Risk of Progression to Type 2 Diabetes Based on Relationship Between Postload Plasma Glucose and Fasting Plasma Glucose Diabetes Division and the Clinical Epidemiology Unit University of Texas Health Science Centre Diabetes Care; Jul 2006; 29 R3 맹치훈

Background Impaired glucose intolerance - time as borderline - “chemical diabetes” Impaired fasting glucose - fasting glucose level 100~125 mg/dL Normal fasting glucose [NFG] and normal glucose tolerance [NGT] - development of DM in 30~40% - preceding ß-cell dysfunction and insulin resistance before onset of IGT - linear relationship of the log of 2-h plasma glucose level  Risk for developing Type 2 DM in substantial number despite of NGT and NFG High risk for progression to overt DM

Objectives Identification of new risk factor for progression of type 2 DM in NGT subjects - study of relationship between the 2-h plasma glucose concentration during OGTT and FPG concentration

Research Design and Methods Subjects - participants of the San Antonio Heart Study - 1,282 aged 25~68 yeare - exclusion of IFG, IGT, overt DM at baseline - complete follow-up examination for 7~8 years Methods - 12-h overnight fasting - OGTT - Blood sampling for plasma glucose and insulin level : baseline time 0, 30, 60, 120 min - HOMA-IR and Matsuda index for insulin resistance - Insulinogenic index : ∆I 0~30 / ∆G 0~30 - Follow-up for 7~8 years

Results Classification A - Division into two groups according to the relationship between the 2-h plasma glucose concentration during OGTT and the FPG concentration 1) 381 subjects : 2-h plasma glucose concentration lower than FPG 2) 901 subjects : 2-h plasma glucose concentration higher than FPG - Odd ratio 2.33  0.75 with addition of insulin resistance and insulinogenic index as independent variables Incidence rates to DM in 7~8 years : 2.9 % Incidence rates to DM in 7~8 years : 5.9 %

Classification B - Division into four groups [ Group I~ IV] according to plasma glucose concentration during OGTT at the time point ( at ’30 ’60 ‘120 min and never) Metabolic Characteristics √

Figure 1 Plasma glucose (A) and Insulin (B) concentration during OGTT at the time ‘0 ’30 ’60 ‘120 and never Insulin resistance as HOMA-IR : increased progressively from Group I to IV Insulin sensitivity as Matsuda Index : declined progressively from Group I to IV Insulinogenic Index ∆I 0~30 / ∆G 0~30 : declined progressively from Group I to IV

Figure 2 Incidence of diabetes after 7~8 years based on the each group I~IV

Classification C – Division into four groups according to 2-h plasma glucose concentration - comparison of the impact of rising 2-h plasma glucose concentration to the development of DM Classification D – Subdivision of each groups according to relationship between FPG and 2-h plasma glucose concentration

Discussion Risk stratification for progression to DM of subjects with NGT and NFG - relationship between FPG concentration and postload plasma glucose concentration - first demonstration - consistent with the degree of insulin resistance and sensitivity according to risk stratification The time reqiured for the plasma glucose level to return to FPG level after glucose ingestion - dependent on insulin response during OGTT and peripheral / hepatic insulin sensitivity - increase insulin resistance + impaired insulin secretion  independent predictors of future development of type 2 DM

Group I : most efficient in normal glucose homeostasis - low ∆Insulin(AUC) / ∆Glucose(AUC) Group II : more insulin resistant than Group I - requirement of a higher ∆Insulin(AUC) / ∆Glucose(AUC) Group III : further worsening of insulin resistance - decreased early-phase insulin secretion calculated by insulinogenic index ( ∆I 0~30 / ∆G 0~30 ) Group IV : most severe insulin resistance + worst ß-cell function Odd ratio Group IV with Group I, II, III (plasma glucose level below FPG at 2-h OGTT) - abolished to just 0.75 by use of insulin sensitivity and secretion as independent variables  stratification based on the FPG and 2-h plasma glucose level ; reflecting insulin resistance and sensitivity

Subjects with Normal OGTT result and stratified to Group IV - not completely “normal” - respect to glucose tolerance and risk for progression to type 2 DM Current notion : safe from risk associated with glucose intolerance in all subjects with 2-h plasma glucose level < 140 mg/dL (OGTT) - not any more consistent with this study Subjects with NGT and NFG and no returning to FPG level after 2-h OGTT - significantly higher risk of progression to type 2 DM - greater insulin resistance and reduced insulin secretion CONCLUSION