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Identification of p...
Identification of pathogenic GCK variants in patients with common type 2 diabetes can lead to discontinuation of pharmacological treatment
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- Thuesen, Anne Cathrine Baun (författare)
- Steno Diabetes Center Copenhagen
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- Jensen, Rasmus Tanderup (författare)
- University of Copenhagen
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- Maagensen, Henrik (författare)
- Steno Diabetes Center Copenhagen
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- Kristiansen, Maja Refshauge (författare)
- Odense University Hospital
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- Sørensen, Henrik Toft (författare)
- Aarhus University Hospital
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- Vaag, Allan (författare)
- Lund University,Lunds universitet,Translationell diabetesforskning,Forskargrupper vid Lunds universitet,Translational Diabetes Research,Lund University Research Groups,Steno Diabetes Center Copenhagen
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- Beck-Nielsen, Henning (författare)
- Odense University Hospital
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Pedersen, Oluf B. (författare)
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Grarup, Niels (författare)
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- Nielsen, Jens Steen (författare)
- University of Southern Denmark,Odense University Hospital
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- Rungby, Jørgen (författare)
- Steno Diabetes Center Copenhagen,University of Copenhagen
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Gjesing, Anette Prior (författare)
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- Storgaard, Heidi (författare)
- Steno Diabetes Center Copenhagen
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- Vilsbøll, Tina (författare)
- University of Copenhagen,Steno Diabetes Center Copenhagen
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- Hansen, Torben (författare)
- University of Copenhagen
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(creator_code:org_t)
- Elsevier BV, 2023
- 2023
- Engelska.
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Ingår i: Molecular Genetics and Metabolism Reports. - : Elsevier BV. - 2214-4269. ; 35
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Background: Functionally disruptive variants in the glucokinase gene (GCK) cause a form of mild non-progressive hyperglycemia, which does not require pharmacological treatment. A substantial proportion of patients with type 2 diabetes (T2D) carry GCK variants. We aimed to investigate whether carriers of rare GCK variants diagnosed with T2D have a glycemic phenotype and treatment response consistent with GCK-diabetes. Methods: Eight patients diagnosed with T2D from the Danish DD2 cohort who had previously undergone sequencing of GCK participated. Clinical examinations at baseline included an oral glucose tolerance test and continuous glucose monitoring. Carriers with a glycemic phenotype consistent with GCK-diabetes took part in a three-month treatment withdrawal. Results: Carriers of pathogenic and likely pathogenic variants had lower median fasting glucose and C-peptide levels compared to carriers of variants of uncertain significance and benign variants (median fasting glucose: 7.3 (interquartile range: 0.4) mmol/l vs. 9.5 (1.6) mmol/l, p = 0.04; median fasting C-peptide 902 (85) pmol/l vs. 1535 (295) pmol/l, p = 0.03). Four participants who discontinued metformin treatment and one diet-treated participant were reevaluated after three months. There was no deterioration of HbA1c or fasting glucose (median baseline HbA1c: 49 (3) vs. 51 (6) mmol/mol after three months, p = 0.4; median baseline fasting glucose: 7.3 (0.4) mmol/l vs. 7.0 (0.6) mmol/l after three months, p = 0.5). Participants did not consistently fulfill best practice guidelines for GCK screening nor clinical criteria for monogenic diabetes. Discussion: Carriers of pathogenic or likely pathogenic GCK variants identified by unselected screening in T2D should be reported, as they have a glycemic phenotype and treatment response consistent with GCK-diabetes. Variants of uncertain significance should be interpreted with care. Systematic genetic screening of patients with common T2D receiving routine care can lead to the identification and precise care of patients with misclassified GCK-diabetes who are not identifiable through common genetic screening criteria.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Nyckelord
- Diagnosis
- MODY (maturity-onset diabetes of the young)
- T2D (type 2 diabetes)
- Treatment
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- ref (ämneskategori)
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Thuesen, Anne Ca ...
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Jensen, Rasmus T ...
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Maagensen, Henri ...
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Kristiansen, Maj ...
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Sørensen, Henrik ...
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Vaag, Allan
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Beck-Nielsen, He ...
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Pedersen, Oluf B ...
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Grarup, Niels
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Nielsen, Jens St ...
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Rungby, Jørgen
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Gjesing, Anette ...
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Storgaard, Heidi
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Vilsbøll, Tina
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Hansen, Torben
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