Assessment of Radial Pulse Wave Analysis, Insulin Resistance, and Glucose Homeostasis in African Americans at High Risk for Developing Type 2 Diabetes Mellitus. We examined the differences in Pulse Wave Analysis (PWA) and glucose homeostasis in non-diabetic African Americans (AA) with and without a family history (first-degree relative) of type 2 diabetes. PWA was assessed at the radial artery using applanation tonometry, and expressed as Augmentation Index (AI). AI was measured at rest and after a single dose of sublingual nitroglycerine (NTG). Glucose homeostasis was assessed by fasting glucose (FG), c-peptide (CP), and following standard 75 gram oral glucose tolerance test (OGTT). Insulin resistance was calculated using homeostasis model assessment (HOMA-IR) The results show that there was no significant difference between baseline AI in the study group (18.5  9.8%) and the control group (23.2  8.0%, p=0.33). AI after NTG did not differ significantly in the 2 groups (study -2.0  9.9%; control 0.8  8.0%, p=0.59), nor did the amount of change in AI from baseline to post NTG (  AI) vary significantly (study  AI 20.0  6.0%; control  AI 22.3  4.8%, p=0.49). There was a significant difference in baseline AI between men (12.7  9.6 %) and women (23.7  6.9%, p=0.01). This sex difference in AI has been described previously in other populations. Using simple linear regression analysis, neither baseline AI, AI after NTG, nor magnitude of  AI showed a significant correlation with any other measured parameter in all subjects combined. In the study group alone, AI after NTG did show a trend for positive correlation with fasting triglycerides (R=0.56, p=0.06); and  AI showed a trend for negative correlation to fasting c-peptide (R= -0.56, p=0.06) and fasting insulin (R= -0.56, p=0.06). In the control group alone,  AI did show a negative correlation with systolic BP (R= -0.92, p=0.01). In conclusion, the results of the current study demonstrated essentially no difference between the two groups in baseline AI, in AI after NTG administration, or in the magnitude of change in AI from baseline to post NTG. Likewise there were no significant differences in glucose homeostasis between the two groups. It is unclear whether this lack of difference between the two groups is a true finding, the result of small sample size, or that the equipment is not sensitive enough to detect subtle differences between the two groups. In addition, our technique did not isolate the endothelium and it’s function from smooth muscle vasodilation caused by NTG. More investigation needs to be done to answer these questions. Abstract Specific Aim Introduction K. Scott Miller, M.D. a, James D. Coyle, Pharm.D. b, Trudy Gaillard, R.N. a, Kwame Osei, M.D. a African Americans (AA) with and without diabetes have higher rates of cardiovascular disease than Caucasians. Studies have shown an impairment in insulin sensitivity and vascular function in healthy AA without known vascular disease when compared to healthy whites. Previous studies by other investigators have also found that first-degree relatives of type 2 diabetics (DM2) had impaired vasodilation when compared with healthy controls, even though there were no significant differences in their clinical characteristics. We speculated that AA who are relatives of type 2 diabetics should show even more endothelial dysfunction than their counterparts who have no family history of DM2. To investigate whether non-diabetic AA with a first-degree relative with DM2 show differences in arterial stiffness using PWA from healthy control AA without a family history of DM2. Subjects, Materials, & Methods We examined the differences in radial artery Augmentation Index (AI) using applanation tonometry, insulin resistance (IR), and glucose homeostasis in non-diabetic AA. The study group (n=12) had a first-degree relative with type 2 diabetes mellitus, while the control group (n=6) did not. The study group had 6 males and 6 females, while the control group had 6 females. The AI is directly affected by arterial stiffness, a key component of atherosclerosis. The AI can also be affected by vasoactive agents or maneuvers that cause arterial relaxation. The AI is defined as the difference between the first and second systolic peaks in the radial artery waveform expressed as a percentage of the pulse pressure. Oral glucose tolerance test was performed in all subjects. Insulin resistance was calculated using the homeostasis model assessment (HOMA). Baseline AI was measured in a fasting, rested state using a SphygomoCor Px/Vx ® system. Sublingual nitroglycerine (NTG) was then administered and the resultant effects studied with a second AI measurement. Baseline AI, AI after NTG (final AI), and magnitude of change in AI after NTG (  AI) were compared between the two groups. Statistical analyses were performed using unpaired Student’s t test for between group analyses. Linear regression was used to determine correlation between variables. Summary of Results 1)There was no difference in baseline AI, AI after NTG, or  AI between the study group and the healthy control group. 2)There was a significantly lower AI in males versus females in the study group. 3)Linear regression analysis showed a significant negative correlation of AI to SBP in the control group. 4)There was no statistical correlation between AI and HOMA-IR or other glycemic parameters. Conclusions In conclusion, we were unable to demonstrate that AA subjects with a first-degree relative with DM2 had vascular dysfunction as compared to healthy controls. This may have been due to small sample size, a technique which did not look specifically at endothelial function, or some inherent difference within the African-American race. More investigation needs to be done to further delineate the relationship between AI and pre- diabetes and the metabolic syndrome, with possible emphasis on endothelial function. We found gender differences in AI in AA subjects. Whether the higher AI in AA females reflects early alterations in vascular function remains unknown. Division of Endocrinology, Diabetes, and Metabolism. The Ohio State University College of Medicine and Public Health. Columbus, Ohio, USA a The Ohio State University College of Pharmacy. Columbus, Ohio, USA. b * * P = 0.01 versus men Table 1. Baseline Clinical and Biochemical Characteristics Of African Americans With and Without a Family History of Type 2 Diabetes. * P = 0.01