Short- and long-term metabolic effects of recombinant human IGF-I treatment in patients with severe insulin resistance and diabetes mellitus
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Short- and long-term metabolic effects of recombinant human IGF-I treatment in patients with severe insulin resistance and diabetes mellitus. / Vestergaard, H; Rossen, M; Urhammer, S A; Müller, J; Pedersen, O.
I: European Journal of Endocrinology, Bind 136, Nr. 5, 05.1997, s. 475-82.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - Short- and long-term metabolic effects of recombinant human IGF-I treatment in patients with severe insulin resistance and diabetes mellitus
AU - Vestergaard, H
AU - Rossen, M
AU - Urhammer, S A
AU - Müller, J
AU - Pedersen, O
PY - 1997/5
Y1 - 1997/5
N2 - In patients suffering from the genetic syndromes of severe insulin resistance it appears that diabetes develops when the adaptive hypersecretion of insulin fails and often these forms of diabetes will be insensitive to insulin treatment. The objective of the present study was to examine the metabolic and hormonal responses to an unchanged insulin therapy with the addition of a subcutaneous administration of recombinant human IGF-I (rhIGF-I) during (a) a short-term (2 weeks) period with rhIGF-I given twice a day in a high dose (80 micrograms/kg body weight) in four patients with extreme insulin-resistant diabetes mellitus and (b) during a long-term (10 weeks) period with rhIGF-I given once a day in a low dose (40 micrograms/kg body weight) in three of the four patients. Two siblings had known mutations in the tyrosine kinase domain of the insulin receptor and a deletion of exon 17 in part of their insulin receptor mRNA, whereas the remaining two patients were suspected to have defects at receptor and/or post-receptor sites. In the short-term study period, plasma glucose levels decreased more than 35% in response to rhIGF-I in all but one patient which was paralleled by reduced levels of serum insulin (25-50%), proinsulin (40-50%) and C-peptide (10-65%) and an improvement in glycaemic control as evaluated by decreased glycosylated haemoglobin and serum fructosamine. During the long-term study period blood glucose-lowering effects of rhIGF-I were seen after 2 weeks of treatment and fasting plasma glucose and serum insulin and C-peptide levels were decreased by 40-55% after 6 weeks in the two siblings with known insulin receptor mutations. After 10 weeks of treatment fasting plasma glucose levels were still decreased whereas fasting serum insulin and C-peptide levels were increased almost to pretreatment values. In conclusion: 2 weeks of high-dose rhIGF-I therapy in insulin-treated patients with severe insulin resistance has a marked lowering effect on fasting plasma glucose and serum insulin levels whereas the metabolic and glycaemic effects of 10 weeks of treatment with low-dose rhIGF-I may be modest and transient.
AB - In patients suffering from the genetic syndromes of severe insulin resistance it appears that diabetes develops when the adaptive hypersecretion of insulin fails and often these forms of diabetes will be insensitive to insulin treatment. The objective of the present study was to examine the metabolic and hormonal responses to an unchanged insulin therapy with the addition of a subcutaneous administration of recombinant human IGF-I (rhIGF-I) during (a) a short-term (2 weeks) period with rhIGF-I given twice a day in a high dose (80 micrograms/kg body weight) in four patients with extreme insulin-resistant diabetes mellitus and (b) during a long-term (10 weeks) period with rhIGF-I given once a day in a low dose (40 micrograms/kg body weight) in three of the four patients. Two siblings had known mutations in the tyrosine kinase domain of the insulin receptor and a deletion of exon 17 in part of their insulin receptor mRNA, whereas the remaining two patients were suspected to have defects at receptor and/or post-receptor sites. In the short-term study period, plasma glucose levels decreased more than 35% in response to rhIGF-I in all but one patient which was paralleled by reduced levels of serum insulin (25-50%), proinsulin (40-50%) and C-peptide (10-65%) and an improvement in glycaemic control as evaluated by decreased glycosylated haemoglobin and serum fructosamine. During the long-term study period blood glucose-lowering effects of rhIGF-I were seen after 2 weeks of treatment and fasting plasma glucose and serum insulin and C-peptide levels were decreased by 40-55% after 6 weeks in the two siblings with known insulin receptor mutations. After 10 weeks of treatment fasting plasma glucose levels were still decreased whereas fasting serum insulin and C-peptide levels were increased almost to pretreatment values. In conclusion: 2 weeks of high-dose rhIGF-I therapy in insulin-treated patients with severe insulin resistance has a marked lowering effect on fasting plasma glucose and serum insulin levels whereas the metabolic and glycaemic effects of 10 weeks of treatment with low-dose rhIGF-I may be modest and transient.
KW - Adolescent
KW - Adult
KW - Blood Glucose
KW - Cardiovascular System
KW - Child
KW - Diabetes Mellitus, Type 2
KW - Drug Administration Schedule
KW - Female
KW - Glucose Tolerance Test
KW - Hormones
KW - Humans
KW - Injections, Subcutaneous
KW - Insulin Resistance
KW - Insulin-Like Growth Factor I
KW - Longitudinal Studies
KW - Male
KW - Recombinant Proteins
KW - Time Factors
M3 - Journal article
C2 - 9186267
VL - 136
SP - 475
EP - 482
JO - European Journal of Endocrinology
JF - European Journal of Endocrinology
SN - 0804-4643
IS - 5
ER -
ID: 92192826