Serum zinc and risk of type 2 diabetes incidence in men: The Kuopio Ischaemic Heart Disease Risk Factor Study

Yary, Teymoor; Virtanen, Jyrki K.; Ruusunen, Anu; Tuomainen, Tomi‐Pekka; Voutilainen, Sari

doi:10.1016/j.jtemb.2015.11.001

Cited by 54 publications

(36 citation statements)

References 23 publications

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“…However, AA was associated with a significantly lower risk of T2D only among those with lower serum zinc concentrations. These findings suggest that zinc may have a role in determining the impact of n-6 PUFAs on the risk of T2D and may also offer a potential explanation for the association of higher serum zinc concentration with increased risk of T2D in this study population (18). However, further studies in other populations are required to confirm our observations.…”

Section: Discussionsupporting

confidence: 68%

“…We previously observed in the KIHD study population that a high serum zinc concentration was associated with a higher risk of T2D (18). Zinc is an essential cofactor for desaturase enzymes (17), and animal studies have indicated that zinc has an important role in the metabolism of n-6 PUFAs (39).…”

Section: Discussionmentioning

confidence: 97%

“…As a secondary analysis we also investigated whether serum zinc concentration may modify the associations between D5D and D6D activities or n-6 PUFAs and risk of T2D. Zinc is an essential cofactor for the desaturase enzymes (17), and we previously found in the KIHD study that higher serum zinc concentrations were associated with a higher risk of T2D (18).…”

Section: Introductionmentioning

confidence: 99%

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Serum n–6 polyunsaturated fatty acids, Δ5- and Δ6-desaturase activities, and risk of incident type 2 diabetes in men: the Kuopio Ischaemic Heart Disease Risk Factor Study

Yary

Voutilainen

Tuomainen

et al. 2016

The American Journal of Clinical Nutrition

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Background: The role of n-6 (v-6) polyunsaturated fatty acids (PUFAs) in type 2 diabetes (T2D) is inconclusive. In addition, little is known about how factors involved in PUFA metabolism, such as zinc, may affect the associations. Objectives: We investigated the associations of serum n-6 PUFAs and activities of enzymes involved in PUFA metabolism, D5 desaturase (D5D) and D6 desaturase (D6D), with T2D risk to determine whether serum zinc concentrations could modify these associations. Design: The study included 2189 men from the prospective Kuopio Ischaemic Heart Disease Risk Factor Study, aged 42-60 y and free of T2D at baseline in 1984-1989. T2D was assessed by selfadministered questionnaires, by fasting and 2-h oral-glucose-tolerance test blood glucose measurement at re-examination rounds 4, 11, and 20 y after baseline, and by record linkage to the hospital discharge registry and the reimbursement register on diabetes medication expenses. Multivariate-adjusted Cox proportional hazards regression models were used to analyze associations. Results: During the average follow-up of 19.3 y, 417 men developed T2D. Those with higher estimated D5D activity (extreme-quartile HR: 0.55; 95% CI: 0.41, 0.74; P-trend , 0.001) and higher concentrations of total n-6 PUFAs (HR: 0.54; 95% CI: 0.41, 0.73; P-trend , 0.001), linoleic acid (LA; HR: 0.52; 95% CI: 0.39, 0.70; P-trend , 0.001), and arachidonic acid (AA; HR: 0.62; 95% CI: 0.46, 0.85; P-trend = 0.007) had a lower risk and those with higher concentrations of g-linolenic acid (GLA; HR: 1.28; 95% CI: 0.98, 1.68; P = 0.021) and dihomog-linolenic acid (DGLA; HR: 1.38; 95% CI: 1.04, 1.84; P-trend = 0.005) and higher D6D activity had a higher (HR: 1.50; 95% CI: 1.14, 1.97; P-trend , 0.001) multivariate-adjusted risk of T2D. Zinc mainly modified the association with GLA on T2D risk, with a higher risk observed among those with serum zinc concentrations above the median (P-interaction = 0.04). Conclusions: Higher serum total n-6 PUFA, LA, and AA concentrations and estimated D5D activity were associated with a lower risk of incident T2D, and higher GLA and DGLA concentrations and estimated D6D activity were associated with a higher risk. In addition, a higher serum zinc concentration modified the association of GLA on the risk of T2D.Am J Clin Nutr 2016;103:1337-43.

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Section: Discussionsupporting

confidence: 68%

Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

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Serum n–6 polyunsaturated fatty acids, Δ5- and Δ6-desaturase activities, and risk of incident type 2 diabetes in men: the Kuopio Ischaemic Heart Disease Risk Factor Study

Yary

Voutilainen

Tuomainen

et al. 2016

The American Journal of Clinical Nutrition

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“…Trace elements, such as zinc (Zn) and copper (Cu), may play a pivotal role in the pathogenesis of diabetes and diabetic vascular complications by mediating oxidative stress (1–4). Several studies have shown that both Zn deficiency and excess of Cu are associated with an increased risk of type 2 diabetes and cardiovascular disease (CVD) (2, 3, 5–9). …”

Section: Introductionmentioning

confidence: 99%

Serum Zn/Cu Ratio Is Associated with Renal Function, Glycemic Control, and Metabolic Parameters in Japanese Patients with and without Type 2 Diabetes: A Cross-sectional Study

2016

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BackgroundZinc (Zn) and copper (Cu) may play a pivotal role in the pathogenesis of diabetes and diabetic complications by mediating oxidative stress. Both Zn deficiency and excess of Cu are associated with an increased risk of type 2 diabetes and cardiovascular disease. We aimed to investigate the relationships between serum Zn/Cu ratio and glycemic status, renal function, and metabolic parameters in patients with and without type 2 diabetes.MethodsWe conducted a cross-sectional study on 355 subjects (149 type 2 diabetic and 206 non-diabetic) in whom serum Zn and Cu levels were measured at the same time. Associations between serum Zn/Cu ratio and clinical data were evaluated using multiple regression analysis. We also evaluated associations between serum Zn/Cu ratio and the prevalence of type 2 diabetes and glycemic control by multivariate logistic regression analysis.ResultsSerum Zn/Cu ratio was positively associated with estimated glomerular filtration rate after adjustment for body mass index (BMI) (β = 0.137, p = 0.014). Plasma B-type natriuretic peptide levels were negatively associated with serum Zn/Cu ratio after adjustment for age, sex, and BMI (β = −0.258, p = 0.032). In patients with type 2 diabetes, serum Zn/Cu ratio was negatively associated with plasma HbA1c levels after adjustment for age, sex, and BMI (β = −0.239, p = 0.003). In addition, multivariate logistic regression analysis revealed that the highest quartile of serum Zn/Cu ratio was associated with a reduced risk of poor (HbA1c ≥ 7%) glycemic control (odds ratio = 0.382; 95% confidence interval, 0.165–0.884; p = 0.025) in patients with type 2 diabetes.ConclusionSerum Zn/Cu ratio was favorably associated with renal function in all subjects and glycemic control in patients with type 2 diabetes. The Zn/Cu ratio, in addition to the individual serum levels of trace elements, is important for metabolism in humans.

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“…This is however not the case, as there is much controversy regarding the associations between zinc and several cardio-metabolic parameters and outcomes [30]. A number of experimental and observational studies have demonstrated associations between high serum zinc concentrations and adverse metabolic outcomes such as the metabolic syndrome [31][32][33] and diabetes [34]. Higher concentrations of serum zinc have also been associated with parameters such as obesity and lipids [30,32].…”

Section: Comparison With Previous Workmentioning

confidence: 99%

Serum zinc concentrations and incident hypertension

Kunutsor

Laukkanen

2016

Journal of Hypertension

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Serum zinc and risk of type 2 diabetes incidence in men: The Kuopio Ischaemic Heart Disease Risk Factor Study

Cited by 54 publications

References 23 publications

Serum n–6 polyunsaturated fatty acids, Δ5- and Δ6-desaturase activities, and risk of incident type 2 diabetes in men: the Kuopio Ischaemic Heart Disease Risk Factor Study

Serum n–6 polyunsaturated fatty acids, Δ5- and Δ6-desaturase activities, and risk of incident type 2 diabetes in men: the Kuopio Ischaemic Heart Disease Risk Factor Study

Serum Zn/Cu Ratio Is Associated with Renal Function, Glycemic Control, and Metabolic Parameters in Japanese Patients with and without Type 2 Diabetes: A Cross-sectional Study

Serum zinc concentrations and incident hypertension

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