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8-Question Quiz on Renal Homeostasis in Type 2 Diabetes

Regulation of glucose homeostasis by the kidney is impaired in persons with type 2 diabetes. Find out what you know about this renal dysfunction and the role of SGLT2 inhibition in reducing hyperglycemia.

The defects in multiple metabolic pathways and organ systems that fuel the progression of hyperglycemia in type 2 diabetes (T2DM) include accelerated lypolysis, incretin deficiency/resistance, hyperglucagonemia, and insulin resistance. Renal function, too, is compromised, impairing the role of the kidneys in regulating glucose homeostasis through gluconeogenesis, glucose uptake and utilization, and glucose reabsorption.

What do you know about renal homeostasis in T2DM and the role of the new sodium glucose cotransporter 2 inhibitors (SGLT2Is) in treating the underlying dysfunction? Try these 8 questions and see where your knowledge gaps lie. (Reference list provided on last page)


1. In the fasting state, the kidneys are responsible for approximately what percentage of glucose released into the circulation via gluconeogenesis?

A. 30 to 35%

B. 20 to 25%

C. 15 to 20%

D. None; the kidneys are not involved in gluconeogenesis.

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Answer: B. 20 to 25%1


2. In the postprandial state, renal gluconeogenesis accounts for approximately what percentage of endogenous glucose release?

A. 30%

B. 40%

C. 60%

D. None; the kidneys are not involved in gluconeogenesis.

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Answer: C. 60%2


3. In patients with type 2 diabetes (T2DM), the renal threshold for glucose excretion is:

A. The same as in patients without T2DM

B. Increased

C. Decreased

D. Variable

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Answer: B. Increased3


4. According to some studies, hyperglycemia in patients with T2DM may be worsened by:

A. Increased renal glucose reabsorption

B. Upregulation of SGLT2

C. Upregulation of renal glucose transporters (GLUTs)

D. Both A and C

E. All of the above

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Answer: E. All of the above4,5


5. Recent studies have suggested that inhibition of sodium glucose contransporter 2:

A. Decreases plasma insulin

B. Increases plasma glucagon

C. Increases endogenous glucose production via hepatic gluconeogenesis

D. None of the above

E. All of the above

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Answer: E. All of the above7


6. Fill in the blanks: SGLT2 accounts for ___% and SGLT1 accounts for ___% of renal glucose reabsorption.A. 75% and 25%, respectively

B. 80% and 20%, respectively

C. 85% and 15%, respectively

D. 90% and 10%, respectively

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Answer: D. 90% and 10%, respectively6


7.  Fill in the blanks: Renal glucose utilization occurs mainly in the ___ while renal glucose production occurs mainly in the ___.A. Cortex and pyramid, respectively

B. Papilla and cortex, respectively

C. Medulla and cortex, respectively

D. None of these. The kidneys are not involved in gluconeogenesis.

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Answer: C. Medulla and cortex, respectively9

8. SGLT2 is expressed mainly in the: A. Renal cortex

B. Renal medulla

C. Renal pyramid

D. Renal papilla

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Answer: A. Renal cortex9


-- How did you do?

-- Are you currently using SGLT2 inhibitors in any of your patients with T2DM?

-- If no, what are your thoughts on this class?

-- If yes, would you tell your colleagues what you're seeing? 

Thank you.



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  • Meyer C, Dostou JM, Welle SL, et al. Role of human liver, kidney, and skeletal muscle in postprandial glucose homeostasis. Am J Physiol Endocrinol Metab 2002;282:E419–E427
  • Wilding JPH. The role of the kidneys in glucose homeostasis in type 2 diabetes:  Clinical implications and therapeutic significance through sodium glucose co-trasporter 2 inhibitors.  Met Clin and Exp 2014;53:1228-1237.
  • Farber SJ, Berger EY, Earle DP. Effect of diabetes and insulin on the maximum capacity of the renal tubules to reabsorb glucose. J Clin Invest. 1951;30:125–129.
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  • E. Ferrannini and A. Solini. SGLT2 inhibition in diabetes mellitus: rationale and clinical prospects.  Nature Reviews Endocrinology. 2012;8:495–502
  • Ferrannini E, Muscelli E, Frascerra S, et al. Metabolic response to sodium-glucose cotransporter 2 inhibition in type 2 diabetic patients. J Clin Invest. 2014;124:499-508. doi: 10.1172/JCI72227. Epub 2014 Jan 27.
  • Wright EM, Turk E. The sodium/glucose cotransport family SLC5. Pflugers Archiv;2004:510–518.
  • Mitrakou A. Kidney: its impact on glucose homeostasis and hormonal regulation.  Diabetes Res & Clin Pract. 2011;93S:S66-S72.
  • Wright EM.  Renal Na(+)-glucose cotransporters. Am J Physiol-Renal Physiology. 2001;280: F10–F18.