[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.

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.

Influence of physical activity on metabolic state within a 3-h interruption of continuous subcutaneous insulin infusion in patients with type 1 diabetes.

BACKGROUND: The aim of this study was to evaluate the influence of physical activity on blood glucose, insulinemia, and ketone bodies level during interruption of insulin delivery. METHODS: We enrolled 12 patients with type 1 diabetes (men with an average age of 33.4±8.66 years, body mass index of 25.7±3.75 mg/m(2), and glycated hemoglobin of 8.4±0.95%). The test was performed after overnight fasting at the usual insulin dosage. The delivery of insulin by the pump was stopped for 3 h, and blood samples were obtained in 30-min intervals for determination of blood glucose, insulinemia, ß-hydroxybutyrate, non-esterified fatty acids, and acid-base balance parameters. A test with (EXE) or without (CON) physical exercise (moderate aerobic exercise) was performed in each patient at random in the course of 2 weeks. Results are presented as median (first quartile; third quartile). RESULTS: Groups CON and EXE did not differ in blood levels of insulin during the test. Regarding time course of glycemia, we found differences only in min 270 for CON versus EXE of 15.2 (13.6; 16.7) and 13.9 (9.1;16.5) mmol/L, respectively (P=0.038). Concerning blood levels of ß-hydroxybutyrate, we found significant differences in min 180-300 of the test: CON of 419 (354; 541), 485 (344; 580), and 107 (63; 156) µmol/L versus EXE of 690 (631; 723), 703 (562; 871), and 241 (113; 507) µmol/L (P<0.01). Comparable results were found in values of total ketone bodies and free fatty acids. CONCLUSIONS: The influence of physical activity during a 3-h interruption of insulin pump treatment is evident, especially in the increase in plasma levels of non-esterified fatty acids and ketone bodies. Correction bolus leads to a rapid increase in insulinemia; however, normalization of blood glucose and ketone bodies is achieved within another 90 min.

Glycemic control improvement through treatment of depression using antidepressant drugs in patients with diabetes mellitus type 1.

OBJECTIVE: Depression is a common disorder among diabetic patients and affects negatively the treatment of their basic disease. The aim of the study was to assess, whether antidepressant medication could positively influence glycemic control of diabetes type 1 in depressive or anxious patients. METHODS: A six-month, double-blinded, randomized, placebo-controlled study was performed to investigate the reaction of type 1diabetic patients (n=21) to treatment of depression and anxiety symptoms using antidepressant drug sertraline. The patients were given sertraline (100 mg/day) or placebo. The evolution of mental change was assessed using Zung Self-Rating Depression Scale (SDS), Hamilton Anxiety Rating Scale (HAMA) and Hamilton Depression Rating Scale (HAMD) along with development of somatic parameters commonly assessed in diabetic patients, especially glycosylated hemoglobin, insulin dose and body weight. The level of active substance in serum of the patients was also measured. RESULTS: Mental state improved at the level of statistical significance of p<0.001 in both patients using antidepressant and placebo. From somatic parameters, body weight and systolic blood pressure increased statistically significantly also in both groups of patients. CONCLUSIONS: The mental state of most patients who successfully completed the study improved regardless of the fact if they were using antidepressant or placebo. No statistically significant connections between the mental and somatic changes were found. This finding points out to the placebo effect of the medication, to the importance of a contact with patients, but also to the need to concentrate on their mental state.

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.

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).