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Adverse biochemical and physiological effects of prostacyclin in experimental brain oedema.

BACKGROUND: Prostacyclin (PGI2) and its stable analogues are known to reduce capillary hydraulic permeability. This study explores the biochemical and physiological effects of i.v. infusion of low-dose PGI2 in an experimental model of vasogenic brain oedema. METHODS: Twenty-seven anaesthetized and mechanically ventilated piglets with brain oedema induced by intrathecal injection of lipopolysaccharide (LPS) were used. Five of the animals received a continuous infusion of PGI2 (1 ng kg(-1) min(-1)) i.v. Four microdialysis catheters were placed in the brain to measure interstitial concentrations of glucose, lactate, and glycerol. Mean arterial pressure (MAP), intracranial pressure (ICP) and temperature were monitored continuously. Low-dose infusion of PGI2 started 1 h before the LPS injection and was constant during the study period. RESULTS: Intracranial pressure increased significantly in animals treated with PGI2. The increase in ICP was associated with significant cerebral biochemical changes: decrease in glucose, increase in lactate, increase in lactate/glucose ratio and increase in glycerol. CONCLUSION: In LPS-induced brain oedema i.v. infusion of low-dose PGI2 caused a further increase in ICP and a perturbation of energy metabolism, indicating cerebral ischemia and degradation of cellular membranes.

Animals↗

Non-invasive glucose monitoring.

Several recent reports claim success in measuring blood glucose non-invasively in human subjects with near-infrared spectroscopy. A critical examination of these published results suggests more fundamental research is needed to verify the validity of these claims. In addition, progress continues in assessing the utility of near-infrared spectroscopy as a non-invasive probe for continuous bioreactor monitoring during fermentation processes. Recent work demonstrates that five critical fermentation components, including glucose, may be measured simultaneously.

Biosensing Techniques↗

Blood glucose monitoring devices.

Blood glucose monitoring can enable people to control their diabetes. People with diabetes will be motivated to continue monitoring only if it is seen to be effective. Patient education will significantly influence people's attitude to blood glucose monitoring, and must reflect individual needs and circumstances.

Blood Glucose Self-Monitoring↗

Insulin pump therapy in young children with type 1 diabetes.

Six 17- to 53-month-old diabetic children had marked metabolic instability characterized by chronic hyperglycemia and frequent or severe hypoglycemia with conventional management that included twice daily insulin injections, diet, and home blood glucose monitoring. Because of the metabolic instability, all were given continuous subcutaneous insulin infusions (CSII) via portable externally worn infusion pump. During 6 months of CSII, there was marked improvement: hemoglobin A1 decreased from 192% +/- 8% (SD) to 152% +/- 31% of the normal mean (P less than 0.02), and hypoglycemic episodes decreased in both severity and frequency. CSII was incorporated into the children's treatment with no appreciable adverse psychologic effects or interference with normal activities. CSII, under carefully controlled clinical conditions, may be of benefit in some preschool children with unacceptable metabolic control of diabetes mellitus.

Blood Glucose↗

Effect of intraperitoneal versus intravenous glucose administration on laser Doppler flow in murine FSaII tumors and normal skin.

The effects of i.p. versus i.v. glucose administration on laser Doppler flow (LDF) were studied in peripheral tissue areas of murine FSaII tumors implanted s.c. in the hind foot dorsum and in normal skin of conscious C3Hf/Sed mice. LDF was monitored prior to and continuously for 90 min following the administration of glucose, galactose, or mannitol at doses of 5 or 10 mg/g. Results showed that i.p. administration of hyperosmolar solutions was followed by a substantial, dose-dependent flow reduction which was indistinguishable for the various agents at equal osmotic load, and similar in tumor tissue and normal skin. Reductions in LDF are, therefore, primarily caused by hypovolemic hemoconcentration following i.p. administration of hyperosmolar sugar solutions. In contrast, i.v. administration of these solutions at 5 mg/g caused an initial flow increase (most probably due to a transient hypervolemic hemodilution), with a return to baseline readings within 5-10 min. At 10 mg/g i.v., a biphasic change in LDF occurred with an initial, temporary increase and a significant decline thereafter with no recovery within the observation period. This drop in LDF most probably is due to a decrease in cardiac output and an increase in viscous resistance to flow. Since comparable changes were observed with all agents and in both tissues investigated, it is concluded that the alterations in flow pattern following injection of hyperosmolar solutions are neither glucose nor tissue specific. Glucose- or tumor-specific effects, if present at all, must be of secondary importance in the animal model chosen.

Animals↗

Pulsatile secretion of growth hormone and insulin in relation to feeding in rats.

In unrestrained male Wistar rats chronically implanted with intracardiac catheters, blood samples were taken every 20 min throughout the 24 h of the diurnal cycle. Plasma concentrations of growth hormone (GH), insulin, and glucose were measured. The pattern of food intake was continuously monitored. The existence of 3-h pulsatile cycles of GH secretion was confirmed. In addition, short bursts of insulin secretion were observed in the middle of every second GH peak-to-peak interval. Food intake appeared to be enhanced during short periods that corresponded with GH release into the blood and was reduced during the GH peak-to-peak periods in which the bursts of insulin secretion were observed. From these observations this study draws a schematic relationship between the rhythmicity of the secretion of GH and insulin and the probability of occurrence of feeding. We speculate that the rhythmic endocrine activity may be causally related to feeding.

Animals↗

Intensive glycemic management in critically ill patients.

BACKGROUND: The effect of an intensive glycemic management protocol was assessed in a heterogeneous population of critically ill adult patients. METHODS: Patients representing 800 consecutive admissions following the institution of the protocol were compared with the 800 admissions immediately preceding the institution of the protocol in a 14-bed mixed medical-surgical intensive care unit (ICU). The protocol used intensive monitoring and treatment to maintain blood glucose values >140 mg/dl. Continuous intravenous insulin was used if glucose values were >200 mg/dl on two successive occasions. RESULTS: Mean glucose decreased from 152.3 mg/dl to 130.7 mg/dl (p < .001), marked by a 56.3% reduction in the percentage of glucose values > or =200 mg/dl, without a significant change in hypoglycemia. There were decreases in the development of new renal insufficiency (p = .034) and in the number of patients receiving transfusion of packed red blood cells (p = .035) during the protocol period. Hospital mortality decreased 29.3% (p = .002), and ICU length of stay decreased 10.8% (p = .011) after institution of the protocol. DISCUSSION: The 29.3% relative reduction in hospital mortality seen among the treatment patients following institution of the protocol probably exceeded the expectations of the initiative's champions. The culture of the ICU regarding glycemic control changed definitively. The protocol was extended to an intermediate care unit, resulting in improvement in glycemic control without an increase in hypoglycemia.

Blood Component Transfusion↗

Management of third-trimester diabetic pregnancies with the use of continuous subcutaneous insulin infusion therapy: a pilot study.

Six women with juvenile-onset diabetes were managed as outpatients during the third trimester of pregnancy with continuous subcutaneous insulin infusion therapy. Twenty-four-hour metabolic profiles for plasma glucose, beta-hydroxybutyrate, and triglycerides were monitored prior to, 1 week, 5 weeks, and 10 weeks after initiation of continuous subcutaneous insulin infusion therapy and compared with the metabolic profiles of 10 normal (nondiabetic) pregnant women. Near-normal metabolic profiles were achieved in these patients after 5 weeks of therapy in this pilot study. Patient motivation, compliance, and understanding of their illness were crucial in achieving the therapeutic goals of normoglycemia.

3-Hydroxybutyric Acid↗

Continuous glucose for treatment of patients with type 1 glycogen-storage disease: comparison of the effects of dextrose and uncooked cornstarch on biochemical variables.

Responses to uncooked cornstarch (UCS), dextrose (Dex), and a 3:1 mixture (UCS:Dex) were determined in seven children with type 1 glycogen-storage disease (GSD-1). UCS maintained blood glucose (BG) and serum insulin concentrations between 3.5 +/- 0.3 and 4.0 +/- 0.4 mmol/L (mean +/- SEM) and 50 +/- 7 and 79 +/- 22 pmol/L, respectively, in six of the seven patients for 4 h. Only four of seven patients completed the 4-h test after UCS:Dex (BG 2.9 +/- 0.3 mmol/L): After Dex, tests had to be stopped in all patients by 150 min after initiation (BG 2.7 +/- 0.4 mmol/L). Two methods of providing dietary glucose overnight, continuous intragastric glucose infusion (COG) and intermittent UCS at 2100 and 0200, were compared by monitoring metabolites and glucoregulatory hormones. The use of UCS in amounts equal to the calculated glucose production rate is an effective method of providing a continuous dietary source of glucose overnight to patients with GSD-1.

Adolescent↗

Type 1 diabetes.

Type 1 diabetes accounts for only about 5-10% of all cases of diabetes; however, its incidence continues to increase worldwide and it has serious short-term and long-term implications. The disorder has a strong genetic component, inherited mainly through the HLA complex, but the factors that trigger onset of clinical disease remain largely unknown. Management of type 1 diabetes is best undertaken in the context of a multidisciplinary health team and requires continuing attention to many aspects, including insulin administration, blood glucose monitoring, meal planning, and screening for comorbid conditions and diabetes-related complications. These complications consist of microvascular and macrovascular disease, which account for the major morbidity and mortality associated with type 1 diabetes. Newer treatment approaches have facilitated improved outcomes in terms of both glycaemic control and reduced risks for development of complications. Nonetheless, major challenges remain in the development of approaches to the prevention and management of type 1 diabetes and its complications.

Adolescent↗

Predictors of youth diabetes care behaviors and metabolic control: a structural equation modeling approach.

OBJECTIVE: To empirically test a biopsychosocial model of predictors of youth diabetes care behaviors and metabolic control. METHODS: A cross-sectional multisite study of youths (N = 222) with T1D (mean age = 12.6) used structural equation modeling to examine interrelations among predictors, with follow-up analyses of covariance (ANCOVAs). RESULTS: Youths' memory skills related to diabetes knowledge which, along with self-efficacy and age, was associated with greater youth responsibility that in turn predicted poorer self-care behaviors. Less frequent/briefer exercise and less frequent blood glucose monitoring/eating were found; the latter directly related to poorer metabolic control. Behavior problems also were associated directly with poorer metabolic control. A parsimonious model found memory directly related to blood glucose testing. CONCLUSIONS: Continued parental supervision of adolescents, along with monitoring diabetes knowledge and efficacy, may help optimize transfer of diabetes care from parents to youths. Behavior problems warrant immediate attention because of their direct and adverse relation to metabolic control.

Adolescent↗

Microdialysis in clinical practice: monitoring intraoral free flaps.

Clinical examination is still the gold standard of postoperative free flap monitoring, but with intraorally situated and/or buried flaps, it can be difficult or impossible. Microdialysis is a sampling technique which offers the possibility to monitor the metabolism of a flap continuously. Ischemia can be detected by monitoring the changes in glucose, lactate, and pyruvate levels in interstitial fluid of the specific tissue. Our aim was to use microdialysis to monitor the metabolism of free flaps used for reconstructions inside the oral cavity/oropharynx and to evaluate the reliability and usefulness of this new monitoring method.Twenty-five consecutive patients who underwent oral cavity/oropharynx cancer resection and immediate reconstruction with free flap were included in the study. A microdialysis catheter was placed into the subcutaneous adipose tissue of the flap in the end of the surgical procedure. Dialysate samples were taken on an hourly basis for 72 hours postoperatively. Routine clinical monitoring was carried out by experienced nursing staff. Clinical findings were recorded and later compared with microdialysis values. Two flaps out of 25 failed in spite of reoperations. In both problem cases, microdialysis indicated ischemia 1 to 2 hours before it became clinically evident. During flap ischemia, the lactate/pyruvate ratio increased, glucose concentrations reduced, whereas lactate level increased when compared with normal values. Our results indicate that microdialysis is safe for the patient and the flap. It can reliably detect flap ischemia at an early stage. This is especially useful in buried flaps when clinical monitoring is difficult. Microdialysis may also reduce the patient discomfort caused by repeated clinical examination of the flap.

Adult↗

Therapy, glycaemic control and complications in type 1 diabetic patients: results from a single centre cohort of 465 subjects.

We analysed the clinical characteristics, the degree of glycaemic control and the prevalence of complications in 465 type 1 diabetic adult patients (232 males), in view of current recommendations for metabolic and blood pressure control. Age and diabetes duration were 45 +/- 17 and 20 +/- 13 years respectively (mean +/- 1 SD). Daily insulin dose was 0.65 +/- 0.24 U/kg b.w. 73% of patients received > or = 3 injections/day, while 11% had continuous subcutaneous insulin infusion. All were practicing home blood glucose monitoring. Current HbA1c was 8.5% [7.7-9.3%] (median [percentiles 25-75]). There was no difference in HbA1c according to number of injections or CSII use. When patients were divided according to HbA1c quintiles, significantly lower prevalences of retinopathy and neuropathy were found in quintile 1 individuals. A mean of 53 severe hypoglycaemic episodes was reported per 100 patients/year, and they were more frequent in subjects exhibiting better glycaemic control. High blood pressure levels were found in 27% of subjects according to JNC-VI criteria. Fasting cholesterol (C), LDL-C, HDL-C and triglycerides were within normal range. However, according to current guidelines emphasizing on lower target thresholds, up to 27% of patients exhibited some degree of dyslipidaemia, in particular LDL-C higher than 3.3 mmol/l. In conclusion, in this large cohort of type 1 diabetic patients regularly attending a University Centre, overall glycaemic control remains above the satisfactory levels inferred from optimization studies. Although mean blood pressure and blood lipids were up to recently deemed adequate, a (too) high proportion of diabetic patients exhibited either hypertension and/or dyslipidaemia according to revised therapeutic goals cut-offs.

Adult↗

Comparison between continuous subcutaneous insulin infusion and multiple injections of insulin. A one-year prospective study.

Twenty insulin-dependent diabetic patients participated in a 1-yr prospective randomized cross-over study comparing multiple subcutaneous injections (MSI) and continuous subcutaneous insulin infusion (CSII) complemented by home blood glucose monitoring. While 4 patients dropped out early, 16 patients completed the study. Patients had severe insulin deficiency documented by absent C-peptide response to glucagon stimulation. A marked improvement in control was observed when mean blood glucose and glycosylated hemoglobin A1 were compared with conventional therapy. No significant differences in the degree of metabolic control achieved, as measured by mean fasting, preprandial, and postprandial capillary blood glucose (CBG), M values, glycosylated hemoglobin A1 concentration, cholesterol and triglyceride levels were seen between MSI and CSII in the sixteen patients who completed the study. However, individual comparisons showed that fasting CBG and M-values were lower under CSII than MSI in seven patients (P less than 0.05). In contrast, two patients exhibited lower M values under MSI than under CSII (P less than 0.01), while for the remaining seven patients the results were similar. After completion of the study, two patients went back to conventional insulin therapy, seven patients remained on the pump, and seven patients chose to stay on MSI. In conclusion, on a long-term basis, the two methods can produce comparable levels of blood glucose and glycosylated hemoglobin in ambulatory insulin-dependent diabetics.

Adolescent↗

Contribution of postprandial versus interprandial blood glucose to HbA1c in type 1 diabetes on physiologic intensive therapy with lispro insulin at mealtime.

OBJECTIVE: To quantitate the contribution of postprandial blood glucose, which improves with the short-acting insulin analog lispro [Lys(B28),Pro(B29)] in type 1 diabetes, to the overall 24-h blood glucose concentration and the long-term HbA1c concentration under conditions of different postabsorptive blood glucose. RESEARCH DESIGN AND METHODS: A total of 24 type 1 diabetic patients on long-term intensive therapy with premeal human regular insulin (Hum-R) and bedtime NPH were randomly assigned to a continuation of Hum-R (group 1, n = 8), lispro (group 2, n = 8), or lispro + NPH (in variable proportions) administered at mealtime (group 3, n = 8) for 3 months, NPH administered at bedtime was continued in all three groups. Data from home blood glucose monitoring were collected, and a 24-h plasma glucose and insulin profile was obtained during a 2-day hospital visit to calculate areas under the postprandial glucose curve (3.5 h after breakfast, 3.5 h after lunch, and 3.0 h after dinner for a total of 10.0 h) and the postabsorptive blood glucose curve (the remaining 14.0 h out of 24.0 h) (AUC). Eight nondiabetic subjects were also studied. RESULTS: The substitution of Hum-R with lispro (group 2) resulted in lower postprandial blood glucose, but greater postabsorptive blood glucose (P < 0.05 vs. group 1). The postprandial blood glucose AUC was lower (161 +/- 19 vs. 167 +/- 20 mg.100 ml-1.h-1), but the postabsorptive blood glucose AUC was greater (155 +/- 22 vs. 142 +/- 19 mg.100 ml-1.h-1) (P < 0.05). Therefore, the 24-h blood glucose AUC was no different (NS). Consequently, HbA1c was no different (NS). This occurred because in group 2, mealtime lispro resulted in normal prandial plasma insulin, but also resulted in lower interprandial concentration (P < 0.05 vs. group 1). When NPH was added to lispro (30% at breakfast, 40% at lunch, 10% at dinner) in group 3, postabsorptive plasma insulin was similar to group 1 (NS), in group 3, the postprandial blood glucose AUC (153 +/- 17 mg.100 ml-1.h-1) was lower and the postabsorptive blood glucose AUC was no different, as compared with group 1 (NS). Therefore, the 24-h blood glucose AUC was lower (147 +/- 17 vs. 155 +/- 21 and 158 +/- 20 mg.100 ml-1.h-1), and HbA1c was lower (6.41 +/- 0.12 vs. 6.84 +/- 0.2 and 6.96 +/- 0.2% (groups 3, 1, and 2 respectively, P < 0.05). Frequency of hypoglycemia was greater in group 2 (P < 0.05), but not in group 3 (NS) vs. group 1.

Adult↗

Perioperative management of the diabetic patient.

The diabetic patient has major surgery more frequently than nondiabetic patients. Although many of these operations are done on an elective basis, desirable perioperative control of blood glucose (ranging from 120-180 mg/dL) remains a therapeutic challenge. In planning the management, the type of diabetes, current treatment, the degree of recent control, the presence of complications, and the type of surgical procedure must all be considered. All insulin-dependent patients and many non-insulin-dependent patients need insulin therapy perioperatively. The variable stress associated with major procedures makes a flexible insulin regimen desirable. This can be provided using a continuous insulin (regular) infusion system and frequent bedside blood glucose monitoring.

Anesthesia↗

Management of diabetes mellitus during surgery.

Patients with diabetes mellitus are subjected to major operations more frequently than those without diabetes. Although many of these operations are done on an elective basis, the perioperative control of blood glucose levels--ranging from 6.7 to 13.3 mmol per liter (120 to 240 mg per dl)--remains a therapeutic challenge. In planning the management, the type of diabetes, current treatment, the degree of recent control, the presence of complications, and the type of surgical procedure must all be considered. All insulin-dependent patients and many non-insulin-dependent ones need insulin therapy perioperatively. The variable stress associated with major procedures such as coronary artery bypass and kidney transplantation makes a flexible insulin regimen desirable, which can be provided using a continuous insulin (regular) infusion system and frequent bedside blood glucose monitoring. Implementing such a regimen facilitates rapid control before an operation and a quick response to blood glucose changes during the procedure and provides a convenient and predictable method of control during the postoperative period.

Diabetes Mellitus↗