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I. INTRODUCTION A. Definition.

 The American Diabetes Association (ADA) defines diabetes mellitus as a group of metabolic diseases characterized by inappropriate hyperglycemia resulting from defects in insulin secretion, insulin action, or both.  Symptoms of acute hyperglycemia include polyuria, polydipsia, polyphagia, weight loss, blurred vision, fatigue, headache, and poor wound healing.  Chronic hyperglycemia can lead to damage and potentially failure of various organs, including the eyes, heart, kidneys, blood vessels, and nerves. B. Classification. There are four clinical classes of diabetes:  Type 1. Type 1 diabetes mellitus (T1DM) is typically characterized by an absolute insulin defi ciency attributed to an autoimmune destruction of the -cells of the islets of Langerhans. Aff ected individuals will have autoantibodies to glutamic acid decarboxylase, pancreatic islet cells, and/ or insulin. T1DM may be diagnosed at any age, but is most likely to be diagnosed prior to the age of 30 years.  Type 2. Type 2 diabetes mellitus (T2DM) is the most common form of DM and is typically identifi ed in individuals over the age of 30 years; however, it has become a more prominent diagnosis in adolescents of certain ethnic origins (e.g., Hispanic, African American). Th ose diagnosed with T2DM are typically overweight or obese, have a positive family history of diabetes, and/or exhibit signs of insulin resistance (e.g., truncal obesity, high triglycerides, low high-density lipoprotein cholesterol [HDL-C], acanthosis nigricans); autoantibodies found in T1DM are absent in T2DM.  Gestational diabetes mellitus. Gestational diabetes mellitus (GDM) is a condition in which women fi rst exhibit levels of elevated plasma glucose during pregnancy. Women previously diag- nosed with diabetes prior to pregnancy are excluded from this classifi cation. Aft er pregnancy, the diagnostic classifi cation of GDM may be changed based on postpartum testing (see III.B.2.b).  Other specific types. Secondary diabetes occurs when the diagnosis of diabetes is a result of other disorders (e.g., Cushing syndrome, acromegaly, cystic fi brosis, Down syndrome, pancreatic disorders) or treatments (e.g., glucocorticoids, antipsychotics). Monogenic DM (formerly maturity-onset diabetes of the young) should be considered in children with an atypical presenta- tion or response to therapy. Adults may present with Latent Autoimmune Diabetes of the Adult (LADA), which is a slow destruction of the pancreatic -cells similar to T2DM, but autoantibod- ies are present as in T1DM.  Categories of increased risk for diabetes (prediabetes): Individuals who have elevated blood glucose levels that do not meet diagnostic criteria for diabetes, but that are too high to be consid- ered normal, are classifi ed as having prediabetes. Prediabetes is a high-risk category for the future development of T2DM. II. PATHOPHYSIOLOGY OF THE DIABETIC STATE A. Normal glucose regulation involves many factors including insulin, counterregulatory hormones, incretin hormones, and amylin. Changes to any of these factors may result in an imbalance in glucose levels. 1. Insulin regulates the metabolism of carbohydrate, protein, and fat as follows:

Promotes the cellular uptake of plasma glucose Stimulates conversion of glucose into energy storage molecules (e.g., glycogen, fat) in the liver, muscles, and adipose cells  Facilitates cellular uptake of amino acids and their incorporation into proteins d. Inhibits production of glucose from liver, muscle glycogen, or amino acids e. Decreases the breakdown of fatty acids to ketone bodies 2. Counterregulatory hormones in diabetes are hormones that work against insulin. Thus, where insulin lowers blood glucose, counterregulatory hormones increase blood glucose. Th e counter- regulatory hormones include:  Glucagon  Growth hormone  Catecholamines (epinephrine and norepinephrine)  Cortisol 3. Incretin hormones: Ingested glucose promotes a more rapid release of insulin from the pancreas than when glucose is given by intravenous injection. This occurs because the incretin hormones, gastric inhibitory peptide (GIP) and glucagon-like peptide-1 (GLP-1) are secreted by the intestines in response to glucose ingestion, before the glucose is absorbed. Postprandial secretion of GLP-1 is diminished in DM, whereas GIP secretion is normal or increased. Actions of GLP-1 include:  Increases glucose-dependent insulin secretion  Inhibits inappropriate glucagon secretion  Increases -cell growth/replication  Slows gastric emptying  Suppresses appetite 4. Amylin is a hormone that is cosecreted with insulin from the pancreatic -cells. Thus, in individuals with T1DM, little to no amylin is produced, whereas in T2DM, amylin is produced, but in an insuffi cient quantity. Amylin lowers postprandial blood glucose levels by the following actions:  Prolongs gastric emptying time  Decreases postprandial glucagon secretion  Suppresses appetite B. Development of diabetes 1. T1DM.  Genetic predisposition o The risk of developing T1DM is increased in the off spring of individuals diagnosed with diabetes  environmental factors o viral (e.g., rubella, Coxsackie B), chemical, or dietary (e.g., cow’s milk  and autoimmunity o result of immune-mediated destruction of the -cells and is characterized by the abrupt onset of clinical signs and symptoms o Anti-insulin or anti--cell antibodies are present in the blood of most individuals at the time of diagnosis of T1DM 2. T2DM.  Genetics Th e risk of off spring development of T2DM is at least 15%.

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g.. 3. Native American. III.. pancreatic disorders) or treatments (e. Latino. Diagnostic testing  A1c tests o reflect the average blood glucose level over the preceding 2 to 3 months o not be done in individuals with abnormal red cell turnover (e.g. cystic fi brosis. 1 hr 180 mg/dL. acromegaly. African American.  weight loss  blurred vision  Fatigue  Headache  frequent vaginal infections  and poor wound healing.4% 4. pregnancy. B. A peripheral site defect o Defects in postre. Down syndrome.  Diagnosis of GDM based on OGTT: Fasting 92 mg/dL. Gestational diabetes mellitus (GDM) screening should occur between weeks 24 to 28 gestation if not previously diagnosed with overt diabetes. some anemias). Cushing syndrome. glucocorticoids. Adults who are overweight (BMI 25 kg/m2).7 to 6.g.  A primary -cell dysfunction only about 50% of -cells are functioning. Secondary diabetes may arise from other disorders (e. Asian American. a ntipsychotics).. 3. polydipsia. recent blood loss or transfusion. polyuria.ceptor binding or a decreased number of insulin receptors can lead to hyperglycemia. 2 hrs 153 mg/dL.5% 2.  Risk factors for diabetes include:  Physical inactivity  First degree relative with diabetes  High-risk ethnicity (e. and polyphagia). Testing in asymptomatic individuals: a.. Prediabetes: relatively high risk for the future development of diabetes  Impaired fasting glucose (IFG): fasting blood glucose 100 to 125 mg/dL  Impaired glucose tolerance (IGT): OGTT results of 140 to 199 mg/dL  A1c 5. Physical findings include:  “polys” (e.g. Diabetes in nonpregnant adults and children  Fasting blood glucose 126 mg/dL  Random (casual) blood glucose and symptoms of hyperglycemia: 200 mg/dL  Oral glucose tolerance test (OGTT) using oral glucose load equivalent to 75 g anhydrous glycerin dissolved in water: 200 mg/dL  A1c 6. Pacific Islander) (4) Women who delivered a baby weighing 9 lb or were diagnosed with GDM  Hypertension ( 140/90 mm Hg or on therapy for hypertension) . CLINICAL EVALUATION A.g. 1..

severe obesity. GLYCEMIC TREATMENT GOALS. glulisine) are mixed with another insulin.  50/50 insulin: 50% protamine lispro insulin with 50% lispro insulin  70/30 insulin: 70% insulin aspart protamine with 30% aspart insulin or 70% NPH with 30% regular insulin  75/25 insulin: 75% protamine lispro insulin with 25% lispro insulin f.  Extemporaneous mixtures which include regular-acting and intermediate-acting insulin are stable for 14 days refrigerated or 7 days at room temperature. aspart (NovoLog). Regular insulin (Humulin regular. Indications. Testing for T2DM in the asymptomatic pediatric population should occur  at the age of 10 years or the onset of puberty (whichever comes first)  children who are overweight  and have at least two risk factors  IV. Asymptomatic adults without risk factors should have screenings beginning at the age of 45 years. Long-acting insulins.  When rapid-acting insulins (e. lispro. PHARMACOLOGIC TREATMENT OF DIABETES MELLITUS A.. Isophane insulin suspension (neutral protamine Hagedorn. NPH) insulin d. V. Lispro (Humalog)..  Insulin is required for glycemic management in individuals with T1DM and may be used in combination with oral agents (e. Types of insulin a. e. pramlintide) as necessary. Two insulins mixed in one syringe. Extemporaneous mixtures. c.g. aspart. metformin) or amylin agonists (e. Intermediate-acting insulin. Glargine (Lantus) and detemir (Levemir) insulins.. and glulisine (Apidra) insulins b. 3. Short-acting insulin. Novolin regular) c.g.g. acanthosis nigricans) History of CVD b. . the preparation should be used immediately.  Glargine and detemir should never be mixed in the same syringe with another insulin..g.     HDL cholesterol level 35 mg/dL and/or a triglyceride level 250 mg/dL Women with polycystic ovarian syndrome (PCOS) Previous testing indicative of prediabetes Clinical conditions associated with insulin resistance (e. before administration. Rapid-acting insulin. Premixed insulin products. Techniques for monitoring glycemic control :  patient self-monitoring blood glucose (SMBG) o include fasting plasma glucose (FPG) and 2-hr postprandial glucose (PPG)  A1c.

Glynase) (b) Glipizide (Glucotrol) (c) Glimepiride (Amaryl) o Meglitinides: Repaglinide (Prandin) o Phenylalanine derivatives: Nateglinide (Starlix) 2. Fortamet. Indication:  The secretagogues are indicated for the management of T2DM only. 4. tolazamide (Tolinase). Biguanides 1. Hypoglycemia b. Insulin may be an initial or adjunctive agent for individuals with T2DM and may be used in combina. Insulin secretagogues (oral hypoglycemic agents) 1.tion with oral agents. GLP-1 agonists (e.or secondgeneration agents. Glucophage XR. Agents:  The only available biguanide is metformin (Glucophage. C . 3. or amylin agonists to achieve glycemic control.traditionally been seen as a fi rst-line agent for the management of T2DM  meglitinide and phenylalanine derivative target postprandial control. G lumetza. 4. Riomet)..g. inhibits lipolysis  Stimulates peripheral uptake of glucose B. Mechanisms of action:  stimulates enhanced secretion of insulin from pancreatic -cells  reduces hepatic glucose output 5. Mechanism of action. Contraindications:  Individuals with severe renal or hepatic dysfunction  Caution should be used in the elderly  It should be noted that neither repaglinide nor nateglinide are effective in patients who have failed sulfonylurea therapy. including the following:  Stimulates hepatic glycogen synthesis  Increased protein synthesis  Facilitates triglyceride synthesis and storage by adipocytes. Indication: . and chlorpropamide (Diabinese) o (Second generation: (a) Glyburide (DiaBeta. Agents  Sulfonylureas generally target fasting blood glucose levels and are classifi ed as first.  sulfonylureas is overall glycemic control. Weight gain. Patient education and other concerns: a. secondary to increased insulin secretion. o The three agents in this class i nclude tolbutamide (Orinase). 2. exenatide). Insulin exerts its eff ects in several ways. can occur.

thereby improving insulin sensitivity. c. LFTs had to be monitored every 2 months during the fi rst year.  Minimal weight loss can be seen initially with this agent. In 2004. Contraindications a. feeling of fullness. cramping.ers of the two available TZDs achieved FDA approval for LFTs to be monitored at baseline. Contraindications  Renal disease: the potential for lactic acidosis.g.  Metformin use has been associated with a reduction in vitamin B12 levels  Miscellaneous eff ects include sweating and a metallic taste. primarily targets fasting blood glucose levels. Use cautiously in persons with anemia. when the agents fi rst became available. but is not a continued effect. d. Pioglitazone is under an ongoing safety review for the potential increased risk of bladder cancer. Rosiglitazone is available only from certain mail order pharmacies for certain individuals under the Avandia-Rosiglitazone Medicines Access Program.tration (FDA).  Hepatic impairment or those with alcoholism or binge drinking  Heart failure:  Intravascular iodinated contrast media 4. the FDA . and periodically thereaft er. which can exacerbate or lead to heart failure. typically in the distal upper or lower limbs of females. nausea. Patient education and other concerns  by GI eff ects (e. Patients should be observed for signs and/or symptoms of heart failure. GI eff ects are self-limiting over 7 to 14 days. or diarrhea).dial infarction. Mechanisms of action:  inhibit hepatic glucose output.  a minor role in decreasing intestinal absorption of glucose. f.. thus  promote glucose uptake by fat and muscles. manufactur. myocar. Rosiglitazone has been associated with increased risk of cardiovascular events (e.. 3. Indication:  glycemic control in T2DM and primarily affect the fasting blood glucose levels. In 2007. D. loss of appetite. Thiazolidinediones (TZDs) 1. angina) and thus its use has been restricted by the Food and Drug Adminis. Th is may result in a small decrease in hemoglobin and hematocrit. Class III/IV heart failure: TZDs may cause fl uid retention. For instance. e. Several linked cases of liver toxicity are owed to troglitazone (Rezulin) which was removed from the market in 1999.   used for the glycemic management of T1DM or T2DM recommended to be initiated at diagnosis of T2DM unless there is an existing contraindication. Manufacturers of Avandia and Actos have taken caution. 5. At this time. Anemia: TZDs may cause plasma volume expansion. at 6 months. 3. TZDs should be used with caution in patients with hepatic dysfunction. FDA mandated manufacturers of TZDs to add CHF as a black box warning.g. but have made great strides in overcoming the stigma associated with the class. abdominal b loating.. b. Agents:  Pioglitazone (Actos)  Rosiglitazone (Avandia) 2. Fracture risk: TZDs have been associated with fractures.

increased risk of severe hypoglycemia in persons with T1DM within 3 hrs of dosing Indicated for adjunctive therapy to basal and bolus insulin: reduce prandial (bolus) insulin by 50% when initiating pramlintide to avoid hypoglycemia Do not mix together with insulin or inject into the same site as insulin Drug–drug interactions: oral medications needing rapid onset (e. gastrointestinal. -Glucosidase inhibitors 1.der. diabetes mellitus. glucagon-like peptide. immediate release. Administration and dosage (Table 46-3) 6. Infl ammatory bowel disease. Acarbose is not recommended in patients with serum creatinine > 2.. Agent Initial Dose (Maximum Dose) Comments Amylin Agonists Pramlintide (Symlin) T1DM: 15 mcg immediately prior to meals (60 mcg t. colonic ulceration. three times a day. type 2 diabetes mellitus. b. 5. c. b.d. Indication: -glucosidase inhibitors are for management of postprandial blood glucose 3. dipeptidyl peptidase.i. or obstructive bowel disorders b. Diabetes Mellitus 941 6. Benefi ts may not be seen prior to 2 to 4 weeks of use. type 1 diabetes mellitus.has not concluded an overall associated risk. which can result in fl atulence.. dose-dependent elevation in serum transaminases can be seen. Acarbose (Precose) b.d. c. Miglitol (Glyset) 2.0 mg/dL and neither agent is recommended in patients with creatinine clearance of 25 mL/min. Patient education and other concerns a. Report unusual weight gain. çcreatinine clearance. DM. timing of regimen). Patient education and other concerns a. Agents a. 5. shortness of breath. Mechanism of action: promote glucose uptake by fat and muscles and inhibit hepatic glucose output by the stimulation of peroxisome-proliferator-activated receptor-gamma (PPAR). GI. exercise. Contraindications a.g.g. 4. medication error. Th e dose should be taken with the fi rst bite of the meal for eff ectiveness. T2DM.) T2DM: 60 mcg immediately prior to meals (120 mcg t.) Adverse effects: nausea/vomiting. analgesics) should be administered 1 hr before or 2 hrs after pramlintide Targets postprandial blood glucose aConsult package insert for detailed prescribing information. which leads to a slower absorption of complex carbohydrates. Acarbose is contraindicated in patients with hepatic impairment. If hypoglycemia occurs within 2 . or swelling of the lower extremities. CrCl. TZDs as a class cause signifi cant weight gain that is likely associated with fl uid retention and fat accumulation. Dosage should be reduced if frequent hypoglycemia occurs without apparent cause (e. E.i. Administration and dosage (Table 46-3) Table 46-3 Continued. IR. twice a day. BID. T1DM. Mechanism of action: Competitive inhibition of alpha-glucosidases in the intestinal brush bor. changes in diet. GLP. TID. with maximum eff ectiveness not seen until 6 to 12 weeks of use. DPP. -glucosidase inhibitors cause increased gas formation in the colon. 4.

Dipeptidyl peptidase-IV (DPP-IV) inhibitors 1. Indication: adjunctive therapy for the management of T2DM 3. gastroparesis) b. Contraindications: Use with caution in persons with cardiovascular disease (e.farction. hypertriglyceridemia-induced pancreatitis. F. nausea. Administration and dosage (Table 46-3) 6.g. patient should be treated with oral glucose if the patient is conscious or intravenous glucose or glucagon if the patient is unconscious. Janumet XR) 8. Agent: Bromocriptine (Cycloset) 2. Metformin/glyburide (Glucovance) 2. Pancreatitis: use cautiously in an individual with a past medical history of pancreatitis and discontinue use if an individual develops pancreatitis while on a DPP-IV inhibitor. it is postulated that bromocriptine may aff ect circadian rhythms. May cause dizziness and fatigue. Bile acid sequestrant 1. G. GLP-1) by the en. Agents a. Individuals with severe GI motility disease (e. psychosis. May cause gastrointestinal discomfort. Metformin/pioglitazone (Actoplus Met. Severe renal impairment or hepatic impairment d. Mechanism of action for improvement in glycemic control is unknown. Liraglutide (Victoza) 2. GI side eff ects will lessen over time. Actoplus Met XR) 5. Mechanisms of action: Prevents the inactivation of incretin hormones (e. 5. dementia. Sitagliptin (Januvia) b. Metformin/rosiglitazone (Avandamet): restricted access medication 4. persistent abdominal pain. Contraindications a. thus inhibiting the breakdown of GLP-1 would allow for increased insulin secretion and decreased hepatic glucose production. arrhythmias). I.mum tolerated dose is achieved. severe skin rash. b.intestinal discomfort. Patient education and other concerns a. G 4. Lactose is also an acceptable alternative in the conscious patient. Dopamine agonist 1. b. Use caution when performing tasks that require mental alertness. Agents a.. Indication: DPP-IV inhibitors are appropriate for use in individuals with T2DM with normal or impaired hepatic and renal function. Administration and dosage (Table 46-3) 6. which may play a role in obesity and insulin resistance. myocardial in. Linagliptin (Tradjenta) 2. Notify prescriber if develop signs/symptoms of pancreatitis (e. Persons with gastroparesis or other severe GI motility disorders due to constipating eff ects 942 Chapter 46 V. Pancreatitis or a history of pancreatitis c. Pioglitazone/glimepiride (Duetact) J..zyme DPP-IV. b. Agent: Colesevelam (Welchol) 2. Oral medications should be taken 1 hr before or 4 hrs aft er colesevelam. Metformin/repaglinide (PrandiMet) 6. Administration and dosage (Table 46-3) 6. 5. c. Take with food to lessen gastro. Contraindications a. Rosiglitazone/glimepiride (Avandaryl): restricted access medication 9. 3. GLP-1 works to stimulate insulin secretion and decrease glucagon secretion from the pancreas during hyperglycemia. b. 4. d. Indication: adjunctive therapy for the management of T2DM 3. Exenatide (Byetta) b. or diffi culty breathing. but timing is variable for each patient. Indication: management of T2DM 3. Saxagliptin (Onglyza) c. Available oral combination products 1. Mechanism of action for improved glycemic control is unknown.g. Metformin/saxagliptin (Kombiglyze) 7. or serum triglyceride concentration 500 mg/dL. Persons with a history of bowel obstruction. Take within 2 hrs aft er waking in the morning. T1DM: DPP-IV inhibitors provide a glucose-dependent insulin secretion and thus are not appropriate for individuals with T1DM. Incretin mimetics (GLP-1 agonists) 1. or vomiting). nausea. however. H.g. 5. Dose will be increased weekly until the maxi.. Hypersensitivity reactions may include angioedema. b. Constipation is the most common adverse eff ect. or vomiting. Metformin/glipizide (Metaglip) 3. Patient education and other concerns a.g. or peptic ulcer disease. Liraglutide is contraindicated . 4.hrs of dosing. Patient education and other concerns a.. Metformin/sitagliptin (Janumet. Contraindications a.

and post-blood glucose monitoring should be used to determine effi cacy of agent.5%: Metformin is the preferred initial agent. 4. 5. therapy should be individualized. Exenatide should be administered within 60 mins of a meal twice daily.g. Sodium glucose transporter 2 (SGLT2) inhibitors: SGLT2 is a transporter in the kidneys that is responsible for approximately 90% of renal glucose reabsorption. Administration and dosage (Table 46-3) 6. Administration sites include the upper arm.presses appetite 5. taking into account the signifi . Inject at least 2 inches away from insulin individuals with a history or family history of medullary t hyroid carcinoma (MTC) and individuals with multiple endocrine neoplasia syndrome type 2 (MEN2). such as gastroparesis 4. Contraindication: Use should be avoided in individuals with gastric motility disorders. GLP-1 agonist. or abdomen. 7. Increases glucose dependent insulin secretion. or -glucosidase inhibitor may be considered when the postprandial blood glucose is of most concern. Emerging treatment options 1. b. Mechanisms of action. Agent: Pramlintide (Symlin) 2. VI. Oral medications needing rapid onset of action (e.6% to 9. Patient education and other concerns a. may produce severe hypoglycemia within 3 hrs of administration. and remoglifl ozin.0%: Dual therapy should be initiated with metformin providing the . this agent targets over-all blood glucose control rather than postprandial as seen with other GLP-1 agonists. but is typically a transient eff ect. thus increasing the urinary excretion of glucose and lower. serglifl ozin. Th ese agents are unique in that they provide an insulin-independent mechanism of action with near absence of hypoglycemia. Indication: enhanced postprandial control in individuals with T1DM or T2DM Diabetes Mellitus 943 3. decreases postprandial glucagon secretion. decreases hepatic g lucose output.sary and less pronounced gastrointestinal eff ects. metformin is the preferred initial agent for the management of T2DM. It may be used in individuals with other thyroid disorders. c. or unusual hoarseness with the use of liraglutide. Patient education and other concerns a. Slows gastric emptying. Th e SGLT2 inhibitors are proposed to inhibit this transporter. A TZD may also be initial therapy when metabolic syndrome and/or nonalcoholic fatty liver disease (NAFLD) is present. L. blood glucose levels.istered 1 hr before. 2. When concomitantly given with insulin. e. thigh. K.cance of the hyperglycemia and the desired target of therapy. d. Report unusual lump or swelling of the neck. Once weekly exenatide (Bydureon)*: Dosed once weekly as a 2 mg subcutaneous injection. c. Mechanisms of action. 1. antibiotics. Monotherapy should be tried for 2 to 3 months with the initiating agent prior to adding other agents to the regimen. Amylin receptor agonist 1. and enhances satiety. Nausea and vomiting may occur with initiation and dose changes. injection into upper arm should be avoided due to variable absorption. d. analgesics) should be admin. b. 6. increases -cell growth and replication. Weight loss is a sustained eff ect unrelated to gastrointestinal eff ects. because it takes 6 weeks for this agent to hit steady state. sup. GLYCEMIC MANAGEMENT OF T2DM A. Administration and dosage (Table 46-3) 6.clude dapaglifl ozin. Treatment based on current A1c level: a. Onset of action is approximately 2 weeks. Do not mix in same syringe as insulin. slows gastric emptying. Agents currently in clinical trials in. Administration is into abdomen or thigh. Unless contraindications exist. Initiation of therapy.5% to 7.. Pre. but a DPP-IV inhibitor. or 2 hrs aft er pramlintide. diffi culty swallowing. Liraglutide may be dosed independent of meals once daily. including hypothyroidism or hyperthyroidism. b. there is no dose titration neces.

A GLP-1. abdominal pain). nausea. Maintaining glycemic control should also be individualized. HYPERGLYCEMIC EMERGENCIES. 4. DPP-IV inhibitor. VIII. 1. and electrolyte imbalance. likely due to severe metabolic changes. but 600 mg/dL.0% (1) Symptomatic: Insulin with or without additional oral agents (2) Asymptomatic: Dual or triple oral therapy with metformin as the backbone. HHS predominantly aff ects elderly individuals and is an extreme manifestation of impaired glucose regulation. c. sulfonylurea.. delay in diagnosis. TZD. A. Consideration should be given to initiating insulin if more than three oral agents are needed to maintain glycemic control or if the A1c remains 8. which leads to hypotonic fl uid losses. Bydureon (long-acting exenatide) was FDA-approved for once weekly injection as adjunct therapy in the management of type 2 diabetes. or other medical complications that can aff ect the elderly . B. DKA. rapid breathing). and mental status changes. polydipsia. and electrolyte imbalance. Pathophysiology a. or have gastrointestinal symptoms (e. or long-acting basal insulin b. resulting in hyperglycemia (2) impairs protein synthesis and promotes breakdown of protein. Treatment may include any of the following as necessary: IV fl uids. Targeted blood glucose control a. Th e chosen therapy should be continued for 2 to 3 months before consideration of an additional agent for glycemic control. Treatment is focused on correction of dehydration. but can also occur in those with T2DM. unless contraindicated.tive urine and serum ketones. Fasting blood glucose target: consider metformin. Signs and symptoms oft en include those typical of hyperglycemia (e. acarbose).g.3. dehydration. which is caused by profound insulin defi ciency.g. and electrolyte depletion. hyperglycemia. potassium. have a fruity odor to the breath. polyuria. Persons may appear lethargic. It is characterized by hyperglycemia.backbone of therapy. Management. meglitinide. Kussmaul respirations (deep. arterial pH 7. typically occurs in persons with T1DM. posi. Insulin defi ciency leads to the following actions: (1) impairs glucose uptake in the peripheral tissues. DKA and HHS diff er in the presence of ketoacidosis and the degree of hyperglycemia (Table 46-4). weight loss. Th erapy with data to delay or prevent the disease progression include metformin. TZD. ketosis.. miglitol. 944 Chapter 46 VII VII. Precipitating factors: illness or infection. Hyperglycemia causes osmotic diuresis. or -glucosidase inhibitor B. thus leading to a loss of lean body mass (3) increases hydrolysis of triglycerides. *In January 2012. and alpha-glucosidase inhibitors (e.lin. dehydration. sodium bicarbonate 15 mEq/L 5.g.. Postprandial blood glucose target: consider GLP-1 agonist. sulfonylurea. blurred vision). 9. HHS is associated with a higher mortality than DKA. 2. or meglitinide may be used in combination with the metformin. and/or sodium bicarbonate. 2. Mixing of the agent is required immediately prior to injection. Th e two most common hyperglycemic emergencies are diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS). insulin. PHARMACOLOGIC THERAPY OF PREDIABETES. which leads to increased hepatic glucose production (further hyperglycemia) and formation of ketone bodies b. inadequate dosing of insulin or discontinuation of insulin 3. vomiting. orlistat. Laboratory fi ndings typically include plasma glucose level 250 mg/dL. rapid-acting insu. dehydration. pioglitazone.5% with dual oral therapy.

1. abdominal pain) Present Negative Serum or urine ketones (nitroprusside reaction) Positive Minimal to none Kussmaul respirations Positive Negative Arterial pH 7.g. nausea. vomiting.3 7. Table 46-4 RECOGNITION OF DKA AND HHS3 DKA HHS Onset Sudden Gradual Affected individuals T1DM (occasionally T2DM) Elderly Plasma glucose Between 250 mg/dL and 600 mg/dL 600 mg/dL Gastrointestinal symptoms (e. However.. HHS does diff er from DKA in that insulin defi ciency is not as profound. thus increased lipolysis does not occur. Pathophysiology: Th e pathogenesis of HHS is not as clear as DKA.individual.3 Serum osmolality 2[(sodium .

immediate hunger. minimal to no ketones.. hypertonic feedings. providing 5 to 10 g of a rapid-acting glucose source can diminish the symptoms without causing signifi cant elevations in blood glucose. However. Diabetes Mellitus 945 Individuals with HHS do have osmotic diuresis that produces dehydration. polypha. Symptoms of mild hypoglycemia include sweating.g. Diabetes Care 2003. argumentativeness. Laboratory fi ndings typically include plasma glucose levels 600 mg/dL. 5. T1DM. Signs and symptoms may include hyperglycemic symptoms (e. and high serum osmolality (measure of dehydration). syrup. Treatment 1. may be given by SQ or IM injection. Th e blood glucose level should be rechecked 15 to 20 mins aft er treatment. normal arterial pH. in HHS. lethargy. 4. 3 pieces of peppermint candy) to raise the plasma glucose level 30 to 45 mg/dL. Some individuals may have neuroglyco. E. severe burns. 2. poor nutrition.gia. type 1 diabetes mellitus. symptoms are the driving determinant rather than an absolute glycemic value since the threshold for the onset of symptoms varies among individuals. or euphoria. so a small snack should be eaten when the individual is able. or jelly placed inside the individual’s check. shaking. Hypoglycemia is diffi cult to defi ne. the person should eat or drink 10 to 15 g of a fast-acting glucose source (e. if possible. decreased wound healing). excess of glucose-lowering agents (insulin or insulin secretagogues). Causes can include advanced age.treat due to mental confusion. polydipsia.mately 1. C. Precipitating factors: illness or infections. IX.5 hrs). lethargy and mild con. or strenuous activity. dialysis. D.suming further carbohydrates. 2. excessive fl uid loss secondary to hyperglycemia. or the use of diuretics 3. and lack of coordination. Mild hypoglycemia: Individuals should check their blood glucose level prior to treating. however. Other types of hypoglycemia 1. or unconsciousness. so the treated person may not immediately feel like con. A. Defi nition. however. B. inappropriate giddiness. However. or slightly above normal. diabetic ketoacidosis. If plasma glucose levels are 50 mg/dL. Some literature states that there is no need to treat pseudohypoglycemia. Position statement: Hyperglycemic crises in patients with diabetes. 3American Diabetes Association. type 2 diabetes mellitus. and hypotonic fl uid loss to a greater extent than seen in DKA. If this is not possible. normal sodium bicarbonate level.g. treatment with 20 to 30 g of carbohydrate may be necessary. caution should be used with aggressive fl uid replacement to avoid fl uid overload in elderly individuals. Treatment goals are similar to DKA. polyuria. c onfusion. If the blood glucose level is low. but typically is represented by plasma glucose levels 70 mg/dL.glucose)/18] Variable 320 mOsm/kg Sodium bicarbonate 15 mEq 15 mEq DKA. Severe hypoglycemia occurs when an individual is unable to self.26:s109–117. Hypoglycemia is the limiting factor for providing aggressive insulin therapy in individuals with T1DM or T2DM. renal disease. but the blood glucose level may be normal. Hypoglycemia unawareness . 2. the glycemic response to glucagon is transient (approxi. severe diarrhea. electrolyte depletion. HHS. Pseudohypoglycemia occurs when the individual perceives hypoglycemic symptoms. If blood glucose levels are low. Nausea and vomiting are primary adverse eff ects of a glucagon injection. which stimulates hepatic glucose production.fusion).. blurred vision. T2DM. hyperosmolar hyperglycemic state. glucagon. Severe hypoglycemia: Individuals able to swallow may be treated with glucose gel. or focal neurological signs that mimic a cerebrovascular accident.. vision changes. 4 oz of fruit juice or regular soda.penia and present with symptoms of crying.g. HYPOGLYCEMIA. decreased mentation (e. then hypoglycemia treatment can be repeated.

whereas in T2DM. Th e goal blood pressure should be 130/80 mm Hg. b. but they may be recognized too late to allow for timely treatment. diabetes is the leading cause of new blindness in the United States. but diabetic retinopathy is the most common. Eye disease. men age 50 or women age 60 with another CVD risk factor).phropathy. Lifestyle modifi cations should include reduction in sodium intake ( 1500 mg/day). PDR occurs in response to the lack of oxygen following capillary closure. Aspirin (75 to 162 mg/day) should be considered for primary prevention in those with T1DM or T2DM who are at increased cardiovascular risk (e. retinal detachment). smoking cessation. and peripheral vascular disease. Attention to multiple risk factors (e. Aspirin is currently not recommended for primary prevention in individuals with diabetes who are at low CVD risk because risks outweigh benefi ts. respectively. 1. B. Statins are the drug of choice in lowering LDL levels and should be initiated in any patient with overt CVD and any patient over the age of 40 without overt CVD but with other CVD risk factors. the focus should return to lowering the LDL levels.g. and increased consumption of fresh fruits and vegetables. vitreal hemorrhage. CHRONIC COMPLICATIONS A. 3. but this may require more than 2 agents at maximum doses in the individual with diabetes. resulting in leakage of blood components through the vessel walls.. it is part of the conglomeration of cardiovascular risk factors. a.toms disappear. c. increased physical activity. but the benefi ts of aspirin for primary prevention is more contro. weight loss (if appropriate). New vessels are formed along the surface of the retina. to meet the blood pressure goal. However. When controlled. Initial therapy should be with either an ACE-I or ARB. such as those associated with neuroglycopenia. and antiplatelet therapy) for prevention of these complications is paramount in the diabetes care plan. Smoking cessation should be recommended at every visit for individuals who smoke because nicotine contributes signifi cantly to the development of both macrovascular and microvascular complications of diabetes. Of note. is 25 times more common in the individual with diabetes.occurs when hormonal counterregulation and autonomic symp.versial. Several signifi cant diabetic eye complications can occur (e. Aspirin should be used as secondary prevention in any individual with diabetes and a history of CVD. Th ese events occur earlier and at a higher rate in those with diabetes than those who do not have diabetes. 2. A goal). Cause: Diabetic retinopathy occurs when damage occurs to the retinal blood vessels. a. regardless of baseline LDL. correcting poor glycemic control will have positive impact on the triglyceride levels. However. individuals do typically have select symptoms. In fact. If aspirin cannot be tolerated. considered a microvascular complication. lipids. 2. Classifi cation: Retinopathy may be classifi ed as proliferative diabetic retinopathy (PDR) or nonproliferative diabetic retinopathy (NPDR). 1. 4. clopidogrel 75 mg/day should be used. Macrovascular complications include three major types: coronary artery. blood pressure. but these new vessels are weak and prone to . Hypertension: Development of hypertension in persons with T1DM is oft en the result of ne.g. Dyslipidemia: Th e primary focus of lipid management is to lower LDL to 100 mg/dL in those without overt CVD and 70 mg/dL in those individuals with overt CVD (optional 946 Chapter 46 X... the triglyceride value may be the primary target when it exceeds 400 mg/dL. a thiazide diuretic can be added. X.g. if necessary. Antiplatelet therapy: Aspirin therapy has cardiovascular morbidity and mortality data when used as secondary prevention. Goals for HDL and triglycerides levels are 40 mg/dL and 150 mg/dL. cerebral vascular.

Screening should occur at least annually with several simple clinical tests. fever. which is the leading cause of end-stage renal disease (ESRD). or opioids. leading to vitreous hemorrhage and/or macular edema. b. C. and avoidance of nicotine-containing products. 2. Prevention: attaining and maintaining glycemic and blood pressure control. PDR can be treated with panretinal photocoagulation to reduce severe vision loss. 1. NPDR can range from mild to severe and is typically progressive. which ranges from Stage 1 (kidney damage with GFR 90 mL/min) to Stage 5 (kidney failure with GFR 15 mL/min or dialysis).striction. is a major pathophysiologic risk factor for foot ul.rupture. numbness. b. Albumin-to-creatinine ratio in random spot collection can be used to screen for microalbu.minuria or macroalbuminuria. serum creatinine. a. or tingling in the lower extremities. a. Autonomic neuropathy involves multiple systems throughout the 6month period to classify an individual as having microalbuminuria or macroalbuminuria. Scr levels can then be used to determine an estimated GFR for staging chronic kidney disease. Levels may be aff ected by exercise within 24 hrs.betic nephropathy. and genitourinary systems. Diabetic nephropathy. Diabetic neuropathies include distal symmetric polyneuropathy (DPN) and autonomic neuropathy.ceration and amputation. dietary protein re. infection. a. Visual alteration can range from mild blurring of vision to severe visual obstruction. 4. Serum creatinine is Diabetes Mellitus 947 used to estimate the glomerular fi ltration rate (GFR) and stage the level of chronic kidney disease (CKD). D. Presentation: Clinical . then in the fi ngers and hands. c. Treatment is for symptomatic relief and may include antidepressants.bration perception (using a 128-Hz tuning fork) and 10-g monofi lament pressure sensation. NPDR occurs prior to growth of new blood vessels along the retina and may remain asymp. Routine dilated eye exams should oc. Approximately 20% to 40% of individuals with diabetes will develop dia. but the standard recommendation is an annual exam.cur within 5 years of diagnosis of T1DM and at diagnosis of T2DM and annually thereaft er. Peripheral neuropathy. Presentation: DPN occurs at the most distal portions of the lower extremities in a “stocking and glove” pattern. gastrointestinal. Assessment: Persistent microalbuminuria is the earliest stage of kidney disease in individuals with T1DM and a marker for the future development in those with T2DM. or signifi cant hyperglycemia or hypertension. b. Serum creatinine should be measured at least annually. ARBs have data to support their use in individuals with T2DM and macroalbuminuria. Treatment for microalbuminuria or macroalbuminuria should be with an ACE-I or ARB to slow the progression of renal disease.tomatic for years. achieving lipid goals. Protective sensation is fi rst diminished in the toes and feet. Prevention measures include optimizing control of blood glucose and blood pressure. Markers of kidney damage (e. heart failure.cular. urine microalbumin levels) are used to detect early stages of kidney disease. 3. (1) Classifi cation (a) Normal: 30 g/mg creatinine (b) Microalbuminuria: 30 to 299 g/mg creatinine (c) Macroalbuminuria : 300 g/mg creatinine (2) Interpreting results: At least two positive screenings should occur within a 3. also known as DPN.g. and the use of ACEI or ARB 3. Treatment: NPDR management is by observation and modifying risk factors. Some individuals may be cleared to have eye exams performed at 2-year intervals. anticonvulsants. including the vi. Aff ected individuals may complain of burning. 1.inine ratio.. 2. regardless of the albumin-to-creat. including the cardiovas. due to the variability in urinary albumin excretion.

constipation. D. Medical Nutrition Th erapy (MNT) is nutrition care that provides assessment.cept is to divide and fi ll a standard-sized dinner plate as follows: half of plate with nonstarchy veg. recognition.g. beans. noodles). 1. for diabetes typically involves signifi cant lifestyle changes.. one-fourth of the plate with meat (3 oz.. leading to mac. 2. Foods that con. glucose. Th e con. XI. a. lipid.thostatic hypotension. erectile dysfunction. creams.etables (e..g. broccoli. However. cuts. stress. and hypoglycemia u nawareness. particularly for the postprandial blood glucose levels.. based on the amount of carbohydrates in diff erent food groups. dietary choices. milk. Self. exercise intolerance. breads. or ir. goal set. and blood pressure goals 2. Pattern control to determine eff ect of sickness. bread. beans. Achievement of glycemic.. Treatment: Improve glycemic control. Dental care. cabbage. A should not be eliminated from the meal plan. Reduction of modifi able risk factors to minimize or prevent the development of chronic c omplications 1. or. looking for abnormalities (e.eration. Physical activity may be gradually incorporated into daily routines with the goal of at least 150 mins per week of moderate-intensity aerobic exercise. Exchanges. PATIENT EDUCATION AND SELF-CARE. Shoes should be properly fi tted and free of foreign objects. and evaluation of outcomes in an attempt to attain and maintain optimal metabolic control (e. Peripheral neuropathy and peripheral vascular disease in individuals with T1DM or T2DM increase the likelihood of developing lower extremity complications and goals should be provided for individuals diagnosed with diabetes and prediabetes. F. Lifestyle changes can oft en be diffi cult and therefore require positive reinforcement and involvement of the person with diabetes in the decision-making process.ritated areas). Reduction in weight. Prevention.g. Toenails should be trimmed straight across with the edges fi led. Implementation of specifi c self-care measures 1. Education and development of self. or ointments applied between the toes may lock in moisture. education. potatoes. corn. Muscle strengthening activities should be performed at least 2 or more days per week. c. d. Lotions. and treatment of acute hypoglycemic and hyperglycemic episodes should be reviewed at every opportunity. Proper foot care is essential to minimize these risks. rice. symptoms associated with the gastrointestinal and gen. collards). A.itourinary tracts may be improved with pharmacologic agents. A serving of fruit may also be combined with the meal in addition to the plate described (Figure 46-1). Carbohydrate counting: Consistency in carbohydrate intake at meals and snacks is essential for achieving glycemic control.tain a signifi cant amount of carbohydrates (e. sores. Total carbohydrate intake should be the focus. B. Smoking cessation 3. b.g. Foot care. blisters. but protein and fat intake should also be considered due to comorbid conditions (e. cooked). one-fourth of plate with starch (e. and physical activity on ability to attain and maintain glycemic goals. and blood pressure goals).manifestations include resting tachycardia. C. 2. A . salad. Shoes should be worn at all times to avoid trauma to a bare foot. Medical attention should be sought if abnormalities are present. if appropriate E. lipid. Th e plate method is a tool to provide portion control with healthier food group choices. Th e feet should be inspected daily. fruit. but progression of the disease will not be aff ected. and potatoes) 948 Chapter 46 XI. but incorporated at regularly scheduled intervals.g. were previously recommended for regulating blood glucose levels. this strategy has been replaced by carbohydrate counting and the plate method. nephropathy. Avoid applying these agents between the toes.. b. cardiovascular disease) associated with diabetes. including dietary changes and activity implementation.

Conditions when alternate site testing may be appropriate include: (1) In pre-meal or fasting state ( 2 hrs since last meal) . others on cost. 0. Needle length: available as original ½ inch (12. higher gauge needles are typically shorter needles. and 1. they are also more fragile. A plethora of meters are available to patients today.30-mL) c. An annual dilated eye exam should be recommended. it is not appropri. Kwikpen (Eli Lilly products): lispro (Humalog).ance of the meter. a. lispro mix (Humalog Mix 50/50. Children usually do better with a meter that requires only a minimal amount of blood sample applied to the strip. Markings may diff er based on size of insulin syringe barrel chosen. Eye care.3-. Barrel sizes include 0. Th us. Syringes up a dose of insulin. Typical gauges for insulin administration range from 28 to 31 gauge. When recommending a meter for an elderly patient. up to 50 units of insulin:0.7 mm) and short 5/16 inch (8 mm) 3.25 cc ( on the development and severity of eye disease.25-mL) b. 3/16 inch (5 mm) d. XII. the higher the gauge.3 cc (0. examination of the gums is essential due to the high prevalence of periodontal disease in this population. Devices a.25-. aspart (Novolog). Barrel size: Syringes for insulin administration are marked in units. Pen needles are available in several lengths: a. Because higher gauge needles are thinner. glulisine (Apidra) b.0 mL) 2. Alternate site testing has become more prominent in all populations. DEVICES FOR DIABETES A. Most devices are prefilled with insulin and are disposable.7 mm) b. Needle gauge simply refers to the “thickness” of the needle and is an inverse relationship (i. 1. ½ plate of nonstarchy vegetables ¼ plate of meat ¼ plate of starch 1 fruit serving Sugar-free beverage Figure 46-1. the cost of the meter and the manual dexterity and vision of the individual should be kept in mind. 5/32 inch (4 mm) C. Meter choices for the visually impaired have tactile markings on the strip or speech output on the meter. 5/16 inch (8 mm) c. aspart mix (Novolog Mix 70/30) c. Home blood glucose monitors.e. It is important to note that insulin pens are for single-person use to prevent the spread of blood-borne illnesses. and still others on appear. Flexpen (Novo Nordisk products): detemir (Levemir).0-mL capacity. However.yearly dental exam is recommended. B. ½ inch (12. 75/25) 2. Meter selection: Some patients choose meter on size. 3. depend.ate in all situations. 0. Solostar (Sanofi Aventis products): glargine (Lantus). up to 30 units of insulin: 0. up to 100 units of insulin: 1 cc (1. beginning 5 years aft er diagnosis of T1DM and at diagnosis of T2DM. Increased frequency of eye exams may be necessary. The plate method.. Diabetes Mellitus 949 Th e recommendation of a particular size of insulin syringe should be the smallest capacity size available for the prescribed dose of insulin: a. the thinner the needle). up to 25 units of insulin: 0.5-. Insulin pens allow for enhanced portability and eliminate the need for coordination in draw. 2. 1. In the absence of teeth in the adult with diabetes.50-mL) d.5 cc (0.

furosemide. Which is the most appropriate treatment to bring his blood glucose to a target of 120 mg/dL? (A) Glargine 20 units (B) Lispro 60 units (C) Aspart 30 units (D) Glulisine 11 units (E) Detemir 24 units 5. protease inhibitors. Which patient meets the diagnostic criteria for diabetes. His fi ngerstick blood glucose value is 452 mg/dL (445 mg/dL on repeat) and his urine is negative for ketones. A 45-year-old obese female has just been diagnosed with diabetes. Otherwise. 2. 1. probenecid 950 Chapter 46 Study Questions Directions: Each of the questions. thiazide diuretics B. Th is is only a partial list of potential drug interactions that may aff ect glycemic control. Potential hypoglycemia. direct glucogenic eff ect. A 400-lb male has just been diagnosed with type 2 . chloramphenicol. statements. she is healthy with no other medical conditions. phenytoin. (B) A teenage boy with a fasting blood glucose of 128 mg/dL and an A1c of 6. salicy. -Blockers D. he may be treated in the offi ce for hyperglycemia. A.lates. sympathomimetics. Altered protein binding of. or other drug interaction with. Consult standard references or drug package inserts for more detailed information. methyldopa. alcohol. XIII. sulfonylurea agents. isoniazid. nonsteroidal anti-infl ammatory drugs (NSAIDs). LDL 122. as a direct hypoglycemic eff ect. spot urine microalbumin 30. Her blood pressure today is 110/75 mm Hg. (D) A morbidly obese male with a random blood glucose value of 102 mg/dL and an oral glucose tolerance test result of 160 mg/dL. or incomplete statements in this section can be correctly answered or completed by one of the suggested answers or phrases. HDL 32. Choose the best answer. 24 units in the morning and 12 units in the evening. Corticosteroids.(2) 2 or more hours aft er taking insulin (3) 2 or more hours aft er exercise b. which would be the most appropriate recommendation for his glycemic control today? Pre-Breakfast: 220 mg/dL Pre-Lunch: 110 mg/dL PreSupper: 90 mg/dL Bedtime: 108 mg/dL 3 am: 62 mg/dL (A) Increase evening dose of Humalog Mix to 15 units (B) Decrease evening dose of Humalog Mix to 10 units (C) Continue current regimen without changes (D) Increase morning dose of Humalog Mix to 28 units (E) Decrease morning dose of Humalog Mix to 20 units 4. TC 180.tors. pentamidine (long-term eff ect). salicylates (large doses). fl uoxetine. A patient is currently on a regimen of Humalog Mix 70/30. monoamine oxidase (MAO) inhibitors. clofi brate. Potential hyperglycemia. (C) A 10-year-old girl with a random blood glucose value of 180 mg/dL and 190 mg/dL. pentamidine (initial eff ect) C. Based on the following averages obtained from his blood glucose meter. MAO inhibi. Alcohol. assuming tests were taken on separate visits? (A) An elderly female with fasting blood glucose values of 102 mg/dL and 132 mg/dL.6%. fenfl uramine. Alternate site testing should not be used if: (1) Th e results from the alternate site do not match how the person feels (2) Symptoms of hypoglycemia are present. A 222-lb male presents to the diabetes care team for routine diabetes management. nicotinic acid. TG 150. as a dose-dependent. SIGNIFICANT DRUG INTERACTIONS AFFECTING GLYCEMIC CONTROL. Prolonged hypoglycemia and masking of hypoglycemic symptoms. which should be started today? (A) Aspirin 81 mg daily (B) Pravastatin 10 mg daily (C) Lisinopril 10 mg daily (D) Irbesartan 150 mg daily 3. Based on ADA guidelines. Per clinic protocol.

He does not eat lunch.d.i. He takes his morning medications at 8 a.2% and he has hepatitis C (AST 150 units/L. (E) Glimepiride 4 mg q. prednisone. Based on her weight of 100 lb. and Lantus. He weighs 228 lb. U-100 (C) NPH insulin. His current medication list includes albuterol nebules.d.d. His A1c today is 6. (D) Th e patient has hyperglycemia induced by his oral glucocorticoid.m. A patient currently takes Amaryl. which would be the most appropriate basal regimen? (A) Levemir 13 units daily (B) Lantus 27 units daily (C) Novolog 4 units three times daily (D) NPH 15 units once daily (E) U-500 1. and sitagliptin for T2DM.. Blood work today shows a random blood glucose of 320 mg/dL and an A1c of 5. Her liver function tests were elevated (AST 132 u/L and ALT 140 u/L) and she tested positive for Hepatitis C. (B) Pioglitazone 30 mg q. ALT 132 units/L). (D) Liraglutide 0. (B) Th e patient has hyperglycemia induced by his inhaled corticosteroid. signifi cant weight gain. A patient has been hospitalized for the past 3 days following a severe asthma exacerbation. but he has no previous history of diabetes. Which would be the best initial agent at this time? (A) saxagliptin (B) metformin (C) pioglitazone (D) glulisine 14. which reveal multiple hypoglycemic events (45 to 62 mg/dL) around 1 p. His A1C is 7. dyslipidemia.6 mg q. Which would be the most appropriate recommendation for glycemic control at this time? (A) Discontinue morning dose of metformin (B) Discontinue evening dose of metformin (C) Discontinue daily dose of pioglitazone (D) Discontinue morning dose of glimepiride (E) Discontinue evening dose of glimepiride 7. and oxygen. A 64-year-old female is taking metformin. Which is the best recommendation at this time? (A) Discontinue metformin only (B) Discontinue pioglitazone only (C) Discontinue sitagliptin only (D) Discontinue metformin and pioglitazone (E) Discontinue all agents for glycemic control Diabetes Mellitus 951 8. and shortness of breath. Which is the most likely cause of presenting symptoms? (A) Amaryl (B) Actos (C) Januvia (D) Lantus 11. to 2 p. Which best describes the mechanism of action of repaglinide? (A) Insulin secretagogue (B) Insulin sensitizer (C) DPP-IV inhibitor (D) GLP-1 agonist (E) -glucosidase inhibitor 9. and mild renal impairment (SCr 1.m. rheumatoid arthritis. U-100 (D) Aspart insulin.d.6). Which would be the most appropriate . (C) Glargine 36 units q. His A1c is greater than 15% and his kidney and liver function are normal. Which would be the most appropriate initial agent for monotherapy? (A) Metformin 850 mg q.d.i. U-500 (B) Regular insulin. He presents to the clinic today concerned about the swelling in his lower extremities. pioglitazone 45 mg. An obese woman (350 lb) has used metformin 1000 mg bid to control her T2DM for the past 2 years. pulmicort. hypertension. U-400 13. Which statement is most appropriate? (A) Th e patient has diabetes and should be discharged on an insulin regimen. Her A1C today is 8%.m. An individual with T2DM currently takes metformin XR 500 mg 2 b. but is being discharged today.d. with supper.m. Januvia. A person newly diagnosed with T1DM will need to start an insulin regimen. A patient presents for treatment of his type 2 diabetes mellitus (T2DM). Which formulation is the best recommendation for a patient needing an intravenous insulin infusion? (A) Regular insulin. 10. pioglitazone. Actos. (C) Th e patient has hyperglycemia induced by his agonist. He brings in his log book and meter today.5 mL twice daily 12. U-100 (E) Aspart insulin. with breakfast and his evening medications at 6 p.2%.diabetes.d. and glimepiride 4 mg b. 6.0%.

A.8. thus he would not choose glargine or detemir as agents due to their longer onset of action.bumin is 30.8 units/hr with steady control aft er being diagnosed with type 1 diabetes mellitus (T1DM). Lispro. and glulisine would all be appropriate choices. Steps to solve: 1. with this patient’s A1c greater than 15%.A. Oral agents and non-insulin injections will bring the A1c down no greater than 1%. Th e answer is B [see X. Based on ADA guidelines. aspart. A patient takes neutral protamine Hagedorn (NPH) 16 units bid and regular insulin 6 units bid. However. Determine TDD: (101)(0. aspirin should be initiated for primary prevention in women greater than age 60. OGTT 200. Th e answer is B [see Table 46-2.1].5 hours aft er discontinuing the continuous insulin infusion (E) 3 hours aft er discontinuing the continuous insulin infusion 952 Chapter 46 Answers and Explanations 1. but the dose should be based on the pointof-care cor. Based on her average blood glucose values below.rection equation ([Current blood glucose-Target blood glucose]/CF). When is the most appropriate time to initiate the detemir? (A) 30 minutes prior to discontinuing the continuous insulin infusion (B) 1 hour prior to discontinuing the continuous insulin infusion (C) 2 hours prior to discontinuing the continuous insulin infusion (D) 1.a].b]. Th e answer is B [see III. 4. Plug into equation: (452–120)/30 11 units 5. fasting blood glucose 126 mg/ dL.betes in the nonpregnant individual is a positive of at least two of the following values: random blood glu.A. insulin is the most appropriate choice. Metformin can be started in addition to the insulin.1. but not as monotherapy. 3. even more. what is the best recommendation for adjusting her insulin regimen? (A) fasting: 82 mg/dL (B) pre-lunch: 180 mg/dL (C) pre-supper: 110 mg/dL (D) bedtime: 98 mg/dL 17. Th e blood glucose needs to come down rapidly in. Metformin would typically be the initial agent of choice in a patient diagnosed with type 2 diabetes. He is to be discharged from the hospital with prescriptions for detemir and glulisine. Determine CF: 1800/60 30 4.A. Weight in kg: Weight is 222lb 101 kg 2.cose 200 mg/dL.offi ce. ACEI and ARBs are recommended for blood pressure control if necessary (not needed here) and when urine microal. diagnostic criteria for dia. A1c 6.recommendation to improve glycemic control without providing further weight gain? (A) sulfonylurea (B) thiazolidinedione (C) GLP-1 agonist (D) amylin agonist 15.B].m.m. (D) metformin may cause vitamin B12 depletion. Th is patient is most likely experiencing rebound hyperglycemia (Symogyi) as evidenced by the hypoglycemia at the 3 a. A patient has been using continuous intravenous i nsulin infusion at 0.7.6) 60 3.5%. Th e answer is D [see V. Regardless of age or gender. . V. readings and elevated fasting readings pre-breakfast. (B) metformin should not be used in patients who are alcoholic. but with other CVD risk factors. Increasing the evening dose will lower the 3 a. All of the following are correct statements about metformin except (A) metformin may cause renal impairment. statin therapy should be initiated in patients with overt CVD or any patient over the age of 40 without overt CVD.c]. 16. Th e answer is C [see VI. Increasing the morning dose will only lower the lunch and supper readings further.4. 2. (C) metformin should be discontinued in women with a SCr 1.

A].A.6. Saxagliptin may be used in patients with hepatic and renal impairment.D.B. Repaglinide is a meglitinide. However. 9. Amylin agonist is not appropriate because it should only be added aft er a basal and bolus insulin have been added. U-100 is the most logical choice for an IV infusion. Th e answer is A [see V. Th e answer is D [see III. 17. XIII.A.3. Both sulfonylureas and TZDs have the potential to increase weight.b.a. Th e answer is B [see V.a.F. hypoglycemia results.9.2. but the metformin itself does not cause renal impairment.B. Diabetes Mellitus 953 14.6.3. In the absence of lunch. Th e answer is A [see V.C.B. V. Th e answer is A [see V. NPH is dosed twice daily. 10. NovoLog is not a basal insulin and U-500 is reserved for patients with severe insulin resistance.tored for peripheral edema. which is compounded by the fact that the patient does not eat lunch. Patients taking a TZD such as Actos should be moni. which works to produce a rapid burst of insulin secretion from the pancreas.a].6. Basal insulin should be initiated at 50% of TDD.F]. Increasing morning NPH will cause further decrease of presupper reading.b].C. such as predni.B.sulin will cause fasting blood glucose to be too low. Table 46-3].sone can induce signifi cant hyperglycemia. Inhaled corticosteroids have no eff ect on the blood glu. but is not con. Table 46-3].(2)].A. 8.9. Metformin and pioglitazone should not be used in a patient with liver disease and elevated LFTs. 13. Th e answer is D [see V.a.6. but should not be given routinely due to the additional cost above that of regular U-100 insulin. Th e answer is C [seeV. TDD is 27 units. Th e answer is B [see V. Table 46-2]. Table 46-3]. whereas GLP-1 agonists and amylin agonists can provide weight loss. V. Rapid acting insulin would help with postprandial blood glucose values.3.ate metformin and pioglitazone.a]. Th e answer is A [see V. Th e morning dose of glimepiride would peak around lunch time when food intake should be occur. Th e answer is C [see V.a. 7.b]. Metformin should not be used in patients with renal disease. Th e answer is B [see V. 11. Regular insulin. weight gain. Aspart may be given in an emergency preparedness situation.sidered a standard recommendation for initial insulin therapy in T2DM. which gives 13. oral steroids. particu.ring.a].A. Metformin and pioglitazone should not be used in liver impairment and metformin must be used cautiously in renal impairment.b.D. Th e pharmacologic agent most responsible for causing hypoglycemia is the sulfonylurea (glimepiride).1.D. Sitagliptin may be used in hepatic impairment.cose of an individual without diabetes and agonists have no eff ect.1.8. and shortness of breath due to its propensity to cause or worsen heart failure. 16. 12.larly in the midaft ernoon when dosed in the morning. VI.6. . V. 15. it can be considered to reiniti. Long-acting insulin should be injected 2 hours prior to discontinuation of a continuous insulin infusion to allow adequate onset time.A.5 units as basal. Th e answer is D [see V.1.b. When the LFTs go back to a normal range. Increasing evening doses of in.