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Troglitazone Ameliorates Insulin Resistance in Patients with Werner’s Syndrome—Author’s Response

Nagasaki University School of Medicine Nagasaki, Japan

Thank you very much for the opportunity to respond to Dr. Minamikawa’s letter (above). The data is interesting, providing the intimal and medial complex thickness (IMT) positively correlate with both endogenous and exogenous insulin in NIDDM patients. Furthermore, troglitazone treatment (400 mg per day for 3 months) significantly resulted in decrease in IMT (-0.196 ± 0.082 mm). The results associated with the first part have been demonstrated in our study showing that the NIDDM patients suffering from arteriosclerosis obliterans (ASO) were observed to be more insulin resistant than those not suffering from ASO (1). In that study, insulin resistance was assessed by the short insulin tolerance test’s K index (KITT) (2.16 ± 0.16 vs. 3.00 ± 0.13%/min, with ASO vs. without, respectively). Although Dr. Minamikawa did not mention in his letter how much insulin resistance the patients had, it is quite possible to speculate that higher levels of plasma insulin may be the reflection by the insulin resistance in their patients.

For the second part, we do not have sufficient data indicating the troglitazone’s preventive or inhibitory effects on atherosclerosis progression in the patients with Werner’s syndrome in our study. We fully agree with the idea that trials of troglitazone in the treatment of Werner’s syndrome should be conducted to test for the attenuation of atherosclerosis. Skin ulcers as clinical manifestation were found in three out of five patients with Werner’s syndrome in our study and not in the remainder (2). Therefore the sensitive examination, for example IMT, should be required to find early changes of atherosclerosis in these patients, and they deserve to have treatment with troglitazone to evaluate the antiatherosclerotic effect of this drug. The research on the pathogenesis of atherosclerosis found in Werner’s syndrome is just beginning to reveal answers. Hypercoagulable condition was observed as manifested by an increase in the level of tissue plasminogen activator (t-PA) and PA inhibitor-1 (PAI-1), and by decrease in the level of thrombomodulin (TM) in 9 patients with Werner’s syndrome (3). Thus, complex risk factors including hyperinsulinemia, insulin resistance, and hypercoagulation would be expected to contribute to the progression of atherosclerosis in Werner’s syndrome as well as in NIDDM. Although exact biochemical action of troglitazone has not been determined, the application of this drug to Werner’s syndrome would delineate possible mechanisms by which anti-atherosclerotic action would be evoked with this.

Footnotes

Address correspondence to: Hironori Yamasaki, M.D., The First Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto Nagasaki, 852 Japan.

Received December 4, 1997.

References

1. Matsumo K, Miyake S, Yano Y, et al. 1997 Insulin resistance and arteriosclerosis obliterance in patients with NIDDM. Diabetes Care. 20:1738–1743.[Abstract]
2. Izumino K, Sakamaki H, Ishibashi M, et al. 1997 Troglitazone ameliorates insulin resistance in patients with Werner’s syndrome. J Clin Endocrinol Metab. 82:2391–2395.[Abstract/Free Full Text]
3. Goto M, Kato Y. 1995 Hypercoagulable state indicates an additional risk factor for atherosclerosis in Werner’s syndrome. Thromb Haemostasis. 73:576–578.[Medline]

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