Insulin-dependent actions of pioglitazone in newly diagnosed, drug naïve patients with type 2 diabetes

Takuya Fukushima
June 2009
Endocrine (1355008X);Jun2009, Vol. 35 Issue 3, p333
Academic Journal
Abstract  The aim of this study was to study the effects of pioglitazone on several diabetic parameters with subjects possessing distinct levels of insulin. Treatment naive patients with type 2 diabetes received 15–30 mg/day pioglitazone monotherapy. At 3 months, levels of insulin, C-peptide, HbA1c, HOMA-R, HOMA-B and BMI were compared with those at baseline between the low (below 5.9 μU/ml, n = 48), medium (11.9–6 μU/ml n = 39) and high (above 12 μU/ml, n = 33) insulin groups. At baseline, differences existed in the levels of HbA1c, insulin, C-peptide, HOMA-R, HOMA-B, and BMI between these groups. In the high-insulin group significant reductions of insulin/C-peptide levels were observed, while in the low-insulin group significant increases of insulin/C-peptide were observed. In the medium-insulin group, no significant changes were observed. In contrast, the HbA1c levels significantly and similarly decreased in all the groups. Significant correlations between the changes of insulin/C-peptide levels with pioglitazone and the baseline insulin/C-peptide levels were observed. HOMA-R showed greater reductions in the high-insulin group, while HOMA-B showed greater increases in the low-insulin group in comparison to other groups. Multiple regression analysis revealed that the baseline insulin level is the predominant determinant of the changes of insulin levels with pioglitazone. These results suggest that pioglitazone appears to have two effects: to reduce insulin resistance (and lower insulin) and to improve beta-cell function (and increase insulin). The predominance of these effects appears to be determined by the insulin levels. Based on these data, a novel physiological model showing that pioglitazone may shift the natural history of diabetes toward an earlier stage (rejuvenation of beta-cell function) will be presented.


Related Articles

  • Parameters Measuring Beta-Cell Function Are Only Valuable in Diabetic Subjects with Low Body Mass Index, High Blood Glucose Level, or Long-Standing Diabetes. Seung Won Lee; Sangheun Lee; Se Hwa Kim; Tae Ho Kim; Byung Soo Kang; Seung Hoon Yoo; Min Kyung Lee; Won Jun Koh; Won Sik Kang; Hyeong Jin Kim // Yonsei Medical Journal;11/1/2011, Vol. 52 Issue 6, p939 

    Purpose: The aim of this study was to identify the most precise and clinically practicable parameters that predict future oral hypoglycemic agent (OHA) failure in patients with type 2 diabetes, and to determine whether these parameters are valuable in various subgroups. Materials and Methods: We...

  • Adiponectin and beta cell dysfunction in gestational diabetes: pathophysiological implications. Retnakaran, R.; Hanley, A.J. G.; Raif, N.; Hirning, C.R.; Connelly, P.W.; Sermer, M.; Kahn, S.E.; Zinman, B. // Diabetologia;May2005, Vol. 48 Issue 5, p993 

    Aims/hypothesis: Gestational diabetes mellitus (GDM) identifies a population of young women at high risk of developing type 2 diabetes and thus provides an excellent model for studying early events in the natural history of this disease. Adiponectin, a novel adipocyte-derived protein with...

  • The impact of ethnicity on glucose homeostasis after gestational diabetes mellitus. Ignell, Claes; Shaat, Nael; Ekelund, Magnus; Berntorp, Kerstin // Acta Diabetologica;Dec2013, Vol. 50 Issue 6, p927 

    The objective of this study was to examine measures of insulin resistance and beta cell function in relation to ethnicity and the development of diabetes after gestational diabetes mellitus (GDM). Glucose homeostasis was assessed during a 75 g oral glucose tolerance test 1–2 years...

  • Failure of β Cell Compensation in Glucose Tolerant Subjects with Increasing Insulin Resistance. Surampudi, Prasanth N.; Al-Sayed, Mohamad; Chang, Everett; Kwan, Connie; Feng, Wei; Chiu, Ken C. // Diabetes;Jun2007 Supplement 1, Vol. 56, pA381 

    It is well acknowledged that in glucose tolerant subjects, β cells compensate for prevailing insulin resistance by maintaining plasma glucose in a relatively narrow physiological range. However, there is little quantitative information on the β cell response in glucose tolerant subjects...

  • Patterns of Obesity Development before the Diagnosis of Type 2 Diabetes: The Whitehall II Cohort Study. Vistisen, Dorte; Witte, Daniel R.; Tabák, Adam G.; Herder, Christian; Brunner, Eric J.; Kivimäki, Mika; Færch, Kristine // PLoS Medicine;Feb2014, Vol. 11 Issue 2, p1 

    : Examining patterns of change in body mass index (BMI) and other cardiometabolic risk factors in individuals during the years before they were diagnosed with diabetes, Kristine Færch and colleagues report that few of them experienced dramatic BMI changes. Please see later in the article...

  • The Role of Helicobacter pylori Seropositivity in Insulin Sensitivity, Beta Cell Function, and Abnormal Glucose Tolerance. Malamug, Lou Rose; Karnchanasorn, Rudruidee; Samoa, Raynald; Chiu, Ken C. // Scientifica;2014, p1 

    Infection, for example, Helicobacter pylori (H. pylori), has been thought to play a role in the pathogenesis of type 2 diabetesmellitus (T2DM). Our aim was to determine the role of H. pylori infection in glucose metabolism in an American cohort. We examined data from 4,136 non-Hispanic white...

  • The hyperbolic law-a 25-year perspective. Stumvoll, M.; Tataranni, P.; Bogardus, C. // Diabetologia;Feb2005, Vol. 48 Issue 2, p207 

    The article focuses on the studies that have been conducted insulin sensitivity. In people with normal glucose tolerance, a decrease in insulin action is accompanied by up-regulation of insulin secretion, and vice versa. This is interpreted as a compensatory increase of insulin secretion, which...

  • Clearance of HCV Improves Insulin Resistance, Beta-Cell Function, and Hepatic Expression of Insulin Receptor Substrate 1 and 2. Kawaguchi, Takumi; Ide, Tatsuya; Taniguchi, Eitaro; Hirano, Eiichi; Itou, Minoru; Sumie, Shuji; Nagao, Yumiko; Yanagimoto, Chikatoshi; Hanada, Shinichiro; Koga, Hironori; Sata, Michio // American Journal of Gastroenterology;Mar2007, Vol. 102 Issue 3, p570 

    OBJECTIVES: Hepatitis C virus (HCV) infection is linked to greater insulin resistance. Although HCV itself is a candidate for the development of insulin resistance, the effects of antiviral treatment on impaired glucose metabolism remain unclear. The aim of this study is to examine the effects...

  • Early Insulinization to Prevent Diabetes Progression. RAZ, ITAMAR; MOSENZON, OFRI // Diabetes Care;Aug2013 Supplement, Vol. 36 Issue S2, pS190 

    The article examines data collected from clinical studies on the role of early insulin treatment in the preservation of ß-cell function in patients with type 2 diabetes. Despite the safety and feasibility of early insulin therapy demonstrated in the ORIGIN study, the authors argue there are...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics