Diabetes Abstracts 1 - Misconceptions

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The influence of type 2 diabetes and glucose-lowering therapies on cancer risk in the Taiwanese.
            (Hsieh et al., 2012) Download
OBJECTIVE: To investigate the association between type 2 diabetes, glucose-lowering therapies (monotherapy with either metformin, sulphonylurea or insulin) and cancer risk in Taiwan. METHODS: Using Taiwan's National Health Research Institutes database of 1,000,000 random subjects from 2000-2008, we found 61777 patients with type 2 diabetes (age >/=20 years) and 677378 enrollees with no record of diabetes. RESULTS: After adjusting for age and sex, we found patients with diabetes to have significantly higher risk of all cancers (OR: 1.176; 95% CI: 1.149-1.204, P < 0.001). Diabetic patients treated with insulin or sulfonylureas had significantly higher risk of all cancers, compared to those treated with metformin (OR: 1.583; 95% CI: 1.389-1.805, P < 0.001 and OR: 1.784; 95% CI: 1.406-2.262, P < 0.001). Metformin treatment was associated with a decreased risk of colon and liver cancer compared to sulphonylureas or insulin treatment. Sulfonylureas treatment was associated with an increased risk of breast and lung cancer compared to metformin therapy. CONCLUSIONS: Taiwanese with type 2 diabetes are at a high risk of breast, prostate, colon, lung, liver and pancreatic cancer. Those treated with insulin or sulfonylureas monotherapy are more likely to develop colon and liver cancer than those treated with metformin.

Impaired glucose metabolism and diabetes and the risk of breast, endometrial, and ovarian cancer.
            (Lambe et al., 2011) Download
BACKGROUND: Epidemiological evidence indicates that individuals with type 2 diabetes are at an increased risk of cancer. Elevated glucose levels, below the diagnostic threshold for diabetes, have also been suggested to be associated with increased cancer risks. METHODS: We investigated possible associations between glucose levels and the risk of breast, endometrial, and ovarian cancer in a cohort of more than 230,000 women, for which information on outcome and potential confounders was obtained by record linkage to population-based registers. RESULTS: Diabetes was associated with an increased risk of postmenopausal breast cancer (HR = 1.22, 95% CI 1.04-1.43). An indication of a slightly elevated breast cancer risk was also found in postmenopausal women with impaired glucose metabolism (HR = 1.11, 95% CI 0.96-1.28). Diabetes (HR = 1.46, 95% CI 1.09-1.96) and impaired glucose metabolism (HR = 1.41, 95% CI 1.08-1.85) were associated with an increased risk of endometrial cancer. No associations were found between glucose levels and ovarian cancer risk. Following adjustment for BMI, estimates were attenuated for endometrial cancer, while point estimates for breast and ovarian cancer remained essentially unchanged. CONCLUSIONS: Our results indicate that glucose levels below the diagnostic threshold for diabetes modify the risk not only of endometrial cancer but possibly also of postmenopausal breast cancer.

Gestational diabetes and risk of incident primary cancer: a large historical cohort study in Israel.
            (Sella et al., 2011) Download
PURPOSE: Gestational diabetes mellitus (GDM), a state of glucose intolerance associated with pregnancy, is increasing in prevalence. Data regarding the cancer risk associated with GDM are sparse and limited to cancers of the breast and pancreas. This study was conducted to examine the risk of incident overall and site-specific malignancies associated with prior GDM in a historical cohort of women in a large health maintenance organization in Israel. METHODS: All pregnant women aged 15-50 years who underwent 50-g glucose challenge tests between 13 March 1995 and 27 May 2009, without history of malignancy, diabetes, and infertility, were included. Clinical and demographic parameters at index date including age, socioeconomic level, BMI, and parity were collected. Diagnosis of gestational diabetes was based on the 100-g oral glucose tolerance test using Carpenter and Coustan criteria. Cancer diagnoses were obtained from the Israel Cancer Register through linkage data. RESULTS: Among the 185,315 women who had undergone glucose challenge during the study period, 11,264 (6.1%) were diagnosed with GDM. During a total follow-up period of 1.05 million person-years (mean = 5.19 +/- 3.9, median = 4.3), 2,034 incident cases of cancer were identified. GDM was associated with a hazard ratio (HR) of 7.06 (95% CI: 1.69-29.45) for pancreatic cancer (nine cases) and a HR of 1.70 (95% CI: 0.97-2.99) for hematological malignancies (177 cases). The association between GDM and hematological malignancies was limited to women with 5 or more years of follow-up (HR = 4.53; 95% CI: 1.81-11.31). CONCLUSION: GDM is associated with an increased risk of pancreatic cancer and hematologic malignancies.

Prospective study on the role of glucose metabolism in breast cancer occurrence.
            (Sieri et al., 2012) Download
High circulating glucose, insulin resistance and obesity appear to be associated with increased risk of breast cancer (BC). We sought further insight into the relation of these variables to BC. We assessed associations of BC risk with serum fasting glucose, insulin, homeostasis model assessment-insulin resistance (HOMA-IR) index and sex-binding hormone globulin (SHBG) in women recruited to the ORDET cohort who gave blood samples in 1987-1992. After a median 13.5 years of follow-up, 356 women developed BC. Four matched controls per case were selected by incidence density sampling, and rate ratios (RR) were estimated by conditional logistic regression. Women in the highest glucose quartile had a significantly greater risk of BC than those in the lowest glucose quartile (RR 1.63; 95% CI: 1.14-2.32; p for trend of 0.003). The association was significant in pre and post menopausal women separately and in women diagnosed after 55 years. Women in the highest HOMA-IR quartile had higher BC risk than the lowest quartile (RR 1.44; 95% CI: 1.03-2.02). Significantly increased BC risk in women diagnosed after 55 years was also present in the highest HOMA-IR quartile; in the same group decreased BC risk was significantly associated with high SHBG. The results of this study add to the existing epidemiological evidence that hyperglycemia and insulin resistance increase BC risk.

Prospective study of hyperglycemia and cancer risk.
            (Stattin et al., 2007) Download
OBJECTIVE: To investigate whether hyperglycemia is associated with increased cancer risk. RESEARCH DESIGN AND METHODS: In the Vasterbotten Intervention Project of northern Sweden, fasting and postload plasma glucose concentrations were available for 33,293 women and 31,304 men and 2,478 incident cases of cancer were identified. Relative risk (RR) of cancer for levels of fasting and postload glucose was calculated with the use of Poisson models, with adjustment for age, year of recruitment, fasting time, and smoking status. Repeated measurements 10 years after baseline in almost 10,000 subjects were used to correct RRs for random error in glucose measurements. RESULTS: Total cancer risk in women increased with rising plasma levels of fasting and postload glucose, up to an RR for the top versus bottom quartile of 1.26 (95% CI 1.09-1.47) (P(trend) <0.001) and 1.31 (1.12-1.52) (P(trend) = 0.001), respectively. Correction for random error in glucose measurements increased these risks up to 1.75 (1.32-2.36) and 1.63 (1.26-2.18), respectively. For men, corresponding uncorrected RR was 1.08 (0.92-1.27) (P(trend) = 0.25) and 0.98 (0.83-1.16) (P(trend) = 0.99), respectively. Risk of cancer of the pancreas, endometrium, urinary tract, and of malignant melanoma was statistically significantly associated with high fasting glucose with RRs of 2.49 (1.23-5.45) (P(trend) = 0.006), 1.86 (1.09-3.31) (P(trend) = 0.02), 1.69 (0.95-3.16) (P(trend) = 0.049), and 2.16 (1.14-4.35) (P(trend) = 0.01), respectively. Adjustment for BMI had no material effect on risk estimates. CONCLUSIONS: The association of hyperglycemia with total cancer risk in women and in women and men combined for several cancer sites, independently of obesity, provides further evidence for an association between abnormal glucose metabolism and cancer.

 

References

Hsieh, MC, et al. (2012), ‘The influence of type 2 diabetes and glucose-lowering therapies on cancer risk in the Taiwanese.’, Exp Diabetes Res, 2012 413782. PubMedID: 22719752
Lambe, M, et al. (2011), ‘Impaired glucose metabolism and diabetes and the risk of breast, endometrial, and ovarian cancer.’, Cancer Causes Control, 22 (8), 1163-71. PubMedID: 21688131
Sella, T, et al. (2011), ‘Gestational diabetes and risk of incident primary cancer: a large historical cohort study in Israel.’, Cancer Causes Control, 22 (11), 1513-20. PubMedID: 21847538
Sieri, S, et al. (2012), ‘Prospective study on the role of glucose metabolism in breast cancer occurrence.’, Int J Cancer, 130 (4), 921-29. PubMedID: 21413010
Stattin, P, et al. (2007), ‘Prospective study of hyperglycemia and cancer risk.’, Diabetes Care, 30 (3), 561-67. PubMedID: 17327321