Urinary Zinc and Incident Type 2 Diabetes: Prospective Evidence from the Strong Heart Study

Objective: Hyperglycemia can increase urinary zinc excretion. We evaluated  the association of higher urinary zinc with newly diagnosis of incident type 2 diabetes (T2DM incidence) in adult populations with a high burden of T2DM from Arizona, Oklahoma, North Dakota and South Dakota. We also assessed the cross-sectional association of urinary zinc levels with prevalent prediabetes.

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

Results: 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 (95%CI) of T2DM comparing 75th vs. 25th percentiles of urinary zinc distribution was 1.21 (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-IR score. Excluding 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. 

Conclusions: 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.