[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.

[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.

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.

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.

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).