Type 1 and Type 2 Diabetes

The molecular and cellular origins of diabetes remain a mystery.  Genetic variation analyzed by genome-wide association or genome-wide sequencing indicates a very small role for genetic variation among patients studied.  CNM scientists have composed and published an alternative model of the origins of obesity-associated Type 2 diabetes that does not emanate from genetic variation, but instead reflects cellular dysfunction caused by nutritional and metabolic alterations in the presence of high levels of fatty acids.  This discovery explains why ‘diabetes genes’ are not a major factor in Type 2 diabetes, and why investigating ‘diabetes resistance’ genes would be a more effective approach to understand and treat this syndrome.  These discoveries are unique in the field of diabetes research and have combined human patient data to validate these findings.  The induced elimination of pancreatic beta cell glucose transport in individuals with high free fatty acid levels severely reduces the availability of glucose and thereby impairs cellular glycolysis and glucose sensing, which further eliminates glucose-stimulated insulin secretion.  These discoveries are integrating into mainstream research of which the pancreatic beta cell is re-established as a central component of disease etiology, and which provides a novel approach to treat and reverse this potentially deadly condition.