Data analysis
We used sampling weights to calculate prevalence estimates for the civilian noninstitutionalized US population. Because of the complex sampling design of the survey, we performed all analyses with SUDAAN.24
We initially computed unadjusted estimates of the likelihood of development of diabetes for different levels of elevated serum transferrin saturation between 1971 and 1974. We attempted to compute analyses for serum transferrin saturation levels of 60% and 62%, but the number of people who developed diabetes with those levels was so small (n
Because we could not determine whether individuals with elevated serum transferrin saturation received treatment for hemochromatosis during the time of the study, we computed a series of analyses assuming that different proportions of individuals received treatment during the time frame. Some national evidence has suggested that few individuals are diagnosed with hemochromatosis. In fact, in the 1996, 1997, and 1998 National Ambulatory Medical Care Surveys, there were 7 visits for hemochromatosis of 64,001 total evaluated visits (0.01% of visits).8 We recomputed the adjusted odds ratios for the samples of people with transferrin saturation rates greater than 45% and 50% after randomly selecting 10% of each group and treating those individuals as though they were undergoing therapeutic phlebotomies.
Results
Table 1 presents the characteristics of the population with baseline characteristics and characteristics measured in the follow-up data collection. A substantial proportion of the adult population had elevated serum transferrin saturation greater than 45%, 50%, and 55%. The incidence of diagnosed diabetes in the cohort was 10.2%.
Among individuals with serum transferrin saturation levels greater than 45% at the NHANES I baseline, 8.9% developed diagnosed diabetes compared with 10.3% who did not have elevated serum transferrin saturation (P = .44). Similarly, among individuals with serum transferrin saturation levels greater than 50% at the NHANES I baseline, 8.1% developed diagnosed diabetes compared with 10.3% who did not have elevated serum transferrin saturation (P = .34); of individuals with transferrin saturation levels greater than 55%, 7.5% developed diabetes compared with 10.2% of those without elevated serum transferrin saturation (P = .38). Table 2 indicates that individuals with elevated transferrin saturation levels are not significantly more likely to develop diagnosed diabetes than individuals without elevated serum transferrin saturation. The lack of a significant relation is present in unadjusted and adjusted analyses.
When we reestimated the models assuming that 10% of the population with elevated serum transferrin saturation (> 45%) were successfully treated, individuals with elevated serum transferrin saturation were not significantly more likely to develop diagnosed diabetes than individuals without elevated serum transferrin saturation. This relation held in unadjusted and adjusted analyses. When we assumed that 10% of the population with elevated serum transferrin saturation at greater than 50% and greater than 55% were successfully treated, individuals with elevated serum transferrin saturation were not significantly more likely to develop diagnosed diabetes than individuals without elevated serum transferrin saturation. These relations remained consistent in unadjusted and adjusted analyses.
TABLE 1
Baseline characteristics of the population collected in National Health and Nutrition Examination Survey I
| Characteristic | Value |
|---|---|
| Male sex | 47.7% |
| Race | |
| European American | 90.7% |
| African American | 8.7% |
| Other | 0.6% |
| Age, mean ± standard error (y) | 47.1 ± 0.2 |
| Obesity (body mass index ≥ 27) | 32.3% |
| Transferrin saturation (cumulative) | |
| > 45% | 8.0% |
| > 50% | 4.6% |
| > 55% | 2.7% |
| > 60% | 1.7% |
| > 62% | 1.4% |
| Total serum cholesterol (>240 mg/dL) | 32.0% |
| Hypertension (informed by physician) | 13.6% |
| Collected in NHFES follow-up | |
| Developed diabetes | 10.2% |
| NHFES, National Health and Nutrition Examination Survey I (NHANES I) merged with the NHANES I Epidemiologic Followup Study. | |
TABLE 2
Unadjusted and adjusted odds of developing diabetes with an elevated serum transferrin saturation level
| Transferrin saturation | Unadjusted OR (CI) | Adjusted* OR (CI) |
|---|---|---|
| Original data | ||
| > 45% | 1.17 (0.78–1.75) | 0.89 (0.59–1.34) |
| > 50% | 1.29 (0.73–2.29) | 0.95 (0.53–1.70) |
| > 55% | 1.40 (0.60–3.27) | 1.03 (0.44–2.43) |
| Assuming 10% treatment | ||
| > 45% | 1.23 (0.8–1.9) | 0.94 (0.61–1.47) |
| > 50% | 1.29 (0.7–2.39) | 0.96 (0.52–1.79) |
| > 55% | 1.41 (0.56–3.58) | 1.05 (0.41–2.67) |
| *Controlling for age, sex, race, hypercholesterolemia, obesity, and hypertension. | ||
| CI, 95% confidence interval; OR, odds ratio. | ||
Discussion
The findings of this study call into question the commonly held assumption that there is a causative relation between the presence of hemochromatosis and the subsequent development of diabetes mellitus. Although diabetes is a common comorbid condition with hemochromatosis,13,14 this may be due to the fact that both conditions are relatively common, not that one disease leads to the development of the other. In this longitudinal analysis, even when examining the likelihood of developing diabetes at different levels of transferrin saturation, the findings suggested that hemochromatosis does not lead to diabetes.
Could the findings of the current study be explained by the fact that people were treated for hemochromatosis, thus reducing the subsequent development of complications such as diabetes? This seems unlikely because few people with hemochromatosis are routinely identified, and even fewer are treated on a chronic basis. On the contrary, the phenomenon that few people with hemochromatosis are diagnosed and treated is the rationale for recent recommendations for screening asymptomatic persons. Further, in unadjusted and adjusted analyses of the current study, people with elevated transferrin saturation were no more likely to develop diabetes than people without elevated transferrin saturation, even after assuming that 10% of the population with elevated transferrin saturation (> 45%, > 50%, and > 55%) were successfully treated.