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

Abstract

OBJECTIVE 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. 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 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 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. 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.

Zinc in Prostate Health and Disease: A Mini Review

“…The Strong Heart Study and associated Strong Heart Family Study taken part by American Indian communities with baseline and two follow-up evaluations carried out approximately between 4 y and 8 y show that higher urinary Zn levels at baseline were associated with T2DM incidence [ 187 ]. The authors also record a similar association between urinary Zn level and pre-diabetes.…”

“…Until such time it is important to understand how to optimize the use of ingested Zn with lifestyle modifications and good health. These include cessation of tobacco smoking habits that cause higher systemic Cd burden [ 169 , 186 ] and compete with Zn binding sites on albumin and MTs; changing excessive alcohol consumption lifestyle known to associate with higher blood Cd levels [ 169 ]; refraining from excessive intakes of high-fat diets to prevent competition on Zn circulation through albumin [ 32 ] and preserve albumin structure for proper function [ 33 ]; minimizing stress to reduce ROS to facilitate stability of ZF proteins [ 124 ]; increasing consumption of fermented or germinated food products to avoid phytates to support Zn binding to albumin for circulation [ 20 ]; manage blood sugar levels to minimize diabetes or pre-diabetes which are known to associate with Zn urinary excretion [ 187 ]; increased plant-based diets to improve Zn transporter regulation by the phytochemical action [ 159 ], and plant fiber to increase gut transit time to optimize Zn absorption.…”

“…The Zn efflux transporter ZnT8 is known for the specific transport of Zn to insulin secretory granules of the pancreatic β cells for the required release of insulin [ 215 ]. Galvez-Fernandez et al, 2022 provide information on the involvement of Zn association with multiple factors leading to type II diabetes including the influence of a variant of the SLC30A8 gene encoding this protein [ 187 ]. In a study by these authors, men with type II diabetes or pre-diabetes showed increased Zn urinary excretion [ 187 ].…”

“…Galvez-Fernandez et al, 2022 provide information on the involvement of Zn association with multiple factors leading to type II diabetes including the influence of a variant of the SLC30A8 gene encoding this protein [ 187 ]. In a study by these authors, men with type II diabetes or pre-diabetes showed increased Zn urinary excretion [ 187 ]. Therefore, at the time of prostate cancer diagnoses, men with type II diabetes or pre-diabetes may require additional clinical support to adequately control blood sugar levels, to suppress diabetes-associated Zn urinary excretion which may otherwise further assist in prostate cancer progression.…”

Method validation for (ultra)-trace element concentrations in urine for small sample volumes in large epidemiological studies: application to the population-based epidemiological multi-ethnic study of atherosclerosis (MESA)

“…Higher urinary Zn levels seems to be associated with Type 2 Diabetes Mellitus (T2DM) incidence and prediabetes prevalence. 14 Cu is tightly regulated because both too much and too little is associated with oxidative cell damage, compromised immune function and organ dysfunction. 15,16 Larger longitudinal studies, in general populations, are needed to evaluate the association of trace element mixtures with various diseases, particularly for chronic low exposure levels.…”