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CLINICAL STUDY

Relationship between plasma insulin concentration and plasma remnant lipoprotein response to an oral fat load in patients with type 2 diabetes

Masumi Ai, MD^*, Akira Tanaka, MD^*,*, Keiko Ogita, MD, Masaaki Sekinc, MD, Fujie Numano, MD, Fujio Numano, MD^* and Gerald M. Reaven, MD

^* Third Department of Internal Medicine, Tokyo Medical and Dental University, Tokyo, Japan
Department of Internal Medicine, Tokyo Metropolitan Kiyose Hospital, Tokyo, Japan
Department of Medicine, Stanford University School of Medicine, Stanford, California, USA

Manuscript received January 17, 2001; revised manuscript received July 18, 2001, accepted August 15, 2001.

^* Reprint requests and correspondence: Dr. Akira Tanaka, Third Department of Internal Medicine, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, Japan 113-8519
tanaka.med3{at}med.tmd.ac.jp

OBJECTIVES

The goal of this study was to evaluate the relative effects of hyperglycemia and hyperinsulinemia on postprandial remnant lipoprotein (RLP) concentrations in newly diagnosed type 2 diabetics.

BACKGROUND

Increases in fasting RLP concentration have been described in type 2 diabetics, as well as in insulin-resistant nondiabetics. Given the atherogenicity of RLPs, we have extended these observations by assessing postprandial RLP concentrations and observing that hyperglycemia was necessary for the increase in RLP concentrations.

METHODS

Patients with type 2 diabetes were subdivided on the basis of their plasma insulin response to oral glucose into hyperinsulinemic (H-DM) and normoinsulinemic (N-DM) groups of 15 patients each. Plasma triglyceride (TG), RLP-TG and RLP cholesterol (RLP-C) concentrations were determined before and 2 and 4 h after an oral fat load in these patients and 10 control (CTL) subjects.

RESULTS

Plasma TG, RLP-TG and RLP-C concentrations peaked 2 h after the fat load in the CTL group, returning to baseline within 4 h. In contrast, concentrations of these variables increased throughout the 4-h study in both groups of patients with type 2 diabetes. Total integrated plasma RLP-TG and RLP-C responses above baseline after the oral fat load were significantly higher in the H-DM group compared with the CTL (p = 0.019 and 0.009, respectively) or N-DM (p = 0.026 and 0.029, respectively) groups. Post-heparin lipoprotein lipase activities and apo E phenotypes were similar in the H-DM and N-DM groups.

CONCLUSIONS

Remnant lipoprotein response to an oral fat load is significantly increased in hyperinsulinemic patients with type 2 diabetes. These changes may increase the risk of coronary heart disease in these individuals.

Abbreviations and Acronyms   apo = apolipoprotein   BMI = body mass index   C = cholesterol   CHD = coronary heart disease   CTL = healthy volunteers   HDL = high-density lipoprotein   H-DM = hyperinsulinemic patient with type 2 diabetes   LPL = lipoprotein lipase   N-DM = normoinsulinemic patient with type 2 diabetes   OPTT = oral fat tolerance test   RLP = remnant lipoprotein   RLP-C = remnant lipoprotein cholesterol   RLP-TG = remnant lipoprotein triglyceride   TG = triglyceride

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