OBJECTIVE -We examined the relationship among iron stores, the metabolic syndrome, and insulin resistance.RESEARCH DESIGN AND METHODS -We conducted a cross-sectional study of 6,044 adults Ͼ20 years of age who participated in the Third National Health and Nutrition Examination Survey. Metabolic syndrome was defined as the presence of at least three of the following: elevated blood pressure, low HDL cholesterol, elevated serum triglycerides, elevated plasma glucose, and abdominal obesity. Insulin resistance was estimated using homeostasis model assessment (for insulin resistance), fasting insulin, and triglyceride-to-HDL cholesterol ratio.RESULTS -After excluding individuals with likely hemochromatosis, mean serum ferritin values in premenopausal women, postmenopausal women, and men were 33.6, 93.4, and 139.9 g/l, respectively. Metabolic syndrome was more common in those with the highest compared with the lowest levels of serum ferritin in premenopausal women (14.9 vs. 6.4%, P ϭ 0.002), postmenopausal women (47.5 vs. 28.2%, P Ͻ 0.001), and men (27.3 vs. 13.8%, P Ͻ 0.001). Insulin resistance also increased across quartiles of serum ferritin for men and postmenopausal women and persisted after adjustment for age, race/ethnicity, C-reactive protein, smoking, alcohol intake, and BMI.CONCLUSIONS -Elevated iron stores were positively associated with the prevalence of the metabolic syndrome and with insulin resistance. Diabetes Care 27:2422-2428, 2004T here is increasing evidence that moderately elevated body iron stores, below levels commonly found in genetic hemochromatosis, may be associated with adverse health outcomes. Elevated serum ferritin levels independently predicted incident type 2 diabetes in prospective studies in apparently healthy men and women (1,2). In cross-sectional studies, elevated ferritin levels have been associated with hypertension (3), dyslipidemia (4,5), elevated fasting insulin and blood glucose (6), and central adiposity (7). The association between elevated iron stores and the metabolic syndrome, however, has been less well explored (8).Although the mechanisms for the potential effect of iron on the risk of metabolic syndrome are unclear, it has been hypothesized that elevated iron stores may interfere with hepatic insulin extraction leading to peripheral hyperinsulinemia (9,10). Others have suggested that iron may catalyze the formation of hydroxyl radicals, which contribute to the development of insulin resistance (11,12).We hypothesized that the metabolic syndrome would be more common in those with moderately elevated serum ferritin levels. To test this hypothesis, we conducted a cross-sectional analysis using representative data from the general U.S. population. RESEARCH DESIGN AND METHODS -The Third NationalHealth and Nutrition Examination Survey (NHANES III) was conducted by the National Center for Health Statistics between 1988 and 1994. The survey was a multistage nationwide probability sample of the civilian, noninstitutionalized U.S. population. The study design included a home ...

Abstract-National guidelines for the prevention and treatment of hypertension recommend sodium reduction, weight loss, the Dietary Approach to Stop Hypertension (DASH) diet, and regular aerobic exercise. However, no trial has assessed the efficacy of simultaneously implementing all of these recommendations. The objective of this study was to determine the effects on blood pressure and other cardiovascular disease risk factors of a comprehensive lifestyle intervention. We conducted a randomized controlled trial of 44 hypertensive, overweight adults on a single blood pressure medication.Participants were randomized to a lifestyle or control group. For 9 weeks, the lifestyle group was fed a hypocaloric version of the DASH diet that provided 100 mmol/d of sodium. This group also participated in a supervised, moderate-intensity exercise program 3 times per week. The control group received no intervention. Outcomes were ambulatory blood pressure, serum lipids, weight, and fitness. At the end of the intervention, mean weight loss in the lifestyle group, net of control, was 4.9 kilograms. In the lifestyle group mean net reductions in 24-hour ambulatory systolic and diastolic blood pressures were 9.5 mm Hg (PϽ0.001) and 5.3 mm Hg (PϽ0.002), respectively. Corresponding changes in daytime systolic and diastolic blood pressures were 12.1 mm Hg (PϽ0.001) and 6.6 mm Hg (PϽ0.001).

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The authors performed a case-cohort study nested within the Atherosclerosis Risk in Communities (ARIC) Study to determine the association between plasma ferritin level and risk of type 2 diabetes mellitus. Persons with incident cases of type 2 diabetes diagnosed over an average follow-up period of 7.9 years (n = 599) were compared with a random sample of the cohort (n = 690). After adjustment for age, gender, menopausal status, ethnicity, center, smoking, and alcohol intake, the hazard ratio for diabetes, comparing the fifth quintile of ferritin with the first quintile, was 1.74 (95% confidence interval: 1.14, 2.65; p-trend < 0.001). After further adjustment for body mass index and components of the metabolic syndrome, the hazard ratio was 0.81 (95% confidence interval: 0.49, 1.34; p-trend = 0.87). From a causal perspective, there are two alternative interpretations of these findings. Elevated iron stores, reflected in elevated plasma ferritin levels, may induce baseline metabolic abnormalities that ultimately result in diabetes. Alternatively, elevated ferritin may be just one of several metabolic abnormalities related to the underlying process that ultimately results in diabetes, rather than a causal factor for diabetes. Longitudinal studies with repeated measurements of glucose and iron metabolism parameters are needed to establish the role of iron stores and plasma ferritin in diabetes development.