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

Abstract 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 A1c (HbA1c) 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 HbA1c were IR. In these nonobese participants, IR was associated with multiple indicators of dysglycemia and cardiometabolic risk.