On the Status and Comparison of Glucose Intolerance in

Female Breast Cancer Patients at Initial Diagnosis and

during Chemotherapy through an Oral Glucose
Tolerance Test
Lin-jie Lu., Rui-jue Wang., Liang Ran., Lu Gan., Yang Bai, Liang-bin Jin, Zi-xiang Yao, Sheng-chun Liu,
Guo-sheng Ren, Kai-nan Wu*, Hong-yuan Li*, Ling-quan Kong*
The First Affiliated Hospital of Chongqing Medical University, Chongqing, China

Abstract
Aims: This study is to estimate the status and comparison of glucose intolerance in female breast cancer patients at initial
diagnosis and during chemotherapy through an oral glucose tolerance test (OGTT), as well as to learn the effect of
chemotherapy on the glucose metabolism of breast cancer patients.

Methods: All the 79 breast cancer patients at initial diagnosis, with the mean age of 53.2 years, and 96 breast cancer
patients before the 5th or 6th cycle of chemotherapy, with the mean age of 51.5 years, participated in the study from
December 2012 to October 2013. After an overnight fast, participants underwent OGTT test, and fasting and 2-hour glucose
levels were measured to identify undiagnosed diabetes and prediabetes (i.e., impaired fasting glucose or impaired glucose
tolerance) in them. Previously diagnosed diabetes among the female breast cancer patients was determined on the self-
report and the medical record.

Results: The overall incidences of total normal glucose tolerance, prediabetes, diabetes in female breast cancer patients at
initial diagnosis and during chemotherapy were 24.1% and 38.5% (p,0.05), 50.6% and 28.1% (p,0.05), and 25.3% and
33.3% (p.0.05), respectively, and the differences of normal glucose tolerance and prediabetes instead of diabetes between
the two groups were statistically significant. About 84% of the total diabetes and prediabetes in the female breast cancer
patients at initial diagnosis and 79.7% of those during chemotherapy need to be diagnosed with OGTT.

Conclusions: Breast cancer patients have high incidences of diabetes and prediabetes. After chemotherapy even with
steroids, some breast cancer patients with abnormal glucose metabolism may even become normal. Isolated hyperglycemia
2 hours after glucose loading is common, and OGTT should be made for breast cancer patients at initial diagnosis and
during chemotherapy.

Citation: Lu L-j, Wang R-j, Ran L, Gan L, Bai Y, et al. (2014) On the Status and Comparison of Glucose Intolerance in Female Breast Cancer Patients at Initial
Diagnosis and during Chemotherapy through an Oral Glucose Tolerance Test. PLoS ONE 9(4): e93630. doi:10.1371/journal.pone.0093630
Editor: Antonio Moschetta, University of Bari & Consorzio Mario Negri Sud, Italy
Received December 21, 2013; Accepted March 5, 2014; Published April 1, 2014
Copyright: ß 2014 Lu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This study was supported by National Natural Science Foundation of China (NSFC)(81372851) (Ling-quan Kong). The funders had no role in study
design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: The authors have declared that no competing interests exist.
* E-mail: huihuikp@163.com (LK); hongy_li@hotmail.com (HL); wukainanwaiwu@126.com (KW)
. These authors contributed equally to this work.

Introduction individuals tended to have poorer survival following treatment

for breast cancer [8,9]. Breast cancer patients often receive steroids
Breast cancer is the commonest one of female malignancies as a component of their chemotherapy. It was believed that
worldwide and another major health problem in developed steroids and chemotherapeutics had profound effects on glucose
countries is diabetes mellitus, both with a raising tendency [1–3]. metabolism, particularly on postprandial hyperglycemia [10,11]. It
Diabetes is associated with multiple factors that may also be the was reported that, in the United States, impaired glucose tolerance
risk factors of breast cancer, such as comorbidities, old age, lack of was an independent predictor for cancer mortality [12] and even a
physical activity, obesity, low parity, genetic predisposition and few days of hyperglycemia had deleterious effects on the immune
metabolic syndrome [4]. Diabetes may take effects on breast system [13].
cancer because of associated end organ damage which may In China, the statistical data indicated that the prevalences of
influence therapy choices, affect therapeutic toxicities, and cause total diabetes (both previously diagnosed diabetes and previously
worse outcomes [5–7]. It was reported that about 16% of breast undiagnosed diabetes) and prediabetes in adults older than 20
cancer patients worldwide had diabetes and that diabetic years were 9.7% (10.6% among men and 8.8% among women)

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 Glucose Intolerance in Breast Cancer Patients

and 15.5% (16.1% among men and 14.9% among women), measured to identify undiagnosed diabetes and prediabetes (i.e.,
respectively. Epidemiologic studies suggest that type 2 diabetes impaired fasting glucose or impaired glucose tolerance) in them.
(T2DM) increases breast cancer risk and goes along with an Previously diagnosed diabetes among the female breast cancer
increased mortality [14]. The previously reported findings have patients was determined on the self-report and the medical record.
not all been consistent, owing to methodological differences in
sampling and to differences in the criteria used to define diabetes Oral glucose tolerance test
[15]. Furthermore, the prevalences of diabetes and prediabetes Participants were instructed to keep their usual physical activity
were probably under estimated in these studies because 2-hour and, diet for at least three days before OGTT. After at least
oral glucose-tolerance tests (OGTT) were not performed in all 10 hours of overnight fasting, venous blood specimen was
participants [16]. It has been reported that isolated hyperglycemia collected in a vacuum tube containing sodium fluoride, for the
2 hours after glucose loading is common among Asian diabetic measurement of plasma glucose. Participants with no history of
patients [17]. In the Shanghai of China diabetes study, 48.6% of diabetes mellitus were given a standard 75-g glucose solution,
patients with newly diagnosed diabetes had isolated hyperglycemia blood samples were drawn at 0, 30, 60 and 120 minutes after the
2 hours after glucose loading, and 75.0% of those with prediabetes glucose load to measure glucose concentrations. Plasma glucose
had isolated impaired glucose tolerance [18]. was measured at The Clinical Endocrine Laboratories of The First
Our previous study on the status of total diabetes and Affiliated Hospital of Chongqing Medical University. The
prediabetes in breast cancer patients after systemic treatment laboratory successfully completed a standardization and certifica-
through OGTT in Southwest of China showed that the overall tion program.
incidences of total diabetes and prediabetes were 21.8% and Their glucose intolerance was evaluated based on a 75 g
43.7%, respectively; about 80% of the diabetes were previously OGTT according to the World Health Organization criteria:
undiagnosed; about 80.0% of the cases of undiagnosed diabetes isolated impaired fasting glucose (IIFG, fasting glucose level,
and prediabetes met the criteria for elevated 2-hour plasma $6.1 mmol/L and ,7.0 mmol/L, and 2-hour glucose level
glucose levels through OGTT instead of the criteria for elevated through OGTT ,7.8 mmol/L), isolated impaired glucose toler-
fasting glucose levels [16]. However, there have been no detailed ance (IIGT, fasting glucose level, ,6.1 mmol/L, and, 2-hour
studies about the status and comparison of isolated hyperglycemia glucose level through OGTT, $7.8 and ,11.1 mmol/L),
2 hours after glucose loading in breast cancer patients at initial combined impaired fasting glucose and impaired glucose tolerance
diagnosis and during chemotherapy through OGTT. (CIFGIGT, fasting glucose level, $6.1 and ,7.0 mmol/L, and 2-
This study is aimed to provide current and reliable data on the hour glucose level through OGTT, $7.8 and ,11.1 mmol/L),
status of total diabetes (both previously diagnosed diabetes and and undiagnosed diabetes (fasting glucose level, $7.0 mmol/L, or
previously undiagnosed diabetes) and prediabetes (i.e., impaired 2-hour glucose level through OGTT, $11.1 mmol/L, or both).
fasting glucose or impaired glucose tolerance) as well as the status Total diabetes includes both previously diagnosed diabetes (PDD)
of isolated hyperglycemia 2 hours after glucose loading in breast and previously undiagnosed diabetes (PUD). Prediabetes was
cancer patients at initial diagnosis and during chemotherapy defined as either impaired fasting glucose (IFG) or, impaired
through OGTT in China, and in the meantime, involves the glucose tolerance (IGT).
research on the effect of chemotherapy on the glucose metabolism
of breast cancer patients. Statistical Analysis
This study was designed to provide accurate estimations of the
Methods status of diabetes, prediabetes in the breast cancer patients at
initial diagnosis and during chemotherapy in the southwest of
Study participants China. The difference of the glucose metabolism status between
This study were conducted in the Breast Cancer Center of female breast cancer patients at initial diagnosis and during
Chongqing, the First Affiliated Hospital of Chongqing Medical chemotherapy were test by Chi-square test. SPSS 20.0 statistical
University, where is situated in the southwest of China. There are software was used for analysis and a P,0.05 was considered
approximately 31.4 million people who live in about significantly different.
82,402.95 km2 area of Chongqing. This study was approved by
The Ethics Committee of the First Affiliated Hospital of
Results
Chongqing Medical University, and all patients gave written
informed consent. The female breast cancer patients received six The overall incidence of total diabetes (25.3%, including 5.1%
cycles of TEC regimen (docetaxel, epirubicin and cyclophospha- PDD & 20.2% PUD) in 79 cases of breast cancer at initial
mide) or CEF regimen (cyclophosphamide, epirubicin and 5- diagnosis was lower than that (33.3%, including 5.2% PDD &
flouracil) every three weeks. The women who were treated with 28.1% PUD) in 96 cases of breast cancer during chemotherapy,
docetaxel received 7.5 mg of dexamethasone (by oral administra- but without significant difference (p.0.05) (seen in Table 1). The
tion) 24 hours, 12 hours, and, immediately before receiving overall incidences of total diabetes and prediabetes in the female
docetaxel (per the product specification). All the 79 breast cancer breast cancer patients at initial diagnosis and during chemother-
patients at initial diagnosis, with the mean age of 53.2 years apy were 75.9% and 61.5%, respectively (seen in Fig.1). About
(ranging from 24 to 75), and 96 breast cancer patients, with the 84.0% of the total diabetes and prediabetes in the female breast
mean age of 51.5 years (ranging from 30 to 72), before the 5th or cancer patients at initial diagnosis and 79.7% of those during
6th cycle of chemotherapy, i.e., in about three weeks after the chemotherapy need only to be diagnosed with OGTT (seen in
previous cycle of chemotherapy, participated in the study from Fig.2). The incidences of previously undiagnosed diabetes in
December 2012 to October 2013. All subjects were informed diabetic breast cancer patients at initial diagnosis and during
about the purpose of the study and signed the informed consent chemotherapy were 80.0% and, 84.4%, respectively (seen in
form. After an overnight fast, all the breast cancer patients except Fig.2). The incidence of prediabetes (50.6%) in breast cancer
the self-reported or medical-recorded patients with diabetes patients at initial diagnosis was significantly higher than that
underwent OGTT, and fasting and 2-hour glucose levels were (28.1%) in those during chemotherapy (p,0.05), meanwhile, the

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 Glucose Intolerance in Breast Cancer Patients

incidences of IIGT in breast cancer patients with prediabetes at studies suggest that diabetes increases breast cancer risk and goes
initial diagnosis and during chemotherapy were 87.5% and along with an increased mortality [21]. It was reported that up to
74.1%,respectively (seen in Table 1 and Fig.2). The incidence of 16% of breast cancer patients worldwide had diabetes and that
normal glucose tolerance (24.1%) in breast cancer patients at diabetic individuals tend to have poorer outcomes following
initial diagnosis was significantly lower than that (38.5%) in those treatment for breast cancer [8].
during chemotherapy (p,0.05) (seen in Table 1). It is reported, in the United States, that compared with those
The incidences of IIFG, IIGT, CIFGIGT, PUD and PDD, having normal glucose tolerance, adults with impaired glucose
among these female adult breast cancer patients at initial diagnosis tolerance had the greatest adjusted relative hazard of cancer
and during chemotherapy, were 1.3% & 1.0%, 44.3% & 20.8%, mortality, suggesting that impaired glucose tolerance is an
5.1% & 6.3%, 20.2% & 28.1%, and 5.1% & 5.2%, respectively independent predictor for cancer mortality [12]. Some studies
(seen in Fig.1). suggest that even a few days of hyperglycemia have deleterious
effects on the immune system [13]. However, there has been
Discussion limited studies about the accurate status and comparison of total
diabetes (previously diagnosed diabetes plus undiagnosed diabe-
Breast cancer is the commonest one of women malignancies tes), prediabetes, post-prandial hyperglycemia in breast cancer
worldwide and another major health problem in developed patients at initial diagnosis and during chemotherapy.
countries is diabetes, both with a raising tendency [1,2]. Precise Our results indicate that diabetes has reached epidemic
knowledge of the complex associations and interactions between proportions in the female breast cancer patients at initial diagnosis
diabetes and breast cancer, which may be named as breast and during chemotherapy in southwest of China. Of the 79 breast
oncodiabetology or, diabeto-oncology, is of great importance for cancer patients at initial diagnosis and 96 cases during chemo-
their prevention and, treatment. Diabetes is clearly an over- therapy, the overall incidences of total diabetes and prediabetes in
whelming pandemic with deathly consequences. The risk of death the female breast cancer patients at initial diagnosis and during
among people with diabetes is twice that of people of a similar age chemotherapy were 75.9% and, 61.5%, respectively. The overall
without diabetes [19]. Diabetic adults have heart disease death incidences of total diabetes (previously diagnosed plus previously
rates that are 2 to 4 times higher than those of adults without undiagnosed diabetes) in the female breast cancer patients at initial
diabetes, and the risk for stroke is also 2 to 4 times higher among diagnosis and during chemotherapy were 25.3% and 33.3%,
people with diabetes [20]. T2DM doubles the risk of all-cause respectively, which were obviously higher than that (8.7%) of
mortality and is also the leading cause of end-stage renal disease, normal Chinese population [23]. And in 80.0% of diabetic breast
blindness, and non-traumatic amputations [21]. It has been cancer patients at initial diagnosis and 84.4% of diabetic breast
reported that diabetes has been associated with substantial cancer patients during chemotherapy, the diabetes are previously
premature death from several cancers, infectious diseases, and undiagnosed. In addition, 50.6% of breast cancer patients at initial
degenerative disorders [22]. In China, because of the rapid change diagnosis and 28.1% of breast cancer patients during chemother-
in life style, there is concern that diabetes may become epidemic. apy have prediabetes, which is an important risk factor for the
The recent statistical data indicated that the prevalence of diabetes development of overt diabetes and cardiovascular disease [26,27].
and prediabetes in female adults older than 20 years was 8.8% and While the prevalence of prediabetes in normal Chinese population
14.9%, respectively [23]. was only 14.8% [23]. Randomized clinical trials have shown that
A link between diabetes and cancer was first proposed in 1934 interventions involving diet and exercise reduce the risk of diabetes
and has been investigated extensively [1,24,25]. Epidemiologic among people with prediabetes [28,29]. Public health measures

Figure 1. Status of glucose intolerance in female normal population and female adult breast cancer patients at initial diagnosis and
during chemotherapy. Abbreviation: NP- Normal Population [14], BCID- breast cancer patients at initial diagnosis, BCDC- breast cancer patients
during chemotherapy, NGT: Normal glucose tolerance, IIFG: Isolated impaired fasting glucose, IIGT: Isolated impaired glucose tolerance, CIFGIGT:
combined impaired fasting glucose and impaired glucose tolerance, PUD: Previously undiagnosed diabetes, PDD: Previously diagnosed diabetes.
doi:10.1371/journal.pone.0093630.g001

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 Glucose Intolerance in Breast Cancer Patients

Figure 2. Component of diabetes and prediabetes among female breast cancer patents after initial diagnosis & during
chemotherapy. Abbreviation: IIFG: Isolated impaired fasting glucose, IIGT: Isolated impaired glucose tolerance, CIFGIGT: Combined impaired fasting
glucose and impaired glucose tolerance, PUD: Previously undiagnosed diabetes, PDD: Previously diagnosed diabetes.
doi:10.1371/journal.pone.0093630.g002

should be undertaken to mitigate the consequences of new cases of diabetes (33.3%) in breast cancer patients during chemotherapy
diabetes in breast cancer patients at initial diagnosis and during increased more obviously than that (25.3%) in breast cancer
chemotherapy. Importantly, about 75.9% of the female adult patients at initial diagnosis and the incidence of previously
breast cancer patients at initial diagnosis and 61.5% of the female undiagnosed diabetes (84.4%) in diabetic breast cancer patients
adult breast cancer patients during chemotherapy in china have during chemotherapy were also much higher than that (80.0%) in
diabetes and prediabetes, but only 5.1% of these patients at initial breast cancer patients at initial diagnosis, but without statistical
diagnosis and 5.2% of cases during chemotherapy were diagnosed difference (p.0.05). Meanwhile, it is also found that the incidence
as diabetes, with most of the diabetes and prediabetes undiag- of prediabetes (50.6%) in breast cancer patients at initial diagnosis
nosed. About 84% of the total diabetes and prediabetes in the was significantly higher than that (28.1%) in those during
female breast cancer patients at initial diagnosis and 79.7% of chemotherapy (p,0.05) and the incidence of normal glucose
those during chemotherapy need only to be diagnosed with tolerance (24.1%) in breast cancer patients at initial diagnosis was
OGTT. So, a large multicentric study involving a whole country significantly lower than that (38.5%) in those during chemotherapy
representative sample of Chinese breast cancer patients at initial (p,0.05). These findings suggest that though chemotherapeutics
diagnosis and during chemotherapy is needed, this may provide an and steroids had certain effects on glucose metabolism, particularly
accurate evaluation of the diabetes and prediabetes burden in on postprandial hyperglycemia, but without statistical difference,
Chinese female adult breast cancer patients at initial diagnosis and and most importantly, after chemotherapy even with steroids,
during chemothherapy. some breast cancer patients with abnormal glucose metabolism
During chemotherapy for breast cancer patients, the glucocor- may become normal with statistical difference. These may be
ticoid dexamethasone is widely used to prevent side effects [30]. It related to the hypothesis of breast oncodiabetology that after
is considered that steroids affect post-meal glucose much more so chemotherapy and / or surgery, diabetes-inducing factors caused
than morning fasting sugars and glucocorticoid administration is by breast cancer cells are completely or partially relieved and the
associated with impairment of insulin sensitivity, elevations in reversible diabetes and prediabetes in breast cancer patients
peripheral glucose levels, and the suppression of the hypothalamic become alleviated or, even become normal, which need to be
– pituitary – adrenal axis [31]. It was reported that glucocorti- further studied.
costeroids (steroids) and chemotherapy had profound effects on These findings, which are firstly based on certain population
glucose metabolism, particularly on postprandial hyperglycemia based study involving one center representative sample of Chinese
[10,11]. Our results indicate that, the overall incidence of total breast cancer women at initial diagnosis and during chemother-

Table 1. comparison of glucose intolerance in female breast cancer patients at initial diagnosis and during chemotherapy through
OGTT.

Normal glucose tolerance Prediabetes Diabetes Total

Group of Initial diagnosis 19 (24.1%)* 40 (50.6%)* 20(25.3%)** 79 (100%)

Group of during chemotherapy 37 (38.5%)* 27 (28.1%)* 32(33.3%)** 96(100%)

*p,0.05,
** p.0.05.
doi:10.1371/journal.pone.0093630.t001

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 Glucose Intolerance in Breast Cancer Patients

apy, should provide an firstly relative accurate estimation of the diagnosis and 74.1% of the subjects with prediabetes during
diabetes and, prediabetes burden in female adult breast cancer chemotherapy had isolated impaired glucose tolerance, which are
patients at initial diagnosis and during chemotherapy in southwest much higher than those of Asian and Chinese normal population.
of China. In addition, the diagnosis of diabetes and prediabetes This means that without OGTT, most of the diabetes and
were firstly established on the basis of both fasting plasma glucose prediabetes in adult breast cancer women at initial diagnosis and
levels and 2-hour plasma glucose levels in an oral glucose- during chemotherapy cannot be confirmed, therefore, OGTT
tolerance test, and these measurements were obtained with the use should be made for the breast cancer patients at initial diagnosis
of stringent quality control procedures. and during chemotherapy (seen in Fig.2).
Several previous studies have documented high prevalence of This study has several limitations. First, it is only small samples
diabetes in breast cancer patients [32]. However, in those studies, and one center based prospective study on the incidences of
OGTT were not performed in the entire study population; diabetes and prediabetes in women breast cancer patients at initial
therefore, the true incidence of undiagnosed diabetes may have diagnosis and during chemotherapy, and a large samples and
been underestimated. Therefore, in the previous research, we multicenter-based study involving a nationally representative
firstly studied the status of total diabetes and prediabetes in breast samples of Chinese female breast cancer patients are needed.
cancer patients after systemic treatment through OGTT in Second, comparison of glucose intolerance in female breast cancer
Southwest of China and found that the overall incidences of total patients at initial diagnosis and during chemotherapy through
diabetes and prediabetes were 21.8% and, 43.7%, respectively; OGTT was not carried out in the same patient.
about 80% of the diabetes were previously undiagnosed; about In summary, our results show that diabetes and prediabetes are
80.0% of the cases of undiagnosed diabetes and, prediabetes met highly prevalent in the female adult breast cancer patients at initial
the criteria for elevated 2-hour plasma glucose levels through diagnosis and during chemotherapy in southwest of China. More
OGTT but not the criteria for elevated fasting glucose levels [16]. troublesome is the finding that the majority of cases of diabetes
In the present study, 80.0% of the cases of diabetes and, 87.5% and prediabetes in the breast cancer women at initial diagnosis
of the cases of prediabetes in breast cancer patients at initial and during chemotherapy in southwest of China are undiagnosed.
diagnosis as well as 84.4% of the cases of diabetes and 74.1% of These results indicate that diabetes has become a major public
the cases of prediabetes in breast cancer patients during health problem in breast cancer patients and that strategies aimed
chemotherapy met the criteria for elevated 2-hour plasma glucose at the prevention, detection, and treatment of diabetes in breast
levels through OGTT, but not the criteria for elevated fasting cancer patients at initial diagnosis and during chemotherapy are
glucose levels. Even accounting for differences in diagnostic needed in China. Chemotherapeutics and steroids had certain
criteria, our study firstly documents high incidences of previously effects on glucose metabolism, particularly on postprandial
undiagnosed diabetes and prediabetes in female adult breast hyperglycemia, but most importantly, after chemotherapy even
cancer patients at initial diagnosis and during chemotherapy in with steroids, some breast cancer patients with abnormal glucose
Southwest of China. metabolism may become normal. Isolated hyperglycemia 2 hours
It has been suggested that isolated hyperglycemia 2 hours after after glucose loading is common, and, OGTT should be made for
glucose loading is common among Asian patients with diabetes. It the breast cancer patients at initial diagnosis and during
was found that in a pooled analysis of Asian cohorts, more than chemotherapy.
half of the subjects with diabetes had isolated hyperglycemia
2 hours after glucose loading and three quarters of the subjects Acknowledgments
with prediabetes had isolated impaired glucose tolerance [17].The
This study through provision of data by the Breast Cancer Center of
latest statistical data for Chinese population also indicated that
Chongqing, Chongqing Medical University, Republic of China. The
46.6% of the cases of diabetes and 70.7% of the cases of opinions, results and conclusions reported in this article are those of the
prediabetes met the criteria for elevated 2-hour plasma glucose authors.
levels in OGTT but not the criteria for elevated fasting glucose
levels, and documented a large increase in the prevalences of Author Contributions
previously diagnosed diabetes, previously undiagnosed diabetes,
and prediabetes in Chinese population [23]. Our results firstly Conceived and designed the experiments: LQK. Analyzed the data: LJL
RJW LR LG. Wrote the paper: LQK LJL RJW LR LG. Interpreted data:
indicate that about 80% of the female adult diabetic breast cancer
LQK. Contributed to the study design: HYL KNW LJL RJW LR LG.
patients at initial diagnosis and 84.4% of the female adult diabetic Contributed to the interpretation of data: HYL KNW. Critically revised
breast cancer patients during chemotherapy had isolated hyper- the manuscript: LQK HYL KNW. Approved the final version of the article
glycemia 2 hours after glucose loading as well as 87.5% of the to be published: LQK HYL KNW LJL RJW LR LG YB LBJ ZXY SCL
female adult breast cancer patients with prediabetes at initial GSR.

References
1. A M (1934) Diabetes and cancer. New Engl J Med 211: 339–349. 7. Schrauder MG, Fasching PA, Haberle L, Lux MP, Rauh C, et al. (2011)
2. Schott S, Schneeweiss A, Sohn C (2010) Breast cancer and diabetes mellitus. Diabetes and prognosis in a breast cancer cohort. J Cancer Res Clin Oncol 137:
Exp Clin Endocrinol Diabetes 118: 673–677. 975–983.
3. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, et al. (2010) Estimates of 8. Wolf I, Sadetzki S, Catane R, Karasik A, Kaufman B (2005) Diabetes mellitus
worldwide burden of cancer in 2008: GLOBOCAN 2008. International journal and breast cancer. Lancet Oncol 6: 103–111.
of cancer 127: 2893–2917. 9. Yerrabothala S, Shaaban H, Capo G, Maroules M, Debari VA (2013) The
4. Ahn J, Schatzkin A, Lacey JV, Jr., Albanes D, Ballard-Barbash R, et al. (2007) Impact of Diabetes Mellitus on Breast Cancer Outcomes: A Single Center
Adiposity, adult weight change, and postmenopausal breast cancer risk. Arch Retrospective Study. Pathol Oncol Res.
Intern Med 167: 2091–2102. 10. Hickish T, Astras G, Thomas P, Penfold S, Purandare L, et al. (2009) Glucose
5. Lipscombe LL, Goodwin PJ, Zinman B, McLaughlin JR, Hux JE (2008) The intolerance during adjuvant chemotherapy for breast cancer. J Natl Cancer Inst
impact of diabetes on survival following breast cancer. Breast Cancer Res Treat 101: 537.
109: 389–395. 11. Oyer DS, Shah A, Bettenhausen S (2006) How to manage steroid diabetes in the
6. Erickson K, Patterson RE, Flatt SW, Natarajan L, Parker BA, et al. (2011) patient with cancer. J Support Oncol 4: 479–483.
Clinically defined type 2 diabetes mellitus and prognosis in early-stage breast
cancer. J Clin Oncol 29: 54–60.

PLOS ONE | www.plosone.org 5 April 2014 | Volume 9 | Issue 4 | e93630

 Glucose Intolerance in Breast Cancer Patients

12. Saydah SH, Loria CM, Eberhardt MS, Brancati FL (2003) Abnormal glucose 22. Emerging Risk Factors C, Seshasai SR, Kaptoge S, Thompson A, Di
tolerance and the risk of cancer death in the United States. Am J Epidemiol 157: Angelantonio E, et al. (2011) Diabetes mellitus, fasting glucose, and risk of
1092–1100. cause-specific death. N Engl J Med 364: 829–841.
13. Furnary AP, Wu Y, Bookin SO (2004) Effect of hyperglycemia and continuous 23. Yang SH, Dou KF, Song WJ (2010) Prevalence of diabetes among men and
intravenous insulin infusions on outcomes of cardiac surgical procedures: the women in China. N Engl J Med 362: 2425–2426; author reply 2426.
Portland Diabetic Project. Endocr Pract 10 Suppl 2: 21–33. 24. Malek M, Aghili R, Emami Z, Khamseh ME (2013) Risk of Cancer in Diabetes:
14. Yang W, Lu J, Weng J, Jia W, Ji L, et al. (2010) Prevalence of diabetes among The Effect of Metformin. ISRN Endocrinol 2013: 636927.
men and women in China. New England Journal of Medicine 362: 1090–1101. 25. Buysschaert M, Sadikot S (2013) Diabetes and cancer: A 2013 synopsis. Diabetes
15. Arif JM, Al-Saif AM, Al-Karrawi MA, Al-Sagair OA (2011) Causative Metab Syndr 7: 247–250.
relationship between diabetes mellitus and breast cancer in various regions of 26. Schmidt MI, Duncan BB, Bang H, Pankow JS, Ballantyne CM, et al. (2005)
Saudi Arabia: an overview. Asian Pac J Cancer Prev 12: 589–592. Identifying individuals at high risk for diabetes: The Atherosclerosis Risk in
16. Ji GY, Jin LB, Wang RJ, Bai Y, Yao ZX, et al. (2013) Incidences of diabetes and Communities study. Diabetes Care 28: 2013–2018.
prediabetes among female adult breast cancer patients after systemic treatment. 27. Levitzky YS, Pencina MJ, D’Agostino RB, Meigs JB, Murabito JM, et al. (2008)
Med Oncol 30: 687. Impact of impaired fasting glucose on cardiovascular disease: the Framingham
17. Qiao Q, Nakagami T, Tuomilehto J, Borch-Johnsen K, Balkau B, et al. (2000) Heart Study. J Am Coll Cardiol 51: 264–270.
Comparison of the fasting and the 2-h glucose criteria for diabetes in different 28. Tuomilehto J, Lindstrom J, Eriksson JG, Valle TT, Hamalainen H, et al. (2001)
Asian cohorts. Diabetologia 43: 1470–1475. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with
18. Jia WP, Pang C, Chen L, Bao YQ, Lu JX, et al. (2007) Epidemiological impaired glucose tolerance. N Engl J Med 344: 1343–1350.
characteristics of diabetes mellitus and impaired glucose regulation in a Chinese 29. Li G, Zhang P, Wang J, Gregg EW, Yang W, et al. (2008) The long-term effect
adult population: the Shanghai Diabetes Studies, a cross-sectional 3-year follow- of lifestyle interventions to prevent diabetes in the China Da Qing Diabetes
up study in Shanghai urban communities. Diabetologia 50: 286–292. Prevention Study: a 20-year follow-up study. Lancet 371: 1783–1789.
19. Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, et al. (2012) Global and 30. Ioannidis JP, Hesketh PJ, Lau J (2000) Contribution of dexamethasone to
regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: control of chemotherapy-induced nausea and vomiting: a meta-analysis of
a systematic analysis for the Global Burden of Disease Study 2010. Lancet 380: randomized evidence. J Clin Oncol 18: 3409–3422.
2095–2128. 31. Munck A (1971) Glucocorticoid inhibition of glucose uptake by peripheral
20. Norhammar A, Schenck-Gustafsson K (2013) Type 2 diabetes and cardiovas- tissues: old and new evidence, molecular mechanisms, and physiological
cular disease in women. Diabetologia 56: 1–9. significance. Perspect Biol Med 14: 265–269.
21. Srokowski TP, Fang S, Hortobagyi GN, Giordano SH (2009) Impact of diabetes 32. Zhang PH, Chen ZW, Lv D, Xu YY, Gu WL, et al. (2012) Increased risk of
mellitus on complications and outcomes of adjuvant chemotherapy in older cancer in patients with type 2 diabetes mellitus: a retrospective cohort study in
patients with breast cancer. J Clin Oncol 27: 2170–2176. China. BMC Public Health 12: 567.

PLOS ONE | www.plosone.org 6 April 2014 | Volume 9 | Issue 4 | e93630