A two-step model for development of non-insulin-dependent diabetes

Abstract

Both insulin resistance and beta-cell dysfunction occur during the development of non-insulin-dependent diabetes mellitus (NIDDM), but controversy exists about which lesion is primary. Based on longitudinal studies in the Pima Indians, a population with the world's highest reported prevalence of NIDDM, a two-step model for development of the disease is proposed. The first step is transition from normal to impaired glucose tolerance, for which insulin resistance is the main determinant, and the second and later step is worsening from impaired glucose tolerance to diabetes, in which beta-cell dysfunction plays a critical role. This hypothesis is consistent with findings from other ethnic groups from many parts of the world.

Fatty acid binding protein 2 and insulin resistance

“…Their characterisitics were as follows [given as arithmetic mean^standard deviation (range)]: ages were 27^6 (19±39) years old; body mass index was 24´24^3´92 (17´58±34´26) kg m 22 ; and waist : hip ratio was 0´803^0´083 (0´649±1´033) cm cm 21 . Impaired glucose tolerance and overt diabetes are associated with insulin resistance [35]. Conversely, insulin sensitivity is impaired in nondiabetic subjects with essential hypertension [34].…”

Determinants of Diabetes Mellitus in the Pima Indians

“…The increase in insulin resistance may be attributable to weight gain (82)(83)(84), aging (85,86), and decreased physical activity (87). Thus, the development of NIDDM can be thought of as occurring in two stages: the first leading to impaired glucose tolerance with hyperinsulinemia (representing partially compensated insulin resistance) and the second leading to overt diabetes with worsening hyperglycemia as a result of failure to maintain sufficient compensatory hyperinsulinemia (perhaps as a result of (3-cell defects or exhaustion) (88). The transition to diabetes is probably caused not only by further increases in insulin resistance, as reflected by the increasing fasting insulin concentration, but also by failure to increase insulin secretion sufficiently in response to hyperglycemia.…”

Lifestyle intervention for prevention of diabetes: determinants of success for future implementation

“…Lifestyle intervention may improve the metabolic profile and reverse the progression towards diabetes (Figure 1). 5 In this manuscript, we summarize the mid-and longterm effects of lifestyle interventions in subjects with IGT to lifestyle intervention outcome, i.e., changes in glucose tolerance or diabetes incidence. In order to develop implementation strategies, it is important to know which factors determine the effectiveness of and adherence to the intervention.…”