title: 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.
authors.affiliation: Metabolism Unit, Department of Internal Medicine and C.N.R. Institute of Clinical Physiology, University of Pisa School of Medicine, Pisa, Italy. ferranni@ifc.cnr.it
authors.forename: Ele
authors.initials: E
authors.lastname: Ferrannini
authors.forename: Monica
authors.initials: M
authors.lastname: Nannipieri
authors.forename: Ken
authors.initials: K
authors.lastname: Williams
authors.forename: Clicerio
authors.initials: C
authors.lastname: Gonzales
authors.forename: Steve M
authors.initials: SM
authors.lastname: Haffner
authors.forename: Michael P
authors.initials: MP
authors.lastname: Stern
mesh_terms: D001786:Blood Glucose / Q000032:analysis* / Q000378:metabolism; D001824:Body Constitution; D001835:Body Weight; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics / Q000503:physiopathology*; D018450:Disease Progression; D005260:Female; D018149:Glucose Intolerance / Q000097:blood / Q000503:physiopathology*; D005951:Glucose Tolerance Test; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors
chemical_list: D001786:Blood Glucose