6 Diabetes

1. Which observation most strongly supports Type 1 rather than Type 2 diabetes?

gradual onset in an obese adult
presence of autoantibodies and low endogenous insulin
strong twin concordance near 90%
absence of ketosis at presentation

2. Which mechanism best explains impaired LDL clearance in diabetes-associated dyslipidemia?

enhanced insulin signaling in hepatocytes
decreased production of cholesterol in liver
reduced effectiveness of normal lipoprotein handling pathways in insulin-deficient/resistant states
absolute absence of circulating LDL particles

3. In the insulin signaling pathway, which event occurs immediately after insulin binds to the α subunits of the insulin receptor?

Direct phosphorylation of glucose to Glucose-6-P.
Autophosphorylation of tyrosine residues on the β subunits.
Translocation of GLUT−4 vesicles to the plasma membrane.
Activation of Hormone Sensitive Lipase in adipocytes.

4. In individuals with uncontrolled diabetes, what is the consequence of the liver’s failure to suppress glucagon secretion?

Suppression of glycogen breakdown to protect the liver.
Rapid clearance of ketone bodies from the blood.
Activation of the MAP kinase pathway for cell growth.
Increased hepatic glucose output and stimulated lipolysis.

5. Increased VLDL production in diabetes is most directly related to increased hepatic availability of:

fatty acids
amino acids
glucose transporters
nucleotides

6. Increased fatty acid mobilization in uncontrolled diabetes most directly results from decreased inhibition of:

acetyl-CoA carboxylase
hormone sensitive lipase
lipoprotein lipase
glycogen synthase

7. A patient has uncontrolled diabetes with elevated blood glucose despite already high plasma glucose. Which defect most directly explains continued hepatic glucose output?

failure of glucagon suppression and impaired insulin action
excessive GLUT4 insertion into hepatocyte membranes
increased glycogen synthesis in liver
increased lipoprotein lipase activity in adipose tissue

8. Which statement best explains why blood glucose may remain high even when some tissues still take up glucose without insulin?

liver continues to release glucose and muscle/adipose uptake is impaired
all tissues require GLUT4 for glucose entry
kidney cannot filter glucose in diabetes
insulin is the only hormone controlling glucose metabolism

9. A patient with untreated diabetes has elevated plasma fatty acids. Which statement best identifies the immediate source of those fatty acids?

direct hydrolysis of VLDL by lipoprotein lipase
adipocyte triacylglycerol breakdown by hormone sensitive lipase
dietary lipid absorption through chylomicron retention only
hepatic de novo fatty acid synthesis stimulated by insulin

10. Why does the lack of insulin in Type 1 Diabetes lead to significant weight loss and muscle wasting?

Increased glucose uptake in muscle leads to osmotic lysis of fibers.
Excessive water retention hides the loss of actual tissue mass.
Insulin toxicity causes the destruction of skeletal muscle cells.
A shift from anabolism to accelerated catabolism, including protein breakdown.

11. What happens to the HbA 1c molecule once it is formed?

It is rapidly converted into an Advanced Glycation End-product.
It is transported to the liver to be converted into sorbitol.
It is enzymatically reversed by insulin therapy.
It remains stable for the life of the red blood cell.

12. Glycosuria occurs when blood glucose concentration exceeds the capacity of renal:

insulin receptors
glucose transporters
glycogen synthase enzymes
lipoprotein lipase

13. In untreated Type 1 diabetes, weight loss occurs despite polyphagia primarily because:

glucose cannot be filtered by the kidney
anabolic pathways are impaired while catabolic pathways accelerate
intestinal glucose absorption is decreased
glucagon secretion is absent

14. Increased hormone sensitive lipase activity in adipose tissue leads directly to higher plasma levels of:

glycogen and pyruvate
fatty acids and glycerol
chylomicrons and HDL
ketone bodies and lactate

15. Which effect of epinephrine would worsen hyperglycemia during acute stress in a diabetic patient?

stimulation of insulin release
inhibition of muscle glycogenolysis
increased hepatic glycogenolysis and gluconeogenesis
suppression of lipolysis in adipose tissue

16. Which biochemical marker provides a long-term (2-3 month) average of blood glucose levels and is formed by the non-enzymatic addition of glucose to hemoglobin?

Advanced Glycation End-products (AGEs)
HbA1c
Schiff base
Sorbitol

17. Which metabolic byproduct accumulates in the liver during massive mobilization of fatty acids and is subsequently used to synthesize ketone bodies?

Acetyl CoA
Glycerol
Lactate
Pyruvate

18. Which metabolic change most directly explains weight loss in untreated Type 1 diabetes?

increased glycogen storage
increased fatty acid synthesis
increased catabolism of fat and protein
decreased gluconeogenesis

19. Which metabolic change is most directly responsible for the rise in circulating ketone bodies in uncontrolled Type 1 diabetes?

decreased fatty acid mobilization from adipose tissue
increased hepatic fatty acid synthesis
increased hepatic β-oxidation following excess adipose lipolysis
increased glycolysis in adipose tissue

20. Glucagon has no effect on muscle. Therefore, glucagon-induced hyperglycemia must arise primarily from actions in:

liver
pancreas
brain
red blood cells

21. Which of the following best explains why Type 2 diabetes is strongly associated with obesity?

obesity eliminates glucagon secretion
adipose-derived factors antagonize insulin action
obesity directly destroys pancreatic beta cells by autoimmunity
obese individuals cannot synthesize GLUT4

22. Which of the following describes the condition known as Hyperosmolar Hyperglycemic Syndrome (HHS)?

Rapid onset of acidosis due to ketone body accumulation in Type 1 DM.
The accumulation of advanced glycation end-products in the kidney.
Extremely high blood sugar and severe dehydration in Type 2 DM without significant ketosis.
A condition caused by excessive insulin administration leading to brain damage.

23. Which change most directly explains increased blood glucose levels in uncontrolled diabetes?

decreased hepatic glycogenolysis
increased glucose uptake in muscle
increased hepatic glucose production combined with reduced peripheral uptake
increased glycogen synthesis in adipose tissue

24. Insulin receptor activation involves which type of enzymatic activity?

tyrosine kinase
serine protease
phospholipase
transaminase

25. Why is ketoacidosis more common in Type 1 diabetes than in Type 2 diabetes?

Type 1 diabetes causes greater glucagon deficiency
Type 1 diabetes causes more severe absolute insulin deficiency
Type 2 diabetes causes total absence of hormone sensitive lipase
Type 2 diabetes completely blocks hepatic β-oxidation

26. Which complication is specifically emphasized as more common in Type 2 diabetes and characterized by profound dehydration with minimal ketosis?

diabetic ketoacidosis
severe fasting hypoglycemia
hyperosmolar hyperglycemic syndrome
autoimmune beta-cell collapse

27. Which biochemical feature of the insulin receptor is central to its signaling mechanism?

ligand-gated chloride channel activity
G-protein coupled receptor activity
receptor tyrosine kinase activity
steroid receptor transcription factor activity

28. The Amadori rearrangement is a critical step in the formation of glycation products. What is the stable product formed immediately after this rearrangement?

Sorbitol
Aldimine
Advanced Glycation End-product (AGE)
Ketoamine

29. Which metabolic change would most directly occur if insulin receptor signaling were impaired?

increased GLUT4 insertion into muscle cell membranes
decreased glycogen synthesis in liver and muscle
decreased fatty acid release from adipose tissue
increased glucose uptake in adipose tissue

30. Increased hormone sensitive lipase activity leads to increased release of which molecules from adipose tissue?

cholesterol and bile acids
glycogen and glucose
fatty acids and glycerol
ketone bodies

31. In muscle and adipose tissue, insulin most directly increases glucose uptake by promoting:

GLUT2 synthesis
glucagon receptor phosphorylation
GLUT4 trafficking to the plasma membrane
glycogen phosphorylase activation

32. HbA1c is useful clinically because it reflects:

current plasma insulin concentration over minutes
average blood glucose over time due to nonenzymatic hemoglobin glycation
degree of glucagon receptor stimulation in liver
extent of ketone body production during fasting only

33. In a healthy person after a carbohydrate-rich meal, which coordinated hormonal change should occur?

insulin rises and glucagon falls
insulin falls and glucagon rises
both insulin and glucagon rise equally
neither hormone changes significantly

34. Which of the following effects is unique to epinephrine’s action on skeletal muscle compared to its action on the liver?

Increased glycogenolysis
Increased lipolysis
Increased glycolysis
Inhibition of insulin release

35. Elevated free fatty acids in uncontrolled diabetes most directly result from increased activity of:

lipoprotein lipase
glycogen phosphorylase
hormone sensitive lipase
acetyl-CoA carboxylase

36. Hyperosmolar hyperglycemic syndrome differs from diabetic ketoacidosis primarily because HHS:

involves significant ketone accumulation
involves extremely high glucose without major ketosis
occurs only in Type 1 diabetes
involves decreased dehydration

37. Which finding best distinguishes classic Type 2 diabetes from Type 1 diabetes?

autoimmune beta-cell destruction is common
insulin resistance with normal, high, or low endogenous insulin can be present
ketoacidosis is usually more frequent
onset is usually sudden in thin children

38. Which statement best distinguishes HbA1c from advanced glycation end products?

HbA1c is an AGE formed only in kidney tissue
HbA1c forms only in Type 1 diabetes
HbA1c is a ketoamine adduct and is not itself classified as an AGE
HbA1c requires reactive oxygen species for initial formation

39. Why can uncontrolled diabetes produce ketosis at the same time as cells are exposed to abundant circulating glucose?

glucose in blood automatically suppresses β-oxidation in liver
insulin is required for key glucose uptake/storage pathways in major target tissues
ketone production occurs only when glucose is absent from plasma
red blood cells convert glucose directly into ketone bodies

40. In uncontrolled diabetes, what causes the ‘spilling’ of glucose into the urine (glycosuria)?

A lack of insulin causes the renal transporters to shut down.
Ketone bodies compete with glucose for the same renal transporters.
Blood glucose levels exceed the capacity of renal glucose transporters.
The kidney actively secretes glucose to lower blood sugar levels.

41. Which metabolic change most strongly contributes to diabetic ketoacidosis?

increased fatty acid synthesis in liver
increased hepatic β-oxidation producing excess acetyl-CoA
decreased gluconeogenesis
decreased lipolysis in adipose tissue

42. Insulin normally promotes protein synthesis partly by increasing:

amino acid uptake into cells
fatty acid oxidation
urea production
glucagon receptor expression

43. A diabetic patient has elevated VLDL and chylomicrons. The most direct enzymatic explanation is decreased activity of:

hormone sensitive lipase
acetyl-CoA carboxylase
pyruvate dehydrogenase
lipoprotein lipase

44. Sorbitol accumulation can damage tissues partly because glucose reduction to sorbitol consumes:

NADPH
ATP
FADH₂
biotin

45. Which long-term complication most directly reflects oxidative and polymerization reactions of early glycation products?

advanced glycation end product formation
C-peptide release
glycogen synthesis
glucagon suppression

46. Advanced Glycation End-products (AGEs) are associated with long-term diabetic complications. Which factor is known to accelerate their formation from Amadori products?

The presence of C-peptide
Tight glycemic control
Reactive Oxygen Species (ROS)
High levels of NADPH

47. In untreated Type 1 diabetes, increased protein breakdown contributes to hyperglycemia primarily because amino acids:

inhibit glucagon release
stimulate glycogen synthesis
provide substrates for gluconeogenesis
directly convert into glucose without enzymatic reactions

48. Increased glycation of proteins occurs when glucose reacts nonenzymatically with:

phosphate groups
amino groups on proteins
lipid bilayers
DNA bases only

49. In uncontrolled diabetes, increased amino acid release from muscle contributes to hyperglycemia because those amino acids are used primarily for:

gluconeogenesis in liver
ketone body utilization in liver
glycogenesis in muscle
bile acid synthesis

50. Depletion of NADPH in tissues with excess sorbitol formation most directly promotes injury by:

blocking glycolysis
increasing reactive oxygen species accumulation
increasing urea cycle flux
decreasing glucagon secretion

51. Which combination best matches the lecture’s description of insulin’s major metabolic roles?

increase lipolysis, increase hepatic glucose release, inhibit glycogenesis
decrease glucose uptake, increase protein breakdown, stimulate HSL
increase glucose uptake, glycogenesis, lipogenesis, and protein synthesis
stimulate gluconeogenesis, glycogenolysis, and ketogenesis

52. How does insulin resistance in Type 2 Diabetes typically affect the location of GLUT−4 transporters in muscle cells?

They are permanently locked in the plasma membrane.
They are redirected to the liver for glucose output.
They are degraded by autoantibodies.
They remain sequestered in intracellular vesicles.

53. Which metabolic effect would most directly result from increased glucagon secretion?

decreased hepatic glucose output
increased glycogen breakdown in liver
increased glucose uptake in adipose tissue
increased triacylglycerol synthesis

54. HbA1c is particularly useful clinically because it reflects:

glucose levels over several months
insulin levels over several hours
glucagon release after meals
fatty acid oxidation rates

55. Which hormonal pattern most strongly favors fuel mobilization in adipose tissue?

high insulin and low glucagon
low insulin and high glucagon
high insulin and high glycogen synthase
low glucagon and low epinephrine

56. Cataract formation in diabetes is linked in the lecture to both sorbitol accumulation and glycation because together they promote:

increased transparency of crystallin proteins
reduced lens osmolarity
opaque cloudiness of the lens
increased mitochondrial β-oxidation in lens cells

57. During the proteolytic processing of insulin, which component is released into the blood in a 1:1 molar ratio with mature insulin and serves as a clinical marker for endogenous β cell function?

Signal sequence
Proinsulin
Mature A chain
C-peptide

58. Which of the following is a direct consequence of decreased Lipoprotein Lipase (LPL) activity in a patient with uncontrolled diabetes?

Rapid weight gain due to increased fat storage.
Stimulation of hepatic fatty acid synthesis.
Increased clearance of LDL cholesterol.
Accumulation of chylomicrons and VLDLs in the blood.

59. Insulin promotes lipid storage in adipose tissue partly by stimulating:

hormone sensitive lipase
lipoprotein lipase
glucagon secretion
β-oxidation

60. Sorbitol accumulation contributes to tissue damage partly because sorbitol increases:

lipid solubility of membranes
osmotic pressure within cells
glycogen storage capacity
insulin receptor activity

61. Epinephrine differs from glucagon in that epinephrine directly promotes:

glycogenolysis in skeletal muscle
glucose uptake in adipose tissue
insulin secretion from beta cells
suppression of glucagon secretion

62. Which feature most strongly contributes to insulin resistance in obesity

reduced fatty acid release from visceral adipose
antagonistic cytokines and fatty acid oxidation by-products
failure of glucose filtration by the kidney
autoimmune destruction of beta cells

63. A patient presents with a blood glucose level of 35 mg/100 mL. Based on the physiological effects of low blood glucose, which symptom is most likely to be observed at this specific threshold?

Permanent brain damage
Convulsions or coma
Sweating and trembling
Subtle neurological signs and hunger

64. What is the primary reason for polydipsia (excessive thirst) in patients with poorly controlled diabetes?

A direct effect of high insulin levels on the brain's thirst center.
The dry mouth sensation caused by sorbitol accumulation in salivary glands.
Dehydration resulting from osmotic diuresis caused by glycosuria.
An autoimmune reaction against the hypothalamus.

65. Decreased activity of lipoprotein lipase in diabetes contributes to increased plasma levels of:

LDL receptors
glucose transporters
VLDL and chylomicrons
glycogen

66. Conversion of glucose to sorbitol contributes to oxidative stress primarily by reducing availability of:

NADH
ATP
NADPH
FAD

67. The triad of polyuria, polydipsia, and glycosuria in uncontrolled diabetes is most directly linked by the fact that excess urinary glucose:

inhibits renal blood flow
decreases osmolarity of filtrate
impairs water reabsorption
directly stimulates ADH degradation

68. Insulin downregulates its own receptor via endocytosis. In a state of chronic hyperinsulinemia, the most direct consequence would be:

increased receptor abundance at the cell surface
enhanced GLUT4-independent uptake in liver
reduced receptor availability and worsened insulin resistance
complete loss of glucagon secretion

69. In the context of fuel metabolism, how does the action of glucagon on skeletal muscle differ from its action on the liver?

Glucagon promotes protein synthesis in muscle to provide amino acids.
Glucagon has no effect on skeletal muscle fuel metabolism.
Glucagon stimulates glycolysis in muscle but gluconeogenesis in the liver.
Glucagon increases glycogenolysis in both tissues to raise blood sugar.

70. According to the provided material, which of the following mechanisms contributes to insulin resistance in the context of obesity?

Upregulation of the insulin receptor to compensate for low glucose.
Increased synthesis of GLUT−4 transporters in skeletal muscle.
Release of antagonistic cytokines and free fatty acids from visceral adipose tissue.
Enhanced phosphorylation of the insulin receptor by glucagon.

71. Insulin normally suppresses hepatic glucose production primarily by inhibiting:

glycolysis
gluconeogenesis
glycogen synthesis
glucose phosphorylation

72. Advanced glycation end products contribute to long-term diabetic complications partly by promoting:

increased insulin sensitivity
structural modification of proteins
decreased ROS formation
increased glucose uptake

73. Which biochemical effect of insulin most directly opposes adipose tissue lipolysis?

activation of hormone sensitive lipase
inhibition of hormone sensitive lipase
inhibition of lipoprotein lipase
stimulation of glucagon release

74. Which metabolic profile is most consistent with uncontrolled diabetes?

low VLDL, low FFA, high HDL
high glucose, high FFA, high VLDL/chylomicrons
low glucose, low ketones, high glycogen synthesis
high insulin sensitivity, low hepatic glucose output

75. Which of the following best describes the metabolic state of an individual with uncontrolled Type 1 Diabetes Mellitus regarding lipid metabolism?

Decreased VLDL production by the liver due to lack of insulin signaling.
Suppression of ketogenesis due to high glucagon-to-insulin ratios.
Enhanced Lipoprotein Lipase (LPL) activity results in rapid clearance of chylomicrons.
Increased activity of Hormone Sensitive Lipase (HSL) leads to massive mobilization of fatty acids.

76. What is the characteristic appearance of the lens in advanced diabetic cataracts, and what biochemical process causes it?

Hardening of the lens due to excessive insulin signaling.
Red coloration caused by micro-hemorrhages from ROS damage.
Clear swelling caused by the depletion of sorbitol.
Opaque cloudiness caused by the glycation of lens proteins.

77. Which hormone is most strongly associated with mobilization of stored fuels during acute stress?

insulin
glucagon
epinephrine
cortisol

78. Which change most directly contributes to increased cardiovascular risk in diabetes?

increased HDL concentration
decreased VLDL concentration
dyslipidemia involving elevated triglyceride-rich lipoproteins
decreased fatty acid mobilization

79. A person with Type 2 diabetes has normal insulin secretion but poor glucose uptake into muscle. Which cellular defect best matches the lecture?

GLUT4 remains sequestered intracellularly
GLUT2 is absent from red blood cells
glucagon receptors are overexpressed in muscle
glycogen phosphorylase is inactive in liver

80. A diabetic patient becomes confused and diaphoretic with glucose below 40 mg/dL. According to the lecture, the most immediate concern is:

convulsions or coma
diabetic ketoacidosis
chronic nephropathy
cataract formation

81. How does epinephrine influence pancreatic endocrine function during acute stress or hypoglycemia?

It has no effect on the pancreas and acts only on the liver and muscle.
It stimulates glucagon release and inhibits insulin release.
It inhibits both insulin and glucagon to preserve glucose for the brain.
It stimulates insulin release to help muscle tissues take up glucose.

82. Which of the following is true regarding the diagnostic threshold for Diabetes Mellitus based on blood glucose levels?

Any glucose level above 100 mg/dL is classified as clinical Diabetes Mellitus.
A diagnosis requires a blood glucose level exceeding 600 mg/dL.
A fasting blood glucose level ≥126 mg/dL (approximately 7 mM) is indicative of DM.
A glucose level of 3.9−5.5 mM confirms a diagnosis of Type 1 DM.

83. In Type 2 diabetes, insulin levels may initially increase because:

beta cells compensate for reduced insulin sensitivity
glucagon secretion is absent
insulin degradation is completely inhibited
insulin synthesis requires fatty acids

84. Insulin resistance associated with obesity is partly due to increased release of signaling molecules from:

skeletal muscle
pancreatic beta cells
visceral adipose tissue
red blood cells

85. Which process contributes most directly to dyslipidemia in uncontrolled diabetes?

increased HDL formation from cholesterol efflux
decreased hepatic glucose production
increased free fatty acid delivery to liver and reduced LPL activity
suppression of adipose hormone sensitive lipase

86. Which statement best explains why uncontrolled diabetes can produce both hyperglycemia and dyslipidemia simultaneously?

insulin deficiency/resistance impairs only carbohydrate metabolism
insulin normally coordinates both glucose disposal and lipid storage
glucagon acts only on cholesterol synthesis
lipid abnormalities are unrelated to hormone action

87. What is the primary mechanism by which sorbitol accumulation leads to cellular injury in diabetic patients?

Sorbitol directly inhibits the insulin receptor's tyrosine kinase activity.
Sorbitol accelerates the enzymatic glycation of hemoglobin.
Increased sorbitol causes a rapid drop in osmotic pressure, leading to cell shrinkage.
Depletion of NADPH leads to an accumulation of Reactive Oxygen Species (ROS).

88. True or False: Glucagon promotes lipolysis in adipose tissue in concert with low levels of insulin.

False
True

89. Decreased GLUT4 presence on the plasma membrane most directly reduces glucose uptake in:

brain tissue
liver tissue
muscle and adipose tissue
pancreatic beta cells

90. Persistent hyperglycemia contributes to neuropathy partly through increased production of:

glycogen
sorbitol
bile acids
ketone bodies

91. In uncontrolled diabetes, hyperglycemia persists partly because insulin normally suppresses which hepatic process?

gluconeogenesis
ketone body oxidation
glycolysis in red blood cells
cholesterol excretion

92. In uncontrolled Type 1 diabetes, which sequence is most accurate?

increased insulin → decreased HSL → decreased FFA → ketosis
low insulin → increased HSL → increased FFA → hepatic ketogenesis
low glucagon → decreased gluconeogenesis → hypoglycemia
increased LPL → increased clearance of chylomicrons → low triglycerides

93. Which statement correctly distinguishes the characteristics of Type 1 and Type 2 Diabetes Mellitus?

Concordance in twins is significantly higher in Type 2 (90%) than in Type 1 (50%).
Type 1 is associated with obesity, while Type 2 patients are usually thin.
Autoantibodies against β cells are a common feature of Type 2 Diabetes.
Ketoacidosis is a frequent complication of Type 2 but rare in Type 1.

94. Which specific enzyme is inhibited by insulin in the adipocyte to prevent the breakdown of stored triacylglycerols?

Hormone Sensitive Lipase (HSL)
Tyrosine Kinase
Lipoprotein Lipase (LPL)
Aldose Reductase

95. Increased ketone body production in uncontrolled diabetes is most directly linked to increased availability of:

oxaloacetate
acetyl-CoA
glycerol-3-phosphate
glucose-6-phosphate

96. Which metabolic change would be expected when insulin levels are low and glucagon levels are high?

increased glycogen synthesis
decreased lipolysis
increased gluconeogenesis
decreased hepatic glucose output