The Evaluation Of Ketones Intensive measurement in women with Gestational diabetes (EVOKING) study

The Evaluation Of Ketones Intensive measurement in women with Gestational diabetes (EVOKING) study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The Evaluation Of Ketones Intensive measurement in women with Gestational diabetes (EVOKING) study Basilio Pintaudi, Loretta Giunta, Giacoma Di Vieste, Michela Vergani, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4789676/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 29 Apr, 2025 Read the published version in Hormones → Version 1 posted 6 You are reading this latest preprint version Abstract Purpose. Women with gestational diabetes mellitus (GDM) are frequently asked to check their ketones levels by measuring ketonuria before breakfast. However, ketosis could be present even before lunch and dinner. Furthermore, blood ketones measurement could be a more accurate test. Our aim was to evaluate the effect of a blood ketones intensive measurement in the detection of ketosis in women with GDM with negative urinary ketone test. Methods. This was a single center, observational, prospective study involving consecutive women with GDM. Only women with negative fasting urinary ketone tests were included. During the same gestational weeks (30-32 weeks) to all women was suggested to perform a blood ketones test before main meals. Ketosis was defined as the presence for at least 25% of the time of fasting blood ketones levels >0.1 mmol/L and >0.2 mmol/L before lunch and dinner. Results. Overall, a total of 101 women (mean age 34.7±4.8 years, pre-pregnancy BMI 28.2±5.2 kg/m 2 ) were studied. Blood ketones were present in 37.6% of the cases before breakfast, 13.9% before lunch and 11.9% before dinner. Women with at least one daily presence of blood ketones were 40.6% of the sample. Fasting blood ketones presence was correlated with ketones presence before lunch (r=0.63, p<0.0001) and before dinner (r=0.55, p<0.0001) and with one hour after breakfast mean glucose levels (r=0.23, p=0.02). Conclusions. Blood glucose ketones testing in women with GDM can detect a great number of ketosis episodes that urinary ketones test. Intensive blood ketones measurement should be recommended to women with GDM. gestational diabetes urinary ketones blood ketones blood glucose INTRODUCTION Gestational Diabetes Mellitus (GDM) represents a pathological condition that complicates almost 10–15% of pregnancies [ 1 , 2 ]. It is defined as an alteration in glucose tolerance with a first recognition during pregnancy that is not pre-gestational diabetes [ 3 ]. Pregnancy outcomes of women with GDM are notoriously worse compared with those of women with normal pregnancy. The offspring of women with GDM has higher risks of developing growth abnormalities, neonatal hypoglycaemia, respiratory distress, malformations, neonatal obstetric trauma, neonatal mortality [ 4 , 5 ]. Therefore, the final goal of GDM management is to allow a normal pregnancy evolution. Usually, women with GDM are included in a clinical specialist path conducted in Centers for diabetes care with particular experience in the management of this condition. Outpatient management of women with GDM sets different goals and consists in the execution of different procedures. Once the diagnosis of GDM has been made, an outpatient visit is scheduled. A careful medical history including a specific investigation on eating habits is collected. A balanced diet therapy is prescribed. Physical activity is suggested. Self-checks are suggested at home to evaluate blood glucose and ketones levels. Medical nutrition therapy is extremely important. Three daily main meals and three snacks are planned, with adequate repartition of carbohydrates in the calculation of the daily caloric intake. Diet balancing is fundamental both for the prevention of blood glucose levels rising and for ketosis. Ketosis is characterized by the presence of ketone bodies. They are produced in condition of relative insulin deprivation and/or prolonged fasting. In the latter case, they are the result of an excessive lipid metabolism activation, compensatory of the reduction of the glucose metabolism due to the carbohydrate shortage. The majority of clinical guidelines for the management of GDM recommends the execution of a test for ketones determination with the scope to identify their possible presence in woman with severe hyperglycemia, weight loss during treatment or in cases of possible fasting ketosis [ 6 , 7 ]. Women with GDM are frequently asked to check their ketones levels by measuring ketonuria before breakfast. The presence of ketones is associated to several adverse outcomes both during pregnancy and in the life of the newborn. However, ketosis status could be present even before main meals (i.e. before lunch and dinner), being the fasting measurement not sufficient in catching all the daily ketosis episodes. In addition, blood ketones measurement could be a more accurate test in detecting ketosis compared with urine test. Aim of this study was to evaluate the effect of a blood ketones intensive measurement in the detection of ketosis in women with GDM with negative urinary ketone test. MATERIALS AND METHODS This is a single center, prospective, observational study involving women diagnosed with GDM between the 24th and the 28th gestational weeks.We have consecutively enrolled patients admitted to the specialist diabetes and pregnancy clinic of the Diabetes Unit of the University of Messina, Italy. Local Ethic Committee approved the protocol and all participating subjects gave a written informed consent. The study was conducted according to the Helsinki Declaration. Inclusion criteria were: age over or equal to 18 years, a diagnosis of GDM, any ethnicity, negative urinary ketone test, signed informed consent. Exclusion criteria were: age under 18 years, a diagnosis of diabetes mellitus (i.e. type 1 or type 2 diabetes) made before or at the beginning of the pregnancy, positive urinary ketone test, any condition that in the opinion of the investigator represented an obstacle for complete adherence to the study. The sample of women involved in this study reflects the typical population, with similar clinical antenatal characteristics, of women we usually care for in our clinic. Self-monitoring blood glucose tests, dietary advices and physical activity prescription was given according to standard care to all participating women. All women have performed ketosis checks for the duration of the study period, from the diagnosis of GDM until the end of pregnancy. Only women with negative fasting urinary ketone tests were included. Home self-monitoring blood glucose tests has been performed in the morning on empty stomach and one hour after the main meals (breakfast, lunch, dinner) according to clinical needs. Women who required insulin therapy performed additional glucose checks (before lunch and before dinner). Ketonuria has been measured on an empty stomach every morning with the Ketodiaburtest System. Ketonuria was defined as the detection of a colour change in the test strip once it has received contact with the urine, corresponding to the colour indicative of positivity. Ketonemia has been measured on an empty stomach every morning through capillary glucose monitoring with the GlucoMen LX plus System. From the 30th and up to the 32nd week of gestation, women have controlled ketonemia in addition to the morning measurement, also before lunch and before dinner. Ketonemia was defined as the presence for at least 25% of the time of fasting blood ketones levels > 0.1 mmol/L and > 0.2 mmol/L before lunch and dinner [ 8 ]. The primary study outcome was the detection rate of blood ketosis episodes during each pre-prandial period (breakfast, lunch, dinner) in women with negative fasting ketonuria. The following information regarding the mother has been collected on a special data collection sheet: age, familiarity for type 2 diabetes, gestational age, pre-gestational body mass index, home glucose profiles, presence of ketonemia or ketonuria, therapy (only diet/diet plus insulin). Statistical analysis In descriptive analyses, continuous variables are summarized as mean and standard deviation. Categorical variables are expressed as percentages. Differences among the groups were analyzed by comparison tests according to the nature of the variable. Pearson’s correlation coefficient was employed to test correlations between fasting, before lunch and before dinner blood ketones levels and blood glucose levels. Several sub-analyses were performed in order to explore possible differences in blood ketones positivity between subgroups: women treated with only diet vs. women treated with diet plus insulin; women aged < 35 years vs. women aged ≥ 35 years; women with vs. without familiarity for type 2 diabetes. Another sub-analysis was performed with the aim to explore possible differences according to pre-pregnancy BMI classes ( 30 Kg/m 2 ). Finally, we performed a comparison analysis between women with blood ketones positivity only before breakfast vs. women with blood ketones positivity before lunch or before dinner. A p value < 0.05 was considered for statistical significance. Analyses were performed using SPSS version 17.0 (Inc., Chicago, Illinois). RESULTS Overall, a total of 101 women (mean age 34.7 ± 4.8 years, pre-pregnancy BMI 28.2 ± 5.2 kg/m2, 59.4% insulin treated) were studied. Clinical characteristics of the studied population and blood ketones and glucose levels before and after meals are reported in Table 1 . Blood ketones were present in 37.6% of the cases before breakfast, 13.9% before lunch and 11.9% before dinner. Women with at least one daily presence of blood ketones were 40.6% of the sample. Fasting blood ketones presence was correlated with ketones presence before lunch (r = 0.63, p < 0.0001) and before dinner (r = 0.55, p < 0.0001) and with one hour after breakfast mean glucose levels (r = 0.23, p = 0.02). When comparing women with positive blood ketones test with those with negative test no differences were detected in clinical and anthropometric mothers’ characteristics, risk factors for GDM nor for insulin treated rate. Sub-analyses results are reported in Table 2 . No differences were detected in blood ketones positivity when compared women treated with only diet vs women treated with diet plus insulin, women aged < 35 years vs. women aged ≥ 35 years, women with vs. without familiarity for type 2 diabetes. No difference according to pre-pregnancy BMI classes was found. When we compared women with blood ketones positivity only before breakfast vs. women with blood ketones positivity before lunch or before dinner we found no differences in antenatal characteristics nor in self-monitoring blood glucose levels (Table 3 ). Table 1 Clinical characteristics of the studied population and blood ketones and glucose levels before and after meals. Age (years) 34.7 ± 4.8 Age ≥ 35 years (%) 54.5 Pre-gestational BMI (kg/m 2 ) 28.2 ± 5.2 Categorical pre-gestational BMI (%) 30 kg/m 2 39.6 Family history of diabetes (%) 53.1 Insulin treated (%) 59.4 Negative fasting urinary ketone test (%) 100 Blood ketones levels before breakfast (mmol/L) 0.10 ± 0.10 Blood ketones levels before lunch (mmol/L) 0.05 ± 0.08 Blood ketones levels before dinner (mmol/L) 0.05 ± 0.08 Fasting blood glucose levels (mg/dl) 94.1 ± 12.7 1-h after breakfast blood glucose levels (mg/dl) 123.1 ± 20.1 1-h after lunch blood glucose levels (mg/dl) 114.4 ± 16.9 1-h after dinner blood glucose levels (mg/dl) 115.3 ± 18.8 Fasting blood glucose levels > 95 mg/dl (%) 36.6 1-h after breakfast blood glucose levels > 130 mg/dl (%) 38.6 1-h after lunch blood glucose levels > 130 mg/dl (%) 13.9 1-h after dinner blood glucose levels > 130 mg/dl (%) 15.8 Table 2 Sub-analyses exploring possible differences in blood ketones positivity between subgroups. Insulin treated Only diet p Age ≥ 35 years Age < 35 years p Familiarity positive for type 2 diabetes Familiarity negative for type 2 diabetes p BMI < 25 kg/m 2 BMI 25–30 kg/m 2 BMI ≥ 30 kg/m 2 p Blood ketones positivity before breakfast 22.8% 14.8% 0.86 19.8% 17.8% 0.76 18.8% 18.8% 0.63 11.9% 8.9% 14.8% 0.87 Blood ketones positivity before lunch 9.9% 4.0% 0.32 8.9% 5.0% 0.43 6.9% 6.9% 0.80 3.0% 4.0% 5.0% 0.83 Blood ketones positivity before dinner 6.9% 5.0% 0.94 8.9% 3.0% 0.13 5.0% 6.9% 0.40 3.0% 4.0% 5.0% 0.83 At least one daily blood ketones positivity 22.8% 17.8% 0.58 22.8% 17.8% 0.78 18.8% 21.8% 0.26 13.9% 8.9% 15.8% 0.64 Table 3 Comparison between women with blood ketones positivity only before breakfast vs. women with blood ketones positivity before lunch or before dinner. Blood ketones positivity before breakfast Blood ketones positivity before lunch or before dinner p Age (years) 34.4 ± 4.4 36.4 ± 3.3 0.44 Age ≥ 35 years (%) 26.8 29.3 0.12 Pre-gestational BMI (kg/m 2 ) 28.4 ± 6.0 27.7 ± 5.3 0.43 Categorical pre-gestational BMI (%) 0.91 30 kg/m 2 25.6 15.4 Family history of diabetes (%) 29.3 17.1 0.58 Insulin treated (%) 31.7 24.4 0.77 Fasting blood glucose levels (mg/dl) 97.3 ± 15.9 92.2 ± 10.0 0.46 1-h after breakfast blood glucose levels (mg/dl) 129.5 ± 18.9 123.5 ± 21.2 0.32 1-h after lunch blood glucose levels (mg/dl) 114.7 ± 16.6 111.2 ± 15.8 0.87 1-h after dinnerblood glucose levels (mg/dl) 120.8 ± 22.1 110.8 ± 17.1 0.50 Fasting blood glucose levels > 95 mg/dl (%) 21.9 14.6 0.88 1-h after breakfast blood glucose levels > 130 mg/dl (%) 31.7 14.6 0.23 1-h after lunch blood glucose levels > 130 mg/dl (%) 4.9 4.9 0.71 1-h after dinnerblood glucose levels > 130 mg/dl (%) 17.1 4.9 0.18 DISCUSSION Our study shows that blood glucose ketones testing in women with GDM could detect a greater number of ketosis episodes that urinary ketones test. We wanted to check for positive ketonemia in women with GDM with negative urinary ketone test in order to explore the greater sensibility of blood test compared with urine test. Fasting blood ketones presence was correlated with ketones positivity during the day and with glucose levels after breakfast. Ketosis control is functional to the quantitative and qualitative monitoring of the prescribed diet. Ketosis presence in pregnancy implies potential risks not only for the pregnancy itself but also for childbirth outcomes. With this regard, evidences exist on the negative association between beta-hydroxy-butyrate, which represents 85% of ketonic bodies detected during the third trimester of gestation, and newborn neuropsychological development [ 9 , 10 , 11 ]. The prescription of acetoacetate dosage in urine is a widely diffused procedure even though the intrinsic limitation of acetoacetate measurement. Urine test detects only acetoacetate giving a semiquantitative results affected by urinary output, thus delayed than beta-hydroxy-butyrate (BHB). Ketonemia assessment, instead, is based on BHB which is the mainly responsible body ketone for diabetic ketoacidosis, offering an exact level with a less rate of positive and false negatives. [ 12 , 13 ] Our results support the higher sensitivity of ketonemia compared to ketonuria, confirming the greater reliability of the former method. In this regard, a Greek study involving 180 women with GDM in their third trimester found a significantly higher prevalence of ketonuria (that was not different from that reported in normal pregnant women) compared to ketonemia. This suggests a weak correlation between fasting urine and serum ketone levels, as women with moderate to high urinary ketone levels often had normal serum ketone levels. Several factors may explain this poor correlation. The renal handling of ketones is complex, involving both reabsorption and excretion, which varies depending on serum ketone levels. Additionally, urinary ketone levels reflect serum ketone levels from several hours earlier, due to the time urine spends in the bladder. Moreover, dehydration can concentrate urine, leading to higher measured ketone levels. Furthermore, BHB levels were associated with omission of the bedtime snack, suggesting the importance of proper adherence to the GMD diet. [ 14 , 15 ] Regarding the timing, the most common attitude adopted in clinical practice is to measure ketonuria or ketonemia before breakfast, assuming that it can be likely to be positive at this time of the day, due to night fasting [ 11 , 14 , 16 ]. We found that the only before breakfast test is not enough. Of considerable importance and validity is a Spanish work in which, with the aim of identifying the best way to delineate the metabolic status of women with GDM, ketonuria and capillary blood glucose measurements were evaluated with timing alternative to the usual ones [ 17 ]. The Authors assessed the effectiveness of only before breakfast ketonuria measurements compared with testing before the three main meals. All women followed an adequate fractionated diet. Measuring only before breakfast did not allow to identify about a third of the cases of women with ketonuria, being this a potential limit to the use of only morning monitoring [ 17 ]. The only study evaluating differences in ketonemia levels in women with GDM compared to pregnant women without GDM [ 8 ] also showed that fasting ketonemia levels did not differ between the two groups, while there was a significant difference in ketonemia levels related to checks carried out before lunch and before dinner. The control of ketonemia during main meals could therefore be advantageous and decisive for the identification of ketosis states not otherwise identified through the routine control of morning ketonuria. This especially in consideration of the fact that ketosis states are indicative of a possible lack of caloric needs which in turn, if not recognized, results in a weight increase below what is recommended. It XXX salso known that an inadequate weight increase is associated with a greater risk of one of the complications of pregnancy, represented by Small for Gestational Age (SGA) children, or children with birth weight below the 10th percentile [ 18 , 19 ]. Our study has some limitations. First, we do not analyzed correlations or associations between ketones levels and neonatal outcomes. A deep investigation of the relationship between blood ketones and pregnancy and neonatal outcomes will be available at the end of the EVOKING study. Information on children development is now lacking because of the limited follow-up period. Strength of our study is the great sample of women with GDM we have enrolled. Our study design allowed to look directly at the potentiality of blood ketones measurement because we have excluded all women with positive urine ketones test. Another strength of our study is having performed several sub-analyses in order to test possible differences in blood ketones positivity between subgroups. In particular, we showed that women treated with only diet had no difference in ketones positivity rate compared with women treated with diet plus insulin. This is an important result because it highlights the need to check for ketones presence not only in women with a more complex management of their pregnancy but also in women with a soft management such as those treated with only diet. No differences were detected even when an analysis according to pre-pregnancy BMI classes was performed. It confirms that also women with a high BMI could have ketones positivity, this going against the notion that women with lower BMI are at higher risk for ketosis. Importantly, we found no differences in clinical characteristics when women with only before breakfast ketones were positive compared with women with blood ketones positivity before lunch or before dinner. This raises problems in detecting the most severe cases of GDM complicated by ketotis because of the absence of predictive or suggestive characteristics indicating high risk of ketosis even before lunch or dinner. CONCLUSION According to the results until now showed, intensive blood ketones measurement should be recommended to women with GDM in order to better manage pregnancies complicated by GDM and to limit potential adverse effects of ketosis. However, studies with a randomized controlled design are needed to confirm or not the data we have reported in our study. Declarations Funding: None. Conflicts of interest/Competing interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Ethics approval: All procedures involving human participants were in accordance with the ethical standards of the institutional research committee (Ethics Committee of the University of Messina, prot. 52/18) and with the 1964 Helsinki declaration and its later amendments. Consent to participate: Informed consent was obtained from all individual participants included in the study. Consent for publication: All authors have read and approved the final version of the manuscript for publication. Availability of data and material: The raw data supporting the conclusions of this manuscript will be made available by the authors. Authors’ contributions: B.P., G.D.V., L. G., A.P., F.C., R.D., and A.D.B. contributed to the study design and acquisition of data, as well as the interpretation of data. B.P. and A.D.B. had the main responsibility for analyzing data and writing the first draft of the paper. B.P., G.D.V., L. G., A.P., F.C., R.D., and A.D.B. critically revised the manuscript. B.P. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. References Corrado F, Pintaudi B, Di Vieste G et al (2014) Italian risk factor-based screening for gestational diabetes. J Matern Fetal Neonatal Med 27:1445–1448 Paulo MS, Abdo NM, Bettencourt-Silva R, Al-Rifai RH (2021) Gestational Diabetes Mellitus in Europe: A Systematic Review and Meta-Analysis of Prevalence Studies. Front Endocrinol (Lausanne) 12:691033. 10.3389/fendo.2021.691033 PMID: 34956073; PMCID: PMC8698118 Metzger BE, Coustan DR (1998) Summary and recommendations of the Fourth International Workshop-Conference on Gestational Diabetes Mellitus. The Organizing Committee. Diabetes Care ;21 Suppl 2:B161-7 Ye W, Luo C, Huang J, Li C, Liu Z, Liu F (2022) Gestational diabetes mellitus and adverse pregnancy outcomes: systematic review and meta-analysis. BMJ 377:e067946. 10.1136/bmj-2021-067946 PMID: 35613728; PMCID: PMC9131781 Sweeting A, Wong J, Murphy HR, Ross GP (2022) A Clinical Update on Gestational Diabetes Mellitus. Endocr Rev 43(5):763–793. 10.1210/endrev/bnac003 PMID: 35041752; PMCID: PMC9512153 ACOG Practice Bulletin No. 190: Gestational Diabetes Mellitus. Obstet Gynecol (2018) ;131(2):e49-e64. 10.1097/AOG.0000000000002501 . PMID: 29370047 ElSayed NA, Aleppo G, Aroda VR, Bannuru RR, Brown FM, Bruemmer D, Collins BS, Hilliard ME, Isaacs D, Johnson EL, Kahan S, Khunti K, Leon J, Lyons SK, Perry ML, Prahalad P, Pratley RE, Jeffrie Seley J, Stanton RC, Gabbay RA, on behalf of the American Diabetes Association (2023) 15. Management of Diabetes in Pregnancy: Standards of Care in Diabetes-2023. Diabetes Care 46(Suppl 1):S254–S266. 10.2337/dc23-S015 PMID: 36507645; PMCID: PMC9810465 Gin H, Vambergue A, Vasseur C et al (2006) Blood ketone monitoring: a comparison between gestational diabetes and non-diabetic pregnant women. Diabetes Metab 32:592–597 Rizzo T, Metzger BE, Burns WJ, Burns K (1991) Correlations between antepartum maternal metabolism and intelligence of offspring. N Engl J Med 325:911–916 Qian M, Wu N, Li L, Yu W, Ouyang H, Liu X, He Y, Al-Mureish A (2020) Effect of Elevated Ketone Body on Maternal and Infant Outcome of Pregnant Women with Abnormal Glucose Metabolism During Pregnancy. Diabetes Metab Syndr Obes 13:4581–4588 PMID: 33268998; PMCID: PMC7701151 Gin H, Vambergue A, Vasseur C et al (2006) Could blood ketone monitoring be a tool for managing gestational diabetes mellitus? Diabetes Care 29:743 Laffel L (1999) Ketone bodies: a review of physiology, pathophysiology and application of monitoring to diabetes. Diabetes Metab Res Rev 15:412–426. https://doi.org/10.1002/(SICI)1520-7560(199911/12)15:63.0.CO;2-8 Taboulet P, Deconinck N, Thurel A, Haas L, Manamani J, Porcher R, Schmit C, Fontaine J-P, Gautier J-F (2007) Correlation between urine ketones (acetoacetate) and capillary blood ketones (3-beta-hydroxybutyrate) in hyperglycaemic patients, vol 33. Diabetes & Metabolism, pp 135–139. 2 https://doi.org/10.1016/j.diabet.2006.11.006 Helen L, Tanner MD, Nitert LK, Callaway HL (2021) Barrett; Ketones in Pregnancy: Why Is It Considered Necessary to Avoid Them and What Is the Evidence Behind Their Perceived Risk? Diabetes Care 1 January 44(1):280–289. https://doi.org/10.2337/dc20-2008 Spanou L, Dalakleidi K, Zarkogianni K, Papadimitriou A, Nikita K, Vasileiou V, Alevizaki M, Anastasiou E (2015) Oct-Dec;14(4):644 – 50 Ketonemia and ketonuria in gestational diabetes mellitus. Hormones (Athens). 10.14310/horm.2002.1610 . PMID: 26732157 (2015) NG Diabetes in pregnancy: management of diabetes and its complications from preconception to the postnatal period. Available on: https://www.nice.org.uk/guidance/ng3 , published: February 2015, last updated: December 2020 Montaner P, Ripollés J, Pamies C, Corcoy R (2011) Measurement of fasting ketonuria and capillary blood glucose after main meals in women with gestational diabetes mellitus: How well is the metabolic picture captured? J Obstet Gynaecol Res 37:722–728 Chiou YL, Hung CH, Liao HY (2018) The Impact of Prepregnancy Body Mass Index and Gestational Weight Gain on Perinatal Outcomes for Women With Gestational Diabetes Mellitus. Worldviews Evid Based Nurs 15:313–322 Metzger BE, Freinkel N (1987) Accelerated starvation in pregnancy: implications for dietary treatment of obesity and gestational diabetes mellitus. Biol Neonate 51:78–85 Cite Share Download PDF Status: Published Journal Publication published 29 Apr, 2025 Read the published version in Hormones → Version 1 posted Editorial decision: Major revisions 12 Sep, 2024 Reviewers agreed at journal 18 Aug, 2024 Reviewers invited by journal 30 Jul, 2024 Editor invited by journal 25 Jul, 2024 Editor assigned by journal 24 Jul, 2024 First submitted to journal 23 Jul, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4789676","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":333698615,"identity":"42a7b3a2-4f32-47de-9a2a-6a8fe28a71a0","order_by":0,"name":"Basilio Pintaudi","email":"data:image/png;base64,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","orcid":"","institution":"Ospedale Niguarda Ca' Granda: Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Basilio","middleName":"","lastName":"Pintaudi","suffix":""},{"id":333698616,"identity":"b6274abe-8bba-408c-892a-6f75f3cab5e9","order_by":1,"name":"Loretta Giunta","email":"","orcid":"","institution":"Azienda Ospedaliera Universitaria Policlinico G Martino: Azienda Ospedaliera Universitaria G Martino di Messina","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Loretta","middleName":"","lastName":"Giunta","suffix":""},{"id":333698617,"identity":"7aeb759a-3ae5-43a2-9a98-bdd3f7933b22","order_by":2,"name":"Giacoma Di Vieste","email":"","orcid":"","institution":"Ospedale Niguarda Ca' Granda: Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Giacoma","middleName":"Di","lastName":"Vieste","suffix":""},{"id":333698618,"identity":"c6a346f2-c83a-4641-9533-963ba70cc678","order_by":3,"name":"Michela Vergani","email":"","orcid":"","institution":"University of Milano–Bicocca: Universita degli Studi di Milano-Bicocca","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Michela","middleName":"","lastName":"Vergani","suffix":""},{"id":333698619,"identity":"4065d17a-8265-47f2-860d-f5295831e692","order_by":4,"name":"Matteo Conti","email":"","orcid":"","institution":"University of Milano–Bicocca: Universita degli Studi di Milano-Bicocca","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Matteo","middleName":"","lastName":"Conti","suffix":""},{"id":333698620,"identity":"2a4bc9e8-3b98-47a1-aae6-f8f7f690f472","order_by":5,"name":"Arianna Pani","email":"","orcid":"","institution":"La Statale: Universita degli Studi di Milano","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Arianna","middleName":"","lastName":"Pani","suffix":""},{"id":333698621,"identity":"3fe1fe53-97a8-473d-9c60-a901a47f836f","order_by":6,"name":"Francesco Corrado","email":"","orcid":"","institution":"Universita degli Studi di Messina","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Francesco","middleName":"","lastName":"Corrado","suffix":""},{"id":333698622,"identity":"813c877f-f754-421c-83b5-a563fcd8595f","order_by":7,"name":"Rosario D'Anna","email":"","orcid":"","institution":"Azienda Ospedaliera Universitaria San Martino: Ospedale Policlinico San Martino","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Rosario","middleName":"","lastName":"D'Anna","suffix":""},{"id":333698623,"identity":"b4f90512-6f80-4a7c-a117-4aac0b40e339","order_by":8,"name":"Antonino Di Benedetto","email":"","orcid":"","institution":"Azienda Ospedaliera Universitaria Policlinico G Martino: Azienda Ospedaliera Universitaria G Martino di Messina","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Antonino","middleName":"Di","lastName":"Benedetto","suffix":""}],"badges":[],"createdAt":"2024-07-23 14:51:02","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4789676/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4789676/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s42000-025-00663-1","type":"published","date":"2025-04-29T15:57:08+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":81987478,"identity":"f546fa7f-067c-47d0-8c1f-478ba3e4b960","added_by":"auto","created_at":"2025-05-05 16:04:01","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":543857,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4789676/v1/c0413299-b3e2-4ae0-8a13-bd0a6fc5e12e.pdf"}],"financialInterests":"","formattedTitle":"The Evaluation Of Ketones Intensive measurement in women with Gestational diabetes (EVOKING) study","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eGestational Diabetes Mellitus (GDM) represents a pathological condition that complicates almost 10\u0026ndash;15% of pregnancies [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. It is defined as an alteration in glucose tolerance with a first recognition during pregnancy that is not pre-gestational diabetes [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Pregnancy outcomes of women with GDM are notoriously worse compared with those of women with normal pregnancy. The offspring of women with GDM has higher risks of developing growth abnormalities, neonatal hypoglycaemia, respiratory distress, malformations, neonatal obstetric trauma, neonatal mortality [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Therefore, the final goal of GDM management is to allow a normal pregnancy evolution. Usually, women with GDM are included in a clinical specialist path conducted in Centers for diabetes care with particular experience in the management of this condition. Outpatient management of women with GDM sets different goals and consists in the execution of different procedures.\u003c/p\u003e \u003cp\u003eOnce the diagnosis of GDM has been made, an outpatient visit is scheduled. A careful medical history including a specific investigation on eating habits is collected. A balanced diet therapy is prescribed. Physical activity is suggested. Self-checks are suggested at home to evaluate blood glucose and ketones levels. Medical nutrition therapy is extremely important. Three daily main meals and three snacks are planned, with adequate repartition of carbohydrates in the calculation of the daily caloric intake. Diet balancing is fundamental both for the prevention of blood glucose levels rising and for ketosis.\u003c/p\u003e \u003cp\u003eKetosis is characterized by the presence of ketone bodies. They are produced in condition of relative insulin deprivation and/or prolonged fasting. In the latter case, they are the result of an excessive lipid metabolism activation, compensatory of the reduction of the glucose metabolism due to the carbohydrate shortage.\u003c/p\u003e \u003cp\u003eThe majority of clinical guidelines for the management of GDM recommends the execution of a test for ketones determination with the scope to identify their possible presence in woman with severe hyperglycemia, weight loss during treatment or in cases of possible fasting ketosis [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWomen with GDM are frequently asked to check their ketones levels by measuring ketonuria before breakfast. The presence of ketones is associated to several adverse outcomes both during pregnancy and in the life of the newborn. However, ketosis status could be present even before main meals (i.e. before lunch and dinner), being the fasting measurement not sufficient in catching all the daily ketosis episodes. In addition, blood ketones measurement could be a more accurate test in detecting ketosis compared with urine test.\u003c/p\u003e \u003cp\u003eAim of this study was to evaluate the effect of a blood ketones intensive measurement in the detection of ketosis in women with GDM with negative urinary ketone test.\u003c/p\u003e"},{"header":"MATERIALS AND METHODS","content":"\u003cp\u003eThis is a single center, prospective, observational study involving women diagnosed with GDM between the 24th and the 28th gestational weeks.We have consecutively enrolled patients admitted to the specialist diabetes and pregnancy clinic of the Diabetes Unit of the University of Messina, Italy. Local Ethic Committee approved the protocol and all participating subjects gave a written informed consent. The study was conducted according to the Helsinki Declaration.\u003c/p\u003e \u003cp\u003eInclusion criteria were: age over or equal to 18 years, a diagnosis of GDM, any ethnicity, negative urinary ketone test, signed informed consent. Exclusion criteria were: age under 18 years, a diagnosis of diabetes mellitus (i.e. type 1 or type 2 diabetes) made before or at the beginning of the pregnancy, positive urinary ketone test, any condition that in the opinion of the investigator represented an obstacle for complete adherence to the study.\u003c/p\u003e \u003cp\u003eThe sample of women involved in this study reflects the typical population, with similar clinical antenatal characteristics, of women we usually care for in our clinic.\u003c/p\u003e \u003cp\u003eSelf-monitoring blood glucose tests, dietary advices and physical activity prescription was given according to standard care to all participating women. All women have performed ketosis checks for the duration of the study period, from the diagnosis of GDM until the end of pregnancy. Only women with negative fasting urinary ketone tests were included.\u003c/p\u003e \u003cp\u003eHome self-monitoring blood glucose tests has been performed in the morning on empty stomach and one hour after the main meals (breakfast, lunch, dinner) according to clinical needs. Women who required insulin therapy performed additional glucose checks (before lunch and before dinner). Ketonuria has been measured on an empty stomach every morning with the Ketodiaburtest System. Ketonuria was defined as the detection of a colour change in the test strip once it has received contact with the urine, corresponding to the colour indicative of positivity. Ketonemia has been measured on an empty stomach every morning through capillary glucose monitoring with the GlucoMen LX plus System. From the 30th and up to the 32nd week of gestation, women have controlled ketonemia in addition to the morning measurement, also before lunch and before dinner. Ketonemia was defined as the presence for at least 25% of the time of fasting blood ketones levels\u0026thinsp;\u0026gt;\u0026thinsp;0.1 mmol/L and \u0026gt;\u0026thinsp;0.2 mmol/L before lunch and dinner [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe primary study outcome was the detection rate of blood ketosis episodes during each pre-prandial period (breakfast, lunch, dinner) in women with negative fasting ketonuria.\u003c/p\u003e \u003cp\u003eThe following information regarding the mother has been collected on a special data collection sheet: age, familiarity for type 2 diabetes, gestational age, pre-gestational body mass index, home glucose profiles, presence of ketonemia or ketonuria, therapy (only diet/diet plus insulin).\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eIn descriptive analyses, continuous variables are summarized as mean and standard deviation. Categorical variables are expressed as percentages. Differences among the groups were analyzed by comparison tests according to the nature of the variable. Pearson\u0026rsquo;s correlation coefficient was employed to test correlations between fasting, before lunch and before dinner blood ketones levels and blood glucose levels. Several sub-analyses were performed in order to explore possible differences in blood ketones positivity between subgroups: women treated with only diet vs. women treated with diet plus insulin; women aged\u0026thinsp;\u0026lt;\u0026thinsp;35 years vs. women aged\u0026thinsp;\u0026ge;\u0026thinsp;35 years; women with vs. without familiarity for type 2 diabetes. Another sub-analysis was performed with the aim to explore possible differences according to pre-pregnancy BMI classes (\u0026lt;\u0026thinsp;25, 25-29.9, \u0026gt;\u0026thinsp;30 Kg/m\u003csup\u003e2\u003c/sup\u003e). Finally, we performed a comparison analysis between women with blood ketones positivity only before breakfast vs. women with blood ketones positivity before lunch or before dinner. A p value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered for statistical significance. Analyses were performed using SPSS version 17.0 (Inc., Chicago, Illinois).\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cp\u003eOverall, a total of 101 women (mean age 34.7\u0026thinsp;\u0026plusmn;\u0026thinsp;4.8 years, pre-pregnancy BMI 28.2\u0026thinsp;\u0026plusmn;\u0026thinsp;5.2 kg/m2, 59.4% insulin treated) were studied. Clinical characteristics of the studied population and blood ketones and glucose levels before and after meals are reported in Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Blood ketones were present in 37.6% of the cases before breakfast, 13.9% before lunch and 11.9% before dinner. Women with at least one daily presence of blood ketones were 40.6% of the sample. Fasting blood ketones presence was correlated with ketones presence before lunch (r\u0026thinsp;=\u0026thinsp;0.63, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) and before dinner (r\u0026thinsp;=\u0026thinsp;0.55, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) and with one hour after breakfast mean glucose levels (r\u0026thinsp;=\u0026thinsp;0.23, p\u0026thinsp;=\u0026thinsp;0.02). When comparing women with positive blood ketones test with those with negative test no differences were detected in clinical and anthropometric mothers\u0026rsquo; characteristics, risk factors for GDM nor for insulin treated rate. Sub-analyses results are reported in Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. No differences were detected in blood ketones positivity when compared women treated with only diet vs women treated with diet plus insulin, women aged\u0026thinsp;\u0026lt;\u0026thinsp;35 years vs. women aged\u0026thinsp;\u0026ge;\u0026thinsp;35 years, women with vs. without familiarity for type 2 diabetes. No difference according to pre-pregnancy BMI classes was found. When we compared women with blood ketones positivity only before breakfast vs. women with blood ketones positivity before lunch or before dinner we found no differences in antenatal characteristics nor in self-monitoring blood glucose levels (Table \u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical characteristics of the studied population and blood ketones and glucose levels before and after meals.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34.7\u0026thinsp;\u0026plusmn;\u0026thinsp;4.8\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u0026thinsp;\u0026ge;\u0026thinsp;35 years (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e54.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePre-gestational BMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28.2\u0026thinsp;\u0026plusmn;\u0026thinsp;5.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCategorical pre-gestational BMI (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;25 kg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e25-29.9 kg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;30 kg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFamily history of diabetes (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e53.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInsulin treated (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e59.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative fasting urinary ketone test (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlood ketones levels before breakfast (mmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.10\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlood ketones levels before lunch (mmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.05\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlood ketones levels before dinner (mmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.05\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFasting blood glucose levels (mg/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e94.1\u0026thinsp;\u0026plusmn;\u0026thinsp;12.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1-h after breakfast blood glucose levels (mg/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e123.1\u0026thinsp;\u0026plusmn;\u0026thinsp;20.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1-h after lunch blood glucose levels (mg/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e114.4\u0026thinsp;\u0026plusmn;\u0026thinsp;16.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1-h after dinner blood glucose levels (mg/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e115.3\u0026thinsp;\u0026plusmn;\u0026thinsp;18.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFasting blood glucose levels\u0026thinsp;\u0026gt;\u0026thinsp;95 mg/dl (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1-h after breakfast blood glucose levels\u0026thinsp;\u0026gt;\u0026thinsp;130 mg/dl (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1-h after lunch blood glucose levels\u0026thinsp;\u0026gt;\u0026thinsp;130 mg/dl (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1-h after dinner blood glucose levels\u0026thinsp;\u0026gt;\u0026thinsp;130 mg/dl (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSub-analyses exploring possible differences in blood ketones positivity between subgroups.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"14\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c13\" colnum=\"13\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c14\" colnum=\"14\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eInsulin treated\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eOnly\u003c/p\u003e \u003cp\u003ediet\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAge\u0026thinsp;\u0026ge;\u0026thinsp;35 years\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAge\u0026thinsp;\u0026lt;\u0026thinsp;35 years\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eFamiliarity positive for type 2 diabetes\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eFamiliarity negative for type 2 diabetes\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003eBMI\u003c/p\u003e \u003cp\u003e\u0026lt;\u0026thinsp;25 kg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c12\"\u003e \u003cp\u003eBMI\u003c/p\u003e \u003cp\u003e25\u0026ndash;30 kg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c13\"\u003e \u003cp\u003eBMI\u003c/p\u003e \u003cp\u003e\u0026ge;\u0026thinsp;30 kg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c14\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlood ketones positivity before breakfast\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e22.8%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e14.8%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e19.8%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e17.8%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e18.8%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e18.8%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e11.9%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e8.9%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e14.8%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e0.87\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlood ketones positivity before lunch\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9.9%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4.0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e8.9%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e5.0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e6.9%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e6.9%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e3.0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e4.0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e5.0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e0.83\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlood ketones positivity before dinner\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6.9%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5.0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e8.9%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3.0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e5.0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e6.9%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e3.0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e4.0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e5.0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e0.83\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAt least one daily blood ketones positivity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e22.8%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e17.8%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e22.8%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e17.8%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e18.8%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e21.8%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e13.9%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e8.9%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e15.8%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e0.64\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison between women with blood ketones positivity only before breakfast vs. women with blood ketones positivity before lunch or before dinner.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBlood ketones positivity before breakfast\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBlood ketones positivity before lunch or before dinner\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34.4\u0026thinsp;\u0026plusmn;\u0026thinsp;4.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36.4\u0026thinsp;\u0026plusmn;\u0026thinsp;3.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.44\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u0026thinsp;\u0026ge;\u0026thinsp;35 years (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.12\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePre-gestational BMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28.4\u0026thinsp;\u0026plusmn;\u0026thinsp;6.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27.7\u0026thinsp;\u0026plusmn;\u0026thinsp;5.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.43\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCategorical pre-gestational BMI (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.91\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;25 kg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e25-29.9 kg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;30 kg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFamily history of diabetes (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.58\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInsulin treated (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.77\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFasting blood glucose levels (mg/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e97.3\u0026thinsp;\u0026plusmn;\u0026thinsp;15.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e92.2\u0026thinsp;\u0026plusmn;\u0026thinsp;10.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.46\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1-h after breakfast blood glucose levels (mg/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e129.5\u0026thinsp;\u0026plusmn;\u0026thinsp;18.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e123.5\u0026thinsp;\u0026plusmn;\u0026thinsp;21.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.32\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1-h after lunch blood glucose levels (mg/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e114.7\u0026thinsp;\u0026plusmn;\u0026thinsp;16.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e111.2\u0026thinsp;\u0026plusmn;\u0026thinsp;15.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.87\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1-h after dinnerblood glucose levels (mg/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e120.8\u0026thinsp;\u0026plusmn;\u0026thinsp;22.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e110.8\u0026thinsp;\u0026plusmn;\u0026thinsp;17.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.50\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFasting blood glucose levels\u0026thinsp;\u0026gt;\u0026thinsp;95 mg/dl (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.88\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1-h after breakfast blood glucose levels\u0026thinsp;\u0026gt;\u0026thinsp;130 mg/dl (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.23\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1-h after lunch blood glucose levels\u0026thinsp;\u0026gt;\u0026thinsp;130 mg/dl (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.71\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1-h after dinnerblood glucose levels\u0026thinsp;\u0026gt;\u0026thinsp;130 mg/dl (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.18\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eOur study shows that blood glucose ketones testing in women with GDM could detect a greater number of ketosis episodes that urinary ketones test. We wanted to check for positive ketonemia in women with GDM with negative urinary ketone test in order to explore the greater sensibility of blood test compared with urine test. Fasting blood ketones presence was correlated with ketones positivity during the day and with glucose levels after breakfast.\u003c/p\u003e \u003cp\u003eKetosis control is functional to the quantitative and qualitative monitoring of the prescribed diet. Ketosis presence in pregnancy implies potential risks not only for the pregnancy itself but also for childbirth outcomes. With this regard, evidences exist on the negative association between beta-hydroxy-butyrate, which represents 85% of ketonic bodies detected during the third trimester of gestation, and newborn neuropsychological development [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe prescription of acetoacetate dosage in urine is a widely diffused procedure even though the intrinsic limitation of acetoacetate measurement. Urine test detects only acetoacetate giving a semiquantitative results affected by urinary output, thus delayed than beta-hydroxy-butyrate (BHB). Ketonemia assessment, instead, is based on BHB which is the mainly responsible body ketone for diabetic ketoacidosis, offering an exact level with a less rate of positive and false negatives. [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eOur results support the higher sensitivity of ketonemia compared to ketonuria, confirming the greater reliability of the former method.\u003c/p\u003e \u003cp\u003eIn this regard, a Greek study involving 180 women with GDM in their third trimester found a significantly higher prevalence of ketonuria (that was not different from that reported in normal pregnant women) compared to ketonemia. This suggests a weak correlation between fasting urine and serum ketone levels, as women with moderate to high urinary ketone levels often had normal serum ketone levels. Several factors may explain this poor correlation. The renal handling of ketones is complex, involving both reabsorption and excretion, which varies depending on serum ketone levels. Additionally, urinary ketone levels reflect serum ketone levels from several hours earlier, due to the time urine spends in the bladder. Moreover, dehydration can concentrate urine, leading to higher measured ketone levels. Furthermore, BHB levels were associated with omission of the bedtime snack, suggesting the importance of proper adherence to the GMD diet. [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eRegarding the timing, the most common attitude adopted in clinical practice is to measure ketonuria or ketonemia before breakfast, assuming that it can be likely to be positive at this time of the day, due to night fasting [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. We found that the only before breakfast test is not enough.\u003c/p\u003e \u003cp\u003eOf considerable importance and validity is a Spanish work in which, with the aim of identifying the best way to delineate the metabolic status of women with GDM, ketonuria and capillary blood glucose measurements were evaluated with timing alternative to the usual ones [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. The Authors assessed the effectiveness of only before breakfast ketonuria measurements compared with testing before the three main meals. All women followed an adequate fractionated diet. Measuring only before breakfast did not allow to identify about a third of the cases of women with ketonuria, being this a potential limit to the use of only morning monitoring [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe only study evaluating differences in ketonemia levels in women with GDM compared to pregnant women without GDM [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] also showed that fasting ketonemia levels did not differ between the two groups, while there was a significant difference in ketonemia levels related to checks carried out before lunch and before dinner. The control of ketonemia during main meals could therefore be advantageous and decisive for the identification of ketosis states not otherwise identified through the routine control of morning ketonuria. This especially in consideration of the fact that ketosis states are indicative of a possible lack of caloric needs which in turn, if not recognized, results in a weight increase below what is recommended. It XXX salso known that an inadequate weight increase is associated with a greater risk of one of the complications of pregnancy, represented by Small for Gestational Age (SGA) children, or children with birth weight below the 10th percentile [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOur study has some limitations. First, we do not analyzed correlations or associations between ketones levels and neonatal outcomes. A deep investigation of the relationship between blood ketones and pregnancy and neonatal outcomes will be available at the end of the EVOKING study. Information on children development is now lacking because of the limited follow-up period.\u003c/p\u003e \u003cp\u003eStrength of our study is the great sample of women with GDM we have enrolled. Our study design allowed to look directly at the potentiality of blood ketones measurement because we have excluded all women with positive urine ketones test.\u003c/p\u003e \u003cp\u003eAnother strength of our study is having performed several sub-analyses in order to test possible differences in blood ketones positivity between subgroups. In particular, we showed that women treated with only diet had no difference in ketones positivity rate compared with women treated with diet plus insulin. This is an important result because it highlights the need to check for ketones presence not only in women with a more complex management of their pregnancy but also in women with a soft management such as those treated with only diet. No differences were detected even when an analysis according to pre-pregnancy BMI classes was performed. It confirms that also women with a high BMI could have ketones positivity, this going against the notion that women with lower BMI are at higher risk for ketosis. Importantly, we found no differences in clinical characteristics when women with only before breakfast ketones were positive compared with women with blood ketones positivity before lunch or before dinner. This raises problems in detecting the most severe cases of GDM complicated by ketotis because of the absence of predictive or suggestive characteristics indicating high risk of ketosis even before lunch or dinner.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eAccording to the results until now showed, intensive blood ketones measurement should be recommended to women with GDM in order to better manage pregnancies complicated by GDM and to limit potential adverse effects of ketosis. However, studies with a randomized controlled design are needed to confirm or not the data we have reported in our study.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eFunding: None.\u003c/p\u003e\n\u003cp\u003eConflicts of interest/Competing interests: The authors \u0026nbsp;declare \u0026nbsp; that \u0026nbsp;the \u0026nbsp;research \u0026nbsp; was \u0026nbsp;conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.\u003c/p\u003e\n\u003cp\u003eEthics approval: All procedures involving human participants were in accordance with the ethical standards of the institutional research committee (Ethics Committee of the University of Messina, prot. 52/18) and with the 1964 Helsinki declaration and its later amendments.\u003c/p\u003e\n\u003cp\u003eConsent to participate: Informed consent was obtained from all individual participants included in the study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eConsent for publication: All authors have read and approved the final version of the manuscript for publication.\u003c/p\u003e\n\u003cp\u003eAvailability of data and material: The raw \u0026nbsp;data \u0026nbsp; supporting \u0026nbsp;the \u0026nbsp;conclusions \u0026nbsp; of \u0026nbsp;this \u0026nbsp;manuscript will be made available by the authors.\u003c/p\u003e\n\u003cp\u003eAuthors\u0026rsquo; contributions: B.P., G.D.V., L. G., A.P., F.C., R.D., and A.D.B. contributed to the study design and acquisition of data, as well as the interpretation of data. B.P. and A.D.B. had the main responsibility for analyzing data and writing the first draft of the paper. B.P., G.D.V., L. G., A.P., F.C., R.D., and A.D.B. critically revised the manuscript. B.P. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eCorrado F, Pintaudi B, Di Vieste G et al (2014) Italian risk factor-based screening for gestational diabetes. J Matern Fetal Neonatal Med 27:1445\u0026ndash;1448\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePaulo MS, Abdo NM, Bettencourt-Silva R, Al-Rifai RH (2021) Gestational Diabetes Mellitus in Europe: A Systematic Review and Meta-Analysis of Prevalence Studies. Front Endocrinol (Lausanne) 12:691033. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fendo.2021.691033\u003c/span\u003e\u003cspan address=\"10.3389/fendo.2021.691033\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003ePMID: 34956073; PMCID: PMC8698118\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMetzger BE, Coustan DR (1998) Summary and recommendations of the Fourth International Workshop-Conference on Gestational Diabetes Mellitus. The Organizing Committee. Diabetes Care ;21 Suppl 2:B161-7\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYe W, Luo C, Huang J, Li C, Liu Z, Liu F (2022) Gestational diabetes mellitus and adverse pregnancy outcomes: systematic review and meta-analysis. BMJ 377:e067946. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1136/bmj-2021-067946\u003c/span\u003e\u003cspan address=\"10.1136/bmj-2021-067946\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003ePMID: 35613728; PMCID: PMC9131781\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSweeting A, Wong J, Murphy HR, Ross GP (2022) A Clinical Update on Gestational Diabetes Mellitus. Endocr Rev 43(5):763\u0026ndash;793. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1210/endrev/bnac003\u003c/span\u003e\u003cspan address=\"10.1210/endrev/bnac003\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003ePMID: 35041752; PMCID: PMC9512153\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eACOG Practice Bulletin No. 190: Gestational Diabetes Mellitus. Obstet Gynecol (2018) ;131(2):e49-e64. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/AOG.0000000000002501\u003c/span\u003e\u003cspan address=\"10.1097/AOG.0000000000002501\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 29370047\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eElSayed NA, Aleppo G, Aroda VR, Bannuru RR, Brown FM, Bruemmer D, Collins BS, Hilliard ME, Isaacs D, Johnson EL, Kahan S, Khunti K, Leon J, Lyons SK, Perry ML, Prahalad P, Pratley RE, Jeffrie Seley J, Stanton RC, Gabbay RA, on behalf of the American Diabetes Association (2023) 15. Management of Diabetes in Pregnancy: Standards of Care in Diabetes-2023. Diabetes Care 46(Suppl 1):S254\u0026ndash;S266. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.2337/dc23-S015\u003c/span\u003e\u003cspan address=\"10.2337/dc23-S015\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003ePMID: 36507645; PMCID: PMC9810465\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGin H, Vambergue A, Vasseur C et al (2006) Blood ketone monitoring: a comparison between gestational diabetes and non-diabetic pregnant women. Diabetes Metab 32:592\u0026ndash;597\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRizzo T, Metzger BE, Burns WJ, Burns K (1991) Correlations between antepartum maternal metabolism and intelligence of offspring. N Engl J Med 325:911\u0026ndash;916\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eQian M, Wu N, Li L, Yu W, Ouyang H, Liu X, He Y, Al-Mureish A (2020) Effect of Elevated Ketone Body on Maternal and Infant Outcome of Pregnant Women with Abnormal Glucose Metabolism During Pregnancy. Diabetes Metab Syndr Obes 13:4581\u0026ndash;4588 PMID: 33268998; PMCID: PMC7701151\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGin H, Vambergue A, Vasseur C et al (2006) Could blood ketone monitoring be a tool for managing gestational diabetes mellitus? Diabetes Care 29:743\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLaffel L (1999) Ketone bodies: a review of physiology, pathophysiology and application of monitoring to diabetes. Diabetes Metab Res Rev 15:412\u0026ndash;426. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1002/(SICI)1520-7560(199911/12)15:6\u0026lt;412::AID-DMRR72\u0026gt;3.0.CO;2-8\u003c/span\u003e\u003cspan address=\"10.1002/(SICI)1520-7560(199911/12)15:6%3C412::AID-DMRR72%3E3.0.CO;2-8\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTaboulet P, Deconinck N, Thurel A, Haas L, Manamani J, Porcher R, Schmit C, Fontaine J-P, Gautier J-F (2007) Correlation between urine ketones (acetoacetate) and capillary blood ketones (3-beta-hydroxybutyrate) in hyperglycaemic patients, vol 33. Diabetes \u0026amp; Metabolism, pp 135\u0026ndash;139. 2\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.diabet.2006.11.006\u003c/span\u003e\u003cspan address=\"10.1016/j.diabet.2006.11.006\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHelen L, Tanner MD, Nitert LK, Callaway HL (2021) Barrett; Ketones in Pregnancy: Why Is It Considered Necessary to Avoid Them and What Is the Evidence Behind Their Perceived Risk? Diabetes Care 1 January 44(1):280\u0026ndash;289. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.2337/dc20-2008\u003c/span\u003e\u003cspan address=\"10.2337/dc20-2008\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSpanou L, Dalakleidi K, Zarkogianni K, Papadimitriou A, Nikita K, Vasileiou V, Alevizaki M, Anastasiou E (2015) Oct-Dec;14(4):644\u0026thinsp;\u0026ndash;\u0026thinsp;50 Ketonemia and ketonuria in gestational diabetes mellitus. Hormones (Athens). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.14310/horm.2002.1610\u003c/span\u003e\u003cspan address=\"10.14310/horm.2002.1610\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 26732157\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e(2015) NG Diabetes in pregnancy: management of diabetes and its complications from preconception to the postnatal period. Available on: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.nice.org.uk/guidance/ng3\u003c/span\u003e\u003cspan address=\"https://www.nice.org.uk/guidance/ng3\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e, published: February 2015, last updated: December 2020\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMontaner P, Ripoll\u0026eacute;s J, Pamies C, Corcoy R (2011) Measurement of fasting ketonuria and capillary blood glucose after main meals in women with gestational diabetes mellitus: How well is the metabolic picture captured? J Obstet Gynaecol Res 37:722\u0026ndash;728\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChiou YL, Hung CH, Liao HY (2018) The Impact of Prepregnancy Body Mass Index and Gestational Weight Gain on Perinatal Outcomes for Women With Gestational Diabetes Mellitus. Worldviews Evid Based Nurs 15:313\u0026ndash;322\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMetzger BE, Freinkel N (1987) Accelerated starvation in pregnancy: implications for dietary treatment of obesity and gestational diabetes mellitus. Biol Neonate 51:78\u0026ndash;85\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"hormones","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"HORM","sideBox":"Learn more about [Hormones](https://www.springer.com/journal/42000)","snPcode":"42000","submissionUrl":"https://www.editorialmanager.com/horm/default2.aspx","title":"Hormones","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"gestational diabetes, urinary ketones, blood ketones, blood glucose","lastPublishedDoi":"10.21203/rs.3.rs-4789676/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4789676/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003ePurpose. Women with gestational diabetes mellitus (GDM) are frequently asked to check their ketones levels by measuring ketonuria before breakfast. However, ketosis could be present even before lunch and dinner. Furthermore, blood ketones measurement could be a more accurate test. Our aim was to evaluate the effect of a blood ketones intensive measurement in the detection of ketosis in women with GDM with negative urinary ketone test.\u003c/p\u003e\n\u003cp\u003eMethods. This was a single center, observational, prospective study involving consecutive women with GDM. Only women with negative fasting urinary ketone tests were included. During the same gestational weeks (30-32 weeks) to all women was suggested to perform a blood ketones test before main meals. Ketosis was defined as the presence for at least 25% of the time of fasting blood ketones levels \u0026gt;0.1 mmol/L and \u0026gt;0.2 mmol/L before lunch and dinner.\u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eResults. Overall, a total of 101 women (mean age 34.7±4.8 years, pre-pregnancy BMI 28.2±5.2 kg/m\u003csup\u003e2\u003c/sup\u003e) were studied. Blood ketones were present in 37.6% of the cases before breakfast, 13.9% before lunch and 11.9% before dinner. Women with at least one daily presence of blood ketones were 40.6% of the sample. Fasting blood ketones presence was correlated with ketones presence before lunch (r=0.63, p\u0026lt;0.0001) and before dinner (r=0.55, p\u0026lt;0.0001) and with one hour after breakfast mean glucose levels (r=0.23, p=0.02).\u003c/p\u003e\n\u003cp\u003eConclusions. Blood glucose ketones testing in women with GDM can detect a great number of ketosis episodes that urinary ketones test. Intensive blood ketones measurement should be recommended to women with GDM.\u003c/p\u003e","manuscriptTitle":"The Evaluation Of Ketones Intensive measurement in women with Gestational diabetes (EVOKING) study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-08-27 15:56:27","doi":"10.21203/rs.3.rs-4789676/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revisions","date":"2024-09-12T16:01:29+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2024-08-18T07:40:26+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-07-30T11:07:29+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"Hormones","date":"2024-07-25T07:09:54+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-07-24T09:37:03+00:00","index":"","fulltext":""},{"type":"submitted","content":"Hormones","date":"2024-07-23T10:36:56+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"hormones","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"HORM","sideBox":"Learn more about [Hormones](https://www.springer.com/journal/42000)","snPcode":"42000","submissionUrl":"https://www.editorialmanager.com/horm/default2.aspx","title":"Hormones","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"48c34e9b-0c97-4ba5-8e19-667d67cfcc33","owner":[],"postedDate":"August 27th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-05-05T15:59:06+00:00","versionOfRecord":{"articleIdentity":"rs-4789676","link":"https://doi.org/10.1007/s42000-025-00663-1","journal":{"identity":"hormones","isVorOnly":false,"title":"Hormones"},"publishedOn":"2025-04-29 15:57:08","publishedOnDateReadable":"April 29th, 2025"},"versionCreatedAt":"2024-08-27 15:56:27","video":"","vorDoi":"10.1007/s42000-025-00663-1","vorDoiUrl":"https://doi.org/10.1007/s42000-025-00663-1","workflowStages":[]},"version":"v1","identity":"rs-4789676","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4789676","identity":"rs-4789676","version":["v1"]},"buildId":"cTy_lsJlmDsVRNrSptgXS","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}