated with cognitive decline • High levels of dietary AGEs are associated with faster decline in memory • High serum methylgluoxal are associated with faster decline in attention • Modifying AGEs in the diet may be a strategy to diminish cognitive compromise	44
Intervention study	To evaluate effect of dietary AGE intake on hormonal and metabolic profile in women with PCOS	2-Month dietary intervention	23 Women with PCOS; age: 23.4 ± 5.7 years	• Modifications of dietary AGEs intake are associated with parallel changes in serum AGEs, metabolic, hormonal, and oxidative stress biomarkers in women with PCOS	50
Cross-sectional study	Is serum level of AGE altered in women with PCOS?	—	29 Women with PCOS; 22 healthy control women; age: 23.4 ± 5.7 years	• PCOS women without overt hyperglycemia have increased AGE levels and elevated RAGE expression when compared with controls	54
Cross-sectional study	Can AGEs predict CAD in diabetics?	—	145 Diabetic and nondiabetic subjects; 63 ± 9 years, 58% men	• Serum AGEs independently predict obstructive CAD and the severity of coronary atherosclerosis irrespective of arterial stiffness in diabetics	66
Cross-sectional study	Is high serum pentosidine concentration associated with increased arterial stiffness and thickness in patients with type 2 diabetes	—	159 Diabetic and nondiabetic subjects; 63 ± 9 years, 58% men	• Serum pentosidine is positively associated with both arterial stiffness and thickness and CVD in patients with type 2 diabetes	67
Cross-sectional study	To examine the role of circulating levels of CML as a biomarker of hip fracture risk	9.22 Years	3373 Subjects; 78 years, 39.8% men	• Increasing levels of CML are associated with hip fracture risk in older adults, independent of hip BMD	71
Cross-sectional study	To examine the role of penile level of AGE in erectile dysfunction	—	N = 38, 62 ± 4 years	• AGES are elevated in diabetic human penile tissue, but not in serum, and are localized to the collagen of the penile tunica and corpus cavernosum	74
Cross-sectional study	To determine whether serum AGE, and circulating total receptor for AGEs (sRAGE) and endogenous secretory receptor for AGEs (esRAGE) are associated with anemia	—	N = 159 women, ≥65 years	• AGEs and circulating RAGE are independently associated with hemoglobin and anemia in older women	77
Cross-sectional study	To examine the relationship between AGE and slow walking speed in older adults	—	N = 944 adults, aged ≥65 years	• In older community-dwelling adults, elevated plasma AGE is independently associated with slow walking speed	78
Cross-sectional study	To examine the role of AGE in peripheral arterial disease	—	N = 170 adults, aged 55 ± 9 years	• Serum AGE (pentosidine) was an independent determinant of ankle-brachial index (ABI), a measure of peripheral arterial disease, in healthy men; Subjects with an ABI less than 1.10 showed higher AGE concentrations	85
Cross-sectional study	To examine the relationship between OSA and AGE	—	N = 190 OSA patents, N = 234 healthy controls	• Serum AGEs were increased in OSA subjects, as compared with controls	86
Cross-sectional study	To examine the relationship between increased serum levels of AGE and severity of sleep disordered breathing	—	N = 105 adults, aged 43.5 ± 9.2 years	• Serum AGE levels correlate with AHI in nondiabetic adult males	87
Cross-sectional study	To examine the relationship between pro-insulin to insulin ratio and plasma AGE level	—	N = 64 patients with type 2 diabetes, aged 62 ± 7 years	• A disproportionate elevation of pro-insulin to insulin ratio, a predictor of beta-cell dysfunction, is positively correlated with plasma AGE level	90
Cross-sectional study	To examine the relationship between AGE level in prostate cancer tissue sample and severity of disease	—	N = 26	• AGE levels are elevated in prostate cancer tissue • Higher the grade of cancer, higher the level of AGE • Subjects of African American decent had higher level of AGE than those from European decent	97
Cross-sectional study	To examine diagnostic value of AGE level in diagnosis of schizophrenia	—	N = 45	• Level of AGE is elevated in a subpopulation of schizophrenic patients	106
Cross-sectional study	To examine role of AGE as a risk factor for metabolic syndrome	—	N = 5848, aged 19-70 years	• Subjects in the highest compared to the lowest quartile category of AGEs intake had higher risk of abdominal obesity and hypertriglyceridemia, 2 markers of metabolic syndrome	114
Crossover interventional study	To examine role of dietary AGEs on inflammatory molecules in diabetic subjects	3-6 Weeks	N = 24, diabetics, aged 52 ± 5 years	• Dietary AGEs are significant contributors to serum AGEs in humans; Sustained reduction in dietary AGEs intake led to reduction in serum AGEs and suppression of inflammatory molecules in diabetic subjects	117
Experimental	To examine role of dietary AGEs on markers of endothelial function in diabetic and nondiabetic subjects	Single exposure	N = 44 stable diabetic subjects and 10 healthy subjects	• There was a significant increase in serum AGEs with altered clinical measures of endothelial function in diabetic and nondiabetic subjects after a single modest AGE-rich beverage	120
Experimental	To examine role of dietary AGEs on vascular function in diabetic subjects	Single exposure	N = 20, diabetic subjects, aged 41-71 years	• In diabetic patients, a high AGE meal induces a more pronounced acute impairment of vascular function than does an otherwise identical low AGE meal	121
Experimental	To examine role of dietary AGEs on vascular function in diabetic subjects	6 Weeks	N = 24, diabetic subjects	• Daily exposure to a diet high in AGE enhances LDL-induced vascular toxicity via redox-sensitive mitogen-activated protein kinase activation	122
Crossover interventional study	To examine role of dietary AGEs on serum AGE and markers of inflammation	Single exposure	N = 19	• In healthy subjects, a high AGE meal does not alter serum AGE or CRP	126
Double-blind, randomized, crossover trial	To examine whether changing dietary AGE intake could modulate insulin sensitivity and secretion in healthy, overweight individuals	2 Weeks	20 participants (6 women and 14 men; mean ± SD body mass index [in kg/m2]: 29.8 ± 3.7)	• A diet that is low in AGEs may reduce the risk of type 2 diabetes by increasing insulin sensitivity	128
Randomized, parallel-arm, controlled dietary intervention	The examine the effects of a diet high or low in AGEs on endothelial function, circulating AGEs, inflammatory mediators, and circulating receptors for AGEs in healthy adults	6 Weeks	N = 24, healthy adults, aged 50-69 years	• In healthy middle-aged to older adults, consumption of a diet high or low in AGEs for 6 weeks had no impact on endothelial function and inflammatory mediators, 2 precursors of cardiovascular disease	131
Cross-sectional study	To examine the role of AGEs on AMD in healthy aged adults	—	N = 4907, healthy adults, aged ≥66 years	• Higher serum AGEs had no significant cross-sectional association with prevalent AMD in healthy older adults in Iceland	132
Longitudinal	To examine the role of AGEs as a predictor of cardiovascular events and renal outcomes in patients with type 2 diabetic kidney disease and hypertension	2.6 Years	N = 450 (137 women, 313 men); subjects with type 2 diabetes and nephropathy, aged 62 ± 7 years	• Serum AGEs could not be identified as an independent risk factor for cardiovascular or renal outcomes in the examined population	133

Abbreviations: AGE, advanced glycation end products; AHI, apnea-hypopnea index; AMD, age-related macular degeneration; BMD, bone mineral density; CAD, coronary artery disease; CKD, chronic kidney disease; CRP, C-reactive protein; CVD, cardiovascular disease; eGFR, estimated glomerular filtration rate; OSA, obstructive sleep apnea; PCOS, polycystic ovary syndrome; RAGE, receptor for AGE.