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ID naloge: 86 Letnik: 2000 Predmet: pediatrija
Spremljanje motoricne aktivnosti med obdobji nezaznavne nocne hipoglikemije pri mladostnikih z insulinsko odvisno sladkorno boleznijo
Avtor: Elizabeta Rajer, Ivan Radan
Mentor: doc.dr. Tadej Batellino
Izhodišca. Hipoglikemija je pogost in nevaren zaplet z inzulinom zdravljene sladkorne bolezni. Njena pogostost raste z intenziviranjem inzulinskega zdravljenja in približevanjem krvnega sladkorja vrednostim zdrave, nediabeticne populacije. Poseben problem predstavljajo nocne hipoglikemije, ki jih bolniki pogosto ne zaznajo in jih je klinicno težko neposredno dokazati. Pogosto preidejo neopažene, vendar njihove posledice niso zato nic manj škodljive. Zanesljiva neinvazivna metoda diagnosticiranja nocnih nezaznavnih hipoglikemij bi prinesla velik napredek k vodenju sladkorne bolezni in kvaliteti življenja bolnikov. Spremljanje razmerja kortizol/kreatinin, merjenje kožne prevodnosti in iskanje specificnih sprememb v EEG, se niso izkazali za zanesljive nacine neinvazivnega dokazovanja nezaznavnih nocnih hipoglikemij, tako da zaenkrat ni znana nobena uporabna neinvazivna metoda.
Hipoteza. Naša hipoteza je bila, da se motoricna aktivnost bolnikov v spanju spreminja glede na nivo krvnega sladkorja in to je mogoce zaznati z aktimetrijo.
Bolniki in metode. Pri osemnajstih mladostnikih z inzulinsko odvisno sladkorno boleznijo (povprecna starost 13,3 ± 1,6 let) smo ponoci (od 23.00 do 06.00 ure) merili koncentracijo krvnega sladkorja in istocasno spremljali motoricno aktivnost z aktimetrom. V podlaktno veno smo jim uvedli intravensko kanilo, iz katere smo preko posebnega katetra s crpalko zbirali vzorce v epruvete. Epruveto smo menjavali vsakih 30 minut. Meritve KS so bile opravljene zjutraj. Na zapestje druge roke smo preiskovancem namestili aktimeter. Med meritvijo smo preiskovance ves cas opazovali, zapisovali morebitna prebujanja in bili pozorni na razvoj znakov hipoglikemije. Pred obdelavo podatkov smo iz analize izlocili vsa obdobja budnosti in obdobje med 05.00 in 06.00 uro zjutraj, ko so se preiskovanci že prebujali. Tako zbrane aktimeterske podatke aktivnosti smo primerjali glede na trenutne koncentracije krvne glukoze. Podatke smo analizirali z analizo variance (ANOVA) in Tukeyevim testom za podrobnejšo analizo razlik med skupinami. S pomocjo regresijske analize smo skušali ugotoviti povezanost motoricne aktivnosti in krvnega sladkorja.
Rezultati. Nezaznavno nocno hipoglikemijo smo zabeležili pri desetih od osemnajstih preiskovancev (55%). Epizode hipoglikemije so trajale povprecno 2,0 ± 1,3 ure (povprecna vrednost ± SD). Med obdobji nocne hipoglikemije se ni nihce spontano prebudil ali kazal znakov hipoglikemije. 184 dobljenih parov podatkov (vrednost krvnega sladkorja in indeks aktivnosti) smo razdelili v tri skupine glede na definicijo hipoglikemije (KS < 3,5 mmmol/l), normoglikemije (KS 3,5-6,1 mmol/l) in hiperglikemije (KS > 6,1 mmol/l). Analiza variance je pokazala statisticno pomembno razliko med skupinami (F2,181 = 4,09; p < 0,02). Nadaljnja analiza s Tukeyevim testom za ugotavljanje znacilnosti razlik med posameznimi skupinami je pokazala statisticno pomembno razliko med hipoglikemicno in normoglikemicno ter med hipoglikemicno in hiperglikemicno skupino preiskovancev. Razlike med normo- in hiperglikemicno skupino nismo našli. Regresijska analiza je pokazala statisticno znacilno povezavo med vrednostjo krvnega sladkorja in indeksom aktivnosti.
Zakljucek. Nezaznavne nocne hipoglikemije so pogost pojav. Naši rezultati kažejo statisticno znacilno povezanost med nizkimi vrednostmi krvnega sladkorja in povecano motoricno aktivnostjo v teh obdobjih. To nakazuje možnost klinicne uporabnosti aktimetrije za odkrivanje nezaznavnih nocnih hipoglikemij. To je za enkrat prvi opis možnosti uporabe kakšne neinvazivne metode za odkrivanje NNH. Za natancno ovrednotenje in za opredelitev aktimetricnih parametrov za posameznega bolnika, so potrebne dodatne raziskave na vecjem številu bolnikov.
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[Abstract / English version]
Monitoring of motor activity during asymptomatic nocturnal hypoglycemia in adolescents with insulin dependent diabetes mellitus
Author: Elizabeta Rajer, Ivan Radan
Mentor: doc.dr. Tadej Batellino
Background. Hypoglycemia is a common and dangerous complication of insulin-dependent diabetes mellitus (IDDM). Its incidence increases with intensification of the treatment aiming at near-normalization of blood glucose. Hypoglycemia is the major impediment of successful intensive insulin treatment. Nocturnal hypoglycemia is a widespread and important problem in children and adolescents with diabetes and a phenomenon that is difficult to recognize clinically. Hypoglycemic episodes often remain unrecognized but their concequences are not less serious then those caused by symptomatic hypoglicemia. Development of a painless, noninvasive methode to detect unawared nocturnal hypoglycemia would represent a significant improvement in the treatment of diabetes and in the quality of patients´ life. Some atempts like morning cortisol/creatinin ratio or EEG monitoring have been made to develop a noninvasive methode to detect night hypoglycemias but none of them was reliable enough.
Hypothesis. Our aim was to test the hypothesis that the motor activity, detectable with an activity monitor, corellates with glycemic level (normo-, hipo and hyperglycemia).
Patients and methods. Motor activity was observed using wirst actigraphy with simultaneously measurment of blood glucose. Eighteen pediatric patients with IDDM were investigated (mean age 13,3 ± 1,6 years). An antebrachial i.v. line was established and blood was sampled half-hourly from 23:00 to 06:00 by means of special catheter connected to a continous pump. Actimeter was placed on the contralateral wirst to record activity in the same time period. Patients were continuously observed and a protocol of awake periods or hypoglycemic signs was written. Before data analysis we excluded all the periodes of wakefullnes and periodes betwen 05:00 and 06:00 am when the patients started to wake up. Data were analysed with ANOVA, further comparison of groups was done by the Tukey test. Correlation between activity and serum glucose levels was tested using the regression analysis.
Results. Nocturnal hypoglycemia was detected in ten of eighteen patients (55 %). All episodes of nocturnal hypoglycemias were asymptomatic, and lasted 2,0 ± 1,3 hours. Analysis of variance of 184 data pairs ( blood sugar vs. activity ), divided into three groups according to the deffinition of hypoglycemia (<3,5mmol/l), normoglycemia (3,5-6,1mmol/l) and hyperglycemia ( > 6,1mmol/l) showed a statistically significant difference between the groups (F2,181 = 4,09; p < 0,02). Further analysis with Tukey´s pairwise comparison procedure to control for multiple testing revealed significant difference in motor activity between hypoglycemia vs. normoglycemia and hypoglycemia vs hyperglycemia group. We found no difference betwen normo vs. hyperglycemia group. Regression analysis showed a significant correlation between motor activity to blood sugar concentration.
Conclusions. Asymptomatic nocturnal hypoglycemia was found in ten of eighteen patients. Significant correlation beetwen motor activity and blood sugar implies the possibility of routine noninvasive monitoring of unawared nocturnal hypoglycemia by actigraphy. Further studies in larger cohort of IDDM patients are needed to evaluate the rutine clinical usefulness of the proposed noninvasive monitoring of asymptomaic nocturnal hypoglycemia.
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