Pathophysiology
Clinical meaning
Type 2 diabetes mellitus (T2DM) is a progressive metabolic disorder characterized by insulin resistance in peripheral tissues (skeletal muscle, liver, adipose tissue) combined with progressive beta-cell dysfunction leading to relative insulin deficiency. The NP must master the ADA diagnostic criteria and understand the pathophysiological basis for each test. Four diagnostic criteria exist (any ONE is sufficient for diagnosis when confirmed on repeat testing): (1) Hemoglobin A1C โฅ6.5%: reflects average glycemia over 2-3 months (the lifespan of a red blood cell); glucose non-enzymatically glycosylates hemoglobin proportional to ambient glucose concentration; advantages include no fasting requirement and low day-to-day variability; HOWEVER, A1C is unreliable in conditions affecting RBC lifespan (hemolytic anemia, sickle cell disease, significant blood loss, iron deficiency anemia, chronic kidney disease, pregnancy) -- these conditions falsely lower A1C by reducing RBC lifespan. (2) Fasting plasma glucose (FPG) โฅ126 mg/dL: reflects hepatic glucose output in the fasting state; normally, the liver produces glucose through glycogenolysis and gluconeogenesis to maintain euglycemia during fasting, regulated by the insulin-to-glucagon ratio; in T2DM, hepatic insulin resistance causes excessive hepatic glucose production despite normal or elevated...