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Prevalence of vascular complications among patients with glucokinase mutations and prolonged, mild hyperglycemia.
- Source :
-
JAMA [JAMA] 2014 Jan 15; Vol. 311 (3), pp. 279-86. - Publication Year :
- 2014
-
Abstract
- 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.<br />Objective: To assess the association between chronic, mild hyperglycemia and complication prevalence and severity in patients with GCK mutations.<br />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).<br />Main Outcomes and Measures: Prevalence and severity of nephropathy, retinopathy, peripheral neuropathy, peripheral vascular disease, and cardiovascular disease.<br />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<.001). Thirty percent of patients with GCK had retinopathy (95% CI, 21%-41%) compared with 14% of controls (95% CI, 7%-23%, P=.007) and 63% of patients with YT2D (95% CI, 51%-73%, P<.001). Neither patients with GCK nor controls required laser therapy for retinopathy compared with 28% (95% CI, 18%-39%) of patients with YT2D (P<.001). Neither patients with GCK patients nor controls had proteinuria and microalbuminuria was rare (GCK, 1% [95% CI, 0.2%-6%]; controls, 2% [95% CI, 0.2%-8%]), whereas 10% (95% CI, 4%-19%) of YT2D patients had proteinuria (P<.001 vs GCK) and 21% (95% CI, 13%-32%) had microalbuminuria (P<.001). Neuropathy was rare in patients with GCK (2% [95% CI, 0.3%-8%]) and controls (95% CI, 0% [0%-4%]) but present in 29% (95% CI, 20%-50%) of YT2D patients (P<.001). Patients with GCK had a low prevalence of clinically significant macrovascular complications (4% [95% CI, 1%-10%]) that was not significantly different from controls (11% [95% CI, 5%-19%]; P=.09), and lower in prevalence than patients with YT2D (30% [95% CI, 21%-41%], P<.001).<br />Conclusions and Relevance: Despite a median duration of 48.6 years of hyperglycemia, patients with a GCK mutation had low prevalence of microvascular and macrovascular complications. These findings may provide insights into the risks associated with isolated, mild hyperglycemia.
- Subjects :
- Adult
Case-Control Studies
Cross-Sectional Studies
Diabetes Mellitus, Type 2 genetics
Female
Glycated Hemoglobin analysis
Humans
Hyperglycemia complications
Male
Middle Aged
Prevalence
Severity of Illness Index
Time Factors
Diabetes Complications
Diabetes Mellitus, Type 2 complications
Glucokinase genetics
Hyperglycemia genetics
Mutation
Subjects
Details
- Language :
- English
- ISSN :
- 1538-3598
- Volume :
- 311
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- JAMA
- Publication Type :
- Academic Journal
- Accession number :
- 24430320
- Full Text :
- https://doi.org/10.1001/jama.2013.283980