[Reactive hypoglycemia in chemical diabetes: continuous monitoring of blood sugar, insulinemia and growth hormone].
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OBJECTIVE: To assess the effectiveness of a pharmaceutical care model on the management of non-insulin-dependent diabetes mellitus (NIDDM) in urban African-American patients. DESIGN: Eligible patients were randomized to either a pharmacist intervention or control group and followed over a 4-month period. Patients in the intervention group received diabetes education, medication counseling, instructions on dietary regulation, exercise, and home blood glucose monitoring, and evaluation and adjustment of their hypoglycemic regimen. Patients in the control group continued to receive standard medical care provided by their physicians. SETTING: A university-affiliated internal medicine outpatient clinic. PARTICIPANTS: The study population consisted of urban African American patients with NIDDM currently attending the clinic. MAIN OUTCOME MEASURES: Primary outcome measures included fasting plasma glucose and glycated hemoglobin concentrations. Secondary outcome endpoints included blood pressure, serum creatinine, creatinine clearance, microalbumin to creatinine ratio, total cholesterol, triglycerides, high-density lipoprotein, and low density lipoprotein concentrations. Quality-of-life assessments were performed in both groups at baseline and at the end of the study. RESULTS: Thirty-nine patients (17 intervention, 22 control) completed the study. The intervention group consisted of 12 women and 5 men with a mean +/- SD age of 59 +/- 12 years, total body weight (TBW) of 93 +/- 22 kg, body mass index (BMI) of 34 +/- 7 kg/m2, and duration of NIDDM 6.8 +/- 6.5 years. The control group consisted of 15 women and 7 men with a mean age of 65 +/- 12 years, TBW of 88 +/- 19 kg, BMI of 33 + 7 kg/m2, and a duration of NIDDM of 6.2 +/- 4.8 y. Significant improvement in glycated hemoglobin (p = 0.003) and fasting plasma glucose (p =0.015) was achieved in the intervention group. No change in glycemia was observed in the control subjects. Statistically significant differences in the final glycated hemoglobin (p = 0.003) and fasting plasma glucose (p = 0.022) concentrations were noted between groups. No significant changes in blood pressure control, lipid profile, renal function parameters, weight, or quality-of-life measures were noted within or between groups. CONCLUSIONS: Our data demonstrate the effectiveness of pharmaceutical care in the reduction of hyperglycemia associated with NIDDM in a group of urban African-American patients.
Using isolated spinach (hybrid 424) chloroplasts deprived of their envelopes (reconstituted chloroplast system), the metabolism of glucose, glucose 1-phosphate, and glucose 6-phosphate via the oxidative pentose phosphate cycle was analyzed. The activity of oxidative pentose phosphate cycle was monitored by continuous sampling of the CO(2) released during the decarboxylation process of 6-phosphogluconate.The rate of CO(2) released in the dark from [C-1-(14)C]glucose 6-phosphate was 4 to 6 micromoles per milligram chlorophyll per hour. A CO(2) release from the C-6 position of [C-6-(14)C]glucose 6-phosphate was hardly measurable within 60 minutes of incubation. Glucose 1-phosphate was readily converted to glucose 6-phosphate without externally added glucose bisphosphate and was metabolized via the oxidative pentose phosphate cycle. The phosphorylation of glucose to glucose 6-phosphate was mediated by hexokinase present in the reconstituted system. This step was rate-limiting for the over-all reaction of the oxidative pentose phosphate cycle with glucose being the substrate (0.5 micromoles per milligram chlorophyll per hour). Addition of hexokinase increased the rate of CO(2) release to 5 micromoles per milligram chlorophyll per hour.The flow of carbon through the oxidative pentose phosphate cycle was greatly reduced upon the addition of NADPH and ATP. Whereas NADPH inhibited the metabolism of [C-1-(14)C]glucose 6-phosphate via the oxidative pentose phosphate cycle, ATP stimulated carbon flow into the 3-phosphoglycerate, dihydroxyacetone phosphate, and bisphosphates pools via the glycolytic pathway mediated by phosphofructokinase. This regulatory phenomenon could also be demonstrated with the reconstituted system undergoing a dark-light-dark transition. Data are presented indicating the conditions under which glucose 6-phosphate or glucose 1-phosphate are metabolized via the oxidative pentose phosphate cycle and the glycolytic pathway.
We have studied the characteristics of insulin therapy and home blood glucose monitoring of 1.200 diabetic patients (590 males, 610 females), mainly type I adults (age: 43 +/- 19 years, mean +/- 1 SD), attending a licensed diabetes center in Belgium which benefits from a National Health Service convention system for providing education and home blood glucose monitoring kits and disposables to diabetic subjects. 50% of these patients were treated with 2 daily insulin injections, while 22% were treated with 3 and 24% with 4 daily injections. 4% of the subjects were treated with a continuous subcutaneous insulin infusion. Patients treated with four daily injections were younger than those treated with other insulin schemes (p < 0.001). Home blood glucose monitoring strip consumption was 2.2 patient-1 day-1. The mean HbA1C level was 8.63 +/- 1.55% [8.54 +/- 1.46 in males and 8.72 +/- 1.62% in females (NS)]. In more than one third of the subjects treated with injections, HbA1C was lower than 8% HbA1C was also below 8% in 50% of patients using 1100-1200 strips year-1.
In vivo 31P nuclear magnetic resonance spectroscopy was used to monitor the time course of intracellular pH in cat cerebral cortex subjected to global cerebral ischemia under control and hyperglycemic pretreatment conditions. Transient (16 minutes) global cerebral ischemia was induced in 14 cats using an inflatable cervical cuff combined with systemic arterial hypotension. Six cats were pretreated with infusion of 1.5 g/kg glucose prior to ischemia. Relative concentrations of high-energy phosphate metabolites and intracellular pH were continuously monitored before, during, and for 2 hours after cerebral reperfusion. During ischemia, intracellular pH fell to the same level and followed a similar time course in both groups. However, during initial reperfusion in the hyperglycemic group, there was a severe further decline (p less than 0.003) in intracellular pH. We suggest that the increased neurologic deficit and mortality found in hyperglycemic animals subjected to cerebral ischemia may be attributed to this transient severe tissue acidosis.
Ultrafiltration (UF) is a filtrate selection method with a wide range of biomedical and clinical applications, including detoxification of blood in hemodialysis and peritoneal dialysis. New is, however, the use of UF as a convenient in vivo sampling method that, for example, has been used in diabetics. Ultrafiltration avoids complicated and time-consuming recovery calculations that are necessary when using in vivo microdialysis, as recoveries of low molecular weight molecules are near 100%. The subcutaneously or intravenously placed UF probes have been studied for off-line sample analysis and for continuous on-line monitoring, in a wide variety of species, including dogs, rats, pigs and humans. This review discusses the potential of in vivo UF as a continuous tissue sampling technique in clinical research areas, and in several major biomedical applications including glucose and lactate monitoring and drug kinetic studies.
Nine healthy volunteers with normal body weights were injected subcutaneously with 125I-labeled soluble human insulin (10 U) in one thigh and 133Xe in the contralateral thigh for the measurement of subcutaneous blood flow on 2 consecutive mornings. On one of the days, standardized massage of both injection sites was performed for 30 min starting 30 min after insulin injection. Serum insulin and plasma glucose were determined intermittently before, during, and after massage, and elimination of radioactivities was monitored continuously by external detectors. During massage, the first-order elimination rate constants of 125I increased approximately sixfold compared with the rise during control (0.19 +/- 0.04 to 0.88 +/- 0.15%/min during the last 15 min of the massage vs. 0.21 +/- 0.03 to 0.32 +/- 0.03%/min during control). Serum insulin increased from 13.8 +/- 1.8 mU/L before massage to a maximal value of 56.4 +/- 8.7 mU/L 10 min after massage (vs. 15.3 +/- 3.0 and 19.7 +/- 2.2 mU/L during control). Plasma glucose fell significantly faster on the massage day, from 10 min after massage onward. No significant alteration in the subcutaneous blood flow was found during or after massage. The results suggest that the pronounced enhancement of insulin absorption induced by massage of the injection site is mainly not blood flow mediated.
In our work we have tried to show that the only appropriate method of treatment for a type I diabetic is that which helps to maintain a near-normal compensation, which does not bother the patient and allows him a flexible way of life, and for which there is a sufficient technical equipment including the possibility of blood glucose monitoring. We have found out that all modes of insulin administration are effective, all can achieve a good compensation. Where the both conventional methods (basal-bolus regimen, multiple doses regimen) fail, we use the continuous subcutaneous insulin infusion (CSII). But we warn of undue optimism, and we recommend to use the CSII treatment only during hospitalization, when an exact blood glucose monitoring can be secured. An out-patient CSII treatment is--according to our experience--possible only when a consiliary supervision or a phone consultation of the patient with the attending team can be provided round the clock. We recommend therefore to use CSII routinely as a method of treatment only when the following preconditions are fulfilled an exact indication, education and motivation, technical equipment, and therapeutic supervision in outpatient treatment.
The enzyme thermistor measures the heat produced by the action of an immobilized enzyme on a substrate present in the sample. Its application in analysis of discrete samples, e.g., in clinical chemistry, is well documented, but it has not been used so far for continuous measurements. We decribe here the application of the enzyme thermistor for continuous monitoring and control of enzyme reactors. An enzyme thermistor filled with coimmobilized glucose oxidase and catalase was used to measure the amount of glucose in the outflow from a column reactor containing immobilized lactase acting on a lactose solution pumped through the reactor. The lactose conversion was kept on a constant level, irrespective of the actual enzymatic activity in the reactor, by regulating the flow through the reactor. The experiments were carried out with aqueous solutions of lactose as well as with whey from cow's milk.
This study examined the effects of serial reductions in energy and fluid intake on two simulated boxing performances separated by 2 days recovery. Eight amateur boxers (age: 23.6 +/- 3.2 years; height 175 +/- 5 cm; body mass [BM] 73.3 +/- 8.3 kg [Mean +/- SD]) performed two simulated boxing bouts (BB) under normal (N-trial) and restricted (R-trial) diets in a counterbalanced design over 5 days. The trials were separated by a 9-day period of normal dietary behavior (X-trial). BM was recorded on days 1, 3, and 5 of each trial. Simulated bouts of three, 3-min rounds with 1-min recovery were completed on days 3 (BB1) and 5 (BB2) of each 5-day trial. Punching force (N) was recorded from 8 sets of 7 punches by a purpose-built boxing ergometer. Heart rate (fC) was monitored continuously (PE3000 Polar Sports Tester, Kempele, Finland), and blood lactate (BLa) and glucose (BG) were determined 4-min post-performance (2300 StaPlus, YSI, Ohio). Energy and fluid intakes were significantly lower in the R-trial (p < .05). Body mass was maintained during the N-trial but fell 3% (p < .05) during the R-trial. There were no significant differences in end-of-bout fC or post-bout BG, but BLa was higher in the N- than the R-trial (p < .05). R-trial punching forces were 3.2% and 4.6% lower, respectively, compared to the corresponding N-trial bouts, but the differences did not reach statistical significance. These results suggest that energy and fluid restrictions in weight-governed sports do not always lead to a significant decrease in performance, but because of the small sample size and big variations in individual performances, these findings should be interpreted with care.
Reye's syndrome is difined as fatty degeneration of the viscera with encephalopathy. The signs are change in consciousness after recovery of a viral illness, vomiting, high fever, and progresseve deterioration of the level of consciousness. Signs of brain stem involvement quickly follow. The clinical findings are: mild elevations of serum transaminases (SGOT and SGPT), normal to slightly elevated bilirubin, abnormal blood-clotting functions, normal to low blood glucose, high blood ammonia, and normal cerebrospinal fluid which may be under increased pressure. Death is due to increased intracranial pressure. Therapy is used to stabilize these signs. It includes: infusion of hypertonic glucose followed by insulin, peritoneal dialysis, and exchange transfusion. Intracranial pressure was monitored continually to determine when therapy should be administered.
Technological changes in the clinical laboratory are usually driven by the goal of patient care optimization. In the last decade, the trend appeared to be directed at clinical laboratory decentralization. A new generation of analytical instruments, the biosensors, is redirecting laboratory testing closer to the patient, at the bedside, in the physician's office, and by the patient at home. These miniaturized biosensors are easy to operate, require small specimen size, and provide reliable results with rapid TAT. Thus far, bedside testing using biosensor technology appears to offer unique opportunities for earlier availability of clinical laboratory data, decision making, and more specific diagnosis, and faster and more frequent monitoring; these may translate into improved patient care and reduced hospital costs. It is likely that this trend will continue into the twenty-first century. Electrochemical sensors (e.g., for electrolytes, glucose, urea, and hematocrit) and pulse oximetry, having gained clinical acceptance, will probably be the leading instrumentation for bedside testing. Continuous monitoring either by near-infrared sensing technology or with an implantable sensor is valuable in the care of the critically ill patient. Acceptance for clinical use will depend on complete data integration and a favorable cost-benefit ratio.
OBJECTIVE: Excessive intestinal gas can be involved in postprandial abdominal symptom generation, but whether the small bowel influences intestinal gas dynamics, depending on the ingested meal, remains to be demonstrated. We compare the intestinal response to a proximal and distal small intestinal gas challenge during different duodenal nutrient components. MATERIAL AND METHODS: We randomly studied 32 healthy subjects, twice, on different days with a gas mixture infused at 12 ml/min either directly into the proximal jejunum or into the ileum; during duodenal lipids, amino acids, glucose, at 1 kcal/min each, or saline (n=8 for each group). Gas evacuation was monitored continuously and abdominal perception and girth changes were assessed. RESULTS: In response to the jejunal gas challenge, duodenal lipids delayed intestinal gas clearance more potently than amino acids (733+/-26 ml and 541+/-108 ml final gas retention; p<0.001), but when gas was directly infused into the ileum the retained volumes were much smaller (271+/-78 ml and 96+/-51 ml; p<0.001). During duodenal glucose, intestinal gas clearance following jejunal or ileal gas infusion was not significantly influenced. Abdominal perception in response to the jejunal and ileal gas challenge only increased slightly during duodenal lipids (2.0+/-0.3 score and 2.3+/-0.6 score; p<0.05 versus control). CONCLUSION: Postprandial intestinal gas clearance is hampered by duodenal lipids and amino acids but not by glucose. Specific inhibitory effects are more pronounced when gas is infused into the jejunum, which underlines the importance of the small intestine in postprandial gas retention.
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Prior to the advent of nuclear magnetic resonance (NMR) spectroscopy, human glucose metabolism was studied through tracer and tissue biopsy methodology. NMR spectroscopy now provides a noninvasive means to monitor metabolic flux and intracellular metabolite concentrations continuously. 13C NMR spectroscopy has shown that muscle glycogen synthesis accounts for the majority of insulin-stimulated muscle glucose uptake in normal volunteers and that defects in this process are chiefly responsible for insulin resistance in type 1 and type 2 diabetes mellitus, as well as in other insulin resistant states (obesity, insulin-resistant offspring of type 2 diabetic parents, elevation of plasma FFA concentrations). Furthermore, using 31P NMR spectroscopy to measure intracellular glucose-6-phosphate, it has been shown that defects in insulin-stimulated glucose transport/phosphorylation activity are primarily responsible for the insulin resistance in these states.
A method to monitor extracellular glucose in freely moving rats, based on intracerebral microdialysis coupled to an enzyme reactor is described. The dialysate is continuously mixed with a solution containing the enzymes hexokinase and glucose-6-phosphate dehydrogenase, and the fluorescence of NADPH formed enables the on-line registration of extracellular glucose. The method is applied to monitor changes in extracellular brain glucose during the infusion of glucose, electrically induced seizure, immobilization stress, and repetitive hypoxia. After glucose loading or after seizure, hippocampus dialysate glucose concentration was increased transiently. During immobilization, there was a short-lasting decrease and, thereafter, an increase in the extracellular hippocampus glucose. During repetitive hypoxia in rats with a unilaterally occluded carotid artery, the content of glucose of striatal dialysates followed closely changes in blood pressure. These results illustrate the usefulness of the method in studying changes in brain glucose concentrations under pathological and physiological conditions.
Ten diabetic pregnant women were studied during the thirty-sixth to fortieth weeks of gestation to determine whether maternal blood glucose levels influence fetal activity. Maternal blood glucose level was monitored and controlled utilizing an artificial pancreas (Biostator) while fetal activity and heart rate were quantitated by continuous ultrasonic and electrocardiac fetal monitoring. Fetal activity was confirmed independently by a maternal controlled event marker. There was no difference in fetal movement with heart rate accelerations between periods of maternal normoglycemia defined as blood glucose levels between 60 and 140 mg/dl (3.3-7.8 mMol/L) and periods of maternal hyperglycemia (blood glucose level greater than 140 mg/dl or 7.8 mMol/L). Maternal blood glucose levels of less than 60 mg/dl (3.3 mMol/L) were accompanied by a significant (p less than 0.001) increase in fetal activity (19.9 +/- 3.9 SEM episodes of fetal movement per 20-minute observation period versus 8.0 +/- 5 episodes during periods of hyperglycemia). These observations indicate that hyperglycemia does not stimulate fetal activity and that the obstetric practice of beverages with high glucose content administered during antepartum testing (in an attempt to increase fetal movement) should be reevaluated in diabetic women.
This study was undertaken to determine the effect on renal function of continuous glucose therapy from early childhood. Twenty-three subjects, median age 13.9 years, range 5.9-26.9 years, with type I glycogen storage disease (GSDI) treated with continuous glucose therapy from a median age of 1.3 years, range 0.1-12.9 years, had 24 h monitoring of metabolites and glucoregulatory hormones on their home feeding regimen to assess metabolic control at approximately yearly intervals for a median duration of 8 years. During the most recent evaluation, 24 h urinary albumin excretion rate (AER), kidney size, and creatinine clearance (Ccr) were measured. CCr was unrelated to age and was increased (> 2.33 ml/s per 1.73 m2) in 10/23 (43%). Mean kidney length exceeded 2SD in 16/23 (70%). AER was normal in all five subjects < 10 years and was increased (> 10 micrograms/min) in 8/23 (35%), all > 10 years of age. AER was significantly greater in subject of similar age who started continuous glucose therapy later in childhood and was significantly higher in subjects with lower mean 24 h plasma glucose concentrations and higher mean 24 h blood lactate concentrations, both at the time of assessment of renal function and over the preceding 5 years. GSDI subjects with persistently elevated concentrations of blood lactate, serum lipids and uric acid are at increased risk of nephropathy. Optimal dietary therapy instituted early in life may delay, prevent, or slow the progression of renal disease.