RESULTS

1. INFLUENCE OF GLYCEMIC EXCURSIONS ON EVENT-RELATED POTENTIAL IN DIABETIC PATIENTS Brenda Dickman, Fuh-Cherng Jeng, Brooke Hallowell, Alexander Sergeev, Dennis Ries, Frank Schwartz INTRODUCTION METHODS RESULTS DISCUSSION • This study demonstrated: • P300 latencies were not significantly different between IDDM and control participants but increased with age. • Scalp distributions of P300 amplitudes were not significantly different between IDDM and control participants. • Daily and acute glucose fluctuation as well as extent of excursions positively correlated to P300 amplitude . • Data obtained in this study are somewhat contradictory to previous findings. Diabetes itself was not shown to be positively correlated to P300 latency or amplitude. However, acute glucose abnormalities as well as the number and extent of glucose excursions were positively correlated to P300 amplitude. Therefore, the ability to control glucose fluctuation may have more influence on event-related potential than diabetes, per se. More data is needed to enhance statistical power. • Participants • Thirteen IDDM patients (6 M, 32.9 ± 7.1 years ) • Thirteen healthy adults (6 M, 26.4 ± 6.4 years ) • Insertion of Insulin Pump • A Medtronic MiniMed CGMS was used to monitor glucose levels in each participant for a three-day period. • Interstitial glucose levels were reported every five minutes. Figure 1a IDDM and controls did not differ significantly in terms of P300 amplitude or latency. Figure 1b P300 amplitudes had similar scalp distribution between the two groups. Patients with insulin-dependent diabetes mellitus (IDDM) are frequently exposed to fluctuating glucose levels and episodes of acute hypo- or hyperglycemia that occur in their daily life. These abnormal glucose fluctuations and excursions are associated with risk for long-term brain injury (Tallroth et al., 1990; Lindgren et al., 1996) and subsequent cognitive dysfunction (Brands et al., 2005; Cooray et al., 2008; Jacobson et al., 2007). Most patients on intensive insulin treatment experience two to three episodes of asymptomatic hypoglycemia per day throughout their life time. This is in addition to the known hypoglycemic episodes. There is great concern that with the more aggressive attempts to reduce the long term complications of diabetes such as retinopathy or kidney disease by way of insulin therapy that we are increasing the risk of brain damage due to glucose fluctuation. Auditory event-related P300 potential has been used to detect the alternation of cognitive dysfunction in patients with long-standing IDDM (Blackman et al., 1992; Cooray et al., 2008; Pozzessere et al., 1991). Studies (Alvarenga et al., 2005; Blackman et al., 1992) have shown P300 latency to be significantly longer in diabetic patients than that in non-diabetic participants. Studies have also suggested that longer P300 latency is associated with lower glucose levels in IDDM (Alvarenga et al., 2005) and NIDDM (Dey et al., 1997) patients. However, none of the studies examined the effects of fluctuating glucose levels on the auditory event-related P300 potential – an indicator for cognitive dysfunction in IDDM patients. Due to the lack of empirical evidence of the specific effects of fluctuations in glucose levels on individuals with IDDM, further investigation is warranted. That is, further investigation of auditory P300 potential and glucose fluctuation may provide a possible option for early detection and prevention of neurophysiologic changes in patients with IDDM. Advanced technologies utilizing Continuous Glucose Measurement System (CGMS) in insulin pumps have allowed the recording of glucose levels at intervals of every five minutes. The ability to measure interstitial glucose levels this frequently allowed us to document asymptomatic hypo- and hyperglycemia, monitor fluctuations of daily glucose levels, and estimate glucose levels during testing. This study was designed to investigate the influence of daily fluctuation versus acute episodic glucose excursions by analysis of the objective auditory P300 potential in correlation with moment-by-moment glucose changes. It was hypothesized that the cognitive P300 potential would be affected primarily by glycemic excursion and not diabetes per se. That is, greater glycemic excursion would result in longer P300 latencies and smaller amplitudes. Table 1 P300 latency was shown to have a positive correlation with age of participant but not with diabetes or glucose excursions. ACKNOWLEDGMENTS This study is supported in part by Diabetes Research Initiative, Appalachian Rural Health Institute. (1/1/2009 – 12/31/2009) . The authors wish to thank Lynn Petrik and Cammie Starner for their assistance with insulin pump insertion. • Experimental Protocol • Two sessions of testing were performedon the second and third day following glucose monitor insertion. • Participants were seated comfortably in a reclining chair in an acoustically and electrically treated sound booth. • Two blocks of P300 recordings were conducted during each session. • Participants pressed a thumb button held in their right hand as quickly as possible following the presentation of a target tone. • 2-minute breaks were givenbetween successive blocks. • Stimulus Generation • Target tone: 2000 Hz tone burst. • Non-target tone: 1000 Hz tone burst. • A total of 200 target and non-target tones were presented in a random sequence (80 target & 120 non-target tones). • Recording Parameters • 64 electrodes mounted in a Neuroscan Quik-Cap at locations based on a modified international 10-20 system (American Clinical Neurophysiology Society, 1994). • Four additional electrodes were placed on the face to monitor eye movements. • Continuous data was recorded and amplified through a Neuroscan SynAmp2 amplifier (24-bit resolution, least significant bit: 0.15 nV), digitized at a rate of 1000 samples/s, and stored on a personal computer for offline analysis. 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Neurophysiological changes during insulin-induced hypoglycaemia and in the recovery period following glucose infusion in Type 1 (insulin-dependent) diabetes mellitus and in normal man. Diabetologia, 33, 319-323. Table 2 P300 amplitude negatively correlated with diabetes and age but positively correlated with glucose levels during testing, number of glucose excursions, and area outside normal glucose levels.