Background: GDM is a condition in which women without previously diagnosed diabetes exhibit high blood glucose levels during pregnancy. Pregnancy causes some insulin resistance in all women, but only a few develop GDM. Objective: To test the hypothesis that women with GDM have impaired regulation of blood iron storage and transport, decreased renal function due to decreased glomerular filtration rate and occurrence of urinary tract infection (UTI). Study design and Methods: Incidence of blood iron storage was investigated in n=30 pregnant kosovar women with GDM after mild of pregnancy and in n=30 pregnant women without GDM (years 2010-2012). Results and Discussion: Baby weights, both systolic and diastolic BP, creatinine, albumin, lymphocytes, monocytes, WBC and granulocytes in both groups were within their normal ranges in both groups. Compared to control group, glucose was higher in women with GDM (mean ± SD: 7.43±2.23 mg/dL vs. 4.33±0.63 mg/dL; P&lt;0.001). Women with GDM had also higher RBC (mean ± SD: 4.4±0.8 % vs. 3.8 ± 0.3 %; P&lt;0.005) and HGB (mean ± SD: 13.0±3.2 g/dL vs. 11.2±1.4 mg/dL; P&lt;0.05), and decreased renal functionality (MDRD-GFR: 92.8 ± 25.8 g/dL vs. 108.2 ± 38.2 g/dL; P&lt;.05).Conclusion: There is a potential association between iron status and GDM. The role of iron from diet and/or from supplementation in GDM pathogenesis needs still to be examined. In additio

Armond Daci

Brikene Elshani

Giangiacomo Beretta

Background: GDM is a condition in which women without previously diagnosed diabetes exhibit high blood glucose levels during pregnancy. Pregnancy causes some insulin resistance in all women, but only a few develop GDM. Objective: To test the hypothesis that women with GDM have impaired regulation of blood iron storage and transport, decreased renal function due to decreased glomerular filtration rate and occurrence of urinary tract infection (UTI). Study design and Methods: Incidence of blood iron storage was investigated in n=30 pregnant kosovar women with GDM after mild of pregnancy and in n=30 pregnant women without GDM (years 2010-2012). Results and Discussion: Baby weights, both systolic and diastolic BP, creatinine, albumin, lymphocytes, monocytes, WBC and granulocytes in both groups were within their normal ranges in both groups. Compared to control group, glucose was higher in women with GDM (mean ± SD: 7.43±2.23 mg/dL vs. 4.33±0.63 mg/dL; P<0.001). Women with GDM had also higher RBC (mean ± SD: 4.4±0.8 % vs. 3.8 ± 0.3 %; P<0.005) and HGB (mean ± SD: 13.0±3.2 g/dL vs. 11.2±1.4 mg/dL; P<0.05), and decreased renal functionality (MDRD-GFR: 92.8 ± 25.8 g/dL vs. 108.2 ± 38.2 g/dL; P<.05).Conclusion: There is a potential association between iron status and GDM. The role of iron from diet and/or from supplementation in GDM pathogenesis needs still to be examined. In addition we have observed a decrease of glomerular filtration rate in women with GDM. Due to the lack of studies on the relationships between GDM and UTI, and to the retrospective design of the present investigation, it is difficult to establish whether UTI may be a GDM causal factor or a consequence of GDM symptoms, signs and/or of its correlated pathologies

A. Daci

B. Elshani

G. Beretta

AIR Universita degli studi di Milano

88 Med Arh. 2013 Apr; 67(2): 88-90  • originAl pAper Gestational Diabetes Mellitus (GDM) in the Republic of Kosovo: a Retrospective Pilot Study. Doi: 10.5455/medarh.2013.67.88-90Med Arh. 2013 Apr; 67(2): 88-90 received: January 18th 2013 | Accepted: March 25th 2013CONFLICT OF INTEREST: NONE DECLAREDoriginal papergestational Diabetes Mellitus (gDM) in the republic of Kosovo: a retrospective pilot Study.Armond Daci1, Brikene Elshani2, Giangiacomo Beretta3Department of Pharmacology, Faculty of Medicine, University of Prishtina, Prishtina, Republic of Kosovo1Department of Pharmaceutical Sciences, University of Milan, Milan, Italy2Gynecological Clinic of Kosovo (Qendra Klinike Universitare e Kosovës, QKUK), University Clinical Center of Kosovo, Prishtina, Republic of Kosovo3Background: GDM is a condition in which women without previously diagnosed diabetes exhibit high blood glucose levels during pregnancy. Pregnancy causes some insulin resistance in all women, but only a few develop GDM. Objective: To test the hypothesis that women with GDM have impaired regulation of blood iron storage and transport, decreased renal function due to decreased glomerular filtration rate and occurrence of urinary tract infection (UTI). Study design and Methods: Incidence of blood iron storage was investigated in n=30 pregnant kosovar women with GDM after mild of pregnancy and in n=30 pregnant women without GDM (years 2010-2012). Results and Discussion: Baby weights, both systolic and diastolic BP, creatinine, albumin, lymphocytes, monocytes, WBC and granulocytes in both groups were within their normal ranges in both groups. Compared to control group, glucose was higher in women with GDM (mean ± SD: 7.43±2.23 mg/dL vs. 4.33±0.63 mg/dL; P<0.001). Women with GDM had also higher RBC (mean ± SD: 4.4±0.8 % vs. 3.8 ± 0.3 %; P<0.005) and HGB (mean ± SD: 13.0±3.2 g/dL vs. 11.2±1.4 mg/dL; P<0.05), and decreased renal functionality (MDRD-GFR: 92.8 ± 25.8 g/dL vs. 108.2 ± 38.2 g/dL; P<.05).Conclusion: There is a potential association between iron status and GDM. The role of iron from diet and/or from supplementation in GDM pathogenesis needs still to be examined. In addition we have observed a decrease of glomerular filtration rate in women with GDM. Due to the lack of studies on the relationships between GDM and UTI, and to the retrospective design of the present investigation, it is difficult to establish whether UTI may be a GDM causal factor or a consequence of GDM symptoms, signs and/or of its correlated pathologies. Key words: Gestational diabetes, preeclampsia, blood iron regulation, urinary tract infections, oxidative stress.Corresponding author: Armond Daci, MS, Msc. Faculty of medicine, University of Prishtina. Phone: +38138512929; cell: +37744418385; E-mail: armondd@hotmail.com.1. inTroDUCTionGDM is a condition in which pregnant women without previously diagnosed di-abetes begin exhibiting high blood glu-cose levels during pregnancy, accounting for the ~ 90% of all pregnancies compli-cated by diabetes (1). GDM affects around the 7% of all pregnancies and, depending on the population sample and diagnostic criteria, its prevalence may range from 1 to 14% (2).Accepted classical risk factors for GDM are: previous diagnosis of GDM or pre-diabetes, impaired glucose tolerance, or impaired fasting glycemia, a family his-tory revealing a first degree relative with type 2 diabetes, maternal age – a woman’s risk factor increases as she gets older (es-pecially for woman over 35 years of age), ethnic background (those with higher risk factors include African-Americans, Afro-Caribbeans, Native Americans, Hispanics, Pacific Islanders, and people originating from south Asia, overweight, obesity or severe obesity increases the risk by a fac-tor 2.1, 3.6 and 8.6, respectively, a previous pregnancy which resulted in a child with a high birth which resulted in a child with a high birth weight (>90th centile, or >4000 g ( 8 lbs 12.8 oz), previous poor obstetric his-tory (3, 4). In addition to this, statistic show a double risk of GDM in smokers (5). Ba-bies born from mothers affected by GDM are typically at increased risk of macroso-mia (6, 7, 8). And of additional problems such as the development of childhood obesity and of type 2 diabetes later in life. Women with GDM are at a significantly higher risk of developing preeclampsia or hypertension after pregnancy compared to healthy subjects (9), probably due to presence of preexisting common risk fac-tors for both GDM and hypertension (10). Other studies have shown that GDM may be also associated to increased blood iron storage and transport (11, 12).In addition, different studies on the prevalence of uri-nary tract infections (UTI), symptomatic and/or asymptomatic bacteriuria in dif-ferent populations of female diabetic pa-tients reported contrasting results, show-ing that they can be either increased (13); or unchanged to this diabetic complication compared to non-diabetic subjects (14).Hence, the aim of this study was (a) to furnish a preliminary description of the pathophysiological conditions of two se-lected population of Kosovar women with and without GDM, and (b) to evaluate the 89 Med Arh. 2013 Apr; 67(2): 88-90  • originAl pAperGestational Diabetes Mellitus (GDM) in the Republic of Kosovo: a Retrospective Pilot Study.effects of diabetes on the impairment of blood iron physiological control, blood pressure and renal functionality status, and susceptibility to develop UTI.2. eXperiMenTAl STUDY DeSign AnD MeTHoDSPatients, pregnant women (n=60) were recruited from the Obstetric-Gy-necologic Clinic of Prishtina (QKUK, Republic of Kosovo) during the years 2010/2012 and divided in two groups on the basis of diagnosis: GDM group (n=30) and control group (CTR, total n=30 with-out GDM, of which n=18 had normal clin-ical pregnancy status and n=12 treated for preeclampsia). All women gave de-livery by Cesarean delivery exception for 6 patients for which delivery was stimu-lated by oxitocin administration. Patients were followed-up from 2010 to 2012. The measurements of blood parameters gly-caemia, creatinine, albumin, lympho-cytes, monocytes, granulocytes, white blood cells, red blood cells, haemoglo-bin, Glomerular filtration rate (GFR) was estimated using the modification of diet in renal disease (MDRD) algorithm [15].Urine analysis with microscopy epithelial cells, leukocytes, bacteria, oxalate crys-tals and erythrocytes, as well as histolog-ical examination were carried out using standard assay procedures of laboratory of Biochemistry of the University Clini-cal Center of Kosovo (UCCK). The pres-ence/absence of vaginal infections was established using standard microbiolog-ical protocols in institute of microbiol-ogy in the University Clinical Center of Kosovo (UCCK). Vaginal wet mount was observed with microscopy by placing the specimen on a glass slide and mixing with a salt solution.Continuous clinical variables were compared by two-tailed pairwise Stu-dent’s t test for independent measure-ments with Bonferroni’s correction for multiple comparisons and discrete vari-ables by Fisher’s exact test. Computations were conducted on original data and on log transformed data to reduce the ef-fect of skewness. Minimal level of signif-icance of the difference was set at P<0.05. The data matrices for computations were built with an OpenOffice Calc Spread-sheet for Linux (v. 3.2.1), and all computa-tions were done with R-commander GUI for R (v. 1.5–6) [16].3. reSUlTS AnD DiSCUSSionIn Table 1 and Table 2 are reported means, standard deviations and quintiles for the monitored physiological param-eters (weights of babies, weeks of gesta-tion at clinical visit, systolic and diastolic BP), blood biochemical parameters (cre-atinine, glucose, albumin, hemoglobin), blood cells profile (lymphocytes, mono-cytes, red blood cells (RBC), white blood cells (WBC) and granulocytes), and re-nal functionality determined in preg-nant women with and without GDM re-spectively.Gestation duration was lower than the full term of 40 weeks for normal de-livery in both groups. The gestation time before delivery was 2.7 weeks shorter in group II (35.8 ± 2.5 weeks) compared to group I (38.5 ± 2.2 weeks, P<0.001). Mean values of babies weight, and mothers’ systolic and diastolic BP, creatinine, al-bumin, WBC and granulocytes in both groups were within their normal ranges, with no significant difference between the two groups (P>0.05). However, for both groups, women falling into the two highest quintiles (IV and V) showed sys-tolic and diastolic BP higher than ref-erence values. In both groups, lympho-cytes and monocytes mean values and quintiles were significantly elevated in respect to the matched reference values for the CTR group (17). Probably resulting from the presence of infections in both groups (see paragraph 3.2). As expected, blood glucose was higher in group I (mean ± SD: 7.43 ± 2.23 mg/dL vs. 4.33 ± 0.63 mg/dL; P<0.001), on account of their di-abetic status. Women in this group had also higher RBC (mean±SD: 4.4±0.8 % vs. 3.8±0.3 %; P<0.005) and HGB (mean ± SD: 13.0 ± 3.2 g/dL vs. 11.2 ± 1.4 mg/dL; P<0.05). Women with GD showed de-creased renal functionality, as evidenced by the significant decrease of their mean GFR value in respect to that of women with preeclampsia (MDRD-GFR: 92.8 ± 25.8 g/dL vs. 108.2 ± 38.2 g/dL; P<0.05).The high concentration of mitochon-dria in placenta, one of the major sources of free radicals in living organism, may be a causal/concurrent condition in the de-velopment of GDM, due to the oxidative stress that may be induced by the impair-ment of their activity. In particular, iron, which is abundant in placenta, is one of the most important generators of highly reactive free radicals in both normal and pathological conditions (18). Our findings that blood iron, in terms of blood HGB and RBC, is significantly elevated in preg-nant women affected by GDM compared with women with preeclampsia (Hb: 13.0 ± 3.2 g/dL vs.11.2 ± 1.4 g/dL; P<.05) are in good agreement with those recently re-ported in a similar study by Afkhami-Ar-dekani et al. (11). In this study the concen-trations of serum ferritin, iron, transfer-rin saturation and HGB, MCV, and MCH were significantly higher in Iranian preg-nant women with GDM (Hb: 13.4 ±1.1 g/dL vs. 11.8 ± 1.4 g/dL; P<.001), indicating a potential association between increased iron status and GDM. A few years earlier, Table 1. Pregnant women with GD (normal ranges in brackets from ref 17. *P<0.05; ***P<0.005; ****P<0.001 compared to CTR group. (tab.2). Values exceeding refernces values are in bold. Table 2. Control pregnant women (normal ranges in brackets from ref. 17. *P<0.05; ***P<0.005; ****P<0.001 compared to CTR group. (tab.2). Values exceeding refernces values are in bold.90 Med Arh. 2013 Apr; 67(2): 88-90  • originAl pAper Gestational Diabetes Mellitus (GDM) in the Republic of Kosovo: a Retrospective Pilot Study. Chan and colleagues concluded that increased iron storage and transport, (e.g. elevated serum ferritin), early in gestation are as-sociated with an increased risk of GDM (12). The results of their study suggested that this associa-tion, at least in part, may be medi-ated by the maternal fat mass and obesity. Similar conclusions were reported in 2002 by Lao and col-leagues working on a population of Chinese pregnant women (19). These authors found that high ma-ternal hemoglobin (more than 13 g/dL) at the initial prenatal visit in a population of Chinese women is an independent risk factor for GDM. In another study the same au-thors found that maternal hepatitis B sur-face antigen (HBsAg) carriage could ex-plain in part the association between in-creased serum ferritin concentration with GD, and that the HBsAg carrier status is an independent risk factor for GDM (20).The decrease of renal functionality we found in pregnant women affected by GDM (115.3±16.0 vs 101.3±18.5 (Table 1 and Table 2) without significant increase of BP, indicated that this loss of renal functionality was probably associated to a glomerular damage still in an early stage of development. By contrast, as shown in Figure 1, the loss of renal functionality observed in pregnant women with GD was paralleled by a highly significant ele-vation of UTI compared to those affected by BP dysfunctions (100% vs. 13.3%, P<0.001). These results were in good ac-cordance with those from previous stud-ies reporting that mothers affected by GDM are at higher risk of complications from UTI along with preeclampsia, hy-pertension, and Cesarean delivery (21). In particular, the predisposition to UTI in DM and GDM may result from sev-eral factors. Susceptibility to this kind of infections seems to increase with longer duration and greater severity of diabetes. As different studies have investigated the role of UTI in preeclampsia (22, 23, 24, 25, 26). The role of UTI in GDM is poorly in-vestigated and understood (27). Only few studies have shown that UTI caused by different bacteria are common in women with GD, and that their growth is proba-bly due the favorable growth conditions induced by high blood and urine glucose. The results of the present study support this conclusion, as well evidenced by the dramatic difference in the UTI prevalence found for the pregnant women belonging to the GDM group and to the CTR group, in which only those in GDM group were affected by diabetes (Figure 1).4. ConClUSionSThe results reported in this study have shown that women affected by GDM have, apart higher blood glucose, enhanced blood iron transport and storage, decreased renal performance and higher prevalence of UTI. Hence, it can be hypothesized that the strik-ingly higher prevalence of UTI in GDM may originate from the cascade of events sum-marized in the scheme reported in Figure 2. The insulin resistance and the increase oxidative stress mediated by the impaired of iron metabolism associated to pregnancy status and further elicited by GDM, leads to the enhancement of blood glucose, which is known to trigger detrimental processes damaging the renal glomerular filtration system, which in turn lead to the progres-sive increase of BP. The consequent rise in urine glucose concentration and enhanced tissue permeability may then ‘open the way’ to the diffusion of microorganisms and pathogens into the urinary tract. These findings, although limited by the low num-ber of subjects involved and by to its retro-spective design, warrant to keep support-ing the research on appropriate measures and methodologies for the prevention, the treatment and the management of all the different multifaceted aspects of GDM in-cluding UTI iron intake monitoring, to en-sure better and safer pregnancy outcomes.reFerenCeS1. Setji T, Brown A, Feinglos M. Gestational Diabetes Mellitus. Clinical Diabetes. 2005;  30(1): 17-24.2. American Diabetes Association. Gestational Diabe-tes Mellitus. Diabetes Care. 2003;  26(1): 103-105.3. Ross G. Gestational diabetes. Aust Fam Physician. 2006;  35(6): 392-396.4. Chu SY, Callaghan WM, Kim SY, Schmid CH, Lau J, England LJ, Dietz PM. Maternal obesity and risk of gestational diabetes mellitus. Diabetes Care. 2007; 30(8): 2070-2076.5. England LJ, Levine RJ, Qian C, Soule LM, Schisterman EF, Yu KF, Catalano PM. Glucose tolerance and risk of gestational diabetes mellitus in nulliparous women who smoke during pregnancy. Am J Epidemiol. 2004; 160(12): 1205-1213.6. Preece R, Jovanovic L. New and future diabetes ther-apies: are they safe during pregnancy? J Matern Fetal Neonatal Med. 2002;  12(6): 365-375.7. Langer O, Rodriguez DA, Xenakis EM, McFarland MB, Berkus MD, Arrendondo F. Intensifi ed versus conven-tional management of gestational diabetes. Am J Ob-stet Gynecol. 1994;  170(4): 1036-1047.8. Esakoff TF, Cheng YW, Sparks TN, Caughey AB. The association between birthweight 4000 g or greater and perinatal outcomes in patients with and with-out gestational diabetes mellitus. American Journal of Obstetrics & Gynecology. 2009;  200(6): 672-674.9. Tobias DK, Hu FB, Forman JP, Chavarro J, Zhang C. Increased Risk of Hypertension After Gestational Diabetes Mellitus: Findings from a large prospective cohort study. Diabetes Care. 2011;  34(7): 1582-1584.10. Yogev Y, Xenakis EM, Langer O. The association be-tween preeclampsia and the severity of gestational di-abetes: the impact of glycemic control. Am J Obstet Gynecol. 2004;  191(5):1655-1660.11. Afkhami-Ardekani M, Rashidi M. Iron status in women with and without gestational diabetes mel-litus. J Diabetes Complications. 2009; 23(3):194-198.12. Chen X, Scholl TO, Stein TP. Association of elevated serum ferritin levels and the risk of gestational diabe-tes mellitus in pregnant women: The Camden study. Diabetes Care. 2006;  29(5): 1077-1082.13. Cousins L. Pregnancy complications among diabetic women. Obstet Gynecol Surv. 1987;  42: 140-149.14. Rizk DE, Mustafa N, Thomas L The prevalence of uri-nary tract infections in patients with gestational dia-betes mellitus. Int Urogynecol J Pelvic Floor Dysfunct. 2001;  12(5): 317-321.15. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new predic-tion equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med. 1999; 130(6): 461-470.16. Fox J. The R Commander: A Basic-Statistics Graphical User Interface to R. J Stat Software. 2005; 14(9): 1-42.17. Abbassi-Ghanavati M, Greer LG, Cunningham FG. Pregnancy and laboratory studies: a reference table for clinicians. Obstet Gynecol. 2009; 114(6): 1326-1331.18. Halliwell B. Free radicals, antioxidants, and human disease curiosity, cause, or consequence? Lancet. 1994; 344(8924): 721-724.19. Lao TT, Chan LY, Tam KF, Ho LF. Maternal hemoglo-bin and risk of gestational diabetes mellitus in Chi-nese women. Obstet Gynecol. 2002;  99(5): 807-812.20. Lao TT, Tse KY, Chan LY, TAM KF, Ho LF. HBsAg carrier status and the association between gestational diabetes. Diabetes Care. 2003;  26(11): 3011-3016.21. Khatun N, Latif SA, Uddin MM. Pregnancy associated complications of mothers with gestational diabetes mellitus. Mymensingh Med J. 2005; 14(2): 196-198.22. Karmon A, Sheiner E. The relationship between uri-nary tract infection during pregnancy and preeclamp-sia. Arch Gynecol Obstet. 2008; 277(6): 479-481.23. Mittendorf R, Lain KY, Williams MA, Walker CK. Preeclampsia. A nested, case-control study of risk factors and their interactions. J Reprod Med. 1996; 41(7): 491-496.24. Le J, Briggs GG, McKeown A, Bustillo G. Urinary tract infections during pregnancy. Ann Pharmaco-ther. 2004; 238(10): 1692-1701.25. Hsu CD, Witter FR. Urogenital infection in pre-eclampsia. Int J Gynaecol Obstet.1995;  49(3): 271-275.26. Conde-Agudelo A, Villar J, Lindheimer M. Mater-nal infection and risk of preeclampsia: systematic re-view and metaanalysis. Am J Obstet Gynecol. 2008; 198(1): 7-22.27. Chen SL, Jackson SL, Boyko EJ. Diabetes mellitus and urinary tract infection: epidemiology, pathogenesis and proposed studies in animal models. J Urol. 2009; 182(6): 51-56. Figure 1. Results of examination between GDM and CTR groupsFigure 2. Prevalence of UTI in GDM

Gestational Diabetes Mellitus GDM in the Republic of Kosovo: a Retrospective Pilot Study

https://air.unimi.it/retrieve/handle/2434/226427/289922/Med%20Arch%202013.pdf

Gestational Diabetes Mellitus (GDM) in the Republic of Kosovo: a Retrospective Pilot Study.

Abstract

Similar works

Full text

Available Versions

AIR Universita degli studi di Milano