The Tuberculous Diabetic

by a control period of at least ten days during which fractional and twenty-four-hour urine specimens are analyzed daily for glucose and, if positive, for ketone bodies and both fasting and postprandial blood sugar levels are determined each day. If blood and urinary glucose remain within acceptable limits as defined above, the patient needs neither insulin nor oral drug and has proved himself an unsuitable subject. If hyperglycemia and glycosuria appear or continue during the control period, the drug to be tested is added to the regimen, with no other change, for the next ten days (test period), during which comparable data are collected and signs of toxicity watched for. A recovery period of similar length terminates the observations. If during the test period normal or nearly normal glucose levels are achieved, it can be concluded that the compound is effective for the patient in question and possibly for others of a similar type. If good control is not obtained, the compound is not as good as insulin for this patient and the opposite conclusions can be drawn. Ideally, a period with a placebo instead of the test substance should follow the recovery period, but this adds materially to the time required and is far less important in hospital than outpatient observations. Obviously, this elaborate and time-consuming kind of study is not suitable for large numbers of patients or for the determination of long-term toxicity. Its purpose is to provide unassailable data on the effect of a given preparation in a few carefully selected subjects with diabetes of various types and degrees of severity. Only after the accumulation of this sort of information should the base of clinical testing be broadened to include ambulatory cases. With respect to office or clinic patients, we are not concerned here with single-dose response tests of a few hours' duration but with the effectiveness and safety of drugs on a maintenance basis. The procedure follows the general scheme just presented but with two important modifications: Insulin must be withdrawn slowly rather than abruptly in order to guard against ketosis, and the "double-blind" method of administering the test drug and a placebo is imperative. The inherent difficulties of this kind of observation are mitigated to some extent by longer control, test and recovery periods; weekly visits at which blood sugar and quantitative (twenty-four-hour) urinary glucose are determined; written records of home urine tests made four times daily; and measurements of body weight. Short-cuts in these procedures have been taken too often in the past, and the tendency to take them is currently increasing with the successive introduction of new forms of the sulfonylureas and other hypoglycemic agents. The fact that a new drug differs from its predecessor by only an atom or two is no guarantee that either its biologic activity or its safety is identical. Witness the example of carbutamide, in which merely the substitution of a methyl for an amino group converted that compound to one (tolbutamide) which is appreciably less toxic and lacks bactericidal properties while retaining essentially the same hypoglycemic potency. In the interest of sound medical practice and public safety, and despite the pressure of commercial competition, each new compound, however similar to others, deserves the same careful clinical testing as if its close relatives had never been heard of.