TY - JOUR
T1 - Hyperinsulinaemic-hypoglycaemic glucose clamps in human research
T2 - a systematic review of the literature
AU - Fabricius, Therese W.
AU - Verhulst, Clementine E. M.
AU - Kristensen, Peter L.
AU - Tack, Cees J.
AU - McCrimmon, Rory J.
AU - Heller, Simon
AU - Evans, Mark L.
AU - Amiel, Stephanie A.
AU - Pieber, Thomas R.
AU - de Galan, Bastiaan E.
AU - Pedersen-Bjergaard, Ulrik
AU - Hypo-RESOLVE Consortium
N1 - Funding Information:
This review has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No. 777460. The JU receives support from the European Union’s Horizon 2020 research and innovation programme and the EFPIA, the T1D Exchange, JDRF, the International Diabetes Federation (IDF), and the Leona M. and Harry B. Helmsley Charitable Trust.
Funding Information:
The authors would like to acknowledge the support of J. Meelby, Information Specialist, Library and Information Services at Nordsj?llands Hospital, Denmark, for her assistance with the systematic search strategy. Some of the data were presented as an abstract at the Annual Dutch Diabetes Research Meeting in 2019 and as a presentation at the EASD Annual Meeting 2020. TWF: None. CEMV: None. PLK has received lecture fees from AstraZeneca. RJM has served on advisory boards for Novo Nordisk and Sanofi, and has received lecture fees from Novo Nordisk and Sanofi. MLE has served on advisory boards and/or received speaker/travel support from Novo Nordisk, Medtronic, Abbott Diabetes Care, Roche, Pila Pharma, Dexcom, Eli Lilly, Astra Zeneca and Zucara. SH has served on advisory boards for Sanofi-Aventis, Eli Lilly, Novo Nordisk and Zealand Pharma, and received lecture fees from Novo Nordisk and AstraZeneca. TRP has received research support from AstraZeneca and Novo Nordisk (paid directly to the university); has served on advisory boards for Adocia, Arecor, AstraZeneca, Eli Lilly, Novo Nordisk and Sanofi; and has received lecture fees from Novo Nordisk. BEDG has received research support from Novo Nordisk. UP-B has served on advisory boards for AstraZeneca, Bristol-Myers Squibb, Sanofi-Aventis, Novo Nordisk and Zealand Pharma, and has received lecture fees from AstraZeneca, Bristol-Myers Squibb, Sanofi-Aventis and Novo Nordisk. The authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work.
Publisher Copyright:
© 2020, The Author(s).
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/4
Y1 - 2021/4
N2 - Aims/hypothesis: The hyperinsulinaemic–hypoglycaemic glucose clamp technique has been developed and applied to assess effects of and responses to hypoglycaemia under standardised conditions. However, the degree to which the methodology of clamp studies is standardised is unclear. This systematic review examines how hyperinsulinaemic–hypoglycaemic clamps have been performed and elucidates potential important differences.Methods: A literature search in PubMed and EMBASE was conducted. Articles in English published between 1980 and 2018, involving adults with or without diabetes, were included.Results: A total of 383 articles were included. There was considerable variation in essential methodology of the hypoglycaemic clamp procedures, including the insulin dose used (49-fold difference between the lowest and the highest rate), the number of hypoglycaemic steps (range 1−6), the hypoglycaemic nadirs (range 2.0–4.3 mmol/l) and the duration (ranging from 5 to 660 min). Twenty-seven per cent of the articles reported whole blood glucose levels, most venous levels. In 70.8% of the studies, a dorsal hand vein was used for blood sampling, with some form of hand warming to arterialise venous blood in 78.8% of these. Key information was missing in 61.9% of the articlesConclusions/interpretation: Although the hyperinsulinaemic–hypoglycaemic clamp procedure is considered the gold standard to study experimental hypoglycaemia, a uniform standard with key elements on how to perform these experiments is lacking. Methodological differences should be considered when comparing results between hypoglycaemic clamp studies.PROSPERO registration: This systematic review is registered in PROSPERO (CRD42019120083).
AB - Aims/hypothesis: The hyperinsulinaemic–hypoglycaemic glucose clamp technique has been developed and applied to assess effects of and responses to hypoglycaemia under standardised conditions. However, the degree to which the methodology of clamp studies is standardised is unclear. This systematic review examines how hyperinsulinaemic–hypoglycaemic clamps have been performed and elucidates potential important differences.Methods: A literature search in PubMed and EMBASE was conducted. Articles in English published between 1980 and 2018, involving adults with or without diabetes, were included.Results: A total of 383 articles were included. There was considerable variation in essential methodology of the hypoglycaemic clamp procedures, including the insulin dose used (49-fold difference between the lowest and the highest rate), the number of hypoglycaemic steps (range 1−6), the hypoglycaemic nadirs (range 2.0–4.3 mmol/l) and the duration (ranging from 5 to 660 min). Twenty-seven per cent of the articles reported whole blood glucose levels, most venous levels. In 70.8% of the studies, a dorsal hand vein was used for blood sampling, with some form of hand warming to arterialise venous blood in 78.8% of these. Key information was missing in 61.9% of the articlesConclusions/interpretation: Although the hyperinsulinaemic–hypoglycaemic clamp procedure is considered the gold standard to study experimental hypoglycaemia, a uniform standard with key elements on how to perform these experiments is lacking. Methodological differences should be considered when comparing results between hypoglycaemic clamp studies.PROSPERO registration: This systematic review is registered in PROSPERO (CRD42019120083).
KW - Diabetes
KW - Diabetes mellitus
KW - Human
KW - Hyperinsulinaemic-hypoglycaemic clamp
KW - Hypoglycaemica
KW - Systematic review
KW - Type 1 diabetes
KW - Type 2 diabetes
KW - Hyperinsulinaemic–hypoglycaemic clamp
KW - Hypoglycaemia
UR - http://www.scopus.com/inward/record.url?scp=85100839572&partnerID=8YFLogxK
U2 - 10.1007/s00125-020-05361-8
DO - 10.1007/s00125-020-05361-8
M3 - Article
C2 - 33566134
SN - 0012-186X
VL - 64
SP - 727
EP - 736
JO - Diabetologia
JF - Diabetologia
ER -
