Overall NHANES response rates were 76–80% throughout the specified years. Of 8,654 participants age 45+, 7,883 completed the laboratory examination and 7,272 had no missing data on specified covariates and were included in a complete case analysis. A total of 1,443 people with DM age 45+ years with sampling weights were representative of approximately 12,333,000 people with DM in the US. People with DM were older, less often White, less highly educated and had lower household income than their counterparts without DM (results not shown).
Compared to middle-aged adults with DM, older adults with DM were more likely to be female, White, have health insurance, have a low income and have access to health care but were less likely to have completed >12 grades of education (). These variables were examined as potential confounders of hospitalization, but after accounting for TEMs only age and access to health care were significantly associated with the outcome and were used in the final models.
Baseline Demographic Characteristics in Diabetes Mellitus, Overall and By Age Group: NHANES 1999–2004.
Age-stratified prevalence of TEMs was examined among people with DM (). Relative to adults ages 45 to 64, prevalence of TEMs was higher among individuals who were 65 or older, most notably for polypharmacy and low GFR. High ALT and frequent mental distress were less prevalent in old age. The prevalence of having any 2 or any 3 physiologic or health status TEMs was high, such that 19.0% (95%CI: 14.8–23.2) of adults ages 45–64 and 38.0 % (95%CI: 33.4–42.5) of adults ages 65+ had any 2 physiologic TEMs and 16.1% (95%CI: 10.2–22.1) of adults 45–64 and 40.9% (95%CI: 35.3–46.5) of adults ages 65+ had any 2 health status TEMs. [ about here]
Prevalence of Physiologic (a) and Health Status (b) Potential Treatment Effect Modifiers among Adults with Diabetes Mellitus, by Age Group: NHANES 1999–2004
Simulated Randomized Controlled Trial with Real Distribution of Treatment Effect Modifiers among Adults with Diabetes Mellitus, NHANES 1999–2004
Example of Potential Impact by Observed Prevalence of TEMs on Treatment in Older Adults
A simulated randomized, controlled trial of a treatment lowering HbA1c by 2% on average was performed (). At a low level of treatment effect modification there was average benefit, or lowering of HbA1c, regardless of numbers of TEMs. However, at small or modest levels of effect modification the benefit was cancelled in 3.9–27.2% of older adults with DM. Furthermore, because TEMs are correlated with increasing age, treatment effect was modified with age at an effect modification level of 0.2 or higher (p-value for interaction term = .001 for 0.2 and <.001 for 0.3 or 0.4). [ about here]
Prevalence in DM and Rate Ratios for Number of Hospitalizations for Mutually Exclusive Patterns of Potential Treatment Effect Modifiers: NHANES 1999–2004.
Clinical Patterns of TEMs among People with DM and Association with Hospitalization Rate
Mutually exclusive clinical patterns of TEMs were examined and those present in >2% of people with DM are shown in . Among people with DM, TEMs were absent in 39.0% (95% CI: 34.5–43.6) and 37.7% (95% CI: 28.9–46.5) for physiologic or health status modifiers, respectively. Most clinical patterns of diabetes and physiologic TEMs were associated with a substantially higher number of hospitalizations. Hospitalization rates within the last year among study participants with DM were greater by a factor of 5.53 (95%CI: 3.06–10.0) among people with both CHF and polypharmacy, compared to people with DM but no physiologic TEMs. Fewer patterns of health status treatment effect modifiers were highly prevalent.
Adding laboratory-based criteria for DM to account for unreported DM as described in Methods resulted in 111 additional cases of DM. Of the unreported cases, 67.4% were middle-aged adults. Results were not altered consistently, substantively nor significantly by adding unreported DM to the sample (results not shown).