(Week 12) Metabolism & Disease MCQ
A patient is experiencing uncontrolled type 1 diabetes with an overproduction of β-hydroxybutyric acid. Which statement is false? (a) The patient will exhale extra amounts of carbon dioxide. (b) Glutamine will be catabolized to reform lost bicarbonate ion. (c) The basic amino acids, lysine and arginine, neutralize the β-hydroxybutyric acid in the blood. (d) The anion of β-hydroxybutyric acid will be excreted in the urine. (e) If this condition is untreated ketoacidosis can lead to coma and death.
(c) The basic amino acids, lysine and arginine, neutralize the β-hydroxybutyric acid in the blood.
What is a cause of cataracts in the eye lens of individuals with diabetes? A) Accumulation of sorbitol and protein precipitation in the lens. B) Precipitation of glucose not oxidized by glycolysis in the lens. C) The absence of membrane transport proteins for pyruvate in the lens cells. D) Lack of regulation of gluconeogenesis in the lens and the accumulation of fructose. E) All of the above contribute to the development of cataracts in diabetes.
A) Accumulation of sorbitol and protein precipitation in the lens.
Which of the following are characteristics of metabolic syndrome? I. insulin resistance II. inflammation III. increased risk for type 1 diabetes. IV. hypersensitivity to insulin A) I, II B) I, II, III C) I, II, III, IV D) I, III E) I only
A) I, II
Excess glucosylation of lens proteins in diabetics leads to A) cataracts. B) retinal degeneration. C) glaucoma. D) ketosis. E) fatty liver disease.
A) cataracts.
Alcohol is classified as a/an A) depressant. B) hallucinogen. C) narcotic. D) stimulant. E) soporific.
A) depressant.
Insulin-dependent (type 1) diabetes A) is associated with a deficiency of pancreatic β-cells. B) is associated with a deficiency of insulin receptors. C) is associated with a deficiency of signal transduction D) can be treated with injections of leptin. E) can be treated with injections of ghrelin
A) is associated with a deficiency of pancreatic β-cells.
Which of the following represents the least invasive means to ascertain the extent to which an individual is overweight or obese? A) BMI B) glucose tolerance test to measure insulin sensitivity C) fasting lipid profile D) fasting plasma glucose concentration E) urine lipid content
Answer A: The BMI is a measure of the relationship between an individual's weight and height. The BMI is calculated by dividing a person's weight in kilograms by the square of their height in meters and is thus completely noninvasive and easy to determine. The medical utility for determining a person's BMI is that this measure describes the body weight relative to height and it, thus, strongly correlates with the total body fat content in adults.
In Type 1 diabetes, the increased production of ketone bodies is primarily a result of which of the following? A) a substantially increased rate of fatty acid oxidation by hepatocytes B) an increase in the rate of the citric acid cycle C) decreased cyclic AMP levels in adipocytes which causes accelerated fatty acid release D) elevated acetyl-CoA levels in skeletal muscle driving ketone body synthesis E) increased hepatic glucose release from glycogen driving acetyl-CoA production
Answer A: The most frequent consequence of poorly controlled T1D is ketoacidosis, referred to as diabetic ketoacidosis, DKA. The hyperketonemia in DKA is the result of insulin deficiency and unregulated glucagon secretion from α-cells of the pancreas. Circulating glucagon stimulates the adipose tissue to release fatty acids which are taken up and oxidized, primarily by the liver. Under these conditions, the level of fatty acid oxidation is in excess of the livers' ability to fully oxidize the excess acetyl-CoA and, thus the compound is diverted into ketones synthesis. The ketones are released into the circulation and because they are acidic, lower the pH of the blood resulting in metabolic acidosis.
Type 2 diabetes can best be characterized as which of the following? A) adequate insulin secretion coupled to impaired postreceptor responses B) being caused by autoimmune destruction of pancreatic β-cells C) correlated to disruptions in glucagon secretion D) lack of insulin receptors on hepatocyte E) resulting in frequent episodes of ketoacidosis
Answer A: Unlike patients with T1D, those with T2D have detectable levels of circulating insulin but these individuals are resistant to the peripheral actions of insulin. In the progression from impaired glucose tolerance to full-blown T2D, the level of insulin secretion declines indicating that patients with T2D eventually have decreased insulin secretion. Additional studies have subsequently demonstrated that both insulin resistance and insulin deficiency is common in the average T2D patient.
Alcoholism is sometimes treated with the drug disulfiram. This drug deters the consumption of alcohol by which of the following mechanisms? A) Activating the excessive metabolism of ethanol to acetate resulting in rapid inebriation with limited alcohol consumption B) Blocking the conversion of acetaldehyde to acetate resulting in rapid accumulation of toxic acetaldehyde adducts C) Inhibiting ethanol absorption so that an individual cannot become intoxicated D) Inhibiting the conversion of ethanol to acetaldehyde, thereby, causing ethanol to be excreted before it can be metabolized E) Preventing the excretion of acetate resulting in severe nausea and vomiting
Answer B: Disulfiram blocks the processing of alcohol in the body by inhibiting acetaldehyde dehydrogenase, thus causing an unpleasant reaction when alcohol is consumed due to a rapid increase in the production of toxic acetaldehyde adducts.
Type 1 diabetics frequently experience ketoacidosis. Administration of insulin decreases the serum concentration of ketone bodies in these patients via which of the following mechanisms? A) decreasing formation of ketone bodies in skeletal muscle B) decreasing lipolysis in adipose tissue C) increasing hepatic activity of carnitine acyltransferase D) increasing hepatic levels of acetyl-CoA E) increasing hepatic oxidation of ketone bodies
Answer B: Insulin action at the level of adipose tissue leads to decreased lipolysis and increased lipogenesis. When insulin binds its receptor on adipocytes it triggers activation of PDE which hydrolyzes cAMP leading to reduced levels of active PKA. Less PKA means less phosphorylation and activation of HSL. This results in less free fatty acid release so that there will be less substrate for the production of ketones by the liver.
You are treating a 38-year-old man whose chief complaint is occasional right upper quadrant pain. Analysis of blood samples shows elevated aspartate transaminase (AST) and alanine transaminase (ALT). History indicates that these same enzymes have shown elevated levels each of the past 3 years during routine blood work in conjunction with his annual physical. His history also indicates reflux esophagitis, hypertension, and hyperlipidemia. You order tests for serologic and biochemical markers for viral hepatitis and autoimmune liver disease and other metabolic liver diseases but these results are negative. The patient has gained 20 kilograms since the age of 18. He consumes less than 5 alcoholic beverages per week. Which of the following is the most likely diagnosis in this case? A) cirrhosis B) nonalcoholic fatty liver disease C) thyrotoxicosis D) Type 1 diabetes E) Type 2 diabetes
Answer B: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the Western world. NAFLD is characterized by fatty infiltration of the liver in the absence of alcohol consumption. One of the most significant contributing factors to the development of NAFLD is insulin resistance in the liver. Additional pathophysiology includes an enhanced state of hepatic oxidative stress and lipid peroxidation, decreased antioxidant defenses, early mitochondrial dysfunction, and iron accumulation.
The sulfonylurea class of drugs used to treat Type 2 diabetes function by which of the following mechanisms? A) activating the PPARγ class of factors leading to increased hepatic glucose metabolism B) binding to and blocking pancreatic K+ channels leading to increased insulin secretion C) interfering with carbohydrate digestion, thus reducing glucose intake D) restricting hepatic glucose output, thereby reducing the hyperglycemia E) stimulating pancreatic glucose metabolism leading to increased insulin secretion
Answer B: The sulfonylurea drugs function by binding to and inhibiting the pancreatic ATP-dependent K+ channel (KATP) that is responsible for glucose-mediated insulin secretion. The normal pancreatic response to increased blood glucose is an increased uptake by β-cells with concomitant oxidation. The increase in glucose oxidation leads to an elevation in the ATP:ADP ratio. This in turn leads to an inhibition of the KATP channel. The net result is a depolarization of the cell leading to Ca2+ influx and insulin secretion.
Which of the following would be evident in Type 1 diabetes? A) decreased glucagon secretion leading to hyperlipidemia. B) decreased insulin receptor response to insulin binding. C) elevated glucagon secretion leading to hyperlipidemia. D) elevated insulin secretion leading to severe hypoglycemia. E) impaired glucagon-dependent inhibition of glycolysis leading to hyperglycemia
Answer C: In addition to the loss of insulin secretion by β-cells of the pancreas in T1D, the function of α-cells is also abnormal. There is excessive secretion of glucagon in T1D patients. Normally, hyperglycemia leads to reduced glucagon secretion. However, in patients with T1D, glucagon secretion is not suppressed by hyperglycemia. The resultant inappropriately elevated glucagon levels exacerbate the metabolic defects due to insulin deficiency.
Ethanol metabolism is associated with a disruption in the NADH:NAD+ ratio. Which of the following is one major consequence of this disruption? A) Altered membrane fluidity resulting in decreased hepatocyte function B) Hyperglycemia due to increased rates of hepatic gluconeogenesis C) Increased production of glycerol 3-phosphate contributing to triglyceride production D) Increased TCA cycle activity resulting in increased oxygen consumption E) Potentiation of CNS activity
Answer C: The altered NADH:NAD+ ratio that in turn inhibits gluconeogenesis, inhibits fatty acid oxidation and the activity of the TCA cycle. The reduction in NAD+ impairs the flux of glucose through glycolysis at the glyceraldehyde-3-phosphate dehydrogenase reaction, thereby limiting energy production. The reduction in cytosolic NAD+ leads to reduced activity of glycerol-3-phosphate dehydrogenase (in the glycerol 3-phosphate to DHAP direction), resulting in increased levels of glycerol 3-phosphate which is the backbone for the synthesis of the triglycerides. Both of these 2 events lead to fatty acid deposition in the liver leading to fatty liver syndrome and excessive levels of lipids in the blood, referred to as hyperlipidemia.
Prolonged ethanol consumption and subsequent metabolism ultimately leads to a condition referred to as steatohepatitis or more commonly, "fatty liver syndrome." Ethanol metabolism results in alteration in the activity of which of the following enzymes, one of the consequences of which is excess lipid deposition in the liver? A) Fatty acyl-CoA oxidase B) Glucose-6-phosphate dehydrogenase C) Glycerol-3-phosphate dehydrogenase D) Lactate dehydrogenase E) Pyruvate dehydrogenase
Answer C: The metabolism of ethanol by the liver leads to a large increase in NADH. This increase in NADH disrupts the normal processes of metabolic regulation such as hepatic gluconeogenesis, TCA cycle function, and fatty acid oxidation. Concomitant with reduced fatty acid oxidation is enhanced fatty acid synthesis and increased triglyceride production by the liver. In the mitochondria, the production of acetate from acetaldehyde leads to increased levels of acetyl-CoA. Since the increased generation of NADH also reduces the activity of the TCA cycle, the acetyl-CoA is diverted to fatty acid synthesis. The reduction in cytosolic NAD+ leads to reduced activity of glycerol-3-phosphate dehydrogenase (in the glycerol 3- phosphate to DHAP direction) resulting in increased levels of glycerol 3-phosphate, which is the backbone for the synthesis of the triglycerides. Both of these 2 events lead to fatty acid deposition in the liver leading to fatty liver syndrome and excessive levels of lipids in the blood, referred to as hyperlipidemia.
Type 1 diabetes is most often characterized by which of the following? A) decreased glucagon secretion leading to hyperlipidemia B) decreased insulin receptor response to insulin binding C) elevated fatty acid oxidation leading to ketonemia D) elevated insulin secretion leading to severe hypoglycemia E) impaired glucagon-dependent inhibition of glycolysis leading to hyperglycemia
Answer C: The most frequent consequence of poorly controlled T1D is ketoacidosis, referred to as diabetic ketoacidosis, DKA. The hyperketonemia in DKA is the result of insulin deficiency and unregulated glucagon secretion from α-cells of the pancreas. Circulating glucagon stimulates the adipose tissue to release fatty acids which are taken up and oxidized, primarily by the liver. Under these conditions, the level of fatty acid oxidation is in excess of the livers' ability to fully oxidize the excess acetyl-CoA and, thus, the compound is diverted into ketones synthesis. The ketones are released into the circulation and because they are acidic lower the pH of the blood resulting in metabolic acidosis.
Type 2 diabetics retain some level of pancreatic function. This fact explains why they rarely manifest which of the following symptoms that is typical in Type 1 diabetics? A) glucose intolerance B) hyperglycemia C) ketoacidosis D) obesity E) polyuria
Answer C: The most frequent consequence of poorly controlled T1D is ketoacidosis, referred to as diabetic ketoacidosis, DKA. The hyperketonemia in DKA is the result of insulin deficiency and unregulated glucagon secretion from α-cells of the pancreas. Since T2D patients have normal pancreatic α-cell function, they do not secrete excess glucagon and, therefore, rarely exhibit ketonemia.
Patients with poorly controlled diabetes have elevated levels of blood glucose. One severe consequence of the hyperglycemia is an increase in glucose attachment to serum proteins. Which of the following proteins, when glycosylated, is an excellent measure of the length of time someone has suffered from an episode of hyperglycemia? A) albumin B) cholesterol C) fatty acids D) hemoglobin E) transferrin
Answer D: Assessment of therapeutic management of the hyperglycemia in T2D is accomplished by routine measurement of the circulating levels of glycosylated hemoglobin, designated as the level of HbA1c, often designated as just A1C. Since hemoglobin is present in red blood cells and these cells have a limited life span of 120 days in the circulation, measurement of HbA1c levels is a relatively accurate measure of the amount of glucose in the blood and the length of time the level has been elevated.
Which of the following is the primary mode of metabolism of ethanol? A) Excretion through the kidneys B) Exhalation from the lungs C) Oxidation in the kidneys D) Oxidation in the liver E) Oxidation in the lungs
Answer D: Metabolism of ethanol occurs within the liver and involves oxidation to acetaldehyde and then to acetate catalyzed by ADH and ALDH, respectively.
Which of the following, associated with obesity, is most highly correlated to the development of the metabolic syndrome? A) elevated serum HDL B) elevated serum total cholesterol C) hyperglycemia D) insulin resistance E) proteinuria
Answer D: The hallmark feature of the metabolic syndrome is indeed insulin resistance. The hyperlipidemia typical in obese individuals leads to progressive insulin resistance, particularly in adipose tissue and skeletal muscle.
Acetate, derived from the oxidation of ethanol, has which of the following fate? A) Due to its toxicity it leads to necrosis of the liver B) It directly enters the TCA cycle and is oxidized C) It is converted into NADH via the action of ADH D) It is excreted in the bile E) It is taken up by nonhepatic tissues and converted to acetyl-CoA
Answer E: Acetate, from whatever source, is converted to acetyl-CoA by ATPdependent acetyl-CoA synthetases (AceCS). Following the consumption of ethanol, acetate levels can be elevated by as much as 20-fold. The primary causes of fatty liver syndrome (hepatic steatosis), induced by excess alcohol consumption, are the altered NADH/NAD+ levels that in turn inhibits gluconeogenesis, inhibits fatty acid oxidation, and inhibits the activity of the TCA cycle. Each of these inhibited pathways results in the diversion of acetyl-CoA into de novo fatty acid synthesis.
Which of the following chronic effects of alcohol consumption is irreversible? A) activation of triglyceride synthesis B) inhibition of fatty acid oxidation C) ketoacidosis D) lactic acidosis E) liver cirrhosis
Answer E: Chronic ethanol consumption and alcohol metabolism contributes to the spectrum of metabolic disorders frequently found in alcoholics. These disorders include fatty liver syndromes such as NAFLD and NASH, hyperlipidemia, lactic acidosis, ketoacidosis, and hyperuricemia. The first stage of liver damage following chronic alcohol consumption is the appearance of fatty liver, which is followed by inflammation, apoptosis, fibrosis, and finally cirrhosis. These negative and toxic changes within the liver are irreversible even when alcohol consumption is terminated.
In Type 1 diabetes there is an associated hyperlipidemia. The best explanation for this is that the level of an enzyme important for fat homeostasis is reduced. Which of the following is this enzyme? A) acyl-CoA dehydrogenase (eg, MCAD) B) carnitine palmitoyltransferase I C) glucose 6-phosphatase D) hepatic lipase E) lipoprotein lipase
Answer E: One of the effects of insulin is to increase the level of lipoprotein lipase (LPL) expression in endothelial cells. The lack of normal levels of circulating insulin in Type 1 diabetics results in impaired regulation of LPL levels. Reduced LPL contributes to the hyperlipidemia associated with T1D.
Obesity, genetic profile, and aging all contribute to the development of Type 2 diabetes. Of the following, which is the most important additive factor for these 3 conditions in the development of Type 2 diabetes? A) elevated hepatic ketogenesis B) elevated pancreatic glucagon secretion C) impaired renal clearance of glucose D) increased adipose tissue activity leading to hyperlipidemia E) muscle resistance to insulin
Answer E: The influence of obesity, genetic profile, and age on overall metabolism is most significant at the level of skeletal muscle sensitivity to the actions of insulin. Due to the overall mass of skeletal muscle in the body, the uptake of glucose by this tissue, and consequently its role in blood glucose homeostasis, is a significant factor in insulin responses. Progressive loss of skeletal muscle sensitivity to insulin leads to increased rates of visceral cell lipolysis and pancreatic β-cell compensation. Eventually, the pancreas can no longer continue compensating for impaired insulin responses and pancreatic β-cell decompensation occurs, further exacerbating the problem. The disrupted insulin response leads to increased hepatic gluconeogenesis, which further increases circulating glucose levels. The overall outcome of these responses is development of progressively worsening Type 2 diabetes.
Which of the following events would be most likely to be observed following acute consumption of alcohol? A) Activation of fatty acid oxidation B) Increased rate of gluconeogenesis C) Increased ratio of NAD+ to NADH D) Inhibition of ketogenesis E) Lactic acidosis
Answer E: The majority of the aberrant metabolic effects of ethanol intoxication stem from the actions of ADH and ALDH and the resultant cellular imbalance in the NADH:NAD+ ratio. Additionally, there is an increased rate of hepatic lactate production due to the effect of increased NADH on direction of the hepatic lactate dehydrogenase (LDH) reaction. This reversal of the LDH reaction in hepatocytes results in reduced capacity of the liver to divert lactate into glucose via gluconeogenesis, resulting in elevated lactate levels in the blood, leading to lactic acidosis.
A fasting blood glucose test level of _________________ is considered normal. A) 50 mg/dL to 69 mg/dL B) 70 mg/dL to 110 mg/dL C) 110 mg/dL to 125 mg/dL D) 126 mg/dL or higher E) None of the above are correct
B) 70 mg/dL to 110 mg/dL
Obesity is associated with all of the following except: A) Osteoarthritis. B) Anxiety. C) Gallstones. D) Diabetes. E) The development of respiratory problems.
B) Anxiety.
Which of the following statements is TRUE regarding the blood glucose level of Type 2 (non-insulin dependent) diabetics tend to compare to that of normal individuals? A) Blood glucose levels of diabetics tend to be very stable, but at a higher level. B) Blood glucose levels of diabetics tend to be variable and higher. C) Blood glucose levels decrease more rapidly following a meal, often dropping lower than is tolerable. D) Blood glucose levels average the same level in diabetics, but reach higher peaks for short periods. E) none of the above
B) Blood glucose levels of diabetics tend to be variable and higher.
Type 2 diabetes I. can develop due to a mutation in the insulin receptor II. can develop in individuals with insulin resistance. III. results in hypersensitivity to insulin release. IV. are treated with drugs that decrease AMPK activity. A) I, II, IV B) I, II C) II, IV D) III, IV E) I, IV
B) I, II
Metformin and thiazolidinediones (TZDs) are used to treat ____ and produce a(an) ______ in AMPK activity. A) type 2 diabetes; decrease B) type 2 diabetes; increase C) type 1 diabetes; decrease D) type 1 diabetes; increase E) both type 1 and type 2 diabetes; decrease
B) type 2 diabetes; increase
A fasting blood glucose test level of _________________ indicates pre-diabetes. A) 50 mg/dL to 69 mg/dL B) 70 mg/dL to 110 mg/dL C) 110 mg/dL to 125 mg/dL D) 126 mg/dL or higher E) 140 mg/dL to 200 mg/dL
C) 110 mg/dL to 125 mg/dL
What percentage of newly diagnosed type 1 diabetes patients have a father, mother or sibling with the disease? A) None B) Approx. 5% C) Approx. 15% D) Approx. 50% E) 100%
C) Approx. 15%
Consider the following statements regarding methanol poisoning Assertion: Administration of ethanol is one of the treatment modalities Reason: Ethanol inhibits alcohol dehydrogenase A) Both Assertion and Reason are true; Reason is the correct explanation for the Assertion B) Both Assertion and Reason are true; Reason is not the correct explanation for the Assertion C) Assertion is true, but Reason is false D) Assertion is false, but Reason is true E) Both Assertion and Reason are false
C) Assertion is true, but Reason is false
Obesity: select the single best answer A) Can occur when energy intake is equal to energy expenditure. B) Is consistent with a body mass index of 20. C) Is more common in low socio-economic class in the West. D) Affects over 50% of women in the UK. E) Is commonly overcome in the long term by dieting.
C) Is more common in low socio-economic class in the West.
A few of the more severe complications of Type 2 of diabetes are neuropathy and retinopathy. Many of the associated pathologies of diabetes arise as a result of which of the following nonenzymatic modifications of various proteins? A) acetylation B) glucuronidation C) glycosylation D) hydroxylation E) oxidation
C) glycosylation
A fasting blood glucose test level of _________________ is indicative of diabetes. A) 50 mg/dL to 69 mg/dL B) 70 mg/dL to 110 mg/dL C) 110 mg/dL to 125 mg/dL D) 126 mg/dL or higher E) 200 mg/dL or higher
D) 126 mg/dL or higher
The following drugs can be used in treating obesity except? A) Orlistat B) Sibutaramine C) Olestra D) Leptin antagonist E) Phentermine
D) Leptin antagonist
What proportion of patients with type 2 diabetes will require insulin therapy at some time in their life? A) Approx 10% B) Approx 20% C) Approx 40% D) Over 50% Right answer. E) 100 %
D) Over 50%
Excess alcohol consumption can lead to Wernicke-Korsakoff syndrome due to the lack of the vitamin thiamine. Which of the following metabolic conversions cannot occur in the absence of thiamine? A) pyruvate + CO2 oxaloacetate B) pyruvate acetyl-CoA + CO2 C) -ketoglutarate succinyl-CoA + CO2 D) phosphoenolpyruvate + CO2 oxaloacetate E) B and C
E) B and C
After an overnight fast, a blood glucose concentration of _______ would suggest that a patient may have Type 2 diabetes. A) 10 μM B) 10 mM C) 10 mg/mL D) 0.2 g/dL E) B and D are correct
E) B and D are correct
Long-term complications of diabetes include _____. A) increased risk for high blood pressure and atherosclerosis. B) impaired sensation in the hands and feet. C) increased risk for kidney failure. D) loss of vision and blindness. E) all the complications listed are correct.
E) all the complications listed are correct.
Which of the following is NOT a risk factor for type 2 diabetes mellitus. A) being overweight B) being a member of a high-risk population C) family history D) sedentary lifestyle E) arthritis
E) arthritis
Which of the following are the consequences of vitamin and mineral deficiencies which can lead to dementia and memory disorders in alcohol abuse? A) Smirnoff's syndrome B) Korsakoff's syndrome C) Helmert syndrome D) Huynh-Feldt syndrome E) Fetal alcohol syndrome
Korsakoff's syndrome: A syndrome involving dementia and memory disorders which is caused by lack of thiamine (vitamin B1) in the brain. Its onset is linked to chronic alcohol abuse and/or severe malnutrition.