The Journal of Clinical Endocrinology & Metabolism, 2022, 107, e3099–e3100

https://doi.org/10.1210/clinem/dgac185
Advance access publication 24 March 2022
Letter to the Editor Response

Response to Letter to the Editor From Pattan et al

“U-shaped Association Between Dietary Zinc Intake and
New-onset Diabetes: A Nationwide Cohort Study in China”
Panpan He,1 Chengzhang Liu,2 and Xianhui Qin1,
1
Division of Nephrology, Nanfang Hospital, Southern Medical University; National Clinical Research Center for Kidney Disease; State Key

Downloaded from https://academic.oup.com/jcem/article/107/7/e3099/6553918 by guest on 13 June 2023

Laboratory of Organ Failure Research; Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure
Research, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangdong Provincial Clinical Research Center for Kidney
Disease, Guangzhou, China
2
Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China
Correspondence: Xianhui Qin, M.D, National Clinical Research Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Division of
Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. Email: pharmaqin@126.com.

To the Editor:
We thank Professor Pattan et al (1) for their insightful
comments.
The intake of micronutrients, such as zinc, on the risk of
diabetes, is an important and interesting topic that remains
to be elucidated. Previous cross-sectional studies (2) had pro-
vided some clues, but this type of design cannot determine tem-
poral and causal relations. Prospective studies (3, 4), however,
reported inconsistent conclusions. Our recent study (5), in a
relatively large-scale, nationally prospective cohort, observed
a U-shaped association between dietary zinc intake and new-
onset diabetes in the general population of Chinese adults, with
an inflection point at about 9.1 mg/day and minimal risk at 8.9
to 12.2 mg/day of dietary zinc intake. However, some important
issues in this field need to be further discussed.
First, although a previous study (2) suggested that serum
zinc concentration was highly correlated with daily zinc in-
take, serum zinc concentration was not available in the China
Health and Nutrition Survey (CHNS) study. As such, we
could not examine the correlation between serum zinc con-
centration and dietary zinc consumption, as well as the re-
lationship between serum zinc concentration and diabetes.
Although the absorption of zinc was a complex process and
may be influenced by several factors, we have further adjusted
not only the intakes of micronutrients including vitamin A,
riboflavin, niacin, vitamin C, copper, magnesium, and iron
but also the intakes of major food groups of zinc, including
aquatic, nut, red meat, and whole grain to reduce the possible
confounding effects. Besides, CHNS does not have detailed
information on dietary supplement use. However, data from
the 2010 to 2012 China Nutrition and Health Surveillance
(6), a nationally representative in China, showed that only
0.21% of the Chinese population reported using zinc supple-
ments. Because of the low supplement proportion of zinc, we
speculate that our results may not be materially changed by
the dietary supplement use.
Second, the associations between dietary zinc intake and
the risk of diabetes are inconsistent in previous studies.
These inconsistent findings might be due to differences in
the target population, dietary zinc intake levels, and sample
size (5). We reported a U-shaped association between dietary
zinc intake and new-onset diabetes among Chinese adults
(n = 16 257) (5). The inflection point we reported in Table
2 was determined using the likelihood-ratio test and boot-
strap resampling method by the R package segmented. We
found that the dietary zinc intake and new-onset diabetes as-
sociation was different by different dietary zinc intake. The
risk of new-onset diabetes was significantly lower in partici-
pants with zinc intake < 9.1 mg/day and higher in those with
zinc intake ≥ 9.1 mg/ day. In Table 3, we divided the dietary
zinc intake into deciles and found that the deciles 2 through
8 (dietary zinc intake: 8.9-<12.2 mg/day) had a lower risk
of new-onset diabetes. These all indicated a U-shaped asso-
ciation between dietary zinc intake and new-onset diabetes.
Consistently, although maybe due to the relatively lower
sample size (n = 1056), the comparisons were not signifi-
cant, a previous conducted in China also showed a potential
U-shaped relation between dietary zinc intake and hypergly-
cemia (7).
Third, the information about new-onset diabetes in CHNS
was documented based on the physicians’ diagnoses at each
follow-up survey, and the fasting blood glucose and hemo-
globin A1c were assessed in the 2009 survey round only.
Therefore, diabetes incidence might be underestimated.
However, when evaluating the dietary zinc intake levels in
the 2009 survey, we found no significant difference in dietary
zinc intake between the undiagnosed diabetes cases and the
laboratory tests identified cases. Thus, the misclassification
might occur virtually independently of dietary zinc intake
and might not cause obvious bias in our study. Moreover,
similar results were detected when the new-onset diabetes
cases were defined only by physicians’ diagnoses (dietary zinc

Received: 17 March 2022. Editorial Decision: 22 March 2022. Corrected and Typeset: 8 April 2022
© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.
This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (https://
creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the
original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@
oup.com
e3100 The Journal of Clinical Endocrinology & Metabolism, 2022, Vol. 107, No. 7
intake < 9.1 mg/day, per mg/day: hazard ratio, 0.74; 95%
CI, 0.57-0.96; dietary zinc intake ≥ 9.1 mg/day, per mg/day:
hazard ratio, 1.12; 95% CI, 1.09-1.15). However, repeated
measurements of fasting glucose and hemoglobin A1c would
have allowed more accurate findings.
Overall, our study suggested a U-shaped association be-
tween dietary zinc intake and new-onset diabetes in general
Chinese adults, with an inflection point at about 9.1 mg/day.
We highly agree with Pattan et al that future studies consid-
ering more potential confounding are needed to confirm our
findings. Further, both the lower and upper reference range
of serum zinc concentration may need to be clearly defined,
especially for glucose metabolism.
Disclosures
No disclosures were reported.
References
1. Pattan V, Chang Villacreses MM, Karnchanasorn R, Chiu KC.
Letter to the Editor From Pattan et al.: U-shaped association
between dietary zinc intake and new-onset diabetes: a nation-
wide cohort study in China. J Clin Endocrinol Metab. 2022; doi:
10.1210/clinem/dgac184
2. Pattan V, Chang Villacreses MM, Karnchanasorn R, Chiu KC,
Samoa R. Daily intake and serum levels of copper, selenium and
zinc according to glucose metabolism: cross-sectional and com-
parative study. Nutrients. 2021;13(11):4044.
3. Fernández-Cao JC, Warthon-Medina M, Moran VH, et al. Zinc
intake and status and risk of type 2 diabetes mellitus: a systematic
review and meta-analysis. Nutrients. 2019;11(5):1027.
4. Chu A, Foster M, Samman S. Zinc status and risk of cardiovascular
diseases and type 2 diabetes mellitus-a systematic review of pro-
spective cohort studies. Nutrients. 2016;8(11):707.
5. He P, Li H, Liu M, et al. U-shaped association between dietary zinc
intake and new-onset diabetes: a nationwide cohort study in China.
J Clin Endocrinol Metab. 2022;107(2):e815-e824.
Downloaded from https://academic.oup.com/jcem/article/107/7/e3099/6553918 by guest on 13 June 2023
6. Gong W, Liu A, Yao Y, et al. Nutrient supplement use among
the chinese population: a cross-sectional study of the 2010-
2012 China Nutrition and Health Surveillance. Nutrients.
2018;10(11):1733.
7. Shi Z, Yuan B, Qi L, Dai Y, Zuo H, Zhou M. Zinc intake and
the risk of hyperglycemia among Chinese adults: the pro-
spective Jiangsu Nutrition Study (JIN). J Nutr Health Aging.
2010;14(4):332-335.