Cerebral perfusion was evaluated in 87 subjects prospectively enrolled in three study groups-healthy controls (HC), patients with insulin resistance (IR) but not with diabetes, and type 2 diabetes mellitus (T2DM). Participants received a comprehensive 8-hour clinical evaluation and arterial spin labeling magnetic resonance imaging (MRI). In order of decreasing significance, an association was found between cerebral blood flow (CBF) and sex, waist circumference, diastolic blood pressure (BP), end tidal CO 2 , and verbal fluency score (R 2 = 0.27, F = 5.89, Po 0.001). Mean gray-matter CBF in IR was 4.4 mL/100 g per minute lower than in control subjects (P = 0.005), with no hypoperfusion in T2DM (P = 0.312). Subjects with IR also showed no CO 2 relationship (slope = − 0.012) in the normocapnic range, in contrast to a strong relationship in healthy brains (slope = 0.800) and intermediate response (slope = 0.445) in diabetic patients. Since the majority of T2DM but few IR subjects were aggressively treated with blood glucose, cholesterol, and BP lowering medications, our finding could be attributed to the beneficial effect of these drugs.

The hypothalamus is important in hunger and metabolism. Although a lot is known about the basic role of the human hypothalamus, less is known about how the in vivo volume is affected in obesity, particularly among adolescents. Based on pediatric body mass index percentiles, 95 participants were assigned to lean or obese groups. All subjects had medical evaluations, including fasting blood tests, to assess insulin sensitivity and circulating CRP and neurotrophins (NGF and BDNF) and an MRI of the brain. Hypothalamic volumes were measured by a segmentation method combining manual and automated steps. Overall, obese participants had descriptively smaller hypothalamic volumes, although this difference did not reach statistical significance; however, among obese participants, females had significantly smaller hypothalamic volumes than their male counterparts. There was a significant interaction between insulin resistance and sex on hypothalamus volume; obese females with significant insulin resistance have smaller hypothalamic volumes than obese males. Obese adolescents had higher circulating CRP and neurotrophin levels. Furthermore, among obese females, BDNF concentrations were inversely associated with hypothalamus volumes (r = −0.48). Given this negative association between BDNF and hypothalamus volumes among obese insulin-resistant females, elevated neurotrophin levels may suggest an attempt at protective compensation.