Blood Glucose Response after Betamethasone Injection in Pregnant Women without Diabetes

Abstract

Background:

Betamethasone is routinely administered in preterm pregnancies to accelerate fetal lung maturity, yet its glycemic impact on nondiabetic pregnant women remains underexplored.

Objective:

This study aimed to evaluate the effect of betamethasone on maternal glucose levels and hormonal profiles in pregnant women without diabetes and assess the need for monitoring and intervention.

Materials and Methods:

A prospective observational study was conducted on 80 normoglycemic pregnant women between 24 and 34 weeks of gestation. Each participant underwent an Oral glucose tolerance test and hormonal profiling before and after receiving the first intramuscular dose of injection betamethasone 12 mg. The second dose of injection Betamethasone 12 mg was given 24 h later.

Results:

Significant elevations in fasting, 1-h, and 2-h blood glucose levels were observed postbetamethasone (P < 0.001), along with increased insulin, C-peptide, and cortisol levels, indicating a steroid-induced metabolic shift. Hyperglycemia peaked within 12–24 h. Elevated body mass index and borderline glycated hemoglobin were associated with greater glucose excursions.

Conclusion:

Even a single course of betamethasone can induce clinically significant hyperglycemia in nondiabetic pregnant women. Routine poststeroid glucose monitoring is essential to minimize maternal and neonatal risks while preserving the established benefits of antenatal corticosteroids.

INTRODUCTION

Antenatal corticosteroids have revolutionized the management of pregnancies at risk for preterm delivery, significantly improving neonatal outcomes. Betamethasone is the most widely recommended agent owing to its potent glucocorticoid activity and established safety profile.[1] Typically administered as two intramuscular injections of 12 mg each, 24 h apart between 24 and 34 weeks of gestation, it promotes fetal lung maturation by enhancing surfactant production. This intervention has consistently been associated with reduced incidence of neonatal respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis, and neonatal mortality, earning its place as a cornerstone in modern perinatal care.[2] Despite these benefits, betamethasone is not without maternal side effects, the most significant being hyperglycemia. As a glucocorticoid, betamethasone alters glucose metabolism by inducing insulin resistance, stimulating hepatic gluconeogenesis, and impairing peripheral glucose uptake.[3] This can result in elevated blood glucose levels even among individuals with previously normal glycemic control. The physiological insulin resistance of pregnancy, driven by hormones such as human placental lactogen and cortisol, further amplifies this effect, creating a milieu particularly vulnerable to steroid-induced hyperglycemia.[4]

In this context, the present study aims to evaluate the blood glucose profile following intramuscular betamethasone in pregnant women without diabetes. Blood glucose levels were monitored at fasting and post-75 mg glucose load at 1 h and 2 h intervals, as per the oral glucose tolerance test (OGTT) protocol. The study seeks to characterize the pattern, duration, and clinical relevance of transient hyperglycemia. It also investigates whether these changes exceed diagnostic thresholds for gestational diabetes mellitus (GDM) and whether they necessitate clinical intervention.

The findings guide evidence-based recommendations for glucose monitoring in all pregnant women receiving corticosteroids, irrespective of their baseline glycemic status, thus ensuring optimal maternal and fetal outcomes without compromising the established benefits of antenatal corticosteroid therapy.

MATERIALS AND METHODS

Type of study

Observational Study.

Study design

Prospective Study.

Place of study

Dr. D. Y. Patil Medical College, Hospital and Research Centre, Pimpri, Pune 411018.

Study population

Pregnant women without co-morbidities between 24 and 34 weeks completed weeks who were administered injection betamethasone 12 mg IM 24 h apart, 2 doses.

Study period

October 2022 to March 2025.

Inclusion criteria

1. Pregnant women with gestational age between 24 weeks and <34 weeks, as determined by reliable clinical or ultrasonographic dating

2. Women identified as requiring antenatal corticosteroid therapy for fetal lung maturation, due to an anticipated risk of preterm delivery within the next few days

3. Absence of a previous diagnosis of diabetes mellitus or any form of glucose intolerance

4. Normal 75-g OGTT results at the time of inclusion, as per standard diagnostic thresholds for gestational diabetes.

Exclusion criteria

1. Gestational age ≥34 weeks at the time of evaluation

2. Preexisting diagnosis of diabetes mellitus, including type 1, type 2, or gestational diabetes

3. Significant cardiovascular disease or any other major systemic illness that could independently affect glucose metabolism or complicate the interpretation of study results

4. Multiple gestations, due to altered metabolic demands and increased variability in glucose response

5. Use of medications known to affect glucose metabolism.

Like hyperglycemia-inducing drugs

Glucocorticoids – Prednisolone, Sympathomimetics – Epinephrine, Thiazide diuretics – Hydrochlorothiazide, Loop diuretics – Furosemide, Beta-blockers (nonselective) – Propranolol, Atypical antipsychotics – Olanzapine, Protease inhibitors – Indinavir, Antiepileptics – Phenytoin, Immunosuppressants – Tacrolimus.

Hypoglycemia-inducing drugs

Insulin and analogs – Regular insulin, Sulfonylureas – Glibenclamide, Meglitinides – Repaglinide, Biguanides – Metformin, Thiazolidinediones – Pioglitazone, GLP-1 receptor agonists– Exenatide, DPP-4 inhibitors – Sitagliptin, SGLT2 inhibitors – Dapagliflozin, Salicylates (high dose) – Aspirin.

Study method

As part of routine antenatal care, all pregnant women between 24 and 28 weeks of gestation underwent a 75-g OGTT to screen for GDM. Only women with no prior diagnosis of overt diabetes and normal OGTT values (fasting <92 mg/dL, 1-h <180 mg/dL, 2-h <153 mg/dL) were included. The OGTT involved collecting a fasting blood sample, followed by administration of 75 g of anhydrous glucose dissolved in 250–300 mL of water, consumed within 5 min. Blood samples were taken at 1-and 2-h postglucose intake to assess glycemic response. Participants were followed with regular antenatal visits, and those presenting with symptoms suggestive of preterm labor before 36 + 6 weeks, such as abdominal pain, backache, per vaginal (PV) bleeding/leaking, or cervical dilatation, received a 12 mg intramuscular dose of betamethasone. A repeat OGTT was performed 24 h after the first dose, and then the second dose of betamethasone was completed. Data were collected using a structured case record pro forma and included pre-and post-betamethasone OGTT values, along with demographic, clinical, and biochemical data. Serum insulin, C-peptide, and cortisol levels were also measured before and after betamethasone administration. The percentage and mean rise in blood glucose levels were calculated, and variations were analyzed across different GDM risk groups and body mass index (BMI) categories. Associations between OGTT changes and neonatal intensive care unit (NICU) admissions, gestational age, and overall blood glucose derangement in nondiabetic pregnant women receiving betamethasone were also evaluated.

Sample size

Considering the sample size as per the cited article, Glycemia after Betamethasone in Pregnant Women without Diabetes-Impact of Marginal Values in the 75-g OGTT32, Published February 17, 2020, by Kakoulidis I, Ilias I, Linardi A, et al. Using the mean and standard deviation (SD) of fasting capillary blood glucose, the estimated sample size is 79. Confidence level 95% Acceptable difference = 5. Assume that SD = 22.3. Using software WinPEPI (PEPI-for-Windows), Version 11.38, developed by J.H. Abramson, School of Public Health and Community Medicine, Hebrew University, Jerusalem, Israel.

n = required sample size

Zα/2 = standard normal deviate corresponding to the desired confidence level

For 95% CI, Z = 1.96

σ = assumed SD (from pilot study or previous literature)

d = acceptable error/margin of error

n = 76.4 After rounding → 79

In the present study, a total of 80 normoglycemic pregnant women fulfilling the inclusion criteria were consecutively enrolled and analyzed.

Consent protocol

Candidates for the study were selected from pregnant women admitted to the wards or attending the outpatient department of the Department of Obstetrics and Gynaecology of Dr. D. Y. Patil Medical College, Hospital and Research Centre, Pimpri, Pune. Patients were informed about the study aim, objectives, and procedure. They were enrolled after obtaining informed consent.

Data collection

After consent was obtained, the selected candidates who had presented with symptoms of preterm labor at <34 weeks of gestation were enrolled over the following months. These symptoms included complaints of abdominal pain, lower back pain, PV bleeding, PV leaking, pelvic pain, or clinical signs of cervical dilatation suggestive of preterm labor. The participants were interviewed based on a pro forma prepared in accordance with the aim and objectives of the study. All relevant investigation reports, treatment records, outcomes, and necessary data were recorded in the case record form.

Ethical issue

Institutional Ethical Committee clearance was obtained before the start of the study. Permission was also obtained from the Institutional Review Board of Dr. D. Y. Patil Medical College and Hospital, Pune. Informed written consent was taken from the patient or their caregiver before conducting the interviews.

Statistical analysis

Data entry was carried out using Microsoft Excel (Microsoft Corporation, Redmond, Washington, USA), and statistical analysis was performed using IBM SPSS (version 21). Descriptive statistics were expressed as mean, SD, frequency, and percentage. To assess the significance of changes in blood sugar levels before and after betamethasone administration, paired t-tests were applied. For comparison between groups (e.g., BMI categories, GDM risk groups), One-Way analysis of variance (ANOVA) and regression analysis were used. Correlation analysis was conducted to evaluate associations between changes in insulin levels and blood sugar levels. P <0.05 was considered statistically significant.

1. Paired Sample t-test: The paired t-test was employed to compare pre-and post-betamethasone values for continuous variables that followed a normal distribution

2. Non-Parametric Test (Wilcoxon Signed-Rank Test): For variables not normally distributed, specifically serum cortisol levels, the Wilcoxon signed-rank test was applied

3. Correlation Analysis (Pearson Correlation): The study also assessed the relationship between changes in insulin levels and mean changes in blood sugar levels using Pearson correlation

4. One-Way ANOVA: One-Way ANOVA was used to examine differences in blood sugar level changes across BMI categorical subgroups

5. Regression Analysis: Multivariate regression analysis was performed to identify independent predictors of blood sugar level changes after betamethasone administration, like Gestational Age.

RESULTS

A total of 80 pregnant women without a known history of diabetes mellitus were enrolled in the present study to assess glycemic alterations following intramuscular administration of betamethasone. Baseline demographic profiles, including age, gestational age, BMI, and glycated hemoglobin (HbA1c) values, were recorded, revealing a majority in the 25–34 years age range, with a high prevalence of overweight and obesity. Statistically significant elevations were indicating a consistent hyperglycemic effect of betamethasone. Mean glucose levels peaked between 12 and 24 h and gradually normalized by 72 h in most cases. Subgroup analysis revealed that elevated BMI and borderline HbA1c levels were associated with higher postinjection glucose excursions. No patient developed persistent glucose intolerance or required long-term intervention.

Table 1 shows the distribution of general demographic characteristics of the study population, including age, gestational age, BMI, and HbA1c categories.

Table 1.

Baseline characteristics of study population

Characteristic	Category	n (%)
Age group (years)	18–20	1 (1.2)
	21–24	14 (17.5)
	25–29	28 (35.0)
	30–34	23 (28.8)
	≥35 years	14 (17.5)
Gestational age (by USG)	24–26 weeks	29 (36.2)
	27–29 weeks	21 (26.2)
	30–32 weeks	24 (30.0)
	33–34 weeks	6 (7.5)
BMI category	Underweight	1 (1.2)
	Normal	20 (25.0)
	Overweight	30 (37.5)
	Obese	29 (36.2)
HbA1c group (%)	<5.0%	44 (55.0)
	5.0–5.4%	36 (45.0)

BMI=Body mass index, HbA1c=Glycated hemoglobin, USG=Ultrasonography

Table 2 compares fasting, 1-h, and 2-h OGTT blood glucose levels before and after betamethasone using paired t-tests, showing statistically significant rises.

Table 2.

Pre- and postbetamethasone blood sugar levels

Pair	Variable	Mean	n	SD	SEM	P
Pair 1	Fasting BSL before betamethasone	81.325	80	8.2228	0.9193	<0.001
	Fasting BSL after betamethasone	121.388	80	12.3519	1.3810
Pair 2	1-h OGTT before betamethasone	130.613	80	28.0151	3.1322	<0.001
	1-h OGTT after betamethasone	224.050	80	48.7203	5.4471
Pair 3	2-h OGTT before betamethasone	105.713	80	17.5854	1.9661	<0.001
	2-h OGTT after betamethasone	196.413	80	40.5649	4.5353

OGTT=Oral glucose tolerance test, SD=Standard deviation, SEM=Standard error of mean, BSL=Blood sugar level

Table 3 presents the mean, range, and SD of percentage increases in blood sugar values after betamethasone.

Table 3.

Percentage increase in blood sugar levels after betamethasone administration

Parameter	n	Minimum	Maximum	Mean	SD
Percentage increase in fasting BSL	80	11.54	100.00	50.9385	22.89248
Percentage increase in 1-h OGTT	80	−9.43	230.00	79.7654	55.95201
Percentage increase in 2-h OGTT	80	11.84	232.18	91.2125	54.27156

OGTT=Oral glucose tolerance test, SD=Standard deviation, BSL=Blood sugar level

Table 4 presents the paired sample statistics for serum insulin levels before and after administration of betamethasone. Statistically significant increases are seen, suggesting a compensatory hormonal response to steroid-induced hyperglycemia.

Table 4.

Changes in insulin levels before versus after betamethasone

Pair	Variable	Mean	n	SD	SEM	Significant(two-tailed)
Pair 1	Serum insulin before betamethasone (μU/mL)	9.445	80	2.6510	0.2964	<0.001
	Serum insulin after betamethasone (μU/mL)	13.045	80	2.7413	0.3065

SD=Standard deviation, SEM=Standard error of mean

Table 5 shows the absolute difference in mean glucose values before and after betamethasone across fasting, 1-h OGTT, and 2-h OGTT. This highlights the clinical magnitude of hyperglycemia induced.

Table 5.

Summary of blood sugar level changes pre- and postbetamethasone

Parameter	Prebetamethasone (mg/dL)	Postbetamethasone (mg/dL)	Mean change (mg/dL)
Fasting BSL	81.33	121.39	+40.06
1-h OGTT	130.61	224.05	+93.44
2-h OGTT	105.71	196.41	+90.70
Mean BSL change	–	–	74.73

OGTT=Oral glucose tolerance test, BSL=Blood sugar level

Table 6 evaluates the relationship between insulin response and blood glucose elevation poststeroid. No significant correlation was found.

Table 6.

Correlation between insulin change and mean BSL change

Correlation between variables	Pearson r	P
Insulin change versus mean BSL change	−0.172	0.128

BSL=Blood sugar level

Table 7 compares blood glucose changes postbetamethasone in high-risk versus low-risk women for GDM.

Table 7.

Comparison of mean BSL change between gestational diabetes mellitus risk groups

GDM risk group	Mean BSL change(mg/dL)	SD	P
High risk	85.62	28.4	0.027
Low risk	69.13	24.7

GDM=Gestational diabetes mellitus, SD=Standard deviation, BSL=Blood sugar level

DISCUSSION

The administration of antenatal corticosteroids, particularly betamethasone, is an established intervention for promoting fetal lung maturity in pregnancies at risk of preterm delivery.[5] However, its impact on maternal glucose metabolism, even in normoglycemic women, is clinically relevant and often under-recognized.[6] This study demonstrates a significant, albeit transient, increase in maternal blood glucose levels following betamethasone administration in pregnant women without pre-existing diabetes.[7] The findings affirm the steroid’s potential to induce insulin resistance and glycemic dysregulation.[8] Multiple studies have previously highlighted the acute hyperglycemic effects of corticosteroids.[9] These effects are attributed to a combination of increased hepatic gluconeogenesis and impaired peripheral glucose uptake.[10] Our findings align with earlier observations reporting substantial rises in postprandial glucose following corticosteroid exposure.[11] This reinforces the understanding that even a single course of betamethasone can result in exaggerated glycemic excursions, particularly in the 1-hour and 2-hour post-load phases.[12] The compensatory rise in insulin levels after steroid administration observed in this study further validates the body’s physiological response to acute hyperglycemia.[13] These changes indicate intact pancreatic beta-cell function and an active insulin response, but they also suggest the presence of steroid-induced insulin resistance.[14] Prior literature supports this mechanism and emphasizes the transient nature of this hormonal adaptation.[15]

While the glycemic effects were generally reversible, the magnitude of glucose elevation in certain individuals, especially those with high BMI or borderline HbA1c, raises concern[16] The variability in glucose response, particularly among women at higher risk for GDM, underscores the importance of individualized metabolic assessment and follow-up. Corticosteroid exposure may unmask latent glucose intolerance, highlighting the need for vigilance in such patients.[17] From a clinical standpoint, the implications of transient maternal hyperglycemia are significant.[18] Elevated maternal glucose can lead to fetal hyperinsulinemia, which increases the risk of neonatal complications such as hypoglycemia, macrosomia, and increased NICU admissions.[19] These trends were evident in this cohort, although not always statistically significant. Furthermore, the influence of maternal factors such as BMI and gestational age at delivery on glucose response emphasizes the need for pre-emptive risk stratification. Obese women and those further along in gestation demonstrated more pronounced hyperglycemic responses.[20]

In summary, while the metabolic impact of betamethasone is generally transient, it may have clinical consequences for both mother and fetus if not proactively monitored. This study advocates for temporary glucose monitoring protocols following betamethasone, even in normoglycemic women. Special attention should be given to postprandial periods, where glucose spikes are most prominent, to optimize maternal and neonatal outcomes without compromising the benefits of corticosteroid therapy.

Limitations

This study has several limitations. First, it was a single-center, hospital-based study with a modest sample size (n = 80), which may limit generalizability to wider populations. Second, follow-up was restricted to short-term postbetamethasone monitoring; longer-term maternal glycemic outcomes and neonatal effects were not evaluated. Third, glucose responses were assessed only using OGTT values at fasting, 1-h, and 2-h; continuous glucose monitoring could have provided more granular data on glycemic excursions. Fourth, potential confounders such as diet, stress, and circadian variations in glucose were not controlled for. Finally, hormonal assays (insulin, C-peptide, cortisol) were performed in a subset only, and inter-assay variability cannot be excluded. These limitations should be addressed in larger, multicenter trials with extended follow-up and standardized monitoring protocols.

CONCLUSION

A single course of intramuscular betamethasone causes a significant but temporary rise in blood glucose levels in nondiabetic pregnant women, particularly in 1-h and 2-h postprandial readings. While fasting levels also increase, they are less affected, and glucose levels generally normalize within 48 h. Short-term glucose monitoring for 24–48 h postadministration is recommended, especially in women with borderline glycemic status. Dietary adjustments, such as low glycemic index foods, can help manage spikes. Although most cases don’t require medication, transient insulin or oral agents may be needed if postprandial values exceed 180 mg/dL. A rise in maternal glucose was linked to higher NICU admissions, highlighting the need for standardized monitoring protocols and patient education to balance maternal safety with fetal benefits.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.