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Unexplained Weight Loss and Decreased Insulin Needs in Severely Obese Type 2 Patients

by Ashley Berry, Mercer University Doctor of Pharmacy Candidate 2011


Is it possible for an obese Type 2 diabetic patient who administers large quantities of insulin daily to be able to suddenly reduce the amount of insulin they are taking and also have a significant reduction in weight? We have recently seen several patients in the Tampa area who have suddenly been able to do so and it is unknown why. The weight loss and insulin reduction of these patients was not due to a change in diet or exercise and my preceptor gave me the assignment to find out why.

While this question is difficult to answer there are some possible explanations as to why this could be occurring such as kidney failure, liver failure, cortisol release, or some other unknown factors.  

If a patient in this population developed kidney failure it would affect the amount insulin needed. This is due to the lack of metabolism or clearance of insulin from the kidneys. Normally, insulin is brought into the kidneys via carrier mediated endocytosis and placed in lysosomes. Once in the lysosome the insulin is then degraded into amino acids. If the kidneys are failing then the body is unable to metabolize the insulin. This means the insulin will remain in the body for longer periods of time. Resulting in a dose reduction of insulin and a decrease in the total amount of insulin required per day. 

In general, liver failure does not directly affect absorption or distribution of insulin. However, it may indirectly cause the dose of insulin to be reduced which could explain this small patient population situation. While this is not completely understood some research has shown there is a change in the steroid receptor coactivators. Steroid receptor coactivators are partly responsible for the production of glucose naturally in the body. In liver failure these steroid receptor coactivators are decreased. The decrease in coactivators results in a decrease in the amount of glucose produced by the liver. On the other hand, it is important to note liver failure has been proven to cause insulin resistance (worsening of diabetes).

Insulin normally suppresses the production of glucose but in liver failure it is proven insulin actually is unable to suppress the production of glucose. This excess production of glucose would cause an increase in the required amount of insulin for the patient. While steroid receptor coactivators research goes against what is proven (liver failure causing insulin resistance) and normally occurs the research does offer a small, but possible, explanation for this unique patient population.

Another possible reason for this population of patients to be able to decrease their insulin requirements and their weight could be due to the decrease in cortisol release. Cortisol is a hormone released from the adrenal gland during times of stress, infections, injury (except damage to adrenal gland resulting in a lack of cortisol release), and inflammation. When cortisol is released there are several effects: one of the effects is to increase the production of glucose from the liver and another effect is that cortisol contributes to insulin resistance. Insulin resistance occurs by decreasing the number of glucose transporters on the cells. A glucose transporter is how the glucose is moved into cells and out of the blood stream. Without a sufficient quantity of transporters it is difficult to get glucose into the cell which results in higher blood glucose and insulin resistance. Patients who have an increase in cortisol release will have an excess of glucose in the blood stream and therefore require more insulin to combat the situation. If an obese Type 2 diabetes patient were to decrease the release of cortisol due to either damage to the adrenal gland, resolution of inflammation, or resolution of infection then it is theoretically possible to decrease the production of glucose and increase the number of transports. This would all result in a decrease in blood glucose and less insulin required for these patients.

While it is assumed via speaking with the patients that there has been no drastic change in diet or exercise, the observation of the weight loss must be noted. It is an arguable point to wondering which came first: the weight loss causing a decrease in insulin or a decrease in insulin use causing a weight loss.

What could cause a patient to loose weight if the weight loss is not due to diet or exercise? Undiagnosed cancer, kidney failure, adrenal gland damage, or liver failure can all lead to an unexplained weight loss in the patients. On the other hand, a decrease in insulin use can cause weight loss too. It is known that insulin does cause weight gain due to the ability of insulin to store excess glucose in muscle and fat cells. Therefore if a patient were to need less insulin it would naturally cause a decrease in weight. Whether the weight loss is due to less insulin usage or due to another medical problem, it is undeniable that these patients are losing weight and using less insulin for one reason or another.

In my opinion, each patient is unique and the reasons they are experiencing this situation is probably different for each of them. I believe that these patients are most likely experiencing this situation due to a combination of many factors. In the meantime, while there is more research needed to fully understand this patient population we should celebrate these patients and their success in requiring less insulin and decreasing their weight


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