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DIABETES MELLITUS- TYPE II

Anjaly Menon 11408028 Genetic Engineering dept.

INTRODUCTION
Diabetes mellitus (DM) is a set of related diseases in which the body cannot regulate the amount of sugar (specifically, glucose) in the blood. glucose in the blood is produced by the liver. In a healthy person, the blood glucose level is regulated by several hormones, including insulin. Insulin is produced by the pancreas.

Insulin allows glucose to move from the blood into liver, muscle, and fat cells People with diabetes either do not produce enough insulin (type 1 diabetes) or cannot use insulin properly (type 2 diabetes), or both (which occurs with several forms of diabetes).
glucose in the blood cannot move into cells, so it stays in the blood. This not only harms the cells that need the glucose for fuel, but also harms certain organs and tissues exposed to the high glucose levels.

TYPES OF DIABETES MELLITUS:


Type 1 diabetes: The body stops producing insulin or produces too little insulin. Its recognized in childhood or adolescence. Also known as juvenile diabetes or insulin-dependent diabetes mellitus(IDDM). Due to progressive failure of the pancreatic beta cells produce insulin. People require daily insulin treatment to sustain life. Type 2 diabetes: In this type,the pancreas secretes insulin, but the body is partially or completely unable to use the insulin; referred to as insulin resistance diabetes. Gestational diabetes It occurs in about 2%5% of all pregnancies and may improve or disappear after delivery. Gestational diabetes is fully treatable but requires careful medical supervision throughout. About 20%50% of affected women develop type 2 diabetes later in life.

Type II Diabetes mellitus(T2DM)


Type 2 diabetes: is a metabolic disorder that is characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency
Also known as Non Insulin Dependent Diabetes Mellitus (NIDDM). The body tries to overcome insulin resistance by secreting more and more insulin. People with insulin resistance develop it when they do not continue to secrete enough insulin to cope with the higher demands.

Type II Diabetes mellitus(T2DM)


At least 90% of patients with diabetes have type 2 diabetes. Type 2 diabetes is typically recognized in adulthood, usually after age 45 years. It used to be called adult-onset diabetes mellitus or NIDDM. These names are no longer used because it also does occur in younger people, and some people with type 2 diabetes need to use insulin. It is usually controlled with diet, weight loss, excercise, and oral medications. More than half of all people with type 2 diabetes require insulin to control their blood sugar levels at some point in the course of their illness.

SYMPTOMS
Some people don't have symptoms, especially when diabetes is diagnosed early.People may have symptoms, such as: polyuria(frequent urination), polydipsia(increased thirst), polyphagia(increased hunger), Having blurry vision. fatigue and weight loass. increased risk of cognitive dysfunction and dementia also.

CAUSES
Combination of lifestyle and genetic factors Environmental toxins Obesity Hypertension Elevated cholesterol amounts.

PREVALENCE Epidemiological studies among migrant Asian Indians in many countries showed higher prevalence of type 2 diabetes compared with the host populations and other migrant ethnic groups. Studies conducted in India in the last decade have highlighted that not only is the prevalence of type 2 diabetes high, but also that it is increasing rapidly in the urban population. Predicted that by the end of 2030 the number of diabetic patients will rise upto 80 million.

Celebrities and personalities affected by diabetes:

1.George Lucas- American film prodcer, (mild type 2) 2.Halle berry, hollywood actress.(type 1 to type 2) 3.Kamal Hassan , actor 4.Sudha chandran , classical dancer.

GENETIC BASIS
There is a stronger inheritance pattern for type 2 diabetes. Those with first-degree relatives with type 2 diabetes have a much higher risk of developing type 2 diabetes. Concordance among monozygotic twins is close to 100%, about 25% of those with the disease have a family history of diabetes. Genes significantly associated with developing type 2 diabetes, were located on various chromosomes(2q,18p,3q,11q etc) obesity (which is an independent risk factor for type 2 diabetes) is strongly inherited. The first locus for T2DM was mapped by Hanis et. al. in 1996- telomeric region of chromosome 2q (2q33q37) endoplasmic reticulum stress pathway is active in adipose tissue and in the liver. Increased activation of c-jun N terminal kinase (JNK), which phosphorylates IRS-1 on serine residues, suppresses insulin action and downstream signaling pathways.

Continued
Insulin secretion by the pancreatic -cell is modulated by multiple stimuli. Oxidative mitochondrial metabolism and adenosine triphosphate (ATP) generation is essential for glucose stimulated insulin secretion. increased ratio of ATP to adenosine diphosphate (ADP) in the -cell triggers a series of events. Over-expression of UCP2 in -cells decreases glucose-stimulated insulin secretion whereas targeted inactivation of the UCP2 gene has the opposite effect. Many mechanisms contributing to T2DM may trigger -cell apoptosis and reduced -cell mass or ability to compensate for insulin resistance.

Decreased IRS-2(insulin receptor substrate) expression, an essential -cell growth factor, may lead to spontaneous -cell apoptosis. (The product of this gene is phosphorylated by the insulin receptor tyrosine kinaseupon receptor stimulation) Multiple pathways may lead to the T2DM phenotype.

PATHOPHYSIOLOGY
For type 2 diabetes mellitus to occur, both defects must exist. For example, all overweight individuals have insulin resistance, but diabetes develops only in those who cannot increase insulin secretion sufficiently to compensate for their insulin resistance. Their insulin concentrations may be high, yet inappropriately low for the level of glycemia.

Impaired glucose tolerance (IGT) is a pre-diabetic state of dysglycemia that is associated with insulin resistance and increased risk of cardiovascular pathology. IGT precede type 2 diabetes mellitus. Beta cell dysfunction is also a major factor.

DIAGNOSIS
Finger stick blood glucose: not as accurate but is easy to perform. Result is available right away. Only accurate to within about 10% of true actual laboratory values. Fasting plasma glucose: The patient will be asked to eat or drink nothing for 8 hours before having blood drawn (usually first thing in the morning). Fasting plasma glucose level 7.0 mmol/L (126 mg/dL). may undergo an oral glucose tolerance test or a glycosylated hemoglobin test ( "hemoglobin A1c") as a confirmatory test. Fasting plasma glucose level 100 but less than 126 mg/dL, then impaired fasting glucose (IFG.) -pre-diabetes.

TREATMENT
Depending on how elevated the patient's blood sugar and glycosylated hemoglobin (HbA1c) are at the time of diagnosis, they may be given a chance to lower blood sugar level without medication. The best way to do this is to lose weight if obese and begin an exercise program. If the amount remain high, the patient will be started on an oral medication, usually a sulfonylurea or biguanide [metformin Glucophage], to help control blood sugar level. A healthy diet, engage in moderate physical activity as often as possible. Right dose of the right medication. May require insulin injections to control their blood sugar levels.

Very overweight patients may consider bariatric (weight loss) surgery. Gastric bypass surgery Laparoscopic gastric banding

MEDICATIONS Many different types of medications are available . Sulfonylureas: stimulate the pancreas to make more insulin. Biguanides: These agents decrease the amount of glucose produced by the liver Alpha-glucosidase inhibitors: These agents slow glucose production by a absorption of the starches Thiazolidinediones: increase sensitivity to insulin. Meglitinides: These agents stimulate the pancreas to make more insulin. Insulins: Human insulin is less likely to cause allergic reactions than animal-derived varieties of insulin provide optimal blood sugar Rapid-acting insulins Humulin R,Humalog,Novolog etc Intermediate-acting insulins Isophane , neutral protamine Hagedorn (NPH) Long-acting insulins Ultralente

Possible Complications
Eye problems. Feet and skin can develop sores and infections, can also cause pain and itching in other parts of the body. Can lead to a heart attack, storke, and other problems Nerves in your body can get damaged, could have problems digesting the food you eat. Can lead to kidney damage Infections of the skin, female genital tract, and urinary tract are also more common.

PREVENTION
You can help prevent type 2 diabetes by keeping a healthy body weight and an active lifestyle. Stay up-to-date with all your vaccinations and get a flu shot every year.

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