Complications and Comorbidities> Hematology/Malignancy>

EPIDEMIOLOGY

• Diabetes associated with increased risk of non-Hodgkin lymphoma (Chao C) and cancer of breast (Larsson SC ), colorectum (Larsson SC ), endometrium (Friberg E), liver (El-Serag HB), and pancreas (Huxley R).
• Negatively associated with risk of prostate cancer (Kasper JS).
• Hypotheses about possible link between diabetes and cancer include:
• - Insulin is known to stimulate cell proliferation (Giovannucci E)
• - Hyperglycemia promotes tumor growth (Saydah S; Rinaldi S)
• - Shared risk factors such as obesity (Giovannucci E), diet, physical inactivity (Roberts CK), hepatitis C (White DL), NAFLD (Clark JM)

• Diabetes associated with:
• - increased risk of death from colon and pancreatic cancers in both men and women;
• - increased risk of death from liver and bladder cancers in men,
• - increased risk of death from breast cancer in women (Coughlin)
• Also reported positive associations with death from:
• - esophagus, liver, and colon/rectum cancers in men, and
• - liver and cervix cancers in women (Jee SH 15644546).

• Meta-analyses  showed diabetes associated with an increased mortality in patients with any cancer [HR of 1.44], cancers of the endometrium (HR, 1.76), breast (HR, 1.61), colorectum (HR, 1.32), and prostate. ((Barone BB 20351229, Snyder CF )
• Meta-analysis showed diabetes associated with increased odds of postoperative mortality across all cancer types [HR=1.5] (Barone BB ).
• Hyperglycemia associated with shorter duration of complete remission in patients with acute lymphocytic leukemia; (Weiser MA )
• Hyperglycemia associated with shorter survival in patients with newly diagnosed glioblastoma. (Derr RL )

• Negatively associated with risk of prostate cancer. (Kasper JS. )
• Androgen deprivation therapy causes changes in body composition, alterations in lipid profiles, and decreased insulin sensitivity. (Faris JE .)
• Androgen deprivation therapy significantly increased risk for diabetes mellitus. (Alibhai SM )

• A meta-analysis (Renehan AG ) showed BMI strongly associated with:
• - oesophageal adenocarcinoma (RR 1.52), thyroid (RR 1.33), colon (RR 1.24), and renal (RR 1.24) cancers. (all p<0.001 )
• - endometrial (RR 1.59), gallbladder (RR 1.59), esophageal (RR 1.51), and renal (RR 1.34) cancers in women. (all p<0.05)
• - weaker positive associations with cancer and malignant melanoma in men
• Patients with gastric bypass surgery had a lower risk of cancer mortality compared to severely obese patients. (Adams TD)

CLINICAL TREATMENT

• Recent studies suggested metformin (Currie CJ ; Bodmer M ) and Thiazolidinediones (Blanquicett C ) decreased the risk of cancer.
• Cumulative insulin use associated with increased cancer mortality rates (Bowker SL. ).

EXPERT COMMENTS

• The above are statistical associations that are subject to a number of confounders, and cannot be considered to prove causality.
• Therefore, in the person with diabetes, more vigilant use of established screening approaches, such as for colon cancer, may be indicated; but generally not indicated to scare patients by emphasizing statistical associations.
• As for treatment, again, use caution in drawing clinical conclusions about using either metformin or insulin based on possible associations with cancer.

REFERENCES