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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is increasing evidence that type 2 diabetes mellitus and glucose intolerance are a cause, not just a consequence, of pancreatic cancer. We examined whether other factors that characterize the insulin resistance syndrome are also risk factors for pancreatic cancer in a prospective cohort study of 631,172 men and women (ages 45+ years) who received health insurance from the Korean Medical Insurance Corporation. The biennial medical evaluations from 1992 to 1995 provided the baseline information for this study. Relative risks (RR) were estimated using proportional hazards models adjusted for age, sex, smoking, and fasting serum glucose (after excluding the first 2 years of follow-up). There were 2,194 incident cases of pancreatic cancer diagnosed in the cohort over a median follow-up of 12 years. There was no evidence that pancreatic cancer risk was associated with total cholesterol, systolic blood pressure, WBC count, or body mass index. Abnormal levels of aspartate aminotransferase and alanine aminotransferase were both associated with a moderately increased risk of developing the disease (40+ versus <20; RR, 1.33; 95% CI, 1.14-1.55; P(trend) = 0.05 and RR, 1.34; 95% CI, 1.16-1.56; P(trend) = 0.02, respectively). Excluding 6 years of follow-up reduced this RR (95% CI) for aspartate aminotransferase to 1.22 (1.01-1.49), but even after excluding 10 years follow-up the RR (95% CI) for alanine aminotransferase was unchanged [1.36 (1.01-1.83)]. Although fasting serum glucose has been found previously to be associated with pancreatic cancer risk in this cohort, most other factors that characterize insulin resistance syndrome were not associated with pancreatic cancer risk. The association with elevated liver enzyme levels is a novel finding that warrants further investigation.
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PMID:Pancreatic cancer and factors associated with the insulin resistance syndrome in the Korean cancer prevention study. 1826 20

A 77-year-old Japanese man was admitted due to hypoglycemia induced by small amount of insulin. He was diagnosed type 2 diabetes in 1978 and the pancreatic cancer in 1993. Resection of the pancreas head and duodenum was performed. Subsequently, anastomotic stenosis appeared to induce appetite loss. His flavor for carbohydrate-rich food accelerated protein malnutrition. Fatty liver and pancreas atrophy were diagnosed in 1999. After he was diagnosed as secondary kwashiorkor, nasal feeding of protein-rich food improved his fatty liver as well as his general condition rapidly. Anastomotic stenosis and pancreas atrophy contributed to a combination of type 2 diabetes and kwashiorkor.
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PMID:Combination of type 2 diabetes and malnutrition worsened by anastomotic stenosis and pancreas atrophy following resection of pancreas head. 1859 45

The prevalence of overweight (body mass index, BMI, between 25 and 30 kg/m2) and obesity (BMI of 30 kg/m2 or higher) is increasing rapidly worldwide, especially in developing countries and countries undergoing economic transition to a market economy. One consequence of obesity is an increased risk of developing type II diabetes. Overall, there is considerable evidence that overweight and obesity are associated with risk for some of the most common cancers. There is convincing evidence of a positive association between overweight/obesity and risk for adenocarcinoma of the oesophagus and the gastric cardia, colorectal cancer, postmenopausal breast cancer, endometrial cancer and kidney cancer (renal-cell). Premenopausal breast cancer seems to be inversely related to obesity. For all other cancer sites the evidence of an association between overweight/obesity and cancer is inadequate, although there are studies suggesting an increased risk of cancers of the liver, gallbladder, pancreas, thyroid gland and in lymphoid and haematopoietic tissue. Far less is known about the association between diabetes mellitus type I (also called insulin dependent diabetes mellitus or juvenile diabetes), type II diabetes (called non-insulin dependent diabetes mellitus or adult onset diabetes mellitus) and cancer risk. The most common type of diabetes mellitus, type II, seems to be associated with liver and pancreas cancer and probably with colorectal cancer. Some studies suggest an association with endometrial and postmenopausal breast cancer. Studies reporting on the association between type I diabetes mellitus, which is relatively rare in most populations and cancer risk are scanty, but suggest a possible association with endometrial cancer. Overweight and obesity, as well as type II diabetes mellitus are largely preventable through changes in lifestyle. The fundamental causes of the obesity epidemic-and consequently the diabetes type II epidemic-are societal, resulting from an environment that promotes sedentary lifestyles and over-consumption of energy. The health consequences and economic costs of the overweight, obesity and type II diabetes epidemics are enormous. Avoiding overweight and obesity, as well as preventing type II diabetes mellitus, is an important purpose to prevent cancer and other diseases. Prevention of obesity and type II diabetes should begin early in life and be based on the life-long health eating and physical activity patterns. Substantial public investments in preventing overweight, obesity and type II diabetes mellitus are both appropriate and necessary in order to have a major impact on their adverse health effects including cancer.
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PMID:Obesity and diabetes epidemics: cancer repercussions. 1863 86

We present a case of a 40-year-old man with strong family history of diabetes. His pancreatic ultrasonography was normal at the discovery of his diabetes. Anti-pancreatic antibodies were negative. The patient was treated by insulin and continued to loose weight. His diabetes remained unstable during the follow-up. Three years later, a pancreatic adenocarcinoma was diagnosed which was locally advanced and could not be removed surgically. This observation argues among several mechanisms explaining diabetes in subjects with pancreatic cancer, in favor of tumor-derived diabetogenic substance and suggests that diabetes mellitus could reveal pancreatic cancer even in the presence of conventional risk factors of type 2 diabetes.
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PMID:Diabetes mellitus as an early symptom of pancreatic cancer diagnosed three years later. 1899 44

The genes TSC1 and TSC2, encoding hamartin and tuberin, respectively, have been shown to be involved in the development of the autosomal dominantly inherited tumor syndrome tuberous sclerosis (TSC). However, inactivation of these genes has also been demonstrated to be associated with sporadic bladder cancer, ovarian and gall bladder carcinoma, non-small-cell carcinoma of the lung, breast cancer, pancreatic cancer, astrocytoma, xanthoastrocytoma, ependymomas, oral squamous cell carcinoma and endometrial cancer. The hamartin/tuberin protein complex plays a central role in the regulation of the mammalian target of rapamycin (mTOR) signalling network. A wide variety of components of the mTOR cascade have been demonstrated to be involved in many different human cancers. Mutations in several mTOR pathway component genes are known to cause specific monogenic human genetic diseases and this signalling cascade has been shown to be of relevance for Alzheimer's disease, type 2 diabetes, obesity and hypertrophy. Consequently, e.g. clinical trials for the treatment with rapamycin, a negative regulator of mTOR, of hamartomas in TSC have already been initiated. Now the first evidence is provided for an involvement of the TSC genes in acute leukemia.
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PMID:New insights into the role of the tuberous sclerosis genes in leukemia. 1925 Jun 71

The development of pancreatic fibrosis has been shown to be a major component in several diseases of the pancreas including pancreatic cancer, chronic pancreatitis, and type 2 diabetes mellitus, but its actual role in the progression of these disorders is still unknown. This fibrosis is characterized by stromal expansion and the excessive deposition of extracellular matrix (ECM) that replaces pancreatic tissue. This eventually leads to dysregulation of ECM turnover, production of cytokines, restriction of blood flow, and often exocrine and endocrine insufficiencies. Activated pancreatic stellate cells (PSCs) have been identified as key mediators in the progression of pancreatic fibrosis, serving as the predominant source of excess ECM proteins. Previously, we found that overexpression of the growth factor heparin-binding epidermal growth factor-like growth factor (HB-EGF) in pancreatic islets led to intraislet fibrosis. HB-EGF binds to and activates two receptors, epidermal growth factor receptor (EGFR) and ErbB4, as well as heparin moieties and CD9/DRAP27. To understand the mechanism underlying the induction of fibrogenesis by HB-EGF, we utilized a hypomorphic allele of Egfr, the Waved-2 allele, to demonstrate that EGFR signaling regulates fibrogenesis in vivo. Using an in vitro cell migration assay, we show that HB-EGF regulates both chemoattraction and stimulation of proliferation of PSCs via EGFR activation.
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PMID:Epidermal growth factor receptor regulates pancreatic fibrosis. 1960 32

Recently, we identified a novel crosstalk between insulin and G protein-coupled receptor (GPCR) signaling pathways in human pancreatic cancer cells. Insulin enhanced GPCR signaling through a rapamycin-sensitive mTOR-dependent pathway. Metformin, the most widely used drug in the treatment of type 2 diabetes, activates AMP kinase (AMPK), which negatively regulates mTOR. Here, we determined whether metformin disrupts the crosstalk between insulin receptor and GPCR signaling in pancreatic cancer cells. Treatment of human pancreatic cancer cells (PANC-1, MIAPaCa-2, and BxPC-3) with insulin (10 ng/mL) for 5 minutes markedly enhanced the increase in intracellular [Ca(2+)] induced by GPCR agonists (e.g., neurotensin, bradykinin, and angiotensin II). Metformin pretreatment completely abrogated insulin-induced potentiation of Ca(2+) signaling but did not interfere with the effect of GPCR agonists alone. Insulin also enhanced GPCR agonist-induced growth, measured by DNA synthesis, and the number of cells cultured in adherent or nonadherent conditions. Low doses of metformin (0.1-0.5 mmol/L) blocked the stimulation of DNA synthesis, and the anchorage-dependent and anchorage-independent growth induced by insulin and GPCR agonists. Treatment with metformin induced striking and sustained increase in the phosphorylation of AMPK at Thr(172) and a selective AMPK inhibitor (compound C, at 5 micromol/L) reversed the effects of metformin on [Ca(2+)](i) and DNA synthesis, indicating that metformin acts through AMPK activation. In view of these results, we tested whether metformin inhibits pancreatic cancer growth. Administration of metformin significantly decreased the growth of MIAPaCa-2 and PANC-1 cells xenografted on the flank of nude mice. These results raise the possibility that metformin could be a potential candidate in novel treatment strategies for human pancreatic cancer.
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PMID:Metformin disrupts crosstalk between G protein-coupled receptor and insulin receptor signaling systems and inhibits pancreatic cancer growth. 1967 49

Pancreatic cancer is generally refractory to most chemotherapeutic agents. We investigated whether hSSTR2 expression and octreotide treatment reverse multidrug resistance of human pancreatic cancer cells. We used pancreatic cancer cells that were transfected by using a lentivirus expression system, which allowed stable expression of the hSSTR2 gene in the pancreatic cancer cells. BxPC-3 cells were transfected with hSSTR2 through a lentivirus vector pWP XL-MOD-SSTR2 in order to enable the expression of hSSTR2. The transfected cells were treated with different concentrations of octreotide and with the chemotherapeutic agents cisplatin, epirubicin, fluorouracil and gemcitabine. The changes in IC50 following treatment with chemotherapeutic agents were determined, and the expression of different MDR indicating marker genes, multidrug resistance gene-1 (MDR1), multidrug resistance-associated protein 2 (MRP2), and lung resistance-related protein (LRP), were evaluated. Octreotide treatment of the transfected cells significantly decreased the IC50 of chemotherapeutic agents in a dose-dependent manner. hSSTR2 gene transfection decreased MDR1, MRP2 and LRP expression by 57, 47 and 56%, respectively (P<0.01), and octreotide treatment (1.6 microg/ml) for 48 h, decreased it further by 88, 73 and 87<, respectively (P<0.01). These data suggested that the down-regulation of MDR genes is responsible for the improvement in the chemotherapeutic sensitivity of hSSTR2-expressing pancreatic cancer cells, when these cells are subjected to octreotide treatment.
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PMID:hSSTR2 expression and octreotide treatment reverses multidrug resistance of BxPC-3 human pancreatic cancer cells. 1988 91

Diabetic ketoacidosis (DKA) has been the hallmark of a life-threatening medical emergency for poorly controlled or newly diagnosed type 1 diabetics. In the last two decades, this traditional association has been challenged with increasing reports of type 2 diabetics presenting with DKA. We report the case of a 75-year-old woman with known type 2 diabetes who presented in DKA and was found to have pancreatic adenocarcinoma. A link between diabetes mellitus and pancreatic cancer has been investigated, but the literature remains inconclusive as to whether diabetes mellitus (DM) is a cause or result of pancreatic cancer or simply the confluence of two common entities. Previous case reports of pancreatic tumors presenting with DKA all represented neuroendocrine tumors. Adenocarcinoma of the pancreas should be considered in the list of precipitants for DKA in type 2 DM.
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PMID:Diabetic ketoacidosis in type 2 diabetics: a novel presentation of pancreatic adenocarcinoma. 2011 82

Epidemiological findings have shown up to two-fold increases in the risks of cancers of the colorectum, breast, endometrium, kidney (renal cell tumours), liver and pancreas among diabetes patients. In the present review, we address the question whether, on the basis of these epidemiological observations, type 2 diabetes should be considered a specific and independent risk factor for these various forms of cancer, due to its particular metabolic characteristics of glucose intolerance and hyperinsulinemia. On the basis of further epidemiological evidence among non-diabetic individuals, as well as recent studies examining the effects of different types of diabetes treatment on cancer risks, we conclude that chronic elevations in fasting and non-fasting blood levels of glucose and/or insulin are plausible independent risk factors for cancer, but that much of the increase in cancer risks associated with these two metabolic factors may occur within the normoglycaemic and insulinemic (non-diabetic) ranges. Furthermore, for some tumour types (e. g. cancer of the endometrium) the associations of risk with type 2 diabetes may to a large extent be due to, and at least partially confounded by, other obesity-related alterations in (e. g. sex steroid) metabolism that in part are independent of glucose and/or insulin metabolism. Specifically for pancreatic cancer, a major question, addressed in detail by other reviews, is whether associations of risk with plasma glucose, insulin or overt type 2 diabetes could be either a cause, or possibly also a consequence of tumour development (or both).
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PMID:Diabetes mellitus type 2 - an independent risk factor for cancer? 2012 70


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