Defining and Characterizing the Progression of Type 2 Diabetes

Defining and Characterizing the Progression of Type 2 Diabetes Vivian A. Fonseca , MD From the Tulane University Medical Center, New Orleans, Louisiana. Corresponding author: Vivian A. Fonseca, vfonseca{at}tulane.edu . Type 2 diabetes is a progressive disease in which the risks of myocardial infarction, stroke, microvascular events, and mortality are all strongly associated with hyperglycemia ( 1 ). The disease course is primarily characterized by a decline in β-cell function and worsening of insulin resistance. The process is manifested clinically by deteriorations in multiple parameters, including A1C, fasting plasma glucose (FPG), and postprandial glucose levels. In this review, we will evaluate our current understanding of the role played by deteriorating β-cell function and other abnormalities linked with the progression of type 2 diabetes. An improved understanding of these abnormalities may provide the scientific groundwork for novel therapies that may help achieve and maintain good glycemic control. CHARACTERISTICS OF DISEASE PROGRESSION Progression from pre-diabetes to overt diabetes Because glucose is a continuous variable, the use of thresholds to make a diagnosis is somewhat arbitrary. The term “pre-diabetes” has become well established and implies a risk of progression to overt diabetes. However, although such progression is well studied in prevention trials, little is known about the rate of progression and the characteristics of such progression in the population at large. Table 1 summarizes some of the factors associated with such progression. Nichols et al. ( 2 ) studied the progression of pre-diabetes to overt disease and observed that 8.1% of subjects whose initial abnormal fasting glucose was 100–109 mg/dl and 24.3% of subjects whose initial abnormal fasting glucose was 110–125 mg/dl developed diabetes over an average of 29.0 months (1.34 and 5.56% per year, respectively). A steeper rate of increasing fasting glucose; higher BMI, blood pressure, and triglycerides; and lower HDL cholesterol predicted diabetes development. View this table: In this window In a new window Table 1 Factors associated with progression of pre-diabetes to diabetes The Baltimore Longitudinal Study of Aging ( 3 ) concluded that although phenotypic differences in rates of progression are partly a function of diagnostic thresholds, fasting and postchallenge hyperglycemia may represent phenotypes with distinct natural … [Full Text of this Article]