The World Health Organization distinguishes among non-diabetic persons a form of
glucose intolerance defined as
impaired glucose tolerance (IGT). The main reason for considering IGT as a diagnostic entity is its prognostic value for the development of
non-insulin-dependent diabetes mellitus (
NIDDM). However, the use of one or two oral
glucose tolerance tests (OGTT) for the definition of IGT and the large variability of the 2-h
glucose level may explain the wide range of the incidence rates reported for
NIDDM in subjects with IGT. It is evident that the pathogenesis of diabetes is still poorly understood. Both
insulin resistance and impaired function of the beta-cell are thought to be important contributing factors in the development of diabetes. The 2-h post-load
glucose level from the OGTT is most powerful for the prediction of the development of
NIDDM. In addition, a fasting hyperinsulinaemia and a low
glucose removal rate, both reflecting
insulin resistance, were found to be associated with a higher risk for the progression of
NIDDM. In the San Antonio Study and in the Hoorn Study high fasting
proinsulin levels, reflecting beta-cell dysfunction, were associated with progression to
NIDDM.
Lipid levels did not predict progression to
NIDDM in most studies. A two-step model for the development of
NIDDM is hypothesized. The first step, the transition from normal to
impaired glucose tolerance, is assumed to depend mainly on the presence of
insulin resistance. The second step, progressing from IGT to diabetes, although accompanied by some further worsening of
insulin resistance, is thought to be primarily dependent on the development of beta-cell dysfunction.