Platelets from older adults exhibit differences in mitochondrial function associated with impaired glucose metabolism

Impaired glucose tolerance (IGT) and insulin resistance (IR), including prediabetes and diabetes, increase risk of developing age-related disorders, such as cardiovascular disorders, kidney disorders, and Alzheimer's disease. We analyzed mitochondrial bioenergetics of platelets collected from 208 adults, 55 years and older, with IGT and IR and without normoglycemic (NG). Platelets from IGT participants exhibited unique mitochondrial bioenergetic profiles exemplified by higher mitochondrial respiration compared with NG. IGT platelets exhibited higher glucose-dependent maximal respiration (Max) and spare respiratory capacities (SRCs) and higher fatty acid oxidation (FAO)-dependent maximal coupled (MaxOXPHOS) and uncoupled (maximal electron transport system) respiration compared with NG. Correlating mitochondrial bioenergetics from all 208 participants with measures of glucose tolerance (oral glucose tolerance test values measured 120 min after glucose administration, and oral glucose tolerance test area under the curve), and historical glucose measures [hemoglobin A1 (HbA1c)] revealed significant positive associations. Most associations were unaltered with age, sex, and body mass index adjustments. Examining NG and IGT participants separately, we found platelet respiration and HbA1c exhibited positive association in NG participants. Significant positive associations emerged between platelet SRC, FAO, FAO+CI (oxygen flux due to FAO + complex I activities), and HbA1c. No significant associations were observed in the IGT group. Given the utilization of blood-based mitochondrial bioenergetic profiling strategies in clinical research, this work provides new insights into the clinical features of IR that can affect platelet mitochondrial bioenergetics.