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Less but better: cardioprotective lipid profile of patients with GCK-MODY despite lower HDL cholesterol level.

Fendler W, Rizzo M, Borowiec M, Malachowska B, Antosik K, Szadkowska A, Banach M, Urbanska-Kosinska M, Szopa M, Malecki M, Mlynarski W - Acta Diabetol (2014)

Bottom Line: Concentrations of the small, highly atherogenic LDL subpopulation were similar among the compared groups.Large HDL percentage was significantly higher in GCK-MODY than in control (p = 0.0003), T1DM (p = 0.0006) and HNF1A-MODY groups (p = 0.0246).A degree of heterogeneity within the groups suggests the existence of interactions with other genetic or clinical factors.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Oncology, Hematology and Diabetology, Medical University of Lodz, 36/50 Sporna Str., 91-738, Lodz, Poland.

ABSTRACT
Patients with diabetes caused by single-gene mutations generally exhibit an altered course of diabetes. Those with mutations of the glucokinase gene (GCK-MODY) show good metabolic control and low risk of cardiovascular complications despite paradoxically lowered high-density lipoprotein (HDL) cholesterol levels. In order to investigate the matter, we analyzed the composition of low-density lipoprotein (LDL) and HDL subpopulations in such individuals. The LipoPrint(©) system (Quantimetrix, USA) based on non-denaturing, linear polyacrylamide gel electrophoresis was used to separate and measure LDL and HDL subclasses in fresh-frozen serum samples from patients with mutations of glucokinase or HNF1A, type 1 diabetes (T1DM) and healthy controls. Fresh serum samples from a total of 37 monogenic diabetes patients (21 from GCK-MODY and 16 from HNF1A-MODY), 22 T1DM patients and 15 healthy individuals were measured in this study. Concentrations of the small, highly atherogenic LDL subpopulation were similar among the compared groups. Large HDL percentage was significantly higher in GCK-MODY than in control (p = 0.0003), T1DM (p = 0.0006) and HNF1A-MODY groups (p = 0.0246). Patients with GCK-MODY were characterized by significantly lower intermediate HDL levels than controls (p = 0.0003) and T1DM (p = 0.0005). Small, potentially atherogenic HDL content differed significantly with the GCK-MODY group showing concentrations of that subfraction from control (p = 0.0096), T1DM (p = 0.0193) and HNF1A-MODY (p = 0.0057) groups. Within-group heterogeneity suggested the existence of potential gene-gene or gene-environment interactions. GCK-MODY is characterized by a strongly protective profile of HDL cholesterol subpopulations. A degree of heterogeneity within the groups suggests the existence of interactions with other genetic or clinical factors.

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Related in: MedlinePlus

Hierarchical clustering plot of lipid profiles. Lipid subfraction levels were standardized across the samples, and Euclidean distance was used to visualize within- and between-group differences. Although the lipid profiles of the majority of patients from the HNF1A- and GCK-MODY groups showed within-group similarities, considerable heterogeneity is evident, which suggests an overlapping effect of environmental and/or other genetic factors
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Fig2: Hierarchical clustering plot of lipid profiles. Lipid subfraction levels were standardized across the samples, and Euclidean distance was used to visualize within- and between-group differences. Although the lipid profiles of the majority of patients from the HNF1A- and GCK-MODY groups showed within-group similarities, considerable heterogeneity is evident, which suggests an overlapping effect of environmental and/or other genetic factors

Mentions: The patients age was not associated with significant changes in either the most atherogenic small LDL (r = −0.1339, p = 0.2803) or HDL (r = 0.0414, p = 0.7404) fractions. Profile analysis by hierarchical clustering showed evident heterogeneity despite statistically significant differences between the groups. Among patients with GCK- or HNF1A-MODY, nine individuals in both groups showed considerable similarities of their lipid profile, suggesting the existence of a MODY-specific effect (Fig. 2). In-depth analysis of patients with GCK-MODY showed that patients with identical mutations clustered more tightly together than individuals with other types of GCK gene alterations (Fig. 3). However, considerable variability was noted between patients with GCK-MODY, suggesting that the clinical phenotype of GCK-MODY may be strongly modulated also by other genetic or environmental factors.Fig. 2


Less but better: cardioprotective lipid profile of patients with GCK-MODY despite lower HDL cholesterol level.

Fendler W, Rizzo M, Borowiec M, Malachowska B, Antosik K, Szadkowska A, Banach M, Urbanska-Kosinska M, Szopa M, Malecki M, Mlynarski W - Acta Diabetol (2014)

Hierarchical clustering plot of lipid profiles. Lipid subfraction levels were standardized across the samples, and Euclidean distance was used to visualize within- and between-group differences. Although the lipid profiles of the majority of patients from the HNF1A- and GCK-MODY groups showed within-group similarities, considerable heterogeneity is evident, which suggests an overlapping effect of environmental and/or other genetic factors
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4127439&req=5

Fig2: Hierarchical clustering plot of lipid profiles. Lipid subfraction levels were standardized across the samples, and Euclidean distance was used to visualize within- and between-group differences. Although the lipid profiles of the majority of patients from the HNF1A- and GCK-MODY groups showed within-group similarities, considerable heterogeneity is evident, which suggests an overlapping effect of environmental and/or other genetic factors
Mentions: The patients age was not associated with significant changes in either the most atherogenic small LDL (r = −0.1339, p = 0.2803) or HDL (r = 0.0414, p = 0.7404) fractions. Profile analysis by hierarchical clustering showed evident heterogeneity despite statistically significant differences between the groups. Among patients with GCK- or HNF1A-MODY, nine individuals in both groups showed considerable similarities of their lipid profile, suggesting the existence of a MODY-specific effect (Fig. 2). In-depth analysis of patients with GCK-MODY showed that patients with identical mutations clustered more tightly together than individuals with other types of GCK gene alterations (Fig. 3). However, considerable variability was noted between patients with GCK-MODY, suggesting that the clinical phenotype of GCK-MODY may be strongly modulated also by other genetic or environmental factors.Fig. 2

Bottom Line: Concentrations of the small, highly atherogenic LDL subpopulation were similar among the compared groups.Large HDL percentage was significantly higher in GCK-MODY than in control (p = 0.0003), T1DM (p = 0.0006) and HNF1A-MODY groups (p = 0.0246).A degree of heterogeneity within the groups suggests the existence of interactions with other genetic or clinical factors.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Oncology, Hematology and Diabetology, Medical University of Lodz, 36/50 Sporna Str., 91-738, Lodz, Poland.

ABSTRACT
Patients with diabetes caused by single-gene mutations generally exhibit an altered course of diabetes. Those with mutations of the glucokinase gene (GCK-MODY) show good metabolic control and low risk of cardiovascular complications despite paradoxically lowered high-density lipoprotein (HDL) cholesterol levels. In order to investigate the matter, we analyzed the composition of low-density lipoprotein (LDL) and HDL subpopulations in such individuals. The LipoPrint(©) system (Quantimetrix, USA) based on non-denaturing, linear polyacrylamide gel electrophoresis was used to separate and measure LDL and HDL subclasses in fresh-frozen serum samples from patients with mutations of glucokinase or HNF1A, type 1 diabetes (T1DM) and healthy controls. Fresh serum samples from a total of 37 monogenic diabetes patients (21 from GCK-MODY and 16 from HNF1A-MODY), 22 T1DM patients and 15 healthy individuals were measured in this study. Concentrations of the small, highly atherogenic LDL subpopulation were similar among the compared groups. Large HDL percentage was significantly higher in GCK-MODY than in control (p = 0.0003), T1DM (p = 0.0006) and HNF1A-MODY groups (p = 0.0246). Patients with GCK-MODY were characterized by significantly lower intermediate HDL levels than controls (p = 0.0003) and T1DM (p = 0.0005). Small, potentially atherogenic HDL content differed significantly with the GCK-MODY group showing concentrations of that subfraction from control (p = 0.0096), T1DM (p = 0.0193) and HNF1A-MODY (p = 0.0057) groups. Within-group heterogeneity suggested the existence of potential gene-gene or gene-environment interactions. GCK-MODY is characterized by a strongly protective profile of HDL cholesterol subpopulations. A degree of heterogeneity within the groups suggests the existence of interactions with other genetic or clinical factors.

Show MeSH
Related in: MedlinePlus