Whether individuals with insulin resistance but without criteria for diabetes exhibit reduced mitochondrial oxidative capacity is unclear; addressing this question could guide research for new therapeutics. We investigated 248 non-diabetic participants from the Baltimore Longitudinal Study of Aging (BLSA) to determine whether impaired mitochondrial capacity is associated with prediabetes, insulin resistance, duration and severity of hyperglycemia exposure. Mitochondrial capacity was assessed as post-exercise phosphocreatine recovery time constant (τPCr) by 31P-magnetic resonance spectroscopy, with higher τPCr reflecting reduced capacity. Prediabetes was defined using the American Diabetes Association criteria from fasting and 2-hr glucose. Insulin resistance and sensitivity were calculated using HOMA-IR and Matsuda Indices. Duration and severity of hyperglycemia exposure were estimated as number of years from prediabetes onset and average oral glucose tolerance test (OGTT) 2h-glucose over previous BLSA visits. Covariates included age, sex, body composition, physical activity and other confounders. Higher likelihood of prediabetes, higher HOMA-IR and lower Matsuda Index were associated with longer τPCr. Among 205 participants with previous OGTT data, greater severity and longer duration of hyperglycemia were independently associated with longer τPC. In conclusion, in non-diabetic individuals a more impaired mitochondrial capacity is associated with greater insulin resistance and higher likelihood of prediabetes.
- Received June 21, 2016.
- Accepted October 7, 2016.
- © 2016 by the American Diabetes Association.