Prediction of Gestational Diabetes Mellitus at First Trimester

Transcription

1 Prediction of Gestational Diabetes Mellitus at First Trimester 1 Samah Maiwed Alsawat, 2 Amal Abdulrahman Hunjur, 3 Reem Moutlaq Alsayali, 4 Sara Mohammad Ali Shafei Abstract: The main objective of this review was to evaluate several potential GDM predictors with consideration to measures and to determine the extent to which GDM can be predicted in the first trimester in low risk pregnancy. Electronic detailed Search was conducted through following databases; PubMed, Embase, Science direct, searching relevant articles which were concerned with Gestational diabetes mellitus (GDM), we restricted our search to only English published articles up to January 2017, with human subject s involvement only. furthermore, we search references lists of selected studies for more useful eligible articles to our objective in this review. Glycosylated hemoglobin A1c (A1C) has many benefits over conventional oral glucose tolerance tests (OGTTs) in pregnancy. Ladies with prediabetes by first trimester A1C are considerably more most likely to have GDM, the low sensitivity of an A1C in this variety renders it a poor test to identify females who will develop GDM. Multimarker models combining protein markers and clinical information have the potential to forecast ladies at a high risk of developing GDM. Keywords: Gestational diabetes mellitus (GDM), first trimester, Glycosylated hemoglobin, Multimarker models. 1. INTRODUCTION Gestational diabetes mellitus (GDM) is characterized by glucose intolerance that is first spotted during pregnancy (1). Its frequency ranges between 2% and 25% depending upon the attributes of the population and the techniques used for medical diagnosis and screening (2). No agreement exists concerning a globally acceptable and optimum test for both diagnosis and screening (3). A number of research studies have actually demonstrated the relationship between GDM and adverse short- and long-lasting maternal-fetal results (4,5). Evaluating for GDM after the 24th gestational week and detecting GDM at the end of the 2nd trimester have been questioned because of the possible delay in attaining the positive effects of pharmacological therapy, diet plan, and exercise on placental vascularity, fetal advancement, and maternal problems (6). Recognizing patients at risk for GDM amongst low-risk pregnancies throughout early gestation might enable more time for interventions that can produce a reduction in both GDM and its associated morbidities (6). In Denmark, pregnant women go through a selective screening treatment for GDM based on risk factors; GDM diagnosis is based upon a 75 g OGTT with a 2 h plasma glucose threshold of 9.0 mmol/l (7). This limit is in accordance with previous recommendations from the European Diabetic Pregnancy Study Group (8). Recently, new diagnostic requirements for GDM were advised by the International Association of Diabetes and Pregnancy Study Groups (IADPSG). These would lower the diagnostic 2 h limit worth of a 75 g OGTT to 8.5 mmol/l. When carried out, this criterion is expected to significantly increase the occurrence of GDM not just in Denmark but likewise internationally, therefore challenging the health economy (9). The IADPSG criteria are based on 2nd trimester OGTT values and proof of adverse perinatal outcomes. This recommendation suggests eliminating obvious diabetes in early pregnancy by determining fasting glucose ( 7.0 mmol/l), random plasma glucose ( 11.1 mmol/l on confirmation) or HbA1c ( 6.5% [ 48 mmol/mol] levels. It was recommended that fasting glucose in the series of mmol/l (which surpasses the IADPSG GDM requirements however does not fulfill the requirements for obvious diabetes) need to be thought about as diagnostic of GDM. A drop in fasting glucose takes place in early pregnancy because of natural physiological changes (10) ; thus, making use of this GDM diagnostic threshold may not determine the same individuals in later and early pregnancy. Moreover, fasting glucose tests and/or OGTTs are raised and lengthy fasting glucose in early pregnancy is not highly predictive of later GDM advancement (11). Page 1625

2 The main objective of this review was to evaluate several potential GDM predictors with consideration to measures and to determine the extent to which GDM can be predicted in the first trimester in low risk pregnancy. 2. METHODOLOGY Electronic detailed Search was conducted through following databases; PubMed, Embase, Science direct, searching relevant articles which were concerned with Gestational diabetes mellitus (GDM), we restricted our search to only English published articles up to January 2017, with human subject s involvement only. furthermore, we search references lists of selected studies for more useful eligible articles to our objective in this review. Screening and diagnosis of GDM: 3. RESULTS Lack of consistent diagnostic criteria for gestational diabetes mellitus has actually frequently caused misunderstandings and under-treatment of GDM. The diagnostic limit worths of various companies are summarized in (Table 1) (12). The just recently proposed International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria are based upon the results of the HAPO study, which showed a constant association of maternal glycemia with negative pregnancy outcomes. The IADPSG agreement panel consisted of leading experts in the field of GDM from a variety of nations, hence their suggestions are expected to "serve as the basis for worldwide endorsed requirements for the medical diagnosis and classification of diabetes in pregnancy" (13), as specified in its 2010 report. The IADPSG recommends screening in all females at the first prenatal check out and a 75 g OGTT between the 24th and 28th week of pregnancy in those not currently detected with obvious diabetes or GDM by early screening. One or more abnormal worth ( 92, 180 or 153 mg/dl for fasting, 1-hour and 2-hour plasma glucose, respectively) after a 75 g OGTT is diagnostic of GDM. Nevertheless, as a result of using these criteria, the total incidence of GDM, hence its overall healing costs will increase. Thus, additional randomized scientific trials are required in order to figure out the cost-effectiveness of the IADPSG requirements and their association with long-term development of diabetes mellitus and metabolic conditions in the mom and the offspring (13). Table 1: GDM diagnostic threshold values from various organizations *Diagnosis of GDM if two or more glucose values equal to or exceeding the threshold values Diagnosis of GDM if one or more glucose values equal to or exceeding the threshold values GDM: Gestational Diabetes Mellitus, OGTT: Oral Glucose Tolerance Test, ADA: American Diabetes Association, ACOG: American Council of Obstetricians and Gynecologists, WHO: World Health Organization, IADPSG: International Association of Diabetes and Pregnancy Groups In March 2010, an agreement panel from the IADPSG; a worldwide agreement group with agents from numerous obstetrical and diabetes companies consisting of the American Diabetes Association (ADA), released new suggestions for the screening and diagnosis of GDM (13). The IADPSG suggest universal screening for gestational diabetes. At the first antenatal visit, IADPSG recommends evaluating pregnant women for GDM using standard requirements to detect diabetes in non-pregnant state to determine females with overt diabetes "pre-existing diabetes". A medical diagnosis of obvious diabetes can be established in ladies who fulfill any of the following criteria: fasting plasma glucose level (FPG) 7.0 mmol/l (126 mg/dl), a casual plasma glucose of 11.1 mmol/l ( 200 mg/dl), or HbA1c 6.5. In the lack of Page 1626

3 indisputable hyperglycemia, the medical diagnosis needs to be verified on a subsequent day. Confirmation of the diagnosis prevents the need for OGTT. A diagnosis of GDM can be made if FPG is > 5.0 mmol/l (90 mg/dl) however <7.0 mmol/l (126 mg/dl) at any gestational age. If early screening is negative, the IADPSG suggests universal screening to be performed at weeks of pregnancy with a 2-hour (h), 75-g OGTT "one-step method". Gestational diabetes is identified, if one or more values equivalent, or surpasses limits; FPG (5.1 mmol/l [92 mg/dl], one h plasma glucose (10 mmol/l [180 mg/dl], and 2-h plasma glucose (8.5 mmol/l [153 mg/dl]. These cut-off worths were chosen arbitrary by the IADPSG based on the HAPO study (4) to express an odds ratio for unfavorable results of a minimum of 1.75 compared with ladies with mean glucose levels in the HAPO study (4). The OGTT needs to be performed after fasting overnight for 8-14 hours, and not decreasing the typical carb consumption for the preceding numerous days (13). In January 2011, the Standards of Care of ADA endorsed the IADPSG recommendations (14). In addition, the Endocrine Society recently backed the IADPSG suggestions (15). The WHO upgraded their recommendations in 2013, and advised glucose cut-off values for GDM corresponding to those proposed by IADPSG (16). The difference from the IADPSG standards is that the new WHO guidelines set a variety of plasma glucose levels to identify diabetes in pregnancy and GDM (16). The past diagnostic criteria advised by the WHO in 1999 (17), for hyperglycemia in pregnancy were those used in non-pregnant people. An issue that has been problematic with these requirements associates with the FPG requirement, as the diagnostic level of 7.0 mmol/l is universally considered to be too expensive. Other companies around the globe are re-addressing their requirements for screening and diagnosis of GDM considering that the development of IADPSG recommendations. On the other side, the American Association of Obstetricians and Gynecologists (ACOG), (18) and the National Institute of Health (NIH) (19) have actually not endorsed the IADPSG suggestions, and still recommend the conventional "2-step approach", where a preliminary screening in between weeks by 50 g oral glucose difficulty test (GCT), and measuring the plasma glucose concentration after one hour. Afterward, a diagnostic 3-hour 100-g OGTT is suggested for those ladies who surpassed the glucose threshold of 7.2, or 7.8 mmol/l (130 or 140 mg/dl) in GCT (18,19). In the 2014 Standards of Care, the ADA readdressed the NIH recommendation in addition to the IADPSG guidelines as there is inadequate data to strongly demonstrate the supremacy of one strategy over the other (20). Hemoglobin A1c Prediction of Gestational Diabetes Less is understood about the utility of A1C during pregnancy. In line with the ADA, the International Association of Diabetes and Pregnancy Study Groups (IADPSG) suggested that females with the very first trimester A1C of > 6.5% be identified with and treated for type 2 diabetes in pregnancy. No global suggestions were made with regard to the management of ladies with a prediabetic-range A1C in pregnancy (21). Nevertheless, in California, the state-sponsored Diabetes in Pregnancy Program likewise known as Sweet Success, advise that females with a prediabetic-range A1C be empirically treated for gestational diabetes mellitus (GDM), and not go through an extra OGTT in either the very first or second trimesters of pregnancy (22). Given that pregnancy is a period of increasing insulin resistance, it is biologically plausible that females with prediabetes are at high risk for GDM. However, the risk associated with prediabetes might pertain to only long-lasting risk for type 2 diabetes and not much shorter term GDM risk. Policies, such as that presented by the California Sweet Success program, might result in overtreatment for GDM and over-labeling of females with prediabetes in pregnancy. Little published information exist regarding the real risk of subsequent GDM in this population (23,24). Fong et al (24) discovered an absolute risk for GDM of 27% amongst women in Southern California who had an A1C of 5.7 to 6.4%. Their research study included an accomplice of women with A1C collected during the second and first trimesters and utilized combined screening techniques (one step vs. two step) for the medical diagnosis of GDM (24). In a potential friend research study from New Zealand, Hughes et al found a higher risk of GDM (64%) within their prediabetic population; however, they specified a prediabetic-range A1C in a different way 5.9 to 6.4%. These females (n 1/4 278) were more likely to develop preeclampsia and experience a shoulder dystocia (25). Neither our study nor the research study by Fong et al discovered differences in perinatal results; nevertheless, both research studies are likely underpowered to do so, specifically the study by Fong et al with only 55 ladies with a prediabetic-range A1C. Of note, all three research studies analyzed birth weight as a result and none found distinctions in birth weight in between women with and without a prediabetic-range A1C (24,25). A1C has several prospective uses during pregnancy. Preferably, an early first trimester A1C is less influenced by physiologic changes of pregnancy and generally reflects pre-pregnancy glycemic direct exposure. Hence, it would be attractive as a easy and easy screening test for GDM. Our study discovers that a first trimester A1C has a low sensitivity (13%) and a low positive predictive worth (29%) in our population for anticipating a favorable second trimester OGTT. We do not feel it should not be utilized to rule in females for GDM treatment as backed Page 1627

4 by the California Sweet Success program. An additional utility of first trimester A1C could be to recognize women who do not need a second trimester OGTT, a troublesome test. The high uniqueness (94%) of A1C in our study is promising; however, in our associate, 5% of ladies with a first trimester A1C < 4.5% (the most affordable reportable worth) had an unusual 2nd trimester OGTT suggesting that there is no very first trimester A1C worth below which all women would have a typical second trimester OGTT. Biomarkers for detecting GDM: One important research study (26) reported that first trimester HOMA-IR values were independent predictors for the development of GDM in logistic regression analysis, and the HOMA-IR value was found to be a much better marker (AUC = 0.75; 95% CI, ) than the other factors. We found that the +LR was 5.2 for the diagnosis of GDM, and when 5.3 was used as a cutoff for the HOMA-IR worth, the level of sensitivity, uniqueness, npv, and ppv were 26.3%, 94.9%, 40%, and 90.9%, respectively. Smirnakis et al (27) identified borderline significance in the multivariate analysis for risk of subsequent GDM for increased HOMA-IR worths at gestational weeks 16-18, independent of other variables that are understood to be connected with GDM. Ozcimen et al (28) determined the risk of GDM utilizing the HOMA-IR worth during the very first trimester and found that a worth of > 2.60 appeared to be a great predictor of GDM. Interestingly, a HOMA-IR value of > 2.60 had a level of sensitivity of 100%, uniqueness of 94%, PPV of 82%, and NPV of 100% for the diagnosis of GDM (28). According to their research study, the HOMA-IR was a distinct test for the diagnosis of GDM. In our research study, we found that the mean HOMA-IR values were 4.04 ± 2.2 in ladies with GDM and 2.3 ± 1.5 in the control group. Smirnakis et al (27) reported HOMA-IR values of 3.5 ± 2.5 in the GDM group and 2.0 ± 1.3 in the control group. Ozcimen et (28) reported that the mean HOMA-IR worths were 4.7 ± 3.9 in women with GDM and 1.3 ± 0.6 in ladies without GDM. The variety of HOMA-IR values was large in women with GDM and narrow in women without GDM, which was a possible reason for the high level of sensitivity and PPV. Another marker, SHBG, is a glycoprotein secreted by the liver that binds to sex steroids in circulation (29). Thadhani et al (30) were the very first group to report that pregnant females with low SHBG levels throughout the very first trimester had a high risk of developing subsequent GDM. They likewise emphasized that evaluation throughout the very first trimester is very important due to the fact that the distinction in IR in between women with typical and abnormal glucose tolerance decreases as the pregnancy progresses (30). Smirnakis et al (27) reported that the mean SHBG levels were ± nmol/l in ladies with GDM and ± 92.1 nmol/l in the control group, which SHBG seemed the optimal marker to predict subsequent GDM throughout the first trimester. In today study, the mean SHBG levels were ± 97.7 nmol/l in females with GDM and ± 92.6 nmol/l in the control group, and reduced SHBG levels were independent predictors for GDM in the low-risk pregnancy group throughout early pregnancy. We likewise reported that an SHBG worth of 141 nmol/l (with a 5% FPR) had a sensitivity of 21.1%, PPV of 34.8%, and NPV of 90.3% for forecasting subsequent development of GDM (AUC = 0.73; 95% CI, ). Caglar et al (31) evaluated the predictive worth of SHBG for the medical diagnosis of GDM at weeks of pregnancy and reported an AUC of (95% CI, ) by ROC analysis. The cutoff worth of displayed the best level of sensitivity and PPV in this examination. Just like our research study results, these authors reported that the SHBG limit of nmol/l (around 15% FPR) had a sensitivity of 46.7%, specificity of 84.1%, PPV of 58.3%, and NPV of 76.8%. Thadhani et al (31) kept in mind that when a SHBG worth of 175 nmol/l was used as a cutoff worth, a twofold increased risk of GDM (OR = 2.2; 95% CI, ) was found compared to the control group. We discovered that an SHBG worth of 141 nmol/l led to a 4.5-fold increased risk of GDM, whereas McElduff et al (32) reported that the SHBG serum concentration could not forecast the presence of GDM, and no difference was spotted between SHBG concentrations of pregnant women receiving or not receiving insulin treatment. Nanda et al (33) found that adiponectin and SHBG levels were lower in patients who established GDM than in the control group, and they reported that the detection rate for GDM increased to 74.1% when these factors were combined with maternal risk factors. They stressed that the detection rate increased to 65% (with a 20% FPR) when these biochemical markers were integrated with maternal risk factors in pregnant women without a history of GDM (33). 4. CONCLUSION Glycosylated hemoglobin A1c (A1C) has many benefits over conventional oral glucose tolerance tests (OGTTs) in pregnancy. Ladies with prediabetes by first trimester A1C are considerably more most likely to have GDM, the low sensitivity of an A1C in this variety renders it a poor test to identify females who will develop GDM. Multimarker models combining protein markers and clinical information have the potential to forecast ladies at a high risk of developing GDM. Page 1628

5 REFERENCES [1] American College of Obstetricians and Gynecologist. Practice Bulletin No. 137: gestational diabetes mellitus. Obstet Gynecol. 2013;122: [2] Hartling, L., Dryden, D.M., Guthrie, A., Muise, M., Vandermeer, B., Donovan, L. Benefits and harms of treating gestational diabetes mellitus: a systematic review and meta-analysis for the U.S. Preventive Services Task Force and the National Institutes of Health Office of Medical Applications of Research. Ann Intern Med. 2013;159: [3] Werner, E.F., Pettker, C.M., Zuckerwise, L., Reel, M., Funai, E.F., Henderson, J. et al, Screening for gestational diabetes mellitus: are the criteria proposed by the international association of the Diabetes and Pregnancy Study Groups cost-effective?. Diabetes Care. 2012;35: [4] HOPA Study Coopeative Research Group, Metzger, B.E., Lowe, L.P., Dyer, A.R., Trimble, E.R., Chaovarindr, U. et al, Hyperglicemia and adverse pregnancy outcomes. N Engl J Med. 2008;358: [5] London, M.B., Mele, L., Spong, C.Y., Carpenter, M.W., Ramin, S.M., Casey, B. et al, The relationship between maternal glycemia and perinatal outcome. Obstet Gynecol. 2011;117: [6] Ray, J.G., Berger, H., Lipscombe, L.L., Sermer, M. Gestational prediabetes: a new term for early prevention?. Indian J Med Res. 2010;132: [7] Jensen DM, Damm P, Sorensen B et al (2003) Proposed diagnostic thresholds for gestational diabetes mellitus according to a 75-g oral glucose tolerance test. Maternal and perinatal outcomes in 3260 Danish women. Diabet Med 20: [8] Lind T, Phillips PR (1991) Influence of pregnancy on the 75-g OGTT. A prospective multicenter study. The Diabetic Pregnancy Study Group of the European Association for the Study of Diabetes. Diabetes 40(Suppl 2):8 13. [9] International Association of Diabetes and Pregnancy Study Groups Consensus Panel, Metzger BE, Gabbe SG et al (2010) International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care 33: [10] Mills JL, Jovanovic L, Knopp R et al (1998) Physiological reduction in fasting plasma glucose concentration in the first trimester of normal pregnancy: the diabetes in early pregnancy study. Metabolism 47: [11] Corrado F, D Anna R, Cannata ML, Interdonato ML, Pintaudi B, Di Benedetto A (2012) Correspondence between first-trimester fasting glycaemia, and oral glucose tolerance test in gestational diabetes diagnosis. Diabetes Metab 38: [12] Alfadhli EM. Gestational diabetes mellitus. Saudi Medical Journal. 2015;36(4): doi: /smj [13] International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care. 2010;33: [14] American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2011;34(Suppl 1):S62 S69. [15] Blumer I, Hadar E, Hadden DR, Jovanovič L, Mestman JH, Murad MH, et al. Diabetes and pregnancy: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2013;98: [16] World Health Organization. Diagnostic criteria and classification of hyperglycaemia first detected in pregnancy. Geneva (CH): World Health Organization; Available from: http: // /books/NBK [17] Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med. 1998;15: [18] Committee on Practice Bulletins--Obstetrics. Practice Bulletin No. 137: Gestational diabetes mellitus. Obstet Gynecol. 2013;12: [19] National Institutes of Health consensus development conference statement: diagnosing gestational diabetes mellitus, March 4-6, Obstet Gynecol. 2013;122: Page 1629

6 [20] American Diabetes Association. Standards of Medical Care in Diabetes Diabetes Care. 2014;37(Suppl 1):S14 S80. [21] Metzger BE, Gabbe SG, Persson B, et al; International Association of Diabetes and Pregnancy Study Groups Consensus Panel. International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care 2010: [22] Guidelines for Diagnosis of Hyperglycemia in Pregnancy 2011 [Internet]. Available at: sweetsuccess.org/portals/0/documents/2011%20dx%20algorithm.pdf. [23] Catalano PM. Carbohydrate metabolism and gestational diabetes. Clin Obstet Gynecol 1994;37(1): [24] Fong A, Serra AE, Gabby L, Wing DA, Berkowitz KM. Use of hemoglobin A1c as an early predictor of gestational diabetes mellitus. Am J Obstet Gynecol 2014;211(6):641.e [25] Hughes RCE, Moore MP, Gullam JE, Mohamed K, Rowan J. An early pregnancy HbA1c >5.9% (41 mmol/mol) is optimal for detecting diabetes and identifies women at increased risk of adverse pregnancy outcomes. Diabetes Care 2014;37(11): [26] Pınar Kumrua, Resul Arisoya. Prediction of gestational diabetes mellitus at first trimester in low-risk pregnancies. Taiwanese Journal of Obstetrics and Gynecology, December 2016, Pages [27] K.V. Smirnakis, A. Plati, M. Wolf, R. Thadhani, J.L. Ecker. Redicting gestational diabetes: choosing the optimal early serum marker. Am J Obstet Gynecol, 196 (2007), pp. 410.e1 410.e7. [28] E.E. Ozcimen, A. Uckuyu, F.C. Ciftci, F.F. Yanik, C. Bakar. Diagnosis of gestational diabetes mellitus by use of the homeostasis model assessment-insulin resistance index in the first trimester. Gynecol Endocrinol, 24 (2008), pp [29] P.H. Petra. The plasma sex steroid binding protein (SBP or SHBG). A critical review of recent developments on the structure, molecular biology and function. J Steroid Biochem Mol Biol, 40 (1991), pp [30] R. Thadhani, M. Wolf, K. Hsu-Blatman, L. Sandler, D. Nathan, J.L. Ecker. First trimester sex hormone binding globulin and subsequent gestational diabetes mellitus. Am J Obstet Gynecol, 189 (2003), pp [31] G.S. Caglar, E.D. Ozdemir, S.D. Cengiz, S. Demirtaş, Sex-hormone-binding globulin early in pregnancy for the prediction of severe gestational diabetes mellitus and related complications. J Obstet Gynaecol Res, 38 (2012), pp [32] McElduff, R. Hitchman, P. McElduff. Is sex hormone-binding globulin associated with glucose tolerance? Diabet Med, 23 (2006), pp [33] S. Nanda, M. Savvidou, A. Syngelaki, R. Akolekar, K.H. Nicolaides. Prediction of gestational diabetes mellitus by maternal factors and biomarkers at 11 to 13 weeks. Prenat Diagn, 31 (2011), pp Page 1630