title: Predictors of and longitudinal changes in insulin sensitivity and secretion preceding onset of type 2 diabetes.
abstract: Identification of individuals at high risk of developing type 2 diabetes is a prerequisite for prevention of the disease. We therefore studied risk factors predicting type 2 diabetes in the Botnia Study in Western Finland. A total of 2,115 nondiabetic individuals were prospectively followed with repeated oral glucose tolerance tests. After a median follow-up of 6 years, 127 (6%) subjects developed diabetes. A family history of diabetes (hazard ratio [HR] 2.2, P = 0.008), BMI (HR for comparison of values below or above the median 2.1, P < 0.001), waist-to-height index (2.3, P < 0.001), insulin resistance (2.1, P = 0.0004), and beta-cell function adjusted for insulin resistance (2.7, P < 0.0001) predicted diabetes. Marked deterioration in beta-cell function with modest changes in insulin sensitivity was observed during the transition to diabetes. The combination of FPG > or =5.6 mmol/l, BMI > or =30 kg/m(2), and family history of diabetes was a strong predictor of diabetes (3.7, P < 0.0001). Of note, using FPG > or =6.1 mmol/l or 2-h glucose > or =7.8 mmol/l did not significantly improve prediction of type 2 diabetes. In conclusion, a marked deterioration in beta-cell function precedes the onset of type 2 diabetes. These individuals can be identified early by knowledge of FPG, BMI, and family history of diabetes.
authors.affiliation: Department of Endocrinology, Wallenberg Laboratory, University Hospital MAS, 20502 Malmö, Sweden. valeri.lyssenko@endo.mas.lu.se
authors.forename: Valeriya
authors.initials: V
authors.lastname: Lyssenko
authors.forename: Peter
authors.initials: P
authors.lastname: Almgren
authors.forename: Dragi
authors.initials: D
authors.lastname: Anevski
authors.forename: Roland
authors.initials: R
authors.lastname: Perfekt
authors.forename: Kaj
authors.initials: K
authors.lastname: Lahti
authors.forename: Michael
authors.initials: M
authors.lastname: Nissén
authors.forename: Bo
authors.initials: B
authors.lastname: Isomaa
authors.forename: Björn
authors.initials: B
authors.lastname: Forsen
authors.forename: Nils
authors.initials: N
authors.lastname: Homström
authors.forename: Carola
authors.initials: C
authors.lastname: Saloranta
authors.forename: Marja-Riitta
authors.initials: MR
authors.lastname: Taskinen
authors.forename: Leif
authors.initials: L
authors.lastname: Groop
authors.forename: Tiinamaija
authors.initials: T
authors.lastname: Tuomi
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D002784:Cholesterol / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005260:Female; D005387:Finland / Q000453:epidemiology; D018149:Glucose Intolerance / Q000097:blood / Q000503:physiopathology*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008055:Lipids / Q000097:blood; D008137:Longitudinal Studies; D008297:Male; D008487:Medical History Taking; D008875:Middle Aged; D011236:Prediabetic State / Q000097:blood / Q000503:physiopathology*; D012307:Risk Factors; D012907:Smoking
chemical_list: D001786:Blood Glucose; D007328:Insulin; D008055:Lipids; D002784:Cholesterol