Cancer - Diabetes

Cancer - Diabetes 
Category: Health Condition/ Disease
Practice Questions
Q1: Are individuals with diabetes at higher risk of developing cancer than those without
diabetes?
Subcategory: Assessment
Updated: 2019-05-14
Key Practice Point #1

Evidence from prospective and retrospective studies suggests that individuals with diabetes (type 1 or type
2) may be at higher risk for certain forms of cancer, experience poorer prognosis and shorter overall
survival rates than individuals without diabetes.
Evidence from cohort and case control studies suggests that prediabetes may be associated with an
increased risk of hepatocellular cancer.
Grade of Evidence: B
Evidence
a. A meta-analysis of observational studies of the association between type 1 diabetes located 15
studies (two case control and 13 cohort studies) for analysis in a search of PubMed and Embase
(April 2017) (1). The studies were conducted in the EU, U.K., Australia, Taiwan and the United
States and involved 13,893 cancer patients followed for eight to 20 years. Overall, type
1 diabetes was associated with an increased risk of developing cancer (OR=1.29, 95%CI: 1.09 to
1.52). Sub-analysis revealed increased risk for liver (OR=2.35), thyroid (OR=1.40), stomach
(OR= 1.44), lung (OR=1.09), pancreas (OR=1.34), ovary (OR=1.17) and kidney (OR=1.37)
cancers while a decreased risk of breast cancer was observed (OR=0.91, 95%CI=0.86 to 0.95).
The potential mechanism accounting for the increased risk of cancer in people with type
1 diabetes has not been identified, but researchers have proposed underlying biological factors,
mutagenic effects of insulin, insulin analogs or exposure to insulin like growth factor 1 (IGF-1) as
possible explanations. The authors identified several limitations of this meta-analysis including
the potential misclassification of study subjects as having type 2 diabetes and limited control for
important additional confounding risk factors, such as tobacco use, physical activity and obesity.
b. A meta-analysis examining the relationship between type 2 diabetes and the risk of colorectal
cancer located 17 studies (15 retrospective, two prospective) for analysis from a search of
EMBASE, Web of Science, Cochrane Library and PubMed databases to January 2016 (2). The
studies were conducted in North America, EU, and Asian countries involving 28,999 patients.
Compared to those who did not have diabetes, diabetes was associated with an approximately
50% increased risk of colorectal adenoma (RR=1.52, 95%CI, 1.29 to 1.80, P<0.001) and an
increased risk of advanced adenoma (RR=1.41, 95%CI, 1.06 to 1.87). While no significant
Cancer - Diabetes
© 2021 Dietitians of Canada. All rights reserved. PAGE 1
difference in gender related risk were found those with known diabetes were found to have 5%
higher risk of colorectal cancer compared to individuals who were newly diagnosed with diabetes.
Potential risk of publication bias and limited adjustment for confounding risk factors were
identified as limitations of this study.
c. A meta-analysis of studies of the association between diabetes and oral cancer located 13
studies (four case control and nine cohort studies) for analysis in a search of MEDLINE and
Embase databases through May 2014 (3). Compared to individuals without diabetes, those with
type 2 diabetes had a higher risk of oral cancer (RR=1.15, 95%CI, 1.02 to 1.29), a higher risk of
oral cancer mortality (RR=1.41, 95%CI, 1.16 to 1.72) and a higher risk of precancerous oral
lesions (RR=1.85, 95%CI, 1.23 to 2.80).
d. A systematic review and meta-analysis examining the relationship between diabetes and
gallbladder cancer located 20 studies (8 case control, 12 cohort studies) for analysis from a
search of EMBASE and MEDLINE databases to August 2014 (4). Compared to those who did
not have diabetes, the presence of type 2 diabetes was associated with a higher overall risk of
gallbladder cancer (RR=1.56, 95%CI, 1.36 to 1.79). No significant difference in gender related
risk of gallbladder cancer was found.
e. A series of analyses have combined type 1 and 2 diabetes in assessing risk of cancer. A meta-
analysis on diabetes and risk of esophageal cancer located 13 studies from PubMed, Medline
and Web of Science databases on August 2016 (5). The studies were conducted in Australia,
Asia, EU, U.K. and North America and involved 20,611 individuals with esophageal cancer and
177,186 control subjects. Meta-analysis calculated the overall risk of esophageal cancer in
individuals with diabetes as RR=1.28, 95%CI, 1.12 to 1.47, P<.001 with males at higher risk
(RR=1.53, 95%CI, 1.44 to 1.62, P<.001) than women (RR=1.23, 95%CI, 0.41 to 3.69, P=0.71).
Relative risk was higher amongst North Americans (RR=1.39, P<.001) and Europeans
(1.37, P=0.04) compared to Asian participants (RR=0.98, P=.96). Several limitations were
identified in this study including the very low quality GRADE assessment of the studies
(attributable to risk of bias and inconsistency), lack of differentiation between type 1 and type 2
diabetes and possible missed confounding and exposure factors influencing the risk of
esophageal cancer.
f. A meta-analysis examining the relationship between diabetes and gastric cancer cancer located
22 cohort studies for analysis from a search of Embase, Cochrane library and PubMed
databases (6). The studies were conducted in North America, EU, U.K. and Asia involving
8,559,861 individuals (13,538 cases of gastric cancer diagnosed) who were followed for between
3.9 and 25 years. In this analysis the presence of diabetes was not associated with an increased
risk in gastric cancer risk (RR=1.10; 95%CI, 0.94 to 1.29, P=0.229) or gastric cancer mortality
(RR=1.28; 95%CI, 0.93 to 1.76). Although no significant difference was found between risk of
gastric cancer associated with diabetes in studies involving men (RR=1.00, n=11 studies) or
studies of women (RR=1.07; n=10 studies) subgroup analysis suggested diabetes was
associated with increased risk of gastric cancer mortality in men when mean age was <55 years
and data was not adjusted for alcohol consumption. In women, diabetes was associated with
increased risk of gastric cancer mortality when the patient population was based in a
Westernized country or when the data was not adjusted for alcohol consumption and tobacco
Cancer - Diabetes
use. The significant heterogeneity (study designs, follow up and patient characteristics) and
differing gastric cancer incidence and mortality between studies were identified as limitations of
this meta-analysis.
g. A meta-analysis and systematic review of studies of the association between diabetes and
bladder cancer located 21 studies for analysis in a search of PubMed, Cochrane Library and
Embase databases through October 2017 (7). The studies involved 13,505,643 patients in Asia,
EU, U.S. and two multinational trials. Compared to individuals without diabetes, those with
diabetes had a higher risk of bladder cancer or cancer mortality (RR=1.28; 95%CI 1.12 to 1.35,
P<.001). Overall risk for men was RR=1.23; 95% CI, 1.06 to 1.42, P=0.005 while in women
overall risk was not significant (RR=1.24; 95%CI, 1.09 to 1.61, P=0.119). Diabetes was not
associated with bladder cancer in men >60 years of age but in women, diabetes was associated
with an increased risk of bladder cancer in women >60 years and in follow up of >10 years. The
authors noted that women were included in a limited number of the studies for analysis, studies
did not adjust for the use of oral hypoglycemic agents and that country-specific incidence of
bladder cancer might influence the overall observed risks.
h. A meta-analysis examining the relationship between diabetes and ovarian cancer located 13
studies for analysis from a search of EMBASE, Cochrane library and PubMed databases to
September 2016 (8). The studies were conducted in North America, EU and Asia involving
3,708,313 patients who were followed for between 3.5 and 15 years. Compared to women who
did not have diabetes, the presence of diabetes was associated with a higher risk of developing
ovarian cancer (RR=1.19; 95%CI, 1.06 to 1.34, P=0.004). The lack of specificity on type of
diabetes and ovarian cancer and significant heterogeneity (follow up and patient characteristics)
were identified as limitations of this meta-analysis.
i. Sex hormones, specifically estrogen and testosterone, may also influence the risk of cancer in
men and women with diabetes. A meta-analysis examining the relationship between diabetes
and gastrointestinal cancer in men and women located 38 studies (29 prospective cohort, nine
retrospective cohort) from a search of EMBASE, PubMed and Cochrane Library databases
through May 2017 (9). The studies involved 18,060,698 participants from EU, Asian and North
American countries. Fifteen of the studies involved individuals with type 2 diabetes and 23
included those with type 1 and type 2 diabetes. Ratio of relative risk assessment found that
women with diabetes had higher risk of gastric cancer (RRR=1.14, 95%CI, 1.06 to 1.22,
P<0.001) and a lower risk of hepatocellular cancer (RRR=0.88, 95%CI, 0.79 to 0.99, P=0.031)
compared to men with diabetes. No sex difference in risk of esophageal, colorectal, pancreatic or
rectal cancers was found between women and men with diabetes.
j. A meta-analysis examining the relationship between blood glucose levels and liver cancer
located eight prospective studies for analysis from a search of EMBASE, Cochrane library and
PubMed databases to October 2016 (10). The studies were conducted in the U.S., EU and Asian
countries involving 1,975 patients who developed liver cancer and were followed for between two
and 22.5 years. Pooled risk revealed an increased risk of developing liver cancer with every 0.56
mmol/L increase in fasting blood glucose levels (RR=1.11, 95%CI, 1.06 to 1.17, P<0.001).
Overall highest compared to lowest fasting blood glucose levels were associated with a 77%
increased risk of liver cancer (RR=1.77, 95%CI, 1.46 to 2.13). The increased risk of liver cancer
Cancer - Diabetes
persisted even after adjusting for other known risk factors, such as smoking, obesity, alcohol
intake and HBV or HCV infection. Lack of information on use of antihyperglycemic agents and
long-term blood glucose data were identified as limitations of this study.
k. Prediabetes may be associated with increased cancer risk. A systematic review and meta-
analysis of the association between prediabetes and hepatocellular cancer located nine studies
(eight cohort, one case control study) from a search of PubMed, Embase and Web of Science
databases (11). The studies involved 1,384,594 participants. Prediabetes was associated with
increased risk of hepatocellular cancer (HR=1.21; 95%CI, 1.13 to 1.30, P<0.00001). Sub-
analysis found that the presence of prediabetes was associated with increased risk of
hepatocellular cancer in both males (HR=1.49, P=0.03 and females (HR=1.24, P=0.04), Asian
subjects (HR=1.19, P<0.00001) and Caucasians (HR=2.12, P=0.001).
Rationale
It is uncertain if diabetes is a confounding or causal risk factor in the development of cancer. The
presence of hyperglycemia, hyperinsulinemia, insulin resistance and/or inflammation in individuals with
diabetes have been proposed as possible explanations influencing the increased incidence of cancer (2).
The presence of an altered metabolic environment may influence the development and growth of tumours
(11).
References
1. Sona MF, Myung SK, Park K, Jargalsaikhan G. Type 1 diabetes mellitus and risk of cancer: a
meta-analysis of observational studies. Jpn J Clin Oncol. 2018 May 1;48(5):426-33. Abstract
available from: https://www.ncbi.nlm.nih.gov/pubmed/29635473
2. Yu F, Guo Y, Wang H, Feng J, Jin Z, Chen Q, et al. Type 2 diabetes mellitus and risk of
colorectal adenoma: a meta-analysis of observational studies. BMC Cancer. 2016 Aug
17;16:642. Abstract available from: https://www.ncbi.nlm.nih.gov/pubmed/27535548
3. Gong Y, Wei B, Yu L, Pan W. Type 2 diabetes mellitus and risk of oral cancer and precancerous
lesions: a meta-analysis of observational studies. Oral Oncol 2015 Apr; 51(4):332-40. Abstract
4. Gu J, Yan S, Wang B, Shen F, Cao H, Fan J, Wang Y. Type 2 diabetes mellitus and risk of
gallbladder cancer: a systematic review and meta-analysis of observational studies. Diabetes
Metab Res Rev. 2016 Jan; 32(1):63-72. Abstract available
from: https://www.ncbi.nlm.nih.gov/pubmed/26111736
5. Xu B, Zhou X, Li X, Liu C, Yang C. Diabetes mellitus carries a risk of esophageal cancer: a meta-
analysis. Medicine (Baltimore). 2017 Sep;96(35): e7944. Abstract available
6. Miao ZF, Xu H, Xu YY, Wang ZN, Zhao TT, Song YX, Xu HM. Diabetes mellitus and the risk of
gastric cancer: a meta-analysis of cohort studies. Oncotarget. 2017 Jul 4;8(27):44881-92.
Abstract available from: https://www.ncbi.nlm.nih.gov/pubmed/28415651
Cancer - Diabetes
7. Xu Y, Huo R, Chen X, Yu X. Diabetes mellitus and the risk of bladder cancer: a PRISMA-
compliant meta-analysis of cohort studies. Medicine (Baltimore). 2017 Nov;96(46):e8588.
Abstract available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5704818/
8. Wang L, Wang L, Zhang J, Wang B, Liu H. Association between diabetes mellitus and
subsequent ovarian cancer in women: a systematic review and meta-analysis of cohort studies.
Medicine (Baltimore). 2017 Apr;96(16):e6396. Abstract available
9. Fang HJ, Shan SB, Zhou YH, Zhong LY. Diabetes mellitus and the risk of gastrointestinal cancer
in women compared with men: a meta-analysis of cohort studies. BMC Cancer 2018 Apr 16;18
(1):422. Abstract available from: https://www.ncbi.nlm.nih.gov/pubmed/29661174
10. Han H, Zhang T, Jin Z, Guo H, Wei X, Liu Y, Chen Q, He J. Blood glucose concentration and risk
of liver cancer: systematic review and meta-analysis of prospective studies. Oncotarget. 2017 Jul
25;8(30):50164-73. Abstract available from: https://www.ncbi.nlm.nih.gov/pubmed/28432278
11. Xu WG, Qian YF, Wu J. The effect of prediabetes on hepatocellular carcinoma risk: a systematic
review and meta-analysis. Minerva Med. 2017 Apr;108(2):185-90. Abstract available
Q2: What are the nutrition recommendations and glycemic targets for individuals with diabetes
and cancer?
Subcategory: Intervention
Updated: 2019-05-14

Recommendation
No specific recommendations were identified in the literature regarding optimal glucose control for
individuals undergoing cancer treatment. Goals for nutrition and glycemic control must be individually
tailored to take into account the individual’s age, co-morbidities, risk factors, cancer type, cancer stage,
prognosis, effects related to cancer treatment and ability to perceive hypoglycemia, and that
are acceptable to the individual.
Evidence Summary
Clinical practice guidelines do not specify glycemic targets for individuals undergoing cancer treatment.
{grade_d}
Clinical guidelines differ in recommended glycemic targets for individuals with co-morbid conditions and
limited life expectancy and for individuals in hospital. These goals must be individually tailored to take into
account the individual’s age, risk factors, effects related to cancer treatment and ability to perceive
hypoglycemia.
Cancer - Diabetes
{grade_c}
Nutrition therapy should be individualized, considering cancer type and address the management of
cancer-related effects (weight change, nausea, vomiting).
{grade_c}
A sick day plan should be implemented, in response to nausea and vomiting, to reduce the risk of
hypoglycemia.
{grade_c}
Dietitians, in collaboration with the individual and multidisciplinary team, should develop a nutrition
palliative care plan.
{grade_c}
The use of enteral nutritional support products specifically formulated for individuals with diabetes may be
useful in meeting the nutritional needs of individuals experiencing hyperglycemia.
{grade_c}
Grade of Evidence: C & D
Evidence
a. Cancer treatment may present acute, long-term and end of life management challenges when
coupled with diabetes. Although clinical practice guidelines do not specify glycemic targets for
individuals undergoing cancer treatment, the Canadian Diabetes Association recommends that
an A1C target of 7.1-8.5% is appropriate for individuals with type 1 or type 2 diabetes who have
multiple co-morbid conditions or limited life expectancy (1). These goals must be individually
tailored to take into account the individual’s age, risk factors, effects related to cancer treatment
and ability to perceive hypoglycemia.
b. Cancer treatment may necessitate hospitalization for individuals with diabetes. Canadian clinical
practice guidelines for hospitalized individuals with diabetes who are non-critically ill are
preprandial glycemic targets of 5-8 mmol/L and random blood glucose levels <10 mmol/L, while
glycemic targets for critically ill individuals with diabetes should be 6-10 mmol/L (1).
c. The Australian Diabetes Society recommends that most individuals who are in hospital achieve
blood glucose targets of <10 mmol/L while avoiding hypoglycemia (2). Individuals receiving end of
life care should be maintained at blood glucose levels 5-15 mmol/L to avoid symptoms of hyper-
or hypoglycemia.
d. Diabetes U.K. recommends that for individuals in hospital, diabetes medications be adjusted to
achieve glycemic targets rather than dietary restriction (3). The use of enteral nutritional support
products specifically formulated for individuals with diabetes may be useful in meeting the
nutritional needs of individuals experiencing hyperglycemia.
Cancer - Diabetes
e. In a review of studies published up to April 2017 in PubMed, EMBASE and Cochrane Library
databases on cancer patients with diabetes, Gallo, et al. described a number of cancer
treatment agents that interfere with insulin production, secretion and sensitivity and consequently
have implications for glycemic control (4). The authors cautioned that blood glucose targets for
those with diabetes and cancer require individualization considering the type of diabetes, type of
cancer, patient life expectancy, treatment and treatment effects with nutritional impact. Those
with lessened life expectancy (hours/days), altered level of consciousness, liver/kidney or heart
dysfunction, limited responsiveness, cognitive impairment or frailty might benefit from less
stringent blood glucose targets (A1C 7.6% to 8.5%).
f. If oral intake is variable due to nausea and vomiting, implementation of sick day nutrition
guidelines and prandial glucose agents and/or short acting insulins (administered post meal to
more accurately reflect carbohydrate consumption) may be useful in reducing the risk of
hypoglycemia (5).
g. Nutrition therapy may be tailored to specific patient needs and cancer type. A mixed methods
study (cross-sectional survey, focus groups) of the experiences of 1,774 Dutch colorectal cancer
survivors found that 17.5% of participants perceived the need for dietary support (6). Younger
age, presence of overweight or obese and diabetes (OR=1.83, 95%CI, 1.12 to 2.98) were all
associated with need for dietary support. Participants expressed a preference for in-person
support rather than digital and receiving nutritional advice tailored to treatment effects (lack of
energy, strength, bowel and stoma complaints). Study participants indicated that this advice
would be most useful at the time of diagnosis and after initial treatment but cautioned that
lifestyle changes, such as weight loss, would be contingent on physical recovery after
treatments.
h. A review of 51 studies of pancreatic cancer and diabetes published in PubMed between 1995 and
2016 described the nutritional consequences of cancer treatment (7). Pancreatic cancer may
have exocrine effects (weight loss, steatorrhea) and/or endocrine nutritional effects (diabetes).
While approximately 50% of individuals diagnosed with pancreatic cancer have pre-existing
diabetes up to 54% may acquire diabetes after pancreatic resection. Nutritional complications
associated with pancreatic surgery may include dumping syndrome, delayed gastric emptying,
weight loss and risk of nutrient deficiencies (B12, fat soluble vitamins A, E, D3 and zinc). Based
on the available studies the reviewers recommended that surgical treatments be delayed and
nutritional support be initiated in the presence of weight loss >10% or albumin <2.5 mg/dL;
nutritional support be implemented prior to surgery in the presence of weight loss 5-10% or
albumin <3 mg/dL; enteral nutrition be offered post-operatively and that multidisciplinary teams
collaborate to provide care.
i. No guidelines for the nutritional management of patients with diabetes in the early and later
stages of terminal cancer were located. A review by King, et al. suggests that all dietary
restrictions related to diabetes be relaxed or removed from the early stage of terminal illness (8).
Early education and collaboration with a multidisciplinary team, including a dietitian, is important
to establish a plan for palliative nutrition care that is acceptable to the individual with diabetes
and their supporters.
Cancer - Diabetes
Comments
Some cancer treatment regimes, such as glucocorticoids, chemoradiation and chemotherapy agents may
be associated with hyperglycemia and require modification of diabetes medications as a result (9).
References
1. Diabetes Canada Clinical Practice Guidelines Expert Committee. Diabetes Canada 2018 clinical
practice guidelines for the prevention and management of diabetes in Canada. Can J Diabetes.
2018;42(Suppl 1):S1-S325. Available from: http://guidelines.diabetes.ca/cpg
2. Australian Diabetes Society. Guidelines for routine glucose control in hospital. 2012. Available
from: http://www.diabetessociety.com.au/position-statements.asp
3. Dyson PA, Twenefour D, Breen C, Duncan A, Elvin E, Goff L, et al. Diabetes UK evidence-based
nutrition guidelines for the prevention and management of diabetes. Diabet Med. 2018 May;35
(5):541-7. doi: 10.1111/dme.13603. Available from: http://www.diabetes.org.uk/nutrition-
guidelines
4. Gallo M, Muscogiuri G, Felicetti F, Faggiano A, Trimarchi F, Arvat E, et al. Adverse glycaemic
effects of cancer therapy: indications for a rational approach to cancer patients with diabetes.
Metabolism. 2018 Jan;78:141-54. Abstract available
5. Jacob P, Chowdhury TA. Management of diabetes in patients with cancer. QJM. 2015 Jun;108
(6):443-8. Abstract available from: https://www.ncbi.nlm.nih.gov/pubmed/25362096
6. Hoedjes M, de Kruif A, Mols F, Bours M, Beijer S, Winkels R, et al. An exploration of needs and
preferences for dietary support in colorectal cancer survivors: a mixed-methods study. PLoS
One. 2017 Dec 18;12(12):e0189178. Abstract available
7. Gilliland TM, Villafane-Ferriol N, Shah KP, Shah RM, Tran Cao HS, Massarweh NN, et al.
Nutritional and metabolic derangements in pancreatic cancer and pancreatic resection.
Nutrients. 2017 Mar 7;9(3). Available
from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5372906/
8. King EJ, Haboubi H, Evans D, Baker I, Bain SC, Stephens JW. The management of diabetes in
terminal illness related to cancer. QJM 2012 Jan; 105(1):3-9. Abstract available
9. Jacob P, Chowdhury TA. Management of diabetes in patients with cancer. QJM. 2015 Jun;108
(6):443-8. QJM. 2015 Jun;108(6):443-8. Abstract available
Q3: What are the effects of hyperglycemia or diabetes in individuals with cancer?
Subcategory: Monitoring/Evaluation
Cancer - Diabetes
Updated: 2019-05-14

Hyperglycemia or diabetes is associated with higher risk of morbidity, cancer-specific mortality and
cancer recurrence rates.
Grade of Evidence: B
Evidence
a. A systematic review of the effects of hyperglycemia on chemotherapy located 11 preclinical (23
cell lines and eight cancer types) and two animal studies for analysis from a search of MEDLINE
(1980 to December 2015) (1). In the rodent studies, hyperglycemia (>15 mmol/L) was associated
with impaired pharmakinetics of chemotherapy agents compared to the response observed in
euglycemic rodents (5 mmol/L). Results from the preclinical studies were inconsistent with
hyperglycemia associated with reduced response to chemotherapy agents in 14 cell lines, no
significant difference in response in four studies and enhanced response in five cell line studies.
The enhanced response to chemotherapy associated with hyperglycemia was proposed to result
from hyperglycemic-stimulated tumour proliferation, which provided more target opportunities for
chemotherapy action. The authors noted challenges in quality assessment of the studies due to
missing information.
b. Diabetes may also impact cancer survival rates. A meta-analysis examining the relationship
between diabetes and prognosis of pancreatic cancer located 18 studies (16 retrospective
cohort, 2 prospective cohort studies) for analysis from a search of EMBASE and Medline
databases to May 2015 (2). The studies involved 16,181 participants from EU, China, and the
U.S. This analysis found that diabetes was associated with shorter overall survival rates
compared to individuals without diabetes (HR=1.19, 95%CI, 1.07 to 1.32, P<0.001). This
association persisted in individuals with localized disease (HR=1.57, 95%CI, 1.00 to 2.46) and
advanced/metastatic cancer (HR=1.42, 95%CI, 1.16 to 1.73). Similar results were also
documented in another systematic review and meta-analysis that found that diabetes negatively
impacted survival rates particularly in patients with new onset diabetes (<2 years duration)
RR=1.54, 95%CI, 1.24 to 1.91, P<0.001 (3).
c. In a systematic review and meta-analysis of the association between diabetes and
hyperglycemia and cervical cancer, researchers located 13 retrospective cohort studies from a
search of Pub Med, Embase, Wanfang and Web of Science databases to December 2016 (4).
The studies involved 11,091 cervical cancer patients and were conducted in Asia and U.S. with
follow up ranging from three to 25 years. Two studies that did not report hazard ratios or data that
could be used to calculate hazard ratios were excluded, leaving 11 studies for analysis (nine
assessed as good quality, two of suboptimal quality). When studies of hyperglycemia were
excluded, diabetes was independently associated with shorter overall survival time with cervical
cancer (HR= 1.57, 95%CI, 1.33 to 1.85, P<0.001) and reduced recurrence free survival (HR=
2.09, 95%CI, 1.28 to 3.41, P=0.003). The authors noted that women of different ages, cancer
Cancer - Diabetes
stage, adjustment for confounding factors and follow-up periods were studied which might
influence the overall observed risks (4). A meta-analysis of 12 cohort studies on diabetes and
ovarian cancer also found that diabetes was associated with higher all-cause mortality (RR=1.44,
95%CI, 1.16 to 1.79) and cancer specific mortality (RR=1.44, 95%CI, 1.08 to 1.93) in women
with ovarian cancer (5).
d. A meta-analysis examining the relationship between diabetes and colorectal cancer prognosis
located 36 studies (15 retrospective, 21 prospective) for analysis from a search of EMBASE,
Web of Science, Google Scholar and PubMed databases to May 2017 (6). The studies were
conducted in North America, EU, Oceania and Asia involving 2,299,012 patients. Compared to
those who did not have diabetes, the presence of diabetes was associated with a lower overall
five-year survival rate of colorectal cancer (colorectal HR=1.18, 95%CI, 1.12 to 1.24; colon cancer
HR=1.19, 95%CI, 1.10 to 1.27; rectal cancer HR=1.16, 95%CI, 1.04 to 1.29). The significant
heterogeneity of the included studies was identified as a limitation of this meta-analysis.
e. A meta-analysis examining the relationship between diabetes and prognosis of women with
breast cancer located 17 studies (10 retrospective cohort, four case control and three prospective
cohort studies) for analysis from a search of Embase and PubMed databases to June 2016 (7).
The studies were conducted in North America, EU and Asia involving 48,315 patients who were
followed for between 32 months and 10.3 years. Compared to women who did not have diabetes,
survival rates (HR=1.51; 95%CI, 1.34 to 1.70) and disease-free survival times (HR=1.28; 95%CI,
1.09 to 1.50) were shorter for those with diabetes. No significant difference was noted in relapse-
free period between women who had diabetes and those that did not. The retrospective nature of
the studies (a potential source of bias), significant heterogeneity (study designs, follow up and
patient characteristics) and inconsistent adjustment for confounding factors were identified as
limitations of this meta-analysis.
f. A review article discusses breast cancer treatment in individuals with diabetes and points out
that several well-known complications of diabetes including nephropathy, neuropathy, heart
disease, impaired wound healing and susceptibility to infection can adversely affect all forms of
cancer therapy including surgical, radiation, chemotherapy, and hormonal therapy (8). Diabetes
is also associated with increased risk of complications after surgery for breast cancer.
g. A meta-analysis examining the relationship between diabetes and prognosis of individuals with
prostate cancer located 17 studies for analysis from a search of Embase and PubMed
databases from January 1970 to August 2016 (9). The studies were conducted in the U.K.,U.S.,
EU and Asia and involved 274,677 men diagnosed with prostate cancer and followed for between
3 to 17 years. Pre-existing diabetes was associated with a 29% increased risk of prostate
cancer associated mortality (RR=1.29, 95%CI,1.22 to 1.38, P<0.01). Sub-group analysis
conducted on three cohort studies involving patients with type 2 diabetes found increased risk of
all cause mortality but no specific association between pre-existing type 2 diabetes (RR=2.01,
95%CI, 1.37 to 2.96, P<0.01) and prostate cancer mortality (RR=1.17, 95%CI, 0.96 to 1.42).
h. A meta-analysis examining the relationship between diabetes and prognosis of individuals with
lung cancer located 12 studies for analysis from a search of Embase and Medline databases to
October 2015 (10). The studies were conducted in the U.S., EU and Asia. Diabetes was
Cancer - Diabetes
associated with reduced overall survival in lung cancer (HR=1.28, CI, 1.10 to 1.49, P=0.001),
significantly in non-small cell lung cancer (HR=1.35, 95%CI, 1.14 to 1.60, P=0.002) but not
significantly in small cell lung cancer (HR=1.33, 95%CI, 0.87 to 2.03, P=0.18). Limitations
identified with the source studies analyzed include differences in duration of follow up, degree of
confounding factors, study populations and confirmation of diabetes.
i. Weiser, et al. reported on outcomes in a cohort of 278 individuals with acute lymphocytic
leukemia: one group developed hyperglycemia, the other remained relatively normoglycemic (11).
While both groups experienced similar rates of mucositis, neutropenia and neuropathy, the group
with hyperglycemia were more likely to experience serious infections and morbidity.
j. Even transient hyperglycemia may be associated with adverse outcomes. A study of 86
individuals without diabetes but diagnosed with febrile neutropenia (a complication associated
with chemotherapy) found higher risk of growth of gram negative bacteria, fungi and higher
mortality rate in those with hyperglycemia compared to those with nomoglycemia (12).
k. Diabetes or hyperglycemia may be associated with an increased risk of chemotherapy-induced
neutropenia (a hematologic toxicity that results in suppression of immunity and increased risk of
hospitalization, morbidity and mortality) (13). A meta-analysis exploring the association between
diabetes or hyperglycemia and chemotherapy-induced neutropenia located 10 studies for
analysis from a search of PubMed, EBSO, ProQuest and Cochrane databases to April 2016. The
single prospective cohort study and nine retrospective cohort studies of 8,688 cases of
chemotherapy-induced neutropenia were conducted in the EU, U.S., Asia and Oman. Diabetes
or hyperglycemia was associated with a higher risk of chemotherapy induced neutropenia
(OR=1.32, 95%CI, 1.06 to 1.64). Limitations identified in this study include the relatively small
number of studies eligible for inclusion, gaps in information reported and lack of adjustment for
confounding factors.
Rationale
The mechanisms that explain the poorer prognosis observed in individuals with diabetes and cancer
remain uncertain, but several hypotheses have been proposed including the influence of chronic
hyperglycemia and elevated insulin levels, which may stimulate cancer growth and/or encourage
progression of the disease, effects of insulin-like growth factor, potential influences of diabetes treatments
and potential interactions of cancer treatment and diabetes (10).
References
1. Gerards MC, van der Velden DL, Baars JW, Brandjes DPM, Hoekstra JBL, Vriesendorp TM, et al.
al. Impact of hyperglycemia on the efficacy of chemotherapy-a systematic review of preclinical
studies. Crit Rev Oncol Hematol. 2017 May;113:235-24. Abstract available
2. Shen H, Zhan M, Wang W, Yang D, Wang J. Impact of diabetes mellitus on the survival of
pancreatic cancer: a meta-analysis. Onco Targets Ther 2016 Mar 22;9:1679-88. Abstract
Cancer - Diabetes
3. Lv X, Qiao W, Leng Y, Wu L, Zhou Y. Impact of diabetes mellitus on clinical outcomes of
pancreatic cancer after surgical resection: a systematic review and meta-analysis. PLoS One.
2017 Feb 3;12(2):e0171370. Abstract available
4. Chen S, Tao M, Zhao L, Zhang X. The association between diabetes/hyperglycemia and the
prognosis of cervical cancer patients. Medicine (Baltimore) 2017 Oct; 96(40): e7981. Abstract
available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5737993/
5. Zhang D, Zhao Y, Wang T, Xi Y, Li N, Huang H. Diabetes mellitus and long-term mortality of
ovarian cancer patients. A systematic review and meta-analysis of 12 cohort studies. Diabetes
Metab Res Rev. 2017 May;33(4). Abstract available
6. Zhu B, Wu X, Wu B, Pei D, Zhang L, Wei L. The relationship between diabetes and colorectal
cancer prognosis: a meta-analysis based on the cohort studies. PLoS One. 2017 Apr 19;12
(4):e0176068. Abstract available from: https://www.ncbi.nlm.nih.gov/pubmed/28423026
7. Zhao XB, Ren GS. Diabetes mellitus and prognosis in women with breast cancer: a systematic
review and meta-analysis. Medicine (Baltimore). 2016 Dec;95
(49):e5602. https://www.ncbi.nlm.nih.gov/pubmed/27930583
8. Wolf I, Sadetzki S, Catane R, Karasik A, Kaufman B. Diabetes mellitus and breast cancer. The
Lancet Oncol. 2005;6(2):103-11. Abstract available
9. Lee J, Giovannucci E, Jeon JY. Diabetes and mortality in patients with prostate cancer: a meta-
analysis. Springerplus. 2016 Sep; 13;5(1):1548. Abstract available
10. Zhu L, Cao H, Zhang T, Shen H, Dong W, Wang L, Du J. The effect of diabetes mellitus on lung
cancer prognosis. Medicine (Baltimore) 2016 Apr; 95(17): e3528. Available
11. Weiser MA, Cabanillas ME, Konopleva M, Thomas DA, Pierce SA, Escalante CP, et al. Relation
between the duration of remission and hyperglycemia during induction chemotherapy for acute
lymphocytic leukemia with a hyperfractionated cyclophosphamide, vincristine, doxorubicin, and
dexamethasone/methotrexate-cytarabine regimen. Cancer. 2004 Mar 15;100(6):1179-85.
Abstract available from: https://www.ncbi.nlm.nih.gov/pubmed/15022284
12. Soysal DE, Karakus V, Seren AR, Tatar E, Celik M, Hızar S. Evaluation of transient
hyperglycemia in non-diabetic patients with febrile neutropenia. Eur J Intern Med. 2012 Jun;23
(4):342-6. Abstract available from: https://www.ncbi.nlm.nih.gov/pubmed/22560382
13. Alenzi EO, Kelley GA. The association of hyperglycemia and diabetes mellitus and the risk of
chemotherapy-induced neutropenia among cancer patients: a systematic review with meta-
analysis. J Diabetes Complications 2017 Jan: 31(1): 267-72. Abstract available
Cancer - Diabetes
Summary of Recommendations and Evidence

Cancer - Diabetes Summary of Recommendations and Evidence
Last Updated: 2019-05-17
This Summary of Recommendations and Evidence synthesizes the Key Practice Point(s) for each
Practice Question (PQ) in this Knowledge Pathway. It is organized by the Nutrition Care Process and
contains statements or recommendations that have been graded using either the PEN or GRADE
approaches to critical appraisal. For additional information on the evidence and references, see the PQs in
this Knowledge Pathway.
Content
ASSESSMENT
1. Diabetes and Cancer Risk
2. Nutrition Recommendations and Glycemic Targets
3. Hyperglycemia or Diabetes Effects
1. Diabetes and Cancer Risk

Evidence Summary
Evidence from prospective and retrospective studies suggests that individuals with diabetes (type 1 or type
2) may be at higher risk for certain forms of cancer, experience poorer prognosis and shorter overall
survival rates than individuals without diabetes.
Evidence from cohort and case control studies suggests that prediabetes may be associated with an
increased risk of hepatocellular cancer.
Grade of Evidence B
Remarks
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2. Nutrition Recommendations and Glycemic Targets

Recommendation
No specific recommendations were identified in the literature regarding optimal glucose control for
individuals undergoing cancer treatment. Goals for nutrition and glycemic control must be individually
tailored to take into account the individual’s age, co-morbidities, risk factors, cancer type, cancer stage,
prognosis, effects related to cancer treatment and ability to perceive hypoglycemia, and that are
acceptable to the individual.
Cancer - Diabetes
Evidence Summary
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Remarks
Some cancer treatment regimes, such as glucocorticoids, chemoradiation and chemotherapy agents may
be associated with hyperglycemia and require modification of diabetes medications as a result.
3. Hyperglycemia or Diabetes Effects

Evidence Summary
Hyperglycemia or diabetes is associated with higher risk of morbidity, cancer-specific mortality and
cancer recurrence rates.
Grade of Evidence B
Remarks
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Key Practice Point #1

Key Practice Point #1

Grade of Evidence: C & D

Key Practice Point #1

Summary of Recommendations and Evidence

1. Diabetes and Cancer Risk

2. Nutrition Recommendations and Glycemic Targets

3. Hyperglycemia or Diabetes Effects

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