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Treatment guidelines for diabetes have become increasingly stringent as most research shows that more aggressive intervention reduces the risks for complications. Community data on the effect of these interventions are lacking.Changes in the pharmacologic treatment of diabetes, blood pressure, and cholesterol in adults with diabetes were analyzed in a longitudinal population-based study of American Indians from 10 independent 3-year time intervals between 1975 and 2004. Trends in drug use were assessed by logistic regression models and trends in glycemia, blood pressure, and cholesterol were assessed by linear models.Among the study participants, the use of any medicine for the treatment of diabetes increased from 53% in 1975–1978 to 67% in 2002–2004, Ptrend < 0.0001. The use of insulin as a single agent declined, and the use of combinations of insulin and oral agents increased. In 1990–1992, 23% of subjects had an A1C <7% and by 2002–2004, the proportion had increased to 33%, Ptrend < 0.0001. The use of anti-hypertensive medicine increased from 21% in 1975–1977 to 58% in 2002–2004, Ptrend < 0.0001, coincident with a decline in mean systolic blood pressure from 137 mmHg in 1975–1977 to 123 mmHg in 2002–2004, Ptrend < 0.0001. The use of lipid-lowering medicine also increased with an accompanying increase in HDL and a decrease in non-HDL cholesterol concentration.Major changes in community treatment patterns for diabetes and related conditions coincided with improvements in glycemia, blood pressure, and cholesterol.