Base Case Results
The model predicted that cardiovascular complications would be the most frequently experienced complications in all patient subgroups (44–54% lifetime incidence coronary heart disease) (). Microvascular complications had lower lifetime incidences that varied with starting age of the simulation and duration of diabetes. The incidence of end-stage renal disease and amputation declined with increasing starting age but rose with increasing duration of diabetes. Conversely, incidence of blindness increased with increasing starting age but declined with increasing disease duration; these patterns reflect the inclusion of age at onset of diabetes as a predictor in the UKPDS blindness model.
Baseline predictions for moderate glucose control and expected benefits of intensive glucose control in older patients with no comorbid illnesses or functional impairments.*
Life expectancy declined with increasing starting age and increasing duration of diabetes. The model’s life expectancy predictions for healthy older patients with new onset diabetes matched expectations from epidemiological studies of mortality and diabetes (50
). Quality-adjusted life expectancy was 1–1.5 years less than unadjusted life expectancy.
The overall magnitude of expected benefits of achieving intensive glucose control compared to moderate glucose control declined as the age of hypothetical patients rose (). With rising starting simulation age, the level of absolute risk reduction declined for end-stage renal disease and amputation but remained stable for blindness and coronary heart disease. Life expectancy and quality of life benefits declined with rising age. The expected benefit of intensive glucose control was 106 (95% Confidence Intervals (CI), 95–117) quality-adjusted days at age 60–64 years of age and declined to 52 (CI, 46–58) days at 75–79 years of age among individuals with no comorbid illness or functional impairment. Increasing duration of diabetes had the opposite effect of increasing the overall expected quality of life benefits of intensive glucose control. For 60–64 year old patients, the overall quality of life benefit increased from 106 days for new-onset diabetes to 114 days for duration of diabetes beyond five years.
Larger differences in the expected benefits of intensive glucose control were observed within each age group with changes in the mortality index score (, Appendix Figure 1). As the index score increased, life expectancy declined. In the case of patients 60–64 years of age with new diabetes, life expectancy declined from 14.6 (CI, 14.4–14.7) years at baseline, to 9.7 (CI, 9.6–9.9) years with 3 additional index points, and to 4.8 (CI, 4.7–4.9) years with 7 additional index points. As life expectancy declined, so did expected benefits. Over the same interval of index points, life expectancy benefits declined from 114 (CI, 101–128) days to 41 (CI, 34–48) days to 5 (CI, 3–8) days, and quality-adjusted benefits declined from 106 (CI, 95–117) days to 44 (CI, 38–50) days to 8 (CI, 5–10) days.
Expected quality of life benefits of intensive glucose control for 60–64 year old and 75–79 year old patients
The negative associations between life expectancy, benefits, and the mortality index score were also observed for patients with greater duration of diabetes. Again, life expectancy declined with an increasing index score. For patients 60–64 years of age and 10–15 years of diabetes, life expectancy declined from 13.5 (CI, 13.3–13.6) years at baseline to 8.0 (CI, 7.9–8.1) years with 4 additional index points and to 3.9 (CI, 3.8–4.0) with 8 additional index points. Over the same intervals, the expected benefits declined from 116 (CI, 103–129) quality-adjusted days, to 36 (CI, 29–43) days, to 8 (CI, 6–11) days ().
When examining these interrelationships by specific complications, we found distinct patterns for different complications (, Appendix Figure 2). For end-stage renal disease, there is a decline in absolute risk reduction as the mortality index score rises, even among patients with extended duration of diabetes (). On the other hand, the benefits of preventing amputation declined but remained close to an absolute risk reduction over 0.5% percent at high index scores, when duration of diabetes exceeded five years (). These distinct patterns reflect differences in the size of baseline incidence rates and differences in assumptions regarding how glucose control affected individual complication rates.
Expected differences in lifetime incidence of specific complications for 60–64 year old and 75–79 year old patients
When we used Framingham models, the predicted rates of cardiovascular disease were lower and life expectancies were higher than in the base case analysis, but expected benefits of intensive glucose control were lower. For patients 60–64 years of age with new diabetes and moderate glucose control, the incidence of coronary heart disease declined from 52% to 37 (CI, 36–38)% and life expectancy increased from 14.6 to 16.1 (CI, 15.9–16.3) years. Despite longer life expectancy, the expected benefits of intensive control were found to be less than half of those observed in the base case (e.g,44 (CI, 38–50) instead of 106 quality-adjusted days) due to the absence of glucose control as a predictor in the Framingham models. With all of these changes, the basic relationship between the mortality index score and expected benefits observed earlier was maintained. Expected benefits for the same 60–64 year old patients declined from 44 (CI, 38–50) days to 16 (CI, 13–19) days with 3 additional index points and to 3 (CI, 2–4) days with 7 additional index points.
In other sensitivity analysis, we generally found that results did not deviate significantly from the base case analysis. When we assumed no inflation of the non-diabetic background mortality rate, life expectancies increased by 2–3 years and the magnitude of expected benefits increased (e.g., 106 to 126 (CI, 115–137) quality-adjusted days for healthy 60–64 year old patents with new diabetes). Expected benefits continued to decline with a rising mortality index score but at slightly higher index scores compared to the base case. For example, in the same 60–64 year old patients mentioned earlier, expected benefits were reduced to less than 20 quality-adjusted days with 10 additional index points instead of 7 index points. In subgroup analyses, we found small differences in these patterns between men and women; for 60–64 year old patients, benefits dropped below 20 quality-adjusted days for men at 5 additional index points while women had this decline at 7 additional index points.
Different comparisons of glucose control levels altered the baseline magnitude of benefits of achieving lower glucose control targets, but did not significantly alter the importance of the index score on the expected benefits. For healthy 60–64 year old patients with new diabetes the benefit was 131 quality-adjusted days for a comparison HbA1C of 9.0% and 7.9% and 52 days for a comparison HBA1C of 7.0% and 6.5%. In the case of the first comparison, the benefit declined to 10 days with 7 additional index points. In the case of the second comparison, the benefit declined to 3 days with 7 additional index points.
In our analyses of utility assumptions, we found that model results were highly sensitive to differences in treatment state utilities. If the every day quality of life experience of intensive glucose control was lower than moderate glucose control by more than 0.02 (i.e., a 2% reduction in daily quality of life from perfect health, 1.00 vs. 0.98), intensive control became a harmful therapy. Model results did not change significantly when using lower utilities for complication states.