Randomized control trial comparing the effect of cilostazol and aspirin on changes in carotid intima-medial thickness.

Antiplatelet drugs are effective in preventing recurrence of atherosclerosis in type 2 diabetes (T2D) patients. However, the efficacy and usefulness of antiplatelet drugs on the progression of carotid intima-media thickness (IMT), a marker for evaluating early atherosclerotic vascular disease, has not been analyzed. We conducted a prospective, randomized, open, 36-month trial comparing cilostazol vs. aspirin. A total of 415 T2D patients (age range 38-83 years; 206 females) without macrovascular complications were randomized to either an aspirin (100 mg/day) or cilostazol (200 mg/day) treatment. Patients underwent B-mode ultrasonography annually to assess the IMT and serum levels of inflammatory markers were measured before and after each treatment. Potential confounders were statistically adjusted, and included lipid profiles, HbA1c, body mass index, waist circumference, anti-hypertensive and statin medications. The decrease in mean left, maximum left, mean right and maximum right IMT were significantly greater with cilostazol compared with aspirin (- 0.094 ± 0.186 mm vs. 0.006 ± 0.220 mm, p < 0.001; - 0.080 ± 0.214 mm vs. 0.040 ± 0.264 mm, p < 0.001; - 0.064 ± 0.183 mm vs. 0.004 ± 0.203 mm, p = 0.015; - 0.058 ± 0.225 mm vs. 0.023 ± 0.248 mm, p = 0.022, respectively). And these differences remained significant after adjustment of potential confounders. Compared with aspirin, cilostazol treatment was associated with significantly increased HDL cholesterol (p = 0.039) and 25-hydroxy vitamin D levels (p = 0.001). Cilostazol treatment was associated with significantly lowered IMT in T2D patients compared to aspirin, independent of conventional cardiovascular risk factors. Cilostazol may inhibit plaque formation and have beneficial effects on atherosclerosis through vasodilatory and antiplatelet effects.

LADA prevalence estimation and insulin dependency during follow-up.

BACKGROUND: Latent autoimmune diabetes in adults (LADA) is a form of autoimmune-mediated diabetes in adults, usually defined by GAD autoantibody positivity. Few epidemiological surveys on LADA in Asians did not come to a conclusive answer regarding prevalence and incidence, because of different criteria used in patient ascertainment. METHODS: We estimated LADA prevalence in a recent type 2 diabetes cohort by the positivity of circulating autoantibodies to pancreatic islet cell antigens (GAD, IA-2 and zinc transporter 8 (ZnT8)) applying a comparable Caucasian criteria. We then observed the development of insulin dependency prospectively for 36 months. RESULTS: Applying the European NIRAD LADA group criteria, we found a high prevalence of LADA (4.4%) in Korean patients with phenotypic type 2 diabetes. This high prevalence of LADA in Korea is noteworthy since the previous population-based LADA prevalence survey reported low prevalence (1.7%). When we consider the low-titre GAD antibodies and the low prevalence of multiple autoantibodies, however, increased LADA prevalence does not necessarily mean increase in future insulin dependency. After 36 months of follow-up, only 3 of 39 patients who were initially classified as LADA have become insulin-dependent. Those three were all positive for multiple autoantibodies (GAD, IA-2 and zinc transporter 8 antibody). Other features of insulin secretion or insulin resistance did not determine future insulin necessity. CONCLUSIONS: Although the LADA prevalence estimated by anti-GAD positivity appeared to increase, the true insulin dependency evidenced by multiple antibody positivity did not increase in Korea.

Association of vascular endothelial growth factor polymorphisms with nonproliferative and proliferative diabetic retinopathy.

CONTEXT: Vascular endothelial growth factor (VEGF) is a potent angiogenic and vascular permeability factor, and its polymorphisms are associated with proliferative diabetic retinopathy (PDR) and macular edema. OBJECTIVE: We investigated the contributions of VEGF gene polymorphisms to nonproliferative diabetic retinopathy (NPDR) as well as PDR. DESIGN, SETTING, AND SUBJECTS: In this study we compared VEGF gene variants in a sample of Korean type 2 diabetes patients with and without diabetic retinopathy (DR) and in healthy controls. Of the diabetes patients, 145 had PDR, 108 had NPDR, and 134 had no retinopathy (noDR). They were all duration matched. Samples were genotyped for rs699947, rs1570360, and rs2010963 polymorphisms. RESULTS: We found a significant association between the A allele at rs699947 with DR (odds ratio = 1.84 (95% confidence interval = 1.28-2.66); P = 0.001 vs. noDR). Patients with NPDR, as well as PDR, had increased incidence of the A allele. The AGG haplotype was more frequently found in patients with DR than in patients with noDR (odds ratio = 4.79 (95% confidence interval = 1.42-16.16); P = 0.006). PDR and NPDR patients exhibited an increased incidence of the AGG haplotype. CONCLUSIONS: VEGF polymorphisms might be a useful predictive marker for the development and progression of DR at an earlier stage of diabetes.