Plasma AGE-peptides and C-peptide in early-stage diabetic nephropathy patients on thiamine and pyridoxine therapy.

AIM: The aim of the study was to evaluate circulatory AGE-peptide levels in diabetic nephropathy and to observe the effects of thiamine (vitamin B1) and pyridoxine (vitamin B6) therapy. METHODS: Type 2 diabetic patients (N.=57) were divided into two groups as "with nephropathy" (N.=27) and "without nephropathy" (N.=30). Diabetic nephropathy patients were treated with either B6 (N.=12) (250 mg/day) or B1+B6 (N.=15) (250 mg/day, each) for five months. At the beginning and the end of the experimentation period, glucose, HbA1c, triglyceride, cholesterol, insulin, C-peptide, thiamine pyrophosphate, pyridoxal phosphate and AGE- peptides were measured. RESULTS: AGE-peptides were higher in the diabetic group with nephropathy than without nephropathy (P=0.005). Within five months AGE-peptides increased in the diabetic group without nephropathy (P=0.042) but not in the group with nephropathy treated either with B1+B6 or B6. In B6 treated group a substantial decrease was observed in HbA1c (P=0.033). B1+B6 or B6 treatment both caused an increase in C-peptide (P=0.006, P=0.004). CONCLUSION: Among the parameters measured, plasma AGE-peptides was the only parameter found to be higher in type 2 diabetes mellitus patients "with nephropathy" than "without nephropathy". However, patients with nephropathy treated with B1+B6 or B6 did not display any further increase in AGE-peptides within five months. Both of the treatments caused an increase in C-peptide.

Increased DNA-glycation in type 2 diabetic patients: the effect of thiamine and pyridoxine therapy.

BACKGROUND: It is well known that advanced glycation plays an important role in the progression of diabetic complications. Although several studies have been done on protein glycation, studies related to DNA glycation is limited. The aim of this study is primarily to investigate DNA glycation in diabetes mellitus and secondarily to observe the effects of vitamins B(1) and B(6). MATERIALS AND METHODS: Patients with diabetes (n=31) were divided into 2 groups as patients with nephropathy (n=17) and without nephro-pathy (n=14). The control group was recruited from age and sex matched healthy individuals (n=30). In the experimental groups, DNA glycation was measured in DNA isolated from leukocytes. HbA(1c), thiamine pyrophosphate (TPP) and pyridoxal 5-phosphate (PLP) levels were determined in whole blood; glucose and insulin levels in plasma. Patients with nephropathy were further divided into 2 groups and were administered either vitamins B(1) + B(6) (n=6) or B(6) (n=11), for 5 months. All the measurements were performed both before and after the vitamin administration period. RESULTS: AGE-DNA levels were found significantly higher in diabetic patients (p<0.05) than the healthy controls. AGE-DNA and PLP levels were negatively correlated in control patients (r= - 0.361, p<0.05). The combined administration of B(1) and B(6) caused a significant decrease in AGE-DNA values (p<0.05). CONCLUSION: This study shows that the combined administration of vitamins B(1) and B(6) to diabetic nephropathy patients causes a decrease in DNA glycation in leukocytes. Importantly the administration of vitamin B(6) alone did not have such an effect. To our knowledge, these are the first reported findings related to glycation of leukocyte nuclear DNA in diabetic nephropathy.

Low-density-lipoprotein peak particle size in a Mediterranean population.

BACKGROUND: The predominance of small, dense low-density lipoprotein (LDL) particles ('LDL phenotype B') has been associated with a three-fold increased risk of myocardial infarction, but the feasibility of the identification of small, dense LDL as independent predictors of coronary artery disease risk in population studies remains questioned. Design We evaluated the LDL peak particle size and its relation with other established risk factors for coronary heart disease in a group of 156 randomized subjects living on the Mediterranean island of Ustica (71 males and 85 women, range of age 20-69 years), representing approximately 30% of the total population. RESULTS: The prevalence of LDL phenotype B subjects was low (approximately 15% in both men and women) and there was a clear trend for both genders in reducing the LDL peak particle size with age. Moreover, LDL phenotype B subjects had higher BMI values, prevalence of diabetes and plasma triglyceride (TG) levels and lower plasma HDL-C concentrations in comparison with LDL phenotype A individuals; in a multivariate analysis, plasma TG levels were the only variable independently associated with LDL peak particle size. CONCLUSIONS: In this population, which appears to be somewhat protected by premature coronary artery disease, a low prevalence of the LDL pattern B was found in both men and women, and plasma TG could have a key role in regulating the LDL peak particle size. The follow up, still ongoing, will provide useful information on the predictive role of LDL peak particle size on cardiovascular risk, at least in a low-risk population.

Distribution of risk factors, plasma lipids, lipoproteins and dyslipidemias in a small Mediterranean island: the Ustica Project.

BACKGROUND AND AIM: The populations of the Mediterranean area have a low incidence of cardiovascular disease (CHD). The aims of this paper are: 1) to present demographic data of the population of Ustica, a small island in the southern part of the Tyrrhenian sea that has reduced communications with the mainland and a diet presumably rich in fish; and 2) to evaluate the distribution of risk factors, plasma lipids, lipoproteins and dyslipidemias in this population. METHODS AND RESULTS: We invited all of the free-living resident population aged more than 14 years (about 800 individuals) to participate in the study; 576 responded, for a participation rate of about 73%. The distribution of cardiovascular risk factors, plasma lipids, lipoproteins and dyslipidemias were evaluated in all of the subjects. More than 60% of the population was out of the normal weight range. Total and low-density lipoprotein cholesterol levels were respectively 207.4 +/- 46.7 and 141.7 +/- 42.4 mg/dL, and similar in males and females. Lipoprotein (a) (Lp[a]) levels presented the classical "skewed" distribution and, among the apolipoprotein(a) isoforms, there was a clear predominance of intermediate-sized kringle IV repeats. Overall, 43% of the subjects had a lipid disorder: the prevalence of hypercholesterolemia was 22.8% (3.2% with severe hypercholesterolemia terolemia > or = 300 mg/dL); low high-density lipoprotein cholesterol levels were found in 22.5%; the so-called lipid triad in 2.1%; and high Lp(a) levels in 6.2%. Large familial clusters were found for some lipid disorders. CONCLUSIONS: A large prevalence of body weight disturbances and high frequency of dyslipidemias are the main characteristics of this population. Ongoing data and future longitudinal studies will better clarify the relative influence of each parameter on CHD risk and total mortality.

ApoE polymorphism in a small Mediterranean island: relationships with plasma lipids, lipoproteins and LDL particle size.

Polymorphisms of apoE gene are able to modulate lipoprotein metabolism at different steps and to influence LDL-cholesterol (LDL-C) levels and also other lipoproteins features. Population studies documented large differences in the frequency of apoE alleles which could be even related to the prevalence of cardiovascular disease. In this study we evaluated the apoE genotypes and allele frequency in 576 subjects living in a small island in the Tyrrhenian Sea and the relative contribution of apoE polymorphism on plasma lipid and lipoprotein profile, including LDL particle size. We found a cumulative frequency of 0.073, 0.866 and 0.061 for epsilon2, epsilon3 and epsilon4 alleles respectively. Moreover epsilon3 subjects had only triglyceride levels significantly lower and LDL-C and lipoprotein (a) (Lp(a)) levels higher than epsilon2 carriers. LDL-particle size was significant smaller in epsilon2 subjects than both epsilon3 and epsilon4 carriers, but the difference disappeared when data were adjusted for triglycerides. In conclusion we have provided further evidence of a low prevalence of epsilon4 allele in a Mediterranean population which may represent a genetic protective factor of these populations. Environmental factors, such as diet, occurring in this area may have attenuated the influence of this gene on plasma lipoproteins.

Italian familial defective apolipoprotein B patients share a unique haplotype with other Caucasian patients.

Familial defective apolipoprotein (apo) B-100 together with familial hypercholesterolemia are the two common genetic conditions that cause hypercholesterolemia. Familial defective apolipoprotein B-100 is due to mutations around codon 3500 of the apo B gene. The most-characterized mutation is a G>A transition at nucleotide 10,708 that results in the substitution of arginine by glutamine at codon 3500 (Apo B Arg3500Gln). Two other mutations are caused by a C>T transition, one at nucleotide 10,800 (Apo B Arg3531Cys) and the other at nucleotide 10,707 (apo B Arg3500Trp). In the present study we describe three new Italian cases of familial defective apolipoprotein B-100 (Apo B Arg3500Gln), one from the Liguria region and two from Sicily, and the haplotype of the apo B gene co-segregating with the mutation. By screening two groups of probands, clinically diagnosed as having Familial Hypercholesterolemia (700 from mainland Italy and 305 from Sicily), the prevalence of familial defective apolipoprotein B-100 due to Arg3500Gln was found to be very low (0.28% and 0.65%, respectively). The Arg3531Cys mutation was not detected in any proband. In the three new families with Arg3500Gln mutation in the present study and in one previously described in Italy, the mutation was associated with a unique apo B haplotype, which is consistent with data previously reported for Caucasian patients [XbaI-, MspI+, EcoRI-, presence of the 5' signal peptide insertion (Ins) allele, and the 49-repeat allele of the 3'-VNTR].