J Korean Med Sci.  2014 Oct;29(10):1353-1359. 10.3346/jkms.2014.29.10.1353.

Impact of ENPP1 K121Q on Change of Insulin Resistance after Web-Based Intervention in Korean Men with Diabetes and Impaired Fasting Glucose

• Kang JY
• Sung SH
• Lee YJ
• Choi TI
• Choi SJ

• KMID: 2129624
• DOI: http://doi.org/10.3346/jkms.2014.29.10.1353

Abstract

Ectoenzyme nucleotide pyrophosphate phosphodiesterase 1 (ENPP1) gene has been studied in relation to type 2 diabetes mellitus (T2DM) and insulin resistance (IR). We hypothesized that the difference in genotype may be one of the factors that affect the outcome of intervention. We genotyped 448 men with fasting glucose> or =5.6 mM/L, including 371 in subjects with K allele (KK) (69 control group [CG]; and 302 intervention group [IG]) and 77 in subjects with Q allele (KQ+QQ) (13 CG and 64 IG). The web-based intervention based on a lifestyle modification was delivered by e-mail once a month for 10 months. In the KK, IG demonstrated significantly decreased levels of fasting serum insulin (FSI) as compared to CG and homeostasis model of assessment of insulin resistance (HOMA-IR). In the KQ+QQ IG group, hemoglobin A1c (HbA1c), FSI and HOMA-IR were significantly decreased, and showed further reduction in the HOMA-IR than KQ+QQ CG. After analysis of covariance, K121Q did significantly influence the change of HbA1c in CG after appropriate adjustment. In a multivariate model, BMI change predicted HOMA-IR change (adjusted beta=0.801; P=0.022) in KK IG subjects with T2DM. ENPP1 K121Q did not influence the change in IR. However, individuals with T2DM carrying the K121 variant are very responsive to the effect of BMI reduction on HOMA-IR.

Keyword

Ectoenzyme Nucleotide Pyrophosphate Phosphodiesterase 1; Diabetes Mellitus; Web-Based Lifestyle Intervention; Insulin Resistance

MeSH Terms

Alleles
Asian Continental Ancestry Group/genetics
Blood Glucose/analysis
Body Mass Index
Diabetes Mellitus, Type 2/blood/*genetics
*Food Habits
Hemoglobin A, Glycosylated/*analysis
Humans
Insulin Resistance/*genetics
Internet
Life Style
Male
Middle Aged
Phosphoric Diester Hydrolases/*genetics
Pyrophosphatases/*genetics
Republic of Korea
Weight Loss/genetics
Blood Glucose
Hemoglobin A, Glycosylated
Phosphoric Diester Hydrolases
Pyrophosphatases

Figure

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  Fig. 1 Flowchart of study participants. FPG, Fasting plasma glucose; T2DM, Type 2 diabetes mellitus.

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  Fig. 2 Association of the change in HOMA-IR and BMI in intervention group with T2DM according to the (A) K allele subjects, (B) Q allele subjects. Δ, Post-Pre; BMI, body mass index; WC, waist circumference; HOMA-IR, homeostasis model of insulin resistance.

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