Mode of Onset of Type 2 Diabetes from Normal or Impaired Glucose Tolerance

Abstract

Fasting plasma glucose concentrations (FPG) predict development of type 2 diabetes. Whether hyperglycemia evolves from normoglycemia gradually over time or as a step increase is not known. We measured plasma glucose and insulin levels during oral glucose testing in 35-to 64-year-old men and nonpregnant women from a population-based survey (Mexico City Diabetes Study) at baseline (n ‫؍‬ 2,279) and after 3.25 (n ‫؍‬ 1,740) and 7 years (n ‫؍‬ 1,711) of follow-up. In subjects with normal glucose tolerance (NGT) on all three occasions (nonconverters; n ‫؍‬ 911), FPG increased only slightly (0.23 ؎ 0.79 mmol/l, mean ؎ SD; P < 0.0001) over 7 years. In contrast, conversion to diabetes among NGT subjects (n ‫؍‬ 98) was marked by a large step-up in FPG regardless of time of conversion (3.06 ؎ 2.57 and 2.94 ؎ 3.11 mmol/l, respectively, at 3.25 and 7 years; P < 0.0001 vs. nonconverters). Likewise, in subjects who converted to diabetes from impaired glucose tolerance (n ‫؍‬ 75), FPG rose by 3.14 ؎ 3.83 and 3.12 ؎ 3.61 mmol/l (P < 0.0001 vs. nonconverters). Three-quarters of converters had increments in FPG above the 90th percentile of the corresponding increments in nonconverters. Converters had higher baseline BMI (30.4 ؎ 4.9 vs. 27.3 ؎ 4.0 kg/m 2 ; P < 0.001) and fasting plasma insulin values (120 ؎ 78 vs. 84 ؎ 84 pmol/l; P < 0.02) than nonconverters; however, no consistent change in either parameter had occurred before conversion. In contrast, changes in 2-h postglucose insulin levels between time of conversion and preceding measurement were significantly (P < 0.0001) related to the corresponding changes in FPG in an inverse manner. We conclude that, within a 3-year time frame, the onset of diabetes is very often rapid rather than gradual and is in part explained by a fall in glucose-stimulated insulin response. Diabetes 53:160 -165, 2004 D evelopment of type 2 diabetes is, to some extent, a predictable event. Several studies in different populations have identified anthropometric and metabolic characteristics that increase the likelihood that a person with initially normal glucose tolerance (NGT) will progress to diabetes over a specified period of time (1-3). Thus, family history of diabetes and obesity are potent risk factors amplified by increasing age. In addition, both fasting hyperinsulinemia and the fasting plasma glucose concentration (FPG) itself mark, independent of one another, an enhanced risk of developing the disease (4,5). In the combined analysis of three prospective studies (6), the presence of one or more components of the metabolic syndrome, namely, hyperinsulinemia, dyslipidemia, hypertension, and glucose intolerance, predicted the emergence of diabetes over 8 years of follow-up. Among individuals with impaired glucose tolerance (IGT), the rate of progression to overt diabetes is higher than among people with NGT by a factor of 2-10 (7,8).That a higher, if still normal, FPG shares with other risk markers the ability to predict future hyperglycemia has led to what probably is the concept prevailing amo...

Coordinate Changes in Plasma Glucose and Pancreatic β-Cell Function in Latino Women at High Risk for Type 2 Diabetes

“…As a result, we were able to identify the more rapid increase in glucose that occurs for any fall in acute ␤-cell function as women actually develop diabetes. Our findings provide a potential explanation for the observation of Ferrannini et al (30) in a different Hispanic-American population that plasma glucose levels rise more rapidly during conversion from impaired or normal glucose tolerance to diabetes than from normal to impaired glucose tolerance.…”

Plasma glucose levels as predictors of diabetes: the Mexico City diabetes study

“…Again, known pathophysiology underlies these stochastic features. Thus, high serum proinsulin concentrations are reputed to stand for early beta cell dysfunction (incomplete processing of proinsulin to insulin) [20]; hypertension co-segregates with manifest diabetes and higher blood pressure levels co-track insulin resistance [21]; low HDL-cholesterol concentrations cluster with insulin resistance [22]; and lower post-load plasma insulin levels have been shown to predict and precede onset of diabetes in the Mexico City population [23]. Therefore, a screening algorithm for diabetes risk could include not only anthropometric but also other traits of the prediabetic state, with or without [24], plasma glucose measures.…”

Impact of weight and weight change on normalization of prediabetes and on persistence of normal glucose tolerance in an older population: the KORA S4/F4 study

“…[11][12][13][14] In some other studies the influence of initial BMI on the progression from NGT to prediabetes was investigated, 15,16 but little is known about the association of weight and weight change with persistence of NGT in older people. 17 Thus, the objective of this study is to assess the role of weight and weight change for the reversion from prediabetes to NGT, and for long-term persistence of NGT in an older population without lifestyle intervention. Moreover, we investigate the effects of waist circumference and change of waist circumference on reversion to NGT and on persistence of NGT.…”