Efficacy of bowel ultrasound to diagnose necrotizing enterocolitis in extremely low birthweight infants.

BACKGROUND: Bowel ultrasound (US) is one of the methods used to enhance diagnostic accuracy of necrotizing enterocolitis (NEC) and its associated complications in premature newborns. AIM: To explore the diagnostic accuracy of BUS in extremely low birth weight (ELBW) infants with NEC. METHODS: A single-center retrospective case-control study included 84 extremely low birth weight (ELBW) infants. The infants were divided into three groups: Group 1 -infants with NEC (n = 26); Group 2 -infants with feeding problems (n = 28); Group 3 -control group (n = 30). RESULTS: The specific BUS findings in premature newborns with NEC (stage 3) included bowel wall thinning, complex (echogenic) ascites, and pneumoperitoneum, p <  0.05. The diagnostic effectiveness of these sonographic signs was 96.8% (sensitivity 75.0% and specificity 97.6%), p <  0.05. These findings with high specificity were associated with the need for surgical intervention, poor outcomes, or increased mortality. Stage 2 NEC which did not require surgery showed impaired differentiation of the bowel wall layers, absent or decreased bowel peristalsis, pneumatosis intestinalis, portal venous gas, or simple ascites, with a diagnostic accuracy of 82.9% (sensitivity 55.6%, specificity 91.4%, p <  0.05). CONCLUSIONS: BUS can be used as an adjunct to abdominal radiography to aid in the diagnosis of infants with suspected NEC by providing more detailed evaluation of the intestine.

Differentiation of CD133-positive pancreatic cells into insulin-producing islet-like cell clusters.

Adult pancreatic stem and progenitor cells could represent an alternative source of insulin-producing tissue for diabetes treatment. In order to identify these cells, we have focused on the human pancreatic cells expressing cell surface molecule CD133, a marker of adult stem cells. We found that population of human CD133-positive pancreatic cells contains endocrine progenitors expressing neurogenin-3 and cells expressing human telomerase, ABCG2, Oct-3/4, Nanog, and Rex-1, markers of pluripotent stem cells. These cells were able to differentiate into insulin-producing cells in vitro and secreted C-peptide in a glucose-dependent manner. Based on our results, we suppose that the CD133 molecule represents another cell surface marker suitable for identification and isolation of pancreatic endocrine progenitors.

Weight, body composition and fat distribution of Czech women in relation with reproductive phase: a cross-sectional study.

A sample of 213 healthy Czech women was classified into four groups according to their reproductive phase: fully reproductive, premenopausal, menopausal and postmenopausal women. Changes in body weight, body composition and fat distribution were studied in those four groups using the classical anthropometric method. Body weight rises till the menopause with no further increase. A decrease in relative contribution of muscle and bone mass was observed. The progressive increase in fat mass with age was clearly demonstrated, both the fat mass weight (r = 0.38, p < 0.001) and its percentage contribution (Matiegka r = 0.40, p < 0.001, Parízkovi r = 0.42, p < 0.001). There is a stronger correlation of central fat indices as WHR (r = 0.57, p < 0.001), abdominal (r=0.56, p < 0.001) and waist circumference (r = 0.50, p < 0.001) than for hip circumference (r = 0.27, p < 0.001) to the age. WHR and waist increase most when fully reproductive and premenopausal women were compared (p < 0.001); less when premenopausal to menopausal women are compared (NS) and the least when menopausal to postmenopausal women were compared (NS). The mean values of 14 skinfolds thickness are shown, the skinfold at the abdomen shows the strongest correlation to the age (r = 0.49, p < 0.001). The results are consistent with the hypothesis of progressive fat centralisation.

Isolation and characterization of human CXCR4-positive pancreatic cells.

The existence of an adult PSC that may be used in the treatment of diabetes is still a matter of scientific debate as conclusive evidence of such a stem cell in the adult pancreas has not yet been presented. The main reason why putative PSC has not yet been identified is the lack of specific markers that may be used to isolate and purify them. In order to increase the list of potential PSC markers we have focused on the human pancreatic cells that express cell surface receptor CXCR4, a marker of stem cells derived from different adult tissues. Here we report that CXCR4-positive pancreatic cells express markers of pancreatic endocrine progenitors (neurogenin-3, nestin) and markers of pluripotent stem cells (Oct-4, Nanog, ABCG2, CD133, CD117). Upon in vitro differentiation, these cells form ILCC and produce key islet hormones including insulin. Based on our results, we assume that CXCR4 marks pancreatic endocrine progenitors and in combination with other cell surface markers may be used in the attempt to identify and isolate PSC.

Metabolic effect of sirolimus versus mycophenolate mofetil on pancreatic graft function in the early posttransplant period.

Metabolic effects of immunosuppressive agents are of great importance in pancreas or islet transplantation. The aim of our study was to compare effects of tacrolimus-based immunosuppression in conjunction with sirolimus (RAPA) versus mycophenolate mofetil (MMF) on glucose metabolism in type 1 diabetic recipients following a simultaneous pancreas and kidney transplantation (SPK). We examined 30 insulin-independent patients after SPK with venous systemic drainage of the pancreatic graft. All recipients had good kidney graft function. Fasting glycemia, insulin levels, glycosylated hemoglobin (HbA(lc)), standard intravenous glucose tolerance test (IVGTT), and trough RAPA levels were assessed in pancreas recipients before elective steroid withdrawal. Insulin sensitivity was evaluated using the homeostasis model assessment (HOMA-IR). The groups did not differ in age, BMI, posttransplant period, steroid daily dose, HbA(lc), and fasting glycemia. We did not find any significant difference in the IVGTT response. Area under the curve of insulin levels during IVGTT and HOMA-IR were significantly lower in the RAPA group. Trough levels of RAPA had no significant impact on any of the examined parameters. Glucose tolerance measured with the use of IVGTT was similar in patients treated with RAPA and MMF. However, recipients on sirolimus treatment had significantly lower insulinemia during the test and consequently more favorable indices of insulin action as assessed by HOMA-IR.

Effect of acute hyperglycaemia on sodium handling and excretion of nitric oxide metabolites, bradykinin, and cGMP in Type 1 diabetes mellitus.

AIMS: The aim of this study was to evaluate the effect of acutely induced hyperglycaemia on renal sodium handling and to explore the role of the bradykinin-nitric oxide-cGMP signalling pathway. PATIENTS AND METHODS: We compared 20 Type 1 diabetic (DM1) patients without microalbuminuria with 15 weight-, age-, and sex-matched healthy controls (C). Clearances of para-aminohippuric acid (CPAH), inulin (Cin), lithium, sodium, and urinary nitrite/nitrate (NOx), cGMP and bradykinin excretion rates were measured in two 90-min periods: a glycaemic clamp-induced euglycaemia (5 mmol/l-period I) and hyperglycaemia (12 mmol/l-period II) (Study 1) and during time-controlled euglycaemia (5 mmol/l-period I and 5 mmol/l-period II) to avoid the effects of time and volume load (Study 2). RESULTS: Cin and CPAH were not significantly different during euglycaemia (period I of Study 1) in DM1 and controls, whereas fractional excretion of sodium was decreased in DM1 (1.84 +/- 0.75 vs. 2.36 +/- 0.67%; P < 0.05) due to an increase in fractional distal tubular reabsorption of sodium (94.01 +/- 1.94 vs. 92.24 +/- 2.47%; P < 0.05). A comparison of changes during Study 1 and Study 2 revealed acute hyperglycaemia did not change renal haemodynamics significantly, while fractional distal tubular reabsorption of sodium increased (DM1: P < 0.05; C: P < 0.01) and fractional excretion of sodium decreased (P < 0.01) in both groups. The urinary excretion rates of NOx were comparable during euglycaemia in DM1 and C. While in C, they significantly increased during Study 1 (period I: 382 +/- 217 vs. period II: 515 +/- 254 nmol/min; P < 0.01) and Study 2 (period I: 202.9 +/- 176.8 vs. period II: 297.2 +/- 267.5 nmol/min; P < 0.05) as a consequence of the water load, no changes were found in DM1. The urinary excretion of bradykinin was lower in DM1 compared with C (0.84 +/- 0.68 vs. 1.20 +/- 0.85 micro g/min; P < 0.01) during euglycaemia; it was not affected by hyperglycaemia. There were no significant differences between DM1 and C and in cGMP urinary excretion rates following hyperglycaemia. CONCLUSION: This study demonstrates that DM1 without renal haemodynamic alterations is associated with impaired renal sodium handling. Moreover, we did not find a relationship between the renal excretion rates of vasoactive mediators and sodium handling due to hyperglycaemia.

[Disorders of parathyroid function in patients on regular dialysis therapy and after kidney transplantation]. / Poruchy funkce prístítných telísek u nemocných v pravidelném dialyzacním lécení a po transplantaci ledviny.

BACKGROUND: Parathyroids dysfunction is a key disorder in the spectrum of renal osteopathy, occurring after renal transplantation and, occasionally, after parathyroidectomy. In our subjects, dysfunction is understood as plus or minus activity. METHODS AND RESULTS: Parathyroidectomy as the primary procedure was performed in 179 patients for all types of hyperparathyrodism. In 70% of cases the secondary hyperparathyroidism was treated, believed to be the most severe condition. Present assessment was focused on postoperative parathyroid hormone levels (pg/ml) in three groups of patients (n = 92). Group 1 with parathyroid gland autoimplants following total parathyroidectomy; Group 2 after partial or subtotal surgery; Group 3 after autologous implantation of cryopreserved parathyroid glands in severe hypoparathyroidism. Group 1 (32 dialysis and 9 non-dialysed patients): 228.9 vs 85.9 pg/ml; ns; hypofunction in 50% and in 33% respectively, afunction in 12.5% of dialysed patients, in non-dialysed patients it was not detected. Group 2 (25 dialysis and 24 non-dialysed patients): 603.3 vs 169.8 (pg/ml); p = 0.01; hypofunction in 16% and in 8% respectively, afunction was not detected. Complete groups 1 and 2 of patients: 197.5 vs 382.3 pg/ml (p = 0.0016). Dialysed patients in Group 1 and 2: 228.9 vs 603.3 pg/ml (p = 0.007); non-dialysed patients: 85.9 vs 169.8 pg/ml; ns. Group 3 (15 dialysed patients): 63.0; hypofunction and afunction in 40%. This group (63.0 pg/ml) vs Groups 1 and 2 of dialysed patients (p = 0.031 and 0.0004), respectively. Basic laboratory findings before operations of tertiary hyperparathyroidism were shown. CONCLUSIONS: After total parathyroidectomy with parathyroids autoimplantation, parathyroid hormone is acceptable to dialysis and non-dialysis patients. Partial parathyroidectomy prevents development of hypoparathyroidism. It is associated, however, with a risk because of hyperparathyrodism recurrence. Cryopreserved autologous parathyroids reach lower parathyroid levels compared with "fresh" parathyroid tissue autoimplants. Parathyroidectomy after successful renal transplantation may be indicated.

Angiotensin II-induced hypertension in bradykinin B2 receptor knockout mice.

The present study was performed to examine the role of endogenous bradykinin (BK) in the development of angiotensin II (Ang II)-induced hypertension in mice. BK B2receptor knockout (B2R-/-) and wild-type (B2R+/+) mice (22to 26 g) were infused with either saline (SAL) or Ang II (40ng/min) via an osmotic minipump implanted intraperitoneally. On day 12after implantation, there was no difference in systolic blood pressure (SBP, tail-cuff plethysmography) between SAL/B2R+/+ and SAL/B2R-/- mice(128+/-5 versus 133+/-6 mm Hg, n=24/group). In contrast, SBP was higher on day 12 of infusion in Ang II/B2R-/- than in Ang II/B2R+/+ mice (173+/-6versus 156+/-5 mm Hg; P<0.05, n=27 and 28). Mean arterial pressure (MAP)was also higher in anesthetized Ang II/B2R-/- mice than in Ang II/B2R+/+mice (139+/-3 versus 124+/-3 mm Hg; P<0.05, n=16 and 14). Unlike Ang II, long-term norepinephrine (NE) infusion via an osmotic minipump (45ng/min) caused equivalent increases in SBP in B2R+/+ and B2R-/- mice measured on day 12 after implantation (151+/-4 versus 149+/-5 mm Hg, n=9and 8). MAP also did not differ on day 13 after implantation between NE/B2R+/+ and NE/B2R-/- mice (120+/-6 versus 122+/-4 mm Hg, n=9 and 8). There were no differences in glomerular filtration rate and urinary sodium excretion among the groups. However, renal plasma flow (RPF) was lower in Ang II/B2R-/- mice than in Ang II/B2R+/+ mice (2.34+/-0.06 versus 4.33+/-0.19 mL x min-1 x g-1; P<0.05). Acute inhibition of NO synthase (NOS)with nitro-L-arginine-methyl ester (0.5 microg x g-1 x min-1) in SAL/B2+/+ and SAL/B2-/- mice caused equal increases in MAP (142+/-1 versus 145+/-1 mmHg) and decreases in RPF (2.06+/-0.06 versus 2.12+/-0.15 mL x min-1 x g-1).However, short-term NOS inhibition caused a greater increase in MAP of Ang II/B2R+/+ mice than of Ang II/B2R-/- mice, such that MAP after NOS inhibition in Ang II/B2R+/+ approached that of Ang II/B2R-/- mice (156+/-2versus 159+/-2 mm Hg). These changes were associated with a decrease in RPF in Ang II/B2R+/+ mice to values similar to those of Ang II/B2R-/- mice before NOS inhibition (2.12+/-0.09 versus 2.34+/-0.06 mL x min-1 x g-1). These results demonstrate that the kallikrein-kinin system selectively buffers the vasoconstrictor activity of Ang II. Furthermore, the enhanced susceptibility of B2R-/- mice to Ang II-induced hypertension and renal vasoconstriction is likely due to an impaired ability to release NO by endogenous kinins.

Increased glucagon-stimulated insulin secretion of cryopreserved rat islets transplanted into nude mice.

Cryopreservation is the only available technique for long-term storage of pancreatic islets. The freezing/thawing protocol may cause considerable loss of viable islet tissue and impair its function in vivo. The aim of this study was to investigate glucose and insulin levels after transplantation of fresh and cryo/thawed rat islets. Rat pancreatic islets were isolated following intraductal collagenase injection and Ficoll gradient purification. After isolation, islets were cultured for 24 h and then either transplanted or frozen after stepwise addition of DMSO according to Rajotte et al. and stored in liquid nitrogen. After rapid thawing islets were stepwise transferred into RPMI medium and cultured for another 24 h. The recipients were athymic mice with streptozotocine-induced diabetes. Two hundred fresh (n=13) or cryo/thawed (n=15) islets were transplanted beneath the renal capsule. Glucose levels were measured for 14 days and blood samples for insulin determination were obtained 15 min after i.p. glucagon (10 mg/kg) administration on day 14. Glucose levels were normalized (<9 mmol/l) in all recipients within 3 days since transplantation. On day 14, mean fasting values+/-SE in fresh and cryo/thawed islet groups were 4.0+/-0.6 and 4.4+/-0.4 mmol/l, respectively (P>0.05). Fasting insulin levels were higher in the cryo/thaw than in the fresh islet group (1.67+/-0.33 vs 0.57+/-0.13 ng/ml; P<0.01). Post-glucagon levels did not differ significantly (1.45+/-0.24 vs 0.86+/-0.24 ng/ml; P=0.06). While glucagon significantly increased insulin levels (P<0.01) in the fresh islet group, no change in insulin levels was observed (P>0.05) in the cryo/thaw group. Immunohistochemical staining demonstrated fragmentation of viable islet tissue which was more apparent in the cryo/thaw group. We conclude that in a short-term study cryo/thawed rat islets produce higher insulin levels than fresh islets transplanted into nude mice. This may be due to better islet survival or loss of feed-back regulation.

[Metabolic sequelae of pancreatic transplantation using two different surgical techniques]. / Metabolické dusledky transplantace pankreatu pri pouzití dvou ruzných chirurgických technik.

BACKGROUND: By transplantation of the pancreas in diabetics type 1 long-term-term independence on exogenous insulin can be achieved. The extent of normalization of the carbohydrate metabolism can depend on the applied surgical technique. The objective of the submitted work was to compare indicators of compensation of diabetes one year after combined transplantation of the kidney and pancreas, using the method of transplantation of a segment of the pancreas with obliteration of the pancreatic duct by a polymer and the method of transplantation of the whole pancreas with drainage of the pancreatic duct into the urinary bladder. METHODS AND RESULTS: The authors examined two groups of recipients, 13 subjects each with full function of the pancreatic graft one year after transplantation where a combined transplantation of the kidney and pancreatic segment (group SP) had been performed or of the kidney and whole pancreas (group CP). The authors investigated the blood sugar level, glycated haemoglobin, intravenous glucose tolerance test, free insulin level and C-peptide as well as some indicators of the lipid metabolism and acid base balance. In both groups normal blood sugar levels were achieved, though the mean values in the course of the day were higher in group SP than in group CP (mean +/- SE 5.48 +/- 0.11 as compared with 4.98 +/- 0.09; p < 0.01). Glycated haemoglobin declined in group SP from the pretransplantation value of 9.31 +/- 0.09 to 6.40 +/- 0.10% and in group CP from 9.49 +/- 0.15 to 4.92 +/- 0.08%. In group CP the glycated haemoglobin after transplantation was significantly lower (p < 0.01), similarly as the coefficient of glucose assimilation (1.83 +/- 0.03 as compared with 1.25 +/- 0.15; p < 0.05). Indicators of the acid base balance did not differ. Recipients in group CP were however permanently treated with bicarbonate. CONCLUSIONS: With both transplantation method it is possible to achieve compensation of diabetes close to normal. The carbohydrate tolerance is however better after transplantation of the whole pancreas.

[Insulin resistance and insulin secretion in type II non-obese diabetics]. / Inzulinová rezistence a sekrece inzulinu u diabetiku II. typu bez obezity.

BACKGROUND: Glucose tolerance depends essentially on insulin secretion and its action in target tissues. Diabetes mellitus type II (insulin-nondependent diabetes) is a disease conditioned by a dysbalance between insulin secretion and effect; it has not been decided whether the cause is insulin resistance or impaired insulin secretion, although a defect of insulin secretion for the manifestation of the disease is generally accepted. The purpose of the submitted study was to assess to what extent insulin secretion and its effect after an oral glucose load and a hyperglycaemic clamp is affected in different groups of non-obese patients with diabetes type II. METHODS AND RESULTS: The authors examined 21 men with diabetes type II (age 41 +/- 2.6 years, BMI 26.2 +/- 3.2, HbA1,c 9.4 +/- 2.9%) in the course of one year after detection of the disease, treated by diet alone. The second group was formed by 20 patients with diabetes type II (age 46.1 +/- 3.6 years, BMI 26.0 +/- 2.1, HbA1,c 6.94 +/- 1.6%) who suffered from diabetes for 5-10 years and who were treated by diet alone. The third group was formed by 32 diabetics type II (age 51.8 +/- 6.1 years, BMI 26.7 +/- 2.2, HbA1,c 8.7 1.2% +/-) who suffered from diabetes for 5-10 years and were treated with oral antidiabetics. The control group was formed by 42 healthy men matched for body weight and age (age 39.9 years, BMI 25.3, blood sugar level 4.8 mmol/l). Although the diabetic groups did not differ in the fasting blood sugar level (8.0-8.29-8.2 mmol/l), the glycosylated haemoglobin HbA1,c level is lowest in the group of diabetics treated by diet alone, similarly as the rise of the blood sugar level 120 mins, following oral administration of 75 g of glucose (10.3 mmol/l, as compared with 16.2 mmol/l and 15.5 mmol/l in the other groups). The authors found in all groups of diabetic patients, as compared with controls, a comparable drop of the insulin effect evaluated as the metabolic glucose clearance during an hyperinsulinaemic euglycaemic (5 mmol/l) or isoglycaemic (fasting blood sugar level) clamp, the insulin level being 75 microU/ml (controls 10.9 +/- 3.3 ml/kg.min., first group 5.35 +/- 2.7 ml/kg.min., second group 5.47 +/- 2.35 ml/kg.min., third group 5.38 +/- 2.1 ml/kg.min. The differences, as compared with controls, were significant in all groups, p < 0.01). At an insulin level of 1500 microU/ml the results are similar (controls 17.4 +/- 3.8 ml/kg.min., as compared with 13.3 +/- 3.3 in the first group, 13.3 +/- 3.0 in the second group and 12.5 +/- 3.0 ml/kg.min. in the third group: statistical significance in all three groups, as compared with controls, is p < 0.05). The authors did not reveal any differences in the specific insulin bond to insulin receptors of erythrocytes. The total glucose consumption during an isoglycaemic clamp in diabetics and a euglycaemic clamp in controls did not differ. In all diabetic groups, as compared with controls, higher C peptide values and insulin values (IRI) were found on fasting and a slower rise and longer persistence of higher levels after oral glucose administration, although an inadequate secretory response during the hyperglycaemic clamp in diabetics is apparent. Hyperinsulinism was significantly higher in the second group. The number of insulin receptors on erythrocytes, the affinity for insulin, regardless whether the receptors were free or occupied, did not differ significantly between groups. CONCLUSIONS: All investigated groups of type II diabetics had a comparable degree of insulin resistance which did not depend on the duration of diabetes, its compensation or the type of treatment. Although impaired insulin action was proved, the total glucose utilization in relation to hyperglycaemia is not reduced. The differences in the degree of glucose intolerance in the investigated groups of diabetics type II depend on the degree of impairment of insulin secretion.

[Glucose utilization and risk of hyperglycemia during simultaneous administration of branched-chain amino acids and fat emulsions in healthy persons]. / Utilizace glukózy a riziko hyperglykémie pri soucasném podávání vetvených aminokyselin a tukové emulze u zdravých osob.

In order to evaluate the effect of substrate competition on glucose utilization, we studied 8 healthy volunteers under three different conditions: 1. Hyperinsulinemic (75 a 550 microU/ml) euglycemic (5 mmol/1) clamp (HEC). 2. HEC with Nutramin VLI infusion given at a rate of 2 ml/kg.h. 3. HEC with infusion of Nutramin VLI (2 ml/kg.h) and Intralipid (0.15 g of fat/kg.h). Glucose utilization was evaluated as the glucose disposal rate during HEC. We have found, that Nutramin VLI given alone or with Intralipid does not significantly decrease glucose utilization at insulinemia of about 75 and 550 microU/ml. We conclude that simultaneous administration of substrates during parenteral nutrition at standard rates does not raise the risk of hyperglycemia in healthy men.

[The effect of fish oil on the secretion and effect of insulin in patients with type II diabetes]. / Vliv rybího oleje na sekreci a úcinek inzulínu u nemocných s diabetem II. typu.

The metabolic effect of 3-week dietary supplementation with a fish oil concentrate was examined in not markedly obese, not hypertriglyceridemic men with non-insulin-dependent diabetes mellitus (NIDDM) treated with hypoglycemic agents. Ten patients were given 15 ml/d of fish oil (Martens Oil, Norway) equivalent to 3.1 g of n-3 fatty acid (FA) per day, and compared to 10 diabetics treated with placebo (15 ml/d saline). While fish oil leads to expected increase in the ratio of n-3 to n-6 FA intake, it does not alter fasting and mixed meal stimulated blood glucose, plasma insulin and C-peptide concentrations. There were no changes in insulin action estimated by the metabolic clearance rates of glucose at plasma insulin levels of about 100 microU/ml and 1400 microU/ml during hyperinsulinemic isoglycemic clamp, and no changes were seen in insulin binding to erythrocytes. Even though our short-term study does not warrant authoritative conclusions, no adverse effects of low-dose fish oil on glucose homeostasis have been found in not markedly obese NIDDM patients treated with oral hypoglycemics.

[Atherosclerotic changes in the carotid artery detected by ultrasound in newly diagnosed type II diabetics]. / Aterosklerotické zmeny na arteria carotis prokázané ultrazvukovým vysetrením u nove zjistených diabetiku II. typu.

In a group of 107 middle-aged men with newly detected diabetes type II the authors investigated by means of a double ultrasonographic examination the incidence of atherosclerotic changes of the carotid artery. The incidence of atherosclerotic lesions on the carotid artery was relatively high (44% of the group), the majority of arterial stenoses was, however, without haemodynamic impact. A frequent finding were calcifications in the sclerotic plaques. Affection of the carotid artery was significantly frequently associated with ischaemic heart disease and ischaemia of the lower extremities. As compared with the results of examinations of the lipoprotein and carbohydrate metabolism, the authors found in men with affected carotid arteries as compared with not affected subjects significantly higher triacylglycerol levels, higher levels of circulating insulin and a higher ratio of total to HDL cholesterol.

[Blood pressure and insulin resistance in type 2 diabetics]. / Krevní tlak a inzulinová rezistence u diabetiku 2. typu.

The authors analyzed in 145 patients with Type 2, diabetes, persisting on average for 10 years, influences affecting the blood pressure reading. 1. In patients treated on account of hypertension (40%) the increase of systolic and diastolic pressure persisted and the fasting concentrations of C peptide were elevated. 2. In patients with elevated levels of diastolic blood pressure and C peptide the rate of cerebrovascular attacks in direct relatives was higher. 3. Higher blood pressure readings were associated with a higher C peptide concentration, signs of ischaemia on the ECG tracing and left ventricular hypertrophy respectively. 4. The higher blood pressure levels were associated also with other manifestations of insulin resistance, i.e. elevated triacylglycerols, low HDL cholesterol levels, raised uric acid levels. 5. Also in stepwise regression analysis the fasting concentration of C peptide held one of the important places among variables which contribute towards variations of systolic blood pressure. 6. These findings support the idea on common pathogenic influences of raised insulin concentrations on metabolism, blood pressure and the development of complications of atherosclerosis.

Insulin action and insulin binding following pancreas transplantation.

Insulin action and insulin specific binding to erythrocytes were examined in ten recipients of a pancreatic segment and renal graft (Group 1), in nine non-diabetic kidney recipients (Group 2) and in ten age- and weight-matched healthy control subjects (Group 3). All transplant recipients were normoglycaemic without need of insulin, received the same immunosuppression and had good renal graft function at 11-18 months post-transplantation, when the investigation was performed. Using the insulin clamp technique, insulin action was expressed as the metabolic clearance rate of glucose at insulin infusion rates of 1.0 (MCRsubmax) and 10.0 (MCRmax) mU.kg-1.min-1. In comparison with the healthy control subjects, fasting free insulin and C-peptide levels were significantly higher in Groups 1 and 2, but no differences between Groups 1 and 2 were found (p greater than 0.05). Mean values +/- SEM of MCRsubmax in Groups 1, 2 and 3 were 6.30 +/- 0.55, 6.09 +/- 0.69 and 10.52 +/- 1.10 ml.kg-1.min-1 respectively, and of MCRmax 12.65 +/- 0.78, 13.14 +/- 0.92 and 19.28 +/- 1.42 ml.kg-1.min-1 respectively. Insulin action was significantly decreased in Groups 1 and 2 at the low as well as the high insulin infusion rates but there was no difference between the two groups of recipients (p greater than 0.05). No differences in binding data (specific binding, number of binding sites per cell) were found. It is concluded that insulin resistance is common to all immunosuppressed organ recipient and is not related to the pancreas graft. The decrease maximal response to insulin and normal insulin binding to erythrocytes tend to suggest a post-receptor defect in insulin action.

[Insulin secretion and insulin resistance in type II diabetes. Relation to fatty acid composition of serum phospholipids]. / Sekrece inzulínu a inzulínová rezistence u diabetu II. typu. Vztahy ve slození mastných kyselin ve fosfolipidech séra.

Non-obese middle-aged men (n = 21) in an early stage after manifestation of Type 2 diabetes mellitus, and free of signs of atherosclerotic complications, when compared with an age-, weight- and sex-matched control group (n = 14), were found to show: 1. a decrease in linoleic acid content and increase in polyunsaturated elongated forms of n-6 and n-3 families fatty acids in serum phospholipids; 2. fasting hyperinsulinemia and impaired dynamics of insulin secretion after glucose load; 3. insulin resistance due to both receptor and postreceptor defect. Under physiologic conditions (i.e., in the control group), the drop in linoleic acid content and the rise in saturated fatty acids were associated with increased insulin secretion, and decrease in maximal insulin action. The nature of the changes in fatty acid pattern, the decrease in linoleic acid in particular, resembles findings made in persons who died middle-aged from serious complications of atherosclerosis. Combined with the relationship between the fatty acid composition of lipids and insulin secretion and action, our findings suggest a common metabolic defect of atherosclerosis and Type 2 diabetes which is probably insulin resistance in glucose metabolism.

[Clinical course of recent insulin-dependent diabetes mellitus and possibilities of controlling it therapeutically]. / Klinický prubeh recentního inzulín dependentního diabetu mellitu a moznosti jeho terapeutického ovlivnení.

Intensive insulin treatment in a recent stage of IDDM promotes metabolic compensation of the disease regardless which regime of conventional or unconventional treatment is used. In thus treated patients more frequently complete or partial metabolic remission is achieved. C-peptide in patients in remission is much higher than in other patients, and conversely there are fewer persons without residual B-cell secretion. The manifestation of diabetes has an impact also on the clinical course of the disease. Normoglycaemia with possible metabolic remission associated with easy insulin administration a flexible lifestyle have a favourable effect on the onset of the life-long disease and eliminate to a minimum factors which have a negative psychosomatic impact on the patient.

Endocrine pancreatic secretion in patients after acute pancreatitis.

In 14 nonobese patients after acute pancreatitis and with normal oral glucose tolerance, the response of insulin, C-peptide, and pancreatic glucagon after 100 g of oral glucose was assessed. The curves of insulin and C-peptide were significantly raised compared with those of controls, and no difference was found between the response of patients with a negative (n = 8) and a positive (n = 6) family history of type II diabetes. The curves of pancreatic glucagon did not differ from those found in controls. Our results indicate that a normal response to glucose after recovery from an attack of acute pancreatitis is maintained at the cost of increased insulin secretion.