Different Effects of Intraperitoneal and Subcutaneous Insulin Administration on the GH-IGF-1 Axis in Type 1 Diabetes.
In type 1 diabetes mellitus, low levels of insulin-like growth factor -1 (IGF-1) and IGF binding protein-3 (IGFBP-3) and high levels of GH and IGFBP-1 are present, probably due to portal vein insulinopenia.



To test the hypothesis that continuous ip insulin infusion (CIPII) has a more pronounced effect than sc insulin therapy on regulation of the GH-IGF-1 axis.



This was a prospective, observational case-control study. Measurements were performed twice at a 26-week interval.



Two secondary care hospitals in the Netherlands participated in the study.



There were a total of 184 patients, age- and gender-matched, of which 39 used CIPII and 145 sc insulin therapy for the past 4 years.



Primary endpoint included differences in IGF-1. Secondary outcomes were differences in GH, IGFBP-1, and IGFBP-3.



IGF-1 was higher with CIPII as compared to SC insulin therapy: 124 μg/liter (95% confidence interval [CI], 111-138) vs 108 μg/liter (95% CI 102-115) (P = .035). Additionally, IGFBP-3 concentrations were higher and IGFBP-1 and GH concentrations were lower with CIPII as compared to SC insulin therapy: 3.78 mg/liter (95% CI, 3.49-4.10) vs 3.31 mg/liter (95% CI, 3.17-3.47) for IGFBP-3, 50.9 μg/liter (95% CI, 37.9-68.2) vs 102.6 μg/liter (95% CI, 87.8-119.8) for IGFBP-1 and 0.68 μg/liter (95% CI, 0.44-1.06) vs 1.21 μg/liter (95% CI, 0.95-1.54) for GH, respectively. In multivariate analysis, IGF-1 had no significant association with HbA1c.



The GH-IGF-1 axis may be affected by the route of insulin administration with CIPII counteracting dysregulation of the GH-IGF1 axis present during sc insulin therapy.
Diabetes Centre (P.R.v.D., S.J.J.L., K.H.G., N.K., H.J.G.B.), Isala, Zwolle, The Netherlands; Department of Internal Medicine (P.R.v.D., H.J.G.B.), Isala, Zwolle, The Netherlands; Department of Internal Medicine (S.J.J.L.), Diakonessenhuis, Utrecht, The Netherlands; Department of Emergency Medicine (S.I.C.), Linköping University, Linköping, Sweden; Department of Clinical and Experimental Medicine (S.I.C., H.J.A.), Linköping University, Linköping, Sweden; Department of Endocrinology (C.A.H., H.J.A.), Linköping University, Linköping, Sweden; Department of Medical and Health Sciences (C.A.H.), Linköping University, Linköping, Sweden; Department of General Practice (K.H.G.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; and Department of Internal Medicine (R.O.B.G., N.K., H.J.G.B.), University of Groningen, University Medical Center Groningen, Langerhans Medical Research Group (N.K.), Zwolle, The Netherlands.
Peter R
PR
van Dijk
Diabetes Centre (P.R.v.D., S.J.J.L., K.H.G., N.K., H.J.G.B.), Isala, Zwolle, The Netherlands; Department of Internal Medicine (P.R.v.D., H.J.G.B.), Isala, Zwolle, The Netherlands; Department of Internal Medicine (S.J.J.L.), Diakonessenhuis, Utrecht, The Netherlands; Department of Emergency Medicine (S.I.C.), Linköping University, Linköping, Sweden; Department of Clinical and Experimental Medicine (S.I.C., H.J.A.), Linköping University, Linköping, Sweden; Department of Endocrinology (C.A.H., H.J.A.), Linköping University, Linköping, Sweden; Department of Medical and Health Sciences (C.A.H.), Linköping University, Linköping, Sweden; Department of General Practice (K.H.G.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; and Department of Internal Medicine (R.O.B.G., N.K., H.J.G.B.), University of Groningen, University Medical Center Groningen, Langerhans Medical Research Group (N.K.), Zwolle, The Netherlands.
Susan J J
SJ
Logtenberg
Diabetes Centre (P.R.v.D., S.J.J.L., K.H.G., N.K., H.J.G.B.), Isala, Zwolle, The Netherlands; Department of Internal Medicine (P.R.v.D., H.J.G.B.), Isala, Zwolle, The Netherlands; Department of Internal Medicine (S.J.J.L.), Diakonessenhuis, Utrecht, The Netherlands; Department of Emergency Medicine (S.I.C.), Linköping University, Linköping, Sweden; Department of Clinical and Experimental Medicine (S.I.C., H.J.A.), Linköping University, Linköping, Sweden; Department of Endocrinology (C.A.H., H.J.A.), Linköping University, Linköping, Sweden; Department of Medical and Health Sciences (C.A.H.), Linköping University, Linköping, Sweden; Department of General Practice (K.H.G.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; and Department of Internal Medicine (R.O.B.G., N.K., H.J.G.B.), University of Groningen, University Medical Center Groningen, Langerhans Medical Research Group (N.K.), Zwolle, The Netherlands.
Simona I
SI
Chisalita
Diabetes Centre (P.R.v.D., S.J.J.L., K.H.G., N.K., H.J.G.B.), Isala, Zwolle, The Netherlands; Department of Internal Medicine (P.R.v.D., H.J.G.B.), Isala, Zwolle, The Netherlands; Department of Internal Medicine (S.J.J.L.), Diakonessenhuis, Utrecht, The Netherlands; Department of Emergency Medicine (S.I.C.), Linköping University, Linköping, Sweden; Department of Clinical and Experimental Medicine (S.I.C., H.J.A.), Linköping University, Linköping, Sweden; Department of Endocrinology (C.A.H., H.J.A.), Linköping University, Linköping, Sweden; Department of Medical and Health Sciences (C.A.H.), Linköping University, Linköping, Sweden; Department of General Practice (K.H.G.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; and Department of Internal Medicine (R.O.B.G., N.K., H.J.G.B.), University of Groningen, University Medical Center Groningen, Langerhans Medical Research Group (N.K.), Zwolle, The Netherlands.
Christina A
CA
Hedman
Diabetes Centre (P.R.v.D., S.J.J.L., K.H.G., N.K., H.J.G.B.), Isala, Zwolle, The Netherlands; Department of Internal Medicine (P.R.v.D., H.J.G.B.), Isala, Zwolle, The Netherlands; Department of Internal Medicine (S.J.J.L.), Diakonessenhuis, Utrecht, The Netherlands; Department of Emergency Medicine (S.I.C.), Linköping University, Linköping, Sweden; Department of Clinical and Experimental Medicine (S.I.C., H.J.A.), Linköping University, Linköping, Sweden; Department of Endocrinology (C.A.H., H.J.A.), Linköping University, Linköping, Sweden; Department of Medical and Health Sciences (C.A.H.), Linköping University, Linköping, Sweden; Department of General Practice (K.H.G.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; and Department of Internal Medicine (R.O.B.G., N.K., H.J.G.B.), University of Groningen, University Medical Center Groningen, Langerhans Medical Research Group (N.K.), Zwolle, The Netherlands.
Klaas H
KH
Groenier
Diabetes Centre (P.R.v.D., S.J.J.L., K.H.G., N.K., H.J.G.B.), Isala, Zwolle, The Netherlands; Department of Internal Medicine (P.R.v.D., H.J.G.B.), Isala, Zwolle, The Netherlands; Department of Internal Medicine (S.J.J.L.), Diakonessenhuis, Utrecht, The Netherlands; Department of Emergency Medicine (S.I.C.), Linköping University, Linköping, Sweden; Department of Clinical and Experimental Medicine (S.I.C., H.J.A.), Linköping University, Linköping, Sweden; Department of Endocrinology (C.A.H., H.J.A.), Linköping University, Linköping, Sweden; Department of Medical and Health Sciences (C.A.H.), Linköping University, Linköping, Sweden; Department of General Practice (K.H.G.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; and Department of Internal Medicine (R.O.B.G., N.K., H.J.G.B.), University of Groningen, University Medical Center Groningen, Langerhans Medical Research Group (N.K.), Zwolle, The Netherlands.
Reinold O B
RO
Gans
Diabetes Centre (P.R.v.D., S.J.J.L., K.H.G., N.K., H.J.G.B.), Isala, Zwolle, The Netherlands; Department of Internal Medicine (P.R.v.D., H.J.G.B.), Isala, Zwolle, The Netherlands; Department of Internal Medicine (S.J.J.L.), Diakonessenhuis, Utrecht, The Netherlands; Department of Emergency Medicine (S.I.C.), Linköping University, Linköping, Sweden; Department of Clinical and Experimental Medicine (S.I.C., H.J.A.), Linköping University, Linköping, Sweden; Department of Endocrinology (C.A.H., H.J.A.), Linköping University, Linköping, Sweden; Department of Medical and Health Sciences (C.A.H.), Linköping University, Linköping, Sweden; Department of General Practice (K.H.G.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; and Department of Internal Medicine (R.O.B.G., N.K., H.J.G.B.), University of Groningen, University Medical Center Groningen, Langerhans Medical Research Group (N.K.), Zwolle, The Netherlands.
Nanne
N
Kleefstra
Diabetes Centre (P.R.v.D., S.J.J.L., K.H.G., N.K., H.J.G.B.), Isala, Zwolle, The Netherlands; Department of Internal Medicine (P.R.v.D., H.J.G.B.), Isala, Zwolle, The Netherlands; Department of Internal Medicine (S.J.J.L.), Diakonessenhuis, Utrecht, The Netherlands; Department of Emergency Medicine (S.I.C.), Linköping University, Linköping, Sweden; Department of Clinical and Experimental Medicine (S.I.C., H.J.A.), Linköping University, Linköping, Sweden; Department of Endocrinology (C.A.H., H.J.A.), Linköping University, Linköping, Sweden; Department of Medical and Health Sciences (C.A.H.), Linköping University, Linköping, Sweden; Department of General Practice (K.H.G.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; and Department of Internal Medicine (R.O.B.G., N.K., H.J.G.B.), University of Groningen, University Medical Center Groningen, Langerhans Medical Research Group (N.K.), Zwolle, The Netherlands.
Hans J
HJ
Arnqvist
Diabetes Centre (P.R.v.D., S.J.J.L., K.H.G., N.K., H.J.G.B.), Isala, Zwolle, The Netherlands; Department of Internal Medicine (P.R.v.D., H.J.G.B.), Isala, Zwolle, The Netherlands; Department of Internal Medicine (S.J.J.L.), Diakonessenhuis, Utrecht, The Netherlands; Department of Emergency Medicine (S.I.C.), Linköping University, Linköping, Sweden; Department of Clinical and Experimental Medicine (S.I.C., H.J.A.), Linköping University, Linköping, Sweden; Department of Endocrinology (C.A.H., H.J.A.), Linköping University, Linköping, Sweden; Department of Medical and Health Sciences (C.A.H.), Linköping University, Linköping, Sweden; Department of General Practice (K.H.G.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; and Department of Internal Medicine (R.O.B.G., N.K., H.J.G.B.), University of Groningen, University Medical Center Groningen, Langerhans Medical Research Group (N.K.), Zwolle, The Netherlands.
Henk J G
HJ
Bilo
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D005260:Female; D019382:Human Growth Hormone / Q000097:blood*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007263:Infusions, Parenteral; D055104:Infusions, Subcutaneous; D007328:Insulin / Q000008:administration & dosage / Q000627:therapeutic use*; D007332:Insulin Infusion Systems; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
D001786:Blood Glucose; D007004:Hypoglycemic Agents; C032231:IGFBP1 protein, human; C515497:IGFBP3 protein, human; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I