Clinical Care/Education/Nutrition ORIGINAL AR T I C L E

Pro g r essive ’s Impact on Driving Simulation Pe rfo rm a n c e Oc c u r rence, awareness, and correc t i o n

DANIEL J. COX, PHD DIANA M. JULIAN, MA ioral training program that increases LINDA A. GONDER-FREDERICK, PHD WILLIAM L. CLARKE, MD aw a r eness of BG fluctuations and results in BORIS P. KOVATCHEV, PHD fewer and less extreme low BG events, has led to fewer motor vehicle crashes at long- te r m follow-up (4.3 years) compared with a control group (1). A 12-month follow-up of BGAT-2, a revised version of BGAT, OB J E C T I V E — Pro g r essive hypoglycemia leads to cognitive-motor and driving impair- demonstrated a 67% reduction in motor ments. This study evaluated the blood (BG) levels at which driving was impaired, im- vehicle violations (1). pa i r ment was detected, and corrective action was taken by subjects, along with the mecha- During direct investigation of the ef- nisms underlying these three issues. fects of hypoglycemia on driving perfo r - mance using a driving simulator, driving RESEARCH DESIGN AND METHODS — Th e r e were 37 adults with type 1 im p a i r ments have been documented at who drove a simulator during continuous euglycemia and prog r essive hypoglycemia. During testing, driving perfo r mance, EEG, and corrective behaviors (drinking a soda or discontinuing moderate hypoglycemia (2.5 mmol/l), but driving) were continually monitored, and BG, symptom perception, and judgement concerni n g not at mild hypoglycemia (3.6 mmol/l) (1). im p a i r ment were assessed every 5 min. Mean ± SD euglycemia perfo r mance was used to quan- These effects were found to be reliable at tify z sc o r es for perfo r mance in three hypoglycemic ranges (4.0–3.4, 3.3–2.8, and 2.8 mmol/l). retesting (1). However, these studies used a relatively simple single-screen driving sim- RE S U LT S — During all three hypoglycemic BG ranges, driving was significantly impaired , ul a t o r , testing 5 min of driving perfo rm a n c e and subjects were aware of their impaired driving. However, corrective actions did not occur during stepped hypoglycemia. This stepped until BG was 2.8 mmol/l. Driving impairment was related to increased neurogenic symp- hypoglycemia methodology had the follow- toms and increased theta-wave activity. Awa r eness of impaired driving was associated with ing two limitations: 1) in a natural environ - ne u r oglycopenic symptoms, increased beta-wave activity, and awareness of hypoglycemia. ment, hypoglycemia is assumed to be pro- High beta and low theta activity and awareness of both hypoglycemia and the need to trea t low BG influenced corrective behavior. gr essive and not a stepped process, and 2) it is assumed that hypoglycemia occurs while C O N C L U S I O N S — Driving perf o rmance is significantly disrupted at relatively mild driving and is not necessarily present at the hypoglycemia, yet subjects demonstrated a hesitation to take corrective action. The longer time of driving initiation. tr eatment is delayed, the greater the neuroglycopenia (increased theta), which precludes cor- P revention of hypoglycemia-re l a t e d rective behaviors. Patients should treat themselves while driving as soon as low BG and/or im- driving crashes relies on both a driver’s pa i r ed driving is suspected and should not begin driving when their BG is in the 5.0–4.0 ability to recognize his/her driving impair- mmol/l range without prophylactic trea t m e n t . ments and then immediately take the cor- rective actions of consuming carbohy- Diabetes Care 23 :1 6 3 –170, 2000 drates and/or pulling off the road. The ability of individuals to make and execute these decisions and what contributes to hile there are no clear data demon- levels around 3.6 mmol/l (5,6) and that such decision-making and behaviors has strating that patients using progressive neuroglycopenia will impair not been investigated. Whave a higher incidence of motor driving. The role of hypoglycemia in im- In an attempt to address these metho- vehicle crashes (1–4), there is little debate pa i r ed driving can be inferred by two re- dological limitations and self-re g u l a t i o n that hypoglycemia produces cognitive- cent studies. Blood Glucose Awareness p rocesses, driving perf o rmance during motor impairments at blood glucose (BG) Training (BGAT), an 8-week psychobehav- euglycemia and pro g ressive hypogly- cemia was compared with a sophisticated driving simulator. Three general issues Fr om the University of Vir ginia Health System, Charlottesville, Virg i n i a . investigated were 1) the BG level at which Ad d r ess correspondence and reprint requests to Daniel J. Cox, PhD, Behavioral Medicine Center, Box driving impairment is first observed, 223, University of Vir ginia Health System, Charlottesville, VA 22908. E-mail: djc4f@virgi n i a . e d u . 2) the BG level at which patients detect Received for publication 23 Februa r y 1999 and accepted in revised form 12 July 1999. driving impairments and take the correc - Ab b re v i a t i o n s : BG, blood glucose; BGAT, Blood Glucose Awa r eness Training; NASA, National Aeron a u - tics and Space Administration. tive action of either consuming glucose or A table elsewhere in this issue shows conventional and Système International (SI) units and conversion discontinuing driving, and 3) the mecha- factors for many substances. nisms underlying both driving impair-

DIABETES CARE, VOLUME 23, NUMBER 2, FEBRUARY 2000 163 Driving impairment and hypoglycemia

Table 1—Subject characteristics for those with and without a recent history of severe mained fasting on the morning of the h y p o g l y c e m i a st u d y . No caffeinated beverages were con- sumed after hospital admission. On the morning of the study, intra- 2 episodes of No history of se v e r e hypoglycemia venous lines were placed in the nondomi- se v e r e hypoglycemia in past 12 months P All subjects nant forea r m. Insulin was continuously in- fused at a constant rate of 1.0 mU kg 1 n 14 23 —— mi n 1, and a 20% dextrose solution was in- Age (years) 33.4 ± 4.7 36.5 ± 8.1 0. 2 1 35.3 ± 7.1 fused at a variable rate to maintain BG be- Duration of 16.0 ± 11.8 18.5 ± 8.8 0. 4 7 17.5 ± 10.0 tween 5.6 and 8.3 mmol/l for the first hour diabetes (years) of testing and then prog r essively lowered to Im p a i re d / n o r mal 4/ 1 0 14 / 9 0. 1 2 18 / 1 9 a BG of 2.2 mmol/l. Adjustments in dex- hypoglycemia awaren e s s tr ose infusion were made every 5 min to Sex (M/F) 7/ 7 9/ 1 4 0. 7 5 16 / 2 1 achieve a fall in BG of 1 mmol l 1 15 Units of insulin 0.64 ± 0.17 0.59 ± 0.17 0. 3 4 0.61 ± 0.17 mi n 1. The protocol was discontinued per day per kilogram once because of severe lethargy , disorienta- Hb A 1 8.6 ± 1.3 8.4 ± 2.0 0. 7 4 8.5 ± 1.8 tion, and . (This subject was then BM I 25.5 ± 4.1 23.0 ± 3.1 0. 0 4 23.9 ± 3.7 dr opped from the study.) Arterialized blood Auto crashes per 20.1 ± 56 43.2 ± 161 0. 6 2 34.7 ± 131 (achieved by warming the hand in a heated 1,000,000 miles glove to 50°C) was sampled for glucose Motor vehicle violations 20.1 ± 46 43.0 ± 109 0. 3 8 34.3 ± 90.1 concentration every 5 min. At the time of per 1,000,000 miles ev e r y BG sample, subjects rated on a seven- Average miles driven/year 13,594 ± 11,147 6,839 ± 3,951 0. 0 4 9,395 ± 8,089 point scale (0 = none, 6 = extreme) four Data are n or means ± SD. ne u r ogenic symptoms (jittery or tense, pounding heart, trembling, sweating), four ne u r oglycopenic symptoms (difficulty con- ments and aware n e s s / c o rrection of dri- Li k e r t scale (0 = never, 1 = rarel y , 2 = some- centrating, uncoordination, visual distur- ving impairme n t s . times, 3 = often, 4 = always) for the ques- bance, light headed or dizzy), “need to trea t tion “To what extent can you tell by your right now,” and “difficulty driving.” Finally, RESEARCH DESIGN AND symptoms that your blood sugar is LOW?” subjects estimated their BG level. ME T H O D S Using this scale, a score of 2 has been During the first hour, subjects watched shown to be associated with impairment of a videotape of someone else driving the Subjects hypoglycemia awareness (11) (Table 1). simulator and drove the simulator them- The study consisted of 37 subjects re- selves for 30 min each. This video condi- cr uited through newsletters, notices posted Procedure tion controlled for our data collection pro- in diabetes clinics, and direct physician re- All subjects attended orientation meetings ce d u r e. The order of watching/driving was fe r ral. All subjects had to have diabetes for and signed consent forms. Subjects were randomized. Euglycemia while driving at least 2 years, have taken insulin since the admitted to the University of Vi rg i n i a ’s s e rved as the control condition against time of diagnosis, be current drivers, and General Clinical Research Center the which individual effects of hypoglycemia not be taking medications that might influ- evening before the study. That evening, we r e compared. The second 30 min of dri- ence hypoglycemia or driving perfor- subjects received a physical exam, were in- ving began when the BG level re a c h e d mance. There were 16 men and 21 tr oduced to the simulator and its opera- 4.0 mmol/l. Euglycemia testing always women, with a mean (± SD) age of 35.3 ± tion, and were allowed to drive the simu- pr eceded hypoglycemia testing for the fol- 7.1 years, mean duration of disease 17.5 ± lator for a minimum of 15 min, or as long lowing two reasons: 1) if neurog l y c o p e n i a 10.0 years, mean insulin units per kilo- as needed for the subject to rep o r t feeling persisted beyond hypoglycemia, we did gram per day 0.61 ± 0.17, and mean glyco- co m f o r table with its operation. While dri- not want it operative during the eugly- sylated hemoglobin 8.5 ± 1.8%. The glyco- ving the simulator, subjects practiced rat- cemia test, and 2) if there were practice ef- sylated hemoglobin assay was determi n e d ing their symptoms and driving perf o r- fects with the driving simulator, then the by a boronate affinity column chrom a t o g - mance on a 0–6 scale, were shown a bottle mo r e conservative approach would be to raphy method, with nondiabetic levels of orange soda (the contents were actually have these operative during hypogly- 6.9%. Upon physical examination, two diet soda) in the glove compartment, and cemia. Figure 1 presents the design of the subjects were found to have postural hy- we r e instructed to drink the soda or pull st u d y . Patients were kept blind to the BG potension. Of the subjects, 23 had a his- of f the road and discontinue driving if they manipulations and actual BG levels. They tory of two or more episodes of severe thought their BG was too low. we r e instructed that the study was investi- hypoglycemia in the past year, and 14 had BG was maintained overnight be- gating the effects of high and low BG on no recent history of severe hypoglycemia; tween 5.6–8.3 mmol/l with intravenous wave activity and driving behaviors. 18 satisfied the criteria of reduced hypo- regular human insulin as per a prev i o u s l y glycemic awareness (1), and 19 had nor- published insulin infusion protocol (2). Driving simulator mal awareness of hypoglycemia. Hypogly- Subjects were given dinner and a bedtime To objectively assess driving in a con- cemia awareness was assessed using a 0–4 snack the evening before the study, but re- t rolled environment, the Atari Researc h

164 DIABETES CARE, VOLUME 23, NUMBER 2, FEBRUARY 2000 Cox and Associates

braking, and three speed control driving pe rf o r mance variables (2).

Awareness and corrective behaviors At each 5-min BG sampling, subjects w e re read aloud the symptoms and the driving impairment items. Subjects gave their 0–6 ratings orally. To cue subjects, the seven-point scale was posted just above the simulator’s center screen. The re s e a rcher also re c o rded whether the subject drank the glucose drink and/or pulled the car off the roa d .

EEG analysis An appropriately sized EEG cap (Electrod e Cap International, Eaton, OH) was placed over the subject’s head. Six electrode sites we r e prep a r ed: a ground just in front of Figure 1—Experimental design: BG manipulations and dependent variables. CZ, an earlobe ref e r ence electrode, and CZ, PZ, P3, and P4. The impedance criterion was 10 K ohms, as measured by a Prep - Driving Simulator was used. It is a rea l i s - The driving course was designed to Check electrode impedance meter. The tic, interactive, fixed platform simulator simulate driving demands of a typical EEG equipment was provided by the Na- that generates accurate and sensitive dri- grade 2 U.S. highway ( Vi rginia Depart- tional Aeronautics and Space Administra- ving perfo r mance data (Fig. 2). The cur- ment of Tr a n s p o rtation). The 16-mile tion (NASA) (Langley, VA), whose re- rent three - s c r een version of the simulator course took 30 min to traverse when fol- s e a rchers investigating the attention of has been used to diffe r entiate 1) visually lowing the posted speed limits. Table 2 pilots in flight simulators rec o m m e n d e d c o m p romised drivers from control sub- lists the driving demands. sites and impedance criteria (7,8). EEG je c t s (2–5), 2) outpatients with Alzheimer’s The simulator rec o r ds data four times signals were amplified and processed by disease from age-matched co n t r ol subjects a second and generates the nine driving the Biopac system, and on-line data analy- (6), 3) young adults with and without at- p e rf o rmance variables listed in Table 3. sis was accomplished using the CREW tention deficit/hyperactivity disorder on T h e re are three steering controls, thre e ( C rew Response Evaluation Wi n d o w ; placebo versus Ritalin (6), 4) middle- aged and senior males both when sober and intoxicated (6), and 6) elderly from v e ry elderly drivers (D.J.C., B. Kierna n , B. P .K., J. Guerri e r , A. Gulliano, C. George , un p u b l i s h e d observations). Additionally, pe rf o r mance on this simulator has corre- lated with age-sensitive cognitive-motor testing, actual on-road driving perf o r- mance, and occurrence of future auto crashes (6–8). The simulator has three 25-in com- puter screens that wrap around the driver, pr oviding a 160-degree visual field, along with a programmed rea r view mirror de- picting rear traffic. The driving environ - ment is realistic, incorporating a typical- sized steering wheel, gas and brake pedals, seat, and seat belt. Driving perfo rm a n c e feedback was provided to the subject visu- ally through the three screens, which up- dated at a rate of 60 times/s; auditory feed- back was provided through quadraphonic speakers delivering engine, tire, and roa d noises; and kinesthetic feedback was pro- vided through the steering wheel and pedal pres s u re . Figure 2—Atari Research Driving Simulator.

DIABETES CARE, VOLUME 23, NUMBER 2, FEBRUARY 2000 165 Driving impairment and hypoglycemia

Table 2—Driving demands during the 16-mile course cemia (P = 0.45, Table 4). There were 14 subjects (38%) who demonstrated ex- tr eme impairments in their driving, with a Fre q u e n c y Composite Driving Impairment score 2 Left turns (driver needs to turn left at specific stop-sign intersections, negotiating 5 SD (98th percentile) worse than their eu- oncoming and cross traffi c ) glycemic perfo r mance (Table 4). Red lights (driver needs to stop) 4 Because research has demonstrated Gr een lights (driver has throu g h w a y ) 8 that hypoglycemic cognitive-motor deficits Stop signs (driver needs to stop) 12 manifest at diffe r ent BG levels for diffe re n t Th r oughway stop sign intersections (side-traffic stops) 8 subjects and that some patients may show Speed limit changes (driver needs to change speeds) 22 adaptation to acute hypoglycemia (7), we Sudden stops (e.g., car in front of driver slams on brakes, object in road comes 4 co m p a r ed the highest (worst) z sc o r e from into view as driver crosses hill crest, car runs red light from left side) one of the three hypoglycemic BG ranges Detours at stop sign intersections (driver needs to obey detour arrow ) 8 for each driving parameter for each subject En c r oaching fixed objects (vehicle parked in driver’s lane) 2 with the euglycemic z sc o r e of 0. For ex- ample, subject A might have driven off- road most at the 4.0–3.4 mmol/l range, NASA) system. The EEG signal was digi- subjects engaged in more driving acros s subject B at the 3.3–2.8 mmol/l range, and tized from the four input channels at a rate the midline (risk midline: P 0.01 with subject C at the 2.8 mmol/l range, so that of 200 samples/s into a circular buff e r. BG 2.8 mmol/l) and more speeding these three scores would be used in the Data were taken from the buffer in four (high speed: P 0.01 with BG between comparison with euglycemia. As seen in data arrays of 512 data points each, i.e., at 4.0 and 2.8 mmol/l) and used brakes more Fig. 3, the driving parameters were each this sample rate, 2.56 s of data were ana- on the open road (inappropriate braking: significantly impaired during some level of lyzed at a time for each input channel. P 0.01 with BG between 4.0 and 2.8 hypoglycemia, with off- r oad driving, dri- St a n d a r d time series techniques were used mmol/l). If we consider that there are a va- ving fast, and applying brakes on the open for this initial data retrieval: each array was riety of impaired driving parameters oc- road being most likely to occur. The mean smoothed using a Tukey-Hanning win- cu r ring simultaneously and combining to Composite Driving Impairment of these d o w, and the power spectrum was esti- contribute to dangerous driving, then we worse scores was 3.3 (99.9th perce n t i l e ) , mated using a fast Fourier transforma t i o n can sum the separate z sc o r es for a Com- which was significantly worse than eugly- (7). Then the total power was computed posite Driving Impairment score for each cemia (t = 4.84, P 0.001). This indicates for each of three EEG bands: theta 4–8 Hz, subject. By definition, the Composite Dri- that at one of the three hypoglycemia BG alpha 8–13 Hz, and beta 13–22 Hz. The ving Impairment score for euglycemia ranges, driving perfo r mance was 3.3 SDs residual power was carried by the freq u e n - would be 0, which was significantly diffe r - worse than the subject’s average eugly- cies 1.6–4 Hz and 23 Hz. The band ent from the hypoglycemic Composite cemic perfo rm a n c e . powers were normalized to produce per- Driving Impairment score during all three When compared with the last 15 min cent power for each band and perc e n t BG ranges (P 0.01), but did not get pro- of euglycemia, during the last 15 min of residual power. This proc e d u r e resulted in gr essively worse with prog r essive hypogly- hypoglycemia subjects failed to stop at stop 12 EEG parameters, the percentage power in three bands for four electrode sites com- puted on 2.56-s data chunks. Table 3—Me a s u r ed driving perfo r mance variables and explanations RE S U LT S Driving variable Ex p l a n a t i o n Hypoglycemia and driving impairment St e e r i n g Based on the subject’s mean euglycemic SD steering St a n d a r d deviation of steering wheel angle while on road, swervi n g pe rf o r mance, z sc o r es were calculated for Off - ro a d Number of times drove off roa d each subject for each continuous variable Risk midline Quadratic risk function that increases the longer and further the car for three BG ranges (4.0–3.4, 3.3–2.8, and cr osses the midline 2.8 mmol/l) during the hypoglycemia Br a k i n g condition. Collisions and percent missed In a p p r opriate braking In a p p r opriate braking when car is in 35-mph, 45-mph, and stops, which may or may not have been acceleration zones possible within a specific BG range, were % Missed stops Pe r centage of missed stop signs and stoplights analyzed by comparing the last 15 min of % Col l i s i o n s Pe r centage of collisions per potentially risky zone the euglycemic and hypoglycemic condi- Speed control tions. The last 15 min ensured that all of Low speed Average percentage below speed limit when car is in 35- and the hypoglycemia data were collected 45-mph speed zones when BG was 4 mmol/l. High speed Average percentage above speed limit when car is in 35- and As seen in Table 4, compared with eu- 45-mph speed zones glycemic driving, during hypoglycemia, SD speed St a n d a r d deviation of speed in 35 and 45 mph zones

166 DIABETES CARE, VOLUME 23, NUMBER 2, FEBRUARY 2000 Cox and Associates

Table 4—Pe rf o r mance at three levels of hypoglycemia based on z sc o r es derived from individual ving impaired (Composite Driving Impair- euglycemic perfo rm a n c e ment score 2 vs. 2) and corrective be- haviors (yes vs. no), found that those demonstrating significant impairments Var i a b l e BG 4.0–3.3 BG 3.3–2.8 BG 2. 8 we r e more likely to take some form of cor- Driving perfo r mance z sc o r e deviation rective action ( 2 = 8.10, P 0.005). fr om euglycemia However, in this analysis, 6 of the 14 SD steering 0.04 (NS) 0.02 (NS) 0.04 (NS) (43%) severely impaired subjects did not Off - ro a d 0.25 (NS) 0.45 (NS) 0.57 (NS) take corrective action. Risk midline 0.05 (NS) 0.17 ( 0. 1 ) 0.11 ( 0. 0 1 ) Low speed 0.01 (NS) 0.05 (NS) 0.37 (NS) Underlying mechanisms High speed 0.23 ( 0. 0 1 ) 0.56 ( 0. 0 0 1 ) 0.26 (NS) To determine factors contributing to poor SD speed 0.09 (NS) 0.09 (NS) 0.23 (NS) driving, we first quantified the effects of In a p p r opriate braking 0.0 (NS) 0.61 ( 0. 0 5 ) 0.00 (NS) hypoglycemia on EEG. During hypogly- Composite driving impairment score 0.83 ( 0. 0 1 ) 1.83 ( 0. 0 0 5 ) 1.52 ( 0. 0 0 5 ) cemia, a significant prog r essive increase of % Subjects significantly impaired 12 26 16 the power of beta-, alpha-, and theta-fre- Awa r eness deviation from euglycemia quencies was observed (P 0.01). As indi- Di f ficulty driving rating 0.30 ( 0. 0 5 ) 0.35 ( 0. 1 ) 0.54 ( 0. 0 1 ) cated in Table 4, the power of beta in- % Subjects who detected their driving 21 22 25 cr eased early in the 3.3–2.8 mmol/l BG im p a i rm e n t range and remained at that level, while % Subjects who detected hypoglycemia 15 33 79 alpha increased but continued to increa s e Co r rective behaviors m o re as BG fell below 2.8 mmol/l and Se l f - t r eated (n) 2 (NS) 1 (NS) 8 ( 0. 0 5 ) theta did not begin to increase until BG fell Stop driving (n) 1 (NS) 1 (NS) 5 (NS) below 2.8 mmol/l. % Subjects who took corrective action 5 3 22 The Composite Driving Impairme n t EEG power z sc o r e deviations from sc o r e was the dependent variable in multi- eu g l y c e m i a ple reg r essions through the origin in which (4–8 Hz) 0.01 (NS) 0.16 (NS) 0.76 ( 0. 0 0 1 ) the predictor variables were theta, alpha, (8–13 Hz) 0.10 (NS) 0.40 ( 0. 0 0 1 ) 0.80 ( 0. 0 0 1 ) and beta z sc o r es, self-rep o r ted neurog l y - (13–22 Hz) 0.02 (NS) 0.30 ( 0. 0 0 1 ) 0.42 ( 0. 0 0 1 ) copenic and neurogenic symptom z sc o re s , P values are in paren t h e s e s . and estimated BG level. At mild to moder- ate hypoglycemia (BG 4.0–2.8 mmol/l), a significant re g ression model (F = 18.3, signs significantly more often (4 vs.1%, P = during hypoglycemia was 2.7 ± 0.4 mmol/l P 0.0001) was calculated that explained 0.01) and were involved in more crashes at (2.3–3.6). A total of 12 vs. 3 subjects 53% of the variance in driving impair- sudden stops (five subjects had sudden- tr eated themselves and/or stopped driving ment, with two significant predictors: per- stop accidents during hypoglycemia com- during hypoglycemia versus euglycemia ceived neurogenic symptoms (partial cor- pa r ed with only one subject during eugly- (P 0.01). A 2 test comparing those dri- relation = 0.53, t = 4.6, P 0.0001) and cemia, 2 = 2.9, P = 0.08).

Awareness and corrective behaviors A similar z sc o r e transformation was per- fo r med on the 0–6 self-rep o r ted impaired driving ratings. Similar to the objective Composite Driving Impairment score , these global self-evaluations were signifi- cantly elevated during mild and moderate hypoglycemia (Table 4). Th e r e were 11 subjects who trea t e d themselves during hypoglycemia (3 trea t e d themselves twice), whereas during eugly- cemia, 3 subjects treated themselves (P 0.02). The mean BG level at which subjects tr eated themselves during hypoglycemia was 2.7 ± 0.5 mmol/l (range 2.1–3.6). Likewise, seven subjects stopped driving during hypoglycemia (three stopped twice), whereas two stopped driving dur- ing euglycemia (P = 0.07). The mean BG Figure 3—Mean maximum z scores for the three levels for hypoglycemia. Bk, braking; Inapp, inap - level at which subjects stopped driving propriate; ML, midline; Sp, speed.

DIABETES CARE, VOLUME 23, NUMBER 2, FEBRUARY 2000 167 Driving impairment and hypoglycemia

Table 5—Post hoc comparisons of diffe r ent subgroups on the Composite Driving Impairme n t While driving perf o rmance was im- sc o re s pa i r ed at mild hypoglycemia, as in prev i - ously published cognitive-motor test stud- ies, the BG range at which driving was Mean Composite Comparison grou p s Driving Impairment scores P im p a i r ed and the exact driving parameters di s r upted were quite idiosyncratic. This Im p a i r ed versus normal hypoglycemia awaren e s s 1.0 vs. 1.9 0. 2 1 becomes obvious when contrasting the Recent history versus no history of severe hypoglycemia 1.3 vs. 1.7 0. 6 1 data presented in Table 4 and Fig. 3. Of Men versus women 1.4 vs. 1.6 0. 8 2 the 21 possibilities in Table 4 (seven dri- Low BG in previous 48 h versus no recent low BG 1.9 vs. 1.2 0. 4 5 ving variables th r ee BG levels), only 5 2 vs. 3 insulin injections per day 1.2 vs. 1.8 0. 5 0 demonstrated significant group eff e c t s . H o w e v e r, when considering a subject’s worst perfo r mance at any hypoglycemic i n c rease in theta (partial correlation = having no recent severe hypoglycemia. level, as in Fig. 3, we see that all of the dri- 0.33, t = 2.7, P 0.01). In other words , Subjects were also dichotomized into ving perfo r mance variables were signifi- driving impairment was associated with those with normal or reduced hypogly- cantly affected at some point during mo r e autonomic arousal and of cemia awareness, as defined by Clarke et hy p o glycemia (all P 0.05). Another il- the at moderate al. (11), and compared. To assess sex dif- lustration of idiosyncrasy is that of the 37 hypoglycemia. However, at BG levels f e rences, male subjects were compare d subjects, only 14 (38%) demonstrated an 2.8 mmol/l, driving impairment was not with female subjects. To investigate overall severe driving impairment rel a t i v e pr edicted by any of the measures . whether recent experience with hypogly- to their euglycemic perf o rmance ( 2 Similar predictor variables were used cemia related to hypoglycemia-impaired SDs). However, this 38% is a conserva t i v e to predict subject awareness of impaired driving, subjects who rep o r ted experienc- estimate of those significantly impaired for driving z s c o res. Recognition of driving ing a BG 3.8 mmol/l within the 48 h be- th r ee reasons. First, the methodology al- im p a i r ment was predicted (R2 = 38, F = f o re testing were compared with those lowed any practice effect to optimize hy- 20.9, P 0.001) by neuro g l y c o p e n i c who rep o r ted no such recent events. Fi- poglycemic driving. Second, the criterion symptoms (partial correlation = 0.55, t = n a l l y, we compared subjects who were of 2 SDs in Composite Driving Impair- 4.4, P 0.001), high beta-wave activity taking one or two versus three or more ment was based on perfo r mance averaged (p a r tial correlation = 0.28, t = 2.3, P (intensive therapy) insulin injections a a c ross the entire 30 min of pro g re s s i v e 0.03), and estimated BG (partial correl a - d a y. As seen in Table 5, these variables hypoglycemia. Consequently, some sub- tion = 0.25, t = 2.1, P 0. 0 5 ) . w e re not related to hypoglycemia-in- jects may have achieved significant driving Fi n a l l y , we used a discriminant analy- duced driving impairme n t s . im p a i r ments at lower BG levels without sis to diffe r entiate subjects who either did their overall average perfo r mance rea c h i n g or did not take corrective action (trea t e d C O N C L U S I O N S — While we and the criteria of exceeding their euglycemic and/or stopped driving) on the basis of the others (5,6,28) have rep o r ted cognitive- driving perf o rmance by the 98th per- EEG, neurogenic and neuro g l y c o p e n i c motor impairments at relatively mild centile (2 SDs). Third, whether driving im- symptoms, estimated BG level, need to hypoglycemia (e.g., 3.6 mmol/l), the only pa i r ment is actually captured is dependent tr eat, impaired driving ratings, and Com- study investigating driving perf o rm a n c e on the demand of the driving scenario. posite Driving Impairment score. Four (9) did not find impairments until BG While neuroglycopenia may render a dri- variables entered a significant discriminant reached 2.5 mmol/l. However, that inves- ver incapable of rapidly processing infor- model that correctly classified 92% of tigation involved a relatively simple simu- mation and responding approp r i a t e l y , un- those who did take a corrective action and la t o r , with relatively nondemanding dri- less such a driving demand is placed on 72% of those who did not. Predictive vari- ving scenarios that lasted only 5 min, the driver, then nothing bad would neces- ables, in order of significance (partial cor- during stepped hypoglycemia. Using a sarily occur. This is clearly illustrated by relations), were as follows: perceived need mo r e sophisticated simulator and scenar- patient rep o r ts describing driving experi- to treat (0.42), estimated BG ( 0.37), and ios and pro g ressive hypoglycemia, this ences in which the impaired driver could low theta ( 0.26) and high beta (0.15). study documented driving impairment at not remember the drive and others had to Thus, subjects were more likely to trea t relatively mild hypoglycemia (4.0–3.4 in t e r vene in some way but no accident oc- themselves the more alert (high beta/low mmol/l). Not only do these current find- cu r red . theta) and the more aware (greater detec- ings parallel previously published neu- Th e r e appears to be a disconnect be- tion of and perceived need to treat low ropsychological deficits at similar BG lev- tween awareness of driving impairment BG) they were. els, but driving impairment was and corrective action. Only 11 of the sub- co n f i r med by subjects’ awareness of dri- jects (30%) actually took corrective action. Post hoc analyses ving impairments. Driving impairm e n t s This disconnection is confirmed and clari- We investigated whether certain sub- during mild to moderate hypoglycemia fied by the discriminant analysis. Correc - g roups were more at risk for hypogly- we r e accounted for by autonomic arou s a l , tive behavior was associated with both cemia-induced impaired driving. Subjects as defined by perceived neurogenic symp- minimal neuroglycopenia (high beta and with a history of repeated severe hypogly- toms, and depression of the central ner- low theta) and awareness both of low BG cemia (more than two events in the past vous system, as defined by incre a s e d and impaired driving. While discriminant 12 months) were contrasted with those theta-wave activity. analysis did not demonstrate that actual

168 DIABETES CARE, VOLUME 23, NUMBER 2, FEBRUARY 2000 Cox and Associates driving impairment (Composite Driving not indicate that diabetes has an increa s e d F, Genrich HE, Brunetti P: A reliable and Im p a i r ment score) contributed to whether driving risk (2,3), these findings cannot be re p roducible test for adequate glucose subjects took corrective action, 2 did implied to have direct relevance to driving co u n t e r- r egulation in type I diabetes melli- demonstrate that taking action was more pr i v i l e g e s . tus. Di a b e t e s 33:732–737, 1984 likely to occur among those most impaired 13 . Szylk JP, Severing K, Fishman GA: Pe r i p h - ( 2 SD elevation in Composite Driving Ac k n o w l e d g m e n t s — This res e a r ch was sup- eral Visual Field Loss and Driving Perf o r - ma n c e . Washington, DC, AAA Foundation Im p a i r ment scores). Although significantly po r ted by National Institutes of Health Gra n t s DK-28288 and RR-00847. for Tra f fic Safety Research Reports, 1991 related to driving impairment, 43% (6 of 14 . Szylk JP, Alexander KR, Severing K, Fish- 14) of the significantly impaired drivers man GA: Assessment of driving perf o r- never took corrective action. Treatment mance in patients with retinitis pigmen- Re f e re n c e s was only significantly more likely to occur tosa. A rch Ophthalmol 1 1 0 : 1 7 0 9 – 1 7 1 3 , 1. Br unner GA, Semlitsch B, Siebenhofer A, during hypoglycemia at very low BG levels 19 9 2 Pieber TR: Driver’s license, driving habits 15 . Szylk JP, Fishman GA, Severing K, Alexan- ( 2.8 mmol/l), which was below the level and traffic safety of patients with diabetes at which driving impairments occurred . der KR, Viana M: Evaluation of driving per- mellitus. Wien Klin Woc h e n s c h r 10 8 : 7 3 1 – fo r mance in patients with juvenile macular This study demonstrates that hypogly- 736, 1996 cemia is a significant factor in impaired dri- dystrophies. Arch Ophthalmol 111:207– 2. Distiller LA, Kramer BD: Driving and dia- 212, 1993 ving and that patients are generally aware betics on insulin therapy. S Afr Med J 86 : 16 . Szylk JP, Brigell M, Seiple W: Effects of age of when their driving perfo r mance is dete- 1018–1020, 1996 and hemianoptic visual field loss on dri- riorating. However, these data also indicate 3. Veneman TF: Diabetes mellitus and traffi c ving. Optom Vis Sci 70:1031–1037, 1993 that patients are not likely to treat their low incidents. Neth J Med 48:24–28, 1996 17 . Cox DJ, Quillian WC, Thorndike FP, Ko- BG while driving. In large part, this ap- 4. Koepsell TD, Wolf ME, McCloskey LM, vatchev BP, Hanna G: Evaluating driving pears to be due to waiting too long before B ruckmer DM, Lourie D, Wagner EH, pe rf o r mance of outpatients with Alzheimer’s taking corrective action. In the current Thompson RS: Medical conditions and disease. J Am Board Fam Pract 11 : 2 6 4 – 2 7 1 , motor vehicle collision injuries in older st u d y , subjects waited to treat themselves 19 9 8 adults. J Am Geriatr Soc 42:695–700, 1994 18 . Cox DJ, Kovatchev B, Morris J, Philips C, until after their BG fell below 2.8 mmol/l. 5. G o n d e r- F rederick LA, Cox DJ, Driesen This is a BG level associated with the grea t - Merkel L: Electroencephalographic and NR, Ryan C, Clarke WL: Individual diffe r - psychometric differences between boys est elevation in theta-wave activity, which ences in the neurobehavioral disrup t i o n with and without attention deficit/hyperac- was negatively associated with self-trea t - during mild and moderate hypoglycemia tivity disorder (ADHD): a pilot study. Ap p l ment. The hesitation to treat low BG or in adults with IDDM. Di a b e t e s 43 : 1 4 0 7 – Psychophysiol Biofeedback 23:179–188, stop driving when hypoglycemic was re- 1412, 1994 19 9 8 cently confirmed with field data in which 6. Driesen NR, Cox DJ, Gonder- F re d e r i c k 19 . Quillian WC, Cox DJ, Kovatchev BP, subjects were asked whether or not they LA, Clarke WL: Reaction time impairme n t Phillips CR: The effects of age and alcohol would drive based on what they thought in insulin-dependent diabetes: task com- intoxication on simulated driving perfo r - their BG was but without knowing their pl e x i t y , blood glucose levels, and individ- mance, awareness, and self-restraint. Ag e ual diff e rences. N e u ro p s y c h o l o g y 9 : 2 4 6 – Ag e i n g 28:59–66, 1999 actual BG (2). Subjects rep o r ted being will- 254, 1995 ing to drive 45% of the time when their ac- 20 . G u e rrier JH, Manivannan P, Pacheco A, 7. Cox DJ, Gonder-F r ederick LA, Julian DM, Wilkie FL: The relationship of age and tual BG was between 2.2 and 2.8 mmol/l. Clarke WL: Long-term follow-up evalua- cognitive characteristics of drivers to per- In general, this study suggests that pa- tion of blood glucose awareness training. fo r mance of driving tasks on an interactive tients should be encouraged to treat them- Diabetes Care 17:1–5, 1994 driving simulator. In P roceedings of the selves immediately, whenever they think 8. Cox DJ, Gonder-F r ederick LA, Kovatchev Human Factors and Ergonomics Society, 39th their BG is low or their driving is im- B, Polonsky W, Schlundt D, Julian D, Annual Meeting, San Diego, CA, 1995. pa i r ed, and not to wait until either they Clarke WL: Reduction of severe hypogly- Santa Monica, CA, Human Factors and Er- become too neuroglycopenic or their dri- cemia (SH) with blood glucose awaren e s s gonomics Society, p. 172–176 ving is too impaired. Furth e rm o r e, these training (BGAT-2) (Abstract). D i a b e t e s 21 . Gu e r rier JH, Cox DJ: The validity of a low (Suppl. 1):27A, 1995 data suggest that it would be prudent for cost driving simulator in assessing driving 9. Cox DJ, Gonder-F r ederick LA, Clarke WL: pe rf o r mance. Hum Factors. In pres s drivers with to measure Driving decrements in type I diabetes dur- 22 . Cox DJ, Taylor P, Kovatchev B: Driving their BG before driving, not to start driving ing moderate hypoglycemia. Di a b e t e s 42 : simulation perfo r mance predicts future ac- when their BG is 5–4 mmol/l without first 239–243, 1993 cidents among older drivers. J Am Geriatr tr eating their BG, and not to drive when 10 . Quillian W, Cox D, Gonder-F r ederick L, So c 47:381–382, 1999 their BG is 4 mmol/l. This study sug- Driesen N, Clarke W: Reliability of driving 23 . Cox DJ, Kovatchev BP, Kiernan B, Quillian gests that drivers should keep fast-acting p e rf o rmance during moderate hypogly- W, Guerrier J, George C: Evaluation of older glucose readily available, e.g., clipped to cemia in adults with IDDM. Diabetes Care dr i v e r ’ s perfo r mance employing driving the visor, so that finding it is not an addi- 17:1367–1368, 1994 si m u l a t o r . In DSC 97 Driving Simulation, tional delay or barrier to self-trea t m e n t . 11 . Clarke WL, Cox DJ, Gonder-F r ederick LA, Co n f e r ence ETNA, TEKNEA. Paris, France, Ho w e v e r , because of the idiosyncrasies of Julian D, Schlundt D, Polonsky W: Re- 19 9 7 duced awareness of hypoglycemia in 24 . Pope AT, Bogart EH, Bartolome DS: Biocy- these findings and the limitations of this IDDM adults: a prospective study of hypo- be r netic system validates index of operator study (small sample size, use of simula- glycemic frequency and associated symp- engagement in automated task. Biol Psychol tion), the direct relevance of these findings toms. Diabetes Care 18:517–522, 1995 40:187–195, 1995 to actual driving risk is unclear. Addition- 12 . Bolli GB, DeFeo P, DeCosmo S, Perriello G, 25 . Pope AT, Bogart EH: Identification of haz- al l y , because this and recent survey data do Ventura M, Massi Benedetti M, Sateusario ar dous awareness states in monitoring envi-

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ronments. Jo u r nal of Aeros p a c e Section 1: tive and motor perfo r mance. Diabetes Care Kovatchev BP: To drive or not to drive: 449–457, 1993 (SAE Technical Paper no. 16:1391–1393, 1993 that is the decision. JA M A 28 2 : 7 5 0 – 7 5 4 , 921136, SAE 1992 Tra n s a c t i o n s ) 28 . Ryan CM, Atchison J, Puczynski S, Puczyn- 19 9 9 26 . Box GEP, Jenkins GM: Time Series Analysis: ski M, Arslanian S, Becker D: Mild hypogly- 30 . McGwin G, Sims RV, Pulley L, Roseman Fo r ecasting and Control, Rev. Ed. San Fran- cemia associated with deterioration of men- JM: Diabetes and automobile crashes in the cisco, CA, Holden-Day, 1976 tal efficiency in children with insulin- el d e r l y . Diabetes Care 22:220–227, 1999 27 . Cox DJ, Gonder-F r ederick LA, Schroe d e r dependent diabetes mellitus. J Pediatr 11 7 : 31 . MacLeod KM: Diabetes and driving: to- DB, Cryer PE, Clarke WL: Disruptive effe c t s 32–38, 1990 wa r ds equitable, evidence-based decision- of acute hypoglycemia on speed of cogni- 29 . Clarke WL, Cox DJ, Gonder-F r ederick LA, making. Diabet Med 16:282–290, 1999

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