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Cancer Research: Opposite associations between alanine aminotransferase and γ-glutamyl transferase levels and all-cause mortality in type 2 diabetes: Analysis of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study.


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Opposite associations between alanine aminotransferase and γ-glutamyl transferase levels and all-cause mortality in type 2 diabetes: Analysis of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study.

Metabolism. 2016 May;65(5):783-93

Authors: Williams KH, Sullivan DR, Nicholson GC, George J, Jenkins AJ, Januszewski AS, Gebski VJ, Manning P, Tan YM, Donoghoe MW, Ehnholm C, Young S, O’Brien R, Buizen L, Twigg SM, Keech AC

Abstract
AIMS: Reported associations between liver enzymes and mortality may not hold true in type 2 diabetes, owing to a high prevalence of non-alcoholic fatty liver disease, which has been linked to cardiovascular disease and mortality in its own right. Our study aimed to determine whether alanine aminotransferase (ALT) or γ-glutamyl transferase (GGT) levels predict mortality in type 2 diabetes, and to examine possible mechanisms.
METHODS: Data from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study were analyzed to examine the relationship between liver enzymes and all-cause and cause-specific mortality over 5years.
RESULTS: Over 5years, 679 (6.9%) individuals died. After adjustment, for every standard deviation increase in ALT (13.2U/L), the HR for death on study was 0.85 (95% CI 0.78-0.93), p<0.001. Conversely, GGT >70U/L, compared with GGT ≤70U/L, had HR 1.82 (1.48-2.24), p<0.001. For cause-specific mortality, lower ALT was associated with a higher risk of cardiovascular death only, whereas GGT >70U/L was associated with higher risks of death due to cardiovascular disease, cancer and non-cancer/non-cardiovascular causes. The relationship for ALT persisted after adjustment for indirect measures of frailty but was attenuated by elevated hsCRP.
CONCLUSIONS: As in the general population, ALT has a negative, and GGT a positive, correlation with mortality in type 2 diabetes when ALT is less than two times the upper limit of normal. The relationship for ALT appears specific for death due to cardiovascular disease. Links of low ALT with frailty, as a potential mechanism for relationships seen, were neither supported nor conclusively refuted by our analysis and other factors are also likely to be important in those with type 2 diabetes.

PMID: 27085785 [PubMed – indexed for MEDLINE]

pubmed: clinical cancer rese…

Cancer Research: Diabetes and cancer, common threads and missing links.


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Diabetes and cancer, common threads and missing links.

Cancer Lett. 2016 Apr 28;374(1):54-61

Authors: Hua F, Yu JJ, Hu ZW

Abstract
Diabetes mellitus is a serious and growing health problem worldwide and is associated with severe acute and chronic complications. Accruing epidemiological and clinical evidence have suggested that an increased cancer incidence is associated with diabetes as well as certain diabetes risk factors and diabetes medications. Several pathophysiological mechanisms for this relationship have been postulated, including insulin resistance and hyperinsulinemia, enhanced inflammation, aberrant metabolic state, endoplasmic reticulum stress, and deregulation of autophagy. In addition to these potential mechanisms, a number of common risk factors, including obesity, may be behind the association between diabetes and cancer. Furthermore, different anti-diabetic medications may modify cancer risk and mortality in patients with diabetes. This Review discusses evidence to support the relationship between diabetes and cancer development as well as the underlying mechanisms. We also discuss the relationship of current diabetes treatments and cancer risk or prognosis. Understanding the mechanisms that connect type 2 diabetes or diabetes treatments to cancer are crucial for establishing the fundamental strategies concerning about primary prevention, early detection and effective therapy against these diseases.

PMID: 26879686 [PubMed – indexed for MEDLINE]

pubmed: clinical cancer rese…

Cancer Research: Nut consumption and risk of cancer and type 2 diabetes: a systematic review and meta-analysis.


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Nut consumption and risk of cancer and type 2 diabetes: a systematic review and meta-analysis.

Nutr Rev. 2015 Jul;73(7):409-25

Authors: Wu L, Wang Z, Zhu J, Murad AL, Prokop LJ, Murad MH

Abstract
CONTEXT: The identification of foods that can decrease the risk of cancer and type 2 diabetes may be helpful in reducing the burden of these diseases. Although nut consumption has been suggested to have a disease-preventive role, current evidence remains inconsistent.
OBJECTIVE: The aim of this systematic review and meta-analysis was to clarify the association between nut consumption and risk of cancer or type 2 diabetes.
DATA SOURCES: Six databases were searched for relevant studies from the time of database inception to August 2014. Reference lists of relevant review articles were hand searched, and authors were contacted when data were insufficient.
STUDY SELECTION: Eligible studies included epidemiological studies (case-control and cohort) or clinical trials that reported an association between nut consumption and the outcome of type 2 diabetes or specific cancers.
DATA EXTRACTION: Two investigators independently extracted descriptive, quality, and risk data from included studies.
DATA SYNTHESIS: Random-effects meta-analysis was used to pool relative risks from the included studies. The I(2) statistic was used to assess heterogeneity. A total of 36 eligible observational studies, which included 30,708 patients, were identified. The studies had fair methodological quality, and length of follow-up ranged between 4.6 years and 30 years. Comparison of the highest category of nut consumption with the lowest category revealed significant associations between nut consumption and decreased risk of colorectal cancer (3 studies each with separate estimates for males and females, RR 0.76, 95% confidence interval [95%CI] 0.61-0.96), endometrial cancer (2 studies, RR 0.58, 95%CI 0.43-0.79), and pancreatic cancer (1 study, RR 0.68, 95%CI 0.48-0.96). No significant association was found with other cancers or type 2 diabetes. Overall, nut consumption was significantly associated with a reduced risk of cancer incidence (RR 0.85, 95%CI 0.76-0.95).
CONCLUSIONS: Nut consumption may play a role in reducing cancer risk. Additional studies are needed to more accurately assess the relationship between nut consumption and the prevention of individual types of cancer, given the scarcity of available data.

PMID: 26081452 [PubMed – indexed for MEDLINE]

pubmed: clinical cancer rese…

Cancer Research: Comparison of Short- and Mid-term Efficacy and the Mechanisms of Gastric Bypass Surgeries on Managing Obese and Nonobese Type 2 Diabetes Mellitus: A Prospective Study.


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Comparison of Short- and Mid-term Efficacy and the Mechanisms of Gastric Bypass Surgeries on Managing Obese and Nonobese Type 2 Diabetes Mellitus: A Prospective Study.

Arch Med Res. 2015 May;46(4):303-9

Authors: Zhang X, Cheng Z, Xiao Z, Du X, Du J, Li Y, Long Y, Yu H, Zhang X, Tian H

Abstract
BACKGROUND AND AIMS: We targeted to investigate the efficacy and the mechanisms of two gastric bypass surgeries, Roux-en-y Gastric Bypass (RYGB) and Billroth II gastrojejunostomy on managing obese patients with T2DM and nonobese T2DM patients, respectively.
METHODS: Seven nonobese T2DM patients with gastric cancer submitted to Billroth II gastrojejunostomy were compared with nine obese T2DM patients undergoing RYGB about their baseline characteristics, weight loss and glycemic control, 3 months and 2 years after surgery. Meanwhile, β-cell function, glucagon-like peptide 1 (GLP-1), peptide YY (PYY) and gastric inhibitory polypeptide (GIP) levels were also investigated.
RESULTS: Significant weight loss and improvement of glycemic control were observed in both groups and in the two follow-up periods. Reduction of body mass index was greater in obese patients with T2DM. The efficacy of Billroth II gastrojejunostomy on controlling blood glucose of nonobese T2DM was similar to that of RYGB on managing obese T2DM. Insulin levels and HOMA-IR were decreased in obese T2DM patients, whereas they remained unchanged in nonobese T2DM patients. Generally, levels of GLP-1 and PYY were increased, whereas GIP levels were decreased in both groups.
CONCLUSIONS: Glycemic control efficacy of Billroth II gastrojejunostomy on managing nonobese T2DM is similar to that of RYGB on treating obese T2DM in the short- and mid-term. The underlying mechanisms of both surgeries may be related to weight loss and gut hormone modulations.

PMID: 26087171 [PubMed – indexed for MEDLINE]

pubmed: clinical cancer rese…

Cancer Research: Obesity and Diabetes: The Increased Risk of Cancer and Cancer-Related Mortality.


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Obesity and Diabetes: The Increased Risk of Cancer and Cancer-Related Mortality.

Physiol Rev. 2015 Jul;95(3):727-48

Authors: Gallagher EJ, LeRoith D

Abstract
Obesity and type 2 diabetes are becoming increasingly prevalent worldwide, and both are associated with an increased incidence and mortality from many cancers. The metabolic abnormalities associated with type 2 diabetes develop many years before the onset of diabetes and, therefore, may be contributing to cancer risk before individuals are aware that they are at risk. Multiple factors potentially contribute to the progression of cancer in obesity and type 2 diabetes, including hyperinsulinemia and insulin-like growth factor I, hyperglycemia, dyslipidemia, adipokines and cytokines, and the gut microbiome. These metabolic changes may contribute directly or indirectly to cancer progression. Intentional weight loss may protect against cancer development, and therapies for diabetes may prove to be effective adjuvant agents in reducing cancer progression. In this review we discuss the current epidemiology, basic science, and clinical data that link obesity, diabetes, and cancer and how treating obesity and type 2 diabetes could also reduce cancer risk and improve outcomes.

PMID: 26084689 [PubMed – indexed for MEDLINE]

pubmed: clinical cancer rese…