Team:BGU Israel/Project/Metabolic Syndrome

From 2014.igem.org

Background


A cluster of cardiometabolic risk factors, including central obesity and insulin resistance, which is diagnosed in quarter of the world adult population.

Current Treatment


There are a lot of medications for the many symptoms of the syndrome, most of them are associated with a lot of side effects, especially in combination of different of drugs.

Background

The metabolic syndrome (MetS) is a cluster of cardiometabolic risk factors including central obesity, insulin resistance, glucose intolerance, dyslipidaemia and raised blood pressure [1]. The international Diabetes Federation (IDF) declared the syndrome ass a combination of the most dangerous risk factors for heart attack [2], which is the leading cause of death in high- or middle-income countries. The prevalence of MetS is increasing worldwide due to the epidemic of overweight and obesity. Today, it is estimated that 20-25% of the world's adult population suffers from MetS.

People with MetS have fivefold greater risk of developing type 2 diabetes (T2D) [3], the most common chronic diseases worldwide and the fourth or fifth leading cause of death in the developed world. Many factors can lead to development of MeS, Genetics, physical inactivity, ageing, a proinflammatory state and hormonal changes, all can have a casual effect depending on ethnic group [4]. However the insulin resistance and central obesity considered the most significant factors.

Insulin Resistance

Insulin resistance occurs when many cells in specific tissues (liver, skeletal muscle and adipose) become less sensitive to insulin and eventually become resistance to it. The absorption of glucose declines and its level in the blood is rising. This triggers the pancreas to produce more insulin in attempt to process the glucose. Once the pancreas is no longer able to produce enough insulin, the person become hyperglycemic and will be diagnosed with type 2 diabetes.

Central Obesity

Obesity strongly contributes to hypertension, high serum cholesterol, low HDL and hyperglycemia. An increment in body mass index (BMI) and especially excess of body fat in the abdomen, raise the risk for serious health consequences in the form of type 2 diabetes, coronary heart disease, cardiovascular disease (CVD) and even cancer [5].

Current Treatment and Side Effects

Because MetS is a cluster of many disorders, there many kinds of medication for each of the symptoms. Statins for example are a group of chemicals which inhibits the synthesis of cholesterol in the liver. Although intensive-dose statin therapy was associated with a reduced risk for CVD, it was also associated with an increased risk for statin-induced adverse events [6]. There are many kinds of insulin sensitizers, the most prominent are Metformin has showed to be delaying in devepment of T2D by the Diabetes Prevention Program (DPP). However like many other sensitizers it influences the whole body. The fact that only specific tissues in the body resistance to insulin (which is also a strong growth factor), makes a high dose treatment very risky. Other drugs like fibrates, Angiotensin inhibitor and Thiazolidinedione, all treat a specific symptom but not the cause of the Disease, and the biggest problem is that combination of them many times can lead to serious side effects.

Therapeutic Lifestyle Changes (TLC) is considered the most beneficial way to prevent or at least delay T2D and CVD. TLC also showed better results in the DPP that drugs therapy [7]. On the other hand, a proper diet and permanent exercise program demand knowledge and ambition, which not always accessible to unhealthy people.

We see the MeS as a growing Epidemic which is crossing countries and ethnics groups. A disease in this scale is worth a better treatment, one without dangerous side effects, which will treat the factors that cause the disorders and not just improve a specific symptom.

References

  1. Kassi E, Pervanidou P, Kaltsas G, Chrousos G (2011) Metabolic syndrome: definitions and controversies. BMC Med 9:48
  2. http://www.idf.org
  3. Stern M, Williams K, Gonzalez-Villalpando C et al. Does the metabolic syndrome improve identifi cation of individuals at risk of type 2 diabetes and/or cardiovascular disease? Diabetes Care 2004 ;27(11):2676-81
  4. Anderson PJ, Critchley JAJH, Chan JCN et al. Factor analysis of the metabolic syndrome: obesity vs insulin resistance as the central abnormality. International Journal of Obesity 2001 ;25:1782
  5. Lee IM, Manson JE, Hennekens CH et al. Body weight and mortality. A 27-year follow up of middle-aged men. JAMA 1993;270:2823-8
  6. Meta-analysis of drug-induced adverse events associated with intensive-dose statin therapy.
  7. Long-Term Safety, Tolerability, and Weight Loss Associated With Metformin in the Diabetes Prevention Program Outcomes Study