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  • Author: Birger Thorsteinsson x
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Louise Færch Department of Cardiology, Department of Growth and Reproduction, Faculty of Health Sciences, Nephrology and Endocrinology H, Hillerød University Hospital, Dyrehavevej 29, DK-3400 Hillerød, Denmark

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Anders Juul Department of Cardiology, Department of Growth and Reproduction, Faculty of Health Sciences, Nephrology and Endocrinology H, Hillerød University Hospital, Dyrehavevej 29, DK-3400 Hillerød, Denmark
Department of Cardiology, Department of Growth and Reproduction, Faculty of Health Sciences, Nephrology and Endocrinology H, Hillerød University Hospital, Dyrehavevej 29, DK-3400 Hillerød, Denmark

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Ulrik Pedersen-Bjergaard Department of Cardiology, Department of Growth and Reproduction, Faculty of Health Sciences, Nephrology and Endocrinology H, Hillerød University Hospital, Dyrehavevej 29, DK-3400 Hillerød, Denmark

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Birger Thorsteinsson Department of Cardiology, Department of Growth and Reproduction, Faculty of Health Sciences, Nephrology and Endocrinology H, Hillerød University Hospital, Dyrehavevej 29, DK-3400 Hillerød, Denmark
Department of Cardiology, Department of Growth and Reproduction, Faculty of Health Sciences, Nephrology and Endocrinology H, Hillerød University Hospital, Dyrehavevej 29, DK-3400 Hillerød, Denmark

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Objective

GH is implicated in the counter-regulatory response to hypoglycemia. We tested whether IGF1 levels are associated with occurrence of severe hypoglycemic events in patients with type 1 diabetes and whether the IGF1 concentration is influenced by glycemic control.

Methods

A total of 228 outpatients with type 1 diabetes were included in a post hoc analysis of a 1-year observational study on severe hypoglycemia. Serum total IGF1 was measured at entry into the study. The occurrence of severe episodes of hypoglycemia, mild symptomatic, and biochemical as well as hypoglycemia awareness status was assessed. Also patients were included in a multiple regression analysis to investigate the role of HbA1c in the IGF1 concentration.

Results

IGF1 levels were associated with neither severe hypoglycemia in the entire cohort (P=0.30) nor in any gender nor when confining the analysis to those with long-standing diabetes (>20 years) (n=112, P=0.68) and those with both long-standing diabetes and undetectable C-peptide (n=51, P=0.067). Levels of IGF1 were associated with neither mild symptomatic hypoglycemia (P=0.24) nor biochemical hypoglycemia (0.089) nor hypoglycemia awareness (P=0.16). At a multiple regression analysis, HbA1c was negatively associated with IGF1 (P=0.001).

Conclusion

In type 1 diabetes, circulating IGF1 levels are negatively associated with glycemic control. However, IGF1 levels were not associated with occurrence of hypoglycemia or hypoglycemia awareness in these patients.

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Peter L Kristensen Department of Cardiology, Nephrology and Endocrinology, Nordsjællands Hospital, Hillerød, Denmark

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Ulrik Pedersen-Bjergaard Department of Cardiology, Nephrology and Endocrinology, Nordsjællands Hospital, Hillerød, Denmark
Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Rikke Due-Andersen Department of Cardiology, Nephrology and Endocrinology, Nordsjællands Hospital, Hillerød, Denmark
Lægerne på Ellemarksvej, Køge, Denmark

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Thomas Høi-Hansen Department of Cardiology, Nephrology and Endocrinology, Nordsjællands Hospital, Hillerød, Denmark
Department of Cardiology, Herlev-Gentofte University Hospital, Herlev, Denmark

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Lise Grimmeshave Department of Cardiology, Nephrology and Endocrinology, Nordsjællands Hospital, Hillerød, Denmark
Novo Nordisk A/S, Søborg, Denmark

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Valeriya Lyssenko Steno Diabetes Center, Gentofte, Denmark
Lund University Diabetes Centre, Skåne University Hospital, Malmø, Sweden

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Leif Groop Lund University Diabetes Centre, Skåne University Hospital, Malmø, Sweden
Finnish Institute for Molecular Medicine (FIMM), Helsinki University, Helsinki, Finland

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Jens J Holst Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Department of Biomedical Sciences, NNF Center for Basic Metabolic Research, The Panum Institute, Copenhagen, Denmark

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Allan A Vaag Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Department of Endocrinology, Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark

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Birger Thorsteinsson Department of Cardiology, Nephrology and Endocrinology, Nordsjællands Hospital, Hillerød, Denmark
Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Introduction

In healthy carriers of the T allele of the transcription factor 7-like 2 (TCF7L2), fasting plasma glucagon concentrations are lower compared with those with the C allele. We hypothesised that presence of the T allele is associated with a diminished glucagon response during hypoglycaemia and a higher frequency of severe hypoglycaemia (SH) in type 1 diabetes (T1DM).

Material and methods

This is a post hoc study of an earlier prospective observational study of SH and four mechanistic studies of physiological responses to hypoglycaemia. 269 patients with T1DM were followed in a one-year observational study. A log-linear negative binomial model was applied with events of SH as dependent variable and TCF7L2 alleles as explanatory variable. In four experimental studies including 65 people, TCF7L2 genotyping was done and plasma glucagon concentration during experimental hypoglycaemia was determined.

Results

Incidences of SH were TT 0.54, TC 0.98 and CC 1.01 episodes per patient-year with no significant difference between groups. During experimental hypoglycaemia, the TCF7L2 polymorphism did not influence glucagon secretion.

Discussion

Patients with T1DM carrying the T allele of the TCF7L2 polymorphism do not exhibit diminished glucagon response during hypoglycaemia and are not at increased risk of severe hypoglycaemia compared with carriers of the C allele.

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