Metabolic syndrome in young Czech women with polycystic ovary syndrome.

METHODS: Sixty-nine young women with polycystic ovary syndrome (PCOS) [age 25.2+/- 4.7 years, with body mass index (BMI) 24.3 +/- 4.8 kg/m2; mean 6 SD] and 73 age-matched healthy females (BMI 22.3 +/- 3.3 kg/m2; mean +/- SD) were evaluated for the occurrence of features of metabolic syndrome according to the Adult Treatment Panel III. RESULTS: Overt metabolic syndrome (the presence of three and more risk factors) was not more common in PCOS women (1/64, 1.6%) than in healthy controls (0/73, 0%). On the other hand, in nearly 50% of PCOS women isolated features of metabolic syndrome, most often a decrease in high-density lipoprotein (HDL) cholesterol, were found. Women with at least one feature of metabolic syndrome were, in comparison with women without any of these features, significantly more obese (P = 0.0001), with lower insulin sensitivity (P = 0.05). When comparing PCOS women according to the degree of insulin sensitivity, as determined by euglycaemic clamp, isolated features of metabolic syndrome were found in 8/17 women above the upper quartile, compared with 11/16 women below the lower quartile of insulin sensitivity (P = 0.20). CONCLUSIONS: Overt metabolic syndrome is only rarely encountered in young Czech females affected by PCOS but its isolated features are relatively frequent, both in young PCOS patients and in age-matched control women.

Does the treatment of primary hyperaldosteronism influence glucose tolerance?

Primary hyperaldosteronism (PH) is frequently considered to be a secondary form of diabetes mellitus (DM). In our previous study we attempted to evaluate the prevalence of DM among patients with PH compared to control subjects with essential hypertension (EH). We have noted a relatively high prevalence of DM and impaired glucose tolerance in PH, but the differences between the PH and EH groups did not reach statistical significance. We performed this study to assess whether the effective treatment of PH (surgical and conservative) would improve the glucose tolerance. We have studied 24 patients with PH of the following two subtypes: aldosterone-producing adenoma (APA) treated with adrenalectomy and idiopathic hyperaldosteronism (IHA) treated with spironolactone. No significant changes of glucose levels were found in the 60th and 120th min of the oral glucose tolerance test (OGTT) in the APA group. On the other hand, fasting glucose levels were decreased significantly after adrenalectomy. Plasma glucose levels were significantly increased in the 60th min, but no differences were found in fasting values and in the 120th min in the IHA group. There was a significantly higher incidence of impaired glucose tolerance (36 per cent before, 45 per cent after treatment) and DM (9 per cent, 18 per cent) in the IHA group compared to the APA group (8 per cent, 32 per cent; DM 0 per cent, 0 per cent). In conclusion, the treatment of PH does not improve glucose tolerance. Mild worsening of glucose tolerance after treatment could be explained by an increase of the body mass index. These data, in accordance with our previous study, do not support the idea that PH is a secondary form of diabetes mellitus.

Association of obesity, diabetes, serum lipids and blood pressure regulates insulin action.

Insulin resistance is present in patients with Type 2 diabetes mellitus as well as in obese patients without diabetes. The aim of our study was to compare insulin action in diabetic and control persons with or without obesity and to evaluate the influence of serum cholesterol, serum triglyceride and blood pressure on metabolic variables of insulin action. We examined 42 Type 2 diabetic patients and 41 control persons with body mass index (BMI) from 21.1 to 64.5 kg x m(-2), and 33 to 71 years old. The isoglycemic hyperinsulinemic clamp technique was performed at an insulin infusion rate of 1 mU x kg(-1) x min(-1) during 120 min. We evaluated the metabolic clearance rate of glucose (MCR(G), ml x kg(-1) x min(-1)) as the most important indicator of insulin action by isoglycemic clamp. The Pearson's correlation and multiple regression models were used to compare studied factors with the insulin action. We found following predictors of insulin resistance expressed in the relationship with MCR(G): BMI (r = -0.68, p<0.001), plasma glucose concentration (r = -0.66, p<0.001), cholesterol (r=-0.55, p<0.001), triglycerides (r = -0.54, p<0.001) and mean blood pressure (r = -0.38, p<0.01). From the multiple regression analysis we conclude that obesity may have even greater influence on the insulin action than diabetes mellitus itself.

Serum leptin levels in patients with primary hyperaldosteronism before and after treatment: relationships to insulin sensitivity.

BACKGROUND: Leptin is a protein hormone produced predominantly by adipocytes that plays a role in food intake regulation and a series of other physiological processes including blood pressure regulation. OBJECTIVES: The aim of our study was to compare serum leptin levels in patients with primary hyperaldosteronism (PA) with those of healthy subjects and to explore the relationship of serum leptin levels and the parameters of insulin action in these patients before and after surgical or pharmacological treatment. METHODS: Serum potassium, leptin, aldosterone, insulin levels and plasma renin activity were measured and hyperinsulinaemic euglycaemic clamp was performed in 11 patients with PA and 11 healthy age-, gender- and body mass index (BMI)-matched subjects. In eight of 11 patients the same measurements were repeated at least 6 months after surgical or pharmacological treatment. RESULTS: The basal serum leptin levels in PA patients did not significantly differ from those of healthy subjects (mean+/-s.e.m. 8.4+/-1.9 vs 11.2+/-1.8 ng/ml, P=0.30), although their insulin sensitivity was significantly impaired (PA patients vs control subjects: glucose disposal rate in the last 20 min of clamp (M) 18.7+/-1.8 vs 30.6+/-3.3 micromol/kg/min, metabolic clearance rate of glucose (MCR(g)) 3.9+/-0.5 vs 7.2+/-1.1 ml/kg/min, P<0.05). The surgical or pharmacological treatment of PA patients increased significantly their serum leptin levels (10.9+/-3.7 vs 8.4+/-1.9 ng/ml, P<0.05) and simultaneously improved their insulin sensitivity. Basal serum leptin levels in both groups correlated positively with BMI and serum insulin levels. The inverse relationship between serum leptin levels and the insulin sensitivity parameters was found in both PA patients before treatment and healthy subjects. These relationships disappeared after treatment of PA patients except for those between serum leptin levels and MCR(g). CONCLUSION: Basal serum leptin levels in untreated patients with PA do not significantly differ from those of healthy subjects, but increase significantly after surgical or pharmacological treatment. The increase in serum leptin levels is paradoxically accompanied by the improvement of insulin sensitivity in these patients.

Insulin sensitivity in non-obese women with polycystic ovary syndrome during treatment with oral contraceptives containing low-androgenic progestin.

BACKGROUND: Combined oral contraceptives (COC) effectively suppress hyperandrogenism in women with polycystic ovary syndrome (PCOS), though deterioration of insulin sensitivity during treatment is assumed. The study aim was to investigate insulin action and androgen production during treatment with COC containing low-androgenic progestin. METHODS: A total of 13 PCOS women and nine controls was enrolled into the study. Only non-obese women with a body mass index (BMI)

[Effect of insulin in polycystic ovary syndrome]. / Pusobení inzulínu u syndromu polycystických ovarií.

BACKGROUND: Polycystic ovary syndrome (PCOS) has been accompanied by insulin resistance. The aim of this study was to compare the insulin action between thin and obese women with PCOS and to analyse its relationship to serum concentration of selected hormones. METHODS AND RESULTS: Total number of 32 women with PCOS between them there were 22 thin and 10 obese subjects was examined in this study. Control group consisted of 21 nonobese healthy women. The insulin action was determined by euglycemic hyperinsulinemic clamp. Normal insulin action found in the group of thin women with PCOS was comparable with that in healthy controls whereas insulin resistance was observed in obese ones. An inverse relationship was found between insulin action and body mass index (r = 0.62, p < 0.01). By using HOMA index this relationship to BMI was on the borderline significance. No correlation was observed between insulin action and serum hormone concentrations (testosterone, androstendione, LH, FSH) but sex hormone binding globulin (SHBG) positively correlated with parameters of insulin action (r = 0.50-0.54). CONCLUSIONS: The insulin action may be normal in thin women with PCOS whereas obesity and other not yet disclosed factors influence development of insulin resistance in women with polycystic ovary syndrome.

[Can hormonal contraceptives affect plasma levels of IGF-1 and IGFBP-1 in slim women with polycystic ovary syndrome?]. / Muze hormonální antikoncepce ovlivnit plazmatickou koncentraci IGF-1 a IGFBP-1 u stíhlých zen se syndromem polycystických ovarií?

BACKGROUND: Polycystic ovary syndrome (PCOS) represents a frequent endocrinopathy among fertile women. Ethiopathogenesis of the syndrome is multifactorial and it is a subject of scientific discussions. Considered is the possibility of intraovarial IGF system disorder affecting maturation of ovarial folicles. The aim of our work was to determine effects of peroral contraceptives with low-androgen progestin on IGF system in PCOS patients and healthy woman controls. METHODS AND RESULTS: 14 patients fulfilling diagnostic criteria of PCOS and 7 healthy controls were included into the study. All persons were examined before and after six months lasting administration of monophasic estrogen-progesteron contraceptive therapy with 35 micrograms of ethinylestradiol per day and 250 micrograms of low-androgen progestin norgestimate per day. In PCOS patients low increase of basal insulinemia levels occurred (16.3 +/- 4.8 vs. 20.8 +/- 4.8 mU.l-1, p < 0.05). IGF-1 serum levels were not influenced (230 +/- 70 vs. 235 +/- 112 pg.ml-1, n.s.), IGFBP-1 serum concentration significantly increased (46.3 +/- 24.1 vs. 75.6 +/- 24.0 pg.ml-1, p < 0.001). Insulinemia in healthy women also slightly increased (15.9 +/- 4.0 vs. 18.4 +/- 4.0 pg.ml-1, p < 0.05). IGF-1 serum concentration significantly increased (140 +/- 65 vs. 241 +/- 89 pg.ml-1, p < 0.001). IGFBP-1 was also higher (45.0 +/- 19.19 vs. 80.0 +/- 15.6 pg.ml-1, p < 0.001). Influence of the hormonal contraception on the followed parameters was estimated using Wilcoxon's test. While BP-1 increase was significant in both groups, the increase of IGF-1 was significant only in healthy controls. CONCLUSIONS: Increased levels of IGFBP-1 were found in both studied groups of women. Women with PCOS had higher serum levels of IGF-1 before the therapy and the treatment did not influence it. Contrary to it, in healthy women the increased value was observed. Explanation of that finding will become the aim of our next study.

Does obesity diminish the positive effect of oral contraceptive treatment on hyperandrogenism in women with polycystic ovarian syndrome?

Polycystic ovarian syndrome (PCOS) is an obvious indication for long-term treatment. Combined oral contraceptives (COC) remain the first choice for the treatment of hyperandrogenism in most patients. However, differences in endocrine and metabolic parameters between obese and lean patients have been postulated. This is the first study evaluating the effect of COC treatment in obese versus non-obese PCOS patients. In total, 28 lean [body mass index (BMI) <25 kg/m(2))] and 15 obese (BMI >30 kg/m(2)) women patients were enrolled in the study. The concentrations of androgens, sex hormone-binding globulin (SHBG) and lipids were measured before and after 6 months of treatment with COC containing low-androgenic progestins. Clinical androgenic symptoms were monitored. There was a lower concentration of SHBG in obese patients, but there were no differences in androgen concentrations between both groups before the study. Highly significant changes in concentrations of testosterone (P < 0.001), androstenedione (P < 0.0001), SHBG (P < 0.001) and LH (P = 0.01) were demonstrated in lean patients, with only less significant changes in SHBG (P < 0.01) and testosterone (P < 0.05) in obese patients during the study. Clinical androgenic symptoms improved significantly (P = 0.05) only in the group of lean women. No reduction in low-density lipoprotein-cholesterol/high-density lipoprotein-cholesterol ratio was observed in either group. In conclusion, the positive effect of COC treatment on androgen production, serum androgen binding capacity, and clinical androgenic symptoms was negatively influenced by an increased BMI.

[Effect of insulin in hypertension with high and low levels of renin]. / Pusobení inzulinu u vysokoreninových a nízkoreninových hypertenzí.

BACKGROUND: Setback in insulin resistance has been described in patients with essential hypertension. The aim of our study was to verify at the receptor and postreceptor levels the presence of insulin resistance in patients with high or low renin activity. METHODS AND RESULTS: Six patients with the renal artery stenosis (20 to 65 years, average age was 51 +/- 12 years, BMI: 27 +/- 2.0 kg.m2) and six patients with primary hyperaldosteronism (28 to 61 years, average age was 50 +/- 13 years, BMI: 26.9 +/- 3.2 kg.m2) were investigated. Their diagnose was confirmed by laboratory examination, computer tomography, and duplex sonography. Blood pressure was monitored for 24 hours with Spacelab tonometer (SBP: 161 +/- 29 mmHg, DBP: 98 +/- 12 mmHg versus SBP: 168 +/- 21 mmHg, DBP: 103 +/- 9 mmHg; plasma renin activity was 8.1 +/- 5.6 versus 0.3 +/- 0.4 ng.ml-1.h-1, p < 0.001; recumbent plasma aldosterone level was 98 +/- 31 versus 358 +/- 103 pg.ml-1, p < 0.001, normal value till 150 pg/ml, serum potassium was 3.9 +/- 0.4 and 3.5 +/- 0.6 mmol/l). All patients had normal course of the oral glucose tolerance test. Six volunteers of corresponding age and BMI formed the control group. Patients had normal values of the basal morning glycemia (4.9 +/- 0.5 and 5.0 +/- 0.6 versus 4.9 +/- 0.6 mmol/l), basal insulinemia level was 28.8 +/- 12.4 and 21.0 +/- 10.2 versus 15.9 +/- 8.8 mU.l-1 in healthy controls. Insulin effect was tested using isoglycemic hyperinsulinemic clamp method on Biostator with insulin infusion of 1 mU.kg.min-1. Plasma potassium concentration was kept at constant physiological levels using linear infusion pump (in patients with primary hyperaldosteronism after the prior supplementation). In patients with high-renin or low-renin hypertension, the glucose consumption during clamping was lower than that of healthy controls (M, glucose disposal rate: 23.7 +/- 4.8 and 19.5 +/- 3.4 versus 33.0 +/- 5.7 mumol.kg.-1.min-1, p < 0.001), increase of the metabolic glucose clearance (MCRG: 5.1 +/- 1.5 and 3.9 +/- 0.7 versus 7.9 +/- 1.4 ml.kg-1.min-1, p < 0.001) and tissue insulin sensitivity index (M/I: 24.3 +/- 10.1 and 26.4 +/- 8.3 versus 38.4 +/- 10.1 mumol.kg-1.min-1 to mU.l-1 x 100, p < 0.001). CONCLUSIONS: Patients with high-renin and low-renin hypertension have the insulin effectiveness significantly impaired. Such insulin resistance probably does not depend on the renin activity, plasma aldosterone concentration or on serum potassium level. The ethiopathogenesis of the described changes will be the aim of our next study.

[Personal experience with surgical treatment of insulinoma]. / Nase zkusenosti s chirurgickou lécbou inzulinomu.

In 1981-2000 at the IIIrd Medical Clinic 60 patients were treated with confirmed organic hyperinsulinism. A surgical operation was indicated in 51 patients. In 42 a localized tumour was removed, in one diffuse adenomatosis was involved. In three of the operated patients a malignant, enddocrinologically active insulinoma was confirmed. Two patients were re-operated on account of a relapse. The remaining 9 patients were treated conservatively from the onset. For localization of the tumour before operation US, CT and angiographic examinations were used. US and angiography were an asset in 25 patients (49%). In some instances we encountered however on angiography falsely positive findings. US was positive before surgery in 12 patients (23%), angiography in 21 (41%) and CT only in 2 (4%). The insulinoma was detected only on surgery in 14 patients (33%) of the operated insulinomas. The tumour was found in the head of the pancreas in 13 patients (31%), in the body of the pancreas in 14 (33%) and in the tail of the pancreas in 15 (36%). Surgery was successful in 82%, while the topographic preoperative examination aroused suspicion of a focus (i.e. insulinoma) only in 49% of the operated patients. A total of 17 patients (8 after surgery and 9 without surgery) were successfully treated with diazoxide, in 9 patients this treatment is still administered. According to the response to diazoxide insulinomas can be divided into "responsive" and "non-responsive" ones. Pharmacological treatment is therefore justified only in the first group of patients. Operated and pharmacologically treated patients have no signs of hyperinsulinism. Our experience indicates that a surgical approach is suitable when the diagnosis is unequivocal, even when there is a negative topographic finding of imaging methods as in 33% of the operated patients the insulinoma was detected only on operation.

Can primary hyperaldosteronism be considered as a specific form of diabetes mellitus?

Aldosterone-producing adenoma (aldosteronoma)--the most frequent form of primary hyperaldosteronism (PH)--is considered a specific form of diabetes mellitus (DM). In a previous study we demonstrated insulin resistance in patients with PH. We have therefore undertaken a study to evaluate the incidence of abnormalities of glucose metabolism in patients with PH (36 subjects) compared to control subjects with essential hypertension (EH) (21 patients). The following parameters were measured in all studied subjects: office blood pressure (by mercury sphygmomanometer in the sitting position), body mass index (BMI), plasma potassium, plasma glucose and insulin levels during oral glucose tolerance test (OGTT) (0, 60, 120 min), plasma renin activity and plasma aldosterone. Although patients with PH tended to have higher stimulated plasma glucose levels after 60 and 120 min compared to EH, these differences did not attain statistical significance. Patients with EH tended to have higher insulin levels at each measured interval, but due to a high variability these differences were again not significant. There were no significant differences between PH and EH in the proportion of diabetics (20% vs. 14%) or patients with impaired glucose tolerance (18% vs. 10%). In conclusion, we have found the absence of significant differences in the frequency of diabetes mellitus, impaired glucose tolerance and insulin resistance in patients with EH and PH. Our data thus do not support the idea of primary hyperaldosteronism as a specific type of diabetes mellitus. Furthermore, our results indicate that glucose metabolic characteristics in essential hypertension and primary hyperaldosteronism tend to be similar. The definitive conclusion with respect to the possible causal relationship between DM and PH, however, can be obtained only on larger groups of subjects, in particular after the evaluation of the effect of surgical/pharmacological treatment of primary hyperaldosteronism.

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.

[Insulin and insulin therapy]. / Inzulin, lécba inzulinem.

The author summarizes basic findings on the formation of insulin, its secretion and bond to insulin receptors and other phenomena at the post-receptor level. He summarizes basic indications for insulin treatment also beyond the sphere of diabetology. In a separate part the author summarizes briefly the history since the discovery of insulin up to the present time with modern therapeutic procedures (insulin injections, insulin pumps). The greatest part of the paper is devoted to contemporary insulin preparations and their use in therapy. A separate section is devoted also to insulin absorption and ways to influence its action. Attention is drawn to some differences in insulin absorption in relation to the site of injection, insulin concentration, body temperature and other factors which can be influenced. The objective of the paper is an overview of insulin and its use in therapy since to discovery of insulin to the present time.

[Diagnosis and treatment of pancreatic islet cell tumors producing vasoactive intestinal polypeptide (VIPoma)]. / Diagnostika a lécba nádoru pankreatických ostruvku produkujících vazoaktivní intestinální polypeptid (VIPom).

The incidence of VIPoma is approximately one per 10 million population. Thus in the Czech Republic this rare disease should be diagnosed once per year. The authors present their experience with the diagnosis and treatment of patient born in 1956, who suffered since 1990 from diarrhoea, at first episodically. In 1992-1994 the diarrhoea was profuse, caused dehydration, hypokalaemia and severe metabolic acidosis without an increase of the anion gap. As a result of dehydration the patient developed acute renal insufficiency. Due to hypokalaemia he developed paroxysmal atrial fibrillation. The diagnosis was based on the clinical finding and later confirmed on laboratory examination by a high VIP serum concentration. For treatment of diarrhoea Sandostatin was used. The tumour was located only after a scan with 123I-VIP in the cauda of the pancreas. Scintigraphy with labelled octreotide, similarly as other imaging methods (sono, X-ray and CT) were not effective. In 1994 left-sided hemipancreatectomy was performed. Although the patient was operated four years after the onset of the disease, no secondaries were detected. After surgery the diarrhoea stopped and no further treatment was necessary.

[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.

The effect of fasting and vitamin E on insulin action in obese type 2 diabetes mellitus.

The influence of either short-term fasting or vitamin E administration on insulin action was studied in two groups of obese Type 2 diabetic patients. Twelve patients underwent 7 days of fasting (group A), whereas 600 mg of vitamin E was administered daily during 3 months in 9 diabetic patients (group B). Insulin action was examined by using hyperinsulinemic isoglycemic clamps (insulin infusion rate, 1.0 mU/kg/min) and insulin receptors on erythrocytes before and after respective regimens. An increase of glucose disposal rate (29.5 +/- 8.9 vs. 24.0 +/- 7.5 mumol/kg/min, p < 0.01) and an increase of metabolic clearance rate of glucose (4.0 +/- 2.5 vs. 2.3 +/- 0.9 mL/kg/min, p < 0.01) were observed in group A after fasting. On the contrary, decreases of glucose disposal rate (21.3 +/- 8.5 vs. 26.6 +/- 9.8 mumol/kg/min, p < 0.02), metabolic clearance rate of glucose (2.9 +/- 0.8 vs. 3.7 +/- 1.7 mL/kg/min, p < 0.05), and insulin receptor number (p < 0.01) were found after vitamin E administration as compared with pretreated values. A worsening of diabetes control as observed by an increase of HbA1C (p < 0.01) was present in the latter group. In summary, we found an improvement of insulin action after short-term fasting in contrast with the worsening of metabolic parameters after vitamin E administration in obese Type 2 diabetic patients.