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

Ele Ferrannini1, Monica Nannipieri1, Ken Williams2, Clicerio Gonzales3, Steve M. Haffner2, and Michael P. Stern2 

1 Metabolism Unit, Department of Internal Medicine and C.N.R. Institute of Clinical Physiology, University of Pisa School of Medicine, Pisa, Italy
2 Division of Clinical Epidemiology, Department of Medicine, University of Texas Health Science Center at San Antonio, Texas
3 Centro de Estudios en Diabetes, American British Cowdray Hospital and Endocrinology and Metabolism Service, Division of Internal Medicine, Specialty Hospital of the National Medical Center, Mexican Social Security Institute, Mexico City, Mexico 

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 &plusmn; 0.79 mmol/l, mean &plusmn; 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 &plusmn; 2.57 and 2.94 &plusmn; 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 &plusmn; 3.83 and 3.12 &plusmn; 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 &plusmn; 4.9 vs. 27.3 &plusmn; 4.0 kg/m2; P < 0.001) and fasting plasma insulin values (120 &plusmn; 78 vs. 84 &plusmn; 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.  


Ferrannini E, Nannipieri M, Williams K, et al. Mode of Onset of Type 2 Diabetes from Normal or Impaired Glucose Tolerance. Diabetes. 2004;53:160-165. 

Last Modified: 2/8/2013