Pre-Prediabetes: Insulin Resistance Is Associated With Cardiometabolic Risk in Nonobese Patients (STOP DIABETES)

Context: Prior studies have demonstrated glycemic and cardiometabolic risk in the prediabetic state. Objective: This work aims to examine if insulin resistance (IR) is associated with markers of glycemic, cardiometabolic, and atherosclerotic risk in nonobese, nonprediabetic individuals compared to insulin-sensitive (IS) individuals matched for body mass index (BMI), sex, and age. Methods: Of 1860 patients from the STOP DIABETES study, 624 had normal fasting plasma glucose, BMI less than 30, and glycated hemoglobin A_1c (HbA_1c) less than 5.7%. All received an oral glucose tolerance test. Insulin sensitivity was quantitated using the Matsuda index: less than the 25th percentile equals IR (n = 151) and 25th percentile or greater equals IS (n = 473). Measures of dysglycemia and cardiometabolic risk were compared between IR individuals (n = 151) and a subset of IS individuals who were matched for BMI, sex, and age (n = 151). Carotid intima media thickness and carotid plaque were measured in 65 IR and 76 IS individuals. Results: Compared to matched IS patients, IR nonobese individuals demonstrated increased indicators of glycemic and cardiometabolic risk, including increased 60-minute plasma glucose and percentage of patients with 60-minute plasma glucose greater than 155 mg/dL; increased 120-minute plasma glucose; unrecognized impaired glucose tolerance and type 2 diabetes, decreased disposition index; increased systolic and diastolic blood pressure; elevated plasma triglycerides (TGs); reduced high-density lipoprotein (HDL) cholesterol; increased TGs/HDL ratio, and high-sensitivity C-reactive protein. The presence, size, and number of carotid plaques was greater in the IR group. Conclusion: Approximately 1 in 4 nonobese patients in this population with normal fasting glucose and HbA_1c were IR. In these nonobese participants, IR was associated with multiple indicators of dysglycemia and cardiometabolic risk.