Obesity: Cause, Consequences and Implications

There are many causes and health implications of obesity. Many people are in illusion about the quantitative parameters of obesity. The obesity can be defined in terms of Weight/Height (^W/_H) ratio or index: where weight is in kilograms (kg) and height is in meters (m). This index should be 25 to 30 normally. If your weight is 47 kg and your height is 1.60 m (160 cm); your ^W/_H index will be 29.375. An ideal weight of an individual with reference to sex, age, height and body build has already been documented somewhere else. The cause of obesity may be genetic, metabolic, physiological, lifestyle or pathological (as in cases of hypothyroidism). Take your weight on the same scale daily for a week. If you are overweight or your ^W/_H index is considerably more than 30, then plan to loose your weight through dieting and exercise. Never starve yourself. You can eat as desired from the unrestricted food items' list but remain within limits on restricted food items' list and keep away from prohibited food items' list:

Unrestricted Food Items' List
Unrestricted food items for the obese are fresh fruits, fresh vegetables, chicken, fish, poached eggs, boiled eggs (do not eat yellows), tea, coffee, skimmed milk and products made from skimmed milk.

Restricted Food Items' List
Restricted food items for the obese are all cereals and products made from cereals. Obese person should avoid eating more than 100 gm cereal products in a day. Fat consumption should not be more than 15 gm in 24 hours.

Prohibited Food Items' List
Prohibited food items for the obese are jams, honey, ice cream, dry fruits, nuts, cold drinks, alcohol, sugar and products containing sugar.


Obesity is associated with hyperlipidemia (elevated level of cholesterol and triglyrerides in blood), hypertension (high blood pressure), non-insulin dependent diabetes mellitus (NIDDM) and high prevalence of some cancers. Other serious implications of obesity are coronary heart disease and renal disease. Abdominal fat has been documented as major risk factor for coronary heart disease. The risk of NIDDM is more in overweight men aged between 25-50 years of age. The patient is said to have severe obesity if his ^W/_H index is more than 40. Natural history and consequences of obesity in children are not well understood till date. Strict dietary control and weight reduction would definitely help patients with severe obesity to overcome its serious implications like - NIDDM, hyperlipidemia, hypertension and coronary heart disease.

Type-2 Diabetes and the role of incretins

The incretins are the hormones, which are released into the blood circulation in response to nutrients we eat. These peptide hormones are generally released within minutes of eating or enteral nutrition. In humans, the major incretins are: (i) Glucagon like peptide-1 (GLP-1) and (ii) Glucose-dependent insulinotropic polypeptide (GIP). GLP-1 is secreted by L-cells in the ileum and colon, while GIP is secreted by K-cells in the duodenum of our alimentary canal. GLP-1 and GIP stimulate insulin secretion by the pancreas and also affect the gut and the brain. Their combine effect make significant contribution in glucose homoeostasis, particularly in scaling down the peak of postprandial glucose level. It has been proved through experimental studies that the GLP-1 has the major incretin effect; that is around 80% of the combine effect of GLP-1 and GIP. These incretins probably act via glycoprotein-coupled receptors.

Non-insulin dependent diabetes mellitus (NIDDM) or type-2 diabetes mellitus (Type-2 DM) is characterized by pancreatic beta-cell dysfunction and variable degree of insulin response. Complex interaction of genetics and environmental factors are responsible for metabolic disorders leading to diabetes. Taming of hyperglycemia through medicines, dietary control and regular exercise is possible. Increasing prevalence of obesity and reduced physical activity is directly related to the increasing prevalence of type-2 DM, worldwide. Oral antidiabetic agents, diet and or exercise and insulin are currently used for the treatment of patients with diabetes. Existing antihyperglycemic agents are often associated with an increased risk of adverse effects (such as weight gain and hypoglycemia) and most often become less effective due to histological/cellular variations (progressive beta cell failure) in the pancreas of the patient.

Incretins provide insulinotropic stimulus and thus lower the blood glucose level by increasing insulin secretion. However, the incretin response to a meal lasts approximately around 3 hours as the incretin molecules have very short half-life (<5 minutes) and are metabolized quickly. An enzyme known as dipeptidyl peptidase-4 (DPP4), produced by endothelial cells, disintegrate the incretin molecules within 2-3 minutes of their secretion. Poor incretin response has been observed in patients with type-2 diabetes during the glucose tolerance test as indicated by reduced level of GLP-1 as compared to normal individuals. The functional response (insulinotropic response) of GLP-1 was found to be intact in patients with type-2 diabetes and that gave new direction to the treatment regimen of diabetes. At present the incretin system has been under active study to find out the effective compounds for the treatment of type-2 diabetes. Pharmaceutical compounds like: (1) GLP-1 'analogues' or GLP-1 receptor agonists which are resistant to breakdown by DPP4 and (2) Incretin enhancers which inhibit the action of DPP4 on GLP-1 molecules, have been under active study for use in new formulations.

Exenatide is already in clinical use after its approval by US-FDA. Exenatide is a biosynthetic form of GLP-1 analogue-exendin-4. Exendin-4 is a naturally occurring GLP-1 found in the saliva of a lizard known as Gila monster. It was approved by US-FDA in 2005 for use in combination with metformin or sulfonylureas or both together. Exenatide is administered twice daily before meals by subcutaneous injections from a pre-filled pen. Incretin enhancers improve the control of glucose level in blood by inhibiting DPP4 action on incretin hormones especially GLP-1 molecules. Incretin enhancer Sitagliptin was approved by US-FDA in 2006 and Vildagliptin was approved by US-FDA in 2007, and both have been used as monotherapy or in combination with antidiabetic drugs like metformin or thiazolidinedione for glycemic control in patients affected by type-2 diabetes.

Important Note: Antihyperglycemic treatment should always be taken in consultation with a physician or specialized diabetologist.