Extreme insulin resistance occurs in patients with primary defects in insulin action at the receptor or postreceptor levels. The condition commonly is associated with acanthosis nigricans and ovarian masculinization. Despite a marked increase in insulin secretion, some patients develop frank diabetes mellitus that does not respond adequately to insulin therapy. Insulinlike growth factor I exerts metabolic effects similar to those of insulin. This study assessed the potential effectiveness of IGF-I as a blood glucose lowering agent in patients with extreme insulin resistance syndromes, including type A insulin resistance, congenital generalized lipodystrophy, and leprechaunism. Among the 11 patients studied, some exhibited mutated insulin receptors, whereas others were suspected to have defects in postreceptor sites. In each patient, plasma glucose levels decreased in response to subcutaneous injections of recombinant human IGF-I (0.1−0.3 mg/kg body wt). The degree of the decrease was roughly comparable with that observed in normal individuals. IGF-I also reduced plasma insulin concentrations. A long-term trial of IGF-I (up to 16 mo) showed that IGF-I (0.1−0.4 mg/kg body wt twice daily) is effective in lowering both fasting and postprandial plasma glucose concentrations with decreases in both fructosamine and HbA1c values. Improvement of acanthosis nigricans was observed in some of the patients. These results suggest that recombinant human IGF-I could be used clinically as a hypoglycemic agent in diabetic patients with extreme insulin resistance in whom insulin treatment is ineffective.
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Original Articles|
May 01 1993
Trial of Insulinlike Growth Factor I Therapy for Patients With Extreme Insulin Resistance Syndromes
Hideshi Kuzuya;
Hideshi Kuzuya
Second Department of Internal Medicine, Kyoto University School of Medicine
Kyoto
Department of Pediatrics, Tonan Hospital
Sapporo
Department of Pediatrics, Yamagata City Hospital
Saiseikan, Yamagata
Department of Internal Medicine, Chiba University School of Medicine
Chiba
Department of Internal Medicine, Teikyo University School of Medicine
Ichihara
Department of Internal Medicine, Faculty of Medicine, University of Tokyo
Tokyo
Department of Pediatrics, Toyohashi City Hospital
Toyohashi
Department of Internal Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University
Toyama
Diabetes Center, Institute of Endocrinology and Metabolic Disease, Kyoto National Hospital
Kyoto
Center for Diabetes Mellitus, Department of Internal Medicine, Osaka Rosai Hospital
Osaka
Department of Endocrinology, Tenri Hospital
Tenri
Department of Internal Medicine, Kobe University School of Medicine
Kobe
Department of Endocrinology and Metabolism, Kobe Children's Hospital
Kobe
Department of Internal Medicine, Nagasaki University School of Medicine
Nagasaki, Nagasaki
Research and Development Group, Fujisawa Pharmaceutical Company
Osaka
Department of Internal Medicine, Kyoto University School of Medicine
Kyoto, Japan
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Nobuo Matsuura;
Nobuo Matsuura
Second Department of Internal Medicine, Kyoto University School of Medicine
Kyoto
Department of Pediatrics, Tonan Hospital
Sapporo
Department of Pediatrics, Yamagata City Hospital
Saiseikan, Yamagata
Department of Internal Medicine, Chiba University School of Medicine
Chiba
Department of Internal Medicine, Teikyo University School of Medicine
Ichihara
Department of Internal Medicine, Faculty of Medicine, University of Tokyo
Tokyo
Department of Pediatrics, Toyohashi City Hospital
Toyohashi
Department of Internal Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University
Toyama
Diabetes Center, Institute of Endocrinology and Metabolic Disease, Kyoto National Hospital
Kyoto
Center for Diabetes Mellitus, Department of Internal Medicine, Osaka Rosai Hospital
Osaka
Department of Endocrinology, Tenri Hospital
Tenri
Department of Internal Medicine, Kobe University School of Medicine
Kobe
Department of Endocrinology and Metabolism, Kobe Children's Hospital
Kobe
Department of Internal Medicine, Nagasaki University School of Medicine
Nagasaki, Nagasaki
Research and Development Group, Fujisawa Pharmaceutical Company
Osaka
Department of Internal Medicine, Kyoto University School of Medicine
Kyoto, Japan
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Michiyo Sakamoto;
Michiyo Sakamoto
Second Department of Internal Medicine, Kyoto University School of Medicine
Kyoto
Department of Pediatrics, Tonan Hospital
Sapporo
Department of Pediatrics, Yamagata City Hospital
Saiseikan, Yamagata
Department of Internal Medicine, Chiba University School of Medicine
Chiba
Department of Internal Medicine, Teikyo University School of Medicine
Ichihara
Department of Internal Medicine, Faculty of Medicine, University of Tokyo
Tokyo
Department of Pediatrics, Toyohashi City Hospital
Toyohashi
Department of Internal Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University
Toyama
Diabetes Center, Institute of Endocrinology and Metabolic Disease, Kyoto National Hospital
Kyoto
Center for Diabetes Mellitus, Department of Internal Medicine, Osaka Rosai Hospital
Osaka
Department of Endocrinology, Tenri Hospital
Tenri
Department of Internal Medicine, Kobe University School of Medicine
Kobe
Department of Endocrinology and Metabolism, Kobe Children's Hospital
Kobe
Department of Internal Medicine, Nagasaki University School of Medicine
Nagasaki, Nagasaki
Research and Development Group, Fujisawa Pharmaceutical Company
Osaka
Department of Internal Medicine, Kyoto University School of Medicine
Kyoto, Japan
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Hideichi Makino;
Hideichi Makino
Second Department of Internal Medicine, Kyoto University School of Medicine
Kyoto
Department of Pediatrics, Tonan Hospital
Sapporo
Department of Pediatrics, Yamagata City Hospital
Saiseikan, Yamagata
Department of Internal Medicine, Chiba University School of Medicine
Chiba
Department of Internal Medicine, Teikyo University School of Medicine
Ichihara
Department of Internal Medicine, Faculty of Medicine, University of Tokyo
Tokyo
Department of Pediatrics, Toyohashi City Hospital
Toyohashi
Department of Internal Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University
Toyama
Diabetes Center, Institute of Endocrinology and Metabolic Disease, Kyoto National Hospital
Kyoto
Center for Diabetes Mellitus, Department of Internal Medicine, Osaka Rosai Hospital
Osaka
Department of Endocrinology, Tenri Hospital
Tenri
Department of Internal Medicine, Kobe University School of Medicine
Kobe
Department of Endocrinology and Metabolism, Kobe Children's Hospital
Kobe
Department of Internal Medicine, Nagasaki University School of Medicine
Nagasaki, Nagasaki
Research and Development Group, Fujisawa Pharmaceutical Company
Osaka
Department of Internal Medicine, Kyoto University School of Medicine
Kyoto, Japan
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Yoshikazu Sakamoto;
Yoshikazu Sakamoto
Second Department of Internal Medicine, Kyoto University School of Medicine
Kyoto
Department of Pediatrics, Tonan Hospital
Sapporo
Department of Pediatrics, Yamagata City Hospital
Saiseikan, Yamagata
Department of Internal Medicine, Chiba University School of Medicine
Chiba
Department of Internal Medicine, Teikyo University School of Medicine
Ichihara
Department of Internal Medicine, Faculty of Medicine, University of Tokyo
Tokyo
Department of Pediatrics, Toyohashi City Hospital
Toyohashi
Department of Internal Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University
Toyama
Diabetes Center, Institute of Endocrinology and Metabolic Disease, Kyoto National Hospital
Kyoto
Center for Diabetes Mellitus, Department of Internal Medicine, Osaka Rosai Hospital
Osaka
Department of Endocrinology, Tenri Hospital
Tenri
Department of Internal Medicine, Kobe University School of Medicine
Kobe
Department of Endocrinology and Metabolism, Kobe Children's Hospital
Kobe
Department of Internal Medicine, Nagasaki University School of Medicine
Nagasaki, Nagasaki
Research and Development Group, Fujisawa Pharmaceutical Company
Osaka
Department of Internal Medicine, Kyoto University School of Medicine
Kyoto, Japan
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Takashi Kadowaki;
Takashi Kadowaki
Second Department of Internal Medicine, Kyoto University School of Medicine
Kyoto
Department of Pediatrics, Tonan Hospital
Sapporo
Department of Pediatrics, Yamagata City Hospital
Saiseikan, Yamagata
Department of Internal Medicine, Chiba University School of Medicine
Chiba
Department of Internal Medicine, Teikyo University School of Medicine
Ichihara
Department of Internal Medicine, Faculty of Medicine, University of Tokyo
Tokyo
Department of Pediatrics, Toyohashi City Hospital
Toyohashi
Department of Internal Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University
Toyama
Diabetes Center, Institute of Endocrinology and Metabolic Disease, Kyoto National Hospital
Kyoto
Center for Diabetes Mellitus, Department of Internal Medicine, Osaka Rosai Hospital
Osaka
Department of Endocrinology, Tenri Hospital
Tenri
Department of Internal Medicine, Kobe University School of Medicine
Kobe
Department of Endocrinology and Metabolism, Kobe Children's Hospital
Kobe
Department of Internal Medicine, Nagasaki University School of Medicine
Nagasaki, Nagasaki
Research and Development Group, Fujisawa Pharmaceutical Company
Osaka
Department of Internal Medicine, Kyoto University School of Medicine
Kyoto, Japan
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Yoshimi Suzuki;
Yoshimi Suzuki
Second Department of Internal Medicine, Kyoto University School of Medicine
Kyoto
Department of Pediatrics, Tonan Hospital
Sapporo
Department of Pediatrics, Yamagata City Hospital
Saiseikan, Yamagata
Department of Internal Medicine, Chiba University School of Medicine
Chiba
Department of Internal Medicine, Teikyo University School of Medicine
Ichihara
Department of Internal Medicine, Faculty of Medicine, University of Tokyo
Tokyo
Department of Pediatrics, Toyohashi City Hospital
Toyohashi
Department of Internal Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University
Toyama
Diabetes Center, Institute of Endocrinology and Metabolic Disease, Kyoto National Hospital
Kyoto
Center for Diabetes Mellitus, Department of Internal Medicine, Osaka Rosai Hospital
Osaka
Department of Endocrinology, Tenri Hospital
Tenri
Department of Internal Medicine, Kobe University School of Medicine
Kobe
Department of Endocrinology and Metabolism, Kobe Children's Hospital
Kobe
Department of Internal Medicine, Nagasaki University School of Medicine
Nagasaki, Nagasaki
Research and Development Group, Fujisawa Pharmaceutical Company
Osaka
Department of Internal Medicine, Kyoto University School of Medicine
Kyoto, Japan
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Masashi Kobayashi;
Masashi Kobayashi
Second Department of Internal Medicine, Kyoto University School of Medicine
Kyoto
Department of Pediatrics, Tonan Hospital
Sapporo
Department of Pediatrics, Yamagata City Hospital
Saiseikan, Yamagata
Department of Internal Medicine, Chiba University School of Medicine
Chiba
Department of Internal Medicine, Teikyo University School of Medicine
Ichihara
Department of Internal Medicine, Faculty of Medicine, University of Tokyo
Tokyo
Department of Pediatrics, Toyohashi City Hospital
Toyohashi
Department of Internal Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University
Toyama
Diabetes Center, Institute of Endocrinology and Metabolic Disease, Kyoto National Hospital
Kyoto
Center for Diabetes Mellitus, Department of Internal Medicine, Osaka Rosai Hospital
Osaka
Department of Endocrinology, Tenri Hospital
Tenri
Department of Internal Medicine, Kobe University School of Medicine
Kobe
Department of Endocrinology and Metabolism, Kobe Children's Hospital
Kobe
Department of Internal Medicine, Nagasaki University School of Medicine
Nagasaki, Nagasaki
Research and Development Group, Fujisawa Pharmaceutical Company
Osaka
Department of Internal Medicine, Kyoto University School of Medicine
Kyoto, Japan
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Yoshiharu Akazawa;
Yoshiharu Akazawa
Second Department of Internal Medicine, Kyoto University School of Medicine
Kyoto
Department of Pediatrics, Tonan Hospital
Sapporo
Department of Pediatrics, Yamagata City Hospital
Saiseikan, Yamagata
Department of Internal Medicine, Chiba University School of Medicine
Chiba
Department of Internal Medicine, Teikyo University School of Medicine
Ichihara
Department of Internal Medicine, Faculty of Medicine, University of Tokyo
Tokyo
Department of Pediatrics, Toyohashi City Hospital
Toyohashi
Department of Internal Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University
Toyama
Diabetes Center, Institute of Endocrinology and Metabolic Disease, Kyoto National Hospital
Kyoto
Center for Diabetes Mellitus, Department of Internal Medicine, Osaka Rosai Hospital
Osaka
Department of Endocrinology, Tenri Hospital
Tenri
Department of Internal Medicine, Kobe University School of Medicine
Kobe
Department of Endocrinology and Metabolism, Kobe Children's Hospital
Kobe
Department of Internal Medicine, Nagasaki University School of Medicine
Nagasaki, Nagasaki
Research and Development Group, Fujisawa Pharmaceutical Company
Osaka
Department of Internal Medicine, Kyoto University School of Medicine
Kyoto, Japan
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Makoto Nomura;
Makoto Nomura
Second Department of Internal Medicine, Kyoto University School of Medicine
Kyoto
Department of Pediatrics, Tonan Hospital
Sapporo
Department of Pediatrics, Yamagata City Hospital
Saiseikan, Yamagata
Department of Internal Medicine, Chiba University School of Medicine
Chiba
Department of Internal Medicine, Teikyo University School of Medicine
Ichihara
Department of Internal Medicine, Faculty of Medicine, University of Tokyo
Tokyo
Department of Pediatrics, Toyohashi City Hospital
Toyohashi
Department of Internal Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University
Toyama
Diabetes Center, Institute of Endocrinology and Metabolic Disease, Kyoto National Hospital
Kyoto
Center for Diabetes Mellitus, Department of Internal Medicine, Osaka Rosai Hospital
Osaka
Department of Endocrinology, Tenri Hospital
Tenri
Department of Internal Medicine, Kobe University School of Medicine
Kobe
Department of Endocrinology and Metabolism, Kobe Children's Hospital
Kobe
Department of Internal Medicine, Nagasaki University School of Medicine
Nagasaki, Nagasaki
Research and Development Group, Fujisawa Pharmaceutical Company
Osaka
Department of Internal Medicine, Kyoto University School of Medicine
Kyoto, Japan
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Yasunao Yoshimasa;
Yasunao Yoshimasa
Second Department of Internal Medicine, Kyoto University School of Medicine
Kyoto
Department of Pediatrics, Tonan Hospital
Sapporo
Department of Pediatrics, Yamagata City Hospital
Saiseikan, Yamagata
Department of Internal Medicine, Chiba University School of Medicine
Chiba
Department of Internal Medicine, Teikyo University School of Medicine
Ichihara
Department of Internal Medicine, Faculty of Medicine, University of Tokyo
Tokyo
Department of Pediatrics, Toyohashi City Hospital
Toyohashi
Department of Internal Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University
Toyama
Diabetes Center, Institute of Endocrinology and Metabolic Disease, Kyoto National Hospital
Kyoto
Center for Diabetes Mellitus, Department of Internal Medicine, Osaka Rosai Hospital
Osaka
Department of Endocrinology, Tenri Hospital
Tenri
Department of Internal Medicine, Kobe University School of Medicine
Kobe
Department of Endocrinology and Metabolism, Kobe Children's Hospital
Kobe
Department of Internal Medicine, Nagasaki University School of Medicine
Nagasaki, Nagasaki
Research and Development Group, Fujisawa Pharmaceutical Company
Osaka
Department of Internal Medicine, Kyoto University School of Medicine
Kyoto, Japan
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Masato Kasuga;
Masato Kasuga
Second Department of Internal Medicine, Kyoto University School of Medicine
Kyoto
Department of Pediatrics, Tonan Hospital
Sapporo
Department of Pediatrics, Yamagata City Hospital
Saiseikan, Yamagata
Department of Internal Medicine, Chiba University School of Medicine
Chiba
Department of Internal Medicine, Teikyo University School of Medicine
Ichihara
Department of Internal Medicine, Faculty of Medicine, University of Tokyo
Tokyo
Department of Pediatrics, Toyohashi City Hospital
Toyohashi
Department of Internal Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University
Toyama
Diabetes Center, Institute of Endocrinology and Metabolic Disease, Kyoto National Hospital
Kyoto
Center for Diabetes Mellitus, Department of Internal Medicine, Osaka Rosai Hospital
Osaka
Department of Endocrinology, Tenri Hospital
Tenri
Department of Internal Medicine, Kobe University School of Medicine
Kobe
Department of Endocrinology and Metabolism, Kobe Children's Hospital
Kobe
Department of Internal Medicine, Nagasaki University School of Medicine
Nagasaki, Nagasaki
Research and Development Group, Fujisawa Pharmaceutical Company
Osaka
Department of Internal Medicine, Kyoto University School of Medicine
Kyoto, Japan
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Katsumi Goji;
Katsumi Goji
Second Department of Internal Medicine, Kyoto University School of Medicine
Kyoto
Department of Pediatrics, Tonan Hospital
Sapporo
Department of Pediatrics, Yamagata City Hospital
Saiseikan, Yamagata
Department of Internal Medicine, Chiba University School of Medicine
Chiba
Department of Internal Medicine, Teikyo University School of Medicine
Ichihara
Department of Internal Medicine, Faculty of Medicine, University of Tokyo
Tokyo
Department of Pediatrics, Toyohashi City Hospital
Toyohashi
Department of Internal Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University
Toyama
Diabetes Center, Institute of Endocrinology and Metabolic Disease, Kyoto National Hospital
Kyoto
Center for Diabetes Mellitus, Department of Internal Medicine, Osaka Rosai Hospital
Osaka
Department of Endocrinology, Tenri Hospital
Tenri
Department of Internal Medicine, Kobe University School of Medicine
Kobe
Department of Endocrinology and Metabolism, Kobe Children's Hospital
Kobe
Department of Internal Medicine, Nagasaki University School of Medicine
Nagasaki, Nagasaki
Research and Development Group, Fujisawa Pharmaceutical Company
Osaka
Department of Internal Medicine, Kyoto University School of Medicine
Kyoto, Japan
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Shigenobu Nagataki;
Shigenobu Nagataki
Second Department of Internal Medicine, Kyoto University School of Medicine
Kyoto
Department of Pediatrics, Tonan Hospital
Sapporo
Department of Pediatrics, Yamagata City Hospital
Saiseikan, Yamagata
Department of Internal Medicine, Chiba University School of Medicine
Chiba
Department of Internal Medicine, Teikyo University School of Medicine
Ichihara
Department of Internal Medicine, Faculty of Medicine, University of Tokyo
Tokyo
Department of Pediatrics, Toyohashi City Hospital
Toyohashi
Department of Internal Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University
Toyama
Diabetes Center, Institute of Endocrinology and Metabolic Disease, Kyoto National Hospital
Kyoto
Center for Diabetes Mellitus, Department of Internal Medicine, Osaka Rosai Hospital
Osaka
Department of Endocrinology, Tenri Hospital
Tenri
Department of Internal Medicine, Kobe University School of Medicine
Kobe
Department of Endocrinology and Metabolism, Kobe Children's Hospital
Kobe
Department of Internal Medicine, Nagasaki University School of Medicine
Nagasaki, Nagasaki
Research and Development Group, Fujisawa Pharmaceutical Company
Osaka
Department of Internal Medicine, Kyoto University School of Medicine
Kyoto, Japan
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Hitoshi Oyasu;
Hitoshi Oyasu
Second Department of Internal Medicine, Kyoto University School of Medicine
Kyoto
Department of Pediatrics, Tonan Hospital
Sapporo
Department of Pediatrics, Yamagata City Hospital
Saiseikan, Yamagata
Department of Internal Medicine, Chiba University School of Medicine
Chiba
Department of Internal Medicine, Teikyo University School of Medicine
Ichihara
Department of Internal Medicine, Faculty of Medicine, University of Tokyo
Tokyo
Department of Pediatrics, Toyohashi City Hospital
Toyohashi
Department of Internal Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University
Toyama
Diabetes Center, Institute of Endocrinology and Metabolic Disease, Kyoto National Hospital
Kyoto
Center for Diabetes Mellitus, Department of Internal Medicine, Osaka Rosai Hospital
Osaka
Department of Endocrinology, Tenri Hospital
Tenri
Department of Internal Medicine, Kobe University School of Medicine
Kobe
Department of Endocrinology and Metabolism, Kobe Children's Hospital
Kobe
Department of Internal Medicine, Nagasaki University School of Medicine
Nagasaki, Nagasaki
Research and Development Group, Fujisawa Pharmaceutical Company
Osaka
Department of Internal Medicine, Kyoto University School of Medicine
Kyoto, Japan
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Hiroo Imura
Hiroo Imura
Second Department of Internal Medicine, Kyoto University School of Medicine
Kyoto
Department of Pediatrics, Tonan Hospital
Sapporo
Department of Pediatrics, Yamagata City Hospital
Saiseikan, Yamagata
Department of Internal Medicine, Chiba University School of Medicine
Chiba
Department of Internal Medicine, Teikyo University School of Medicine
Ichihara
Department of Internal Medicine, Faculty of Medicine, University of Tokyo
Tokyo
Department of Pediatrics, Toyohashi City Hospital
Toyohashi
Department of Internal Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University
Toyama
Diabetes Center, Institute of Endocrinology and Metabolic Disease, Kyoto National Hospital
Kyoto
Center for Diabetes Mellitus, Department of Internal Medicine, Osaka Rosai Hospital
Osaka
Department of Endocrinology, Tenri Hospital
Tenri
Department of Internal Medicine, Kobe University School of Medicine
Kobe
Department of Endocrinology and Metabolism, Kobe Children's Hospital
Kobe
Department of Internal Medicine, Nagasaki University School of Medicine
Nagasaki, Nagasaki
Research and Development Group, Fujisawa Pharmaceutical Company
Osaka
Department of Internal Medicine, Kyoto University School of Medicine
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Address correspondence and reprint requests to Hideshi Kuzuya, MD, Second Department of Internal Medicine, Kyoto University School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606, Japan.
Diabetes 1993;42(5):696–705
Article history
Received:
March 04 1992
Revision Received:
December 30 1992
Accepted:
December 30 1992
PubMed:
8482426
Citation
Hideshi Kuzuya, Nobuo Matsuura, Michiyo Sakamoto, Hideichi Makino, Yoshikazu Sakamoto, Takashi Kadowaki, Yoshimi Suzuki, Masashi Kobayashi, Yoshiharu Akazawa, Makoto Nomura, Yasunao Yoshimasa, Masato Kasuga, Katsumi Goji, Shigenobu Nagataki, Hitoshi Oyasu, Hiroo Imura; Trial of Insulinlike Growth Factor I Therapy for Patients With Extreme Insulin Resistance Syndromes. Diabetes 1 May 1993; 42 (5): 696–705. https://doi.org/10.2337/diab.42.5.696
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