The plasma glucose and insulin response to a standardized meal test breakfast was compared with the time-honored glucose tolerance test in the same normal healthy subjects. The amplitude of glycemic excursion and between-subject variation was less with the more physiologic standardized test meal than with that seen with the glucose tolerance test. The glucose tolerance test's prime function is to amplify any glucose intolerance, thus aiding diagnosis, whereas a standardized meal gives a more clinically relevant metabolic status. The administration of serial test meals during the same day in a smaller group of normal subjects indicated, as seen previously with repeated glucose tolerance tests, a diminishing carbohydrate tolerance during the day.
Based on prevailing hypotheses about the role of renin in essential hypertension, both Laragh and Buhler independently predicted that angiotensin-converting enzyme (ACE) inhibitors would become less effective with increasing age, as elderly hypertensive patients tend to have low plasma renin activity. We have investigated this situation in a large postmarketing surveillance study with enalapril. Following a 2-week no-treatment period, a total of 11,710 patients with essential hypertension received 10–20 mg of enalapril once daily for 6 weeks. BP was measured on two occasions prior to enalapril treatment, and on two occasions during enalapril treatment (after 2 and 6 weeks). Enquiry for symptom events was also made on each of these four occasions. Systolic BP (SBP) prior to enalapril treatment rose steeply with increasing age, whereas diastolic BP (DBP) rose only very slightly with age and reached a plateau by the 5th decade. The fall in SBP in response to enalapril increased with increasing age, but DBP was relatively uninfluenced by age. However, when corrected for initial BP, the percentage changes in both SBP (13%) and DBP (14%) were not different across the age range studied. Prior to receiving enalapril, 67.8% of patients were reporting symptoms, and this showed a positive correlation with age. During enalapril therapy, the overall level of symptom events reported fell significantly in all age groups (35.0%) but more so in the elderly, such that at the end of the study no significant age-related difference was detected. In all age groups, more than half of the events reported during enalapril therapy were of an improvement in general well-being. This study further supports the view that, contrary to earlier predictions, ACE inhibitors are at least as effective in elderly hypertensive patients as in younger patients. This may also be accompanied by a significant reduction in the number of adverse events reported, particularly in the most elderly. As age and BP are both continuous variables and are related to each other, they must be considered as continuous variables in the assessment of treatment effects. To use arbitrary definitions for the elderly (e.g. > 60 years or > 65 years) will only serve to exaggerate age-related phenomena and may lead to inappropriate recommendations for drug use.
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