Silvie Lacigova

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

IntroductionIt 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.MethodsGlucose 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.ResultsDifferences 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.ConclusionA 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.

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.

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 Scheffes 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.

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.

Analysis of continuous patient data from the Czech National Register of patients with type 1 and type 2 diabetes using insulin pump therapy

AIM Patient data from the Czech National Register of patients treated with Continuous Subcutaneous Insulin Infusion (CSII) were evaluated to compare treatment indication, efficacy and safety with specific regard to the type of diabetes (T1 vs. T2). METHODS Evaluation was done on complete data sets of at least 3 years from patients with either T1 diabetes (n=730, 93.1%) or T2 diabetes (n=54, 6.9%) between 1995 and 2006. RESULTS HbA(1c) decreased from 9.65 (+/-0.07) and 9.66 (+/-0.05) for T1 and T2 respectively to 8.24 (+/-0.07) for T1 and 8.52 (+/-0.27) for T2 after 1 year of treatment, 8.34 (+/-0.07) and 8.54 (+/-0.26) after 2 years and 8.44 (+/-0.07) and 8.71 (+/-0.25) after 3 years (adjusted mean values, +/-SEM). This reduction is significant for both diabetes types. Results gathered from the safety analysis revealed almost comparable results for both patient groups (rates of adverse events of 42.5 and 34.8 for T1 and T2, per 100 patients and year). CONCLUSION Both patient groups achieved substantial reduction of HbA(1c). Safety evaluation showed that fewer patients with T2 diabetes were affected by adverse events. According to that CSII treatment for patients with T2 diabetes is similarly effective with a slightly better safety profile.

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.

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.

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

ZusammenfassungEINLEITUNG: Ziel unserer Studie war es, den Einfluss einer Langzeitbehandlung mit Insulinpumpen (CSII) auf Parameter des metabolischen Syndroms bei insulinresistenten schlecht eingestellten Typ 2 Diabetikern zu untersuchen. PATIENTEN UND METHODEN: Es wurden 13 adipöse (BMI >30 kg/m2) Patienten (8 Frauen, 5 Männer; mittleres Alter 58,8 ± 9,06 Jahre), die mindestens 12 Monate mit hohen Insulindosen (>0,8IU/kg/24 h) behandelt worden waren, in die Studie aufgenommen. Bevor die CSII Behandlung begonnen wurde, wurden alle Patienten nochmals bezüglich der Behandlung des Diabetes mellitus und des metabolischen Syndroms geschult. Parameter der Blutzuckerkontrolle wurden erfasst. Zur Evaluierung der Insulinresistenz wurden hyperinsulinämische euglykämische Clamp-Untersuchungen durchgeführt. Die Untersuchungen wurden nach 6 Monaten der Therapie mit CSII wiederholt. Der Wilcoxon-Vorzeichen-Rang-Test sowie Spearmans Rangkorrelationskoeffizient wurden zur statistischen Berechnung verwendet. Die Ergebnisse werden als Mediane (1. und 3. Quartile) angegeben. ERGEBNISSE: Bezüglich der Langzeitkontrolle der Glykämie traten keine Änderung nach der Behandlung mit CSII auf: Das HbA1c lag vor der CSII bei 9,6% (8,95; 10,60), nach 6 Monaten bei 9,80 (9,50; 10,20) %, der BMI änderte sich von 33,0 (32,1; 34,2) auf 32,9 (32,0; 34,5) kg/m2 und die tägliche Gesamt-Insulindosis war ebenfalls praktisch gleich (69,0 (65,0; 94,0) vs. 68,0 (58,9; 92,4) IU/24 h). Allerdings wurde eine statistisch signifikante Besserung der Insulinresistenz: M Wert CSII: 2,55 (1,92; 3,15) vs. 3,32 (2,23; 4,49) mg/kg/min (p < 0,01) nach CSII, sowie folgender Risikofaktoren der Atherosklerose (Koagulation, endotheliale Dysfunktion) gefunden: Fibrinogen 3,44 (3,13; 3,86) vs. 3,24 (2,77; 3,38) g/l, Faktor VII 115 (101; 128) vs. 109 (93; 119) %, Faktor 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) festgestellt. SCHLUSSFOLGERUNGEN: Eine 6-monatige Insulinpumpentherapie führte bei übergewichtigen Typ 2 Diabetikern unabhängig von der Blutzuckereinstellung zu einem Abfall der Insulin-resistenz, und zu einer Besserung von Parametern des Fettstoffwechsels, der Koagulation des Bluts und der endothelialen Funktion.SummaryINTRODUCTION: 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 Spearmans 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.

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

ZusammenfassungHINTERGRUND UND ZIELE: Die kardiovaskuläre autonome Neuropathie (KAN) ist bei Patienten mit Typ 1 Diabetes mellitus (DM1) mit einer erhöhten Morbidität und Mortalität verbunden. Diese Komplikation kann über lange Zeit ohne Symptome einhergehen. Ziel dieser Studie war es die Prävalenz, den Schweregrad und mögliche Vorhersageparameter der asymptomatischen KAN zu erfassen. PATIENTEN UND METHODEN: 107 Patienten mit DM1 (52 Männer, 55 Frauen, Alter 39,8 ± 12,4 Jahre [18–72]; Dauer des DM1: 16,6 ± 9,5 Jahre [0,5–43], Alter bei Manifestation 23,5 ± 12,8 Jahre [1–54], BMI 25,1 ± 3,2 [1,9–33,91]) wurden untersucht. Das Vorliegen einer KAN wurde mit Hilfe von Standard-Reflex-Testen (Ewing Batterie) erhoben und die Patienten wurden entsprechend den Ergebnissen in drei Gruppen eingeteilt: Gruppe 0 ohne KAN, Gruppe I mit erstgradiger KAN und Gruppe 2 mit zweitgradiger KAN. Wir erhoben außerdem die mit KAN am häufigsten einhergehenden chronischen Komplikationen des DM1, Episoden schwerer Hypoglykämie, zeitliche Parameter des DM1 (Patientenalter, Dauer des DM1, Alter bei Manifestation) und außerdem DM1-spezifische Parameter wie glykosyliertes Hb, BMI, kardiovaskuläre Erkrankungen und Blutdruck. Die Vorhersagbarkeit einer KAN wurde entsprechend den erhobenen Korrelationen beurteilt. ERGEBNISSE: Nur 50 der 107 der Patienten (46%) zeigten keine KAN. Bei 38 Patienten (36%) fanden wir eine erstgradige , bei 19 (18%) eine zweitgradige KAN. KAN korrelierte mehr mit der Dauer des DM1 (p < 0,001), als mit dem Alter der Patienten (p < 0,05). Es bestand eine grenzwertig signifikante Korrelation (p = 0,053) mit dem glykosylierten Hb. Weiters haben wir eine signifikant positive Korrelation zwischen KAN und dem Auftreten von chronischen Komplikationen (periphere Neuropathie: p < 0,001), Retinopathie: p < 0,001, Nephropathie: erhöhtes Kreatinin: p < 0,03, Albuminurie: p < 0,01) gefunden. Obwohl der Blutdruck bei allen Patienten im Normalbreich (124,2/74,5 ± 11,5/7,8 mmHg) lag, wurde eine positive Korrelation mit der KAN (p < 0,05) bestätigt. Zu den akuten Komplikationen des DM1 bestand keine Korrelation. SCHLUSSFOLGERUNGEN: Unsere Studie zeigt, dass die asymptomatische KAN bei Patienten mit DM1 sehr häufig ist. Mit Hilfe von multifaktorieller logistischer Regression konnten wir zeigen, dass bei gleichzeitigem Vorliegen von Albuminurie, peripherer Neuopathie und erhöhtem systolischem Blutdruck eine hohe Wahrscheinlichkeit für das zusätzliche Vorhandensein einer KAN besteht.SummaryBACKGROUND 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, 1st degree CAN; Group II, 2nd 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 (HbA1c), 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 1st degree CAN in 38 patients (36%) and 2nd 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 HbA1c 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).