INTRODUCTION:

Gestational Diabetes Mellitus occurs when a women’s pancreatic function is not sufficient to overcome the diabetogenic environment of pregnancy. The amount of GDM varies in direct proportion to the prevalence of type II diabetes.¹ In GDM “Glucose intolerance resulting in the Hyperglycaemia with variable severity with onset or first recognition during pregnancy”. Insulin Pregnancy is a potentially glucose intolerant condition. Sensitivity decreases as the pregnancy advances. At later stage of pregnancy, some women develop Gestational diabetes Mellitus (GDM) particularly obese with pre-existing insulin resistance. Insulin is recognised as the “gold standard” for the treatment of GDM.¹

The most common risk factors are obesity, older maternal age, strong family history of diabetes of GDM, increased incidence of hypertensive disorders during pregnancy, including gestational hypertension, preclampsia and eclampsia.

COMPLICATIONS:

Short-term complications: hypoglycaemia (very low blood glucose), Hyperosmolar hyperglycemic nonketotic syndrome (HHNS), that is extremely high blood sugar. Long-term complications: Diabetic retinopathy, Diabetic nephropathy, Diabetic neuropathy and Macrovascular complications.²

MANAGEMENT:

· Weight loss

· Healthy intake

· Regular exercise

· Blood aldohexose observance

· Diabetic medications or insulin therapy Oral hypoglycemics (Metformin, Sulphonylureas, Meglitinides, Thiazolidinediones, DDP-4 inhibitors, GLP-1 receptor agonists, SGLT2 inhibitors). Screening for GDM should be performed between the 24th and 28th weeks of gestation that are of average to high risk of developing diabetes. The main purpose of identifying GDM is to detect women at risk of adverse perinatal outcomes. Approximately 4% of all pregnancies are complicated by GDM while the prevalence may range from 1-14% of all pregnancies depending on the population and the method of screening. For many years, fast-acting (regular) insulin, and intermediate-acting (isophane) insulin have been the preferred insulin for the treatment of GDM. Human insulin does not normally cross the placenta.³

The exact pathology of DM was unclear but some of the factors may often contribute to the disease progression. In our body, glucose will be transferred from the blood into the cells, the endocrine hormone like insulin is needed. In our body pancreas produces 2 special endocrine cells such as α and β –cells, β-cells are involved in the insulin production.

TYPES OF DIABETES: 1. Type-1 (IDDM or Juvenile onset) - due to autoimmune or viral diseases. 2. Type-2 (NIDDM or adult onset) - due to genetic factors Gestational diabetes - Following pregnancy.³

Diabetes is a serious public health problem that threatens the quality of life of patients. The success of long-term maintenance therapy for diabetes depends largely on the patients compliance with a therapeutic plan.⁴

Gestational diabetes mellitus is characterized by a rise in glucose intolerance and is first acknowledged during pregnancy. The condition negatively impacts about 2% to 8% of all pregnant women worldwide and is on the rise.⁵ Women who are exposed to being diagnosed with type 2 diabetes are additionally at high risk of GDM.⁶ Insulin resistance develops throughout a typical pregnancy as feto-placental hormone concentrations rise. Parental hyperglycaemia, which is common in GDM, induces fetal elevated levels of insulin and excessive growth of insulin-sensitive cells, leading to excessive, imbalanced foetal growth, increased stress at birth, shoulder impingement, and neonatal deaths.⁵Insulin resistance is increased during pregnancy. The maintenance of euglycemia is accomplished through a compensatory increase in insulin secretion. GDM screening is usually done between 24 and 28 weeks of pregnancy. An oral glucose tolerance test is used to make the diagnosis, although the criteria differ around the world. GDM is associated with an elevated risk of unfavorable pregnancy outcomes as well as a long-term risk of childhood obesity and type 2 diabetes in both mothers and offspring.⁷ If glucose targets are not attained, care during pregnancy consists of blood glucose monitoring and medical nutrition therapy, which includes calorie restriction, physical exercise, and pharmacotherapy.⁸

Lifestyle Modifications:

The first-line treatment options for GDM are lifestyle modifications such as nutrition therapy and regular physical activity, or a combination of the two. These therapies are a low-cost strategy to improve glycaemic control without using insulin. In addition, polyunsaturated fatty acids and vitamin D supplementation have been utilized to manage GDM.

Fig 2: Management of gestational diabetes

Reduced consumption of dietary fibre has been positively linked to GDM. Dietary fiber consumption-especially that of cereal and fruit—was substantially and negatively correlated with the incidence of GDM.⁹

Regular physical activity during pregnancy benefits both mother and baby by enhancing cardiopulmonary muscle tone or function. It also lowers the chances of a condition known as gestational diabetes and postpartum obesity (lifestyle maternal nutrition). Due to concerns about potential negative effects on the mother and fetus, physical exercise was discouraged during pregnancy; however, several studies have shown that women who engage in mild to moderate physical activity do not have any negative consequences for either party.^[9] Changes in lifestyle are essential to the therapy of GDM. It has been hypothesized that lifestyle changes alone are adequate to regulate blood glucose in 70–80% of women diagnosed with GDM. The most important tactics for attaining strict control of blood glucose levels are regular tracking of one's own blood sugar levels, accompanied by suitable nutrition therapy. Patients who have become pregnant are required to consume a suitable number of calories, protein, and micronutrients.¹⁰

Dietary fibre:

Fibre consumption, especially water-soluble fibre, is effective in minimizing blood levels of cholesterol and moderating glycaemic fluctuations. Low-GI foods typically include more fibre, but this is occasionally the case. In a combination meal, high-fibre foods can fulfil the same goal as low-GI diets.¹¹

Protein:

Sufficient protein consumption while pregnant is critical to avoid the loss of parental reserves and the breakdown of muscles to meet fetal demands. Most nutrition standards suggest a protein consumption of ten to twenty percent of one's daily EI, or sixty to eighty g of protein per day.¹² The existing evidence shows that consuming more protein from vegetables, white meat, and fish, while decreasing processed and red meat consumption, is advantageous in the management of GDM and may improve the response to insulin. The positive effect of plant-based protein on GDM may not be due to the type of protein but rather to a decrease in other nutrients linked with a greater chance of GDM, such as carbohydrates and saturated fats.¹¹

Table 1: The basic principle of signal system

Principles	Green	Yellow	Red
Refined cereals and sugars	Low	Moderate to high	High
Saturated fat	Low	Low	High
Total fat	Low	Moderate	High
Glycaemic index	Low	Moderate to high	High
Fibre	High	Low	Negligible
Cooking method	Steaming, boiling, roasting, grilling, less fat in cooking	Pan fried, sauteed, moderate amount of fat in cooking	Deep fried, rich in fat and sugar, rich sauce-cream dressing
Processing	Rich in fibre, parboiled	Low fibre, refined, miled	Low fibre, ready to eat, highly processed
How much to eat	Eat as permitted	Moderate	Restrict

Carbohydrate:

Carbohydrates are considered an essential component for GDM women. The quantity and type of carb will both affect glucose levels. As a result, high carbohydrate consumption during a meal can result in hyperglycemia. Simple carbs typically cause greater gastric elevations than more complicated carbs. A daily diet consisting of three substantial meals and three short snacks between them is suggested to prevent overeating concurrently, particularly to minimize significant amounts of sugar-based foods and, as a result, minimize postprandial blood glucose.¹¹

Fig 3: The blood glucose levels according to different strategies for daily food intake. Blue curve illustrates the normal meal pattern and red curve illustrates meal pattern in women with gestational diabetes mellitus (GDM) to avoid excessive blood glucose fluctuations and to preserve the planes number of calories to be ingested blue arrows: Three main meals. Red arrows: three main meals and three snacks.

Vitamins and Minerals:

The need for vitamins and minerals increases during pregnancy. Folates are essential vitamins during pregnancy. Folate is required for the formation of amino acids, which facilitate the replication of cells, making it essential for fetal growth. Low gestational intakes of folate enhance an infant's likelihood of premature birth and brain abnormalities.¹¹

Table 2: Recommendations of specific micronutrients during Pregnancy

Micronutrient	NNR	IOM
Folic acid, µg/day	500	600
25-Hydroxyvitamin D, µg/day	10	5
Calcium, mg/day	900	1000
Iron, mg/day	40	27

Calcium:

During gestation, the body's demand for calcium doubles. The need for supplements is determined by the woman's dietary habits. Calcium dietary supplements, on the other hand, may have a beneficial impact on glycemic management in women with diabetes. Finally, it is recommended that women with gestational diabetes consume 900–1000 mg of calcium every day during pregnancy.¹¹

Iron:

The most prevalent micronutrient shortfall throughout women's reproductive years is iron insufficiency. Women have higher iron requirements due to the elimination of iron during menstruation. Furthermore, many women have low iron levels when they get pregnant and are not getting enough iron in their diet to meet the increased demand during pregnancy.¹⁶

Monitoring glucose and weight recommendations:

Due to the rising prevalence of obesity and glucose intolerance during pregnancy, guidelines for weight gain during pregnancy have become a changing target in recent decades. The weight recommendations differ slightly by country. Many countries, however, refer to the Institute of Medicine (IOM) of National Academies' recommendations for GWG, which were updated in 2009 based on pre-pregnancy data. BMI (Body Mass Index).

Table 3: Recommendations for total weight gain during singleton pregnancy

Pre-Pregnancy BMI	Total Weight Gain (Range in kg)
Under weight (<18.5 kg/m²)	12.5-C18
Normal weight (18.5-24.9 kg/m²)	11.5-16
Overweight (25.029.9 kg/m²)	7-11.5
Obese (≥30 kg/m²)	5-9

Weight goals are particularly highlighted if glucose standards are not met, but they are also promoted independently of glucose levels.⁴ Small dietary changes can enhance glycaemic control.⁸ Checking the blood glucose level four times a day is a standard procedure. Initial morning glucose testing can exclude hyperglycaemia from fasting, and follow-up measurements one or two hours after meals can guarantee appropriate management.¹⁰ Depending on the severity of the hyperglycaemic disease in pregnancy, the patient monitors his or her own blood glucose levels 4–7 times each day. As previously stated, the goal for blood sugar control is venous plasma glucose levels of 100 mg/dl or less before meals and 120 mg/dl or less two hours after meals.¹³

Insulin:

Insulin analogs (lispro and aspart) have been proven in studies to be more effective than conventional human insulin for attaining target blood sugar levels and reducing the risk of macrosomia.⁹ Insignificant levels of human insulin pass through the placenta; hence, it is safe to use during pregnancy.¹³ Pharmacological treatment is advised after 1-2 weeks of the diet if glycaemic objectives are not met. Insulin that acts quickly is used to cover glucose spikes that occur after meals, whereas insulin that acts more slowly is used to support the liver's synthesis of glucose during fasting.¹¹ The intermediate-acting neutral protamine Hagedorn (NPH) insulin and the long-acting analogs insulin glargine and insulin detemir are two options for basal insulin coverage in GDM treatment. Rapid-acting insulin normally begins working 30 minutes or 1 hour after subcutaneous injection, reaches its full effectiveness between 2 and 4 hours, and the effect can extend for 6–8 hours. Intermediate insulin acts for 1-2 hours after subcutaneous injection, has maximal effectiveness between 4 and 8 hours, and has a half-life of 12 to 18 hours. Long-acting insulin acts for 3–4 hours after subcutaneous injection, peaks between 8 and 10 hours, and can last up to 20 hours. As a result, combining various insulin preparations to approximate daily physiological insulin secretion is advantageous. Insulin delivery should begin with a low dose that is gradually increased, and insulin types and regimens should be tailored to the individual.¹⁵

Glyburide:

Glyburide, a second-generation oral sulfonylurea, produces cellular membrane depolarization by enhancing insulin release from the pancreatic beta-islet cells. Glyburide has been demonstrated to be more efficacious than first-generation drugs and to have a superior safety profile.⁷ Metformin and glyburide were just as effective as insulin in controlling blood sugar levels during the treatment of GDM. The only noteworthy distinction in the two medications' results was that metformin caused the mother's weight gain to be reduced during pregnancy. A few studies revealed that kids of GDM moms receiving glyburide had a greater prevalence of macrosomia and neonatal hypoglycaemia. On the other hand, when glyburide or metformin are used instead of insulin, a meta-analysis revealed that there is no consistent evidence for an increase in any unfavourable outcomes for mothers or new-borns.

Metformin:

Metformin is being evaluated as a possible insulin alternative in the treatment of type 2 diabetes.⁹ Because many women with GDM have moderately high blood sugar levels, oral medicines such as metformin are also an alternative when nutritional therapy and physical activity fail to sufficiently regulate glucose. Metformin enhances peripheral insulin tolerance and has not been linked to obesity or low blood sugar when taken alone. Furthermore, metformin has been used to promote ovulation and fertility in patients with polycystic ovarian syndrome, and it may be taken until the end of the initial phase of pregnancy to lower the likelihood of spontaneous abortion.¹³Biguanides are a group of oral hypoglycemic agentsthat are chemically and pharmacologically distinct from the sulfonylureas. One biguanide, phenformin, was briefly used in the United States more than 30 years ago but was withdrawn from the market because it produced severe lactic acidosis in some patients. Metformin (Glucophage) was used in Europe for many years before it was approved for use in the United States in 1995. Metformin is the only approved biguanide for the treatment of patients with NIDDM that are refractory to dietary management alone. Metformin does not affect insulin secretion but requires the presence of insulin to be effective. The exact mechanism of metformin’s action is not clear, but it does decrease hepatic glucose production and increase peripheral glucose uptake. When used as monotherapy, metformin rarelycauses hypoglycemia. Metformin works best in patients with significant hyperglycemia and is often considered first-line therapy in the treatment of mild to moderate type II overweight diabetics who demonstrate insulin resistance.¹⁷

CONCLUSION:

Even though GDM is one of the most frequent disorders during pregnancy, a paucity of data from well-designed research casts some doubt on the need for screening and care of this condition. Because the illness relates to both maternal and foetal difficulties, it is critical to assess and manage women at the proper gestational age to reduce bad consequences. Glycaemic management can be achieved safely by combining dietary and pharmacological therapies. Metformin and glyburide have been demonstrated to be equally effective as insulin in the treatment of type 2 diabetes.A clinical dietitian should provide dietary advice to all women with GDM, as dietary counselling is a vital component in the management of GDM. Understanding the effect of nutrition on blood glucose levels is critical for avoiding issues such as difficulties during delivery, C-sections, LGA-babies, and developing type 2 diabetes later in life. The woman should be advised on how to build a diversified diet to prevent hyperglycaemia. Individuals' clinical conditions must be identified throughout time in dealing with their intolerance to carbohydrates during pregnancy. To summarize, GDM is related to an increased risk of unfavourable health outcomes for both mothers and kids, not only during the perinatal period but also in the long term. Thus, GDM prevention and control must be prioritized throughout pregnancy, that is, prior to pregnancy, during pregnancy, and after pregnancy. The primary and major strategies should be nutrition counselling and regular exercise. If lifestyle changes alone are insufficient to maintain hypoglycaemia, OADs and insulin should be considered.

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Received on 15.01.2024 Revised on 24.05.2024

Accepted on 06.10.2024 Published on 07.12.2024

Available online on December 30, 2024

Res.J. Pharmacology and Pharmacodynamics.2024;16(4):301-305.

DOI: 10.52711/2321-5836.2024.00052