title: Pharmacological treatment of insulin resistance at two different stages in the evolution of type 2 diabetes: impact on glucose tolerance and beta-cell function.
abstract: The purpose of this study was to compare the impact of treating insulin resistance with a thiazolidinedione drug before vs. at the onset of diabetes on glucose levels and beta-cell function. Nondiabetic Hispanic women of Mexican or Central American descent with prior gestational diabetes mellitus (GDM) were randomized to troglitazone (early intervention), 400 mg/d, or placebo (later intervention). Women who developed diabetes were placed on open-label troglitazone. Glucose tolerance, insulin resistance, and beta-cell function were measured at randomization, at the diagnosis of diabetes, and 8 months post trial to determine the long-term impact of the two treatment strategies on glucose levels and beta-cell function. During a mean follow-up of 4.3 yr between baseline and posttrial tests, glucose tolerance (oral glucose tolerance test glucose area, P = 0.04) and insulin resistance (MINMOD SI, P = 0.02) worsened more in women randomized to late intervention (n = 69) than to early intervention (n = 57). Insulin secretion (acute insulin response in the iv glucose tolerance test, P = 0.09) and beta-cell compensation for insulin resistance (disposition index, P = 0.07) also tended to worsen more in the late intervention group. Among women in the late intervention group who developed diabetes, oral glucose tolerance test glucose area (P = 0.0001) and beta-cell function (P < or = 0.04) deteriorated significantly during development of diabetes on placebo and then did not change significantly (P > 0.50) during treatment with troglitazone and posttreatment washout. In high-risk Hispanic women, amelioration of insulin resistance can stabilize glycemia at the time diabetes develops. These findings highlight the role of insulin resistance in the genesis of progressive beta-cell dysfunction during the evolution of type 2 diabetes.
authors.affiliation: Department of Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, California 90033, USA.
authors.forename: Anny H
authors.initials: AH
authors.lastname: Xiang
authors.forename: Ruth K
authors.initials: RK
authors.lastname: Peters
authors.forename: Siri L
authors.initials: SL
authors.lastname: Kjos
authors.forename: Jose
authors.initials: J
authors.lastname: Goico
authors.forename: Cesar
authors.initials: C
authors.lastname: Ochoa
authors.forename: Aura
authors.initials: A
authors.lastname: Marroquin
authors.forename: Sylvia
authors.initials: S
authors.lastname: Tan
authors.forename: Howard N
authors.initials: HN
authors.lastname: Hodis
authors.forename: Stanley P
authors.initials: SP
authors.lastname: Azen
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Buchanan
mesh_terms: D000328:Adult; D001786:Blood Glucose; D002839:Chromans / Q000008:administration & dosage*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000517:prevention & control*; D005260:Female; D018149:Glucose Intolerance / Q000188:drug therapy*; D006630:Hispanic or Latino; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D007515:Islets of Langerhans / Q000187:drug effects* / Q000502:physiology; D045162:Thiazolidinediones / Q000008:administration & dosage*; D013997:Time Factors; D000077288:Troglitazone
chemical_list: D001786:Blood Glucose; D002839:Chromans; D007004:Hypoglycemic Agents; D007328:Insulin; D045162:Thiazolidinediones; D000077288:Troglitazone