Risk Factors for Insulin Resistance, Metabolic Syndrome, and Diabetes in 248 HFE C282Y Homozygotes Identified by Population Screening in the HEIRS Study

Metab Syndr Relat Disord. 2016 Mar;14(2):94-101. doi: 10.1089/met.2015.0123. Epub 2016 Jan 15.

Abstract

Background: We sought to identify risk factors for insulin resistance, metabolic syndrome (MetS), and diabetes mellitus in 248 non-Hispanic white HFE C282Y homozygotes identified by population screening.

Methods: We analyzed observations obtained prospectively in a postscreening examination: age; sex; body mass index (BMI); systolic/diastolic blood pressure; metacarpophalangeal (MP) joint hypertrophy; hepatomegaly; complete blood counts; alanine/aspartate aminotransferase levels; elevated C-reactive protein (>0.5 mg/dL); transferrin saturation; serum ferritin; homeostasis model assessment-insulin resistance (HOMA-IR); and MetS.

Results: Twenty-six participants (10.5%) had diabetes diagnoses. A significant trend across HOMA-IR quartiles was observed only for blood neutrophils. Logistic regression on HOMA-IR fourth quartile revealed positive associations: age (P = 0.0002); male sex (P = 0.0022); and BMI (P < 0.0001). HOMA-IR fourth quartile predicted MetS (P < 0.0001). Logistic regression on diabetes revealed positive associations: age (P = 0.0012); male sex (P = 0.0068); MP joint hypertrophy (P = 0.0167); neutrophils (P = 0.0342); and MetS (P = 0.0298). Serum ferritin did not predict HOMA-IR fourth quartile, MetS, or diabetes.

Conclusions: In screening C282Y homozygotes, age, male sex, and BMI predicted HOMA-IR fourth quartile. HOMA-IR fourth quartile alone predicted MetS. Diabetes was associated with greater age, male sex, MP joint hypertrophy, greater blood neutrophil counts, and MetS.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aged
  • Body Mass Index
  • Canada / epidemiology
  • Chi-Square Distribution
  • Diabetes Mellitus / diagnosis
  • Diabetes Mellitus / epidemiology
  • Diabetes Mellitus / genetics*
  • Female
  • Genetic Association Studies
  • Genetic Markers
  • Genetic Predisposition to Disease
  • Genetic Testing
  • Hemochromatosis / diagnosis
  • Hemochromatosis / epidemiology
  • Hemochromatosis / genetics*
  • Hemochromatosis Protein / genetics*
  • Homozygote*
  • Humans
  • Insulin Resistance / genetics*
  • Linear Models
  • Logistic Models
  • Male
  • Metabolic Syndrome / diagnosis
  • Metabolic Syndrome / epidemiology
  • Metabolic Syndrome / genetics*
  • Middle Aged
  • Odds Ratio
  • Phenotype
  • Prevalence
  • Prospective Studies
  • Risk Factors
  • Sex Factors
  • United States / epidemiology
  • White People / genetics

Substances

  • Genetic Markers
  • HFE protein, human
  • Hemochromatosis Protein