Electrochemiluminescence assays for insulin and glutamic acid decarboxylase autoantibodies improve prediction of type 1 diabetes risk.

We recently developed new electrochemiluminescence (ECL) insulin autoantibody (IAA) and glutamic acid decarboxylase 65 autoantibody (GADA) assays that discriminate high-affinity, high-risk diabetes-specific autoantibodies from low-affinity, low-risk islet autoantibodies (iAbs) detected by radioassay (RAD). Here, we report a further validation of the ECL-IAA and -GADA assays in 3,484 TrialNet study participants. The ECL assay and RAD were congruent in those with prediabetes and in subjects with multiple autoantibodies, but only 24% (P<0.0001) of single RAD-IAA-positive and 46% (P<0.0001) of single RAD-GADA-positive were confirmed by the ECL-IAA and -GADA assays, respectively. During a follow-up (mean, 2.4 years), 51% of RAD-IAA-positive and 63% of RAD-GADA-positive subjects not confirmed by ECL became iAb negative, compared with only 17% of RAD-IAA-positive (P<0.0001) and 15% of RAD-GADA-positive (P<0.0001) subjects confirmed by ECL assays. Among subjects with multiple iAbs, diabetes-free survival was significantly shorter if IAA or GADA was positive by ECL and negative by RAD than if IAA or GADA was negative by ECL and positive by RAD (P<0.019 and P<0.0001, respectively). Both positive and negative predictive values in terms of progression to type 1 diabetes mellitus were superior for ECL-IAA and ECL-GADA, compared with RADs. The prevalence of the high-risk human leukocyte antigen-DR3/4, DQB1*0302 genotype was significantly higher in subjects with RAD-IAA or RAD-GADA confirmed by ECL. In conclusion, both ECL-IAA and -GADA are more disease-specific and better able to predict the risk of progression to type 1 diabetes mellitus than the current standard RADs.

Effect of cold acclimatization on exercise economy in the cold.

We sought to determine if cold acclimatized men display higher economy (i.e. lower oxygen consumption at a given workload) during graded cycle ergometry in the cold (5°C). After completing a familiarization trial 1 week prior, five cold weather athletes (CWA) and eight physically active men (NON) underwent graded exercise tests to volitional fatigue in 5°C. The protocol always started at 60 W and increased by 20 W each minute. Oxygen consumption (VO(2)), respiration rate (RR), tidal volume (TV), and respiratory exchange ratio (RER) were determined via open circuit spirometry. Individuals were matched for body size and minutes of weekly physical activity. Repeated measures analyses of variance were conducted across time (workload) and cold acclimatization was entered as a between subjects factor. VO(2) peak was not different between groups but CWA had lower VO(2) at 60 and 240 W. CWA also had lower RR at 180 and 260 W as well as lower RER at 240 and 260 W. At submaximal workloads, cold acclimatized men have higher exercise economy than non-acclimatized men. This could have implications for those who work in this context.

Test-retest reliability of Purdue Pegboard performance in thermoneutral and cold ambient conditions.

In the cold, Purdue Pegboard (PP) performance declines. The purpose of this study was to determine if this cold-induced impairment is consistent across days (i.e. test-retest reliability) in 5°C. In thermoneutral air (25°C), 14 men were familiarised to the dominant hand (PPa) and bimanual (PPb) PP tasks. They then experienced two 90-min cold exposures (Day 1, Day 2) while wearing ∼1 clo. Bare hands were maintained throughout. Performance on both tasks showed high reliability from day to day (intraclass correlations >0.700) in both thermoneutral and cold conditions. However for both tasks, room temperature performance did not predict performance in the cold (intraclass correlations <0.450). When screening applicants for manual labour in the cold, one must consider that room temperature dexterity does not correlate with dexterity in the cold. It is recommended that a 60-min period of cold exposure be employed to assess manual dexterity in these workers. STATEMENT OF RELEVANCE: This study shows that PP performance in room temperature does not predict performance in the cold but performance in the cold is consistent from day to day. When screening applicants for manual labour in the cold, it is recommended that dexterity tests be conducted in the same ambient conditions.

Mood and selective attention in the cold: the effect of interval versus continuous exercise.

Both mood and cognitive function are altered in cold environments. Body warming through exercise may improve Stroop interference score and lessen total negative mood. The purpose of this study was to determine the effect of equal caloric bouts of interval (INT) and continuous (CONT) exercise on mood and selective attention in the cold. Eleven young men underwent two experimental trials in 5°C air. Both trials consisted of 90 min acute cold exposure (ACE), 30 min exercise (INT vs. CONT), and 60 min recovery (REC). The Profile of Mood States (POMS) and Stroop Color Word Test (SCWT) were administered at four time points. Mean body temperature decreased during ACE, increased during exercise, and decreased during REC. Repeated measures analysis of variance revealed a main effect for time for several of the POMS sub scores. In particular, negative mood was significantly decreased after exercise relative to ACE and then significantly increased during REC. Further, CONT appears to be more effective than INT at decreasing negative mood. Components of the SCWT supported both the arousal and distraction theories for simple perception, but no significant effects were shown for the interference score. In the cold, exercise decreases negative mood but does not appear to affect selective attention. Further mechanistic studies could determine the best mode and intensity of exercise for improving cognitive function in the cold.

Pain and thermal sensation in the cold: the effect of interval versus continuous exercise.

Military and factory work often involves exposure to cold temperatures. With prolonged exposure, individuals report feeling cold and develop pain in their hands, both of which might be alleviated by endogenous heat production via exercise. The purpose of this study was to evaluate how interval (INT) and continuous (CONT) cycle ergometry alter thermal sensation, hand pain, mean finger temperature, and skin surface temperature gradient (forearm-finger) following immobility in moderate cold. Fourteen young men underwent two trials (each was three total hours in 5°C) consisting of a 90-min period of acute cold exposure (ACE), 30 min of exercise (INT or CONT), and a 60-min recovery period (REC). INT and CONT were isoenergetic, reflecting 50 ± 1% of each individual's VO(2) peak. All perceptual scales were significantly correlated during ACE (i.e., test-retest reliability). As expected, individuals felt colder and reported more hand pain during ACE, as compared to thermoneutral conditions. Relative to ACE, both INT and CONT increased mean finger temperature, which was associated with warmer thermal sensation and less hand pain. During REC in 5°C, individuals felt colder and reported more hand pain than during exercise. Although there were no perceptual differences between INT and CONT, moderate exercise in general can cause subjective feelings of warmth and less hand pain in people acutely exposed to moderate cold.

The influence of interval versus continuous exercise on thermoregulation, torso hemodynamics, and finger dexterity in the cold.

The purpose of this study was to evaluate how interval (INT) and continuous (CONT) exercise alter body temperatures and manual dexterity in the cold (5 degrees C). Fourteen young men underwent two trials consisting of a 90-min period of acute cold exposure (ACE), 30 min of exercise (INT or CONT), and a 60-min recovery period (REC). Participants donned approximately 1 clo but the hands remained bare for the entire protocol so that a steep decline in dexterity performance occurred prior to the initiation of exercise. INT and CONT were isoenergetic, reflecting 50 +/- 1% of each individual's VO(2) peak. Rectal (Tre) and skin temperatures were monitored continuously and dexterity testing was conducted at ten time points throughout each 3-h trial. In addition, oxygen consumption (VO(2)) and torso hemodynamics were assessed via indirect calorimetry and impedance cardiography (ICG), respectively. As expected, finger temperature and dexterity declined during ACE, relative to baseline. Both modes of exercise increased finger temperature and dexterity, relative to ACE. However, CONT was more effective than INT at increasing finger temperature on the dominant hand, which was associated with better dexterity scores during REC. Tre was not different between trials but a significant increase in stroke volume was found following CONT. Perhaps elevated stroke volume during post-exercise REC plays a role in finger rewarming and dexterity performance. Further mechanistic studies are needed to confirm the role of cardiovascular function in the enhancement of manual performance in the cold.