Metformin Associated With Increased Survival in Type 2 Diabetes Patients With Pancreatic Cancer and Lymphoma.

BACKGROUND: The biguanide drug metformin is one of the most commonly used medications for the treatment of type 2 diabetes mellitus. Diabetics are at an increased risk for cancer. Previous studies have demonstrated improved outcomes in patients taking metformin suffering from prostate, colon, lung, thyroid, and esophageal cancers. Metformin's main antineoplastic mechanism of action is thought to be mediated through inhibition of mammalian target of rapamycin, inhibition of hypoxia-inducible factor 1 (HIF-1) alpha, and activation of p53. We investigated the overall survival of type 2 diabetic patients on metformin with pancreatic cancer and lymphoma using the Computerized Patient Record System at the Veterans Affairs Medical Center, Memphis TN. METHODS: Lymphoma and pancreatic cancer patients with type 2 diabetes were sorted into an experimental (metformin) group and a control (nonmetformin) group. Patients were compared on baseline characteristics including race, body mass index, and age. Cancer outcomes including overall survival, metastasis, recurrences, and incidence of new malignancies were recorded. Hemoglobin A1C, creatinine and cancer treatment modalities were recorded and compared. Statistical analyses used included unpaired t tests and Chi-squared tests. RESULTS: There was significantly greater overall long-term survival in the metformin group compared to the nonmetformin group for lymphoma (5.89 vs 1.29 years, P < 0.001) and for pancreatic cancer (0.68 vs 0.22 years, P = 0.016). Cancer treatment modalities in both groups were comparable. CONCLUSIONS: Metformin is associated with a significant, positive effect of increased overall survival in type 2 diabetes patients with pancreatic cancer and lymphoma. These results are encouraging, and prospective studies should be done to further investigate metformin's effects in cancer.

Metformin: Possible Use of a Diabetes Drug in Treatment of Cancer.

The biguanide drug metformin used for treating Type 2 diabetes has anticancer properties and affects many pathways involving glucose metabolism, energy balance, and cell survival. A number of retrospective clinical studies have indicated a reduced risk of cancer and improved cancer outcomes in Type 2 diabetic patients taking metformin. Several of its effects are mediated through the induction of cellular stress and subsequent activation of AMP kinase, but many other mechanisms act independently of AMP kinase activation. Metformin has been shown to inhibit the effects of tumor necrosis factor (TNF)-alpha. TNF-alpha interferes with insulin signaling to produce insulin resistance in the insulin signaling pathway and promotes apoptosis through NF-KB in the apoptosis pathway. In addition, metformin reduces cellular proliferation by decreasing the amount of available insulin or by directly affecting the mammalian target of rapamycin complex involved with regulating protein synthesis. It can prevent tumors from acquiring stem cell-like properties, upregulate apoptotic pathways, and bolster the immune system's fight against cancer. Gaining a greater understanding of metformin's various mechanisms of action will continue to elucidate metformin's role as an effective treatment for cancer.

Climatic and watershed controls of dissolved organic matter variation in streams across a gradient of agricultural land use.

Human land use has led to significant changes in the character of dissolved organic matter (DOM) in lotic ecosystems. These changes are expected to have important environmental and ecological consequences. However, high spatiotemporal variability has been reported in previous studies, and the underlying mechanisms remain inadequately understood. This study assessed variation in the properties of stream water DOM within watersheds across a gradient of agricultural land use with grazing pasture lands as the dominant agricultural type in the southeastern United States. We collected water samples under baseflow conditions five times over eight months from a regional group of first- to fourth-order streams. Samples were analyzed for dissolved organic carbon (DOC) concentration, DOM quality based on absorbance and fluorescence properties, as well as DOM biodegradability. We found that air temperature and antecedent hydrological conditions (indicated by antecedent precipitation index and stream water sodium concentrations) positively influenced stream water DOC concentration, DOM fluorescence index, and the proportion of soil-derived, microbial humic fluorescence. This observation suggests that elevated production and release of microbial DOM in soils facilitated by high temperature, in conjunction with strong soil-stream hydrological connectivity, were important drivers for changes in the concentration and composition of stream water DOM. By comparison, watersheds with a high percentage of agricultural land use showed higher DOC concentration, larger proportion of soil-derived, humic-like DOM compounds, and higher DOC biodegradability. These observations reflect preferential mobilization of humic DOM compounds from shallow organic matter-rich soils in agricultural watersheds, likely due to enhanced soil erosion, organic matter oxidation and relatively shallow soil-to-stream flow paths.

Prediabetes as a toxic environment for the initiation of microvascular and macrovascular complications.

Prediabetes is a state characterized by impaired fasting glucose or impaired glucose tolerance. Evidence is increasingly demonstrating that prediabetes is a toxic state, in addition to being a harbinger of future development of diabetes mellitus. This minireview discusses the pathophysiology and clinical significance of prediabetes, and approach to its management, in the context of the worldwide diabetes epidemic. The pathophysiologic defects underlying prediabetes include insulin resistance, ß cell dysfunction, increased lipolysis, inflammation, suboptimal incretin effect, and possibly hepatic glucose overproduction. Recent studies have revealed that the long-term complications of diabetes may manifest in some people with prediabetes; these complications include classical microvascular and macrovascular disorders, and our discussion explores the role of glycemia in their development. Finally, landmark intervention studies in prediabetes, including lifestyle modification and pharmacologic treatment, are reviewed.