Metformin reduces risk for pancreatic cancer
Key review points:
Pancreatic cancer is asymptomatic in early stage and usually detected in advance stage when become symptomatic. Late presentation of pancreatic cancer when it is advanced carries poor prognosis. Most important risk factor associated with pancreatic cancer is smoking which contributes to 20 to 30% of cases. Other risk factors associated with pancreatic cancer are obesity, chronic pancreatitis and alcohol. Diabetes mellitus or glucose intolerance is present in 75% of patients with pancreatic cancer. There is bidirectional relationship between pancreatic cancer and diabetes. The studies showed increased risk of pancreatic cancer in patients with long standing diabetes mellitus and vice versa. Patients with diabetes mellitus had a 40% increased risk of pancreatic cancer. Patients with type 2 mellitus have insulin resistance and hence, hyperinsulinemia. Insulin is growth factor which leads to proliferation of cells and decreases apoptosis. Insulin also decreases insulin-like growth factor (IGF) binding protein production thereby increasing the amount of bioavailable IGF-1 . IGF-1 is a more potent mitogen than insulin and promotes pancreatic cancer cell proliferation and invasion. The diabetes mellitus which is induced by pancreatic cancer is thought to be due to release of products from tumor rather direct infiltration by tumor cells. Metformin is commonly used in the treatment of type 2 diabetes mellitus. Metformin also reduces the risk of pancreatic cancer. Metformin acts primarily through its effect on AMP activated protein kinase (AMPK). Metformin decreases ATP production by inhibiting complex I of electron transport chain. The decrease in ATP production leads to AMPK activation. AMPK activation leads to disruption of insulin/IGF-1 signaling through inhibition of mammalian target of rapamycin (mTOR). Inhibition of mTOR decreases protein synthesis and cell growth. Metformin in combination with inhibitors of mTOR can improve survival in pancreatic cancer. Researchers concluded that there is better need of understanding the anticancer mechanism of action of metformin, pharmokinetics and pharmodynamics of metformin, relationships between risk factors such as DM and development and progression of pancreatic cancer to identify further molecular targets and advance potential therapies.
© Springer Healthcare Ltd; 2014obile.
Type 2 diabetes patients on vegetarian diet have good glycaemic control
Cardiovasc Diagn Ther 2014;4(5):373-382
Diabetes is one of the leading causes of non-communicable diseases among adults. It is estimated to affect more than 439 million adults worldwide by year 2030. The morbidity and mortality associated with diabetes is major burden on healthcare. In order to reduce morbidity and mortality associated with diabetes the patient should have good glycemic control. One of the factors widely studied for the glycemic control is diet of diabetics. There are numerous studies which investigated the role of diet in control of diabetes. Recently a systematic review and meta-analysis of controlled clinical trials was conducted in which the association between vegetarian diet and glycemic control was studied in type 2 diabetes mellitus. In this study patient included were those more than 20 years of age, vegetarian diet used as an intervention, fasting blood sugar and glycosylated hemoglobin (HbA1c) was measured to look for outcome and the duration was more than four weeks. It was seen that patients on vegetarian diet had significant reduction in HbA1c but minimal or no effect on fasting blood sugar. There can be several mechanisms which can be associated with good glycaemic control on vegetarian diet. One of the mechanisms is decrease in energy which further leads to weight loss and hence, decreases insulin resistance. The accumulation of intramyocellular lipid is associated with insulin resistance. High fat content in the diet leads to increase in intramyocellular lipid. As the vegetarian diet contains less fat the concentration of intramyocellular lipid decreases and also the insulin resistance. Dietary fiber also helps in achieving good glycemic control. Fibers in intestine causes slow absorption of sugar which lowers the glycemic index of carbohydrates. Bacterial fermentation of fiber also causes increase in production of short chain fatty acids. Short chain fatty acids have beneficial effect on glucose and energy homeostasis. Hence, we can conclude that vegetarian diet can have good glycemic control.
© Springer Healthcare Ltd; 2014obile.
Non alcoholic fatty liver disease impairs hepatic glucose production but not peripheral glucose disposal
Clin Med. 2014 September; 3(3): 1050–1063
In obesity lipid is deposited in non adipose tissues like islets, skeletal muscle and liver. This fat is called as ectopic fat. In obesity this occurs because of insulin resistance. The deposition of fat leads to lipotoxicity in these tissues. The lipotoxicity in liver impairs hepatic glucose metabolism by reducing its suppression of hepatic glucose production (HGP). Non alcoholic fatty liver disease (NAFLD) impairs suppression of production of glucose which leads to hyperglycemia. NAFLD that is why associated with obesity and type 2 diabetes mellitus. Caloric restriction is one of the measures to improve insulin resistance and glucose metabolism. Recently a study was conducted in obese adults with increase in liver fat content who were put on caloric restriction to see its effect on hepatic glucose production, peripheral glucose disposal and hepatic triglyceride accumulation. There were eight participants in this study aged between 21-52 years, BMI more than 30 kg/m2, non diabetic and fat content more than 5.6%. These individuals were put on caloric restriction of less than 800 kcal/day which contained carbohydrate less than 10%. The researchers found “the visceral fat which decreased by 1/3 (p = 0.007). These changes were accompanied by a shortening of the waist line by 5 cm (p = 0.04). Due to these changes in body composition, the classification of the group as a whole improved from obesity to overweight based on the universal cutoff value of BMI at 30 kg/m2 (p = 0.0004). Plasma TG (p = 0.04) and FFA (p = 0.01) concentrations decreased significantly whereas HDL and LDL did not (p > 0.05). Fasting plasma glucose remained the same as before the treatment. The 2-hour plasma glucose decreased modestly without reaching statistical significance (p = 0.1). Fasting and 2-hour insulin concentrations were lowered by 20%”. Hence, we can conclude that caloric restriction can reduce fat content in liver which corrects hepatic glucose production.
© Springer Healthcare Ltd; 2014obile.
Diabetic Foot
