2015 RESEARCH - Leading to a Cure for T1D?? –

                          Brain Centered Control & the Role of Leptin



       Prior to 1921, those physicians who were seeking a cure for T1D were focused on the brain as the center for glucose regulation. However, with the discovery of insulin in 1921, focus shifted to the “insulin” or “islet centered approach” for management of the disease rather than a search for its cure. For the last 95 years, physicians have been trained solely in the art of insulin management.

        What has been overlooked is the other half of the glucose balancing equation.

Insulin stimulates the secretion of the hormone Leptin produced by fat cells (adipocytes).  In turn, leptin, as part of a biofeedback mechanism for glucose balance, impacts the hypothalamus of the brain which employs nerve relays to reduce insulin production by pancreatic beta cells. In the case of the type 1 diabetic, insulin deficiency leads to leptin deficiency which disrupts the brain centered gluco-regulatory system (BCGS) leading to a hyperglycemic state.

        In the last five years, a group of German and U.S researchers have suggested a need to revive the concept of a BCGS that helps maintain glucose homeostasis. The new model suggests that there are two sides to glucose regulation – one, insulin dependent controlled by islet cells - the other, is the insulin-independent component, called glucose effectiveness ( GE) which is controlled by the brain.

          These researchers suggest that because activation of either regulatory system can compensate for failure of the other, defects in both may be required for diabetes to develop. They have noted that uncontrolled type 1 diabetes ( aka Brittle Diabetes) and deficiencies in insulin and leptin go hand in hand. Disruptions in these two hormones would cause brain dysfunction.  Animal studies have shown that giving large amounts of leptin or infusing leptin into the hypothalamus of the brain of animals with T1D  eliminates the need for insulin.

           BDF will continue to watch any research advances along these lines. According to those holding to the theory of brain centered control, the existing course of action viz., islet centered management will not lead to a cure because you’re tackling only 50% of the problem. The other 50% needed to effect a cure is to treat the mechanisms dealing with brain centered and insulin-independent regulation of glucose which involves the utilization of the hormone leptin.

             An individual diagnosed with brittle type 1 diabetes may want to begin discussions with their endocrinologist about brain centered control and the role of leptin and leptin deficiencies in this process. Tests for fasting blood insulin and leptin are available.   Other tests to be considered; CRP – can bind leptin and prevent it from getting into the brain effectively; Cortisol – can effect the release of leptin and insulin; Melatonin levels are impacted by leptin and insulin deficiencies; C – peptide is a useful marker of insulin production.

            BDF is of the opinion that as a diagnosed Brittle Diabetic, discussions of this type are necessary if the application of the insulin centered management approach is not working for you.