Hyperglycemia can increase urinary zinc excretion. We evaluated the association of higher urinary zinc level with new diagnosis of incident type 2 diabetes mellitus (T2DM) in adult populations with a high burden of T2DM from AZ, OK, and ND and SD. We also assessed the cross-sectional association of urinary zinc levels with prevalent prediabetes.


We included 1,339 adults free of T2DM at baseline (1989–1991) followed through 1998–1999 in the Strong Heart Study (SHS) and 1,905 family members of SHS participants followed as part of the Strong Heart Family Study (SHFS) through 2006–2009.


T2DM incidence was 14.7% (mean follow-up 6.6 years) in the SHS and 13.5% (mean follow-up 5.6 years) in the SHFS. After adjustment for sex, site, education, smoking status, BMI, and estimated glomerular filtration rate, the hazard ratio of T2DM in comparing 75th vs. 25th percentiles of urinary zinc distribution was 1.21 (95% CI 1.08, 1.36) in the SHS and 1.12 (0.96, 1.31) in the SHFS. These associations were attenuated but significant in the SHS after adjustment for HOMA of insulin resistance (HOMA-IR) score. With exclusion of participants with prediabetes at baseline, urinary zinc remained significantly associated with T2DM in the SHS. In cross-sectional analyses, prediabetes was associated with higher urinary zinc levels.


Urinary zinc levels were associated with T2DM incidence and prediabetes prevalence even after adjustment for HOMA-IR in populations with a high burden of T2DM. These results highlight the importance of zinc metabolism in diabetes development.

This article contains supplementary material online at https://doi.org/10.2337/figshare.20610612.

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