Is the Renal Threshold for Glucose Exceeded in Diabetic Patients?

[mktsgm]

Hi,

Wikipedia in its article on 'Glycosuria' says that the renal threshold for glucose (RTG) reabsorption in the kidney is around 160-180 mg/dL. Beyond which the glucose starts to excrete in the urine. But in diabetic people blood glucose exceeds in range of 300-400 mg/dL is prevalent. How this is possible? What prevents the the excretion of excess glucose into urine?

Does it mean more glucose is reabsorbed in the nephrons above its threshold limit? Also, as the glucose is co-transported with sodium, does it mean that glucose reabsorption is tightly coupled with sodium reabsorption? Does sodium play any role in crossing the glucose threshold limit?

Or is it possible that the excess glucose (beyond RTG) is actually excreted out of blood in the kidney but the hyperglycemia is caused by the fresh gluconeogenesis of the body?

Or is it possible that both these mechanisms (RTG is exceeded as well as fresh gluconeogenesis) cause in furthering the hyperglycemia?

Is it possible to measure this state?

Thanks in advance.

 

[jim mcnamara]

The proximal tubule can only reabsorb a limited amount of glucose. When the blood glucose level exceeds about 160 to 180 mg/dl the proximal tubule becomes overwhelmed and begins to excrete glucose in the urine. This point is called the renal threshold for glucose (RTG).

-- from Wikipedia
What this means:
Proximal tubule's "job" is to remove sugar, some sodium and chloride ions, and some water. This is removed from what would normally go on to become urine. When glucose gets too high it cannot remove it all and let's some glucose pass into the urine. It is still actively keeping some sugar out of urine, just not all of it.

They key concept is that the proximal tubule does not stop working, it just cannot handle all of the sugar load. You can see that your body wants to keep sodium, sugar, chloride and water for future use. Just being completely removed from blood is not allowed. So, if it all gets flushed out into the ureter/bladder this is bad.

With diabetes, control of blood sugar level is broken. So the kidney cannot deal with it and let's sugar and more water, too, go. This is why diabetics become abnormally thirsty - extra water loss in urine.

 

[mktsgm]

Thanks Jim.

It is understandable that excess glucose is excreted from urine when the threshold is crossed. As the glucose reabsorption is an active/facilitated process the Kidneys cannot reabsorb all the glucose and is bound to excrete some glucose in urine.

But in diabetes this is precisely NOT happening. If the threshold holds good, no one should have a Glucose reading of above 180! Isn't it?

My question is, why this is not happening? Kidneys work overtime to reabsorb more glucose above threshold, just to make a person diabetic!?

 

[Andy Resnick]

I'm not sure I understand your question(s). Blood D-glucose is normally 5 mmol/L (I think that comes out the same as your numbers) and is 99.6% resorbed in the proximal tubule by a combination of Na-glucose symporters that couple 1:1 Na: glucose (SLC5A2) and 2:1 Na:glucose (SLC5A1), it is the Na concentration gradient that makes glucose resorption so efficient (and also why some salt is added to glucose energy drinks).

When plasma glucose increases beyond about 10 mmol/L (hyperglycemia), urinary glucose also rises because the symporters are saturated (Michaelis-Menten kinetics), resulting in excretion of glucose- this is 'prerenal glucosuria' because the kidneys are functioning normally.

Now, even if plasma glucose levels are normal (or even low), defects in one or both of the symporters will also result in urinary excretion of glucose- this is "renal glucosuria, because the defect is in the kidney.

Drawing a connection with diabetes is a little tricky for a few reasons, but broadly speaking insulin acts to reduce plasma glucose levels and the kidney isn't really involved- recall that the kidney receives about 25% of cardiac output, so the kidney can't simply excrete all the excess glucose.

Does that help?

 

[Hanni5]

Kidneys can not work overtime to reabsorb more glucose because there is no mechanism for that once the urine leaves the proximal tubules. The flow is only one way. Imagine a conveyor belt carrying apples and workers have to pick out the rotten ones. They can't pick out more than N from the constant flow of apples. If there are more than N rotten apples, some will get through. In this analogy the workers are the glucose transpoter molecules, the conveyor belt is the proximal tubule and the rotten apples are the glucose molecules.