[Metabolic syndrome in patients with diabetes mellitus type 1, prevalence, impact on morbidity and mortality]. / Metabolický syndrom u nemocných s diabetes mellitus 1. typu, prevalence, vliv na morbiditu a mortalitu, komplexní prístup k nemocnému.

Aim of this retrospective observational study was to determine the prevalence of metabolic syndrome (MS) in patients with diabetes mellitus type 1 (DM1Z) at baseline (in 2003) and find the parameters that determine the difference between group with (MS+) and without MS (MS-). Did the presence of MS affect morbidity and mortality in the subsequent 10 years? METHODS: 278 patients were enrolled to the study with age average 39 ± 13 years with medical history of diabetes 15.9 ± 9 years. The IDF criteria were used for MS diagnosis. Anthropometric and biochemical parameters, prevalence and incidence of microangiopathic and macroangiopathic complications were checkedat baseline and after 10 years. RESULTS: MS was diagnosed in 16.2 % (45) patients. MS+ group was older (p < 0.001), with a longer duration of DM (p < 0.05), which is manifested in the elderly patients (p < 0.01), with higher weight (p < 0.001), less compensation (p < 0.05), a higher value of blood pressure (p < 0.001) and reduced glomerular filtration rate (p < 0.001). MS correlated from microvascular complications with proteinuria (p < 0.001), with peripheral and cardiovascular autonomic neuropathy (p < 0.001) and with retinopathy (p < 0.01). Patients with MS had often chronic ischemic heart disease (p < 0.01), with absence of other macroangiopatic complications. After 10 years the number of patients with newly diagnosed retinopathy (p < 0.05), with chronic ischemic heart disease (p < 0.01) and with other macroangiopathy (p < 0.05) increased in MS+ group. The number of other microvascular complication sincreased, but similarly in both groups. On the other hand, in MS+ group both systolic (p < 0.01), diastolic pressure (p < 0.05) significantly decreased and values of glycosylated hemoglobin (p < 0.05) improved compared to group MS- within 10 years. 18 patients died, with higher incidence in MS+ group (p < 0.05; 13.3 % vs 5.2 %). Cardiovascular autonomic neuropathy was observed as the most serious risk factor for mortality (p < 0.05), also age was almost significant (p = 0.08). CONCLUSION: The prevalence of MS is increasing even patients with DM1T are affected. The study shows the negative impact of MS on diabetic complications and mortality and demonstrates that early diagnosis and treatment of individual components of MS as very important.Key words: cardiovascular diseases - diabetes mellitus type 1 - insulin distance - metabolic syndrome - microvascular complications - mortality.

The influence of cardiovascular autonomic neuropathy on mortality in type 1 diabetic patients; 10-year follow-up.

AIM: The aim of our retrospective study was to answer the question if the presence of cardiovascular autonomic neuropathy (CAN) affects mortality in type 1 diabetic patients during a 10-year follow-up. METHODS: Patients with type 1 diabetes mellitus examined for CAN in 2003 were enrolled in this retrospective study. A total of 278 patients were included and divided into two groups according to the presence or absence of CAN (111 CAN+, 167 CAN-). The group characteristics and outcomes were compared at baseline and after ten years (in 2013). RESULTS: In the follow-up period, a total of 18 patients died; CAN+ (14/111; 12.6%) and CAN- (4/167; 2.4%) (P < 0.001). At baseline, the CAN+ patients were older (47 vs. 33 years; P < 0.001), had longer duration of diabetes (20 vs. 12 years; P < 0.05), had worse glycemic control assessed by HbA1c (73 vs. 68 mmol/mol; P < 0.05), higher systolic (130 vs. 120 mmHg; P < 0.001) and diastolic (80 vs. 70 mmHg; P < 0.01) blood pressure and had more diabetic complications. In our analysis we found the strongest predictor of mortality to be the presence of CAN (P < 0.01) and the blood pressure value at baseline (P < 0.05). Other baseline characteristics, including the duration of diabetes, age and the presence of micro- and macrovascular complications were not significant. The statistical analysis was performed using logistic regression step-wise analysis. CONCLUSIONS: During the 10-year follow-up, CAN+ patients had a 5-fold higher mortality rate than CAN- patients. The strongest predictor of mortality was the presence of CAN.

Monogenic glucokinase diabetes and pregnancy: a case study.

It is estimated that up to 3 % of patients with gestational diabetes have glucokinase diabetes, termed also maturity-onset diabetes of the young type 2. The disorder has autosomal dominant inheritance. There is a 50 % risk of transmission of the gene to next generation. Two scenarios with different approach to the treatment may occur in pregnancy with glucokinase diabetes: either the fetus inherits the glucokinase mutation and the treatment of maternal hyperglycemia by insulin could increase the risk of fetal growth restriction, or the fetus is without glucokinase gene mutation and untreated hyperglycemia of the mother increases the risk of macrosomia and perinatal morbidity and insulin therapy is necessary. This article describes the outcome of two pregnancies in a patient with monogenic diabetes with glucokinase deficiency. A specific approach to the treatment is discussed.

[Has the pregnancy outcome of women with pregestational diabetes mellitus improved in ten years?]. / Zlepsil se osud gravidit zen s pregestacním diabetes mellitus za deset let?

INTRODUCTION: In spite of progress in medicine, studies from a number of countries indicate steadily increased risk of perinatal morbidity and mortality in the offspring of diabetic mothers. No data regarding the pregnancy outcome in women with diabetes mellitus type 1 and 2 (pregestational DM) have been published in the Czech Republic. The aim of the study was to evaluate the pregnancy course of women with pregestational DM and outcome of their offspring and to assess whether it has improved in ten years. METHODS: A retrospective evaluation of pregnancy outcome of pregestational DM women followed up in the University Hospital Pilsen in years 2000-2009 (Group A, n = 107) and comparison with the period 1990-1997 (Group B, n = 39) were performed. Wilcoxon non-paired test, contingency tables, step-wise logistic regression and step-wise linear multiple regression methods were used for statistical analyses. RESULTS: Data is presented as median (interquartile range). Women from the Group A were older 28 (25, 31) vs 25 (22, 27) years, p = 0.01. Otherwise, the groups did not statistically significantly differ in diabetes duration, BMI, and representation of women with type 2 diabetes. A better glycemic control (HbA1c, mmol/mol) was achieved in the Group A in all trimesters - 1st trimester: 59 (47, 67) vs 66 (56, 76), 2nd trimester: 46 (40, 52) vs 54 (48, 59) and 3rd trimester: 46 (40, 51) vs 53 (47, 60), p = 0.01. The caesarean section rate decreased (65.2 % vs 87.5 %, p < 0.05). The incidence of the respiratory distress syndrome after adjustment for age and diabetes duration also decreased (8.9 % vs 18.2 %, p < 0.05). A decreasing trend in the rate of premature delivery before 34th week of gestation (1.1 % vs 6.3 %) and neonatal mortality (1.1 % vs 2.9 %) was observed, however, the differences were not statistically significant. CONCLUSION: The achieved improved glycemic control led to only a partial improvement in the course of pregnancy and outcome of the offspring of diabetic mothers.

[Life expectancy of people with type 1 diabetes in the past and today]. / Zivotní prognóza osob s diabetem 1. typu dríve a dnes.

The life expectancy of Type 1 diabetes mellitus (T1DM) dramatically improved after the discovery of insulin in 1922, but was still 25 years shorter than that of non-diabetic population. Some people with T1DM, however, lived to the same age as a non-diabetic population and had no late complications of diabetes. They began to be awarded medals in appreciation of their long life with diabetes. They also became the subject of a research examining why they lived so long and what was the difference between them and those patients with T1DM, whose lives were much shorter. The paper deals with the differences observed in the ´medallists´ and discusses various hypotheses that might account for them. It seems that reliable control of diabetes within the first 20 years following the diagnosis is very important, in relation to the existence of "glycemic memory" which may significantly affect life expectancy in the following years. Human lifespan in general has been linearly extended since the early 19th century and the same holds for lifespans of people with T1DM. This is due to the higher quality control of glycemia on the one hand, and a better prevention and treatment of complications. It is observed that the incidence of terminal stages of diabetic nephropathy has been dropping, the primary as well as secondary prevention of cardiovascular complications, cardiological treatment and heart surgery have been improving. Manifest proteinuria, diabetic neuropathy and hypertension appear to be major prognostic factors of increased mortality. If these indicators are not present, the life expectancy of patients with T1DM does not significantly differ from that of the non-diabetic population.Key words: diabetic nephropathy - glycemia - glycemic memory - ICHS - late complications of diabetes - mortality - prognosis - type1 diabetes mellitus.

[Celiac disease in adult patients with type 1 diabetes mellitus]. / Celiakie u pacientu s diabetes mellitus 1. typu.

OBJECTIVE: To assess the prevalence of celiac disease in adult patients with type 1 diabetes mellitus (T1DM). Influence the new started treatment of celiac disease on glycemic control and body mass index (BMI) of the patients. Prevail the anti-transglutaminase antibody (atTG) positivity one year after commencement of the therapy. METHODS: A retrospective assessment of celiac disease targeted screening in 465 adult T1DM patients at Diabetes Center, 1st Medical Department, University Hospital in Pilsen (80 % of all T1DM patients) from 1. 1. 2007 until 1. 7. 2011. Enterobiopsy was indicated in case of atTG-A (or atTG-G) positivity. In patients with newly started gluten-free diet, HbA1c and BMI within a year after diagnosis of celiac disease were compared to a year period six months after treatment commencement (3-4 visits), atTG was evaluated one year after treatment beginning. Paired T-test was used for statistical evaluation. RESULTS: The prevalence of all forms of celiac disease in the studied group was 10.5 %. Celiac disease diagnosed in childhood was found in 1.1 % patients (5/465). Positivity of atTG was newly observed in 9.5 % (44/465) patients. Three patients with atTG > 300 kIU/l refused the enterobiopsy examination. Celiac disease is highly plausible. The influence of gluten-free diet on BMI and HbA1c could not be evaluated due to the lack of compliance. 22 patients had a potential form of celiac disease (negative histology). Positive enterobiopsy was found in 19 patients (4.1 %). Another 3 patients had to be excluded from the subgroup of 22 patients (newly indicated gluten-free diet) as the HbA1c values and BMI were affected by the primary diagnosis of T1DM. Subgroup characteristics: 9 women and 7 men, mean age 38 ± 12 years, diabetes duration 21 ± 13 years, celiac disease diagnosed 20.7 ± 13 years since first diagnosis of T1DM. No statistically significant change in HbA1c (67 ± 11.4 vs 69 ± 13.9 mmol/mol) was observed in the studied period, however and a significant change of BMI from 25.4 ± 4.2 to 25.9 ± 4.3 (p < 0.01) was found. The atTG positivity prevailed in 47 % (9/19) of patients after one year. CONCLUSION: A total prevalence of the celiac disease in the group of adult T1DM patients was 10.5 %. No significant change in HbA1c occurred following treatment, a significant change of BMI was observed. The atTG positivity prevailed in 47 % of patients after one year.

Comparison of a low-glycemic index vs standard diabetic diet.

AIM: There is insufficient evidence for the efficacy of a low-glycemic index (GI) diet in the management of diabetes. The goal of this study was to measure the effect of a low GI versus a standard diabetic diet in adults with diabetes type 2. METHODS: This was an open label, randomized, crossover study. Twenty persons with type 2 diabetes were randomized to two groups. Each group followed a standard diabetic diet or a low glycemic index diet for 3 months. The effectiveness of the two diets was evaluated using a hyperinsulinemic euglycemic clamp with endogenous glucose production measurement, indirect calorimetry and bioimpedance analysis. Outcome measures were body mass, BMI, body fat, glycosylated hemoglobin, fasting glucose, lipid profile, insulin sensitivity and hepatic glucose production. RESULTS: Body mass after 3 months following the diabetic diet was 93 kg (83-104) vs. low glycemic index diet 92 kg (85-104) P<0.05, BMI 31.3 kg/m(2) (27.5-35.9) vs. 30.7 kg/m(2) (27-35.3) P<0.05, body fat 28% (25.5-43) vs. 27% (23-43) P<0.05 (median and interquartile range). There was no statistically significant difference between diets for glycosylated hemoglobin, fasting glucose, lipid profile, insulin sensitivity or hepatic glucose production. CONCLUSIONS: The results are comparable with other studies showing a modest effect of a low GI diet in the management of diabetes. We found a modestly greater weight loss, body fat and BMI reduction on the low GI diet.

Differences in skin microcirculation on the upper and lower extremities in patients with diabetes mellitus: relationship of diabetic neuropathy and skin microcirculation.

INTRODUCTION: During recent years, the role of microcirculation has received increasing attention especially for its potential pathogenic role in the development of diabetes complications, particularly diabetic foot syndrome. The aim of this study was to evaluate the differences in the skin microcirculatory reactivity on the upper and lower extremities (UE and LE, respectively) in the patient with type 2 diabetes mellitus (T2DM). We also evaluated the changes in the skin microcirculation independently of the individual test for peripheral diabetic neuropathy (DN) diagnosis (Semmes-Weinstein monofilaments, Bio-Thesiometer [Bio-Medical Instrument Co., Newbury, OH], and Neuropad(®) [TRIGOcare International GmbH, Wiehl, Germany]). PATIENTS AND METHODS: Fifty-two patients with T2DM were enrolled. Microvascular reactivity was measured by laser Doppler iontophoresis, using 1% acetylcholine chloride (ACH) and 1% sodium nitroprusside. RESULTS: Significant reduction of perfusion was found in LE compared with UE when using ACH. In patients with DN skin microvascular reactivity on LE and UE was reduced, compared with patients without DN. Impaired skin microvascular reactivity to ACH (dominant on LE) was demonstrated in all patients who were positive in at least one of the tests for the presence of DN. CONCLUSIONS: Reactivity of the skin microcirculation is worse on the foot than on the hand. This study confirmed a close relationship of DN and impaired skin microcirculation. It seems that autonomous neuropathy (assessed using the Neuropad) precedes the manifestation of somatosensory neuropathy.

"Mesodiencephalic" modulation in the treatment of diabetic neuropathy.

OBJECTIVE: Aim of the study was to verify the efficacy of "mesodiencephalic" modulation (MDM), as named by the commercial promoters, in reducing symptoms accompanying painful diabetic neuropathy and in improving mental health. METHODS: 32 patients with type 1 and 2 diabetes mellitus, with painful neuropathy, were enrolled in the prospective, double-blind, placebo-controlled, cross-over study. The modulation was performed using MDM electrotherapeutic device (ZAT a.s), sham modulation was used as a placebo. Pain relief (visual analogue scale-VAS; total symptom score-TSS) and changes in mental state (Beck Depression Inventory-BDI-II; OSWESTRY and SF-36 questionnaires) were evaluated. RESULTS: The study was completed by 30 patients. Pain evaluation: VAS: pain relief was statistically insignificantly higher after real (R) compared to sham (S) modulation (-0.7 vs. -0.3; p=0.06), effect of both modulations was equal after 1 month (-0.4 vs. 0.0; p=0.46). TSS: the effect of R and S modulation did not differ immediately after the procedure (-1.3 vs. -1.0; p=0.27), nor after 1 month (-1.5 vs. -0.34; p=0.9). Psychological tests: according to SF-36, the physical health improved considerably after R compared to S (2.5 vs. -2.0; p<0.01), however, changes in the mental health were equal (-1.5 vs. 0.0; p=0.78). Oswestry (0 vs. 0; p=0.95) and BDI-II (-0.5 vs. -1.0; p=0.42) were comparable after R and S modulation. Order of the procedures (R vs. S) did not affect results. CONCLUSION: The study did not demonstrate any positive effect of MDM on painful diabetic neuropathy compared to placebo, relative to pain or mental state evaluations. The study emphasizes the need of using placebo-controlled studies, especially when testing a new analgesic drug or a method for pain modulation.

Influence of physiological and supraphysiological hyperinsulinemia on skin microcirculation in healthy volunteers.

AIM: To examine skin perfusion in dependency on insulinemia in healthy subjects. METHODS: All volunteers were informed in detail about the procedures and signed informed consent. The protocol of this study was approved by the ethical committee. In our study, a two stage hyperinsulinemic euglycemic clamp was performed, with insulinemia 100 and 250 mIU/mL and glycemia 5.0 mmol/L (3% standard deviation). Before the clamp and in steady states, microcirculation was measured by laser Doppler flowmetry and transcutaneous oximetry and energy expenditure was measured by indirect calorimetry. Results (average and standard deviation) were evaluated with paired t-test. RESULTS: Physiological (50 mIU/L) insulinemia led to higher perfusion in both tests; hyperemia after heating to 44%-1848% (984-2046) vs 1599% (801-1836), P < 0.05, half time of reaching peak perfusion after occlusion release 1.2 s (0.9-2.6) vs 4.9 s (1.8-11.4), P < 0.05. Supraphysiological (150 mIU/L) insulinemia led to even higher perfusion in both tests; hyperemia after heating to 44%-1937% (1177-2488) vs 1599% (801-1836), P < 0.005, half time to reach peak perfusion after occlusion release 1.0 s (0.7-1.1) vs 4.9 s (1.8-11.4), P < 0.005. A statistically significant increase occurred in tissue oxygenation in both insulinemia. The difference in perfusion and oxygenation between physiological and supraphysiological hyperinsulinemia was not statistically significant. CONCLUSION: The post occlusive hyperemia test in accordance with heating test showed significantly increasing skin perfusion in the course of artificial hyperinsulinemia. This effect rises non-linearly with increasing insulinemia. Dependency on the dose was not statistically significant.

The influence of insulin pump treatment on metabolic syndrome parameters in type 2 diabetes mellitus.

INTRODUCTION: The aim of our study was to evaluate the influence of long-term insulin pump treatment (CSII) on the parameters of metabolic syndrome in insulin-resistant patients with poorly controlled type 2 diabetes mellitus. PATIENTS AND METHODS: Thirteen obese (BMI>30) patients (8 women, 5 men), average age 58.8+/-9.06 years, treated with an intensified insulin regimen with high doses of insulin (>0.8 IU/kg per 24 h) for at least 12 months were enrolled in the study. Prior to CSII treatment, all patients were reeducated regarding diabetes treatment and metabolic syndrome, and glycemic control parameters were assessed. Insulin resistance was evaluated with the hyperinsulinemic euglycemic clamp test. All tests were repeated after six months of CSII treatment. The Wilcoxon matched-pairs signed-rank test and Spearman's rank correlation coefficient were used for statistical evaluation. Results are presented as median (1st quartile; 3rd quartile). RESULTS: There were no changes in long-term glycemic control during the course of CSII treatment: HbA1c prior to CSII 9.60 (8.95; 10.60) vs. after 6 months 9.80 (9.50; 10.20) %, BMI 33.0 (32.1; 34.2) vs. 32.9 (32.0; 34.5), total daily insulin dose 69.0 (65.0; 94.0) vs. 68.0 (58.9; 92.4) IU/24 h in observed patients. There was a statistically significant improvement in insulin resistance: M value 2.55 (1.92; 3.15) vs. 3.32 (2.23; 4.49) mg/kg per min (P<0.01), and improvement in atherosclerosis risk factors (blood coagulation and endothelial dysfunction): fibrinogen 3.44 (3.13; 3.86) vs. 3.24 (2.77; 3.38) g/l, factor VII 115 (101; 128) vs. 109 (93; 119)%, factor VIII 230 (148; 260) vs. 188 (126; 225)%, vWF:RiCo 162 (141; 193) vs. 128 (100; 132)%, PAI-1 39 (30; 44) vs. 30 (25; 36) AU/ml, thrombomodulin Ag 4.1 (3.7; 4.4) vs. 3.7 (3.45; 4.05) ng/ml (P<0.01). CONCLUSIONS: Six months of CSII treatment led to decrease in insulin resistance and improvement in parameters of lipid metabolism, blood coagulation and endothelial dysfunction independently of glycemic control and weight.

Change in glucometer settings as a cause of sudden deterioration of glycemic control in type 2 diabetes.

The subject matter of this case report is "sudden deterioration" of glycemic control in a thus far well-complying patient with type 2 diabetes. It describes possible impacts of glucometer technical failure associated with other unfavorable circumstances. An error in displaying glycemia was discovered when analyzing data from glucometer in a computer using software (DIABASS PRO, Mediaspect GmbH, Konstanz, Germany) for data evaluation, and other possible complications (especially hypoglycemia episodes) resulting from inadequate treatment correction were thus prevented.

Influence of cardiovascular autonomic neuropathy on atherogenesis and heart function in patients with type 1 diabetes.

AIM: Cardiovascular autonomic neuropathy (CAN) increases mortality of patients with type 1 diabetes (Type 1 DM). We set out to find out whether the presence of CAN in asymptomatic, normotensive Type 1 DM affects endothelial function (marker of atherogenesis) and left ventricle function (marker of cardiomyopathy). METHODS: Twenty-one Type 1 DM with CAN (Group A) and 35 Type 1 DM without CAN (Group B) were enrolled in the study. None of them suffered from any cardiovascular disease nor advanced chronic complications of diabetes. Both groups were comparable in age, glycemic control, BMI, and blood pressure. Markers of endothelial dysfunction and chronic inflammation were used as indicators of incipient atherogenesis. Left ventricle function was evaluated using echocardiography. RESULTS: Both groups did not differ in any parameter of atherogenesis. However we found a statistically significant difference in values characterizing systolic and diastolic left ventricle functions between the groups. CONCLUSIONS: CAN is not associated with elevation of markers of endothelial dysfunction and chronic inflammation in normotensive asymptomatic Type 1 DM. However CAN is associated with the impairment of systolic and diastolic left ventricle function and can thus be regarded as one of the risk factors of diabetic cardiomyopathy.

Influence of fiber on glycemic index of enteral nutrition.

BACKGROUND: Enteral nutrition is indicated in patients with malnutrition due to inadequate peroral intake. A number of these patients have diabetes mellitus or impaired glucose tolerance. The aim of the study was to evaluate the influence of fiber-enriched enteral nutrition on postprandial glycemia and insulinemia. METHODS: Ten healthy volunteers consumed the following solutions: A. 50 g of glucose, B. enteral formula containing 50 g of saccharides, and C. enteral formula containing 50 g of saccharides enriched with 2.3 g of fiber/100 mL. Postprandial glycemia and insulinemia were measured in time period after administration of specified nutrition. Time courses of glycemia and insulinemia were used for calculation of areas under the curve (AUC). The glycemic (GlyI) and insulinemic (InsI) indices of the nutrition were subsequently derived from AUC. Every measurement was performed 3 times for given type of nutrition. RESULTS: Results are presented as median and interquartile range. GlyI of enteral nutrition was 85.76 (82.71-87.82), GlyI of enteral nutrition with fiber was 84.61 (80.31-94.39). InsI of enteral nutrition was 114.15 (106.55-137.71); InsI of enteral nutrition with fiber was 104.10 (96.71-127.96). The GlyI and InsI results did not differ significantly. Addition of fiber into enteral nutrition did not influence postprandial glycemia in comparison with common enteral nutrition. CONCLUSIONS: Added fiber in polymerous enteral nutrition does not influence postprandial glycemia compared with polymerous enteral nutrition without fiber.

Could we predict asymptomatic cardiovascular autonomic neuropathy in type 1 diabetic patients attending out-patients clinics?

BACKGROUND AND AIMS: Diabetic cardiovascular autonomic neuropathy (CAN) is associated with increased morbidity and mortality. This complication may be asymptomatic for a long time. The aim of this study was to assess the prevalence, severity and predictors of asymptomatic CAN in patients with type 1 diabetes mellitus (DM1). PATIENTS AND METHODS: 107 patients with DM1 were enrolled: 52 men and 55 women aged 39.8 +/- 12.4 years (18-72), duration of DM 16.6 +/- 9.5 years (0.5-43), age at DM manifestation 23.5 +/- 12.8 years (1-54) and BMI 25.1 +/- 3.2 (18.9-33.91). CAN was assessed using standard cardiovascular reflex tests (Ewing battery) and the patients were divided into three groups according to the results: Group 0, without CAN; Group I, 1(st) degree CAN; Group II, 2(nd) degree CAN. We assessed the most frequent relationships between CAN and chronic complications, episodes of severe hypoglycemia, time-related parameters (age of patients, duration of diabetes, age at manifestation), glycosylated hemoglobin (HbA(1)c), BMI, cardiovascular diseases and blood pressure, and determined the predictability of CAN on the basis of these relationships. RESULTS: Only 50 of the 107 patients (46%) showed no CAN. We found 1(st) degree CAN in 38 patients (36%) and 2(nd) degree CAN in 19 (18%). CAN correlated more significantly with the duration of diabetes (p < 0.001) than with age (p < 0.05). The relationship between CAN and HbA(1)c was on the borderline of statistical significance (p = 0.053). We found a positive correlation between CAN and the presence of chronic complications [peripheral neuropathy (p < 0.001), retinopathy (p < 0.001), and some markers of nephropathy: creatinine (p < 0.03), albuminuria (p < 0.01)]. Although blood pressure was within the physiological range (124.2/74.5 +/- 11.5/7.8 mmHg) in all patients, a positive correlation with CAN was confirmed (p < 0.05). No relationship with occurrence of severe hypoglycemia was found. CONCLUSIONS: According to our results, asymptomatic CAN is very frequent in patients with DM1. By using multifactorial logistic regression (step-wise) analysis we demonstrated that if albuminuria, peripheral neuropathy and elevated systolic BP are present simultaneously, there is a high probability that the patient also has CAN (84.9% of initial group correctly predicted, p < 0.001).

Glycemia influences on glucose metabolism in sepsis during hyperinsulinemic clamp.

BACKGROUND: We investigated glucose metabolism in septic patients during hyperglycemic clamps and compared the different levels of insulinemia and glycemia. METHODS: In 10 non-diabetic stable septic patients on mechanical ventilation with baseline glycemia >6 mmol/L and continuous insulin infusion, 3 steps of hyperinsulinemic clamp were performed after 8 hours without caloric intake. In step 1, the targets were insulinemia of 250 mIU/L and glycemia of 5 mmol/L; in step 2, insulinemia of 250 mIU/L and glycemia of 10 mmol/L; in step 3, insulinemia of 1250 mIU/L and glycemia of 5 mmol/L. Glucose uptake was calculated as the amount of glucose per time needed to maintain the target level of glycemia. Glucose oxidation was calculated from indirect calorimetry and urinary nitrogen losses. Values are provided as means +/- SD. A two-way analysis of variance and Scheffe's method were used for statistical analysis and p < .05 was considered significant. RESULTS: At step 1, glucose uptake was lower than at step 2 (3.8 +/- 2.48 mg/kg/min and 7.9 +/- 3.45 mg/kg/min, respectively; p < .001). Glucose oxidation was also lower at step 1 (2.6 +/- 0.98 and 4.2 +/- 1.85 mg/kg/min, respectively; p < .01). Glucose storage was low at step 1 (0.7 +/- 1.39) and increased at step 2 (3.5 +/- 2.18; p < .05). In step 3, glucose uptake was 7.0 +/- 2.1, oxidation was 3.6 +/- 1.37, and storage was 2.9 +/- 2.79. There was no significant difference in all these parameters between steps 2 and 3. Energy expenditure between steps 1, 2 and 3 did not change (2294 + 307.42, 2334 + 341.53, and 2342 + 426.67 kcal/day, respectively). Alanine in plasma dropped significantly (p < .05): 10 mmol/L (311 +/- 55.88 mmol/L) at glycemia compared with 5 mmol/L (390 +/- 76 micromol/L) at insulinemia 250 mIU/L. It did not differ significantly from the values obtained at glycemia 5 mmol/L and insulinemia 1250 mIU/L (348 +/- 70.68 mmol/L). Even if the level of cytokines in sepsis was higher, there was no correlation between the insulin level in plasma (250 and 1250 mIU/L), glycemia (5 and 10 mmol/L) and cytokine level (IL-1beta, IL-2, IL-6, IL-8 and TNFalpha). CONCLUSION: At insulinemia 250 mIU/L, a glucose level of 10 mmol/L seems to increase glucose uptake, oxidation, and storage compared with glycemia 5 mmol/L. This glucose uptake and oxidation at glycemia 10 mmol/L is comparable with the effect of extremely high insulinemia (1250 mIU/L) clamped at glycemia 5 mmol/L. A higher level of blood glucose or a high level of insulinemia significantly increases glucose uptake but not energy expenditure.

Effects of carrier solution on insulin bioavailability.

BACKGROUND: The aim of our study is to assess the influence of the base solution on the availability of biologic insulin expressed in the value of total insulin using the radioimmunoassay method and to monitor the influence of the base solution on the total insulin concentration over time. METHODS: Total insulin in a saline and in a total nutrient admixture was measured using the RIA method. In 15 experiments, the application of the saline by a perfusor (8 IU Actrapid HM, 100 IU/1 mL + 20 mL saline) was carried out at time intervals of baseline, 5, 10, 30, 60, 90, and 210 minutes. The application of the total nutrient admixture (8 IU Actrapid HM + 20 mL total nutrient admixture) was carried out in the same way. The MANOVA, ANOVA and paired t test with Bonferroni correction were then used for statistical evaluation. RESULTS: The average values of insulin concentration in saline at given time intervals were 21.5 +/- 11.3 mIU/L (5.4% of the theoretically calculated concentration). The level of insulin in the total nutrient admixture did not change over time, and it reached the values of 115.2 +/- 22.3 (28.8% of the theoretically calculated concentration). Changes in insulin concentration in time were found only in the saline (ANOVA time effect p < .001 for saline; p = .26 for total nutrient admixture). CONCLUSIONS: The availability of insulin was significantly higher in the total nutrient admixture solution than in the saline in the 3.5-hour experiment. The dependence of insulin concentration on time is present only in saline, and the main changes in insulin bioavailability are within first 60 minutes. The difference could be caused by smaller insulin absorption to the syringe walls and to the set, owing to the amino acids in the mixture. The question whether the amino acid concentration affects insulin bioavailability stays opened to other studies.

Aspects of oxidative stress in children with type 1 diabetes mellitus.

Diabetes mellitus is considered to be one of a rank of free radical diseases. The existence of hyperglycemia produces increased oxidative stress (OS) via non-enzymatic glycation, glucose autoxidation, and alterations in polyol pathway activity with subsequent influences on the whole organism. In childhood, Type 1 diabetes prevails and is characterized by its autoimmune character with progressive destruction of beta cells and lack of insulin in genetically predisposed patients. Our study focused on diabetic children and their 1st degree relatives and confirmed increased oxidative stress in diabetic children as well as a similar tendency in their siblings. Following this, we carried out a one-year study comprising diabetic children supplemented with vitamins E and C. The vitamin treatment improved diabetes control and reduced markers of oxidative stress substantially when compared with non-supplemented diabetic children. As oxidative stress impairs not only lipids and proteins, but also DNA, we attempted to examine the level of DNA strand breaks as well as DNA repair processes using comet assay modifications. Though children with Type 1 diabetes demonstrated increased oxidative stress (lower SOD and GSH when compared with healthy children), their oxidative DNA damage (measured as DNA strand breaks) were not substantially altered compared with normals. On the other hand, their DNA repair capacity was significantly increased. This demonstrates a stimulated DNA repair process that is most certainly a response to the permanently elevated state of oxidative stress. Owing to the presented results, it is appropriate to ponder the increased influence of oxidative stress on children with Type 1 diabetes and to take into account this fact when considering their treatment.

Influence of insulin on glucose metabolism and energy expenditure in septic patients.

INTRODUCTION: It is recognized that administration of insulin with glucose decreases catabolic response in sepsis. The aim of the present study was to compare the effects of two levels of insulinaemia on glucose metabolism and energy expenditure in septic patients and volunteers. METHODS: Glucose uptake, oxidation and storage, and energy expenditure were measured, using indirect calorimetry, in 20 stable septic patients and 10 volunteers in a two-step hyperinsulinaemic (serum insulin levels 250 and 1250 mIU/l), euglycaemic (blood glucose concentration 5 mmol/l) clamp. Differences between steps of the clamp (from serum insulin 1250 to 250 mIU/l) for all parameters were calculated for each individual, and compared between septic patients and volunteers using the Wilcoxon nonpaired test. RESULTS: Differences in glucose uptake and storage were significantly less in septic patients. The differences in glucose oxidation between the groups were not statistically significant. Baseline energy expenditure was significantly higher in septic patients, and there was no significant increase in either step of the clamp in this group; when comparing the two groups, the differences between steps were significantly greater in volunteers. CONCLUSION: A hyperdynamic state of sepsis leads to a decrease in glucose uptake and storage in comparison with healthy volunteers. An increase in insulinaemia leads to an increase in all parameters of glucose metabolism, but the increases in glucose uptake and storage are significantly lower in septic patients. A high level of insulinaemia in sepsis increases glucose uptake and oxidation significantly, but not energy expenditure, in comparison with volunteers.