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What is known and Objective: To evaluate the effects of an olmesartan/amlodipine single pill combination compared with olmesartan or amlodipine monotherapies on blood pressure control, lipid profile, insulin sensitivity and some adipocytokines levels. Methods: Two hundred and seventy-six patients were enroled in the study and were randomly assigned to take olmesartan 20 mg, amlodipine 10 mg, or a single pill containing an olmesartan/amlodipine combination 20 mg/5 mg for 12 months. We evaluated at the baseline, and after 6 and 12 months: body weight, body mass index, systolic and diastolic blood pressure (SBP and DBP), fasting plasma glucose (FPG), fasting plasma insulin (FPI), lipid profile, adiponectin (ADN), resistin (r), interleukin-1β (IL-1β) and interleukin-5 (IL-5). At the baseline, and after 6 and 12 months, patients underwent an euglycemic, hyperinsulinemic clamp to assess insulin sensitivity ( M value). Results and Discussion: There was a similar decrease in SBP and DBP after 6 and 12 months in all groups, even if olmesartan/amlodipine combination gave a major decrease in SBP and DPB compared with amlodipine and olmesartan monotherapies. Olmesartan/amlodipine combination decreased FPG after 12 months compared with amlodipine monotherapy. Olmesartan/amlodipine combination decreased FPI and HOMA index and increased M value both compared with baseline and compared with olmesartan and amlodipine monotherapies. Both olmesartan and olmesartan/amlodipine increased ADN and reduced r, without significant differences between the two groups. Regarding interleukins, no differences emerged in group to group comparison. What is new and Conclusion: Olmesartan/amlodipine combination resulted more effective than olmesartan and amlodipine monotherapies in reducing blood pressure, and in increasing insulin sensitivity parameters, but not resulted more effective in improving adipocytokines and interleukins levels analysed, compared with amlodipine or olmesartan monotherapy in hypertensive patients in this double-blind, randomized clinical trial. [ABSTRACT FROM AUTHOR]

Resistin is overexpressed in human adipose tissue of obese individuals and is likely to modulate insulin sensitivity. Resistin is, therefore, a candidate gene for insulin resistance. We searched for polymorphisms in the resistin gene by single strand conformation polymorphism and direct sequencing. An ATG triplet repeat in the 3'-untranslated region was identified and considered for association with insulin resistance. Three alleles were identified (allele 1: 8 repeats, allele frequency, 0.3%; allele 2: 7 repeats; allele frequency, 94.5%; allele 3: 6 repeats; allele frequency, 5.2%). Two hundred and three unrelated white Caucasian nondiabetic subjects from Sicily and 456 from the Gargano area (center east coast of Italy) were analyzed. Among Sicilians, subjects carrying allele 3 had a lower fasting insulin and insulin resistance index (homeostasis model assessment of insulin resistance; P < 0.001 for both) and glucose (P = 0.025) and insulin (P = 0.002) levels during the oral glucose tolerance test. In subjects from Gargano, those carrying allele 3 had lower fasting plasma glucose levels and serum triglycerides (P = 0.01 for both). When the 2 populations were analyzed together, subjects carrying allele 3 had lower fasting insulin levels (P < 0.005), homeostasis model assessment of insulin resistance (P < 0.005), and serum triglycerides (P = 0.01). In conclusion, our data suggest that subjects carrying allele 3 of the resistin gene are characterized by relatively high insulin sensitivity.

Resistin is a newly identified hormone secreted by adipocytes that inhibits insulin action on peripheral tissues. The aim of our study was to investigate whether genetic variability at this locus is associated with the risk of type 2 diabetes. By sequencing 32 subjects with type 2 diabetes, we identified 8 single nucleotide polymorphisms (SNPs) in the 5'-flanking region and introns of the resistin gene. Allele and genotype distributions were determined for all 8 SNPs in 312 cases with type 2 diabetes and 303 nondiabetic controls, all of Caucasian origin. No significant association with type 2 diabetes was found at any of the polymorphic loci. However, an interactive effect of genotype at SNP 6 (IVS2 + 181G-->A) and obesity was a significant determinant of type 2 diabetes risk in this population. The relative risk of diabetes for the A/A genotype was 4.8 (95% confidence interval, 1.1-21.0) in individuals above the median for body weight, but only 0.7 (95% confidence interval, 0.2-2.1) in those below the median. This difference between relative risks was significant (chi(2) = 4.5; P = 0.03). A similar, but much weaker, interaction with obesity was observed for SNPs in linkage disequilibrium with SNP6. In conclusion, resistin does not appear to be a major gene for type 2 diabetes. However, our data suggest a synergistic effect of sequence differences at the resistin locus and obesity on risk of type 2 diabetes. Further studies are needed to confirm this finding in other populations.