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Definition :

    • Diabetes mellitus is a syndrome of impaired metabolism of carbohydrates, fats and also proteins.

    • It is caused either by the lack of insulin secretion or decreased sensitivity of the tissues to insulin.

Types :

    • Type 1 :
        • It is also called Insulin Dependent diabetes Mellitus.

        • It is caused by lack of Insulin Secretion.

    • Type 2 :
        • It is also called Non – insulin dependent Diabetes Mellitus

        • Initially, it is caused due to decreased sensitivity of the target tissues to Insulin.

        • This reduced sensitivity of the tissues to Insulin is also called Insulin resistance.

Types and their Influence on Bodily mechanisms :

    • In both Type 1 and Type 2 diabetes Mellitus the metabolism of all the main foodstuffs get altered.

    • The basic and foremost effect of the Insulin deficiency or insulin resistance on the glucose metabolism is to prevent the efficient uptake of glucose by the body cells, except those of the brain cells.

    • As a result of this process, blood glucose concentration increases, and cell utilization of glucose decreases drastically.

    • Moreover the utilization of fats and proteins increases.

Type 1 Diabetes Mellitus :

    • Diseases that impair production of insulin or those injury to the beta cells of pancreas can lead to type 1 Diabetes Mellitus.

    • Causes :
        • Viral infections

        • Autoimmune disorder

        • Heredity determining the susceptibility of the beta cells to destruction by these insults.

    • Clinical features :

       

        • Usual onset of this type is about 14 years of age.

        • And hence this type is also called Juvenile type of Diabetes Mellitus.

        • However this type of Diabetes can occur at any age, including adulthood, following disorders that leads to destruction of pancreatic cells.

        • Type 1 diabetes mellitus can develop after the following sequelae :

           

            • Raising up of plasma glucose to 300 – 1200 mg/100mL;

            • Increased utilization of fats for energy and for formation of cholesterol by the liver;

            • Depletion of body’s proteins.

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Features :

    • Increased blood glucose level causes increased level of glucose in the urine.

    • High levels of glucose in the blood causes the glucose to filter into the renal tubes and the excess spills into the urine.

    • This spillage of glucose occurs when the blood glucose rises above 180mg/100mL.

    • This above level is called the blood threshold level of glucose.

    • When the blood glucose level rises to 300 – 500 mg/100 mL – occurs in people with untreated diabetes – 100 or more grams of glucose can be lost in urine everyday.

    • Increased blood glucose level also causes dehydration.

    • The very high levels of glucose in the blood can severe cell dehydration throughout the cells in the body.

    • In addition to direct cellular dehydrating effect of excessive glucose, the loss of glucose in the urine causes osmotic diuresis.

    • This is because the osmotic effect glucose in the renal tubules prevents the absorption fluids.

    • The overall effect is the massive loos of fluid in the urine, causing dehydration of extracellular fluid, which in turn causes compensatory dehydration of intracellular fluid.

    • Thus polyuria, increased dehydration – both intracellular and extracellular, are the classic symptoms of Diabetes.

    • Chronic increased levels of glucose causes tissue injury.

    • Poor blood glucose control for a longer period affects the blood vessels of different tissues throughout the body leading to structural changes and inadequate blood supply to the tissues.

    • This situation in turn leads to increased risk for heart attack, stroke, end-stage kidney disease, retinopathy and blindness and also ischemia and also gangrene of the limb.

Changes related with chronic rise in the blood glucose :

    • Chronic rise in the blood glucose can also lead to damage to many other tissues, and thereby causing peripheral neuropathy and autonomic nervous system dysfunction.

    • These abnormalities can result in impaired cardiovascular reflexes, impaired bladder control, decreased sensation in the extremities.

    • In addition, hypertension secondary to renal injury, and atherosclerosis, secondary to abnormal lipid metabolism, often develop in patients with diabetes.

    • And also the above things amplify the tissue damage caused by elevated blood glucose.

    • Diabetes mellitus causes increased utilization of fats and metabolic acidosis.

Features related with metabolism of Fats and Proteins :

    • The shift from carbohydrates to fat metabolism in diabetes increases the release of keto acids, such as acetoacetic acid and beta – hydroxybutyric acid, into plasma resulting in severe metabolic acidosis.

    • This scenario leads rapidly to diabetic coma and death unless the patient is treated with large amounts of insulin.

    • Excess fat utilization in the liver that occurs over a long time causes large amounts of cholesterol in the circulating blood and increase in deposition of cholesterol in the arterial walls.

    • This leads to severe arteriosclerosis and other vascular problems.

    • Diabetes also causes depletion of Body’s proteins.

    • Failure to utilize glucose for energy causes increase in depletion of proteins.

    • And therefore a person suffering from diabetes experiences a rapid weight loss and also asthenia despite eating large amounts of food.

    • Without treatment, these metabolic abnormalities can cause severe wasting of the body tissues and death within few weeks.

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Type 2 Diabetes Mellitus :

    • Type 2 diabetes mellitus occurs due to the resistance to insulin by the body tissues.

    • This type is far more common than type 1 .

    • The age of onset is usually above 30 years, often between the ages of 50 and 60.

    • Therefore this syndrome is often referred to Adult onset Diabetes.
 

Factors causing Type 2 diabetes mellitus :

    • Obesity, Insulin resistance, and Metabolic syndrome usually precede the Development of Type 2 diabetes mellitus.

    • In contrast to type 1 diabetes, in type 2 there is usually an increase in blood level of insulin concentration – Hyperinsulinemia.

    • Hyperinsulinemia occurs as a compensatory response by the pancreatic beta cells for insulin resistance, a diminished sensitivity of target tissues to insulin.

    • The development of insulin resistance and impaired glucose metabolism is usually a gradual process, beginning with excess weight gain and also obesity.

    • Insulin resistance is a part of cascade of disorders that is often called “Metabolic syndrome”.

    • Several of the metabolic abnormalities associated with the syndrome increase the risk of cardiovascular disease, and insulin resistance predisposes to the development of type 2 diabetes mellitus which is also a major of cardiovascular disease.

Other Factors that can cause Insulin Resistance and Type 2 Diabetes :

    • Although the patients with type 2 diabetes are overweight or accumulation of visceral fat, this condition can occur as a result of genetic conditions.

    • These genetic conditions that impair insulin signaling in the peripheral tissues.

    • With prolonged insulin resistance, even the increased level of insulin is not sufficient to maintain the normal glucose regulation.

Clinical characteristics :

Clinical features of diabetes mellitus

Physiology of diagnosis of diabetes mellitus :

Urinary Glucose :

    • A normal human being loses untraceable amounts of glucose in the urine.

    • Whereas a diabetic patient loses small to large amount of, in proportion to the severity of the disease and the intake of carbohydrates.

Fasting blood Glucose and Insulin Levels :

    • The fasting blood glucose level in the early morning is about 80 -90 mg/100mL , and 110mg/100mL is considered to be the upper limit of normal.

    • A fasting blood glucose level indicates the risk of Diabetes Mellitus or at least the marked insulin resistance.

    • In patients with type 1 diabetes mellitus, the insulin levels in the blood is untraceable or very low in fasting.

    • And even after the meals the insulin levels are very low.

    • But in patients with type 2 diabetes mellitus, the insulin levels are several fold higher than normal.

    • And also usually it increases to a greater extent after the ingestion of standard glucose load during a glucose tolerance test.

Glucose tolerance test :

    • When a normal fasting person ingests 1 g of glucose per kilogram of body weight, the blood glucose level rises from about 90mg/100mL to 120mg/100mL and falls back to below normal in about 2 hours.

    • In persons with diabetes, the fasting blood glucose level is always above 110mg/100mL and often above 140mg/100mL.

    • In addition, results of the glucose tolerance tests are almost always abnormal.

    • If patients with diabetes mellitus ingests glucose, these people exhibit a much greater than normal rise in the blood glucose level.

    • The glucose level falls back to normal only after 4 to 6 hours.

    • Further more it fails to falls below the control level.

    • The slow fall of this curve indicates either of the following two things :
        • The normal rise in insulin secretion after glucose ingestion does not occur

        • The person has decreased sensitivity to insulin

    • A diagnosis of diabetes mellitus can usually be established on the basis of this curve.

    • And the type 1 and 2 can be distinguished from each other by measuring the levels of plasma insulin using this curve.

Glucose tolerance test curve - Diabetes Mellitus

Why do wounds heal slowly in diabetes ?

    • It is well known that chronic hyperglycemia impairs some host defense mechanisms and is associated with increased mortality due to infection in diabetic patients.

    • Several studies have now confirmed that hyperglycemia per se or the metabolic abnormality of diabetes is sufficient to explain the impaired immune response in patients responding to infections.

    • There are multiple defects in the immune function in diabetes unlike people without diabetes.

    • Serum immunoglobulin levels have been reported to be reduced in diabetic patients compared to normal subjects.

    • Moreover, diabetics have reduced blood circulation to the extremities.

    • This impairs wound healing particularly in the lower extremities.

    • The antibiotics will be unable to reach the target tissues due to poor blood supply.

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Treatment of Diabetes :

Type 1 Diabetes Mellitus :

    • Effective treatment for type 1 is nothing but the administration of insulin so that the patient will have normal carbohydrate, fat and protein metabolism.

    • Insulin is available in longer acting and regular forms.

    • Regular insulin act for about 3 to 8 hour, whereas longer acting insulin lasts as long as 10 to 48 hours.

    • Each patient is provided with an individualized pattern of treatment with combination of longer and regular acting insulin.

    • In the past, the insulin used for treatment was derived from animal Pancreas.

    • However, human insulin has become more widely used because immunity and sensitization against animal insulin develops in some patients, thus limiting the effectiveness.

Type 2 Diabetes Mellitus :

    • In many instances, type 2 diabetes can be effectively treated in the early stages by exercise, weight reduction and also by caloric restriction.

    • And also no exogenous administration of insulin is required.

    • Drugs

       

        • that increase insulin sensitivity – Thiazolidinediones,

        • Drugs that suppress liver glucose production – Metformin,

        • Drugs that cause additional release of insulin by the pancreas – Sulfonylureas may also be used.

    • But however in the later stages, insulin administration is usually required to control the blood glucose levels.

    • Drugs that mimic the actions of incretin GLP – 1 have been developed for the treatment of type 2 Diabetes Mellitus.

    • These drugs enhance the secretion of insulin and are intended to be used in conjunction with other antidiabetic drugs.

    • Another therapeutic approach is to inhibit the enzyme dipeptidyl peptidase 4, which inactivates GLP – 1 and GIP.

    • By blocking the actions of DPP-4, the incretin effects of GLP-1 and GIP can be prolonged, leading to increased insulin secretion and improved control of blood glucose levels.

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