Gestational diabetes mellitus (GDM) is a condition characterized by hyperglycemia first identified during pregnancy, representing a significant public health problem due to the associated maternal and fetal risks (p. 1). This study aimed to evaluate the importance of the glycemic curve, using the Oral Glucose Tolerance Test (OGTT), in the diagnosis and monitoring of GDM (p. 1). This is a literature review based on national and international guidelines and current scientific literature (p. 1). The results demonstrate that the OGTT is considered the gold standard for the diagnosis of GDM, allowing for the early detection of glycemic abnormalities and contributing to the reduction of maternal-fetal complications (p. 1). It is concluded that the glucose curve is an essential tool in clinical and laboratory practice (p. 1).

Keywords: gestational diabetes, glucose curve, TOTG, Diagnosis (p. 1)

ADA, American diabetes association; T2D, type 2 diabetes mellitus; GDM, gestational diabetes mellitus; GLUT-4, glucose transporter type 4; HAPO, hyperglycemia and adverse pregnancy outcomes; hPL, human placental lactogen; IDF, international diabetes federation; IRS-1, insulin receptor substrate 1; WHO, world health organization; PGH, placental growth hormone; SBD, Brazilian diabetes society; OGTT, oral glucose tolerance test

Gestational Diabetes Mellitus (GDM) is a metabolic disorder characterized by impaired glucose tolerance, resulting in hyperglycemia of varying severity, with onset or first diagnosis occurring during pregnancy (p. 1). It is one of the most prevalent medical complications during pregnancy, having a substantial impact on public health systems due to the high risk of maternal and perinatal morbidity (pp. 1–2). In the global epidemiological landscape, estimates from the International Diabetes Federation (IDF) indicate that approximately 16.7% (one in six) of live births are associated with some form of hyperglycemia during pregnancy, with GDM accounting for the vast majority of these cases (p. 2).¹

The clinical relevance of GDM is based on its close association with adverse obstetric outcomes (p. 2). For the pregnant woman, the persistence of elevated blood glucose levels significantly increases the incidence of hypertensive disorders, such as preeclampsia, in addition to increasing rates of operative deliveries (cesarean sections) and the risk of developing type 2 diabetes mellitus (T2DM) in the years following delivery (p. 2). In the fetal and neonatal context, the repercussions include macrosomia, neonatal hypoglycemia, shoulder dystocia, preterm birth, and an epigenetic predisposition to the development of obesity and metabolic syndrome throughout childhood, adolescence, and adulthood (p. 2).²

Given the transgenerational impact of this condition, timely screening and accurate diagnosis are essential for patient care (p. 2). The Oral Glucose Tolerance Test (OGTT) with a 75-g load of anhydrous glucose has established itself as the gold standard for diagnosing gestational diabetes (pp. 1–2). This test allows for mapping the dynamic response of maternal metabolism to controlled glucose stress, identifying failures in homeostasis that would not be detected by fasting blood glucose testing alone (p. 2). The present study is justified by the need to consolidate scientific evidence regarding the accuracy of the OGTT, discussing its clinical sensitivity and its direct implications for mitigating adverse maternal-fetal outcomes (pp. 1–2).³

General objective

To evaluate the importance of the glucose curve in the diagnosis and monitoring of gestational diabetes mellitus (p. 3).

Specific objectives

1. To describe the pathophysiology of GDM (p. 3);
2. Analyze diagnostic criteria (p. 3);
3. Identify the relevance of TOTG (p. 3);
4. Discuss maternal-fetal complications (p. 3);
5. Evaluate glycemic monitoring (p. 3).

This study was a qualitative literature review with a descriptive approach, structured through the analysis of international guidelines and scientific articles focused on the diagnosis and monitoring of Gestational Diabetes Mellitus (GDM) (p. 3). Data collection was conducted through systematic searches in scientifically relevant indexed databases, specifically PubMed and SciELO (p. 3). Additionally, official documents and clinical guidelines issued by leading institutions in the field were consulted, including the Brazilian Diabetes Society (SBD), the World Health Organization (WHO), the American Diabetes Association (ADA), and the International Diabetes Federation (IDF) (p. 3).

For study selection, the following health descriptors (DeCS/MeSH) were used, combined using Boolean operators: “gestational diabetes,” “glucose curve,” “oral glucose tolerance test,” “laboratory diagnosis,” and “pregnancy” (p. 3). The search strategy was restricted to publications in Portuguese and English (p. 3).

The inclusion criteria included scientific articles published between 2015 and 2026, available in full, that directly addressed the diagnosis, screening, or monitoring of DMG (p. 3). Duplicate studies, non-peer-reviewed publications, articles with explicit methodological inconsistencies, or those lacking direct clinical relevance to the proposed topic were excluded (p. 3).

The selection process took place in two independent stages: initially, titles and abstracts were screened to verify thematic eligibility; subsequently, the selected texts were read in full (p. 3). Data analysis was conducted in a descriptive and integrated manner, generating a critical synthesis grounded in the evidence with the highest methodological rigor from the current literature (p. 3).

Theoretical foundation

Pathophysiology of gestational insulin resistance

Normal pregnancy involves profound adaptive metabolic changes coordinated by the trophoblastic syncytium, aimed at ensuring a continuous flow of nutrients for full fetal development (pp. 1, 4). Under the influence of insulin-counterregulatory hormones secreted by the placenta

— primarily human placental lactogen (hPL), placental growth hormone (PGH), progesterone, cortisol, and prolactin — a physiological state of insulin resistance is induced in the mother, progressing from the second trimester of pregnancy (pp. 1, 4). These hormones block intracellular insulin receptor signaling pathways (such as the phosphorylation of insulin receptor substrate-1, IRS-1), reducing peripheral glucose uptake mediated by GLUT-4 transporters in maternal muscle and adipose tissue (p. 4).⁴

In normophysiological pregnancies, the maternal pancreas compensates for this peripheral resistance by promoting adaptive hyperplasia and hypertrophy of beta cells, resulting in an increase of up to 250% in basal and postprandial insulin secretion (pp. 1, 4). However, as postulated. In their comprehensive review of gestational diabetes mellitus (GDM), McIntyre et al. (2019) note that women who develop the condition exhibit latent chronic dysfunction of pancreatic beta cells. When metabolic demand peaks at the end of the second trimester, the pancreas in these patients fails to maintain compensatory hyperinsulinism, leading to chronic maternal hyperglycemia and the development of GDM (pp. 1, 4).⁴

Diagnostic criteria and the metabolic dynamics of TOTG

The laboratory diagnosis of GDM is based on the identification of abnormalities in glycemic homeostasis (p. 4). Currently, the 75-g anhydrous glucose OGTT performed between the 24th and 28th week of gestation is the international protocol recommended by consensus by the World Health Organization (WHO) and the American Diabetes Association (ADA) (pp. 2, 4). The three-point analysis of the glucose curve assesses metabolism at critical time points: fasting (reflecting basal hepatic glucose production), after 1 hour (reflecting the first phase of insulin secretion and gastric emptying), and after 2 hours (reflecting the second phase of secretion and peripheral clearance of the glucose load) (pp. 2, 4).²

The cutoff values used for diagnosis are listed below:

Source: Adapted from SBD² and WHO⁵ (p. 4).

According to current guidelines from the Brazilian Diabetes Society (SBD), an abnormality in just one of the three points on the glycemic curve confirms a definitive diagnosis of postprandial hyperglycemia (p. 4). This unified, highly sensitive approach was established to ensure that subtle post-load metabolic abnormalities receive prompt clinical intervention, thereby preventing underreporting of at-risk patients (p. 4).²

Clinical evidence and impacts on perinatal outcomes

The empirical validation of current cutoff points stems primarily from the historical context of the pioneering Hyperglycemia and Adverse Pregnancy Outcomes.⁶ study, which evaluated more than 25,000 pregnant women and demonstrated a linear and continuous association between maternal blood glucose levels and an increase in adverse perinatal outcomes, without the presence of a clear safety threshold or limit (p. 5).⁶

Expanding on these findings, the long-term follow-up study HAPO Follow-up Study⁷ confirmed that intrauterine exposure to maternal hyperglycemia, even at modest levels in the TOTG, correlates directly with an increased risk of glucose intolerance and obesity in offspring a decade after birth, highlighting the role of fetal programming (p. 5).⁶

Furthermore, a robust meta-analysis conducted by Farrar et al.,⁸ in the Cochrane Database of Systematic Reviews demonstrated that active treatment of these patients diagnosed via the OGTT drastically reduces the occurrence of macrosomia and shoulder dystocia, corroborating the high clinical utility of standardized universal screening via the glucose curve (pp. 1, 5).⁸

Analysis of the compiled data reveals a consensus in the contemporary literature regarding the analytical superiority of the Oral Glucose Tolerance Test (OGTT) in the diagnosis of gestational diabetes mellitus (GDM) (pp. 5–6). While fasting blood glucose alone is limited to recording the patient’s baseline metabolic state, the OGTT introduces a dynamic overload that challenges the cellular adaptive homeostatic mechanisms described in the theoretical framework, revealing early failures in compensatory insulin secretion (pp. 2, 5–6)(Table 1).⁴

Discussion of scientific studies

As summarized in Table 1, the correlation between maternal blood glucose levels and perinatal prognosis is not strictly linear (pp. 5–6). The seminal findings of the HAPO study⁶ established that even slight fluctuations in blood glucose 1 hour and 2 hours after glucose ingestion severely impact the intrauterine environment (pp. 5–6). This phenomenon is robustly supported by data from the HAPO Follow-up Study (2018), indicating that the harmful effects of this threshold hyperglycemia persist in the long term, causing epigenetic changes that predispose offspring to obesity in the first decade of life (pp. 2, 5).⁷

This continuous nature of metabolic risk justifies the highly sensitive diagnostic criteria validated by the American Diabetes Association³ and the World Health Organization (WHO, 2013) (pp. 5–6). The validation of the meta-analysis by Farrar et al.,⁸ reinforces this perspective by demonstrating that the identification and subsequent early intervention in pregnant women who exceed the stipulated cutoff limits substantially reduce rates of serious complications, such as shoulder dystocia and fetal macrosomia (pp. 1–2, 6).⁸

Critical analysis of the glucose curve

The establishment of fasting cut-off points ≥ 92 mg/dL, 1-hour ≥ 180 mg/dL, and ≥ 2-hour 153 mg/dL acts as a refined early screening system (pp. 4, 6). As postulated by McIntyre et al. (2019), a significant proportion of pregnant women with early beta-cell dysfunction maintain basal fasting glycemic homeostasis but exhibit metabolic collapse following a 75-g glucose load (pp. 1, 6).⁴

The graphical analysis confirms the clinical relevance of three-point time-based monitoring (pp. 6–7). Therefore, the guideline adopted by the Brazilian Diabetes Society,² which establishes a definitive diagnosis of GDM based on a change in just a single data point on the curve, safeguards the safety of the mother-fetus pair (pp. 4, 6). This methodological sensitivity ensures the timely inclusion of the patient in nutritional therapy protocols and continuous glucose monitoring, mitigating adverse outcomes before transgenerational structural or functional damage becomes established in the fetus (pp. 2, 6–7).²

The glucose curve, obtained through the 75-gram Oral Glucose Tolerance Test (OGTT), has established itself as an indispensable tool in the diagnosis of gestational diabetes mellitus (pp. 1, 7). The test’s ability to dynamically assess the metabolic response confers superior analytical sensitivity, enabling the early detection of insulin secretion abnormalities that would go unnoticed in isolated baseline assessments, such as fasting blood glucose (pp. 6–7).

The rigorous application of this laboratory protocol, combined with careful interpretation of reference parameters, enables the immediate implementation of therapeutic interventions (p. 7). Measures such as nutritional therapy, lifestyle modification, and, when necessary, pharmacological intervention robustly reduce the incidence of severe acute complications, such as fetal macrosomia and shoulder dystocia (pp. 2, 7). Furthermore, recent scientific data reiterate that early diagnosis acts preventively against chronic outcomes and negative epigenetic inheritance in offspring, mitigating risks of obesity and glucose intolerance in childhood and adulthood (pp. 2, 7).

Given the epidemiological scenario of high global prevalence of GDM, the need for systematic and universal screening during prenatal care, guided by updated clinical guidelines, is reinforced (pp. 2, 7). It is therefore concluded that TOTG plays a central role in modern obstetric care, serving as a watershed moment for optimizing maternal-fetal outcomes and promoting intergenerational public health (pp. 1, 7).

None.

The author declares no conflicts of interest.

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