Once the end stage kidney disease has been established, carbohydrate metabolism may be vulnerable for may alterations. Loss of insulin sensitivity

Carbohydrate and insulin metabolism in chronic kidney disease

 

Once the end stage kidney disease has been established, carbohydrate metabolism may be vulnerable for may alterations. Loss of tissue sensitivity to insulin is a fundamental error, however, disturbed insulin secretion and metabolism also have sharing role. Normally, the kidney plays a crucial role in insulin metabolism. Insulin filtration underwent freely via the kidney. Inside the renal tissues, 60% of the total insulin filtration occurs via the kidney glomeruli and 40% could be extracted through the peri-tubular vessels.

NORMAL RENAL HANDLING OF INSULIN

A given mw (molecular weight) of 6000 may permit the free insulin filtration by the kidney. Insulin can have degraded into amino acids inside the proximal renal tubules. Currently, lower than one % of the cleared insulin can present in urine. As renal insulin filtration is about 200 mL/min, that evidently exceeding the natural glomerular filtration rate (GFR) of 120 mL/min. These figures mean that daily metabolism of insulin is about 6-8 units that can be metabolized by the kidney which equals one quarter of the daily pancreatic production.

INSULIN DEGRADATION

Until persistent decline in GFR has been established, insulin clearance alterations are minimal. The diminished filtration of insulin can be compensated via peri-tubular uptake of insulin until there is persistent decline of the GFR to < 15-200 mL/min. At this point of renal failure course, dramatic decline of insulin filtration occurs that could be associated also by a hepatic drop of insulin metabolism. The latter effect can be induced via the toxic effects of uremic metabolites. Adequate dialysis, however, can reverse this effect. These manifestations may be more evident on insulin-dependent kidney patients.

Diminished renal tissues sensitivity to the insulin effect is currently seen in mostly ALL patients with end-stage renal disease that could be responsible of the altered glucose metabolism to a large extent. In addition, there is dramatic decline in clearing insulin via the kidney which is may be associated with concomitant drop in hepatic (by the liver) insulin clearance. Furthermore, a tendency of insulin secretion to be blunted. On the other hand, non-diabetic patients with kidney dysfunction did not usually develop hyperglycemia despite the altered insulin metabolism except for those with genetic liability to develop diabetes mellitus.

In regard to insulin requirements, patients with diabetes and renal dysfunction may be vulnerable for two phases. First, development of insulin resistance with deterioration of diabetes control, Second, progressive decline in insulin clearance with improving glucose tolerance. The latter effect may permit patients depending on a lower doses of insulin to shift their therapy to an oral hypoglycemic or even to complete insulin withdrawal. Development of spontaneous hypoglycemia, however, is uncommonly observed in CKD patients.

 

CLINICAL IMPLICATIONS 

The increased insulin levels (hyperinsulinemia) that results from resistance to insulin may be also a contributing factor to the evolution of hypertriglyceridemia that commonly observed in CKD patients. Insulin stimulates the hepatic VLDL triglyceride production and indirectly (via diminished sensitivity of lipoprotein lipase to insulin) decrease the rate of VLDL degradation. Moreover, hyperinsulinemia may also alter fibrinolysis via enhancing the plasminogen activator inhibitor-1 synthesis. Consequently, it may have a role in the diminished systemic fibrinolytic activity that characterizing CKD patients.

N.B. This Blogger is created to declare how to manage DM in CKD patients.

REFERENCES

1. Alvestrand, A. Carbohydrate and insulin metabolism in renal failure. Kidney Int 1997; 52(Suppl 62):S48.
2. Moen MF, Zhan M, Hsu VD, et al. Frequency of hypoglycemia and its significance in chronic kidney disease. Clin J Am Soc Nephrol 2009; 4:1121.