Overview Goals of diabetes treatment lower serum glucose to physiologic range keep insulin levels in physiologic range eliminate insulin resistance best initial step in management: weight loss, contractile-based exercise weight loss is more important for insulin sensitivity than is a low-carb diet Modalities of diabetes treatment type I DM insulin low-sugar diet type II DM exercise diet insulin 6 classes of drugs shown below Class Example ↑ Insulin secretion ↑ Insulin utilization ↓ Glucose production ↓ Glucose absorption Weight Hypoglycemia Insulin Insulin ↑ ++ Sulfonylureas Glyburide ++ + + ↑ ++ Meglitinides Nateglinide ++ + + ↑ ++ Biguanides Metformin + ++ None Glitazones (thiazolidinediones) Pioglitazone ++ +/- ↑↓ + α-glucosidase inhibitors Acarbose ++ None GLP-1 mimetics (incretin mimetics) Exenatide ++ + ↓ + Amylin analog Pramlintide + + + Insulin Insulin is only given parenterally (subcutaneous or IV) Various preparations have different durations of action Other preparations include aspart (rapid), detemir (long) Preparation Onset (hrs) Peak (hrs) Duration (hrs) Lispro (rapid-acting) 15 min 0.5-1.5 3-4 Regular (short-acting) 0.5-1 2-4 5-7 NPH (intermediate) 1-2 6-12 18-24 Glargine (long-acting) 1 None >24 Mechanism bind transmembrane insulin receptor activate tyrosine kinase phosphorylate specific substrates in each tissue type liver ↑ glycogenesis store glucose as glycogen muscle ↑ glycogen and protein synthesis ↑ K+ uptake fat increase triglyceride storage Clinical use type I DM type II DM life-threatening hyperkalemia increases intracellular K+ stress-induced hyperglycemia Toxicity hypoglycemia hypersensitivity reaction (very rare) Insulin Synthesis first generated as preproinsulin with an A chain and B chain connected by a C peptide. c-peptide is cleaved from proinsulin after packaging into vesicles leaving behind the A and B chains Sulfonylureas Drugs first generation tolbutamide chlorpropamide second generation glyburide glimepiride glipizide Mechanism glucose normally triggers insulin release from pancreatic β cells by increasing intracellular ATP → closes K+ channels → depolarization → ↑ Ca2+ influx → insulin release sulfonylureas mimic action of glucose by closing K+ channels in pancreatic β cells → depolarization → ↑ Ca2+ influx → insulin release continued use results in ↓ glucagon release ↑ insulin sensitivity in muscle and liver Clinical use type II DM stimulates release of endogenous insulin cannot be used in type I DM due to complete lack of islet function Toxicity first generation disulfiram-like effects especially chlorpropamide second generation hypoglycemia weight gain Megltinides Drugs nateglinide repaglinide Mechanism binds to K+ channels on β-cells → postprandial insulin release different site than sulfonylureas Clinical use type 2 diabetes mellitus may be used as monotherapy, or in combination with metformin Toxicity ↑ risk of hypoglycemia at even greater risk in those with renal failure weight gain Biguanides Drugs metformin Mechanism ↓ hepatic gluconeogenesis exact mechanism unknown appears to inhibit complex 1 of respiratory chain may also ↑ insulin sensitivity ↑ glycolysis ↓ serum glucose levels ↓ postprandial glucose levels Clinical use first-line therapy in type II DM Toxicity no hypoglycemia no weight gain lactic acidosis is most serious side effect contraindicated in renal failure Glitazones (thiazolidinediones) Thiazolidinediones, also known as the "-glitazones" Drugs pioglitazone rosiglitazone Mechanism bind to nuclear receptors involved in transcription of genes mediating insulin sensitivity peroxisome proliferator-activating receptors (PPARs) ↑ insulin sensitivity in peripheral tissue ↓ gluconeogenesis ↑ insulin receptor numbers ↓ triglycerides Clinical use type II DM as monotherapy or in combination with other agents contraindicated in CHF associated with increased risk of MI (in particular rosiglitazone) Toxicity weight gain edema hepatotoxicity CV toxicity less risk of hypoglycemia vs. sulfonylureas α-glucosidase inhibitors Drugs acarbose miglitol Mechanism inhibit α-glucosidases in intestinal brush border delayed sugar hydrolysis delayed glucose absorption ↓ postprandial hyperglycemia ↓ insulin demand Clinical use type II DM as monotherapy or in combination with other agents Toxicity no hypoglycemia GI upset Amylin mimetics Drugs pramlintide Mechanism synthetic analogue of human amylin that acts in conjunction with insulin ↓ release of glucagon delays gastric emptying Clinical use type I and II DM Toxicity hypoglycemia if given with insulin nausea diarrhea GLP-1 analogs Drugs exenatide Mechanism GLP-1 is an incretin released from the small intestine that aids glucose-dependent insulin secretion basis for drug mechanism is the observation that more insulin secreted with oral glucose load compared to IV exenatide is a GLP-1 agonist ↑ insulin ↓ glucagon release the class of dipeptidyl peptidase inhibitors ↓ degradation of endogenous GLP-1 e.g.) sitagliptin, -gliptins Clinical use type II DM Toxicity nausea, vomiting pancreatitis hypoglycemia if given with sulfonylureas SGLT-2 Inhibitors Drugs canagliflozin empagliflozin Mechanism glucose is reabsorbed in the proximal tubule of the nephron by the sodium-glucose cotransporter 2 (SGLT2) SGLT2-inhibitors lower serum glucose by increasing urinary glucose excretion the mechanism of action is independent of insulin secretion or action Clinical use type II DM Toxicity dehydration urinary and genital infections
QUESTIONS 1 of 13 1 2 3 4 5 6 7 8 9 10 11 12 13 Previous Next Lab Values Blood Hematologic Cerebrospinal Sweat, Urine, and BMI Blood, Plasma, Serum Reference Range ALT 8-20 U/L Amylase, serum 25-125 U/L AST 8-20 U/L Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL Calcium, serum (Ca2+) 8.4-10.2 mg/dL Cholesterol, serum Rec: < 200 mg/dL Cortisol, serum 0800 h: 5-23 μg/dL //1600 h: 3-15 μg/dL 2000 h: ≤ 50% of 0800 h Creatine kinase, serum Male: 25-90 U/LFemale: 10-70 U/L Creatinine, serum 0.6-1.2 mg/dL Electrolytes, serum Sodium (Na+) 136-145 mEq/L Chloride (Cl-) 95-105 mEq/L Potassium (K+) 3.5-5.0 mEq/L Bicarbonate (HCO3-) 22-28 mEq/L Magnesium (Mg2+) 1.5-2.0 mEq/L Estriol, total, serum (in pregnancy) 24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL 28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL Ferritin, serum Male: 15-200 ng/mLFemale: 12-150 ng/mL Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL Female: premenopause: 4-30 mIU/mL midcycle peak: 10-90 mIU/mL postmenopause: 40-250 pH 7.35-7.45 PCO2 33-45 mmHg PO2 75-105 mmHg Glucose, serum Fasting: 70-110 mg/dL2-h postprandial:<120 mg/dL Growth hormone - arginine stimulation Fasting: <5 ng/mLProvocative stimuli: > 7ng/mL Immunoglobulins, serum IgA 76-390 mg/dL IgE 0-380 IU/mL IgG 650-1500 mg/dL IgM 40-345 mg/dL Iron 50-170 μg/dL Lactate dehydrogenase, serum 45-90 U/L Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL Female: follicular phase: 5-30 mIU/mL midcycle: 75-150 mIU/mL postmenopause 30-200 mIU/mL Osmolality, serum 275-295 mOsmol/kd H2O Parathyroid hormone, serume, N-terminal 230-630 pg/mL Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L Phosphorus (inorganic), serum 3.0-4.5 mg/dL Prolactin, serum (hPRL) < 20 ng/mL Proteins, serum Total (recumbent) 6.0-7.8 g/dL Albumin 3.5-5.5 g/dL Globulin 2.3-3.5 g/dL Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h Thyroxine (T4), serum 5-12 μg/dL Triglycerides, serum 35-160 mg/dL Triiodothyronine (T3), serum (RIA) 115-190 ng/dL Triiodothyronine (T3) resin uptake 25%-35% Urea nitrogen, serum 7-18 mg/dL Uric acid, serum 3.0-8.2 mg/dL Hematologic Reference Range Bleeding time 2-7 minutes Erythrocyte count Male: 4.3-5.9 million/mm3Female: 3.5-5.5 million mm3 Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/hFemale: 0-20 mm/h Hematocrit Male: 41%-53%Female: 36%-46% Hemoglobin A1c ≤ 6 % Hemoglobin, blood Male: 13.5-17.5 g/dLFemale: 12.0-16.0 g/dL Hemoglobin, plasma 1-4 mg/dL Leukocyte count and differential Leukocyte count 4,500-11,000/mm3 Segmented neutrophils 54%-62% Bands 3%-5% Eosinophils 1%-3% Basophils 0%-0.75% Lymphocytes 25%-33% Monocytes 3%-7% Mean corpuscular hemoglobin 25.4-34.6 pg/cell Mean corpuscular hemoglobin concentration 31%-36% Hb/cell Mean corpuscular volume 80-100 μm3 Partial thromboplastin time (activated) 25-40 seconds Platelet count 150,000-400,000/mm3 Prothrombin time 11-15 seconds Reticulocyte count 0.5%-1.5% of red cells Thrombin time < 2 seconds deviation from control Volume Plasma Male: 25-43 mL/kgFemale: 28-45 mL/kg Red cell Male: 20-36 mL/kgFemale: 19-31 mL/kg Cerebrospinal Fluid Reference Range Cell count 0-5/mm3 Chloride 118-132 mEq/L Gamma globulin 3%-12% total proteins Glucose 40-70 mg/dL Pressure 70-180 mm H2O Proteins, total < 40 mg/dL Sweat Reference Range Chloride 0-35 mmol/L Urine Calcium 100-300 mg/24 h Chloride Varies with intake Creatinine clearance Male: 97-137 mL/minFemale: 88-128 mL/min Estriol, total (in pregnancy) 30 wks 6-18 mg/24 h 35 wks 9-28 mg/24 h 40 wks 13-42 mg/24 h 17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 hFemale: 2.0-8.0 mg/24 h 17-Ketosteroids, total Male: 8-20 mg/24 hFemale: 6-15 mg/24 h Osmolality 50-1400 mOsmol/kg H2O Oxalate 8-40 μg/mL Potassium Varies with diet Proteins, total < 150 mg/24 h Sodium Varies with diet Uric acid Varies with diet Body Mass Index (BMI) Adult: 19-25 kg/m2 Calculator ( ) xy AC 7 8 9 ÷ 4 5 6 × 1 2 3 - 0 . = + Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK (M1.EC.107) A 55-year-old male is hospitalized for acute heart failure. The patient has a 20-year history of alcoholism and was diagnosed with diabetes mellitus type 2 (DM2) 5 years ago. Physical examination reveals ascites and engorged paraumbilical veins as well as 3+ pitting edema around both ankles. Liver function tests show elevations in gamma glutamyl transferase and aspartate transaminase (AST). Of the following medication, which most likely contributed to this patient's presentation? Review Topic QID: 100408 1 Glargine 3% (5/178) 2 Glipizide 16% (28/178) 3 Metformin 19% (34/178) 4 Pioglitazone 58% (104/178) 5 Pramlintide 2% (3/178) M1 Select Answer to see Preferred Response PREFERRED RESPONSE 4 (M1.EC.201) A 53-year-old male presents to your office for a regularly scheduled check-up. The patient was diagnosed with type II diabetes mellitus two years ago. To date, diet, exercise, and metformin have failed to control his elevated blood glucose. Past medical history is also significant for hypertension. The patient does not smoke or use cigarettes. Laboratory values show a hemoglobin A1c (HbA1c) of 8.5%. You decide to add sitagliptin to the patient’s medication regimen. Which of the following is the direct mechanism of action of sitagliptin? Review Topic QID: 106238 1 Inhibits degradation of endogenous incretins 58% (95/164) 2 Inhibits alpha-glucosidases at the intestinal brush border 4% (6/164) 3 Activates transcription of PPARs to increase peripheral sensitivity to insulin 21% (35/164) 4 Depolarizes potassium channels in pancreatic beta cells 4% (6/164) 5 Increases secretion of insulin in response to oral glucose loads and delays gastric emptying 12% (20/164) M1 Select Answer to see Preferred Response PREFERRED RESPONSE 1 Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK (M1.EC.75) A simple experiment is performed to measure the breakdown of sucrose into glucose and fructose by a gut enzyme that catalyzes this reaction. A glucose meter is used to follow the breakdown of sucrose into glucose. When no enzyme is added to the sucrose solution, the glucose meter will have a reading of 0 mg/dL; but when the enzyme is added, the glucose meter will start to show readings indicative of glucose being formed. Which of the following diabetic pharmacological agents, when added before the addition of the gut enzyme to the sucrose solution, will maintain a reading of 0 mg/dL? Review Topic QID: 106870 1 Insulin 0% (0/7) 2 Glyburide 0% (0/7) 3 Metformin 29% (2/7) 4 Acarbose 71% (5/7) 5 Exenatide 0% (0/7) M1 Select Answer to see Preferred Response PREFERRED RESPONSE 4 (M1.EC.1) A 45-year-old African-American male presents to the family medicine physician to assess the status of his diabetes. After reviewing the laboratory tests, the physician decides to write the patient a prescription for miglitol and states that it must be taken with the first bite of the meal. Which of the following bonds will no longer be cleaved when the patient takes miglitol? Review Topic QID: 107077 1 Phosphodiester bonds 0% (0/12) 2 Glycosidic bonds 83% (10/12) 3 Peptide bonds 8% (1/12) 4 Cystine bonds 0% (0/12) 5 Hydrogen bonds 8% (1/12) M1 Select Answer to see Preferred Response PREFERRED RESPONSE 2 (M1.EC.70) A patient presents to the emergency room in an obtunded state. The patient is a known nurse within the hospital system and has no history of any medical problems. A finger stick blood glucose is drawn showing a blood glucose of 25 mg/dL. The patient's daughter immediately arrives at the hospital stating that her mother has been depressed recently and that she found empty syringes in the bathroom at the mother's home. Which of the following is the test that will likely reveal the diagnosis? Review Topic QID: 106480 1 Genetic testing 0% (0/24) 2 C-peptide level 75% (18/24) 3 24 hr cortisol 4% (1/24) 4 Fasting blood glucose 4% (1/24) 5 Urine metanephrines 4% (1/24) M1 Select Answer to see Preferred Response PREFERRED RESPONSE 2 Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK (M1.EC.1) A 45-year-old woman presents to your office with a serum glucose of 250 mg/dL and you diagnose diabetes mellitus type II. You intend to prescribe the patient metformin, but you decide to order laboratory tests before proceeding. Which of the following basic metabolic panel values would serve as a contraindication to the use of metformin? Review Topic QID: 100302 1 K+ > 4.0 12% (2/16) 2 Na+ > 140 6% (1/16) 3 HCO3- > 30 0% (0/16) 4 Glucose > 300 0% (0/16) 5 Creatinine > 2.0 81% (13/16) M1 Select Answer to see Preferred Response PREFERRED RESPONSE 5
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