Diabetes Mellitus: Pathophysiology, Pharmacology, and Management

Diabetes Mellitus A group of metabolic diseases involving hyperglycemia due to impaired insulin secretion, action, or both Insulin affects the use of glucose, and the metabolism of proteins and fats Carbohydrates, proteins, and fats are digested in the intestine, where they are broken down into their basic units:  Carbohydrates into sugars.  Proteins into amino acids.  Fats into fatty acids and glycerol. Types    of diabetes: Type 1 diabetes Type 2 diabetes Gestational diabetes Disease manifestations:  Polydipsia (excessive thirst)  Polyuria (excessive urine output  Polyphagia (excessive hunger) – not always seen  Unexpected weight loss  Casual (random) plasma glucose of 200 mg/dL or higher  Oral glucose tolerance test >200mg/dL Risk Factors:  Family hx of diabetes  Obesity  Race/ethnicity (African American, Hispanic American, native America, Asian American, and pacific islander)  >45 yrs  Hx of impaired fasting glucose or impaired glucose tolerance  Hypertension  HDL levels <35mg/dL  Triglyceride levels >250mg/dL  Hx of gestational diabetes  Delivery of infants over 9lbs Type 1 Diabetes Mellitus Pathophysiology  Complete autoimmune (self) destruction of the beta cells of the pancreas located in the islets of Langerhans  Beta cells produce insulin, once destroyed the body can no longer produce insulin to meet ongoing physiologic needs  Common in children Risk Factors  Genetic predisposition o Markers often found in most type I patient  Environmental factors: trigger an abnormal autoimmune response that cause antibodies to respond by destroying beta cells o Viral: Mumps rubella o Chemical: Smoke and cured meat Symptoms  Polydipsia o Excessive thirst because they are losing all of their fluid through polyuria o Dry mouth  Polyphagia o Energy production decreases and person feels constant hunger to due cell starvation. Glucose cannot get into the starving cells because of lack of insulin.  Malaise, fatigue due to cell starvation  Polyuria o Caused by osmotic diuresis, when glucose levels are so high that glucose is excreted in the urine. Water follows the glucose concentration passively, leading to abnormally high urine output.  Weight loss  Malaise  Fatigue  Bed wetting Treatment:  Required lifelong daily insulin replacement therapy (subcut or IV pump) Type 2 Diabetes Mellitus Pathophysiology  Cellular insulin resistance and impaired insulin secretion Risk Factors  Family history o 2-4x more likely  Obesity  Physical inactivity  Race  HTN, high cholesterol, and high triglycerides o HTN and diabetes go hand in hand o Glucose starts coating the veins and arteries which leads to atherosclerosis Symptoms  Polyuria  Polydipsia o Dry mouth  Fatigue  Malaise  Fruity breath  Slow onset disease o Blurred vision o Fatigue o Paresthesia o Skin infections  Don’t heal as well  Sugar that builds up and blocks circulation  When blood sugar is elevated wound healing is slow Treatment  Exercise & Diet  Oral and injectable medications  Insulin  Treatment of type 2 is a 5-step process involving escalations of treatment as the severity of insulin resistance increases o Step 1: Implement diet and exercise therapy o Step 2: Initiate therapy with 1 oral hypoglycemic. Medication choice is dependent on body composition and severity of hyperglycemia o Step 3: Treat with 2 oral hypoglycemics (preferably from different classes to maximize benefits) o Step 4: Treat with 3 oral hypoglycemics or with one oral hypoglycemic plus insulin o Step 5: Treat with insulin alone Gestational Diabetes Pathophysiology  Glucose intolerance with its onset during pregnancy usually around the 24th week or first detected in pregnancy.  Insulin does not cross over the placenta  Usually there is an existence of pancreatic beta-cell dysfunction prior to pregnancy and the development of insulin resistance during pregnancy (increasing peripheral insulin resistance is a normal pregnancy finding) with no compensatory increase in insulin secretion  Usually resolves after delivery and with weight loss Risks  Associated with either neonatal complications such as macrosomia, hypoglycemia, and birth trauma or maternal complications such as preeclampsia and cesarean birth.  Higher risk of developing type 2 diabetes later in life if insulin is needed during pregnancy Treatment  Diet & exercise  Subcut insulin  Metformin and glyburide (only oral antidiabetic medication prescribed during pregnancy) Acute Complications Hyperglycemia  Elevated blood glucose levels o Fruity breath o Polyuria o Polydipsia o Dry mouth o Nausea o Fatigue o Blurred vision o Headache o Flushed dry skin o Abdominal cramping, NVD  Can result from: o Unmanaged diabetes in beginning stages o Medication undertreatment o Medication noncompliance o Excessive carb intake  Management: o Fast acting insulin  Aspart; Novolog  Lispro; Humalog  Glulisine; Apidra o Dosage calculated by BGL o Recheck Q15mins o Monitor LOC (mental state & responsiveness to therapy) o Monitor electrolytes & pH levels (dehydration; sodium & potassium levels) Hypoglycemia  Blood sugar <70 mg/dL o Pallor o Tremors o Diaphoresis (sweating) o Palpations, tachycardia o Tremors o Polyphagia o Visual disturbances o Weakness o Lack of coordination o Paresthesia o Behavioral changes: Confusion/Agitation/Irritability o Tiredness o Coma o Death  Can result from: o Medication overtreatment o Unplanned physical activity o Nutritional changes  Management: o 15-20g rapid-acting, concentrated carbohydrate without proteins or fats  4oz regular soda  4-6oz fruit juice  8oz skim milk  1 tbsp honey  Commercially prepared glucose tablets  Glucagon 1mg IM (if NPO; no IV)  ½ amp (25mL) D50W IV push (if NPO w/ IV) o Re-test in 15mins  If BGL <70-75 mg/dL, re-treat & re-check in 15mins o Once BGL stabilize provide snack containing protein and carbohydrate if clients next meal is longer than 1hr away  Milk or cheese with crackers o Monitor LOC (mental state & responsiveness to therapy) o Monitor electrolytes & pH levels (fluid overload syndrome; hypokalemia) Diabetic ketoacidosis (DKA) *Medical emergency* Ketones are produced from the breakdown of fats. Their accumulation in the blood is toxic for the body. This situation arises when the body lacks insulin and must use its fat reserves for the energy it normally gets from glucose.  Most common with type 1 diabetics  Hyperglycemia - usually a blood glucose >300 mg/dL  Ketones in the urine  Increased RR  Fruity breath odor (acetone odor)  NVD   Abdominal pain Decreased LOC, confusion, agitation Hyperglycemic-hyperosmolar state (HHS) *Medical Emergency* During a hyperglycemic episode, the accumulation of glucose in the blood increases the frequency and volume of urination. This can cause excessive water loss and significant dehydration. This can be followed by a drop in blood pressure leading to decreased consciousness and eventually to coma if the HHS is left untreated.  Most common with type 2 diabetes  Severe hyperglycemia – typically >600 mg/dL  Slight or no ketosis  Profound dehydration (dry mouth, sunken eyes, dry skin) Chronic Complications Macrovascular complications (Increase the risk of early death)  Coronary artery disease  Cerebrovascular accident (CVA)  Peripheral vascular disease Microvascular complications (due to hyperglycemia-induced thickening of retinal and glomerular basement membranes; results from alterations in small blood vessels that supply tissues and organs)  Retinopathy o Affects vision over time o Can lead to complete or partial vision loss  Neuropathy o Affects the function of the kidneys over time o Can lead to renal failure  Nephropathy o Autonomic neuropathic changes  GI disturbances  Bladder dysfunction  Postural hypotension  Sexual dysfunction o Sensory neuropathic changes  Carpal tunnel syndrome in hands  Paresthesia or lack of sensation in the feet Infections (Slow to heal)  Skin  Urinary tract  Vagina  Ulcers of the extremities Pregnancy complications  Higher risk for perinatal infant mortality & congenital anomalies  Large birth weight baby  Perinatal hypoglycemia o Hyperglycemic in womb and quickly become hypoglycemic once delivered  Hypertensive disorders  Untreated maternal hyperglycemia: o Spontaneous abortion o Increased neonatal mortality Foot infections    High glucose damages the capillaries causing reduced blood flow peripherally Foot problems most often happen when there is nerve damage, also called neuropathy. This can cause tingling, pain (burning or stinging), or weakness in the foot. It can also cause loss of feeling in the foot, so you can injure it and not know it. Poor blood flow or changes in the shape of your feet or toes may also cause problems. Factors that affect foot complications: o o Neuropathy  Although it can hurt, diabetic nerve damage can also lessen your ability to feel pain, heat, and cold. Loss of feeling often means you may not feel a foot injury. Skin changes Diabetes can cause changes in the skin of your foot. At times your foot may become very dry. The skin may peel and crack. This problem is caused by nerve damage that affects your body’s ability to control the oil and moisture in your foot. Calluses  Calluses, if not trimmed, get very thick, break down, and turn into ulcers (open sores). Poor circulation  Poor circulation (blood flow) can make your foot less able to fight infection and to heal. Diabetes causes blood vessels of the foot and leg to narrow and harden. Foot ulcers  Keeping off your feet is very important. Walking on an ulcer can make it get larger and force the infection deeper into your foot. Amputation  People with diabetes are far more likely to have a foot or leg amputated than other people. The problem? Many people with diabetes have peripheral artery disease (PAD), which reduces blood flow to the feet.  o o o o Exercise and Activity Exercise is a key treatment component for diabetes Exercise reduces blood glucose levels by promoting the uptake of glucose by activated muscle cells Monitor blood glucose levels safely Precautions:  Do not exercise with BGL (blood glucose levels) >250 mg/dL o Release of glucagon, growth hormone, and catecholamines prompt the liver to release more glucose which will further increase BGL o Refrain until BGL is near expected reference range  Clients who take insulin are more likely to experience hypoglycemia with activity  Monitor BGL prior to, during, and after exercise  Proper footwear o Inspect feet after exercising  Avoid exercise in extreme heat or cold  Avoid activity during periods of poor metabolic control  Snacks and glucose replacement prior to and during exercise  Those with cardiovascular risks need medical clearance DIET AND EXERCISE FOR CHILDREN WITH DIABETES MELLITUS (Ricci textbook) Provide sufÏcient calories and good nutrition for normal growth and development. The diet should be low in saturated fats and concentrated carbohydrates. Learn to identify carbohydrate, protein, and fat foods.  Make adjustments during periods of rapid growth and for issues such as travel, school parties, and holidays. Consult a dietitian with expertise in diabetes education as needed.  Provide three meals per day and midafternoon and bedtime snacks. Consistency of intake can help prevent complications and maintain near-normal blood glucose levels. Encourage the child to exercise routinely to help the body use insulin efÏciently, thus reducing the insulin requirement. Encourage the child to participate in age-appropriate sports.  When exercising, monitor insulin dose and nutritional and fluid intake, and observe for hypoglycemic reactions. Add an extra snack containing 15 to 30 g carbohydrate for each 45 to 60 minutes of exercise. Avoid exercising excessively when insulin is peaking. Illness & Infection Commonly causes increases in BGL Hospitalized clients prescribed special diets may be at higher risk for hypoglycemia (NPO status) Stress Has been shown to increase BGL due to hormonal release in addition to daily routine changes Monitor BGL frequently when undergoing stress Nutrition Goals:  Achieving metabolic control  Optimal blood lipid levels (blood pressure)  Maintaining acceptable body weight Registered Dietitians  Particularly in early stages of diagnosis Medical Nutritional Therapy (MNT)  Nutritional plan geared toward prevention and management of diabetes and overall healthy lifestyles  Helps incorporate good dietary choices  Lifelong therapy for diabetics    Provider determines calorie levels based on: o Client’s health o Energy needs o Activity o Health status o Child, pregnant, older client adjustments are made Medication is not a substitute for MNT; they work hand in hand Can be helpful in preventing type 2 diabetes Medication Treatment & Management Oral medications (hypoglycemics) Generally prescribed for type 2 diabetics who cannot achieve glycemic control with diet & exercise alone Should not be prescribed unless a client has diet & exercise planning in place Combination approach may help better manage blood glucose of some clients Six types of Oral Hypoglycemics Sulfonylureas Stimulates release of insulin from islet cells of pancreas Patient must have a functioning pancreas for this drug to work (NOT USED IN TYPE 1 DM) Drug will lower blood glucose regardless of whether BG is high or low Work by increasing insulin secretion by the beta cells of the pancreas  Drugs include:  glyburide  glipizide (prototype)  glimepiride  Side effects: o Weight gain & hypoglycemia o Nausea and diarrhea  Interactions: o Alcohol use may cause Antabuse-like reaction including N/V, palpations, and flushing and hypoglycemia o NSAIDs, oral anticoagulants, salicylates, MAOIs  Can be used as monotherapy or in combination with: o Insulin o Metformin o thiazolidinediones (class of antihyperglycemic agents that reduce insulin resistance) o Alpha-glucosidase inhibitors (class of antihyperglycemic agents that delay the digestion and absorption of carbohydrates and decrease a postprandial increase in blood glucose) Meglitinides (glinides) Stimulates release of insulin from this islet cells of pancrease (patient must have functioning pancreas) Work by increasing insulin secretion by the beta cells of the pancreas  Drugs include:  Repaglinide (prototype)  nateglinide  Side effects: o Target postprandial glycemia and may cause hypoglycemia if not taken with food  The word postprandial means after a meal; PPG concentrations refer to plasma glucose concentrations after eating.  Approved for monotherapy or in combination with: o metformin o thiazolidinediones Biguanides Decreases absorption of glucose from intestines Decreases synthesis of glucose by the liver Increases sensitivity of insulin receptors in the tissues which decreases insulin resistance Work by reducing hepatic glucose production while increasing insulin action on muscle glucose uptake  They have also been used for clients with metabolic syndrome and polycystic ovarian syndrome  Drugs include  metformin (Glucophage)  Side effects: o Gastrointestinal side effects o Vitamin B12 and folic acid deficiencies  o Can be o o o o Lactic acidosis used as monotherapy or in combination with: Insulin Sulfonylureas Non- Sulfonylurea secretagogues Thiazolidinediones Thiazolidinediones (glitazones) Reduces insulin resistance of tissue so insulin must be available (clients may need concurrent administration of insulin injections/metformin/sulfonylurea that stimulate pancreas to release insulin improves sensitivity to insulin by acting as an agonist at receptor sites involved in insulin responsiveness and subsequent glucose production and utilization. Therefore, decreasing insulin resistance. Requires insulin for activity.  Drugs include:  Pioglitazone (Actos)  Side effects: o May decrease the effectiveness of oral contraceptives o Should be used cautiously in clients who have heart failure  Can be used as monotherapy or in combination with: o Metformin Alpha-glucosidase inhibitors Breaks down carbohydrates in the intestines reducing sudden rise in postprandial blood glucose that occurs after meals Helps to improve glycemic control by lowering A1C levels but does not cause hypoglycemia if used alone Work by delaying carbohydrate digestion  Alpha-glucosidase inhibitors target postprandial glucose; their effects are not systemic  Does not depend on the presence of insulin at all  Drugs include:  acarbose  miglitol  Side effects: o Gastrointestinal side effects  Can be used in monotherapy or in combination therapy with sulfonylurea Dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) Work by augmenting naturally occurring incretin hormones, which promote the release of insulin and decrease the secretion of glucagon  The result is reduced fasting and postprandial glucose levels  Incretin hormones are gut peptides that are secreted after nutrient intake and stimulate insulin secretion together with hyperglycaemia. GIP (glucose-dependent insulinotropic polypeptide) und GLP-1 (glucagon-like peptide-1) are the known incretin hormones from the upper (GIP, K cells) and lower (GLP-1, L cells) gut.  Drugs include:  Sitagliptin Combination therapies  metformin & glyburide o metformin – Biguanides: Work by reducing hepatic glucose production while increasing insulin action on muscle glucose uptake o glyburide – Sulfonylureas: Work by increasing insulin secretion by the beta cells of the pancreas  metformin & glipizide o metformin – Biguanides: Work by reducing hepatic glucose production while increasing insulin action on o glipizide – Sulfonylureas: Work by increasing insulin secretion by the beta cells of the pancreas  metformin & rosiglitazone o metformin –Biguanides: Work by reducing hepatic glucose production while increasing insulin action on o rosiglitazone – Thiazolidinediones (glitazones): improves sensitivity to insulin by acting as an agonist at receptor sites involved in insulin responsiveness and subsequent glucose production and utilization. Therefore, decreasing insulin resistance. Requires insulin for activity. Injectable Medications Used for type 1 & type 2 diabetics that cannot be controlled by diet and oral hypoglycemics and gestational diabetes Insulin helps the body use and store energy. Insulin is secreted by the beta cells of the pancreas in response to glucose levels in the blood. Secretion is also prompted by amino acids, fatty acids, and ketone bodies. InsufÏcient insulin decreases the metabolism of complex molecules, which results in hyperglycemia/uncontrolled diabetes. Rapid & Short Acting Insulin Used for management of postprandial increases in blood glucose Given right before meals Should be used in conjunction with an intermediate or long-acting agent Rapid Acting:  insulin lispro  insulin aspart  insulin glulisine  Onset: 15 – 20 mins  Peak: 30min – 2.5hrs  Duration: 3 – 6hrs Short acting: Administered before meals to control postprandial hyperglycemia Injected Subcut to ensure basal glycemic control May be infused intravenously in emergency situations  Regular insulin  Onset: 30 – 60mins  Peaks: 1 – 5hrs  Duration: up to 10hrs Intermediate-acting Insulin Intended for once or twice a day dosing to control blood glucose Delayed action (makes it less effective for mealtime increases in BGL)  Neutral protamine Hagedorn (NPH) insulin  Onset: 60 – 120mins  Peaks: 6 – 14hrs  Duration: 16 – 24hrs Long-acting Insulin Intended to provide basal glucose control Once a day at the same time each day  Insulin glargine o Onset: 70mins o Peakless o Duration: 18 – 24hrs  Insulin detemir o Onset: 3 – 4hrs o Peaks: 12 – 24hrs  Small amounts are released slowly resulting in relatively constant effect over time o Duration: varies with dosage Combination/Mixed Insulin Typically composed of intermediate-acting and short-acting insulin Numbers indicate percentage of each type of insulin  Humulin 70/30 (70% NPH and 30% regular insulin) Methods of Delivery Insulin Pens Small pre-filled cartridges (typically containing 150-300 units) in a pen-like device Cartridge is marked in 1-unit increments Self-administration Contains only 1 type of insulin New pens are refrigerated; once pierced they can be kept at room temperature until empty up to 30 days  Attach a new needle  Hold pen vertically  Perform an air shot to expel any air    Dial in the exact dose of insulin needed Cleanse the selected site Inject by pushing the button Insulin Pumps Continuous Subcut regular rapid-acting insulin delivered by a small external device at 1 unit/hr Purpose: to provide continuous glycemic control with insulin to stimulate normal pancreatic function Prescribed for type 1 diabetics, and type 2 diabetics who have become insulin dependent Delivers basal rate needed; client then calculated additional insulin needed based on meals  Change needle or catheter every 1-3 days  Rotate needle sites and keep them 1” apart o Because Insulin is a hormone it can cause excess growth of fat beneath the skin called lipodystrophy  Client is allowed to remove pump for short periods (showers)  Carbohydrate counting is common method used to determine how much additional insulin to take; BGL can also be used  Risk of malfunction which can lead to risk of DKA  Basal glucose levels may decrease over time resulting in drops in BGL (risk for hypoglycemia if unaware of drop)  Client teaching: o Proper hygiene o Needle disposition o Nutrition management o How to administer insulin manually Teaching Nutrition, meal planning, and weight control (foundations of management) Emphasize the importance of foot, skin, and dental care Do not soak feet Inspect daily for skin changes/temperature changes Use lotion on feet – not in between toes Use pumice stone to smooth corns/calluses Cut toenails straight across Make sure shoes are not too tight Elevate feet when possible Do not smoke (vasoconstriction) See doctor for any wounds not healing Demonstrate the use of medications and monitoring supplies and methods Females: implications of pregnancy Stress management and psychosocial challenges Relationship between diet and exercise Exchange list, glycemic index, and MyPlate Monitoring glycosylated hemoglobin (HbA1c) A blood test that provides long-term measure of glucose control Measures the glucose attached to a hemoglobin molecule for the life of a RBS (about 120 days) to provide an average blood glucose readings for a period of 2-3mo Unaltered by eating habits the day before the test ADA recommends an HbA1c <7% for adult, nonpregnant clients who have diabetes Blood pressure & cholesterol goals BP <130/80mm Hg LDL <100mg/dL Triglycerides <150mg/dL HDL males >40MG/DL females >50mg/dL STRESS - Illness, surgery, and infection can cause a release in hormones that increases BGL Can lead to hyper and hypoglycemia Coping skills Check BGL more frequently