Biological predictors of insulin resistance associated with posttraumatic stress disorder in young military veterans

• Case-control study including military veterans with PTSD and combat-exposed controls.
• Increased cardiometabolic risk markers HOMA-IR, prediabetes and metabolic syndrome in PTSD.
• Heart rate, serum BDNF and inflammatory cytokines predict increased HOMA-IR in PTSD.

Posttraumatic stress disorder (PTSD) is associated with increased risk for Type 2 diabetes and cardiovascular disease (cardiometabolic disease), warranting research into targeted prevention strategies. In the present case–control study of 160 young (mean age 32.7 years) male military veterans, we aimed to assess whether PTSD status predicted increased markers of cardiometabolic risk in otherwise healthy individuals, and further, to explore biological pathways between PTSD and these increased markers of cardiometabolic risk. Toward these aims, we compared measures of cardiometabolic risk, namely insulin resistance (IR) (HOMA-IR), metabolic syndrome (MetS) and prediabetes, between 80 PTSD cases and 80 controls without PTSD. We then determined whether PTSD-associated increases in HOMA-IR were correlated with select biological variables from pathways previously hypothesized to link PTSD with cardiometabolic risk, including systemic inflammation (increased C-reactive protein, interleukin-6, and tumor necrosis factor α), sympathetic over-activity (increased resting heart rate), and neuroendocrine dysregulation (increased plasma cortisol or serum brain-derived neurotrophic factor (BDNF)). We found PTSD diagnosis was associated with substantially higher HOMA-IR (cases 4.3 ± 4.3 vs controls 2.4 ± 2.0; p < 0.001), and a higher frequency of MetS (cases 21.3% vs controls 2.5%; p < 0.001), but not prediabetes (cases 20.0% vs controls 18.8%; p > 0.05). Cases also had increased pro-inflammatory cytokines (p < 0.01), heart rate (p < 0.001), and BDNF (p < 0.001), which together predicted increased HOMA-IR (adjusted R2 = 0.68, p < 0.001). Results show PTSD diagnosis in young male military veterans without cardiometabolic disease is associated with increased IR, predicted by biological alterations previously hypothesized to link PTSD to increased cardiometabolic risk. Findings support further research into early, targeted prevention of cardiometabolic disease in individuals with PTSD.