Background: Postural tachycardia syndrome (POTS) is characterized by excessive upright tachycardia and disabling presyncopal symptoms, which are exacerbated after consuming a high-carbohydrate meal; it is unknown, however, what is the precise underlying mechanism. We seek to investigate the effect of glucose intake on orthostatic hemodynamic changes and gastrointestinal hormone secretion in POTS. Methods: Prospective, case-control study, 12 women with POTS who reported a postprandial worsening of their POTS symptoms and 13 age-matched female controls received 75-g oral glucose and 20 mg/kg acetaminophen to assess nutrient absorption. Hemodynamic, gastrointestinal hormone and acetaminophen levels were measured for up to 120 minutes postingestion while supine and standing. Results: Patients with POTS had significant orthostatic tachycardia, 48.7±11.2 versus 23.3±8.1 bpm, P =0.012 and elevated upright norepinephrine levels, 835.2±368.4 versus 356.9±156.7 pg/mL, P =0.004. After oral glucose, upright heart rate significantly increased in POTS, 21.2±11.9% versus 6.0±19.9%, P =0.033 with a concomitant decline in upright stroke volume, −10.3±11.90% versus 3.3±13.7%, P =0.027; total peripheral resistance, blood pressure and cardiac output remained unaltered. Acetaminophen rate of appearance was similar between groups ( P =0.707), indicating comparable nutrient absorption rates. POTS had increased plasma levels of C-peptide ( P =0.001), GIP (glucose-dependent insulinotropic polypeptide; P =0.001), peptide YY ( P =0.016), and pancreatic polypeptide ( P =0.04) following glucose consumption, but only GIP had a time-dependent association with the worsening upright tachycardia and stroke volume fall. Conclusions: The glucose-induced worsening orthostatic tachycardia in POTS was associated with a decline in SV; these changes occurred while GIP, a splanchnic vasodilator, was maximally elevated.

CD36 is a membrane protein involved in fatty acids uptake that is expressed in the endothelium, which has been associated with endothelial dysfunction in African Americans (AA). One in four AA is G-allele carriers for coding CD36 SNP rs3211938, which results in ~50% reduction in its expression. We reported that potentiating nitric oxide action (NO) with sildenafil restored endothelial dysfunction in conduit arteries in G-allele carriers. In this study, we tested the hypothesis that in G-allele carriers, sildenafil would improve insulin-induced microvascular recruitment (MBV) in response to fat infusion. We recruited 25 healthy AA (17 non-carriers [ages 34 ± 7.4] and eight G-allele carriers [42 ± 7.4 yrs]). Subjects underwent three visits: Visit 1: Saline infusion and hyperinsulinemic euglycemic clamp (HIE clamp). Visit 2: Lipid infusion and HIE clamp and Visit 3: Lipid infusion and HIE clamp after a four-week sildenafil treatment (60 mg/day). During each visit, the subjects underwent an assessment of MBV at baseline (bsl), after 3-hour insulin (Ins) infusion (40mu/m 2 /min) and after Ins and L-arginine (10mg/kg/min) for 30 min. infusion (Ins+L-arg). Ins+L-arg (saline day) increased the % change in MBV in both groups. However, this increase was less in carriers as compared to non-carriers (13.6±42.4 and 38.9±74.4), Fig. A. Intralipid (IL) infusion increased MBV but only in non-carriers, Fig. B . Treatment with sildenafil in the presence of IL infusion induced a decline in MBV in G-allele carriers Fig. C . In conclusion, healthy AAs with CD36 deficiency had a poor insulin-induced microvascular recruitment and appeared to be worsened by potentiating NO function with sildenafil.