Most observational studies indicate that hormone replacement therapy (HRT) protects women from cardiovascular disease. Two recent randomized trials, however, showed no reduction in coronary events with HRT in postmenopausal women. A randomized study evaluating subclinical atherosclerosis showed a beneficial effect of estrogen. In the current study we evaluated the association between HRT and coronary artery atherosclerosis, as quantified by coronary artery calcium score. Current users of HRT were significantly more likely to have a coronary artery calcium score less than 100 and were less likely to have a score greater than 400 than non-HRT users. After adjustment for cardiac risk factors, current use of HRT was associated with a significant reduction of coronary artery calcium score (-28; 95% confidence interval, -48 to -10). The average age of users was 59 yr, the mean duration of use was 9 yr, and the duration of HRT use was significantly associated with a reduction in coronary artery calcium. These results suggest that HRT suppresses atherosclerosis in the coronary arteries. The failure to modify the cardiovascular event rate in clinical trials could result from the adverse effect of HRT on complicated lesions. Additional mechanistic studies may help identify therapeutic strategies that could maximize a potential benefit of HRT on early atherogenesis while minimizing adverse proinflammatory and procoagulant effects on complicated plaque lesions.

Rapid-acting inhaled (Afrezza) and injected mealtime insulins are available for patients with type 2 diabetes who are also treated with basal insulin. In this interim analysis of a single-site, observational, investigator initiated study, time spent in glycemic goal range (70-180 mg/dL) without significant hypoglycemia (primary endpoint) was assessed in the intent-to-treat population of patients with type 2 diabetes (N=25; 60%M; age 62y; wt 95.7±4.4kg; A1c 8.3±0.2%). Patients were titrated from pre-meal insulin plus basal insulin to inhaled insulin plus basal insulin over 2 weeks and followed for 14 weeks. At Week 14, mean (±SE) times spent above (>180 mg/dL; -1.7±3.2 mins; P=0.60), in (70 180 mg/dL; -1.2±2.6 mins; P=0.65), and below (<70 mg/dL; +2.9±2.5 mins; P=0.26) glycemic goal range were not significantly different from baseline. However, A1c significantly decreased from baseline at Week 14 (-0.76%±0.18; P=0.0002). At Week 14, Quality of Life (QoL) Total score did not significantly change from baseline (+0.19±0.13; P=0.15). However, Useful (+0.46±0.20; P=0.03), Freeing (+0.92±0.24; P=0.0008), and Difficult ( 0.68±0.28; P=0.02) QoL subdomains significantly improved from baseline at Week 14. There were no deaths, no serious hypoglycemic events, but 4 patients discontinued (3 upper respiratory tract, 1 diarrhea). Five patients experienced cough, 2 patients chest mucus/congestion, and 2 patients cough/chest congestion. Most upper respiratory events were associated with use of >60 units/day inhaled insulin. Although this interim analysis did not achieve its primary endpoint of significant increase of time spent in glycemic goal range, possibly caused by patients not self-adjusting post-prandial dosing as instructed. Patients treated with inhaled insulin with background basal insulin for 14 weeks experienced significant reduction of A1c and significant improvements of Useful, Freeing, and Difficult QoL subdomains compared to baseline. Disclosure M. Kipnes: None. A. Salhin: None. T. Ryan: None. J. Vadakekalam: None. V. Pamar: None. F. Trigoso: None. F. Akhrass: None. Funding MannKind Corporation