Question 1
A 42 year old patient with type 1 diabetes presents to the endocrine clinic with multiple hypoglycaemic episodes, one requiring ICU admission. There is a strong family history of cardiovascular disease. He has some micro-albuminuria. What is the appropriate HbA1C target?
(A) 6.0
(B) 6.5
(C) 7.0
(D) 7.5
(E) 8.0
E: According to australian guidelines
Question 2
Which of the following has the highest risk factor for the development of type 1 diabetes?
(A) Offspring of type 1 diabetic woman
(B) Offspring of type 1 diabetic man
(C) HLA identical sibling who has developed type 1 diabetes
(D) Diabetic parent
(E) Rotavirus infection
C: All of the above are associated risk factors. Interestingly, there is 3x higher risk of the offspring of a type 1 diabetic man having diabetes compared to the mother having diabetes. In type 2 diabetes, this is the other way around, where the offspring of type 2 diabetic women have 2 - 3 fold greater risk of developing diabetes than the offspring of men with this disease. RPA Course 2015
Question 3
With regards to the pathophysiology and genetics of type 2 diabetes, what is the most important genetic marker of type 2 diabetes?
(A) Homobox 1
(B) Fibrilin 2
(C) Transcription factor 7-like 2
(D) Glucokinase
(E) HNF-4-alpha
C: This is a gene involved in beta cell function. Indeed the vast majority of gene defects that are identified relate to beta cell function compared to insulin resistance. RPA Course 2015, Mol. Endocrinol. 22 (11): 2383–92.
Question 4
Which single gene mutation is responsible for MODY phenotype that is exquisitely sensitive to sulphonylureas?
(A) HNF-4alpha
(B) Glucokinase
(C) HNF-1alpha
(D) IPF-1
(E) NeuroD1
C: RPA Course 2015, = MODY 3. Mutations in glucokinase is associated with MODY2 which result in mild hyperglycaemia and minimal complications.
Question 5
With regards to prevention of type 2 diabetes in an at risk group, which intervention has the best evidence?
(A) Rosiglitazone
(B) Pioglitazone
(C) Metformin
(D) Islet cell transplantation
(E) Ramipril
A: Note that in the diabetes prevention study, patients enrolled in interventions aimed at losing weight via diet and exercise showed a relative rik reduction of 58% compared to placebo. Rosiglitazone and ramipril were studied in a 2 x 2 factorial design in the DREAM study, and rosiglitazone was shown to reduce new DM by > 60% in people with IGT or IFG and reduce ALT, at the cost of a sall increase in chronic heart failure.
Question 6
Which of the following hypoglycaemic agents is known to promote weight loss?
(A) Gliclazide
(B) Metformin
(C) Pioglitazone
(D) Sitagliptin
(E) Exenatide
E: Exanatide is a GLP-1 analogue, similar to human GLP-1 but with a longer half life. Its trade name is byetta. It is approved in combination with one or two other drugs through the PBS. Metformin is weight neutral. Gliclazide is a sulfonylurea. Pioglitazone binds and activates the PPAR-gamma receptor which iscentral to insulin action. Sitagliptin is an oral DPP4 inhibitor, increasing endogenous GLP-1 half life by inhibiting its degradation. Trade name for sitagliptin is januvia. The main advantage of DPP4 inhibitors is that it can be taken as a tablet. This is contrast to exenatide.
Question 7
What is the main side-effect of exenatide "byetta"
(A) Nausea
(B) Headache
(C) Fatigue
(D) Rash
(E) Abdominal pain
A: This can be explained by the mechanism of action. GLP-1 inhibits gastric emptying. Weight loss with byetta is 3kg in 6 months and 5 kgs in 2 years.
Question 8
What is true with regards to intensive glycemic control and diabetes?
(A) There is a beneficial macrovascular effect short term
(B) There is a beneficial macrovascular effect long term
(C) There is an increase in all cause mortality driven by increasing hypoglycaemias
(D) Tight glycaemic control has no effect on macrovascular disease
(E) HbA1c target of <7.5 should be aimed for in patients with recurrent hypoglycaemias
B: The so-called legacy effect was shown after long term follow up of patients with type 1 diabetes and type 2 diabetes, even after the trial period where the HbA1c converged to similar values. This same legacy effect is not seen in blood pressure lowering trials. Patients with recurrent hypoglycaemia should have a HbA1c target of <8 rather than <7.5. RPA Course 2015
Question 9
Which of the following glucose transporters is upregulated on myocytes and adipocytes in response to the action of insulin?
(A) GLUT1
(B) GLUT2
(C) GLUT4
(D) Na/I symporter
(E) SGLT3
C: GLUT 4. Myocytes and adipocytes also express GLUT-4 in their cytoplasm, which translocates to the cell membrane in response to insulin. Once glucose enters the cell, it is phosphorylated by a hexokinase (glucokinase in hepatocytes and β cells) and then either stored as glycogen or metabolized through glycolysis. Glycolysis is the conversion of glucose-6-phosphate to pyruvate and generation of adenosine triphosphate (ATP). The pyruvate that is produced can be reduced to lactate under anaerobic conditions or it can be oxidized via the tricarboxylic acid (Krebs) cycle, resulting in greater amounts of ATP. Pediatr Endocrinol Rev. 2011 Sep; 9(1): 463–475
Question 10
What channel does gliclazide inhibit in order to produce its insulin secretagogue effect?
(A) K(ATP) channels
(B) Na/K ATPase
(C) DHP gated Ca channels
(D) Na channels
(E) Inward rectifier K channel
A: By inhibiting K(ATP) channel, resting permeability to outward K current is decreased, therefore there is relative membrane depolarisation, increased open probability of voltage gated Ca channels leading to increased intracellular calcium, eventually leading to fusion of insulin containing vesicles.
Question 11
What is the first physiological response to hypoglycaemia with regards to the glucose homeostatic hormones?
(A) Glucagon rises
(B) Adrenaline rises
(C) Growth hormone rises
(D) Cortisol rises
(E) Insulin falls
E: Pediatr Endocrinol Rev. 2011 Sep; 9(1): 463–475
Question 12
Which of the following drugs, including empagliflozin, is known to reduce the cardiovascular event rate in high risk groups with type 2 diabetes?
(A) Metformin
(B) Pioglitazone
(C) Saxagliptin
(D) Exenatide
(E) Liraglutide
E: Liraglutide, when added to placebo caused a significant decrease in the rates of the cardiovascular endpoint of the LEADER trial. It was a double blind randomised trial enrolling over 9300 patients. The primary composite outcome in the time-to-event analysis was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The primary outcome occurred in significantly fewer patients in the liraglutide group (608 of 4668 patients [13.0%]) than in the placebo group (694 of 4672 [14.9%]) (hazard ratio, 0.87; 95% confidence interval [CI], 0.78 to 0.97; P<0.001 for noninferiority; P=0.01 for superiority). Fewer patients died from cardiovascular causes in the liraglutide group (219 patients [4.7%]) than in the placebo group (278 [6.0%]) (hazard ratio, 0.78; 95% CI, 0.66 to 0.93; P=0.007). The rate of death from any cause was lower in the liraglutide group (381 patients [8.2%]) than in the placebo group (447 [9.6%]) (hazard ratio, 0.85; 95% CI, 0.74 to 0.97; P=0.02). DOI: 10.1056/NEJMoa1603827
A 42 year old patient with type 1 diabetes presents to the endocrine clinic with multiple hypoglycaemic episodes, one requiring ICU admission. There is a strong family history of cardiovascular disease. He has some micro-albuminuria. What is the appropriate HbA1C target?
(A) 6.0
(B) 6.5
(C) 7.0
(D) 7.5
(E) 8.0
E: According to australian guidelines
Question 2
Which of the following has the highest risk factor for the development of type 1 diabetes?
(A) Offspring of type 1 diabetic woman
(B) Offspring of type 1 diabetic man
(C) HLA identical sibling who has developed type 1 diabetes
(D) Diabetic parent
(E) Rotavirus infection
C: All of the above are associated risk factors. Interestingly, there is 3x higher risk of the offspring of a type 1 diabetic man having diabetes compared to the mother having diabetes. In type 2 diabetes, this is the other way around, where the offspring of type 2 diabetic women have 2 - 3 fold greater risk of developing diabetes than the offspring of men with this disease. RPA Course 2015
Question 3
With regards to the pathophysiology and genetics of type 2 diabetes, what is the most important genetic marker of type 2 diabetes?
(A) Homobox 1
(B) Fibrilin 2
(C) Transcription factor 7-like 2
(D) Glucokinase
(E) HNF-4-alpha
C: This is a gene involved in beta cell function. Indeed the vast majority of gene defects that are identified relate to beta cell function compared to insulin resistance. RPA Course 2015, Mol. Endocrinol. 22 (11): 2383–92.
Question 4
Which single gene mutation is responsible for MODY phenotype that is exquisitely sensitive to sulphonylureas?
(A) HNF-4alpha
(B) Glucokinase
(C) HNF-1alpha
(D) IPF-1
(E) NeuroD1
C: RPA Course 2015, = MODY 3. Mutations in glucokinase is associated with MODY2 which result in mild hyperglycaemia and minimal complications.
Question 5
With regards to prevention of type 2 diabetes in an at risk group, which intervention has the best evidence?
(A) Rosiglitazone
(B) Pioglitazone
(C) Metformin
(D) Islet cell transplantation
(E) Ramipril
A: Note that in the diabetes prevention study, patients enrolled in interventions aimed at losing weight via diet and exercise showed a relative rik reduction of 58% compared to placebo. Rosiglitazone and ramipril were studied in a 2 x 2 factorial design in the DREAM study, and rosiglitazone was shown to reduce new DM by > 60% in people with IGT or IFG and reduce ALT, at the cost of a sall increase in chronic heart failure.
Question 6
Which of the following hypoglycaemic agents is known to promote weight loss?
(A) Gliclazide
(B) Metformin
(C) Pioglitazone
(D) Sitagliptin
(E) Exenatide
E: Exanatide is a GLP-1 analogue, similar to human GLP-1 but with a longer half life. Its trade name is byetta. It is approved in combination with one or two other drugs through the PBS. Metformin is weight neutral. Gliclazide is a sulfonylurea. Pioglitazone binds and activates the PPAR-gamma receptor which iscentral to insulin action. Sitagliptin is an oral DPP4 inhibitor, increasing endogenous GLP-1 half life by inhibiting its degradation. Trade name for sitagliptin is januvia. The main advantage of DPP4 inhibitors is that it can be taken as a tablet. This is contrast to exenatide.
Question 7
What is the main side-effect of exenatide "byetta"
(A) Nausea
(B) Headache
(C) Fatigue
(D) Rash
(E) Abdominal pain
A: This can be explained by the mechanism of action. GLP-1 inhibits gastric emptying. Weight loss with byetta is 3kg in 6 months and 5 kgs in 2 years.
Question 8
What is true with regards to intensive glycemic control and diabetes?
(A) There is a beneficial macrovascular effect short term
(B) There is a beneficial macrovascular effect long term
(C) There is an increase in all cause mortality driven by increasing hypoglycaemias
(D) Tight glycaemic control has no effect on macrovascular disease
(E) HbA1c target of <7.5 should be aimed for in patients with recurrent hypoglycaemias
B: The so-called legacy effect was shown after long term follow up of patients with type 1 diabetes and type 2 diabetes, even after the trial period where the HbA1c converged to similar values. This same legacy effect is not seen in blood pressure lowering trials. Patients with recurrent hypoglycaemia should have a HbA1c target of <8 rather than <7.5. RPA Course 2015
Question 9
Which of the following glucose transporters is upregulated on myocytes and adipocytes in response to the action of insulin?
(A) GLUT1
(B) GLUT2
(C) GLUT4
(D) Na/I symporter
(E) SGLT3
C: GLUT 4. Myocytes and adipocytes also express GLUT-4 in their cytoplasm, which translocates to the cell membrane in response to insulin. Once glucose enters the cell, it is phosphorylated by a hexokinase (glucokinase in hepatocytes and β cells) and then either stored as glycogen or metabolized through glycolysis. Glycolysis is the conversion of glucose-6-phosphate to pyruvate and generation of adenosine triphosphate (ATP). The pyruvate that is produced can be reduced to lactate under anaerobic conditions or it can be oxidized via the tricarboxylic acid (Krebs) cycle, resulting in greater amounts of ATP. Pediatr Endocrinol Rev. 2011 Sep; 9(1): 463–475
Question 10
What channel does gliclazide inhibit in order to produce its insulin secretagogue effect?
(A) K(ATP) channels
(B) Na/K ATPase
(C) DHP gated Ca channels
(D) Na channels
(E) Inward rectifier K channel
A: By inhibiting K(ATP) channel, resting permeability to outward K current is decreased, therefore there is relative membrane depolarisation, increased open probability of voltage gated Ca channels leading to increased intracellular calcium, eventually leading to fusion of insulin containing vesicles.
Question 11
What is the first physiological response to hypoglycaemia with regards to the glucose homeostatic hormones?
(A) Glucagon rises
(B) Adrenaline rises
(C) Growth hormone rises
(D) Cortisol rises
(E) Insulin falls
E: Pediatr Endocrinol Rev. 2011 Sep; 9(1): 463–475
Question 12
Which of the following drugs, including empagliflozin, is known to reduce the cardiovascular event rate in high risk groups with type 2 diabetes?
(A) Metformin
(B) Pioglitazone
(C) Saxagliptin
(D) Exenatide
(E) Liraglutide
E: Liraglutide, when added to placebo caused a significant decrease in the rates of the cardiovascular endpoint of the LEADER trial. It was a double blind randomised trial enrolling over 9300 patients. The primary composite outcome in the time-to-event analysis was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The primary outcome occurred in significantly fewer patients in the liraglutide group (608 of 4668 patients [13.0%]) than in the placebo group (694 of 4672 [14.9%]) (hazard ratio, 0.87; 95% confidence interval [CI], 0.78 to 0.97; P<0.001 for noninferiority; P=0.01 for superiority). Fewer patients died from cardiovascular causes in the liraglutide group (219 patients [4.7%]) than in the placebo group (278 [6.0%]) (hazard ratio, 0.78; 95% CI, 0.66 to 0.93; P=0.007). The rate of death from any cause was lower in the liraglutide group (381 patients [8.2%]) than in the placebo group (447 [9.6%]) (hazard ratio, 0.85; 95% CI, 0.74 to 0.97; P=0.02). DOI: 10.1056/NEJMoa1603827
