Diabetes Mellitus PDF

Diabetes mellitus Insulin Preparation Oral Hypoglycemic Agents PD-501 Dr. Faheema Siddiqui Endocrine glands: Pancreas  1 million islets of Langerhans interspersed throughout the pancreatic gland Pancreatic islet cells and their secretory products  Insulin...

Diabetes mellitus Insulin Preparation Oral Hypoglycemic Agents PD-501 Dr. Faheema Siddiqui Endocrine glands: Pancreas  1 million islets of Langerhans interspersed throughout the pancreatic gland Pancreatic islet cells and their secretory products  Insulin production is more or less constant within the beta cells  Its release is triggered by food, chiefly food containing absorbable glucose Diabetes mellitus is a complicated, chronic disorder characterized by either insufficient insulin production by the beta cells of pancreas or by cellular resistance to insulin. Insulin insufficiency results in elevated blood glucose levels, or hyperglycemia. As a result, individuals with diabetes at risk for a no. of disorders, including myocardial infarction, cerebrovascular accident (stroke), blindness, kidney disease, and lower limb amputations. complications such as retinopathy, nephropathy, and neuropathy Insulin and the oral antidiabetic drugs, along with diet and exercise, are the cornerstones of treatment for diabetes mellitus. Classic signs and symptoms of diabetes (polyuria, polydipsia, ketonuria, and unexplained weight loss) combined with a random plasma glucose ≥200 mg/dL (11.1 mmol/L). A FPG ≥126 mg/dL (7.0 mmol/L). Fasting means no caloric intake for at least 8 hours. Diabetes mellitus is a complicated, chronic disorder characterized by either insufficient insulin production by the beta cells of the pancreas or by cellular resistance to insulin. Insulin insufficiency results in elevated blood glucose levels, or hyperglycemia. As a result of the disease, individuals with diabetes are at greater risk for a number of disorders, including myocardial infarction, cerebrovascular accident (stroke), blindness, kidney disease, and lower limb amputation. There are 4 main types of diabetes:  Type 1—Insulin-dependent diabetes mellitus (IDDM). Former names juvenile diabetes. Has a rapid onset, occurs before the age of 20 years, produces more severe symptoms than type 2 diabetes, and is more difficult to control. Major symptoms of type 1 diabetes include hyperglycemia, polydipsia (increased thirst), polyphagia (increased appetite), polyuria (increased urination), and weight loss. Treatment of type 1 diabetes is particularly difficult to control because of the lack of insulin production by the pancreas.  further subdivided into immune and idiopathic causes  Treatment requires a strict regimen that typically includes a carefully calculated diet, planned physical activity, home glucose testing several times a day, and multiple daily insulin injections. Types 2. Type 2 diabetes: —Noninsulin-dependent diabetes mellitus (NIDDM). produce insulin in insufficient amounts and therefore must have insulin supplementation to survive. Results from insulin resistance, a condition in which cells fail to use insulin properly, sometimes combined with an absolute insulin deficiency Type 2 diabetes mellitus affects about 90% to 95% of individuals with diabetes. Either have a decreased production of insulin by the beta cells of the pancreas or a decreased sensitivity of the cells to insulin, making the cells insulin resistant 3. Gestational diabetes:  High blood glucose level during pregnancy  It may precede development of type 2 DM  GDM affects about 7% of all pregnancies and is defined as “any carbohydrate intolerance with onset or first recognition during pregnancy.” 4. Other:  Pancreatectomy, pancreatitis, nonpancreatic diseases, drug therapy  Congenital diabetes, which is due to genetic defects of insulin secretion,  Cystic fibrosis-related diabetes  Steroid diabetes induced by high doses of glucocorticoids  Several forms of monogenic diabetes  ❊Nursing Alert Pregnancy makes diabetes more difficult to manage. Insulin requirements usually decrease in the first trimester, increase during the second and third trimester, and decrease rapidly after delivery. The patient with diabetes or a history of gestational diabetes must be encouraged to maintain good metabolic control before conception and throughout pregnancy. Frequent monitoring is necessary. Nursing Diagnoses Checklist ✓ Confusion related to adverse drug reaction (hypoglycemia) ✓ Anxiety related to diagnosis, fear of giving own injections, dietary restrictions, other factors (specify) ✓ Ineffective Coping related to inability to accept diagnosis, other factors (specify) ✓ Fear related to diagnosis, consequences of diabetes ✓ Ineffective Health Maintenance related to inability to comprehend drug regimen, lack of equipment to monitor drug effects, lack of knowledge ✓ Risk for Ineffective Therapeutic Regimen Management related to lack of knowledge, misunderstanding, or complexity of prescribed treatment program, other factors Risk factors for type 2 diabetes include: Obesity Older age Family history of diabetes History of gestational diabetes (diabetes that develops during pregnancy but disappears when pregnancy is over) Impaired glucose tolerance Minimal or no physical activity Race/ethnicity (African Americans, Hispanic/Latino Americans, American Indians, and some Asian Americans) Obesity is thought to contribute to type 2 diabetes by placing additional stress on the pancreas, which makes it less able to respond and produce adequate insulin to meet the body’s metabolic needs. Many individuals with type 2 diabetes are able to control the disorder with diet, exercise, and oral antidiabetic drugs. However, about 40% of those with type 2 diabetes do not have a good response to the oral antidiabetic drugs and require the addition of insulin to control the diabetes.  Glutamic acid decarboxylase anaerobic metabolism Process of Insulin Release virus express on MHC cell then cytotoxic cell recognize autoimmune activate susceptible gene HLA DR3 HLADR4 stimulate b cell and autoimmune disease cause diabetes, vitiligo, RA,Systemic lupus Type-1 Diabetes Type II Metabolic syndrome fasting glucose >100 mg/dl triglyceride >150 mg/dl HDL: female ≤ 50 mg/dl , male ≤ 40 mg/dl bp 150/85 BMI: female ≥35 male ≥ 40 Decrease intracellular response Hyperinsulinmia so less stimulation of glu Amylin deposition transporter so less glu get into around beta cell the cell so more glucose in blood damage beta cell Type-2 Diabetes Mechanism of Insulin Release Postprandial Glucose Metabolism in the Nondiabetic Individual After food is ingested, blood glucose concentrations rise and stimulate insulin release. ▪ It promotes the uptake of glucose, fatty acids, and amino acids and their conversion to storage forms in most tissues. ▪ Insulin also inhibits hepatic glucose production by suppressing glucagon and its effects. ▪ In muscle, insulin promotes the uptake of glucose and its storage as glycogen. ▪ It also stimulates the uptake of amino acids and their conversion to protein. ▪ In adipose tissue, glucose is converted to free fatty acids and stored as triglycerides. ▪ The liver does not require insulin for glucose transport, but insulin facilitates the conversion of glucose to glycogen and free fatty acids. Diabetes mellitus  Diabetes mellitus / Diabetes, is a group of metabolic diseases  High blood sugar levels because  the body does not produce enough insulin, or  because cells do not respond to the insulin that is produced  High blood sugar produces the classical symptoms of diabetes includes, 1. Polyuria (frequent urination) 2. Polydipsia (increased thirst) 3. Polyphagia (increased hunger) Clinical Manifestation glomerulus filtered renal tubule cant tolerate so reabsorb capability diminish glucose osmotically hyperosmotic polyuria hyperosmolar blood so thirst polydypsia hypothalamus osmo receptor stimulate increaase thirst Glycated Hb Microalbuminurea, CKD Blood vessel inflammation so LDL deposition atherosclerosis In the vessel and around basement membrane  Microalbuminurea, CKD Aldoreductase Sorbitol dehydrogenase Peripheral artery disease Gastrophresis Neurogenic bladder Urine retention Somatic sensory nerve damage: loss sensation so Burning, tangling Lead to foot ulcer microanyrism, brain Schwan cell Vasoconstrition haemorage Demylination Orthostatic How to treat chronic complications  Acute and Chronic complications of diabetes Acute and Chronic symptoms of diabetes  Acute complications:  Hyperglycemia  diabetic ketoacidosis  nonketotic hyperosmolar coma  Long-term complications:  cardiovascular disease  chronic renal failure  retinal damage  Adequate treatment of diabetes is thus important, as well as blood pressure control and lifestyle factors such as smoking cessation and maintaining a healthy body weight Main symptoms of Diabetes Diabetic ketoacidosis  Complications of diabetes mellitus A. Acute  1. Diabetic ketoacidosis (DKA)  Low insulin levels cause the liver to turn to fat for fuel (ie, ketosis); ketone bodies are intermediate substrates in that metabolic sequence  This is normal when periodic, but can become a serious problem if sustained  Elevated levels of ketone bodies in the blood decrease the blood's pH, leading to DKA. On presentation at hospital, the patient in DKA is typically dehydrated, and breathing rapidly and deeply. Abdominal pain is common and may be severe  The level of consciousness is typically normal until late in the process, when lethargy may progress to coma  Ketoacidosis can easily become severe enough to cause hypotension, shock, and death  Urine analysis  2. Diabetic coma  Diabetic coma is a medical emergency in which a person with diabetes mellitus is comatose (unconscious) because of one of the acute complications of diabetes:  1. Severe diabetic hypoglycemia  2. Diabetic ketoacidosis advanced enough to result in unconsciousness from a combination of severe hyperglycemia, dehydration and shock, and exhaustion  3. Respiratory infections  The immune response is impaired in individuals with diabetes mellitus  Cellular studies have shown that hyperglycemia both reduces the function of immune cells and increases inflammation  The vascular effects of diabetes also tend to alter lung function, all of which leads to an increase in susceptibility to respiratory infections such as pneumonia and influenza among individuals with diabetes Chronic complications  Chronic elevation of blood glucose level leads to damage of blood vessels (angiopathy)  The endothelial cells lining the blood vessels take in more glucose than normal, since they do not depend on insulin  They then form more surface glycoproteins than normal, and cause the basement membrane to grow thicker and weaker  In diabetes, the resulting problems are grouped under "microvascular disease" (due to damage to small blood vessels) and "macrovascular disease" (due to damage to the arteries) Microangiopathies can lead to:  Diabetic cardiomyopathy, damage to the heart, leading to diastolic dysfunction and eventually heart failure  Diabetic nephropathy, damage to the kidney which can lead to chronic renal failure, eventually requiring dialysis  Diabetes mellitus is the most common cause of adult kidney failure worldwide in the developed world.  Diabetic neuropathy, abnormal and decreased sensation, starting with the feet but potentially in other nerves, later often fingers and hands  When combined with damaged blood vessels this can lead to diabetic foot  Other forms of diabetic neuropathy may present as mononeuritis or autonomic neuropathy  Diabetic amyotrophy is muscle weakness due to neuropathy  Diabetic retinopathy, growth of friable and poor-quality new blood vessels in the retina as well as macular edema (swelling of the macula), which can lead to severe vision loss or blindness  Retinal damage (from microangiopathy) makes it the most common cause of blindness among non-elderly adults in the US Macrovascular disease leads to cardiovascular disease, to which accelerated atherosclerosis is a contributor:  Coronary artery disease, leading to angina or myocardial infarction ("heart attack")  Diabetic myonecrosis ('muscle wasting')  Peripheral vascular disease, which contributes to intermittent claudication (exertion-related leg and foot pain) as well as diabetic foot  Stroke (mainly the ischemic type) Cont..  Diabetic foot, often due to a combination of sensory neuropathy (numbness or insensitivity) and vascular damage, increases rates of skin ulcers (diabetic foot ulcers) and infection and, in serious cases, necrosis and gangrene  Diabetic encephalopathy  It is the increased cognitive decline and risk of dementia observed in diabetes  Causes Genetic defects of β-cell Exocrine Pancreatic Defects Function  Chronic pancreatitis Infections  Pancreatectomy  Cytomegalovirus infection  Pancreatic neoplasia  Coxsackievirus B Drugs Endocrinopathies Growth  Glucocorticoids hormone excess (acromegaly)  Thyroid hormone  Cushing syndrome  β-adrenergic agonists  Hyperthyroidism  Pheochromocytoma  Glucagonoma  Diagnosis  Fasting plasma glucose level ≥ 7.0 mmol/L (126 mg/dL).  Plasma glucose ≥ 11.1 mmol/L (200 mg/dL) two hours after a 75 g oral glucose load as in a glucose tolerance test.  Symptoms of hyperglycemia and casual plasma glucose ≥ 11.1 mmol/L (200 mg/dL).  Glycated hemoglobin (Hb A1C) ≥ 6.5%  Glucose tolerance test: is a medical test in which glucose is given and blood samples taken afterward to determine how quickly it is cleared from the blood  The test is usually used to test for diabetes Insulin Insulin: Chemistry  Insulin is synthesized as the prohormone proinsulin, an  86-amino-acid single-chain polypeptide. Cleavage of proinsulin and cross-linking result in the 2-chain 51- peptide insulin molecule and a 31-amino-acid residual C- peptide. Neither proinsulin nor C-peptide appears to have any physiologic actions. nsulin is a peptide hormone containing two chains cross-linked by disulfide bridges. Effects Insulin has important effects on almost every tissue of the body. When activated by the hormone, the insulin receptor, a transmembrane tyrosine kinase, phosphorylates itself and a variety of intracellular proteins when activated by the hormone. The major target organs for insulin action include: 1. Liver—Insulin increases the storage of glucose as glycogen in the liver. This involves the insertion of additional GLUT2 glucose transport molecules in cell plasma membranes 2. Skeletal muscle—Insulin stimulates glycogen synthesis and protein synthesis. Glucose transport into muscle cells is facilitated by insertion of GLUT4 transporters into cell plasma membranes 3. Adipose tissue—Insulin facilitates triglyceride storage by activating plasma lipoprotein lipase, increasing glucose transport into cells via GLUT4 transporters, and reducing intracellular lipolysis. Administration of exogenous insulin can ameliorate metabolic abnormalities in type II diabetes: It compensates for reduced endogenous insulin secretion, reduces excessive hepatic glucose production, and stimulates glucose uptake, enhancing both glucose oxidation and storage in the muscle tissue. In diabetes mellitus, particularly in Type 2 diabetes, insulin resistance occurs when cells in the body do not respond effectively to insulin. This resistance can involve various mechanisms, including alterations in insulin receptors and downstream signaling pathways. However, the process of exogenous insulin binding to the receptor remains fundamentally the same. Insulin Resistance and Receptor Function: In insulin resistance, the number of insulin receptors may be reduced, or the receptor function may be impaired. Post-receptor signaling pathways may also be defective, resulting in a diminished biological response to insulin Binding of Exogenous Insulin: 1. Despite the resistance, exogenous insulin administered to a patient with diabetes still binds to the insulin receptors on the cell surface in the same manner as in non-resistant cells. 2. Exogenous insulin enters the bloodstream and circulates to target tissues, such as liver, muscle, and fat cells. 1.Receptor Recognition and Binding: 1. Insulin receptors, which are composed of alpha and beta subunits, recognize and bind to exogenous insulin. 2. The binding occurs at the extracellular alpha subunits of the receptor, leading to a conformational change. 1.Receptor Activation: 1. Even in insulin resistance, the initial binding of insulin to its receptor typically remains intact, allowing the receptor to undergo autophosphorylation on the intracellular beta subunits. 2. However, the degree of this activation may be reduced due to the presence of fewer receptors or defective receptors. Impaired Signal Transduction: The key issue in insulin resistance lies in the impaired signal transduction after receptor activation. Phosphorylation of insulin receptor substrates (IRS) may be decreased or abnormal, leading to reduced activation of downstream signaling pathways such as PI3K/Akt. This results in less effective translocation of GLUT4 to the cell membrane in muscle and fat cells, reducing glucose uptake. Additionally, impaired signaling may affect glycogen synthesis, protein synthesis, and other metabolic processes regulated by insulin 1.Exogenous Insulin and Overcoming Resistance: 1. Higher doses of exogenous insulin may be required to achieve the desired metabolic effects in insulin-resistant individuals. 2. The increased insulin concentration helps to partially overcome the resistance by ensuring that enough insulin receptors are activated to produce a physiological response. In summary, while exogenous insulin binds to insulin receptors in insulin-resistant cells in a similar manner to how it does in non-resistant cells, the subsequent signaling and metabolic responses are impaired. This impairment necessitates higher doses of insulin to achieve glycemic control in patients with Type 2 diabetes. The challenge in managing insulin resistance involves not just increasing insulin levels but also addressing underlying factors contributing to the resistance, such as obesity, inflammation, and genetic predispositions. Insulin Preparations Human insulin is manufactured by bacterial recombinant DNA technology. The available forms provide 4 rates of onset and durations of effect that range from rapid-acting to long-acting. The goals of insulin therapy are to control both basal and postprandial (after a meal) glucose levels while minimizing the risk of hypoglycemia. Insulin formulations with different rates of onset and effect are often combined to achieve these goals. Onset, Peak, and Duration of Action Onset, peak, and duration are three properties of insulin that are of clinical importance. Onset—when insulin first begins to act in the body Peak—when the insulin is exerting maximum action Duration—the length of time the insulin remains in effect To meet the needs of those with diabetes mellitus, various insulin preparations have been developed to delay the onset and prolong the duration of action of insulin. When insulin is combined with protamine (a protein), the absorption of insulin from the injection site is slowed and the duration of action is prolonged. The addition of zinc also modifies the onset and duration of action of insulin. Insulin preparations are classified as rapid-acting, intermediate-acting, or long-acting. 1. Rapid-acting— Three insulin analogs (insulin lispro, insulin aspart (Novarapid), and insulin glulisine) have rapid onsets 5 to 15 min and early peaks of activity 30 min and are active for 5 hours. The 3 rapid- acting insulins have small alterations in their primary amino acid sequences that speed their entry into the circulation without affecting their interaction with the insulin receptor. The rapid-acting insulins are injected immediately before a meal and are the preferred insulin for continuous subcutaneous infusion devices. They also can be used for emergency treatment of uncomplicated diabetic ketoacidosis. The natural amino acid sequence of the insulin βchain at positions 28 (proline) and 29 (lysine) is inverted to form lispro. This change results in an insulin molecule that more loosely self-associates into hexamers than does regular insulin. Consequently, the active monomeric form is more readily available, resulting in an onset of activity (15 minutes), peak action (60–90 minutes), and duration (3–4 2. Short-acting—Regular insulin is used intravenously in emergencies or administered subcutaneously in ordinary maintenance regimens, alone or mixed with intermediate- or long-acting preparations but it requires administration 1 h or more before a meal. Peak effect: 2 h D.O.A: Up to 8 hours 3. Intermediate-acting—Neutral protamine Hagedorn insulin (NPH insulin) addition of zinc and protamine that exhibits a delayed onset and peak of action. NPH insulin is often combined with regular and rapid-acting insulins. Peak effect 6 hour duration 18 hour 4. Long-acting— Insulin glargine and insulin detemir are modified forms of human insulin that provide a peakless basal insulin level lasting more than 20 h, which helps control basal glucose levels without producing hypoglycemia. DETEMIR: Peak effect 6-8 hour Duration: 24 hour Glargine: Steady delivery: 24 hour no peak effect Longer effect because of addition of fatty acid chain Extent and duration of action of various types of insulin Insulin Delivery Systems  A. Standard Delivery: subcutaneous injection using conventional disposable needles and syringes.  B. Portable Pen Injectors  C. Continuous Subcutaneous Insulin Infusion Devices (CSII, Insulin Pumps): Patients who use an insulin pump most often use a rapid- acting insulin instead of regular insulin.  ADVERSE REACTIONS The two major adverse reactions seen with insulin administration are hypoglycemia (low blood glucose or sugar) and hyperglycemia (elevated blood glucose or sugar). CONTRAINDICATIONS Insulin is contraindicated in patients with hypersensitivity to any ingredient of the product (eg, beef or pork) and when the patient is hypoglycemic. PRECAUTIONS Insulin is used cautiously in patients with renal and hepatic impairment and during pregnancy (Pregnancy Category B and Category C, insulin glargine and insuli aspart) and lactation (may inhibit milk formation with large doses of insulin). Insulin appears to inhibit milk production in lactating women and could interfere with breastfeeding. Lactating women may require adjustment in insulin dose and diet ASSIGNMENT Oral antidiabetic agents NONINSULIN ANTIDIABETIC DRUGS Four well-established groups of oral antidiabetic drugs are used most commonly to treat type 2 diabetes. These include insulin secretagogues, the biguanide, thiazolidinediones, and `-glucosidase inhibitors. Three novel agents—pramlintide, exenatide, and sitagliptin—target endogenous regulators of glucose homeostasis. Oral antidiabetic agents  Insulin secretagogues:  Sulfonylureas  Meglitinide  D-phenylalanine derivative  Biguanides  Thiazolidinediones  Alpha-glucosidase inhibitors  Amylin analog  Glucagon-like polypeptide-1 (Glp-1) receptor agonists  Dipeptidyl peptidase-4 (dpp-4) Inhibitors INSULIN SECRETAGOGUES: SULFONYLUREAS  Are conventionally divided into first-generation and second- generation agents basis in potency and adverse effects.  Second-generation agents are more common and effective and have fewer side effects and drug interactions, the older compounds probably will be discontinued.  Are used with caution in patients with cardiovascular disease or in elderly patients, in whom hypoglycemia would be dangerous.  Mechanism of Action: 1. increase insulin release from the pancreas 2. reduction of serum glucagon levels 3. closure of potassium channels in extrapancreatic tissue Cont.. Insulin Release from Pancreatic Beta Cells  Sulfonylureas bind to a high-affinity sulfonylurea receptor that is associated with ATP-sensitive potassium channel. Binding of a sulfonylurea inhibits the efflux of potassium ions through the channel and results in depolarization. Depolarization opens a voltage-gated calcium channel and results in calcium influx and the release of preformed insulin. Classification FIRST-GENERATION Second GENERATION SULFONYLUREAS SULFONYLUREAS  Tolbutamide  Glyburide  Chlorpropamide  Glipizide  Tolazamide  Glimepiride Insulin secretagogues are not effective in patients who lack functional pancreatic B cells. Both have a rapid onset and short duration of action that make them useful for administration just before a meal to control postprandial glucose levels. Mechanism of Action: Increase Blood glucose level Decrease Blood glucose level Decrease ATP production Increase ATP production Inhibition of potassium Potassium efflux continues channel (k channel close) Hyperpolarization Potassium efflux stop results in Depolarization Calcium influx decrease and Calcium influx and trigger insulin release decreases release of insulin Toxicities— The older sulfonylureas (tolbutamide and chlorpropamide) are extensively bound to serum proteins, and drugs that compete for protein binding may enhance their hypoglycemic effects. Occasionally these drugs cause rash or other allergic reactions. Weight gain is common and is especially undesirable in the large fraction of patients with type 2 diabetes who already are overweight. B. Biguanides 1. Mechanism and effects—Metformin, the primary member of the biguanide group, reduces postprandial and fasting glucose levels. Biguanides inhibit hepatic and renal gluconeogenesis, with increased glucose to lactate conversion by enterocytes. Reduce hepatic glucose production through activation of the enzyme amp-activated protein kinase (ampk). Other effects include stimulation of glucose uptake and glycolysis in peripheral tissues, slowing of glucose absorption from the gastrointestinal tract, and reduction of plasma glucagon levels. A drawback to metformin is that it requires multiple daily dosing and its dose also must be titrated to minimize GI effects. After the dose is established, it is possible to use a long acting product that can be dosed once daily. GI disturbances such as diarrhea, bloating, anorexia, abdominal discomfort, nausea, and metallic taste often dissipate with time and can be minimized by initiating metformin in a single, 500- or 850-mg dose at breakfast or with the patient’s largest meal of the day. Consistently taking metformin with food significantly minimizes the GI side effects. The dosage should be slowly increased (e.g. 500 mg/day every 2 weeks) until the appropriate clinical effect is achieved or the patient is taking the maximum dose (1,000 mg twice daily or 850 mg three times a day) or extended-release formulation. If patient continues to experience GI symptoms, an alternative approach is to use Acarbose is eliminated from consideration because slow titration is required to minimize GI effects. Rosiglitazone or pioglitazone (thiazolidinediones) also can be used as monotherapy like metformin (if no evidence of microvascular complications like liver or renal functions ) Biguanides Toxicity Gastrointestinal distress (nausea, diarrhea), and they can cause lactic acidosis, especially in patients with renal or liver disease. lactic acidosis is likely due to inhibition of gluconeogenesis by blocking pyruvate carboxylase, the first step of gluconeogenesis, which converts pyruvate to oxaloacetate. Blocking this enzyme leads to accumulation of lactic acid. C. Thiazolidinediones 1. Mechanism and effects—The thiazolidinediones, rosiglitazone and pioglitazone, increase target tissue sensitivity to insulin by activating the peroxisome proliferator-activated receptor-gamma nuclear receptor (PPAR-γ receptor). This nuclear receptor regulates the transcription of genes encoding proteins involved in carbohydrate and lipid metabolism. A primary effect of the thiazolidinediones is increasing glucose uptake in muscle and adipose tissue. They also inhibit hepatic gluconeogenesis and have effects on lipid metabolism and the distribution of body fat. Toxicity Thiazolidinediones can cause fluid retention, which presents as mild anemia and edema and may increase the risk of heart failure. In the field of molecular biology, the peroxisome proliferator- activated receptors (PPARs) are a group of nuclear receptor proteins that function as transcription factor regulating the expression of genes. PPARs play essential roles in the regulation of cellular differentiation, development and metabolism (carbohydrate, lipid and protein). It is expressed predominantly in adipose tissue but is expressed in other tissues as well. Upon the binding of the agonists, PPAR-γ heterodimerizes Synthetic agonists of PPAR-γ, thiazolidinediones (TZDs), have been developed to improve glucose tolerance by enhancing insulin sensitivity and restoring the function of β-cells in diabetic subjects. insulin sensitive will require smaller amounts of insulin to lower blood glucose levels. People with low insulin sensitivity, also referred to as insulin resistance D. Alpha-Glucosidase Inhibitors Mechanism Acarbose and miglitol are carbohydrate analogs that act within the intestine to inhibit α-glucosidase, an enzyme necessary for the conversion of complex starches, oligosaccharides, and disaccharides to the monosaccharides that can be transported out of the intestinal lumen and into the bloodstream. As a result of slowed absorption, postprandial hyperglycemia is reduced. These drugs lack an effect on fasting blood sugar. Toxicities—The primary adverse effects of the α-glucosidase inhibitors include flatulence, diarrhea, and abdominal pain resulting from increased fermentation of unabsorbed carbohydrate by bacteria in the colon. Patients taking an α-glucosidase inhibitor who experience hypoglycemia should be treated with oral glucose (dextrose) and not sucrose, because the absorption of sucrose will be delayed. Beta cell secrets amylin Pramlinitide it allows insulin doses to reduce, however risk of hyperglycemia is still there. Side effect: N, and modest wt loss E.Pramlintide is an injectable synthetic analog of amylin, a 37- amino acid hormone produced by pancreatic B cells. Pramlintide suppresses glucagon release, slows gastric emptying, and works in the CNS to reduce appetite. The major adverse effects associated with pramlintide are hypoglycemia and gastrointestinal disturbances. F. Exenatide and Linglutinide (incretin mimetics) Glucagon-like peptide-1 (GLP-1) is a member of the incretin family of peptide hormones, which are released from endocrine cells. The incretins stimulated insulin release from pancreatic B cells, retard gastric emptying, inhibit glucagon secretion, and produce a feeling of satiety. The major adverse effects are GI disturbances, and hypoglycemia. The drug has also caused serious and sometimes fatal acute pancreatitis. Two peptide GLP-1 and GIP GIP: Glucose dependent insulin polypeptide  Incretin are metabolic hormones secreted by GI in response to food ingestion function to increase release of insulin dipeptidyl peptidase-4 (DPP-4). Incretins stimulated insulin release from pancreatic B cells, retard gastric emptying, inhibit glucagon secretion, and produce a feeling of satiety G. Sitagliptin Sitagliptin is an oral inhibitor of dipeptidyl peptidase-4 (DPP- 4), the enzyme that degrades GLP-1 and other incretins. Like exenatide, sitagliptin are synthesize to mimic GLP-1 and resistant to degradation by this enzyme and promotes insulin release, inhibits glucagon secretion, and has an anorexic effect. The most common adverse effects are headache, nasopharyngitis, and upper respiratory tract infection. H. Canagliflozin The sodium-glucose transporter 2 (SGLT2) accounts for 90% of renal glucose reabsorption, and its inhibition causes glycosuria and lowers glucose levels in patients with type 2 diabetes. The SGLT2 inhibitors canagliflozin and dapagliflozin are approved for clinical use. The main adverse effects are increased incidence of genital infections and urinary tract infections. The osmotic diuresis can also cause hypotension. Which of the following would the nurse mostly likely choose to terminate a hypoglycemic reaction? A. Regular insulin B. NPH insulin C. Orange juice D. Crackers and milk Answers 1. c 2. Which of the following would be the correct method of administering insulin glargine? A. Within 10 minutes of meals B. Immediately before meals C. Anytime within 30 minutes before or 30 minutes after a meal D. At bedtime Answers 2. d 3. Which of the following symptoms would alert the nurse to a possible hyperglycemic reaction? A. Fatigue, weakness, confusion B. Pale skin, elevated temperature C. Thirst, abdominal pain, nausea D. Rapid, shallow respirations, headache, nervousness Answers 3. c 4. A patient with diabetes received a glycosylated hemoglobin test result of 10%. This indicates. A. the diabetes is well controlled B. poor blood glucose control C. the need for an increase in the insulin dosage D. the patient is at increased risk for hypoglycemia Answers 4. b 5. In patients receiving oral hypoglycemic drugs, the nurse must be aware that hypoglycemic reactions. A. will most likely occur 1 to 2 hours after a meal B. may be more intense than reactions seen with insulin administration C. may be less intense than reactions seen with insulin administration D. may occur more frequently in patients receiving oral hypoglycemic drugs Answers 5. c 1. A patient is prescribed 40 units NPH insulin mixed with 5 units of regular insulin. What is the total insulin dosage? Draw a line on the syringe below showing the total insulin dosage. Describe how you would prepare the insulins. 10 20 30 40 50 60 70 80 90 100 UNITS 5 15 25 35 45 55 65 75 85 Answers Draw an arrow to the number 45. q2. A patient is prescribed metformin (Glucophage) 1000 mg BID PO. The drug is available in 500-mg tablets. The nurse administers.What is the total daily dosage of metformin?. Answers 2, 2 tablets at each dose; total daily dose 2000 mg 3. A patient is prescribed rosiglitazone (Avandia) 8 mg PO daily. Available are 2-mg tablets. The nurse would administer ____. Answers 4 tablets 4. A patient is prescribed insulin Humulin L 32 U. Choose the correct label for the insulin. Answer 4. Label B References: 113