Diabetes mellitus type 1 and 2 can cause cataracts. In this article, we are going to take a look at the mechanism by which diabetes causes cataracts. The diabetic cataract mechanism involves the aldose reductase pathway.
What happens in a Healthy Individual?
The following figure shows what happens when a healthy individual eats a high amount of glucose. The adequate secretion of insulin stimulates the uptake of glucose by insulin dependent cells such as liver, adipose tissue and skeletal muscle, which are more capable of storing high amounts of glucose. This is done by an insulin dependent glucose transporter in the cell memebrane of cells in those tissues called GLUT 4. for better understanding of glucose transporters, read the article on glycolysis.
What happens in Diabetes Mellitus?
In diabetes mellitus (type 1) there is an absolute deficiency of Insulin. Therefore, there is an elevation of blood glucose level. Hence, increased levels of glucose enters into non-insulin dependent cells. Subsequently, the elevated intracellular glucose concentrations and an adequate supply of NADPH cause aldose reductase to produce a significant increase in amount of sorbitol (lens, retina, Schwann cells, RBC). In normal cells, an enzyme called Sorbitol dehydrogenase converts the sorbitol into Fructose. Following that, Fructose enters several biochemical pathways. (see Fructose Metabolism)
The figure below shows what happens to glucose that enters in high amounts to normal non-insulin-dependent cells.
Glucose +NADPH →[Aldose Reductase]→ Sorbitol + NADP+
Sorbitol + NADH → [Sorbitol Dehydrogenase] → Fructose + NAD +
However, Sorbitol DH is absent in certain cells such as Retina, Lens, Kidney and nerves.Moreover, Sorbitol cannot pass through cell membranes. Therefore, sorbitol accumulates in these cells. Sorbitol has an osmotic effect. · It drags water into these cells. Water retention causes swelling and bursting of cells in the lens. This causes cataract. It leads to pathological phenomena such as peripheral neuropathy and microvascular problems leading to nephropathy and retinopathy. The figure below summarizes this diabetic cataract mechanism.
