Meal test for glucose-dependent insulinotropic peptide (GIP) in obese and type 2 diabetic patients.

Glucose-dependent insulinotropic peptide (GIP) contributes to incretin effect of insulin secretion which is impaired in Type 2 diabetes mellitus. The aim of this study was to introduce a simple meal test for evaluation of GIP secretion and action and to examine GIP changes in Type 2 diabetic patients. Seventeen Type 2 diabetic patients, 10 obese non-diabetic and 17 non-obese control persons have been examined before and after 30, 60 and 90 min stimulation by meal test. Serum concentrations of insulin, C-peptide and GIP were estimated during the test. Impaired GIP secretion was found in Type 2 diabetic patients as compared with obese non-diabetic and non-obese control persons. The AUCGIP during 90 min of the meal stimulation was significantly lower in diabetic patients than in other two groups (p<0.03). Insulin concentration at 30 min was lower in diabetic than in non-diabetic persons and the GIP action was delayed. The deltaIRI/deltaGIP ratio increased during the test in diabetic patients, whereas it progressively decreased in obese and non-obese control persons. Simple meal test could demonstrate impaired GIP secretion and delayed insulin secretion in Type 2 diabetic patients as compared to obese non-diabetic and non-obese healthy control individuals.

[Diagnostics and treatment of organic hyperinsulinism--experience in 105 cases]. / Diagnostika a lécba organického hyperinzulinismu--zkusenosti u 105 pacientu.

BACKGROUND: Organic hyperinsulinism causes hypoglycaemia manifesting mainly in the fasting state. We summarize our experience with diagnosis and treatment of 105 patients with organic hyperinsulinism. METHODS AND RESULTS: The diagnosis was confirmed in all patients by spontaneous hypoglycemia and neuroglycopenic symptoms, both developed during fasting test. Endoscopic ultrasonography was the most reliable method for the insulinoma localization (77% of insulinomas confirmed by surgery in the same location within the pancreas), less positive results were obtained by digital subtraction angiography (29%) and still less was found by computed tomography (18%). The localization remains unclear in about 20-25% of insulinomas despite of combined different exploring techniques. Surgical removal of insulinoma by enucleation is the best way of treatment, in some cases laparoscopic removal is a method of choice. From total number of 95 surgically treated patients the successful removal of insulinoma was performed in 84 patients (88%) and another 3 had histopathology diagnosis of micronodular polyadenomatosis. CONCLUSIONS: Insulinoma was not found during surgery and subsequent thorough histopathology investigation of the whole resecate in 8 patients which have to be treated like other non-surgically treated patients by diazoxide together with diabetic diet.

Paraoxonase 1 gene polymorphisms and enzyme activities in diabetes mellitus.

Paraoxonase 1 (PON1), an antioxidant enzyme closely associated with HDL (high-density lipoproteins), preserves LDL (low-density lipoproteins) against oxidation. Less protection may be therefore supposed by decreased PON1 activity. This study was undertaken to investigate the association of PON1 gene polymorphisms with diabetic angiopathy and to evaluate the relationship of these polymorphisms with PON1 activity. Total of 86 Type 1 (T1DM) and 246 Type 2 (T2DM) diabetic patients together with 110 healthy subjects were examined. DNA isolated from leukocytes was amplified with polymerase chain reaction (PCR) followed by restriction enzyme digestion. The products were analyzed for L55M and Q192R polymorphisms in coding region and for -107 C/T and -907 G/C in promotor sequence of PON1. Serum enzyme activity was measured spectrophotometrically. Significant differences were found between T1DM or T2DM and control persons in L55M polymorphism (allele M more frequent in T1DM and T2DM vs. controls, p<0.05) and Q192R polymorphism (R allele less frequent in T1DM and T2DM vs. controls, p<0.01) of the PON1 gene. Serum PON1 activity was significantly decreased in T1DM (110+/-68 nmol/ml/min) and T2DM patients (118+/-69 nmol/ml/min) compared to the control persons (203+/-58 nmol/ml/min), both p<0.01. The presence of MM and QQ genotypes was accompanied by lower PON1 activity than of LL and RR genotypes (p<0.05), respectively. Better diabetes control was found in patients with LL than with MM genotypes and similarly in RR genotype than QQ genotype with p<0.05. Significantly different allele frequencies were found in diabetic patients with macroangiopathy than in those without it (M: 0.59 vs. 0.44. R: 0.12 vs. 0.19, p<0.01). The association of PON1 polymorphisms, lower PON1 activity and poorer diabetes control found in patients with macroangiopathy further support the idea of genetic factors contributing to the development of vascular disorders in diabetes.

The influence of n-3 polyunsaturated fatty acids and very low calorie diet during a short-term weight reducing regimen on weight loss and serum fatty acid composition in severely obese women.

Polyunsaturated fatty acids of n-3 series (n-3 PUFA) were shown to increase basal fat oxidation in humans. The aim of the study was to compare the effect of n-3 PUFA added to a very low calorie diet (VLCD), with VLCD only during three-week inpatient weight reduction. Twenty severely obese women were randomly assigned to VLCD with n-3 PUFA or with placebo. Fatty acids in serum lipid fractions were quantified by gas chromatography. Differences between the groups were determined using ANOVA. Higher weight (7.55+/-1.77 vs. 6.07+/-2.16 kg, NS), BMI (2.82+/-0.62 vs. 2.22+/-0.74, p<0.05) and hip circumference losses (4.8+/-1.81 vs. 2.5+/-2.51 cm, p<0.05) were found in the n-3 group as compared to the control group. Significantly higher increase in beta-hydroxybutyrate was found in the n-3 group showing higher ketogenesis and possible higher fatty acid oxidation. The increase in beta-hydroxybutyrate significantly correlated with the increase in serum phospholipid arachidonic acid (20:4n-6; r = 0.91, p<0.001). In the n-3 group significantly higher increase was found in n-3 PUFA (eicosapentaenoic acid, 20:5n-3, docosahexaenoic acid, 22:6n-3) in triglycerides and phospholipids. The significant decrease of palmitoleic acid (16:1n-7) and vaccenic acid (18:1n-7) in triglycerides probably reflected lower lipogenesis. A significant negative correlation between BMI change and phospholipid docosahexaenoic acid change was found (r = -0.595, p<0.008). The results suggest that long chain n-3 PUFA enhance weight loss in obese females treated by VLCD. Docosahexaenoate (22:6n-3) seems to be the active component.

Short-term very low calorie diet reduces oxidative stress in obese type 2 diabetic patients.

Oxidative stress is higher in obese diabetic than in non-diabetic subjects. This pilot study evaluates oxidative stress during short-term administration of a very low calorie diet in obese persons. Nine obese Type 2 diabetic patients (age 55+/-5 years, BMI 35.9+/-1.9 kg/m2) and nine obese non-diabetic control subjects (age 52+/-6 years, BMI 37.3+/-2.1 kg/m2) were treated by a very low calorie diet (600 kcal daily) during 8 days stay in the hospital. Serum cholesterol, triglycerides, non-esterified fatty acids (NEFA), beta-hydroxybutyrate (B-HB), ascorbic acid (AA), alpha-tocopherol (AT), plasma malondialdehyde (MDA) and superoxide dismutase (SOD) activity in erythrocytes were measured before and on day 3 and 8 of very low calorie diet administration. A decrease of serum cholesterol and triglyceride concentrations on day 8 was associated with a significant increase of NEFA (0.30+/-0.13 vs. 0.47+/-0.11 micromol/l, p<0.001) and B-HB (0.36+/-.13 vs. 2.23+/-1.00 mmol/l, p<0.001) in controls but only of B-HB (1.11+/-0.72 vs. 3.02+/-1.95 mmol/l, p<0.001) in diabetic patients. A significant decrease of plasma MDA and serum AT together with an increase of SOD activity and AA concentration (p<0.01) was observed in control persons, whereas an increase of SOD activity (p<0.01) was only found in diabetic patients after one week of the very low calorie diet. There was a significant correlation between NEFA or B-HB and SOD activity (p<0.01). We conclude that one week of a very low calorie diet administration decreases oxidative stress in obese non-diabetic but only partly in diabetic persons. Diabetes mellitus causes a greater resistance to the effects of a low calorie diet on oxidative stress.

Screening for associated autoimmunity in type 1 diabetes mellitus with respect to diabetes control.

As an autoimmune disease, type 1 diabetes mellitus (DM) can be associated with other autoimmune disorders. The aim of this study was to detect subclinically associated autoimmune thyroid disease, coeliac disease, and Addison's disease. The presence of autoantibodies was evaluated with special regard to the control of diabetes and to the clinical status of the patient. Fifty-one type 1 diabetic patients (22 men, 29 women, mean age 37+/-11 years, mean duration of diabetes 16+/-13 years) were included into this study. Specific antibodies to islet antigens--glutamic acid decarboxylase (GAD65), protein thyrosine phosphatase IA-2alpha, and to thyroid autoantigens--thyroid microsomal peroxidase (TPO) and thyroglobulin (TG) and also thyroid stimulating hormone (TSH) were measured by RIA. Autoantigens of the small intestine--tissue transglutaminase autoantibodies (ATTG), IgA and IgG antibodies to gliadin (AGA-IgA, AGA-IgG) were evaluated by ELISA. Endomysial autoantibodies (EMA) and adrenal cortex antibodies (ACA) were detected by indirect immunofluorescence microscopy. Eleven new cases of thyreopathy (22 % of patients) were detected by the assessment of thyroid autoantibodies and TSH. Two new cases of thyreotoxicosis were diagnosed during the study. Coeliac disease was diagnosed in at least two cases. Addison's disease was not diagnosed, although the ACA were positive in two patients. No influence of single or combined autoantibody positivity on the control of diabetes was found if normal organ function was preserved. In both patients with thyreotoxicosis the control of diabetes was worsened and improved after treatment. The screening of autoantibodies in type 1 diabetic patients could reveal subclinical cases of AITD or coeliac disease. Subclinical forms of these disorders have no influence on diabetes control. However, impaired organ function may be associated with the worsened control of diabetes as we demonstrated on two newly diagnosed cases of thyreotoxicosis. We suggest the need for the follow-up of patients with positive autoantibodies because further deterioration of the respective organs can be expected.

The influence of short-term fasting on serum leptin levels, and selected hormonal and metabolic parameters in morbidly obese and lean females.

The aim of our study was to compare the changes of serum leptin levels after 24-h fasting in morbidly obese and lean females and to search for hormonal and metabolic factors responsible for the changes in serum leptin levels. Fourteen morbidly obese and twelve lean females were included in the study. The blood for leptin, insulin, cortisol, blood glucose (BG), beta-OH-butyrate (beta-OH), dehydroepiandrosterone (DHEA) and DHEA-sulphate (DHEA-S) measurements was withdrawn before and after a 24-h fast. Basal body mass index (BMI), serum leptin, insulin and beta-OH levels were significantly higher in the obese compared to the lean group. The 24-h fasting decreased significantly BMI, serum leptin (by 20% in obese vs. 62% in lean subjects), insulin (by 23.3% in obese vs. 23.1% in lean subjects) and increased beta-OH (by 36% in obese vs. 1300% in lean subjects). Basal serum leptin levels correlated positively with BMI in both groups and with insulin levels in the obese group. The multiple regression analysis using delta leptin as dependent and the basal values of the rest of studied parameters as independent variables revealed that in lean subjects serum cortisol together with DHEA-S and BMI accounted for 71% of variations of the change of serum leptin levels (delta leptin = 0.31- 0.0101 cortisol + 0.0012 DHEA-S + 0.37 BMI). In obese subjects the 43.9% of variations of the change of serum leptin levels was explained by BMI together with age and DHEA-S levels (delta leptin = 36.09 + 0.35 BMI - 0.717 age- 0.008 DHEA-S). The drop of serum leptin levels after 24-h starvation is significantly blunted in obese compared to lean subjects. The reason for the difference is probably the insulin resistance possibly further modified by different DHEA-S levels.

Impaired insulin action in primary hyperaldosteronism.

The presence of insulin resistance is frequently found in essential hypertension. There are, however, only sparse data with respect to the potential presence of insulin resistance in patients with secondary hypertension. We have therefore undertaken a study to reveal the potential occurrence of insulin resistance in primary hyperaldosteronism (PH). The hyperinsulinemic euglycemic clamp technique together with the evaluation of insulin receptor characteristics were used to study insulin resistance in 12 patients with PH. The measured parameters were compared to normal values in control subjects. We have found a significantly lower glucose disposal rate (M, micromol/kg/min) (18.7+/-6 vs. 29.3+/-4), decreased tissue insulin sensitivity index (M/I, micromol/kg/min per mU/l x100) (23.7+/-9.8 vs. 37.5+/-11.6) and also lower metabolic clearance rate of glucose (MCRg, ml/kg/min) (3.8+/-1.5 vs. 7.0+/-1.1) in patients with primary hyperaldosteronism. The insulin receptor characteristics on erythrocytes did not differ in primary hyperaldosteronism as compared to control healthy subjects. We thus conclude that insulin resistance is also present in secondary forms of hypertension (primary hyperaldosteronism) which indicates the heterogeneity of impaired insulin action in patients with arterial hypertension.

Insulin action in primary hyperaldosteronism before and after surgical or pharmacological treatment.

The relationship between arterial hypertension and insulin resistance has long been established. We used primary hyperaldosteronism as a model of the relationship between secondary hypertension and insulin sensitivity. Our group consisted of 9 patients with arterial hypertension caused by primary hyperaldosteronism. Five of these patients with aldosterone producing adenoma were operated on and four patients with idiopathic hyperaldosteronism were treated with spironolactone. Hyperinsulinaemic euglycaemic clamp technique was performed before and at least 6 months following the treatment to evaluate the insulin action. Significantly lower glucose disposal rate (M), insulin sensitivity index (M/I) and decreased metabolic clearance rate of glucose (MCR(G)) were found in patients before treatment as compared to healthy controls. In both treated groups the blood pressure and plasma potassium concentrations returned to normal values, whereas plasma aldosterone levels were normalised only after surgical removal of the adenoma. Significantly improved insulin action (M/I: 30.2 +/- 5.9 vs. 51.4 +/-12.2 micromol.kg(-1).min(-1) per mU.l(-1) x 100, p = 0.017) was observed in patients after operation of aldosterone producing adenoma. In contrast, spironolactone treatment of patients with idiopathic hyperaldosteronism did not significantly influence insulin action (M/I: 24.5 +/- 7.3 vs. 18.7 +/- 7.6 micromol.kg(-1).min(-1) per mU.l(-1) x 100, p = 0.198). Since plasma aldosterone concentrations have been normalised only in patients after removal of the adenoma whereas they remained increased in spironolactone treated group, we suppose that aldosterone itself could play a role in the development of impaired insulin action.

Insulin action and fibrinolysis influenced by vitamin E in obese Type 2 diabetes mellitus.

Increased oxidative stress, hypofibrinolysis and insulin resistance are present in obese Type 2 diabetic patients. It is supposed that treatment with antioxidant alpha-tocopherol (vitamin E) could not only decrease free radical production, but also ameliorate insulin action. We evaluated the effect of 3 months administration of vitamin E (600 mg daily) on insulin action examined by hyperinsulinemic clamp in 11 obese Type 2 diabetic patients. Oxidative stress and fibrinolysis were also determined. The administration of vitamin E caused a decrease of glucose disposal rate (26.6 +/- 9.5 vs 21.3 +/- 7.5 micromol/kg/min, P < 0.02) and of metabolic clearance rate of glucose (3.7 +/- 1.6 vs 2.9 +/- 0.8 ml/kg/min. P < 0.02). A decrease of insulin receptor number was observed on erythrocytes after vitamin E (284 +/- 84 vs 171 +/- 59 pmol/l, P < 0.01). Significantly higher plasma malondialdehyde (MDA) concentration documented an increased oxidative stress in diabetic patients as compared with healthy persons (3.13 +/- 0.68 vs 1.89 +/- 0.18 micromol/l, P<0.001). An inverse relationship was found between MDA concentration and insulin sensitivity expressed by glucose disposal rate (r = -0.73). Vitamin E further worsened the hypofibrinolysis documented by a decrease of tissue plasminogen activator (P < 0.01) without changes in its inhibitor PAI-1. In conclusion. our results demonstrate that higher doses of vitamin E may further deteriorate insulin action and fibrinolysis in obese Type 2 diabetic patients.

Relationship of serum N-acetyl-beta-glucosaminidase activity to oxidative stress in diabetes mellitus.

Serum N-acetyl-beta-glucosaminidase activity was evaluated in 40 Type 1 and 40 Type 2 diabetic patients and compared with parameters of diabetes control and oxidative stress. Significantly increased mean serum N-acetyl-beta-glucosaminidase activity was found in both groups of diabetic patients as compared with the corresponding group of healthy persons (p < 0.01). Oxidative stress measured by plasma malondialdehyde concentration was significantly higher in Type 2 than in Type 1 diabetic patients (p < 0.01) but in comparison with control subjects it was higher only in Type 2 diabetes. Plasma malondialdehyde concentration positively correlated with body mass index (r=0.77, p<0.001) and with serum N-acetyl-beta-glucosaminidase activities (r=0.57, p <0.001). Treatment of 10 Type 2 diabetic patients with antioxidant alpha-tocopherol caused a significant decrease in malondialdehyde concentration (p < 0.001) which was accompanied by a decrease of N-acetyl-beta-glucosaminidase activity (p < 0.01). We conclude that serum N-acetyl-beta-glucosaminidase activity may be influenced by oxidative stress which is more pronounced in Type 2 than in Type 1 diabetic patients.

The evaluation of thyroid and islet autoantibodies in type 1 diabetes mellitus.

Type 1 diabetes mellitus is an autoimmune disease in which the presence of different autoantigens can often be found. The aim of our study was to evaluate the prevalence of antibodies against insulin (IA) and autoantibodies against glutamic acid decarboxylase (anti-GAD), tyrosine phosphatase IA-2 (anti-IA-2), thyroid microsomal peroxidase (anti-TPO) and thyroglobulin (anti-TG) in 55 randomly selected Type 1 diabetic patients (34 males, 21 females). Mean age of these patients was 39 +/- 12 yrs, mean duration of diabetes 18 +/- 13 yrs. Positivity of anti-GAD was found in 29 (58%) patients, anti-IA-2 in 13 (25%) patients, IA in 46 (85%) patients, anti-TPO in 10 (21%) and anti-TG in 11 (23%) patients. Simultaneous positivity of thyroid and islet autoantibodies was found in 6 (11%) patients whereas the positivity at least one of them was in 38 (69%) patients. No relationship between glycated hemoglobin and autoantibody concentration was found in the whole group of patients. The autoimmune thyroid disease was newly detected in 4 patients from high concentration of thyroid autoantibodies together with impaired TSH and T4 values and ultrasonography finding. No clinical evidence of thyroid disease was previously found in these patients. Positivity of anti-GAD or anti-IA-2 was found in almost 65% and of any thyroid autoantibody in almost 30% of our patients. Four patients with autoimmune thyroid disease were newly identified. We conclude that the evaluation of thyroid autoantibodies in Type 1 diabetic patients may improve the diagnosis of thyroid disease in very early stage and thus prevent consequent complications.

[The effect of body weight on insulin activity]. / Ovlivnení pusobení inzulinu telesnou hmotností.

Insulin resistance is found patients with diabetes mellitus type 2 as well as in obese subject without diabetes. The objective of our investigation was to compare the action of insulin in morbidly obese subject with and without diabetes and in diabetic subject with different degrees of obesity. A total of 36 diabetic were examined, divided according to the BMI into morbidly obese (DMTO: BMI > 40 kg/m-2.n = 6) those with medium severe obesity (DMSO: BMI 31-40 kg.m-2.n = 16), with slight overweight DMLO. BMI 26-91 kg.m-2.n = 9) and non-obese diabetics (DMBO). BMI 21-26 kg.m-2.n = 5). The group of morbidly obese non-diabetic subject (NDTO, BMI > 40 kg.m-2.n = 5) and non-obese healthy subject (C, BMI < 26 kg.m-2, n = 12) served as control. All examined subject were of similar age the diabetic subject had similar values of indicator of diabetic control (HbA1c was 7.1 +/- 0.5%). The examination was made using the method of an isoglycaemic hyperinsulinaemic clamp on a Biostator at an insulin infusion rate of 1mU.kg-1.min-1 for a period of 20 minutes. The results of the index of tissue sensitivity to insulin revealed a markedly deteriorated action of insulin in morbidly obese diabetes and non-diabetics in relation to control group of healthy slim controls (M/I, DMTO: 12.4 +/- 7.3 and NDTO: 9.2 +/- 4.1, p < 0.001, mumol.kg-1.min-1 na mU.l-1 x 100), in midly and medium obese diabetics the insulin resistance was of difference grades (M/I, DMLO: 34.2 +/- 9.3, p < 0.05, and DMSO: 25.9 +/- 18.5 p < 0.001 mumol.kg-1.min-1 na mU.l-1 x 100. Non-obese diabetic and non-diabetic subject had a normal insulin action (M/I, DMBO: 58.3 +/- 29.4 and C: 48.9 +/- 5.0 mumol.kg-1.min-1 per mU.l-1 x 100. The metabolic glucose clearance differed however between diabetic and non-diabetic subject (MCRG, DMTO: 2.0 +/- 0.4, p < 0.001, DMSO: 3.8 +/- 2.4, p < 0.001, DMSO: 5.4 +/- 1.7, p < 0.05 v.s. C: 8.6 +/- 1.1 and NDTO: 3.8 +/- 1.5, p < 0.001 ml.kg-1.min-1). The statistical significance is related to the control group of slim healthy subject. From this ensues that no significant difference was found between slim diabetic and non-diabetic subjects in the majority of parameters expressing the action of insulin with the exception of the metabolic glucose clearance. At the same time the authors found in the whole group of 53 examined subject a statistically significant correlation between the BMI and the index of tissue sensitivity for insulin (M/I) (r = -0.55, p < 0.001). On examination of characteristics of insulin receptors on erythrocytes the authors found a reduced number in diabetic subject as compared with the two control groups (p < 0.05). It may thus be concluded from this investigation that the BMI has a decisive role in the action insulin.

[Personal experience with the treatment of organic hyperinsulinism]. / Nase zkusenosti s lécbou organického hyperinzulinismu.

In 1981-1997 at the Third Medical Clinic 52 patients with confirmed organic hyperinsulinism were treated. Forty-three were operated and the remaining nine were treated conservatively. An insulinoma was removed surgically in 35 patients, in one female microadenomatosis was detected. The operation was successful in 84%, while topographic preoperative examination aroused suspicion of a focus (i.e. insulinoma) only in 49% of the operated patients. A total of 11 patients (four after surgery and seven not operated) were treated successfully with diazoxide, in nine patients this treatment is still administered. According to the response to diazoxide it is possible to differentiate "responsive" and "non-responsive" insulinomas. Pharmacological treatment is thus justified only in the first group of patients. Surgically and pharmacologically treated patients have no signs of hyperinsulinism. The authors experience suggests that surgical treatment is indicated when the diagnosis is unequivocal even when the topographic finding of imaging methods is negative, as in 35% of operated patients the insulinoma was found only on operation.

[The effect of insulin in primary hyperaldosteronism]. / Pusobení inzulinu u primárního hyperaldosteronismu.

BACKGROUND: Deteriorated insulin resistance was described in patients with essential hypertension. The objective of the present study was to test at the receptor and postreceptor level the presence of insulin resistance in hypertension with primary hyperaldosteronism. METHODS AND RESULTS: The diagnosis of primary hyperaldosteronism was assessed by means of biochemical and imaging methods in 123 hypertensive patients with a normal glucose tolerance (mean age 49.8 +/- 12.9 years, range 20-65 years, BMI 28.3 +/- 4.8 kg/m2). The blood pressure was monitored for 24 hours by a Spacelab tonometer (systolic BP 168 +/- 21 mm Hg, diastolic BP 103 +/- 9 mm Hg, plasma aldosterone in a recumbent position 426 +/- 472 pg/ml (normal values under 150 pg/ml), concentration of serum potassium 3.6 +/- 0.6 mmol/l. The control group was formed by seven volunteers matched for age and BMI. The patients had a normal basal blood sugar level in the morning (5.0 +/- 0.6 mmol/l), the basal insulinaemia was 19.5 +/- 10.2 mU/l. The insulin resistance was examined using the method of an euglycaemic hyperinsulinaemic clamp on Biostator at an insulin infusion rate of 1 mU/kg/min. Concurrently insulin receptors on red blood cells were assessed. The plasma potassium concentration was maintained by means of insulin receptors on erythrocytes. The potassium plasma concentration was maintained by means of a linear dosage device with potassium at constant physiological levels (after previous supplementation). In patients with primary hyperaldosteronism the authors observed, as compared with healthy controls, a lower glucose consumption during the clamping (glucose disposal rate 18.7 +/- 4.8 vs 29.3 +/- 3.7 mumol/kg/min, p < 0.01), a rise of the metabolic glucose clearance (3.8 +/- 1.5 vs. 7.0 +/- 1.1 ml/kg/min, p < 0.01 and an index of tissue sensitivity for insulin) 23.7 +/- 9.8 vs. 37.5 +/- 11.6 mumol/kg/min per mU/l x 100, p < 0.02). The characteristics of insulin receptors in patients with primary hyperaldosteronism did not differ from normal values. No correlation was found between the plasma concentration of aldosterone and the index of tissue sensitivity for insulin (r = 0.011, NS). CONCLUSIONS: It may be stated that primary hyperaldosteronism is associated with insulin resistance at the postreceptor level. Its pathogenesis has not been elucidated so far and will be the object of future research.

Effect of long lasting terguride treatment on mutual relationship between glycide and lipid parameters in SHR/N-cp Koletsky rats.

Experiments were performed in the genetically hypertensive obese rats of Koletsky type (SHR/N-cp) and in their lean siblings. The effect of long lasting terguride treatment on glycide and lipid metabolism was monitored. Terguride decreases insulinemia in all groups of rats. In all groups of rats terguride increases tolerance glucose. Terguride increases insulin binding to erythrocytes in all groups of rats except SHR/N-cp obese females. The mentioned drug decreases plasma triglycerides in SHR/N-cp obese females. On the other hand, this drug increases plasma triglycerides in SHR/N-cp obese males. Correlation between basal glycemia and insulin binding to erythrocytes as well as between triglycerides and insulinemia which was found in control SHR/N-cp lean males is missing under the terguride treatment. Similarly, correlation between plasma triglycerides and insulinemia, glucose tolerance and insulinemia, basal glycemia and insulinemia, plasma triglycerides and basal glycemia are missing under the terguride treatment in SHR/N-cp lean females. Under the terguride treatment there appears correlation between insulin binding to erythrocytes and basal glycemia. We found in SHR/N-cp obese males opposite changes in number of correlations when we compare control and terguride animals. While in controls only one correlation was detected, i.e., correlation between glucose tolerance and insulin binding to erythrocytes, then under the terguride treatment there appear correlations when basal glycemia is computed versus insulin binding to erythrocytes or to glucose tolerance and/or to triglycerides. Moreover, there is under the terguride treatment correlation insulin binding to erythrocytes versus plasma triglycerides or versus insulinemia. While in SHR/N-cp lean of both sexes and in SHR/N-cp obese males profound changes in the number of statistically significant correlation coefficients were found when controls are compared with animals under the terguride treatment, the different picture we found in SHR/N-cp obese females, i.e., under the terguride treatment correlation basal glycemia versus insulinemia or versus insulin binding to erythrocytes as well as correlation insulin binding to erythrocytes versus insulinemia is present in controls as well as in terguride treated animals. In comparison with controls under terguride only two correlations are missing, i.e., glucose tolerance versus insulinemia or versus insulin binding to erythrocytes.

Development of lipid and glycide abnormalities in genetically hypertensive obese Koletsky rats and in their lean siblings.

Experiments were performed in the genetically hypertensive Koletsky rats and in their lean siblings at the age of two and three months. In the study of development of glycide and lipid abnormalities animal represents control for itself. At the age of two months Koletsky obese rats show relative to their lean controls elevation of plasma triglycerides (males +184%, female +152%) and insulin (males +169%, females +201%). During one month plasma triglycerides elevated in lean males +9%, in lean females 0%, but in obese males +21%, in obese females +139%. Considering insulinemia similar results were obtained. Thus during one month insulin elevates in lean males +19%, in lean females +23%, but in obese males +80%, in obese females +144%. During one month glucose intolerance is elevated as well only in obese rats. Total plasma cholesterol during period of one month shows no changes in both substrains of rats. Similar picture can be found in basal glycemia. In all groups of rats no changes were registered except one, i.e., obese females show decrease. Considering the substrain differences in basal glycemia then at age of one as well as two months obese of both sexes show elevation. As to the body weight at the age of two as well as three months there is increase in obese rats. The changes of body weight during one month are expressively higher in obese rats.

Muscle GLUT-4 and insulin binding to erythrocytes and to adipose, liver and muscle tissue in genetically hypertensive obese rats and in their lean siblings: effect of long lasting terguride treatment.

Experiments were performed in the genetically hypertensive obese rats of Koletsky type (SHR/N-cp) and in their lean siblings of both sexes. Insulin binding to erythrocytes and to adipose tissue, lever tissue and muscle tissue was monitored in the control animals and in the animals under the long lasting terguride treatment. In control animals insulin binding shows substrain and tissue dependence being elevated in lean rats except insulin binding to erythrocytes where inverse is true. Terguride increases percentage of specific insulin binding to erythrocytes in all groups except obese females, terguride increases percentage of specific binding to adipose tissue except lean females, the mentioned drug remained without effect in muscle tissue in all group except lean females where drug induced elevation was detected. The effect of terguride in liver tissue was monitored only in males of both substrains, elevation was found only in lean. GLUT-4 was analyzed only in muscle tissue. The effect of terguride was found in obese females, i.e., in the group which shows reduced GLUT-4 relative to lean females.

The effect of glycosaminoglycan sulodexide on oxidative stress and fibrinolysis in diabetes mellitus.

Glycosaminoglycan sulodexide may influence morphology and functional properties of the basement membranes in microvessels. The aim of this study was to evaluate the effect of sulodexide administration on albuminuria and on different biochemical variables indicating endothelial dysfunction, oxidative stress and fibrinolysis in diabetic patients. Twenty diabetic patients of both types with micro- or macroalbuminuria were selected for sulodexide treatment. Daily dose of 600 U (60 mg) was injected intramuscularly five days a week. Fifteen doses were applied during 3 weeks. The patients were examined before and after treatment as well as 6 months later. No changes of diabetes control were observed during the study and after 6 months of wash-out period. Significant decrease of albuminuria (p < 0.001) was observed during the sulodexide administration with the following increase to pretreated values during the wash-out period. A decrease of serum N-acetyl-beta-glucosaminidase (NAG) activity (p < 0.03) at the end of treatment as compared to pretreated values was found in the whole group of diabetic patients. Slight reduction of oxidative stress expressed by malondialdehyde and superoxide dismutase was apparent after treatment but no simultaneous change in fibrinolysis was observed. Sulodexide may have some protective effects influencing functional properties of the basement membrane as manifested by lowered albuminuria. In addition, it may slightly decrease oxidative stress in diabetic patients and it could stabilize endothelial cells.