The Connection
In his 1988 Banting lecture, Reaven noted that resistance to insulin was common among patients with coronary artery disease.⁴ Some of these patients were frankly diabetic, but others had mildly impaired glucose tolerance and some had normal glucose tolerance. He also identified other CVD risk factors that were associated with resistance: hypertension, elevated triglycerides, and low high-density lipoprotein (HDL) cholesterol. He named this cluster ‘syndrome X.’ He attributed the co-existence of CVD risk factors and diabetes to elevated free fatty acids. The latter are increased with increasing visceral adiposity and lead to excessive triglyceride production by the liver, increased glucose output by the liver, and increased resistance to insulin in muscle cells. The rising insulin level will usually balance the resistance by increasing insulin production. In some, due to genetics, lipid or glucose toxicity, or ‘overproduction,’ insulin production fails to maintain strides with the resistance leading to various degrees of glucose intolerance. The UK Prospective Diabetes Study ⁵ of several thousand type 2 diabetic patients gave evidence that at the time of diagnosis of diabetes, half of beta cell function was gone. Thereafter, over the next 10–15 years, the function would continue to decline, leading to the failure of the oral antiglycemic medications and the need for insulin treatment. The implication, then, is early treatment of glucose intolerance and the associated CVD risk factors will lead to reduction in CVD events.

Diagnosing Diabetes
Diabetes is diagnosed only by the plasma glucose (see Table 1). If fasting glucose is greater than 125mg/dl on two consecutive occasions or if the second hour plasma glucose following a 75 glucose oral drink is greater than 199mg/dl on two consecutive occasions then the diagnosis of diabetes is secured.⁶ As mentioned above, glucose intolerance is a continuum—it is recognized that between ‘normal glucose’ and diabetes there exists a prediabetes condition. There are two forms of prediabetes: impaired fasting glucose (IFG) and impaired glucose tolerance (IGT). IFG is diagnosed when the fasting plasma glucose is 100–125mg/dl on two consecutive periods and IGT is diagnosed when the second hour following a 75g oral glucose drink is 140–199mg/dl on two consecutive periods. It is important to properly diagnose these conditions. A person with prediabetes suffers an 11% chance/year of developing diabetes.⁷ Owing to the clustering of other CVD risk factors, such diagnosed patients have a greater risk of developing CVD. Owing to the genetic nature of glucose intolerance, family members of patients with prediabetes are also at increased risk for the same.