Original Data

Rev Diabet Stud, 2006, 3(1):21-30 DOI 10.1900/RDS.2006.3.21

ENPP1 K121Q Polymorphism is not Related to Type 2 Diabetes Mellitus, Features of Metabolic Syndrome, and Diabetic Cardiovascular Complications in a Chinese Population

Miao-Pei Chen1, Fu-Mei Chung1, Dao-Ming Chang1, Jack C-R Tsai1, Han-Fen Huang1, Shyi-Jang Shin2, Yau-Jiunn Lee1

1Department of Clinical Research, Pingtung Christian Hospital, Pingtung, 90000 Taiwan.
2Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, 80307 Taiwan.
Address correspondence to: Yau-Jiunn Lee, e-mail: t3275@ms25.hinet.net


BACKGROUND: Ectoenzyme nucleotide pyrophosphate phosphodiesterase 1 (ENPP1) is known to influence insulin sensitivity by inhibiting insulin receptor signaling. A DNA polymorphism in the ENPP1 gene at exon 4 (K121Q) was demonstrated to be associated with insulin resistance, type 2 diabetes mellitus (T2DM), and a risk of early myocardial infarction, albeit with controversy. Our aim was to investigate any association of ENPP1 K121Q alleles with T2DM, features of the metabolic syndrome, and diabetic cardiovascular complications in a Chinese population of Han origin. METHODS: The ENPP1 K121Q polymorphism was determined by a restriction fragment-length polymorphism-polymerase chain reaction in 1,862 patients with T2DM and 844 non-diabetic subjects. RESULTS: The genotype distributions or Q-allele frequency were not statistically different between the diabetic and non-diabetic groups. The anthropometric parameters, systolic and diastolic blood pressures, lipid profiles, and serum creatinine levels of subjects with different ENPP1 K121Q polymorphisms were not statistically different in the two groups or even in the pooled data. When sub-group analyses of diabetic subjects were stratified according to BMI levels (greater or less than 27), gender, age of diabetes onset (older or younger than 60 years), and the presence or absence of a diabetic family history; this polymorphism was still not associated with T2DM. Nor was the ENPP1 K121Q polymorphism associated with the prevalence of coronary artery disease and ischemic cerebrovascular disease in patients with T2DM. CONCLUSION: The ENPP1 K121Q polymorphism is not related to T2DM, features of the metabolic syndrome, or diabetic macrovascular complications in a Chinese population.

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Rev Diabet Stud, 2006, 3(1):31-38 DOI 10.1900/RDS.2006.3.31

The Effect of PPARγ-Agonism on LDL Subclass Profile in Patients with Type 2 Diabetes and Coronary Artery Disease

Riikka Lautamäki1, Pirjo Nuutila1,2, K.E. Juhani Airaksinen2, Aila Leino3, Heikki Hiekkanen4, Marian Turiceanu1, Murray Stewart5, Juhani Knuuti1, Tapani Rönnemaa2

1Turku PET Centre, University of Turku, Turku, Finland.
2Department of Medicine, University of Turku, Turku, Finland.
3Department of Clinical Chemistry, Turku University Hospital, Turku, Finland.
4Department of Biostatistics, University of Turku, Turku, Finland.
5GlaxoSmithKline, United Kingdom.
Address correspondence to: Tapani Rönnemaa, e-mail: tapani.ronnemaa@utu.fi


Patients with type 2 diabetes (T2DM) often present a preponderance of small, dense LDL particles (small-LDL), which are associated with a high risk of myocardial infarction. Some studies suggest that PPARγ-agonists increase LDL cholesterol but have divergent effects on various LDL subclasses in T2DM patients. We studied the effect of rosiglitazone on the LDL subclass profile in T2DM patients with verified coronary artery disease (CAD). 58 patients with T2DM (HbA1c < 8.5%) and CAD were enrolled in a 16-week, randomized, double-blind and placebo-controlled trial with rosiglitazone 8mg/day (n = 29) or placebo (n = 29). The LDL subclass profile was measured with gel electrophoresis. Rosiglitazone improved insulin sensitivity and glycemic control. Total cholesterol did not change after rosiglitazone treatment (p = 0.062, ANCOVA adjusted for gender and baseline values), whereas LDL (including IDL) cholesterol increased from 2.33 ± 0.48 to 2.67 ± 0.61 mmol/l (p = 0.002 vs. baseline, p = 0.0497 vs. placebo) and large buoyant LDL (large-LDL > 250Å) increased from 1.31 ± 0.36 to 1.46 ± 0.42 mmol/l (p = 0.010 vs. baseline, p = 0.044 vs. placebo) in the rosiglitazone group. No significant changes occurred to the concentration of small-LDL (< 250Å), the average LDL particle size, or HDL or triglyceride concentrations. Whole-body insulin sensitivity was associated with the average LDL particle size after intervention in the whole population (r = 0.40, p = 0.002) and in the rosiglitazone group (r = 0.43, p = 0.020). In conclusion, in T2DM patients with CAD, rosiglitazone treatment significantly increases the concentration of large (buoyant) LDL cholesterol, but not of small dense LDL cholesterol. The long term consequences of this divergent effect of rosiglitazone on LDL subfractions require further exploration.

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