[Clinical value of insulin resistance in fasting normoglycemia].

Aim of the study was to clarify the question of the presence of manifestations of insulin resistance (IR) in fasting normoglycemia and to assess their association with risk of development and presence of clinically overt cardiovascular diseases (CVD) caused by atherosclerosis. We included into this study 1127 men and women older than 55 years with normal blood serum level of glucose in fasting state (<6.1 mmol/l) without diabetes mellitus selected from a random sample of Moscow inhabitants (n=1186). In participants selected for this study we determined risk factors, calculated indexes of IR (HOMA-IR) and functional capacity of pancreatic -cells (HOMA-%B) using fasting levels of glucose and insulin. The examined subsample was divided into quartiles according to values of HOMA-IR. It was shown that in the 4-th quartile HOMA-%B was substantially higher than in other quartiles. With this values of body mass index and waist circumference were also highest in the 4-th quartile. Fasting insulin level compared with glucose level contributed more to determination of values of indexes of both IR and functional capacity of pancreatic -cells. In the upper 4-th quartile signs of atherogenic dyslipidemia appearing as higher concentration of triglycerides and lowered concentration of high density lipoprotein cholesterol manifested to the greatest degree. At statistical analysis of probability of CVD with clinical manifestations it was shown that in the 4-th quartile of distribution of HOMA-IR (>2.7) values of odds ratio (OR) of development of arterial hypertension (AH), total CVD, angina pectoris, history of brain stroke were elevated. With that in the 3-rd quartile of distribution i.e. at HOMA-IR >1.9 there were higher ORs of development of AH, CVD, angina pectoris. Thus even in the range of normal fasting glucose concentrations in subjects older than 55 years we detected IR associated with elevated risk of development of atherosclerosis related CVD. For detection of IR it is appropriate to measure in blood serum not only concentration of glucose but also fasting insulin level with subsequent calculation of HOMA-IR and HOMA-%B indexes.

[Metabolic peculiarities of dyslipoproteinemias unrelated to high level of blood cholesterol].

The aim of this study was to reveal whether atherogenic or nonatherogenic properties of dyslipoproteinemias (DLP) not related to high level of blood total cholesterol (C) and low density lipoprotein C (LDL C) are determined only by shifts in serum triglycerides (TG) and/or high density lipoprotein cholesterol (HDL C) levels, or by other lipoprotein system alterations, if any. Biochemical factors regulating both lipid and carbohydrate metabolism were analyzed in two subsamples of Moscow residents aged 55 years with DLP: "high TG and low HDL C" and "normal TG and high HDL C" in comparison with randomly selected subsample assumed as "normal". Specific biochemical indexes of atherogenicity of DLP "high TG and low HDL C" were found, namely: increased apo B/AI ratio; disturbed functional activity of HDL in promoting reverse cholesterol transport expressed as elevated apo AII/AI ratio, decreased apo AI and phospholipids (PL) levels, decreased ratios of C/apo AI and C/PL in HDL, and decreased cholesterol-accepting capacity of HDL. Moreover, while fasting glucose level in subjects from this group remained unchanged, their fasting insulin level and HOMA-IR index were increased. Thus, DLP "high TG and low HDL C" is characterized by some specific metabolic features underlying its involvement into pathogenesis of atherosclerosis and type 2 diabetes mellitus. On the other hand, differences in biochemical parameters of antiatherogenic DLP "normal TG and high HDL C" from random subsample appeared to be opposite to differences from random subsample found for DLP "high TG and low HDL C", being in line with the present concept about their role in determining the antiatherogenicity of this kind of DLP.

Association of serum apolipoprotein A-II concentration with combined hyperlipidemia and impaired glucose tolerance.

We studied the relationship of serum apolipoprotein A-II concentration with biochemical parameters of lipid and carbohydrate metabolism, type of hyperlipidemia, and insulin sensitivity in male patients with hyperlipidemia. High concentration of apolipoprotein A-II was associated with increased indices of atherogenic lipoproteins and high-density lipoprotein-mediated reverse cholesterol transport, combined hyperlipidemia, and decreased insulin sensitivity calculated with consideration for glucose and insulin levels in glucose tolerance test and body weight.

[Low density lipoproteins in patients with cholelithiasis and cholesterosis of the gallbladder].

AIM: To study heterogenic forms of LDLP and LP(a) in blood serum of patients with cholelithiasis (CL) and gallbladder cholesterosis (GBC). MATERIAL AND METHODS: Native gradient (3-12%) electrophoresis in polyacrylamide gel, rocket immunoelectrophoresis with antibodies to apo(a) were made in 20 patients with CL and 20 with GBC, 13 controls without gastrointestinal disease. Correlation of retardation factor (Rf) of LDLP and LP(a) with blood lipids, cholesterol (C) and triglycerides (TG) levels, body mass index (BMI) and age was studied. CL and GBC risk factors were analysed basing on a retrospective assessment in random representative samples of patients (100 CL and 100 GBC patients). RESULTS: There was a shift of the main peak in LDLP spectrum in the direction of smaller particles in GBC (Rf = 0.171 +/- 0.003) which was significant in comparison with CL group (Rf = 0.146 +/- 0.004, p < 0.001) and control (Rf = 0.114 +/- 0.013, p < 0.05). The analysis of LDLP Rf distribution in patients with different C levels has shown that LDLP small particles can occur in a normal C level: 75% in GBC and 50% in CL groups. Prevalence of small dense LDLP was recorded in both groups (87.5% cases) in hypercholesterolemia. Compared to control, LP(a) concentration was significantly elevated both in GBC (23.7 +/- 4.9 mg/dl) and CL (15.7 +/- 4.4 mg/dl) patients (control--7.5 +/- 1.4 mg/dl, p < 0.01), p > 0.5 in comparison between the groups. The correlation analysis found no correlations between LP9(a), other lipids, BMI and age in both study groups while Rf of LDLP correlated with C and TG levels (r = 0.596 and r = 0.226, respectively, p < 0.05), age and BMI (r = 0. 533 and r = 0.363, respectively, p < 0.05) in CL and did not correlate in GBC. CONCLUSION: A C level in CL changes with age and BMI while in GBC high LDLP C level was caused by other factors. No correlation of LP(a), LDLP Rf with age, body mass and blood lipids indicates that the above factors are independent in development of GBC.

Low-density lipoprotein subfractions during abdominal and gluteofemoral obesity.

Subfractional spectrum of plasma low-density lipoproteins in people with normal body weight and patient with obesity was studied by gradient electrophoresis (3-12%) in polyacrylamide gel. Low-density lipoprotein subfractions in fasting patients with abdominal and gluteofemoral obesity were primarily presented by small particles (compared to people with normal body weight). The composition of low-density lipoprotein subfractions underwent most pronounced changes in patients with abdominal obesity after single fat load.

Study on the role of SH-groups in the activity of muscle pyruvate dehydrogenase.

The kinetics of inactivation of the pyruvate dehydrogenase component of the pigeon breast muscle pyruvate dehydrogenase complex in the presence of 5,5'-dithiobis (2-nitrobenzoate) is biphasic. The rate constants for the fast and slow phases of the inactivation reaction are close to those for modification of two classes of SH-groups differing in their reactivities towards the inhibitor. The reaction order with respect to the inhibitor concentration suggests that the two distinct SH-groups are essential for the enzyme activity. Modification of these SH-groups results in inhibition of the overall activity of the pyruvate dehydrogenase complex and of the 2-hydroxyethyl thiamine pyrophosphate - acceptor oxidoreductase activity of its decarboxylating component. Thiamine pyrophosphate exerts a protective effect on the enzyme only at the slow phase of the enzyme inactivation and SH-modification. As a result of interaction between the holoenzyme and pyruvate (or apoenzyme and 2-hydroxyethyl thiamine pyrophosphate) the rate of the enzyme inactivation is increased. This is associated with masking of non-essential SH-groups and with an increase of the accessibility of two essential SH-groups to the inhibitor. The data obtained suggest the interrelationship between the essential SH-groups and the 2-hydroxyethyl thiamine pyrophosphate-acceptor oxidoreductase activity of pyruvate dehydrogenase.