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Biomedical subjects

W Clarke

Publications and source records attributed to W Clarke.

At least 19 recordsLinked to original sources

Accelerated escape from GH autonegative feedback in midpuberty in males: evidence for time-delimited GH-induced somatostatinergic outflow in adolescent boys.

A single injected pulse of GH inhibits the time-delayed secretion of GH in the adult by way of central mechanisms that drive somatostatin and repress GHRH outflow. The marked amplification of spontaneous GH pulse amplitude in puberty poses an autoregulatory paradox. We postulated that this disparity might reflect unique relief of GH-induced autonegative feedback during this window of development. The present study contrasts GH autonegative feedback in: 1) normal prepubertal boys (PP) (n = 6; Tanner genital stage I, chronologically aged 8 yr, 9 months to 10 yr, 1 month; median bone age 8.5 yr); 2) longitudinally identified midpubertal boys (MP) (n = 6; Tanner genital stages III/IV, aged 12 yr, 6 months to 15 yr, 6 months; median bone age 15 yr); and 3) healthy young men (YM) (n = 6, aged 18-24 yr; bone age >18 yr). Subjects each underwent four randomly ordered tandem peptide infusions on separate mornings while fasting: i.e. 1) saline/saline infused iv bolus at 0830 h and 1030 h; 2) saline/GHRH (0.3 microg/kg i.v. bolus) at the foregoing times; 3) recombinant human (rh) GH (3 microg/kg as a 6-min square-wave i.v. pulse)/saline; and 4) rhGH and GHRH. To monitor GH autofeedback effects, blood samples were obtained every 10 min for 5.5 h beginning at 0800 h (30 min before GH or saline infusion). Serum GH concentrations were quantitated by ultrasensitive chemiluminometry (threshold 0.005 microg/liter). On the day of successive saline/saline infusion, MP boys maintained higher serum concentrations of: 1) GH ( microg/liter), 2.2 +/- 0.25, compared with PP (0.61 +/- 0.10) or YM (0.88 +/- 0.36) (P = 0.011); 2) IGF-I ( micro g/liter), 493 +/- 49 vs. PP (134 +/- 16) and YM (242 +/- 22) (P < 0.001); 3) T (ng/dl), 524 +/- 58 vs. PP (<20) (P < 0.001); and 4) E2 (pg/ml),19 +/- 3 vs. PP (< 10) (P = 0.030) (mean +/- SEM). Consecutive saline/GHRH infusion elicited comparable peak (absolute maximal) serum GH concentrations (micrograms per liter) in the three study groups, i.e. 18 +/- 5.0 (PP), 9.6 +/- 1.7 (MP), and 14 +/- 5.3 (YM) (each P < 0.01 vs. saline; P = NS cohort effect). Injection of rhGH attenuated subsequent GHRH-stimulated peak serum GH concentrations (micrograms per liter) to 7.8 +/- 1.9 (PP), 5.8 +/- 1.2 (MP), and 4.8 +/- 1.1 (YM) (each P < 0.01 vs. saline; P = NS pubertal effect). GH autofeedback reduced non-GHRH-stimulated (basal) serum GH concentrations by 0.74 +/- 0.28 (PP), 5.7 +/- 1.7 (MP) and 1.4 +/- 0.27 (YM) fold, compared with saline (P = 0.016 for MP vs. PP or YM). In addition to greater fractional autoinhibition, MP boys exhibited markedly accentuated postnadir escape (4.6-fold steeper slope) of suppressed GH concentrations (P < 0.001 vs. PP or YM). Linear regression analysis of data from all 18 subjects revealed that the fasting IGF-I concentration negatively predicted fold-autoinhibition of GHRH-stimulated peak GH release (r = -0.847, P = 0.006) and positively forecast fold-autoinhibition of basal GH release (r = +0.869, P < 0.001). In contrast, the kinetics of rhGH did not differ among the three study cohorts. In summary, boys in midpuberty manifest equivalent responsiveness to exogenous GHRH-stimulated GH secretion; heightened susceptibility to rhGH-induced fractional inhibition of endogenous secretagogue-driven GH release, compared with the prepubertal or adult male; and accelerated recovery of GH output after acute autonegative feedback. This novel tripartite mechanism could engender recurrent high-amplitude GH secretory bursts that mark sex hormone-dependent activation of the human somatotropic axis.

Adolescent↗

Analysis of free drug fractions by ultrafast immunoaffinity chromatography.

A chromatographic method was developed for measuring the nonbound (or free) fraction of drugs by using millisecond-scale extractions on small immunoaffinity columns. The design of this system was developed by considering the dissociation rates of (R)- and (S)-warfarin from the binding protein human serum albumin (HSA) and by performing computer simulations of the immunoaffinity extraction of these drugs. The final system was tested by using it to measure the free fractions of (R)- or (S)-warfarin in samples with known concentrations of these agents and HSA. The free warfarin fraction was extracted in 180 ms by a 2.1-mm-i.d. sandwich microcolumn that contained a 1.1-mm layer of an anti-warfarin antibody support. The nonretained peaks from this immunoaffinity column were passed through a series internal surface reversed-phase columns and a fluorescence detector for the analysis of any protein-bound warfarin that remained in the sample. The experimental results were found to have good agreement with those predicted from the known equilibrium constants for the binding of (R)- and (S)-warfarin with HSA. This approach can be modified for other analytes by changing the types of antibodies that are used in the immunoaffinity column and by using an appropriate detector for the nonretained drug fraction.

Chromatography, Affinity↗

Development of sandwich HPLC microcolumns for analyte adsorption on the millisecond time scale.

A new class of columns is reported that uses only microgram quantities of active support and that provides for the retention of biological compounds and other analytes on the millisecond time scale. This was accomplished by packing standard HPLC supports into layers as small as 60 microm in length and using only 90 microg of support material. This provided columns with effective residence times in the millisecond time range when routine HPLC flow rates and pressures were used. The retention of analytes by such columns was examined under both adsorption- and diffusion-limited conditions. The RPLC adsorption of hemoglobin (a system with diffusion-limited retention) was found to give 95% binding in as little as 4 ms. The adsorption of fluorescein by an anti-fluorescein antibody column (an adsorption-limited system) gave 95% retention in 100-120 ms. One application examined for these columns was their use in a chromatographic-based competitive binding immunoassay. This used bovine serum albumin (BSA) as the model analyte, and fluorescein-labeled BSA was used for detection. The resulting approach had a contact time of 180 ms between the sample and an anti-BSA immunoaffinity microcolumn and provided a signal within 5-25 s after sample injection. The columns developed in this work should also be useful in other situations that involve a small amount of a stationary phase or that require short column residence times.

Animals↗

Sustained effects of gene-activated matrices after CNS injury.

We show that when gene-activated matrices (GAM) are placed between the proximal and distal stumps of severed rat optic nerves, DNA is retained within the GAM, promoting sustained transgene expression in the optic nerve, in the GAM itself, and, more importantly, in axotomized retinal ganglion cells (RGC). Plasmids that encode basic fibroblast growth factor (FGF2), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT3) promote sustained survival of RGC for over 3 months after the initial injury. These findings suggest that immobilized DNA implanted into a CNS lesion will be delivered by axon terminal uptake and retrograde transport to axotomized neurons. GAM may therefore be a useful agent for promoting sustained neuron survival and axon regeneration. Whether further optimization of the matrices, plasmids, promoters, and genes present in the GAM will promote even more survival or, alternatively, axon regeneration remains to be determined.

Animals↗

Blood glucose awareness training (BGAT-2): long-term benefits.

OBJECTIVE: Blood glucose awareness training (BGAT) has been shown to improve awareness of blood glucose (BG) fluctuations among adults with type 1 diabetes. This study investigates the long-term (12-month) benefits of BGAT-2. RESEARCH DESIGN AND METHODS: A total of 73 adults with type 1 diabetes participated in a 6-month repeated baseline design with a 12-month follow-up. At 6 months and 1 month before BGAT-2 and at 1,6, and 12 months after BGAT-2, subjects used a handheld computer for 50 trials and completed psychological tests. Throughout assessment, subjects completed diaries, recording occurrences of diabetic ketoacidosis, severe hypoglycemia, and motor vehicle violations During follow-up, 50% of the subjects received booster training. RESULTS: During the first and last halves of both the baseline period and the follow-up period, dependent variables were generally stable. However, from baseline to follow-up, BGAT-2 led to 1) improved detection of hypoglycemia and hyperglycemia; 2) improved judgment regarding when to lower high BG, raise low BG, and not drive while hypoglycemic; 3) reduction in occurrence of diabetic ketoacidosis, severe hypoglycemia, and motor vehicle violations; and 4) improvement in terms of worry about hypoglycemia, quality of life, and diabetes knowledge. Reduction in severe hypoglycemia was not associated with a worsening of metabolic control (HbA1). The presence or absence of booster training did not differentially affect these benefits. CONCLUSION: BGAT has sustained broad-ranging benefits, independent of booster intervention.

Anxiety↗

Bedside glucose testing. Applications in the home and hospital.

Point-of-care testing is an increasingly popular means of delivering diagnostic testing closer to the site of patient care. Although point-of-care glucose testing devices have been around for over a decade, concerns about the quality of the results still plague the industry. Changes in federal and state laws that treat point-of-care testing as an extension of the core laboratory promise to improve the quality of testing. The most challenging aspect of quality testing is selection of the appropriate method (core laboratory versus point-of-care test) for the optimal patient outcome.

Blood Glucose↗

Driving mishaps and hypoglycaemia: risk and prevention.

Driving is a complex, multi-task activity that can be affected by cognitive impairment resulting from episodes of severe hypoglycaemia. Intensive insulin therapy increases the likelihood of severe hypoglycaemia but there have been few studies examining effects on driving skills. A survey carried out recently indicated that patients with type 1 diabetes had twice the incidence of driving accidents than their non-diabetic spouses or patients with type 2 diabetes. The motor accidents were associated with more frequent low blood glucose while driving and less frequent self-monitoring. In driving simulation tests it was found that driving has an intrinsic metabolic demand that can contribute to hypoglycaemia. Driving performance began to deteriorate at around 3.6 mmol/l but drivers frequently did not recognise and failed to treat the hypoglycaemia. Those who did self-treat had more driving relevant symptoms and less neuroglycopenia quantified by EEG alpha-theta differences. Patients should be recommended not to begin driving if blood glucose is below 4.5 mmol/l and should not continue to drive if they suspect that blood glucose has fallen below 4 mmol/l while driving. If hypoglycaemia is suspected patients should immediately pull off the road, measure blood glucose if possible, treat themselves as necessary and not resume driving until glucose and cognitive-motor function return to normal. The problems of driving and hypoglycaemia should be discussed with patients with diabetes and behavioural interventions instigated. To this end, Blood Glucose Awareness Training (BGAT) and Hypoglycaemia Anticipation, Awareness and Treatment Training (HAATT) have been developed and shown to markedly reduce incidence of driving mishaps.

Accidents, Traffic↗

Antibody immobilization to high-performance liquid chromatography supports. Characterization of maximum loading capacity for intact immunoglobulin G and Fab fragments.

This study examined various factors that affect the maximum amount of intact immunoglobulin G (IgG) or Fab fragments that can be covalently immobilized to silica and other HPLC-grade supports for use in immunoaffinity chromatography or immunoextractions. Factors that were considered included the amount of surface area available for immobilization, the pore size of the support, the type of immobilization method and the nature of the support matrix. The main factor in determining the extent of immobilization was found to be the relationship between the support's surface area and the ability of the IgG or Fab fragments to reach this surface. Access to the support surface was a function of the size of the protein being immobilized and the support porosity, with maximum immobilization being obtained with supports having pore sizes of approximately 300 A for intact IgG and 100 A for Fab fragments. Some differences in the maximum level of immobilization were noted between different coupling methods. Supports like Poros and Emphaze gave similar results to those seen with HPLC-grade silica when a comparison was made between materials with comparable pore sizes. Many of the trends observed in this work for IgG and Fab fragments should apply to other proteins that are to be immobilized to HPLC supports.

Antibodies↗

Microbial quality of water in rural communities of Trinidad.

A cross-sectional study was conducted in four rural communities of northeastern Trinidad to determine the microbial quality of water supply to households and that quality's relationship to source and storage device. Of the 167 household water samples tested, total coliforms were detected in 132 of the samples (79.0%), fecal coliforms in 102 (61.1%), and E. coli in 111 (66.5%). There were significant differences among the towns in the proportion of the samples contaminated with coliforms (P < 0.001) and E. coli (P < 0.001). Of 253 strains of E. coli studied, 4 (1.6%) were mucoid, 9 (3.6%) were hemolytic, and 37 (14.6%) were nonsorbitol fermenters. Of 69 isolates of E. coli tested, 10 (14.5%) were verocytotoxigenic. Twenty-eight (14.0%) of 200 E. coli isolates tested belonged to enteropathogenic serogroups. Standpipe, the most common water source, was utilized by 57 (34.1%) of the 167 households. Treated water (pipeborne in homes, standpipes, or truckborne) was supplied to 119 households (71.3%), while 48 households (28.7%) used water from untreated sources (rain, river/stream, or well) as their primary water supply. The type of household storage device was associated with coliform contamination. Water stored in drums, barrels, or buckets was more likely to harbor fecal coliforms (74.2% of samples) than was water stored in tanks (53.3% of samples), even after controlling for water source (P = 0.04). Compared with water from other sources, water piped into homes was significantly less likely to be contaminated with total coliforms (56.9% versus 88.8%, P < 0.001) and fecal coliforms (41.2% versus 69.8%, P < 0.01), even when the type of storage device was taken into account. However, fecal contamination was not associated with whether the water came from a treated or untreated source. We concluded that the drinking water in rural communities in Trinidad was grossly unfit for human consumption, due both to contamination of various water sources and during household water storage.

Humans↗

Development of a theoretical model for chromatographic-based competitive binding immunoassays with simultaneous injection of sample and label.

This study examined the theory and behavior of an HPLC-based chromatographic competitive binding immunoassay with the simultaneous injection of sample and a labeled analyte analogue. Equations based on nonlinear chromatographic theory were derived to describe the calibration curve for this assay in a system with adsorption-limited kinetics and homogeneous binding sites. These equations related the assay response (B/Bo) to the column's binding capacity, the moles of injected analyte or labeled analogue, and the flow rate/adsorption kinetics of the system. There was good agreement between the predicted theoretical response and experimental data obtained for the binding of human serum albumin (HSA) to an immobilized anti-HSA antibody column. This theory was also successful in describing the changes that occurred in the calibration curve when the flow rate or amount of labeled analogue applied to the column was varied. A comparison was made between the results of this study and previous theoretical work that examined the behavior of a related, sequential injection competitive binding method. On the basis of the results reported in this work, several general guidelines were developed for the design and optimization of simultaneous injection methods for use in such areas as clinical testing, pharmaceutical analysis, and environmental monitoring.

Adsorption↗

Prevalence of elevated blood leads and exposure to lead in construction trades in Iowa and Illinois.

BACKGROUND: Despite lowering of the permissible exposure level for lead in construction from 200 to 50 microg/m3 in 1993, excessive lead exposure continues to be a problem. Relatively little data are available from the Midwestern U.S. on the environmental lead concentrations generated during various construction activities and the potential for worker exposure. This study characterized the prevalence of blood lead concentrations in high-risk construction trades in Iowa/Illinois, and identified risk factors for occupational exposure to lead in these construction workers. METHODS: A sample of 459 workers was selected from the total population of all union members from trade groups of painters, plumbers/pipefitters, ironworkers, laborers, and electricians. Participants completed an interviewer-administered questionnaire obtaining information on demographics, symptoms, occupational history, work practices, personal protective equipment, and training. Venous blood samples were collected from each participant and analyzed for blood lead (using atomic absorption spectroscopy) and free erythrocyte protoporphyrin levels. RESULTS: Blood lead levels (BLLs) of construction workers ranged from 0.1 to 50 microg/dL. Geometric mean blood lead concentrations by trade group were: laborers (7.6 microg/dL, n = 80); painters (5.9 microg/dL, n = 83); ironworkers (5.2 microg/dL, n = 87); plumbers (4.4 microg/dL, n = 82); electricians (2.4 microg/dL, n = 91). Blood lead levels for painters and laborers were significantly higher than other trade groups, and levels for electricians were significantly lower (p < 0. 01). Participants reported working primarily on commercial and industrial projects including new construction, renovation, and demolition. There were significant differences between the types of projects performed by different trade groups with laborers performing more highway/bridge renovation (p < 0.01), and plumbers reporting more residential remodeling (p = 0.05), repair of water lines containing lead (p = 0.04), or work on lead joints (p < 0.01). In addition to trade, elevated blood lead levels were associated with the type of construction project (especially bridge renovation and residential remodeling) and activities that include welding, cutting, rivet busting. The age of the home in which the worker lived, and hobbies such as casting/smelting lead for bullets or sinkers, were also important risk factors. Compliance with OSHA's Construction Lead Standard, and implementation of good occupational health and safety practices in general, was poor. CONCLUSIONS: Blood lead levels of 459 construction workers differed by the type of trade, type of project and specific job activity owing to differences in the inherent exposure potential of each task. Although the numbers of workers performing lead abatement projects were small, the trend for lower BLL in this group provides evidence that training, implementation of engineering controls, and proper use of personal protective equipment such as respirators is effective in controlling lead poisoning.

Adult↗

Clinical comparability of albuterol delivered by the breath-actuated inhaler (Spiros) and albuterol by MDI in patients with asthma.

STUDY OBJECTIVE: This study compares the efficacy and safety of one and two actuations of albuterol sulfate powder delivered via a breath-actuated, effort-assisted, investigational inhaler (Spiros, Dura Pharmaceuticals, Inc) and albuterol delivered via a conventional propellant-driven metered dose inhaler (Ventolin, Glaxo, Inc). DESIGN: Randomized, double-blind, placebo-controlled, 5-way crossover study. PARTICIPANTS: Sixty patients with mild-to-moderate asthma (FEV1 59% predicted) were enrolled and 44 completed the study. MEASUREMENTS AND RESULTS: FEV1 values over 6 hours were analyzed by ANCOVA and the Finney relative potency model. The relative potency of the inhalers (albuterol MDI: albuterol DPI) was 1.132 (90% CI, 0.680 to 2.252) indicating 1.132 actuations of albuterol MDI provided the same bronchodilation as one actuation of albuterol DPI. ANCOVA analyses further indicated that there were no significant differences between the two delivery systems with respect to FEV1, FVC, FEF25-75%, or PEF. Both inhalers had similar effects on serum potassium levels, QTc interval, blood pressure, and heart rate. CONCLUSIONS: In patients with mild-to-moderate asthma in this study, the albuterol DPI was determined to be therapeutically comparable to albuterol MDI in the delivery of one and two actuations of albuterol.

Administration, Inhalation↗

Role of the toxic neutrophil count in the early diagnosis of Kawasaki disease.

OBJECTIVE: To determine whether the toxic neutrophil count (TNC), defined as the sum of the number of peripheral blood neutrophils with vacuoles plus the number with toxic granulations per 100 neutrophils examined, can be used as an aid to early diagnosis of Kawasaki disease (KD). METHODS: Prospective evaluation at a tertiary care pediatric hospital of 56 acutely febrile children with at least one other clinical criterion for KD. Clinical characteristics and TNC were compared for 3 groups of patients: those with (1) definite KD, (2) probable KD, and (3) unlikely KD. The sensitivity and specificity of the TNC at various cutoff points was determined. RESULTS: We evaluated 56 patients (Group 1, N=27; Group 2, N=4; Group 3, N=25). Mean TNC (TNC/mm3) were higher in the patients with definite KD compared to patients with unlikely KD (38 vs 24; p=0.037). At a TNC cutoff of > or =70, the test had a specificity of 100%, but a sensitivity of only 18%. The likelihood ratio (the number of times more likely this TNC result is to be found in KD versus non-KD subjects) was 8.89. At a cutoff of > or =10, the test had a high sensitivity of 92% and specificity of 38%. CONCLUSION: No laboratory test replaced the need for careful clinical evaluation in cases of suspected KD. The TNC may be a useful adjunct to the clinical assessment of children with KD, particularly at the extremes of measurement.

Child↗

Stochastic model of self-regulation decision making exemplified by decisions concerning hypoglycemia.

The following sequence-internal condition --> symptom perception --> appraisal --> decision-models various symptom-based self-regulation processes. A formal mathematical model describes the first three steps by continuous variables and the decisions at the fourth step by binary variables. The stochastic transitions between the sequential steps are quantified by transition probabilities. The model is illustrated by blood glucose level estimation and detection and treatment of hypoglycemia in 78 patients with insulin-dependent diabetes mellitus. These patients made 50 to 70 data collection trials over 3 to 4 weeks recording perceived symptoms, cognitive-motor performance, subjective estimates of blood glucose, decisions about treatment of hypoglycemia, and driving. A statistical estimation of the model's parameters demonstrates the utility of this approach for understanding the awareness, detection, and treatment of hypoglycemia as a process of symptom-based decision making.

Adult↗

Assessment of risk for severe hypoglycemia among adults with IDDM: validation of the low blood glucose index.

OBJECTIVE: To evaluate the clinical/research utility of the low blood glucose index (LBGI), a measure of the risk of severe hypoglycemia (SH), based on self-monitoring of blood glucose (SMBG). RESEARCH DESIGN AND METHODS: There were 96 adults with IDDM (mean age 35+/-8 years, duration of diabetes 16+/-10 years, HbA1 8.6+/-1.8%), 43 of whom had a recent history of SH (53 did not), who used memory meters for 135+/-53 SMBG readings over a month, and then for the next 6 months recorded occurrence of SH. The SMBG data were mathematically transformed, and an LBGI was computed for each patient. RESULTS: The two patient groups did not differ with respect to HbA1, insulin units per day, average blood glucose (BG) and BG variability. Patients with history of SH demonstrated a higher LBGI (P < 0.0005) and a trend to be older with longer diabetes duration. Analysis of odds for future SH classified patients into low- (LBGI <2.5), moderate- (LBGI 2.5-5), and high- (LBGI >5) risk groups. Over the following 6 months low-, moderate-, and high-risk patients reported 0.4, 2.3, and 5.2 SH episodes, respectively (P = 0.001). The frequency of future SH was predicted by the LBGI and history of SH (R2 = 40%), while HbA1, age, duration of diabetes, and BG variability were not significant predictors. CONCLUSIONS: LBGI provides an accurate assessment of risk of SH. In the traditional relationship history of SH-to-future SH, LBGI may be the missing link that reflects present risk. Because it is based on SMBG records automatically stored by many reflectance meters, the LBGI is an effective and clinically useful on-line indicator for SH risk.

Adult↗

The psychosocial impact of severe hypoglycemic episodes on spouses of patients with IDDM.

OBJECTIVE: No previous studies have examined the psychosocial impact of severe hypoglycemic episodes in IDDM patients on their spouses. This study compared spouses of IDDM patients with and without a history of recent severe hypoglycemia (SH) using traditional measures of psychosocial status and marital conflict, as well as diabetes-specific measures. RESEARCH DESIGN AND METHODS: A total of 61 nondiabetic spouses (23 wives and 38 husbands) of IDDM patients participated in the study. Spouses completed a battery of traditional psychometric measures (depression, anxiety, marital conflict) and diabetes-specific measures (fear of hypoglycemia, marital conflict over diabetes, sleep disturbance caused by hypoglycemia). Scores of spouses of IDDM patients with and without a recent history of SH were compared with t tests. RESULTS: Spouses of IDDM patients with and without a recent history of SH showed no differences on traditional psychometric measures of depression, anxiety, and marital conflict. However, spouses of patients with a recent history of SH showed significantly more fear of hypoglycemia, marital conflict about diabetes management, and sleep disturbances caused by hypoglycemia. Exploratory analyses of variance (ANOVAs) found no differences on psychometric measures between wives and husbands, with the exception that husbands of SH patients reported more sleep disturbance. Nondiabetic spouses, on average, showed greater fear of hypoglycemia than their diabetic partners. CONCLUSIONS: Although SH in IDDM patients can have a significant impact on the psychosocial status of their spouses, in this study the negative impact was restricted to areas of life that are directly related to diabetes and its management. Thus, SH per se is not necessarily associated with significant increases in spousal anxiety, depression, or marital conflict, but may be associated with types of diabetes-specific psychosocial distress that are not easily identified by traditional psychometric measures.

Adult↗

Symmetrization of the blood glucose measurement scale and its applications.

OBJECTIVE: To introduce a data transformation that enhances the power of blood glucose data analyses. RESEARCH DESIGN AND METHODS: In the standard blood glucose scale, hypoglycemia (blood glucose, < 3.9 mmol/l) and hyperglycemia (blood glucose, > 10 mmol/l) have very different ranges, and euglycemia is not central in the entire blood glucose range (1.1-33.3 mmol/l). Consequently, the scale is not symmetric and its clinical center (blood glucose, 6-7 mmol/l) is distant from its numerical center (blood glucose, 17 mmol/l). As a result, when blood glucose readings are analyzed, the assumptions of many parametric statistics are routinely violated. We propose a logarithmic data transformation that matches the clinical and numerical center of the blood glucose scale, thus making the transformed data symmetric. RESULTS: The transformation normalized 203 out of 205 data samples containing 13,584 blood glucose readings of 127 type 1 diabetic individuals. An example illustrates that the mean and standard deviation based on transformed, rather than on raw, data better described subject's blood glucose distribution. Based on transformed data: 1) the low blood glucose index predicted the occurrence of severe hypoglycemia, while the raw blood glucose data (and glycosylated hemoglobin levels) did not; 2) the high blood glucose index correlated with the subjects' glycosylated hemoglobin (r = 0.63, P < 0.001); and 3) the low plus high blood glucose index was more sensitive than the raw data to a treatment (blood glucose awareness training) designed to reduce the range of blood glucose fluctuations. CONCLUSIONS: Using symmetrized, instead of raw, blood glucose data strengthens the existing data analysis procedures and allows for the development of new statistical techniques. It is proposed that raw blood glucose data should be routinely transformed to a symmetric distribution before using parametric statistics.

Adult↗