Does seasonality of births in diabetes mellitus reflect pathogenetic differences?

OBJECTIVES: This study indicates that the seasonality of births of patients with DM1 and DM2 has occurred in their adolescence or adulthood. BACKGROUND: Patients with Diabetes mellitus type 2 (DM2) with the maturity onset have different seasonal birth patterns from those with Diabetes mellitus type 1 (DM1) with the maturity onset, or DM1children. METHODS: Monthly numbers of births of 81 and 236 children with DM1 and DM2, respectively, in adolescent or adult age, were adapted to different actual length of calendar months. The 12- and 6-month rhythm was tested using the cosinor regression with 95% confidence interval versus the hypothesis of null seasonality. RESULTS: Regarding DM1 with maturity onset, annual and semiannual rhythm was significant in both genders, with the increase in birth numbers from November to January and decrease in March, April and August. In DM2, only female data displayed a significant annual rhythm, with an increase in birth from April to August and decrease from October to December.  CONCLUSION: The birth seasonality related to DM1 in adolescent or adult age appears to be reciprocal, compared to DM1 in childhood. For DM2, the seasonality of births was found only in females. The increase in female fecundity seems to be related to an increase in the risk of DM2 in female offspring. The outcomes could help in identifying environmental and endogenous factors related to seasonality cycle (Tab. 1, Fig. 1, Ref. 18).

The Derer´s biological - cosmic week and the Halberg´s circaseptan chronome.

There are three common periodic intervals in the life of each human being from time immemorial: the day, the week and the year. The first one is given by the Earth´s rotation, the latter one by its revolution around the Sun. These both do have clear biomedical counterparts. The 7-day week, basically linguistically "period of change" (or a similar period, e.g.10 days in Egypt or 8 days in Etrutria) was obviously originally considered mainly as a product of a societal agreement. Two groups of Czechoslovak clinicians-scientists, however, noted in forties of the XXth century an approximately week period in human laboratory data, after similar attempts abroad a few years earlier. In fifties, L.Dérer, respecting the mathematical and biological principles in medicine and supported by the mathematician A.Huta, demonstrated the presence of the "6-day" rhythm in blood leukocyte counts in patients with leukemia, treated by cytostatics. Posing the question "Where is it from?", he considered also cosmic influences but was unable to study this issue more deeply due to his premature decease. Two decades later, the "Dérer´s circaseptans" found wide confirmation not only in human medicine but also in biology. The pioneering role here belongs to Franz Halberg, USA, the godfather of the "circadians" (originally "Halberg´s paranoia") since the fifties. The possible geocosmic roots of circaseptans are supposed in the geomagnetic activity from interplanetary space, generating under the influence of the Sun rotation the periods around 6-7 days. This is presently documented, surprisingly, also by analysing the Dérer´s original data using more advanced, inferentially statistical method - the Halberg cosinor regression. Thus, the optimal approximation has been achieved for the period of 6.75 days - the 4th harmonics of the Bartels solar rotation cycle. Accordingly, the week can be now, after Dérer and Halberg, understood also - same as day and year - as a biological - geocosmic phenomenon, a geomagnetic week, genetically acquired in the course of billions years´ of evolution, encoded in our chronome. The personality of Ladislav Dérer should, in the history of the Czech and Slovak biomedical sciences, be permanenly standing by such giants as the well known Jan Evangelista Purkyne ("Purkinje") or as Bohumil Nemec, discoverer of the mechanism of positive geotropism of plant roots (Fig. 3, Ref. 28).

Time course of nontyphoid salmonellosis in Slovakia 1957-2008.

AIM: To test in time salmonellosis data the hypothesis respecting the Moon gravity. METHODS: Daily numbers of admissions at Clinic of Infectology 2005-2006 were processed on significance level alpha = 0.05, after finding out their non-Poisson distribution, by cosinor regression in relation to the cycle new moon--full moon--new moon, lasting in average 29.53 days. In yearly incidence of this disease in Slovakia 1957-2008, presence of 18.6-year periodicity, connected with nutation of Moon axis, was tested. RESULTS: In agreement with our results 20 years ago, statistically significant 14.76-day rhythm was revealed,with pronounced swings downwards and upwards near full and new moon again. It is matching the cycling of lunar gravity. In the yearly data, statistically significant 18.6-yearly period, roughly reciprocal against the lunisolar gravitation, is apparent. It has been confirmed by cross-linear regression. CONCLUSIONS: This study may testify to a causal relationship between the gravity and the occurrence of salmonellosis. The 18.6-years' cycling could explain the allegedly global phenomenon--steep decrease of incidence since about 2000. Nevertheless, it succeeds to an equally long and steep increase since 1990, corresponding so far to the found periodicity without proving a supposed new trend.The next years will decide whether the decrease will continue in the sense of this trend towards eradication of this disease or repeated increase will occur in the frame of continuing periodicity. Our findings are indirectly supported by the laboratory documentation of increased virulence of Salmonella in microgravity, published from NASA laboratories 10 years ago. Its practical exploitation for protecting the health of crew of cosmic flights is expected (Fig. 4, Ref. 15).

Circa(ultra)dians of single extrasystoles in chronic respiratory failure versus health at lowland.

BACKGROUND: The circa- and ultradians of the single extrasystoles' frequency in patients with chronic respiratory insufficiency (CRI) in lowlands (Kosice 210 m) were studied by the testing of following null hypotheses: their average frequency as well as rhythmicity is the same as at health. METHODS: In 54 elderly males with CRI, mean numbers of supraventricular (SV) and ventricular (VE) extrasystoles were calculated for each 24 hours. The Halberg cosinor regression was used to test the presence of the 24-hour rhythm and its 2nd to 10th harmonics, i.e. ultradians with the period lengths of 12 to 2.4 hours. The resulting approximating function for either extrasystole type included its point, 95% confidence for mean and 95% tolerance for one individual. The results were compared with those obtained at health at alpha = 0.05. RESULTS: The daily mesors in CRI were 20.9 for SV, for VE 17.6 extrasystoles per hour and subject. This was significantly (20.3 (SV) and 17.0 (VE)) higher than at health. Significant periodic harmonic components were 3 in CRI versus 6 at health for SV and 6 in CRI versus 1 at health for VE. The dominating CRI rhythm was the 8 hour ultradian for SV and circadian for VE while at health the circadian rhythm was leading for every type of extrasystoles. CONCLUSION: The most remarkable effect of CRI versus health at lowlands is a marked increase of the frequency of every type of extrasystoles. SV extrasystoles exert more rhythmicity at health while the VE in disease (Tab. 1, Fig. 1, Ref. 20).

Circa- and ultradians in the occurrence of simple extrasystoles in healthy men at lowland in the light of inferential statistics.

PURPOSE: An exact description of circadian and ultradian rhythms of simple extrasystoles in healthy subjects is lacking. Thirty-seven healthy male subjects, aged 50-76, were randomly taken. Simple extrasystoles from 24-hour Holter ECG were registered and calculated per each hour and processed by cosinor regression. Their occurrence is formulated by 95% confidence and tolerance corridors for supraventricular and ventricular extrasystoles. RESULTS: The number of extrasystoles is relatively low, dispersion of ventricular extrasystoles is significantly higher than supraventricular ones. A significant increase of their frequency versus the general zero trend straight line was found only around 9 a.m. In supraventricular ones a significant increase around 6-7 a.m., 9 a.m., noon, and 4-5 p.m. and a significant depression around 1-2 a.m. and 10 p.m. was present. Only the 24-hour rhythm is significantly present (alpha=0.05) in ventricular beats while in supraventricular ones also the period lengths of 12, 6, 4, 3.4 and 2.4 hours are significant. The significant difference between supraventricular and ventricular extrasystoles exists in the 24-hour amplitudes and 6-hour acrophases. CONCLUSION: One circadian and several ultradian rhythms of simple extrasystoles are present in healthy male subjects over 50 years of age. The 95% tolerance chronograms can be exploited in clinical practice.

Yearly and perhaps transyearly human natality patterns near the equator and at higher latitudes.

Data on the daily numbers of births in Davao, Philippines, available from 1993 to 2003 are re-analyzed herein by linear-nonlinear rhythmometry, as are data from Italy and Japan. A transyear, characterizing the solar wind and other non-photic physical environmental factors, corresponds to a spectral peak of the near-equatorial natality series. This component with a period of about 1.3 years is found to have an amplitude larger than the calendar year, the amplitude ratio being 134%. Whereas the transyear is validated nonlinearly, the 95% confidence interval for the period extending from 1.21 to 1.38 years and the 95% confidence interval for the amplitude not overlapping zero (P < 0.05), the annual variation is only demonstrable by linear least squares analysis. The results bring added evidence for an influence of non-photic environmental effects on human physiology, in this case data collected near the equatorial region, Davao being situated at 7 degrees N, 126 degrees E. They are in keeping with some degree of generality of a rule of reciprocity among mutually supporting physical and biological periodicities. They do not detract from the fact that in other longer data sets at higher latitudes, the calendar year, presumably reflecting climatic influences, dominates the spectrum.

Geographic and extraterrestrial aspects of morbidity and/or mortality patterns from myocardial infarction and stroke.

Two authors (M.K. and M.M.) provided insight into a manuscript submitted by them elsewhere for publication and kindly offered for meta-analysis data on the monthly incidence from January 1989 up to December 2004, of 6094 cerebral infarctions, 414 intracerebral and 277 subarachnoid hemorrhages, cases admitted at the Neurological Clinic in Nové Zamky, Slovakia. Spectral components with a period exceeding (beyond = trans) the length of the calendar year--transyears--reported originally by M.K. and M.M. are here also documented linearly on original data without and after detrending by the fit of first- or second-order polynomials. For intracerebral and subarachnoidal hemorrhage, the zero-amplitude (no-rhythm) assumption is rejected (P < 0.05, not corrected for multiple testing) for the transyear but not for a precise 1.0-year trial period. As reported earlier by M.K. and M.M., the transyear's amplitude is larger than the calendar year's amplitude for all three series of stroke incidence in Slovakia. The putative importance of the new findings stems from earlier and new analyses revealing other spectral components that are presumed signatures of magnetoperiodisms, e.g. about 50- and 7-year components in about five decades of diagnostically unqualified, pooled data on stroke in Minnesota. There is, however, the danger of relatively small numbers providing artifacts for loosely defined transyears. The original cosinor approach by M.K. and M.M., testing anticipated periods, had its strength. The observation of a quindecadal component in mortality from strokes in Minnesota supports the presence of signatures of effects from extraterrestrial space in acute human pathology such as strokes, myocardial infarctions and sudden cardiac death. Magnetoperiodic mechanisms remain to be investigated further as added strokes accumulate in Nové Zamky and greater Slovakia as well as for sudden cardiac death where transyears have been documented in the Czech Republic, in Arkansas and particularly in Minnesota, but not elsewhere (as yet?). This study is also a plea for worldwide access to morbidity, mortality and natality data that constitute a largely unexploited treasure, brought to the fore mainly for relatively short-term comparisons of the effect of interventions against the fiction of imaginary baselines.

Secular rhythms and Halberg's paraseasonality in the time occurrence of cerebral stroke.

OBJECTIVES: To obtain the optimal information concerning the time course of the morbidity od cerebral stroke. BACKGROUND: Recently, long years' cycling, similar to that in sun and geomagnetic activity, is observed in various biomedical variables. Other discovery is that of transyear (over one year) and cisyear (under one year) rhythms,originating also in the sun, in medicine. SUBJECTS: There were 6100 patients with cerebral infarction, 415 with intracerebral and 277 with subarachnoid hemorrhage admitted at Clinic of Neurology in Nové Zámky (area with 70 km radius and 180 000 inhabitants). Their monthly numbers were registered since January 1989 up to December 2004. METHODS: The data were processed by Halberg's cosinor regression. Presence of linear trend and of the period lengths of 10.5 (solar Schwabe-cycle), 5.25, 7.04 (geomagnetic activity cycling), 3.52, 1.70, 1.50, 1.30 (solar wind cycling), 1.20, 1.00 and 0.50 years was tested. Level of statistical significance was set at alpha = 0.05. RESULTS: In all three time series, significant linear trends were found with the estimated monthly increase by 0.8% of the estimated starting mesor value for infarction, 1.2% for cerebral and 1.9% for subarachnoid hemorrhage. Both the solar and geomagnetic cycling with their second harmonics were significant in all three clinical diagnoses. The transyear with period length of 1.3 year was significant in both hemorrhages while in infarction only its borderline significance was achieved. Nevertheless, its amplitude was always higher (by 15 to 83%) than that of 1.00 year estimated cosinusoid. CONCLUSION: All presented time series document increasing trends in the morbidity on cerebral stroke in the given geographic area. The presence of secular, years lasting cycles adds to relatively long list of similar chronocosmoepidemiologic analyses, so far generally ignored due to insufficient understanding of inferential statistics and chronobiology among doctors. The transyear paraseasonality represents a new element in these studies. To honour the nestor of the world chronobiology, who highly acknowledged the work of Ladislav Dérer, the designation "Halberg's paraseasonality" is proposed (Tab. 2, Fig. 3, Ref. 17).

[Complex therapy of chronic hepatic encephalopathy supplemented with probiotic: comparison of two studies]. / Komplexná liecba chronickej hepatálnej encefalopatie doplnená probiotikom. Porovnanie dvoch stúdií.

BACKGROUND: Several reports about usefulness of probiotics, including Enterococcus faecium in the treatment of chronic hepatic encephalopathy in patients with liver cirrhosis have been recently published. The results obtained by the administration of Enterococcus faecium M-74 + selenium will be evaluated and compared with those published by Loguercio et al. for Enterococcus faecium SF 68. METHODS AND RESULTS: Fifteen patients with liver cirrhosis, portal hypertension and chronic hepatic encephalopathy were treated, beside the standard therapy, also with one capsule of probiotic "Enterococcus faecium M-74 + Selenium" per day in three four-week periods, separated by two fortnight pauses. During the treatment, every patient was examined 9-times. The severity of chronic hepatic encephalopathy was evaluated with the aid of the portal systemic encephalopathy index, calculated from 5 parameters (mental stage, asterixis, number connecting test, blood ammonia, EEG). The indexes of initial and final values were compared. The time course of blood ammonia levels and that of results from number connecting test in either study were mutually compared on the basis of interval estimates of quadratic regression function. Significant improvement of the portal systemic encephalopathy index after the treatment was found: it decreased in average by 70% (55 to 85%, interval 95% confidence interval). The mental stage improved and the asterixis disappeared. The blood ammonia levels as well as the results from the number-connecting test after 8-9 weeks significantly approached the normal pattern. EEG findings improved and they were often normalised. Our starting blood ammonia levels (increased by 31% above norm) and results from the connecting test (increased by 60%) were significantly lower accordingly the Loguercio et al. (increased by 243 and 238%, respectively). During the treatment, the values in our study decreased by 25% and 30%, in the compared study by 50% and 70%. CONCLUSIONS: Our results proved the hypothetical favourable effect of probioticum Enterococcus faecium M-74 + Selenium on chronic hepatic encephalopathy. Interestingly, a markedly higher relative therapeutic effect has been achieved in more serious disorder in comparison with the less severe disorders in the present study.

Insulin gene profile cycles with season of birth of future diabetic children and their relatives.

BACKGROUND: HLA class II gene pattern and IA-2A antibody positivity, revealing selected risks for prediction of type 1 diabetes mellitus (DM1), were previously shown to be cycling roughly in parallel with seasonally fluctuating frequencies of births of future diabetic children. Is this also true for insulin genotyping? Is this also true for births of the healthy close relatives of children with DM1? PATIENTS AND METHODS: In 98 Slovak children with DM1 and in 60 healthy parents and siblings, two single nucleotide polymorphisms of the insulin gene (-23 Hph I; +1127 Pst I) were typed. Results were expressed as score 0 (maximal risk) up to 2 (minimal risk or protection), or 0-4 for the sum of both scores. Birth seasonality of these risk scores was tested by Halberg cosinor regression. RESULTS: Results were similar for the two alleles; therefore, the summed risk score was evaluated. The DM1 risk from the insulin gene pattern in births of future diabetics cycled significantly semi-annually, with maxima around the spring and autumn equinoxes. In the relatives, a significant annual and extremely pronounced quarterly peaking rhythm was found, with maximum risk in births around the autumn equinox and shortly after the winter solstice. Significant protection peaks are present in late winter, spring and summer. CONCLUSION: The highest frequency of Coxsackie infections in the Slovakian child population, and of 'diabetic' births and manifestations, found earlier together with maximal risks from HLA II and IA-2A antibodies in late summer and early autumn, is now confirmed also for the insulin gene pattern in diabetic children and even also for their healthy close relatives.

Some lung cellular parameters reflecting inflammation after combined inhalation of amosite dust with cigarette smoke by rats.

Cellular changes were followed in lung cell suspensions after 175 day inhalation by rats of concentrations 30 mg/m3 or 60 mg/m3 of amosite asbestos every second day combined with daily exposure to cigarette smoke at 30 mg of total particulate matter (TPM)/m3 air. Concomitantly, lung inflammation was assessed by changes in the bronchoalveolar lavage fluid (BALF). A dose-dependent rise in the BALF inflammatory parameters was found. The rise of the proportion of binucleate (BNC) and multinucleate cells (MNC) in lung cell suspensions was also dose-dependent. It is concluded that, in the experimental assessment of effects of fibrogenic dusts, the number of BNC and of MNC in lung cell suspensions may serve as a useful semiquantitative biomarker of the inflammation.

IA-2A positivity rate at manifestation of type 1 diabetes mellitus in Slovak children culminates in September.

BACKGROUND: New cases of type 1 diabetes mellitus (DM1) in Slovak children accumulate in late summer, autumn and winter. HYPOTHESES: Children manifesting the disease in these seasons have higher autoantibody positivity than those first diagnosed in spring or summer. PATIENTS AND METHODS: One hundred and fifty Slovak children (and adolescents), aged 1-14 (15-17) years at the manifestation of DM1, born 1978-2000, with the disease manifested 1989-2001, were investigated at diagnosis by IA-2A, GADA and IAA autoantibody positivity, using standard radioimmunoassay procedures. The resulting risk score values (0-1) were related to calendar days of diagnosis. Their annual, semi-annual and quarterly periodicity was tested using Halberg's cosinor regression. RESULTS: Only IA-2A positivity at the time of diagnosis showed significant seasonal cycling, with the acme around the autumn equinox and with the nadir in spring. There was no increase of this positivity in winter. CONCLUSION: The maximum autoantibody levels were found for those manifesting the disease in late summer and early autumn--the only time of year in Slovakia when both the numbers of births of future diabetic children as well as those of manifestation of new cases are significantly above average.

[Importance of determining serologic markers in patients with celiac disease]. / Význam vysetrenia serologických markerov u pacientov s celiakiou.

BACKGROUND: Coeliac disease is presently considered to be an autoimmune disorder. Basis for the diagnosis is the invasive histochemical examination of the intestinal biopsy. Pathologic changes are classified into three grades according to the villous atrophy. Due to the autoimmune process, the patients serum levels of the specific and nonspecific antibodies, more which easily accessible to investigation, are increase. METHODS AND RESULTS: One hundred thirty six probands (32 with coeliakia, 72 with other gastrointestinal disorders and 32 healthy ones) were included into the study. The antiendomysial, antireticular and antigliadin antibodies were examined. Results were compared with the histological finding in the gut sample. The highest sensitivity was found for antigliadin IgA antibodies (81%) and antiendomysial antibodies (75%). High specificity of the reaction in healthy subjects as well as in those with other gastrointestinal disorders (up to 100%), was found for antiendomysial and antireticular antibodies. CONCLUSIONS: The most appropriate screening test the diagnosis of coeliac disease, appears to be the examination of the antigliadin antibodies of the class IgA and that of antiendomysial antibodies. On the basis of serology, today's high rate of underdiagnosing the disease can be prevented. However, the tests cannot differentiate between different degrees of the histological damage of the gut.

Daily birth numbers in Passo Fundo, South Brazil, 1997-1999: trends and periodicities.

Between October 6, 1997 and April 30, 1999, 5011 births (mean: 8.76 per day) were registered in the city of Passo Fundo, South Brazil. The sequence of 572 daily birth numbers was not random (iteration test). Neyman distribution (m = yen ) showed the best fit. Clusters of days with higher birth numbers alternated with days with low numbers of births. Periodogram analysis revealed a significant periodicity of 6.98 days. The cosinor regression, testing 10 a priori supposed period lengths, found significant seasonality peaking in August-September and significantly highest birth numbers on Thursdays. Among the lunar and solar rotation cycles, the tropic lunar cycle and its 4th harmonic were most pronounced, in agreement with results concerning natality in Germany obtained by Svante Arrhenius in the 19th century. These findings confirm Derer-Halberg's concept of multiseptans. In addition to cycling, a significantly increasing linear trend with a daily increase of 0.0045 births was encountered. This documents a growth of the population in agreement with national statistical data.

Daily birth numbers in Passo Fundo, South Brazil, 1997-1999: trends and periodicities

Between October 6, 1997 and April 30, 1999, 5011 births (mean: 8.76 per day) were registered in the city of Passo Fundo, South Brazil. The sequence of 572 daily birth numbers was not random (iteration test). Neyman distribution (m = Ñ) showed the best fit. Clusters of days with higher birth numbers alternated with days with low numbers of births. Periodogram analysis revealed a significant periodicity of 6.98 days. The cosinor regression, testing 10 a priori supposed period lengths, found significant seasonality peaking in August-September and significantly highest birth numbers on Thursdays. Among the lunar and solar rotation cycles, the tropic lunar cycle and its 4th harmonic were most pronounced, in agreement with results concerning natality in Germany obtained by Svante Arrhenius in the 19th century. These findings confirm Derer-Halberg's concept of multiseptans. In addition to cycling, a significantly increasing linear trend with a daily increase of 0.0045 births was encountered. This documents a growth of the population in agreement with national statistical data

Trends of childhood diabetes incidence in Slovakia 1985-2000: accelerated increase in the years 1990-2000.

BACKGROUND: A sudden rise in the incidence of childhood diabetes (DM 1) in Central and Eastern Europe over the last decade has been reported. AIM: To compare in Slovakia incidence trends in the 80s with those in the 90s. SUBJECTS AND METHODS: The data from the Slovak Register of Diabetic Children diagnosed in 1985-2000 (n=1818) were divided into 6 groups according to sex and age at diagnosis (0-4, 5-9, 10-14). Trends were computed separately for 1985-1990 and 1990-2000. The 95% confidence estimates of linear regression coefficients and as percentages from the estimated starting values in 1985 and 1990, were calculated by the linear regression based on statistical inferential approach. RESULTS: Non-significant increasing or decreasing trends were found in 6 gender/age groups 1985-1990. In the 90s, however, significantly increasing trends were present in each of 6 groups. They were significant (p<0.05) in the male groups and in the total of all cases. The overall incidence rise (+0.03 cases per 100000 children per year) was nonsignificant in the 80s but significant in the 90s (+0.63/100000/year). As a result, the incidence rate of childhood diabetes in Slovakia rose from 6.01 new cases per 100000 children per one year in 1985 to 13.53/100000/year in 2000. CONCLUSION: The overall DM 1 incidence increaseed from the 1980s (80s) to the 1990s (90s), expressed in the number of new cases, is more than a 20-fold absolutely and almost 10-fold in relative terms. This was not due to an improvement in diagnosis in 1990s. Both the gender and age heterogeneity were present. (Tab. 2, Fig. 2, Ref. 25.).

Onset of spontaneous pneumothorax and the synodic lunar cycle.

The relation between spontaneous pneumothorax events and synodic lunar cycle was studied in a retrospective analysis of patients with a first or recurrent spontaneous pneumothorax. The study included a total of 244 patients, 203 males and 41 females. The data were arranged along the first (new moon) to 28th day (one day before another new moon) of the synodic lunar cycle. Periodogram analysis revealed a 14-day rhythm, significant for the male and pooled sample. Cosinor analysis found the whole synodic lunar cycle and its 2nd, 4th and 5th harmonics as significant. Maximal accumulation of cases happened 1 week before and 1 week after the new moon. Mechanisms of a putative moon influence are not clear.

Risk factors for glucose intolerance in active acromegaly

In the present retrospective study we determined the frequency of glucose intolerance in active untreated acromegaly, and searched for risk factors possibly supporting the emergence of the diabetic condition. Among 43 patients, 8 (19 percent; 95 percent CI: 8-33 percent) had diabetes mellitus and 2 (5 percent; 1-16 percent) impaired glucose tolerance. No impaired fasting glycemia was demonstrable. The frequency of diabetes was on average 4.5 times higher than in the general Slovak population. Ten factors suspected to support progression to glucose intolerance were studied by comparing the frequency of glucose intolerance between patients with present and absent risk factors. A family history of diabetes and arterial hypertension proved to have a significant promoting effect (P<0.05, chi-square test). A significant association with female gender was demonstrated only after pooling our data with literature data. Concomitant prolactin hypersecretion had a nonsignificant promoting effect. In conclusion, the association of active untreated acromegaly with each of the three categories of glucose intolerance (including impaired fasting glycemia, not yet studied in this connection) was defined as a confidence interval, thus permitting a sound comparison with the findings of future studies. Besides a family history of diabetes, female gender and arterial hypertension were defined as additional, not yet described risk factors

Risk factors for glucose intolerance in active acromegaly.

In the present retrospective study we determined the frequency of glucose intolerance in active untreated acromegaly, and searched for risk factors possibly supporting the emergence of the diabetic condition. Among 43 patients, 8 (19%; 95% CI: 8-33%) had diabetes mellitus and 2 (5%; 1-16%) impaired glucose tolerance. No impaired fasting glycemia was demonstrable. The frequency of diabetes was on average 4.5 times higher than in the general Slovak population. Ten factors suspected to support progression to glucose intolerance were studied by comparing the frequency of glucose intolerance between patients with present and absent risk factors. A family history of diabetes and arterial hypertension proved to have a significant promoting effect (P<0.05, chi-square test). A significant association with female gender was demonstrated only after pooling our data with literature data. Concomitant prolactin hypersecretion had a nonsignificant promoting effect. In conclusion, the association of active untreated acromegaly with each of the three categories of glucose intolerance (including impaired fasting glycemia, not yet studied in this connection) was defined as a confidence interval, thus permitting a sound comparison with the findings of future studies. Besides a family history of diabetes, female gender and arterial hypertension were defined as additional, not yet described risk factors.