Nutritional influences on gestational diabetes: A review on macronutrient and micronutrient impacts

Epidemiological insights

As per the 2021 data, the global prevalence is 14.7%.^[7] The International Diabetes Federation declared that 1 in 6 pregnant women is affected by GDM.^[8] The prevalence has doubled in the past decade due to the increase in other metabolic disorders and high rates among certain ethnic groups, such as African, Hispanic, Indian, and Asian mothers, when compared to Caucasian women.^[9] In high-risk populations, the recurrence risk in future pregnancies is about 68% and nearly one-third of mothers develop overt diabetes within 5 years of delivery.^[2]

In India, according to the National Health Family Survey-5 (2019–2021), the prevalence was 0.8% with a high preponderance in elderly pregnant women compared to the younger age group.^[10] GDM prevalence rose from 0.48% in 15–19 years to 3.91% in 40–44 years. States such as Uttar Pradesh, Meghalaya, and Karnataka together accounted for nearly 30% of reported cases. GDM prevalence was notably higher in South India than in North India. The NHFS relies on self-reported data, so the chances of underestimation are high. According to a systematic review done in 2024 by Mantri et al., the pooled prevalence of GDM in India is 13% with the rural population showing 10% and the urban population showing 12%.^[11] Prevalence varied markedly across states, from 0% in Manipur to as high as 42% in urban Tamil Nadu, highlighting stark regional disparities in screening, diagnosis, and healthcare access. Southern states consistently reported higher prevalence compared to other regions. One of the important findings was that GDM rates increased progressively with maternal age and socioeconomic status.

Risk factors and their multifaceted complications

The main risk factors for GDM are obesity, sedentary lifestyle, family history of type 2 diabetes mellitus, previous history of macrosomic child or GDM, and polycystic ovarian syndrome (PCOS). Ethical groups such as Asia Pacific and South Asia are more susceptible because high abdominal obesity, low muscle mass, and high insulin resistance are prevalent in these regions compared to other parts of the world.^[9] Among the risk factors, obesity is one of the most common risks associated with nearly 31% of GDM mothers.^[2]

GDM causes both short-term and long-term risks to both the mother and fetus. Maternal complications include abortion, pre-eclampsia, difficult delivery, or cesarean section, and fetal complications such as macrosomia, hypoglycemia, hyperbilirubinemia, respiratory distress syndrome, fetal anomalies, and fetal demise are linked to GDM. Babies born to mothers with GDM are at high risk for cardiovascular disease and metabolic disorders early in life compared to others.^[1,2]

Pathophysiology

Normal pregnancy is a condition of physiological insulin resistance that develops during mid-pregnancy and persists till the end. Human placental lactogen, human placental growth factors, estrogen, progesterone, tumor necrosis factors, and adipokines secretion peak during the second trimester. These hormones act on the main Insulin signaling pathway, namely, the Insulin Receptor Substrate- Phosphoinositide-3-kinase/Akt (IRS–PI3K–Akt) pathway. The hormones structurally alter peripheral insulin receptors’ beta-subunit, diminish phosphorylation of tyrosine kinase, and remodel insulin receptor substrate-1 (IRS-1) and phosphatidylinositol 3-kinase, disrupting the insulin action and creating an insulin-resistant environment.^[12] These changes take place to spare the uninterrupted glucose supply to the growing fetus. The mother’s pancreas tries to compensate with hyperplasia and high insulin secretion initially, but with the increasing insulin resistance at the cellular level and the risk factors contributing to this, there is a steady increase in serum glucose levels.

In GDM, insulin resistance impairs insulin signaling, reduces tyrosine kinase phosphorylation, and decreases Glucose Transporter type 4 (GLUT4) activation, leading to elevated maternal glucose levels.^[13] Hepatic gluconeogenesis increases, worsening hyperglycemia. Lipid metabolism is altered, with exaggerated hyperlipidemia, elevated free fatty acids, reduced lipoprotein lipase, and increased ketogenesis, contributing to fetal macrosomia and oxidative stress. Chronic low-grade inflammation in adipose tissue is driven by altered adipokines, including elevated leptin, resistin, and visfatin, and decreased adiponectin. Placental cytokines further amplify systemic inflammation. Inflammatory mediators such as intracellular adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM), and monocyte chemoattractant protein (MCP) recruit immune cells, which release interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α), worsening insulin resistance.^[14]

Diagnosis and management

The American Diabetes Association recommends screening using a one-step or two-step procedure for high-risk mothers, irrespective of their gestational age, at the earliest.^[15] Risk factors include

• Severe obesity

• GDM during a previous pregnancy or delivery of a macrosomic baby

• Presence of glycosuria

• Diagnosis of PCOS

• Strong family history of type 2 diabetes.

In the two-step procedure, initially, a 50 g oral glucose load is given, and a 1 h post-load value of >140 mg/dL warrants the second step of confirmation using a 100 g oral glucose load. Any two values more than the following cutoff of fasting >95 mg/dL,1 h >180 mg/dL, 2 h more than 155 mg/dL, and 3 h more than 140 mg/L confirm the diagnosis. In the single-step procedure, a 75 g oral glucose load is given, and one of the values of fasting >95 mg/dL, 1 h >180 mg/dL, and 2 h >155 mg/dL confirms the diagnosis. According to the International Association of Diabetes and Pregnancy Study Groups criteria, an oral glucose tolerance test (OGTT) is done using 75 g of glucose at 24–28 weeks, and if any one of the cutoffs is met, that is, ≥ 92 mg/dL in fasting or 1-h ≥180 mg/dL (or) 2-h ≥153 mg/dL warrants GDM diagnosis.^[15]

The mainstay of the treatment is diet and exercise. Nutritional therapy might help to achieve the glycemic targets in about 80–90% of women.^[5] Mothers are advised to check their glucose levels frequently to maintain the target levels. The carbohydrate intake should be reduced to 35–45% of the total calories and distributed over three meals and 2–4 snacks, including bedtime snacks. This reduces post-prandial glucose peak and also ensures adequate nutrition to the mother and the fetus.^[6] Furthermore, preventing excessive weight gain during pregnancy with moderate exercise is advised for GDM mothers. If the medical nutrition therapy and exercise fail to achieve glycemic goals for a woman with GDM, insulin therapy should be initiated.^[8]

Role of dietary carbohydrates in the pathogenesis of GDM

Carbohydrate is the principal macronutrient for the energy demands of the mother, fetus, and placenta during pregnancy, and it is the key macronutrient in the pathogenesis of GDM. It is well known that the quantity and quality of carbohydrates play a major role in the regulation of blood glucose. Hence, significance is given to the dietary carbohydrate intake in GDM. High-glycemic-index foods, such as processed and refined foods, can lead to a rapid rise in post-prandial glucose levels, contributing to insulin resistance, which is a hallmark of GDM.^[19,20] Simple sugars are rapidly absorbed, leading to sharp post-prandial spikes in maternal blood glucose. In GDM, where insulin resistance impairs glucose clearance, these spikes are prolonged and more pronounced. The excess maternal glucose readily crosses the placenta, exposing the fetus to high glucose levels. This stimulates the fetal pancreas to produce more insulin, leading to fetal hyperinsulinemia.^[13] Conversely, complex carbohydrate-containing foods such as whole grains and legumes, and fruits release glucose gradually, thereby balancing the glucose levels throughout the day.^[20] The gut microbiota also has a role in carbohydrate metabolism. Changes in the composition of the gut microbiota, influenced by dietary carbohydrates, may affect the production of short-chain fatty acids and other metabolites that can impact insulin sensitivity.^[20]

Role of proteins in the pathogenesis of GDM

Slightly higher levels of protein consumption are recommended in pregnancy, whereas carbohydrates and fat are similar to the pre-pregnant levels. The role of protein in GDM is still unclear. However, dietary proteins and amino acids have an important role in blood glucose regulation. Animal proteins like red meat are implicated in causing diabetes mellitus and GDM, conversely, plant-based proteins and other animal proteins such as poultry, fish, and dairy products reduce the risk.^[21] This distinction could be due to the associated cholesterol and saturated fats in animal protein and variations in amino acid composition. Branched-chain amino acids (BCAAs), namely, valine, leucine, and isoleucine, have been linked to insulin resistance.^[22,23] The reason is that animal proteins are rich in BCAA, which results in a 200% rise in post-prandial glucose compared to fasting. These BCCAs stimulate insulin secretion through the mammalian target of rapamycin (mTOR) pathway and downregulate IRS-1 through serine phosphorylation.^[24] This inhibits the Insulin Receptor Substrate- phosphoinositide-3-kinase/Akt pathway (PI3K-Akt) signaling pathway, impairing GLUT4 translocation and reducing glucose uptake in skeletal muscle and adipose tissue. The chronic stimulation of the mTOR pathway causes B-cell exhaustion. Adequate serum protein and, in turn, dietary protein are required for the secretion of various hormones such as insulin, glucagon, and other counter-regulatory hormones. Plant proteins are rich in fiber, antioxidants, and phytochemicals, which improve insulin sensitivity and reduce inflammation.^[25]

Role of dietary fats in the pathogenesis of GDM

Fatty acids also play a key role in glucose homeostasis. Increased circulating free fatty acid inhibits insulin-mediated glucose uptake, worsening the existing insulin resistance. There are minimal studies about dietary fats and the risk of GDM. Even the existing studies have proved inconsistent findings. High intake of animal fat, cholesterol, and saturated fats poses a high risk for GDM because saturated fats impact insulin signaling and induce endothelial inflammation and dysfunction.^[26] These lipids activate protein kinase C, which phosphorylates IRS-1 at serine residues, inhibiting insulin signaling and GLUT4 translocation. Furthermore, the toxic lipid intermediates, such as diacyl glycerol and ceramides, in the insulin-sensitive tissue cause altered insulin receptors.^[27] Saturated fats activate Toll-like receptor 4 on immune cells and adipocytes, triggering nuclear factor-kappa B (NF-κB) pathway activation. This leads to the production of pro-inflammatory cytokines (e.g., TNF-α and IL-6), which further impair insulin action and promote systemic inflammation – hallmarks of GDM.^[28] They also produce an oxidative stress-rich environment due to the production of reactive oxygen, leading to pancreatic beta cell dysfunction. In contrast to all the actions mentioned above by the saturated and trans fats, monounsaturated and omega-3 fatty acids are beneficial.^[29] The omega-3 fatty acids help in the synthesis of resolvins and protectins, which help in resolving inflammation. They also reduce the activation of NF-κB, thus decreasing the secretion of inflammatory mediators. In addition, the overall quality of the diet, including the types of fats consumed and the context of the overall dietary pattern, is likely to be a crucial factor in determining its impact on GDM risk. Table 2 shows the various studies done around the world on the association of diet with the risk of GDM.^[29-32]