Diabetes Mellitus PDF

DIABETES MELLITUS Presented by Mathew Akanling  Definitions This is a set (group) of metabolic diseases characterized by elevated level of glucose in the blood (hyperglycemia) resulting from defects in insulin secretion, insulin action, or both. It can also be defined a...

DIABETES MELLITUS Presented by Mathew Akanling  Definitions This is a set (group) of metabolic diseases characterized by elevated level of glucose in the blood (hyperglycemia) resulting from defects in insulin secretion, insulin action, or both. It can also be defined as a chronic systemic disease characterized by either a deficiency of insulin or a decreased ability of the body to use insulin. It is sometimes referred to as “high sugars” by both clients and health care providers.  Incidence Statistics indicate that as of 1995, there were 135 million DM patients worldwide, 285 million in 2010, 366 million in 2011, and is expected to reach 552 million in 2030, with 80% of DM patients living in low and middle income countries. Prevalent in the elderly with up to 50% of patients older than 65 years. About 183 million (50%) patients living with diabetes are undiagnosed, with 4.6 million deaths occurring worldwide in 2011.  According to a WHO data published in April 2011, Diabetes Mellitus Deaths in Ghana reached 2,752 or 1.47% of total deaths. The rapid rise has been attributed to an increasing aging population, increasing unhealthy lifestyles, poor dieting and dropping levels of physical exercise.  Classification There are four major classifications; 1. Type 1 (Juvenile or Insulin Dependent Diabetes Mellitus): It affects 5% to 10% of people who have diabetes. It has juvenile onset, usually diagnosed before 30 years of age. It generally requires daily insulin treatment. Causes: genetic, immunologic and environmental. 2. Type 2 (Non-Insulin Dependent Diabetes Mellitus). Approximately 90% to 95% of people with diabetes have type 2 diabetes (CDC, Data Factsheet, 2002). It has an adult onset, usually after 40 years of age, and also common in certain ethnic and racial populations. It’s also known as stable diabetes. Causes: heredity, obesity, environmental factors. 3. Gestational Diabetes Mellitus (GDM) This develops in up to 14% of pregnant women and increases their risk for hypertensive disorders. This type usually occurs during the second half of pregnancy. Mothers are likely to have big babies. It’s common in women with a family history of diabetes. Obesity is also a risk factor. 4. Diabetes mellitus associated with other conditions: This type is associated with situations such as intake of certain drugs e.g. oral contraceptives and corticosteroids. Also with certain hormonal conditions such as Adrenal insufficiency – hypoglycaemia (low cortisol), Cushing’s syndrome – Hyperglycaemia (high cortisol). It accounts for 1 to 2% of all diagnosed cases of diabetes mellitus.  Pathophysiology In normal physiology, insulin is secreted by beta cells in the islets of Langerhans in the pancreas. After a meal, insulin secretion increases and moves glucose from the blood into muscle, liver and fat cells. In these cells, insulin:  Transports and metabolizes glucose for energy Stimulates storage of glucose in the liver and muscle in the form of glycogen Signals the liver to stop the release of glucose Enhances storage of dietary fat in adipose tissue Accelerates transport of amino acids (derived from dietary protein) into cells Insulin also inhibits the breakdown of stored glucose, protein and fat.  The periods between meals and overnight (fasting periods), the pancreas continues to release small amounts of insulin (basal insulin). Glucagon (another pancreatic hormone secreted by the alpha cells of the islets of Langerhans) is released when blood glucose levels decrease and stimulates the liver to release stored glucose. Together, insulin and glucagon maintain a constant level of glucose in the blood by stimulating the release of glucose from the liver (thru glycogenolysis and gluconeogenesis).  In type 1 DM, there is destruction of pancreatic beta cells leading to absolute insulin deficiency. This could be as a result of genetic, immunologic or environmental (eg viral) factors. It is believed that, genetic susceptibility is an underlying cause though the event leading to destruction is not well understood. The genetic tendency has been found in people with certain human leukocyte antigen (HLA) types.  There’s also evidence of autoimmune responses in which antibodies are directed against the normal body tissues, responding to these tissues as if they were foreign. Auto antibodies against islet cells and against endogenous (internal) insulin have been detected in people at the time of diagnoses and even several years before the development of clinical signs of type 1 diabetes.  Environmental factors such as viruses or toxins that may initiate the destruction of the beta cells are being investigated. Regardless of the specific cause, the destruction of the beta cells lead to decreased insulin production, unchecked glucose production by the liver and fasting hyperglycaemia. In addition, glucose derived from food cannot be stored in the liver but remains in the blood stream leading to post prandial (after meals) hyperglycaemia.  If the renal threshold (180-200mg/dl or 9.9 to 11.1mmol/L) is exceeded, the kidney may not reabsorb all the filtered glucose leading to glycosuria. The excess glucose excreted in the urine is accompanied by excessive loss of fluids and electrolyte (osmotic diuresis) resulting in polydipsia. In people with insulin deficiency, glycogenolysis and gluconeogenesis occur unrestrained and contribute to further hyperglycaemia. They are therefore prone to DKA (diabetic ketoacidosis).  In Type 2 DM, the problems are insulin resistance and impaired insulin secretion. Insulin resistance- there is a decrease in sensitivity to insulin. Insulin normally has receptors to which it binds to initiate its action of glucose metabolism. In type 2, these intracellular reactions are diminished making insulin less effective at stimulating glucose uptake by the tissues and at regular glucose release by the liver.  The exact mechanism that leads to insulin resistance and impaired insulin secretion in type 2 diabetes are unknown although genetic factors are thought to play a role. To overcome insulin resistance and prevent build up of glucose in the blood, increased amount of insulin must be secreted to maintain the glucose level at a normal or slightly elevated level. If the beta cells cannot keep up with the increased demand for insulin, glucose level rises in the blood and type 2 DM develops.  Despite the impaired insulin secretion in type 2 DM, there is still enough insulin to prevent breakdown of fat and the accompanying production of ketone bodies. Therefore DKA does not typically occur in type 2 diabetes. However, uncontrolled type 2 DM may lead to hyperglycemic hyperosmolar non-ketotic syndrome (HHNS). Because type 2 is associated with a slow progressive glucose intolerance, its onset may go undetected for many years.  Risk factors for developing type 2 DM Race/ethnicity ( eg African Americans, Hispanics, native Americans, Asians, native Hawaaians or other Pacific Islanders) Obesity (≥ 20% over desired body weight or BMI ≥ 27kg/m2 Age ≥45 years Previously identified impaired fasting glucose or impaired glucose tolerance Hypertension (≥ 140/90mmHg) HDL cholesterol levels ≤ 35 mg/dL, (0.90mmol/L) and/or triglyceride level ≥ 250mg/dL (2.8mmol/L) Family history of DM (parents or siblings with diabetes) History of gestational diabetes or delivery of babies over 9 lb  CLINICAL FEATURES Hyperglycemia (elevated blood glucose level leads to common clinical manifestations of DM). Polyuria (increased urination) Polydipsia (increased thirst) Polyphagia (increased appetite) Weight loss may occur as the body cannot get glucose and turns to other energy sources such as fats and proteins  Fatigue and weakness may be experienced as the body cells lack needed energy from glucose Glycosuria (occurs when Renal threshold of glucose is exceeded) Prone to bacterial and fungal infections e.g. candidiasis in women Visual disturbances/blurred vision (secondary to chronic exposure of ocular lens and retina to hyperosmolar fluids)  Paraesthesia in extremities (tingling or numbness of the hands in feet) Poor wound healing (due to impaired vascular activity) Sexual dysfunction (due to micro and macro vascular changes, blood vessels are sclerosed) There may be acetone breath (fruity, sweet odour) due to DKA Common manifestations of DM type 1  Diagnostic investigations Urine chemistry: elevated glucose and ketones. Blood chemistry – Fasting blood sugar ≥ 7.0mmol/L suggest DM. Random blood sugar: ≥11.1mmo/L Oral Glucose tolerance test (OGTT) ≥ 11.1mmol/L HbA1c (glycosylated haemoglobin) – this gives an average of blood glucose levels measured over the previous 3 months. Normal values : 4% - 8% BUE – annually Eye examination – annually  Criteria for the diagnosis of DM Symptoms of diabetes plus random plasma glucose concentration equal to or greater than 200 mg/dL (11.1 mmol/L). Random is defined as any time of day without regard to time since last meal. The classic symptoms of diabetes include polyuria, polydipsia, and unexplained weight loss. or Fasting plasma glucose greater than or equal to 126 mg/dL (7.0 mmol/L). Fasting is defined as no caloric intake for at least 8 hours.  or 2-hour postload glucose equal to or greater than 200 mg/dL (11.1 mmol/L) during an oral glucose tolerance test. The test should be performed as described by the World Health Organization, using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water. In the absence of unequivocal hyperglycemia with acute metabolic decompensation, these criteria should be confirmed by repeat testing on a different day. The third measure is not recommended for routine clinical use.  Management The therapeutic goal for diabetes management is to achieve normal blood glucose levels (euglycemia) without hypoglycemia and without seriously disrupting the patient’s usual lifestyle and activity. There are five components of diabetes management: Nutritional management Exercise Monitoring, that is self monitoring of blood glucose (SMBG) Pharmacologic therapy Education  The treatment varies because of changes in lifestyle, physical and emotional status as well as advances in treatment methods. Therefore, diabetes management involves constant assessment and modification of the treatment plan by health professionals and daily adjustments in therapy by the patient.  Medications Two or more types of drugs are used for best effect. Older patients may first be tried on diet. 1. Sulphonylureas– best taken with meals. Acts by stimulating the pancreas to secret insulin Therefore, a functioning pancreas is necessary for these agents to be effective, and they cannot be used in patients with type 1 diabetes. First-Generation Sulfonylureas acetohexamide (Dymelor) 250–1500mg in divided doses chlorpropamide (Diabinese) 100 – 500mg single dose tolazamide (Tolinase) 100 – 750mg divided doses tolbutamide (Orinase) 500 – 2000mg divided doses  Second-Generation Sulfonylureas glipizide (Glucatrol) 5–25mg (D) glipizide (Glucatrol XL) 5mg (S) glyburide (Micronase) 2.5 – 10mg (D) glimepiride (Amaryl) 1 – 2mg (S) Glibenclamide (glyburide) 5mg  ` 2. Biguanides – best taken with or just after meals. produces its antidiabetic effects by facilitating insulin’s action on peripheral receptor sites. Therefore, it can be used only in the presence of insulin. Biguanides have no effect on pancreatic beta cells. Biguanides used with a sulfonylurea may enhance the glucose- lowering effect more than either medication used alone. Metformin (Glucophage + Glucophage XL): 500mg – 1g 12 hourly 3. Alpha Glucosidase Inhibitors acarbose (Precose) 1,500mg (D) miglitol (Glyset) They work by slowing down the absorption of glucose in the intestinal system resulting in a lower post prandial blood glucose level. 4. Thiazolidinediones (TZDs) – These enhance insulin action at the receptor sites. pioglitazone (Actos) 15–30mg (S) rosiglitazone (Avandia) 4mg (S or D) (may be used alone or in combination with sulfonylurea 5. Non-sulfonylurea insulin secretagogues Repaglinide (Prandin) 0.5–4 mg (D) categorized as Meglitinides Nateglinide (Starlix) 180 – 360mg (D) categorized as a D-phenylalanine derivative These lower glucose level by stimulating the release of insulin from the beta cells. 6. Dipeptidyl Peptidase -4 (DPP-4) inhibitor Sitaglipton (Januvia) Vildaglipton (Galvus) They increase and prolong the action of incretin, a hormone that increases insulin release and decreases glucagon levels with the result of improved glucose control.  Insulin This is used by all patients with type 1DM. It is to replace what the body cannot produce on its own. It can also be used temporarily in the following conditions; Type 2 diabetes during the period of stress example surgery or infection. During pregnancy May be necessary on long term basis for patients whose plasma glucose cannot be controlled at acceptable level despite weight control and adherence to dietary regulations and oral antidiabetic agents  Types of insulin The type of insulin is based on how fast it works and how long it lasts. 1. Rapid-acting insulin: clear lispro (Humalog) aspart (Novolog) glulisine (Apidra) 2. Short acting insulin: clear regular (Humulin R) Novolin R ReliOn R 3. Intermediate-acting insulin: cloudy NPH (Neutral Protamine Hagedorn) –Humulin N Novolin N ReliOn N 4. Long Acting insulin: clear Glargine (Lantus) Detemir (Levemir) 5. Combination therapy (premixed): cloudy NPH/regular 70/30 (Humulin 70/30, Novolin 70/30, ReliOn 70/30) NPH/regular 50/50 (Humulin 50/50) Lispro protamine/ lispro 75/25 (Humalog mix 75/25) Lispro protamine/ lispro 50/50 (Humalog mix 50/50) Aspart protamine/aspart 70/30 (Novolog Mix 70/30)  Insulin (Brand) Onset Peak Effective Duration 1. Rapid-Acting Aspart (NovoLog) 5-15 min 30-90 min