[Show abstract][Hide abstract] ABSTRACT: Beyond statin therapy for reducing low density lipoprotein cholesterol (LDL-C), additional therapeutic strategies are required to achieve more optimal reduction in cardiovascular risk among diabetic patients with dyslipidemia. To evaluate the effects and the safety of combined treatment with omega-3 fatty acids and statin in dyslipidemic patients with type 2 diabetes, we conducted a randomized, open-label study in Korea. Patients with persistent hypertriglyceridemia (≥200 mg/dL) while taking statin for at least 6 weeks were eligible. Fifty-one patients were randomized to receive either omega-3 fatty acid 4, 2 g, or no drug for 8 weeks while continuing statin therapy. After 8 weeks of treatment, the mean percentage change of low density lipoprotein (LDL) particle size and triglyceride (TG) level was greater in patients who were prescribed 4 g of omega-3 fatty acid with statin than in patients receiving statin monotherapy (2.8%±3.1% vs. 2.3%±3.6%, P=0.024; -41.0%±24.1% vs. -24.2%±31.9%, P=0.049). Coadministration of omega-3 fatty acids with statin increased LDL particle size and decreased TG level in dyslipidemic patients with type 2 diabetes. The therapy was well tolerated without significant adverse effects.
[Show abstract][Hide abstract] ABSTRACT: Research on the relationship between urinary albumin excretion and serum cystatin C in diabetes is restricted to cross-sectional studies. In this study, we investigated how well serial measurements of serum cystatin C level reflect changes in the urinary albumin excretion rate.
We enrolled and retrospectively collected data on 1,058 participants with type 2 diabetes who were older than 18 years and who had more than 3 years of follow-up with serial measurements of albuminuria and serum cystatin C at an outpatient clinic.
With the use of a linear mixed model, we found that the albuminuria level for each patient over time corresponded with the annual change in serum cystatin C-based estimated glomerular filtration rate (cysC-eGFR) but did not correspond with the creatinine-based eGFR calculated by the modification of diet in renal disease formula (MDRD-eGFR). The discrepancy in the direction of the trend was smaller with cysC-eGFR than with MDRD-eGFR.
Serum cystatin C level reflects the trend in albuminuria level more accurately than serum creatinine level in Korean type 2 diabetes mellitus patients.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to determine the effect of common adiponectin gene polymorphisms on dietary intervention-mediated changes in adiponectin levels and homeostasis model assessment of insulin resistance (HOMA-IR) indexes.
A total of 363 subjects with impaired fasting glucose (IFG) or newly diagnosed type 2 diabetes followed a dietary intervention (replacement of cooked refined rice with whole grains and an increase in vegetable intake) and regular walking for 12 weeks without any medication. Adiponectin gene single nucleotide polymorphisms (SNPs) (45, 276, and -11377) were examined in these subjects.
After this dietary intervention, fasting glucose levels decreased in all three SNP 45T>G genotype groups. Subjects with the SNP 45TT genotype showed increased adiponectin levels and decreased HOMA-IR indexes. Haplotype analysis revealed that homozygous carriers of the TG haplotype (45TT and 276GG) and heterozygous carriers of the TG haplotype (TG/X) showed a reduction in the HOMA-IR index after adjustment for baseline levels. Significant differences were observed in changes in HOMA-IR indexes and adiponectin concentrations according to the 45-276 TG haplotype in overweight-obese, but not in normal-weight subjects: the greatest decrease in HOMA-IR indexes and the greatest increase in adiponectin levels were shown in overweight-obese subjects with the TG/TG haplotype.
ADIPOQ genetic variants can affect circulating adiponectin levels and insulin resistance indexes in subjects with IFG or newly diagnosed type 2 diabetes in response to dietary intervention.
Diabetes care 02/2009; 32(4):552-8. · 7.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Increased levels of inflammatory markers, such as interleukin-6 (IL-6), are associated with type 2 diabetes (T2DM). We investigated the association of IL-6 gene polymorphisms with T2DM and circulating levels of IL-6 in Koreans.
A total of 1477 subjects with normal glucose tolerance and 476 T2DM patients were included.
We examined IL-6 -174G-->C, -572C-->G, -597G-->A and -1363G-->T promoter region polymorphisms. The main outcome measures were the odds ratio (OR) on T2DM risk and serum concentrations of IL-6 and high-sensitivity C-reactive protein (hs-CRP).
Homozygosity for the rare G allele IL-6 -572C-->G was associated with a higher risk of T2DM [OR 1.69 (95%CI 1.11-2.58), P = 0.015]. Serum IL-6 concentrations were associated with the IL-6 -572C-->G genotype in control subjects (G/G: 2.33 +/- 0.41: C/G: 1.53 +/- 0.09: C/C: 1.72 +/- 0.08 ng/l, P = 0.023). Also in the control group, subjects homozygous for the rare G allele showed significantly higher concentrations of hs-CRP than C/C and C/G carriers (G/G: 13.6 +/- 2.9: C/G: 9.2 +/- 0.6: C/C: 7.8 +/- 0.4 mg/l, P = 0.003). The C-allele at the IL-6 -174 SNP was very rare (< 0.01) and -597G-->A and -1363G-->T were monomorphic in this population.
Our data demonstrate that the IL-6 -572G/G genotype is associated with higher serum IL-6 and hs-CRP concentrations and with increased risk for T2DM.
[Show abstract][Hide abstract] ABSTRACT: We investigated the association between the Gly82Ser (G82S) polymorphism in the receptor for advanced glycation end products (RAGE) gene and circulating levels of soluble RAGE (sRAGE), advanced glycation end products (AGEs), and inflammatory markers in nondiabetic/nonobese Koreans. A total of 1096 men and 580 women aged 30 to 69 years and with body mass index of 18.5 to 29.9 kg/m(2) were recruited. Anthropometrics, lipid profiles, glucose, insulin, insulin resistance (IR), RAGE G82S polymorphism, sRAGE, AGEs, and inflammatory markers were measured. There was a significant association between G82S genotypes and plasma sRAGE concentrations (P < .001). sRAGE concentrations were significantly higher in subjects with the G/G genotype (1038 +/- 33 pg/mL) than in those with the G/S (809 +/- 19 pg/mL) or the S/S (428 +/- 43 pg/mL) genotype. Furthermore, the G82S genotypes in the RAGE gene were associated with serum AGE (P = .033), homeostasis model assessment for insulin resistance (HOMA-IR) (P < .001), plasma tumor necrosis factor alpha (TNF-alpha) (P = .033), serum C-reactive protein (CRP) (P= .002), and urinary excretion of 8-epi-prostaglandin F(2alpha) (P = .028) after adjusting for sex, age, body mass index, cigarette smoking, and alcohol drinking. Subjects with the S/S genotype showed higher levels of serum AGE, HOMA-IR, plasma TNF-alpha, serum CRP, and 8-epi-prostaglandin F(2alpha) than those with the G/G or G/S combination. The sRAGE levels showed a negative relation with high-sensitivity CRP (r = -0.250; P < .001). The AGE concentrations showed a positive relation with TNF-alpha levels (r = 0.398; P < .001). Subjects with homozygosity for the minor S allele (S/S) of the G82S polymorphism had higher risk factors for cardiovascular disease, such as low sRAGE levels, inflammation, oxidative stress, and IR, compared with those bearing at least one G allele.
[Show abstract][Hide abstract] ABSTRACT: A mutation in codon 631 of exon 11 of the RET proto-oncogene is extremely rare in the patients with multiple endocrine neoplasia type 2A (MEN 2A). We report here on a rare extracellular mutation of the RET gene that led to the substitution of a tyrosine for an aspartate in codon 631 (D631Y, GAC to TAC) in two Korean families with MEN 2A. Eleven individuals from two unrelated families were found to have the D631Y germline mutation. Among them, medullary thyroid carcinoma (MTC) was identified in five patients: four of them had MEN 2A and one had familial MTC. They had tumors 2 cm or less in the greatest dimension that were limited to the thyroid, and they had a relatively old age above 30 at the time of diagnosis. Pheochromocytoma was detected in six patients including the four patients who had MEN 2A. All had adrenal tumors greater than 3 cm in the greatest dimension, and four of them had bilateral tumors. Two of six patients suffering with pheochromocytoma had no clinical evidence of MTC at the time of diagnosis. None had any evidence of hyperparathyroidism. This genetic profile might be related to the less vigorous clinical disease behavior and the late onset of MTC. In addition, pheochromocytoma might be the first manifestation prior to the development of MTC in some patients with the D631Y mutation. This report is the first description of the clinical characteristics of the D631Y germline mutation in the families with MEN 2A.
[Show abstract][Hide abstract] ABSTRACT: Homeostasis model assessment of insulin resistance (HOMA-IR) is a less invasive, inexpensive, and less labor-intensive method to measure insulin resistance (IR) as compared with the glucose clamp test. The aim of this study was to evaluate the validity of HOMA-IR by comparing it with the euglycemic clamp test in determining IR. We assessed the validity of HOMA-IR by comparing it with the total glucose disposal rate measured by the 3-hour euglycemic-hyperinsulinemic clamp in subjects with type 2 diabetes (n = 47), impaired glucose tolerance (n = 21), and normal glucose tolerance (n = 22). There was a strong inverse correlation (r = -0.558; P < .001) between the log-transformed HOMA-IR and the total glucose disposal rate. There was moderate agreement between the 2 methods in the categorization according to the IR (weighted kappa = 0.294). The magnitude of the correlation coefficients was smaller in the subjects with a lower body mass index (BMI <25.0 kg/m2 , r = -0.441 vs BMI > or =25.0 kg/m2 , r = -0.615; P = .032), a lower HOMA-beta cell function (HOMA- beta <60.0, r = -0.527 vs HOMA- beta > or =60.0, r = -0.686; P = .016), and higher fasting glucose levels (fasting glucose < or =5.66 mmol/L, r = -0.556 vs fasting glucose >5.66 mmol/L, r = -0.520; P = .039). The limitation of the validity of the HOMA-IR should be carefully considered in subjects with a lower BMI, a lower beta cell function, and high fasting glucose levels such as lean type 2 diabetes mellitus with insulin secretory defects.