Changes in metabolic processes in humans during a 120-day antiorthostatic hypokinesia

The activities of organ- and tissue-specific diagnostically significant enzymes, including aspartate aminotransferase, alanine aminotransferase, γ-glutamyl transferase, alkaline phosphatase, total and prostatic acid phosphatase, glutamate dehydrogenase, choline esterase, amylase, lactate dehydrogenase, oxybutyrate dehydrogenase, and creatin phosphokinase (muscular and cardiac isoenzymes), as well as the concentrations of total cholesterol and the cholesterol of high- and low-density lipoproteins, the ratios of their concentrations, and the level of triglycerides, were studied during an experiment with 120-day antiorthostatic (?7°) hypokinesia (ANOH) in the blood of six volunteers (men, 21 to 36 years old). In addition, the indices of lipid peroxidation (LPO) and antioxidant activity were determined, including the concentrations of diene conjugates, malonic dialdehyde, Schiff bases and tocopherol, and the total antioxidant activity. It was found that a 120-day ANOH in this experiment did not result in the formation of deep metabolic shifts accompanied by unfavorable changes in organs and tissues. The changes in cholesterol metabolism during hypokinesia were expressed in the redistribution of cholesterol fractions with the dominance of atherogenic forms and a higher risk of atherogenesis. All of the observed metabolic changes were easily reversible and eliminated during the first month of the recovery period. No signs of a higher intensity of free-radical processes were observed during any of the examination periods due to activation of the antioxidant defense system.     

Glycemic index in diabetes

The Glycemic Index (GI) is a rating system that ranks carbohydrate-containing foods according to their postprandial blood glucose response relative to the same quantity of available carbohydrate of a standard such as white bread or glucose. The concept of GI was first introduced in the early 80's by Jenkins and coworkers. Since then, numerous trials have been undertaken, many indicating benefits of a low GI diet on glycemic control, as well as lipid profiles, insulin and C-peptide levels, inflammatory and thrombolytic factors, endothelial function and regulation of body weight. As a result, a low-GI diet may prevent or delay the vascular complications of diabetes. However, despite many studies supporting the benefits of the Glycemic Index as part of the treatment of diabetes mellitus, several areas of controversy have been raised in the literature and are addressed here. Clinicians treating diabetic patients should be aware of the potential benefits of low-GI foods in the prevention and treatment of diabetes and its complications.     

Impact of Prandial Plus Basal vs Basal Insulin on Glycemic Variability in Type 2 Diabetic Patients

ObjectiveTo determine whether metformin-treated patients with type 2 diabetes given an analogue mixture of basal and rapid-acting insulins (insulin lispro protamine suspension plus insulin lispro) would have less glycemic variability than patients given basal insulin glargine.MethodsTwo post hoc analyses were used to compare 7-point blood glucose profiles from 3 published studies comparing basal plus prandial premixed insulin lispro mixtures with insulin glargine in metformin-treated patients with type 2 diabetes. Glycemic variability indices used included standard deviation of mean daily blood glucose, coefficient of variation, M-value, mean amplitude of glycemic excursion, and J-index.ResultsPatients on the twice-daily insulin lispro mix 75/25 (75% insulin lispro protamine suspension/25% insulin lispro) plus metformin regimen had significantly lower standard deviation, M-value, and J-index than patients on the insulin glargine plus metformin regimen, but not lower coefficient of variation or mean amplitude of glycemic excursion. Patients on the 3 times daily insulin lispro mix 50/50 (50% insulin lispro protamine suspension/50% insulin lispro) plus metformin regimen had significantly lower values for all 5 indices than patients on the insulin glargine plus metformin regimen.ConclusionUse of basal plus prandial insulin lispro mixtures at 2 or 3 meals was associated with lower glycemic variability in metformin-treated patients with type 2 diabetes. (Endocr Pract. 2009;15:343-348)     

Accuracy of Continuous Glucose Monitoring Measurements in Normo-Glycemic Individuals

BackgroundThe validity of continuous glucose monitoring (CGM) is well established in diabetic patients. CGM is also increasingly used for research purposes in normo-glycemic individuals, but the CGM validity in such individuals is unknown. We studied the accuracy of CGM measurements in normo-glycemic individuals by comparing CGM-derived versus venous blood-derived glucose levels and measures of glycemia and glycemic variability.MethodsIn 34 healthy participants (mean age 65.7 years), glucose was simultaneously measured every 10 minutes, via both an Enlite^® CGM sensor, and in venous blood sampled over a 24-hour period. Validity of CGM-derived individual glucose measurements, calculated measures of glycemia over daytime (09:00h-23:00h) and nighttime (23:00h-09:00h), and calculated measures of glycemic variability (e.g. 24h standard deviation [SD]) were assessed by Pearson correlation coefficients, mean absolute relative difference (MARD) and paired t-tests.ResultsThe median correlation coefficient between CGM and venous glucose measurements per participant was 0.68 (interquartile range: 0.40–0.78), and the MARD was 17.6% (SD = 17%). Compared with venous sampling, the calculated measure of glycemia during daytime was 0.22 mmol/L higher when derived from CGM, but no difference was observed during nighttime. Most measures of glycemic variability were lower with CGM than with venous blood sampling (e.g., 24h SD: 1.07 with CGM and 1.26 with venous blood; p-value = 0.004).ConclusionIn normo-glycemic individuals, CGM-derived glucose measurements had good agreement with venous glucose levels. However, the measure of glycemia was higher during the day and most measures of glycemic variability were lower when derived from CGM.     

Glycemic Variation and Hypoglycemia in Patients with well-Controlled Type 1 Diabetes on a Multiple Daily Insulin Injection Program with use of Glargine and Ultralente as Basal Insulin

ObjectiveTo evaluate glycemic variation and hypo-glycemia in patients with well-controlled type 1 diabetes receiving multiple daily insulin injections during glargine and Ultralente use as basal insulin in a clinical trial.MethodsTwenty-two patients (12 men and 10 women, median age, 43 years), with a hemoglobin A1c level < 7.8%, were randomized in a crossover design to receive either insulin glargine or Ultralente insulin as basal insulin for 4 months each, with insulin aspart as prandial insulin. Continuous glucose monitoring and the Fear of Hypoglycemia questionnaire were used at baseline and at the end of each treatment period.ResultsWhereas the mean amplitude of glycemic excursions showed a correlation with the area under the curve of blood glucose < 3.89 mmol/L per day, the number of periods during the day with hypoglycemia was significantly correlated with the M value. Measures of glycemic variation did not differ significantly between glargine and Ultralente treatment. With use of glargine therapy, the SD of blood glucose levels showed a tendency to be lower and the SD of nocturnal blood glucose concentrations was significantly lower. Glucose concentrations were significantly lower during the 1 hour before and the 3 hours after lunch with use of Ultralente. The “Worry” scale on the Fear of Hypoglycemia questionnaire was less during Ultralente therapy and correlated with the number of times blood glucose concentrations were < 3.89 mmol/L daily.ConclusionMeasures of glycemic variability and hypoglycemia need to be studied more in clinical trials of glycemic control in patients with type 1 diabetes. Glycemic variability is less, particularly at night, with glargine as basal insulin. (Endocr Pract. 2007;13:244-250)     

Onboard medical support system for future of aerospace system flights

A project of an onboard medical support system (OMSS) for future aerospace system (ASS) flights is proposed. The following systems are suggested to be the main components of the OMSS: the basic system for automated estimation of blood redistribution (BSAEBR) in the body, protection and prophylactic means (PPM) for crew members, and the automated PPM control loop. The proposed BSAEBR includes four measurement channels for recording the basic physiological parameters (electrocardiogram, rheoencephalogram, venous-arterial pulsogram of neck blood vessels, and pulsogram of earlobe vessels), the changes in which are used to calculate, by means of a computer, the integrated parameter. The creation of lower body negative pressure (LBNP) was selected as a PPM. The automated PPM control loop individually selects the LBNP modes according to (1) the intensity of the body reactions and (2) individual characteristics of the physiological state. A working laboratory bench model of the OMSS has been manufactured and tested in two series of experiments simulating the conditions of a space flight. In the first series, 29 volunteers were exposed to ?10 deg antiorthostatic hypokinesia (ANOH) for 6–8 h, as well as ANOH + LBNP. In the second series, 26 volunteers were exposed to the combination of ANOH, Coriolis acceleration, and optokinetic stimulation every 5–7 h for three days. The results have demonstrated that the use of the given OMSS ensures, on average, a 17–32% improvement of the psychophysiological parameters of an operator, with the changes in the head circulatory parameters being more favorable.     

Incretion of Insulin by Pancreas and Its Inactivation in Women during Long-Term Head-down Tilt Bed Rest

An increase in insular activity in response to hyperglycemia when performing a glucose tolerance test (GTT) during normal physical activity in eight women volunteers was found to be associated with increased blood concentrations of insulin provided by an increase in secretion rate and a decrease in inactivation rate. After 81 days of stay in long-term –6° head-down tilt bed rest (bed rest), flattened glycemic curves (with low hyperglycemic lifting) observed during the GTT, what was indicated high insular activity. An increase in the insular activity was evidencing also by a smaller peak of the blood concentration of glucose from 5 min after intravenous nfusion of 20 mL of 40% glucose solution at 120 minute of the GTT. In bed rest on empty stomach no significant changes in the concentrations of insulin and C-peptide were observed. The dynamics of hormone during the GTT was showed that the appearance of flattened glycemic curves when performing GTT during bed rest was associated with more pronounced, than under the usual conditions, an increase in insulin concentration in response to hyperglycemia. An increase in the blood insulin concentration when performing GTT in bed rest was mainly provided by increased hormone secretion rate in the pancreas, but not by a decrease in its inactivation rate. If you use regular exercises for prevention of hypokinesia under conditions of bed rest, an increase in insulin concentration during GTT was mainly provided by a decrease in its inactivation rate and not by an increase in secretion rate.     

Metformin versus Insulin in the Management of Pre-Gestational Diabetes Mellitus in Pregnancy and Gestational Diabetes Mellitus at the Korle Bu Teaching Hospital: A Randomized Clinical Trial

ObjectiveTo determine if metformin monotherapy or metformin in combination with insulin is equally effective as insulin monotherapy at glycemic control in diabetes mellitus in pregnancy among Ghanaians.MethodsThis was a study involving 104 pregnant women with type 2 diabetes mellitus (T2DM) or gestational diabetes mellitus (GDM) at 20-30 weeks gestation. Participants were randomized into metformin and insulin treatment groups. Starting dose of metformin was 500 mg once a day and increased gradually over two (2) weeks, to meet glycemic targets. Insulin was added if targets could not be reached on metformin alone at maximum doses. Total daily dose of premixed insulin at initiation was calculated as 0.3 IU/kg body weight and titrated upwards to achieve glycemic control. Glycemic profile monitoring was done every two weeks.ResultsThe two hour post prandial blood glucose (2HPG) levels were significantly lower in the metformin group than the insulin group (p= 0.004).ConclusionThe findings of this study suggest that metformin monotherapy is effective in achieving glycemic targets in the management of diabetes in pregnancy. It is more effective than insulin in lowering the 2HPG level.

Trial Registration

Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12614000942651     

Role of reactions of large-capacity blood vessels in the pathogenesis of experimental cardiogenic shock]

Reaction of the capacitance vessels of the abdominal cavity and the pelvis was studied in dogs with the cardiotoxic myocardial necrosis complicated by the cardiogenic shock. The deposit of a significant volume of the circulating blood in the venous part of the vascular reservoir of the abdominal cavity and the pelvis was observed in the course of the first minutes of acute myocardial necrosis. A substantial role of reduction of the venous return to the heart in the pathogenesis of the hemodynamic disturbances accompanying the development of the cardiogenic shock is emphasized.     

Abdominal compartment syndrome in polytrauma

Authors inform about the group of 8 patients with abdominal compartment syndrome (ACS) occurred as a complication in large blunt injury of abdominal cavity. To the ACS diagnose, the measurement of intracystic pressure is used routinely, whose values correlate fully with values of intraabdominal pressure (IAP). In case of increasing values of IAP over 25 mm Hg with positive clinical signs of ACS, authors indicate decompression laparotomy with temporary closing of abdominal cavity by sterile plastic foil or Ethizip. This preventive temporary laparostomy is recommended also in serious injuries of abdominal cavity in patients with fatal haemorrhage, treated by the method of staged laparotomy with tamponade of abdominal cavity and with massive blood and volume resuscitation.     

Linking periodontal disease with obesity and blood glucose

It is of interest to evaluate the association of obesity and blood glucose level with periodontitis. Patients (150 with age range 26-68 years) were included based on WHO obesity criteria, undiagnosed for periodontitis, with Body Mass Index (BMI) ≥ 30 and systemically healthy. These patients underwent periodontal examination followed by blood analysis for lipid profile and blood sugar level. The periodontal status was determined using parameters such as Plaque index (PI), gingival index (GI), Probing depth (PPD) and Clinical attachment loss (CAL). 103 (68.7%) patients had >190 of triglyceride values. Data shows that periodontitis has no statistical significance with total cholesterol, HDL, LDL and moderate significance with VLDL, triglycerides. Glycemic control of the patients is assessed using postprandial blood sugar (PPBS) and Fasting Blood Sugar (FBS). Data shows that 129(86.6%) had FBS (mg/dl) <100 and 21 (14.0%) had FBS (mg/dl) >100. So the number of patients with FBS (mg/dl) < 100 were more i.e., 129 (86.6%). The PPBS values were in 136 (90.7%) had PPBS (mg/dl) <140 and only 14(9.3%) had PPBS (mg/dl) >140 group of patients were said have glucose intolerance. Thus, there is no change in lipid profile with established periodontitis in obese individuals. However, altered glycemic control is observed.     

Cardiovascular Function in Humans Using Thigh Cuffs during Seven Days of Simulated Microgravity

Data are summarized on changes in the human cardiovascular system associated with the use of cuffs during seven days of antiorthostatic hypokinesia simulating weightlessness. Eight subjects participated in two series of experiments, of which one was carried out with and the other (the control) without cuffs wrapped snugly around the upper third of the thighs. The parameters of the systemic hemodynamics, the cardiac function, and the hemodynamics of the cervicocephalic region and the lower limbs recorded under control and experimental conditions were analyzed. Without cuffs, changes in the hemodynamics during antiorthostatic hypokinesia were caused by displacement of body fluids in the cranial direction. The subjects responded favorably to the use of cuffs during antiorthostatic hypokinesia: most of their hemodynamic parameters remained at the baseline level, and signs of venous stasis in the cervicocephalic region were alleviated. Although the leg veins were distended in subjects wearing thigh cuffs during antiorthostatic hypokinesia, no pathological changes in the veins were detected during or after the experiment. Cuff usage during antiorthostatic hypokinesia lasting for seven days did not produce a cumulative effect on the cardiovascular system. These results justify the use of thigh cuffs in the initial period of adaptation to simulated or real weightlessness.     

Retrospective Study of Glycemic Control Following Transition from the Intensive Care Unit in A National Sample of U.S. Hospitals

Objective: Retrospective study to evaluate glycemic control outcomes after transition from the intensive care unit (ICU) to a non-ICU area in a national sample of U.S. hospitals.Methods: Mean point-of-care blood glucose (POC-BG) data were assessed overall and at 24 hours before and up to 72 hours after the transition. Comparisons in glucose variability (standard deviation of POC-BG data) were assessed. Impact on glycemic control was evaluated after accounting for hospital characteristics through logistic regression analysis.Results: POC-BG data were obtained from 576 hospitals. Overall mean (SD) POC-BG values in ICU versus non-ICU areas were 176 (24) versus 169 (21) mg/dL (P<.01). Mean (SD) of the ICU POC-BG data were 76 (16) versus 73 (16) mg/dL in the non-ICU data (P<.01). However, when comparing values of POC-BG in the last 24-hour ICU period with those from up to 72 hours posttransition, we found no differences, indicative of overall stable glycemic control and variability after transition. Any deterioration of glucose control following the transition was significantly associated with hospital size (P<.01): the smallest hospitals had the highest percentage of these cases. In addition, geographic region showed significant variability (P = .04), with hospitals in the Midwest and West having the highest proportion of cases in which glycemic control worsened following the transition.Conclusion: Glycemic control and variability did not change after transition from the ICU, but outcomes may depend on certain hospital characteristics. Inpatient glycemic control assessment should move beyond just cross-sectional studies and consider the impact of transitioning across inpatient areas. Other statistical approaches to studying this question should be evaluated.Abbreviations: DM = diabetes mellitus ICU = intensive care unit POC-BG = point-of-care blood glucose     

Energy metabolism in muscle tissue during hypokinesia of various durations

The state of energy metabolism in skeletal muscles and myocardium of albino rats was studied under long hypokinesia. It is established that on the 30th-70th days of hypokinesia endogenic fatty acids, whose oxidation promotes the uncoupling of oxidative phosphorylation and inhibition of the creatine phosphokinase reaction, are the main substrate of energy metabolism. In blood there occurs hyperlipemia and a decrease in the glucose content. A further immobilization results in predominance of succinate-dependent respiration, in blood there occurs a certain decrease in lipemia, normalization of the glucose level and an increase in the urea content.     

In vitro electron paramagnetic resonance characterization of free radicals: relevance to exercise-induced lipid peroxidation and implications of ascorbate prophylaxis

This study tested the hypothesis that exercise-induced oxidative stress is caused by free radical-mediated damage to polyunsaturated fatty acids (PUFA) which can be prevented following ascorbate prophylaxis. Hyperfine coupling constants (HCC) of alpha-phenyl-tert-butylnitrone (PBN)-adducts were measured via room temperature electron paramagnetic resonance (EPR) spectroscopy in the venous blood of 12 subjects at rest and following maximal exercise during a randomized double-blind placebo-controlled trial and compared to those observed following room-air incubation (2 h at 37 degrees C) of L-alpha-phosphatidycholine, linoleic acid, alpha-linolenic acid and arachidonic acid. All adducts exhibited similar HCC [a(N) 13.6 Gauss (G) and a beta(H) 1.8 G] with the exception of L-alpha-phosphatidycholine [a(N1)=13.4 G, a beta(H1)=1.6 G (37%) and a(N2)=14.9 G, a beta(H2)=0.3 G (63%)] consistent with the trapping of lipid-derived alkoxyl and oleate radicals, respectively. Ascorbate pre-treatment ablated radical formation in both systems. These findings identify circulating PUFA as a potential source of secondary radicals that are capable of initiating oxidative stress in the exercising human.     

Correction of venous congestion in abdominal organs under antiorthostatic conditions

The effect of a diuretic on the ultrasound pattern of venous congestion in abdominal organs in a healthy subject staying in an antiorthostatic position (AOP, 15°) for 12 h was studied. After furosemide administration, the circulating plasma volume (CPV), total water content of the body, and extracellular fluid volume decreased more than without the treatment. Overall hypohydration of the body prevented the dilation of hepatic veins typical of an AOP while not affecting noticeably the venous congestion in the portal vein system. In addition, the administration of the diuretic prevented the activation of bile secretion and an increased gastric juice secretion under antiorthostatic conditions. Thus, it was demonstrated that pharmacological hypohydration, by decreasing the CPV and the blood pressure in the inferior vena cava, unloads hepatic veins and prevents enhanced secretion in organs of the digestive system under the conditions of gravitational redistribution of body fluids.     

Impact of high-intensity interval training and sprint interval training on peripheral markers of glycemic control in metabolic syndrome and type 2 diabetes

Glycemic control is essential to reduce the risk of complications associated with metabolic syndrome (MetS) and type 2 diabetes (T2D). Aerobic and resistance exercise performed alone or in combination improve glycemic control in both conditions. However, perceived lack of time and commitment are considered principal barriers to performing exercise regularly. High intensity interval training (HIIT) and sprint interval training (SIT) can be performed in a fraction of the time required for continuous aerobic exercise. A substantial scientific evidence indicates that HIIT/SIT improve glycemic control to a similar or greater extent than aerobic exercise in populations without MetS or T2D. Likewise, growing evidence suggest that HIIT/SIT improve the glycemic control during MetS and T2D. The aim of this review is to discuss the effects of interval training protocols on peripheral markers of glucose metabolism in patients with MetS and T2D.     

Long-term antiorthostatic hypokinesia stimulates storage of osmotically inactive sodium in the human body

Changes in the water and sodium balances and in the states of the fluid compartments of the human body observed in experiments performed with healthy subjects exposed to long-term (120 days) antiorthostatic hypokinesia (ANOH) were analyzed. A hypothesis was suggested that the normal dietary consumption of sodium could be associated with the accumulation of osmotically inactive sodium in the body of a healthy person (independently of changes in the total water content). The results agree with the assumption that considerable amounts of osmotically inactive sodium may be stored in the human body. This hypothesis was confirmed by the inversion of the correlation between the cumulative sodium balance and the total water content of the body found both in the group-averaged data and in individual data. This nonsmotic sodium accumulation may take place not only during deviations from its normal consumption, but also during its regular dietary supply. Accumulation of sodium in these stores and its depletion are not associated with any significant changes in the volumes of body fluids. Infradian rhythmic changes in the sodium balance observed in some subjects exposed to the long-term ANOH, which were not caused by any periodic external influences, indicated the existence of a specific mechanism regulating the sodium content of the body. This mechanism must be significantly more inert and less precise than the fast regulation of the volume, osmolality, and ionic composition of extracellular fluids.     

Prolonged hypokinesia and its influence on the tissues and vessels of the extremities in experiments]

The work describes the results of complex investigation of the state of the supporting-motor apparatus of extremities of dogs subjected to six-month-long restriction of motor activity and the following reparation during a month. Intravital rentgenological, anatomical, histochemical and electron microscopic methods were used. It was shown that continuous hypokinesia resulted in substantial alterations of the vascular bed in the macro-micro-ultrastructural level, disturbance of metabolism, focal reconstruction of tissues of the extremities by the type of natural death of ultrastructural elements without a following reparation. A one-month term appeared to be insufficient for reparation of structural disorders. Special attention was given to reactions of the vascular system. Signs of blood transport via extracapillary pathways from the arterial bed into the venous bed were noted.     

The effect of portal hypertension on the structure of the pancreas in rats during the early periods of the experiment]

The model of Hiari disease obtained by a 50% constriction of the rat's posterior portal vein under the diaphragm was used in order to study the response of different structures of the pancreas on the 1st, 3, 5, 7, 15th days of experiment. The arterial vessels were found to have fairly active responses to venous congestion. The greatest load in sustaining microcirculation falls to large arteries, so they are more subjected to dystrophies, the severeness of which is proportional to the thickness of the vessels walls. In later terms of the experiment smaller arterial vessels are involved. Within a month blood circulation in the organ deteriorates and there appear small hemorrhages. The venous congestion results in a change of the structure and secretion of the acinous and insular cells of the pancreas.