Supplemental Digital Content is Available in the Text.Cross-sectional observational study in a cohort of 232 diabetic polyneuropathy patients confirmed higher severity of neuropathy and predominant loss-of-function sensory profile in painful cases.

Both the human leucocyte antigen (HLA) DRB1 and the HLA DQB1 gene loci play a role in the development and progression of autoimmune diabetes mellitus (T1DM). Similarly, the insulin promoter variable number tandem repeats (INS-VNTR) polymorphism is also involved in the pathogenesis of diabetes mellitus (DM). We studied the association between each of these polymorphisms and DM diagnosed in patients older than age 35 years. Furthermore, we analysed possible interactions between HLA DRB1/DQB1 and INS-VNTR polymorphisms. Based on C-peptide and GADA levels we were able to distinguish three types of diabetes: T1DM, latent autoimmune diabetes in adults (LADA) and T2DM. INS-VNTR was genotyped indirectly by typing INS-23HphI A/T polymorphism. The genotype and allele frequencies of INS-23HphI did not differ between each of the diabetic groups and group of healthy subjects. We did, however, observe an association between the INS-23HphI alleles, genotypes and C-peptide secretion in all diabetic patients: A allele frequency was 86.2% in the C-peptide-negative group vs. 65.4% in the C-peptide-positive group (P(corr.) < 0.005); AA genotype was found to be 72.4% in the C-peptide-negative group vs. 42.6% in the C-peptide-positive groups (P(corr.) < 0.01). The HLA genotyping revealed a significantly higher frequency of HLA DRB1*03 allele in both T1DM and LADA groups when compared to healthy subjects: T1DM (25.7%) vs. control group (10.15%), odds ratio (OR) = 3.06, P < 0.05; LADA (27.6%) vs. control (10.15%), OR = 3.37, P < 0.01. The simultaneous presence of both HLA DRB1*04 and INS-23HphI AA genotype was detected in 37.5% of the T1DM group compared to only 9.2% of the healthy individuals group (OR = 5.9, P(corr.) < 0.007). We summarize that in the Central Bohemian population of the Czech Republic, the INS-23HphI A allele appears to be associated with a decrease in pancreatic beta cell secretory activity. HLA genotyping points to at least a partial difference in mechanism, which leads to T1DM and LADA development as well as a more diverse genetic predisposition in juvenile- and adult-onset diabetes. The simultaneous effect of HLA and INS-VNTR alleles/genotypes predispose individuals to an increased risk of diabetes development.

Background/Aims: Tocotrienols has been shown to inhibit the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase activity; however, the published animal and human studies yield conflicting results. We investigated the effects of a 4-week dietary supplement of either γ-tocotrienol (86% γ-T3) or a mixture of tocotrienols (29.5% α-T3, 3.3% β-T3, 41.4% γ-T3, 0.1% δ-T3: mix-T3) on the plasma lipid profile in hamsters receiving a high fat diet. Methods: The hamsters were randomized into 7 groups: no treatment, 16 mg/day/kg BW simvastatin, 23, 58, 263 mg/day/kg BW γ-tocotrienol, and 39 or 263 mg/day/kg BW for the mixture of tocotrienols. Plasma lipid levels were measured after 2 and 4 weeks of treatment. Results: In all groups treated with tocotrienol total cholesterol levels were decreased, ranging from 7 to 23% after 2 weeks of treatment and from 7 to 15% after 4 weeks. Low-density lipoprotein plasma levels changed accordingly: a decline of 6–37% after 2 weeks and of 12–32% at the end of the study was observed. After 4 weeks of treatment, total cholesterol and low-density lipoprotein plasma levels were significantly reduced in the 263 mg/day/kg BW mixed tocotrienols and the 58 mg/day/kg BW and 263 mg/day/kg BW γ-tocotrienol groups when compared to the no treatment group. Plasma triglycerides and high-density lipoprotein levels did not change significantly. Conclusion: This study provides further evidence that tocotrienols lower total cholesterol and low density lipoprotein plasma levels in hamsters and that γ-tocotrienol is a more potent agent than a mixture of tocotrienols.

Authors analyze actual situation in treatment of cardiovascular diseases in older patients. Different groups of recommended drugs are discussed separately; possible risks for elderly patients are stressed. Angiotensin converting enzyme inhibitors-this group is widely used in older patients because of their hypotensive effect, positive influence on cardiac failure, and positive modulation of endothelial dysfunction. The risk of hyperkalemia must be considered. Antiaggregants and anticoagulants are proved as potent prophylactic treatment, but the associated risk of gastrointestinal bleeding must be weighed very carefully. Bradycardia related to β-blockers, especially in combination with other medications lowering the heart rate must be taken into account. Otherwise, this group brings the highest profit in cardiovascular diseases as for morbidity and mortality. Attention is paid to calcium channel blockers, statins, diuretics, nitrates, and digoxin. A table listing the possible side effects and clinical symptoms of overdose by medications most frequently used in the elderly concludes the article.

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