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Biomedical subjects

L A Gonder-Frederick

Publications and source records attributed to L A Gonder-Frederick.

At least 19 recordsLinked to original sources

Self-treatment of hypoglycemia while driving.

OBJECTIVE: While it is clear that progressive diabetic hypoglycemia leads to neuroglycopenia, which impairs driving, it is not clear what contributes to patients' detection and subsequent self-correction of hypoglycemia/driving impairments. Drivers with Type 1 Diabetes Mellitus (T1DM) who did and did not engage in self-treatment during experimental hypoglycemia driving are compared physiologically and psychologically. METHOD: 38 drivers with T1DM drove a sophisticated driving simulator during euglycemia and progressive hypoglycemia. Subjects were continually monitored for driving performance, EEG activity and whether they self-treated with a glucose drink. Every 5 min measures were taken of blood glucose (BG) and epinephrine levels, perceived neurogenic and neuroglycopenic symptoms and driving ability. For the four weeks prior to this hospital study, subjects participated in a field study. Using a hand-held computer just prior to routine self-measurements of BG, subjects rated neurogenic and neuroglycopenic symptoms and made judgements about BG level and ability to drive as they did in the hospital. RESULTS: Drivers who did and did not self-treat did not differ in terms of their pre-hospital exposure to hypoglycemia, their depth and rate of BG fall during experimental testing, or their epinephrine response to hypoglycemia. Subjects who self-treated detected more neurogenic and neuroglycopenic symptoms than those who did not self-treat. They also experienced less EEG defined neuroglycopenia during the progressive hypoglycemic drive as compared to those who did not self-treat. Perceived need to self-treat and EEG parameters correctly classified 88% of those who did treat from those who did not self-treat. Further, subjects who self-treated were more aware of hypoglycemia and when not to drive while hypoglycemic in the field study. CONCLUSION: There is a narrow window between a patient's detection of hypoglycemic symptoms and the need to self-treat, and neuroglycopenia, which impairs self-treatment. Consequently, drivers with T1DM should be vigilant for signs of hypoglycemia and driving impairment (e.g. trembling, uncoordination, visual difficulties) and encouraged to treat themselves immediately when they suspect hypoglycemia while driving.

Accidents, Traffic↗

Progressive hypoglycemia's impact on driving simulation performance. Occurrence, awareness and correction.

OBJECTIVE: Progressive hypoglycemia leads to cognitive-motor and driving impairments. This study evaluated the blood glucose (BG) levels at which driving was impaired, impairment was detected, and corrective action was taken by subjects, along with the mechanisms underlying these three issues. RESEARCH DESIGN AND METHODS: There were 37 adults with type 1 diabetes who drove a simulator during continuous euglycemia and progressive hypoglycemia. During testing, driving performance, EEG, and corrective behaviors (drinking a soda or discontinuing driving) were continually monitored, and BG, symptom perception, and judgement concerning impairment were assessed every 5 min. Mean +/- SD euglycemia performance was used to quantify z scores for performance in three hypoglycemic ranges (4.0-3.4, 3.3-2.8, and <2.8 mmol/l). RESULTS: During all three hypoglycemic BG ranges, driving was significantly impaired, and subjects were aware of their impaired driving. However, corrective actions did not occur until BG was <2.8 mmol/l. Driving impairment was related to increased neurogenic symptoms and increased theta-wave activity. Awareness of impaired driving was associated with neuroglycopenic symptoms. increased beta-wave activity, and awareness of hypoglycemia. High beta and low theta activity and awareness of both hypoglycemia and the need to treat low BG influenced corrective behavior. CONCLUSIONS: Driving performance is significantly disrupted at relatively mild hypoglycemia, yet subjects demonstrated a hesitation to take corrective action. The longer treatment is delayed, the greater the neuroglycopenia (increased theta), which precludes corrective behaviors. Patients should treat themselves while driving as soon as low BG and/or impaired driving is suspected and should not begin driving when their BG is in the 5.0-4.0 mmol/l range without prophylactic treatment.

Adult↗

Hypoglycemia and the decision to drive a motor vehicle by persons with diabetes.

CONTEXT: Laboratory studies have shown impairments in driving performance among subjects with type 1 diabetes mellitus when their blood glucose (BG) level is between 2.6 and 3.6 mmol/L (47-65 mg/dL). However, to our knowledge, no data exist examining subjects' decisions to drive at various BG levels during their daily routine. OBJECTIVE: To examine type 1 diabetic subjects' decisions to drive during their daily routine based on perception of BG levels compared with actual measured BG levels. DESIGN AND SETTING: Two separate groups of patients were recruited 2 years apart from 4 academic medical centers. PARTICIPANTS: All subjects were adults with type 1 diabetes who were drivers and who performed at least 2 BG tests per day. Group 1 (initial) subjects (n = 65) had a mean (SD) age of 38.6 (8.9) years with a mean (SD) diabetes duration of 20.5 (10.6) years, were taking 38.8 (16.8) U/d of insulin, and had a mean (SD) glycosylated hemoglobin (HbA1) level of 10.0% (1.9%). Group 2 (replication) subjects (n = 93) were 35.8 (8.0) years old with a mean diabetes duration of 17.0 (10.6) years, were taking 40.0 (15.5) U/d of insulin, and had a mean (SD) HbA1 level of 8.5% (1.6%). Each subject used a handheld computer to record data on symptoms, cognitive function, insulin dosage, food, activity, estimated and actual BG levels, and whether he/she would drive. Data were entered 3 to 6 times per day for a total of 50 to 70 collections per subject during a 3- to 4-week period. MAIN OUTCOME MEASURES: Decisions to drive when subjects estimated their BG level to be less than 2.2 mmol/L (40 mg/dL), 2.2 to 2.8 mmol/L (40-50 mg/dL), 2.8 to 3.3 mmol/L (50-60 mg/dL), 3.3 to 3.9 mmol/L (60-70 mg/dL), 3.9 to 10 mmol/L (70-180 mg/dL), and more than 10 mmol/L (>180 mg/dL), and driving decisions when actual BG levels were in these ranges. RESULTS: Subjects stated they would drive 43% to 44% of the time when they estimated their BG level to be 3.3 to 3.9 mmol/L (60-70 mg/dL), and 38% to 47% of the time when their actual BG level was less than 2.2 mmol/L (40 mg/dL). Logistic regression analysis demonstrated that number of autonomic symptoms, degree of impairment on cognitive function tests, and BG level estimate predicted 76% to 80% of decisions to drive (P<.01 for all). Approximately 50% of subjects in each group decided to drive at least 50% of the time when their BG level was less than 3.9 mmol/L (70 mg/dL). CONCLUSIONS: Our data suggest that persons with type 1 diabetes may not judge correctly when their BG level is too low to permit safe driving and may consider driving with a low BG level even when they are aware of the low level. Health care professionals should counsel their patients about the risk of driving with hypoglycemia and the importance of measuring BG level before driving.

Adult↗

Biopsychobehavioral model of severe hypoglycemia. II. Understanding the risk of severe hypoglycemia.

OBJECTIVE: To evaluate the clinical/research utility of the biopsycho-behavioral model of severe hypoglycemia in differentiating patients with and without a history of severe hypoglycemia and in predicting occurrence of future severe hypoglycemia. RESEARCH DESIGN AND METHODS: A total of 93 adults with type 1 diabetes (mean age 35.8 years, duration of diabetes 16 +/- 10 years, HbA1 8.6 +/- 1.8%), 42 of whom had a recent history of recurrent severe hypoglycemia (SH) and 51 who did not (NoSH), used a handheld computer for 70 trials during 1 month recording cognitive-motor functioning, symptoms, blood glucose (BG) estimates, judgments concerning self-treatment of BG, actual BG readings, and actual treatment of low BG. For the next 6 months, patients recorded occurrence of severe hypoglycemia. RESULTS: SH patients demonstrated significantly more frequent and extreme low BG readings (low BG index), greater cognitive-motor impairments during hypoglycemia, fewer perceived symptoms of hypoglycemia, and poorer detection of hypoglycemia. SH patients were also less likely to treat their hypoglycemia with glucose and more likely to treat with general foods. Low BG index, magnitude of hypoglycemia-impaired ability to do mental subtraction, and awareness of neuroglycopenia, neurogenic symptoms, and hypoglycemia correlated separately with number of SH episodes in the subsequent 6 months. However, only low BG index, hypoglycemia-impaired ability to do mental subtraction, and awareness of hypoglycemia entered into a regression model predicting future severe hypoglycemia (R2 = 0.25, P < 0.001). CONCLUSIONS: Patients with a history of severe hypoglycemia differed on five of the seven steps of the biopsychobehavioral model of severe hypoglycemia. Helping patients with a recent history of severe hypoglycemia to reduce the frequency of their low-BG events, become more sensitive to early signs of neuroglycopenia and neurogenic symptoms, better recognize occurrence of low BG, and use fast-acting glucose more frequently in the treatment of low BG, may reduce occurrence of future severe hypoglycemia.

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↗

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↗

Reduced awareness of hypoglycemia in adults with IDDM. A prospective study of hypoglycemic frequency and associated symptoms.

OBJECTIVE: To prospectively evaluate the frequency and severity of hypoglycemic episodes in IDDM subjects who declare themselves to have reduced awareness of hypoglycemia, to validate their self-designations in their natural environment, and to determine objectively the presence or absence of autonomic and neuroglycopenic symptoms associated with their low blood glucose (BG) levels. RESEARCH DESIGN AND METHODS: A total of 78 insulin-dependent diabetes mellitus (IDDM) subjects (mean age 38.3 +/- 9.2 years; duration of diabetes 19.3 +/- 10.4 years) completed two sets of assessments separated by 6 months. The assessments included reports of frequency and severity of low BG, symptoms associated with low BG, and a BG symptom/estimation trial using a hand-held computer (HHC). Diaries of hypoglycemic episodes were kept for the intervening 6 months. HbA1 levels were determined at each assessment. RESULTS: Of the subjects, 39 declared themselves as having reduced awareness of hypoglycemia (reduced-awareness subjects). There were no differences between these reduced-awareness subjects and aware subjects with regard to age, sex, disease duration, insulin dose, or HbA1. During the HHC trials, reduced-awareness subjects were significantly less accurate in detecting BG < 3.9 mmol/l (33.2 +/- 47 vs. 47.6 +/- 50% detection, P = 0.001) and had significantly fewer autonomic (0.41 +/- 0.82 vs. 1.08 +/- 1.22, P = 0.006, reduced-awareness vs. aware) and neuroglycopenic (0.44 +/- 0.85 vs. 1.18 +/- 1.32, P = 0.004, reduced-awareness vs. aware) symptoms per subject. Prospective diary records revealed that reduced-awareness subjects experienced more moderate (351 vs. 238, P = 0.026) and severe (50 vs. 17, P = 0.0062) hypoglycemic events. The second assessment results were similar to the first and verified the reliability of the data. CONCLUSIONS: IDDM subjects who believe they have reduced awareness of hypoglycemia are generally correct. They have a history of more moderate and severe hypoglycemia, are less accurate at detecting BG < 3.9 mmol/l, and prospectively experience more moderate and severe hypoglycemia than do aware subjects. Neither disease duration nor level of glucose control explains their reduced awareness of hypoglycemia. Reduced-awareness individuals may benefit from interventions designed to teach them to recognize all of their potential early warning symptoms.

Adult↗

Frequency of severe hypoglycemia in insulin-dependent diabetes mellitus can be predicted from self-monitoring blood glucose data.

Severe hypoglycemia is associated with insulin-dependent diabetes mellitus and may occur more frequently as metabolic control approaches normal. The goal of this study was to determine whether the frequency of severe hypoglycemia could be predicted by the following predictor variables: 1) frequency and degree of low blood glucose (BG) readings, 2) degree of BG variability during routine self-monitoring blood glucose (SMBG) readings, and 3) level of glycemic control measured by glycosylated hemoglobin-A1 (HbA1). Seventy-eight insulin-dependent diabetes mellitus subjects from 3 different sites had their glycosylated HbA1 assayed and then performed 50 SMBG recordings during the next 2-3 weeks. Over the following 6 months, subjects recorded their severe hypoglycemic episodes (stupor or unconsciousness). There was no difference in the number of severe hypoglycemic episodes between subjects in good vs. poor metabolic control. A higher frequency of severe hypoglycemia during the subsequent 6 months was predicted by frequent and extreme low SMBG readings and variability in day to day SMBG readings. Regression analysis indicated that 44% of the variance in severe hypoglycemic episodes could be accounted for by initial measures of BG variance and the extent of low BG readings. Patients who recorded variable and frequent very low BG readings during routine SMBG were at higher risk for subsequent severe hypoglycemia. Individuals who had lower glycosylated Hb levels were not at higher risk of severe hypoglycemic episodes.

Adult↗

Individual differences in neurobehavioral disruption during mild and moderate hypoglycemia in adults with IDDM.

This study investigated the neurobehavioral effects of mild and moderate hypoglycemia in adults with insulin-dependent diabetes mellitus (IDDM). On 2 consecutive days, 26 subjects were tested in a counterbalanced, randomized, single-blind, crossover design. On the experimental day, subjects performed tests at 6.4, 3.6, and 2.6 mmol/l and again after glycemic recovery to 6.3 mmol/l. On the control day, subjects performed tests four times at euglycemia. Three months after testing, 15 subjects repeated the experimental day protocol. Results demonstrated that both mild and moderate hypoglycemia significantly disrupted performance. However, performance deterioration varied substantially across individual subjects. Men exhibited significantly more deterioration than women at mild hypoglycemia, and subjects with a history of unconsciousness due to hypoglycemia exhibited more deterioration than subjects with no such history. Individual deterioration scores during repeat testing significantly correlated with performance during original testing. Recovery from hypoglycemia-related impairment varied across individuals and was correlated with degree of impairment during hypoglycemia. These results suggest that the glycemic threshold for onset and recovery from neurobehavioral deterioration with hypoglycemia, as well as degree of impairment experienced, varies across individuals. Furthermore, these individual differences are stable across time.

Adult↗

Disruptive effects of acute hypoglycemia on speed of cognitive and motor performance.

OBJECTIVE: To directly examine whether hypoglycemia differentially slows cognitive versus motor function, to evaluate the reliability of hypoglycemic-related slowing, and to examine factors contributing to individual differences. RESEARCH DESIGN AND METHODS: IDDM subjects (n = 10) were administered a pure cognitive and a pure motor neuropsychological test at euglycemia (5.4 mmol), blood glucose nadir (2.6 mmol), postnadir (3.6 mmol), and again at euglycemia (6.7 mmol). To assess the practice effect, matched control subjects were tested at similar time intervals. RESULTS: Concurrent and test-retest reliability for all tests was robust (r = 0.68-0.94). Only cognitive tasks demonstrated impairment at nadir (P < 0.04). Individual differences, in terms of cognitive impairment, were significantly correlated with levels of blood glucose at nadir and baseline performance. CONCLUSIONS: Cognitive tasks appear to be more sensitive to neuroglycopenia than motor tasks. Cognitive impairment caused by hypoglycemia is reliable and differs across subjects. Individuals who show reliable sensitivity to cognitive impairments of hypoglycemia should avoid moderately low blood glucose levels.

Adult↗

Multifactorial origin of hypoglycemic symptom unawareness in IDDM. Association with defective glucose counterregulation and better glycemic control.

To assess potential relationships between unawareness of hypoglycemic symptoms and both defective glucose counterregulation and therapy-associated altered glycemic thresholds, symptoms and hormonal responses to hypoglycemia were quantitated during standardized insulin infusion tests in 41 patients with insulin-dependent diabetes mellitus (IDDM). The glycemic thresholds for both neurogenic and neuroglycopenic symptoms (and those for both epinephrine and pancreatic polypeptide release) were at lower plasma glucose concentrations in both patients with defective (n = 9, 22%) and those with adequate glucose counterregulation and, among the latter, in patients with lower compared with higher glycosylated hemoglobin levels. The data are consistent with the concept that both defective glucose counterregulation and improved glycemic control contribute to excessive hypoglycemia in IDDM by reducing awareness of symptoms of developing hypoglycemia and by impairing physiological defenses against hypoglycemia. Thus, hypoglycemic symptom unawareness is multifactorial in origin and may be partly reversible.

Awareness↗

Accuracy of blood glucose estimation by children with IDDM and their parents.

OBJECTIVE: To evaluate the accuracy of blood glucose symptom recognition and subjective blood glucose estimation in insulin-dependent diabetic (IDDM) children and their parents. RESEARCH DESIGN AND METHODS: Blood glucose estimation questionnaires were completed 4 times/day at home during routine activities. A sequential sample of 19 families, who attended a pediatric diabetes clinic, with IDDM children less than 12 yr old and IDDM duration of greater than or equal to 9 mo comprised the study. RESULTS: Error grid analysis showed that both children and parents demonstrated poor accuracy, making clinically significant errors as frequently as clinically accurate estimates. The most common error was the failure to detect extreme blood glucose levels, with a significant tendency to underestimate hyperglycemia. Children often reported hypoglycemia when blood glucose was hyperglycemic. Confidence in the ability to estimate blood glucose was unrelated to measured accuracy. CONCLUSIONS: IDDM children and their parents demonstrated a higher rate of blood glucose estimation errors than IDDM adolescents and adults in previous studies. Even in families who use self-monitoring of blood glucose frequently, self-reported ability to recognize symptoms and estimate blood glucose should be viewed with caution. Families with IDDM children need more education about errors in symptom recognition and blood glucose estimation. They should also be encouraged to use self-monitoring of blood glucose before treating children's reported hypoglycemic symptoms whenever possible.

Adult↗

Environmental stress and blood glucose change in insulin-dependent diabetes mellitus.

Blood glucose (BG) response to psychological stress in insulin-dependent diabetes mellitus (IDDM) patients has not been firmly established. We report a study designed to address the gaps and methodological difficulties reviewed. Subjects with IDDM were exposed to two sessions (12 weeks apart) of two 20-min standardized stressors (active and passive) and a control condition administered in counterbalanced order. To measure BG response, subjects were connected to a glucose/insulin infusion system providing continuous BG measurement. Mood checklist measures were obtained at prestressor, poststressor, and recovery periods. During the first session of testing, the active stressor was associated with significantly more absolute change in BG response than the passive stressor. Results also indicate that IDDM subjects' BG response to this active stressor was idiosyncratic but significantly reliable over time.

Arousal↗

Glucose enhancement of performance on memory tests in young and aged humans.

Recent findings indicate that glucose administration enhances memory processes in rodents. This study examined the effects of glucose on memory in humans. After drinking glucose- or saccharin-flavored beverages, college-aged and elderly humans were tested with modified versions of the Wechsler Memory Scale. Beverages and tests were administered in a counter-balanced, crossover design, enabling within subject comparisons. The major findings were: (1) glucose enhanced memory in elderly and, to a lesser extent, in young subjects; and (2) glucose tolerance in individual subjects predicted memory in elderly, but not in young subjects on both glucose and saccharin test days.

Adolescent↗

Mood changes associated with blood glucose fluctuations in insulin-dependent diabetes mellitus.

Individuals with insulin-dependent diabetes mellitus (IDDM) and their healthcare practitioners believe that extreme blood glucose (BG) fluctuations are characterized by changes in subjective mood states and emotional behavior, as well as physical symptoms. This study examined relationships between BG levels and self-reported mood in a group of 34 IDDM adults. The method followed a within-subject, repeated-measures design employed in previous studies of physical symptoms associated with diabetic glucose. Four times each day, participants completed a mood/symptom checklist just prior to a self-measurement of BG until 40 checklists had been completed. Half the items on the checklist described physical symptoms and half described mood states. In addition, half the mood items described negative states and half described positive states. Within-subject correlations and regressions showed that moods were related to BG for the majority of participants and that, like physical symptoms, mood-BG relationships were highly idiosyncratic. Low BG levels tended to be associated with negative mood states, primarily self-reported "nervousness." Positive mood items were almost always associated with high BG. High BG levels also frequently correlated with negative mood states, although the negative mood items that tended to relate to high glucose (anger, sadness) differed from those that tended to relate to low BG. The implications of these findings for self-treatment and glucose perception in the IDDM individual are discussed.

Adult↗