Long-term Consequences of Diabetes Mellitus

9. Long-term Consequences of Diabetes Mellitus

Chronic hyperglycemia has deleterious effects on insulin-producing pancreatic beta-cells and on insulin target tissues (glucotoxicity; see above). But long-term hyperglycemia also seems to be the major factor contributing to other complications frequently seen in diabetic cats. These are diabetic neuropathy, nephropathy and retinopathy. The two main underlying mechanisms are glycation of proteins and osmotic damage due to the accumulation of sugar alcohols.

Glycation of Proteins and Accumulation of Sugar Alcohols

An early pathologic change of DM is increased unspecific, non-enzymatic glycosylation (or glycation) of proteins, which cause abnormal aggregation of collagen fibrils and the production of superoxide radicals. This results in damage to the connective tissue and basal membranes. Further, osmotic cell damage seems to occur due to the accumulation of the sugar alcohol sorbitol which is not freely permeable to the cell membrane. Sorbitol is generated from glucose through aldose reductase activity. While only small amounts of sorbitol are generated under normal conditions, hyperglycemia can lead to the accumulation of considerable amounts of sorbitol by an "overflow" mechanism when normal glucose utilization via hexokinase is saturated.

Diabetic Neuropathy, Retinopathy and Cataract

The exact prevalence of diabetic neuropathy, nephropathy and retinopathy in cats is unknown. Diabetic neuropathy leads to hindlimb weakness and a typical plantigrade stance (Figure 3). The pathology seems to share many similarities with human diabetic neuropathy (Mizisin et al, 2007).

Interestingly, if intensive glucose-lowering therapy is initiated rapidly after diagnosis, at least some of these changes seem to be reversible and gait normalizes. Even though diabetic nephropathy and retinopathy also occur in cats, diabetic retinopathy is only rarely observed in clinical practice. Experimentally induced hyperglycemia has been shown to lead to retinal changes only after several years of duration, and these changes could only be detected using specific diagnostic techniques (personal communication; Dr. M. Richter, Division of Ophthalmology, Vetsuisse Faculty, University of Zurich).

Similarly, and in contrast to dogs, diabetic cataracts are also very rare in diabetic cats (Figure 22). It has been suggested that the generation of sorbitol in older diabetic cats was much lower than in dogs and young cats because of the lower aldose reductase activity in old cats (Richter et al, 2002). Excess sorbitol is responsible for the damage to the lens. Even though DM is very infrequent in young cats, young diabetic cats often present typical lens opacity as in diabetic dogs, probably because of their high aldose reductase activity (Richter et al, 2002). A recent study challenged the view of a generally low occurrence of diabetic cataracts in cats (Williams & Heath, 2006). This study showed that lens opacities occur much more frequently than previously suggested. In addition, these opacities occurred at a much younger age in diabetic than in non-diabetic cats.

Figure 22. Cataract in a diabetic cat. (by courtesy: Prof. B. Spiess, Vetsuisse-Faculty University of Zurich).