Prevalence of Vascular Complications Among Patients With Glucokinase Mutations and Prolonged, Mild Hyperglycemia

IMPORTANCE Glycemic targets in diabetes have been developed to minimize complication risk. Patients with heterozygous, inactivating glucokinase (GCK) mutations have mild fasting hyperglycemia from birth, resulting in an elevated glycated hemoglobin (HbA1c) level that mimics recommended levels for ty...

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Bibliographic Details
Published in:JAMA : the journal of the American Medical Association 2014-01, Vol.311 (3), p.279-286
Main Authors: Steele, Anna M, Shields, Beverley M, Wensley, Kirsty J, Colclough, Kevin, Ellard, Sian, Hattersley, Andrew T
Format: Article
Language:English
Subjects:
Adult
Biological and medical sciences
Case-Control Studies
Cross-Sectional Studies
Diabetes
Diabetes Complications
Diabetes Mellitus, Type 2 - complications
Diabetes Mellitus, Type 2 - genetics
Epidemiology
Female
General aspects
Glucokinase - genetics
Glycated Hemoglobin - analysis
Humans
Hyperglycemia
Hyperglycemia - complications
Hyperglycemia - genetics
Male
Medical research
Medical sciences
Middle Aged
Mutation
Prevalence
Public health. Hygiene
Public health. Hygiene-occupational medicine
Severity of Illness Index
Time Factors
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Summary:IMPORTANCE Glycemic targets in diabetes have been developed to minimize complication risk. Patients with heterozygous, inactivating glucokinase (GCK) mutations have mild fasting hyperglycemia from birth, resulting in an elevated glycated hemoglobin (HbA1c) level that mimics recommended levels for type 1 and type 2 diabetes. OBJECTIVE To assess the association between chronic, mild hyperglycemia and complication prevalence and severity in patients with GCK mutations. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional study in the United Kingdom between August 2008 and December 2010. Assessment of microvascular and macrovascular complications in participants 35 years or older was conducted in 99 GCK mutation carriers (median age, 48.6 years), 91 nondiabetic, familial, nonmutation carriers (control) (median age, 52.2 years), and 83 individuals with young-onset type 2 diabetes (YT2D), diagnosed at age 45 years or younger (median age, 54.7 years). MAIN OUTCOMES AND MEASURES Prevalence and severity of nephropathy, retinopathy, peripheral neuropathy, peripheral vascular disease, and cardiovascular disease. RESULTS Median HbA1c was 6.9% in patients with the GCK mutation, 5.8% in controls, and 7.8% in patients with YT2D. Patients with GCK had a low prevalence of clinically significant microvascular complications (1% [95% CI, 0%-5%]) that was not significantly different from controls (2% [95% CI, 0.3%-8%], P=.52) and lower than in patients with YT2D (36% [95% CI, 25%-47%], P
ISSN:0098-7484
1538-3598
1538-3598
DOI:10.1001/jama.2013.283980