Gestational Diabetes

 

Overview

Gestational diabetes mellitus (GDM) can be defined as glucose intolerance diagnosed in the second or third trimester of pregnancy with no previous diagnosis of diabetes before pregnancy (Joy A Dugan, 2019). Many studies found that gestational diabetes occurs in 2.2–8.8% of pregnancies (Cheung, 2009). gestational diabetes is seen in up to 14% of the population worldwide (José Alberto Laredo-Aguilera, 2020). In some countries, the frequency may reach as much as around 25.5% of pregnancies affected by gestational diabetes based on the International Association of Diabetes and Pregnancy Study Groups criteria (Irma Silva-Zolezzi, 2017).

A degree of intolerance of glucose developed during pregnancy is associated with a risk of future complications such as hypertension, high blood pressure, urinary tract infection, diabetes in the future, excess amniotic fluid building up during pregnancy, or increased operative intervention (Begum, 2016).

To determine the glucose level in the blood to be hyperglycemia, the International Association of Diabetes in Pregnancy Study Groups (IADPSG) derived a value by a Hyperglycaemia Adverse Pregnancy Outcome (HAPO) study data for pregnant women without known diabetes should have a 75 g on oral glucose tolerance test at 24–28 weeks gestation (Ryan, 2011).

The presence of high glucose levels in the blood may result in a short-term or long-term negative impact on the mother and the infant such as the increased risk of obesity in the infant and the mother leading to the development of type 2 diabetes mellitus in the future (Irma Silva-Zolezzi, 2017)

The increasing trend on increase in gestational diabetes may be due to suboptimal lifestyle and nutrition (Irma Silva-Zolezzi, 2017). The major risk factors for gestational diabetes are maternal age, ethnicity, family history of type 2 diabetes mellitus, history of gestational diabetes in a prior pregnancy, high-risk ethnicity, history of Polycystic ovary syndrome (PCOS), less physical activity, hypercholesterolemia, poor pregnancy outcome, pre-existing hypertension or cardiovascular disease, or a prior large baby ≥4000 g (Michelle Lende, 2020; Cheung, 2009; Begum, 2016; Caitlin MacGregor, 2020).

Diabetes mellitus is the most prevalent disease worldwide, affecting almost 370 million people and 4.8 million deaths annually (Irma Silva-Zolezzi, 2017).

Many studies have observed that maternal obesity is the root cause of gestational diabetes (Sarah R Murray, 2020; Emma C Johns, 2018; Michelle Lende, 2020). Obesity is defined as a body mass index of ≥30 Kg/m^{2 (Michelle Lende, 2020; Begum, 2016; Caitlin MacGregor, 2020)}.

Gestational diabetes (GDM) can be classified into two types, which are A1GDM and A2GDM. Management of gestational diabetes with nutritional therapy and without medications known as A1GDM (diet-controlled gestational diabetes). If diabetes needs medication to control glucose and cannot be controlled by diet is called A2GDM (Bryan S Quintanilla Rodriguez, 2022).

Majority of the gestational diabetes is asymptomatic and unsuspected for women weeks of pregnancy. Hence asymptomatic pregnant women need to be screened at 24-28 weeks' gestation (Dugan & Ma-Crawford, 2019; Mayo, 2019). The other signs or symptoms observed during gestational diabetes are more frequent urination and increased thirst (Mayo, 2019).

Pathophysiology of Gestational Diabetes

In pregnant women, there is a 60% reduction in insulin sensitivity. A study on rats was conducted to know the pathophysiology of gestational diabetes (Michelle Lende, 2020).

During pregnancy, maternal glucose is transported across the placenta to the fetus due to the concentration gradient formed between the fetus and the maternal glucose level. The fetus diverts a large amount of glucose towards itself causing demand in the maternal glucose level. This demand increases the production of glucose in the mother and results in glucose build-up in the blood. This in turn increases the demand for insulin production by pancreatic β-cell mass. When the β-cell expansion fails a relatively inadequate rise in insulin secretion leads to GDM (Michelle Lende, 2020). In women with normal functions during pregnancy, the pancreas compensates for the secretion of insulin for physiologic insulin resistance. But when the maternal pancreas fails to respond to the increased insulin requirements from the pancreatic beta cells causes gestational diabetes (Dugan & Ma-Crawford, 2019).

This is similar to patients with type 2 diabetes. However, in a majority of the cases, the post-partum maternal insulin sensitivity quickly returns to normal (Chloe A Zera, 2021; Begum, 2016).

Prevention

Effective and safe exercise and increased intake of fresh fruits have proven that it has reduced the risk of gestational diabetes. In addition, they should consume a limited quantity of dry fruits and sausages. Below are the preventive measures that can be taken to prevent gestational diabetes.

·        Health food: high fibre but low fat and calories contained fruits, vegetables, and whole grains

·        Physically active: a brisk daily walk, a short walk, and 30 minutes of moderate activity

·        Initiate pregnancy at a healthy weight: weights lost before or during planning to get pregnant

·        Keeping track of weight gain: maintain a reasonable level of weight gain during the gestational period (Irma Silva-Zolezzi, 2017; Polina Viktorovna Popova, 2017; Bryan S Quintanilla Rodriguez, 2022)

Diagnosis

In 1973 a study was conducted to describe the screening test for gestational diabetes of 50 g, 1-hour oral glucose tolerance test. This was considered the most reliable method to determine if one has gestational diabetes. The normal range during pregnancy is 130 mg/dL (7.22 mmol/L). Any value ≥140 mg/dL (7.77 mmol/L) is considered to be GDM (Bryan S Quintanilla Rodriguez, 2022).

In 1985, a routine screening test for pregnant women was conducted considering the high risk for gestational diabetes (Michelle Lende, 2020). Standards of Medical Care in Diabetes, the American Diabetes Association (ADA) recommends single-step and two-step processes to determine GDM (Dugan & Ma-Crawford, 2019).

·        One-step fasting test includes a 75 g oral glucose tolerance test at 1 hour and 2 hours. Any values ≥92 mg/dL at fasting or ≥180 mg/dL after 1 hour or ≥153 mg/dL after 2 hours will be diagnostic for gestational diabetes (Dugan & Ma-Crawford, 2019)

·        A confirmatory test is necessary by 100 g, 3-hour oral glucose tolerance test, and the normal values are at 1 hour: ≤180 mg/dL, 2 hours: ≤155 mg/dL, and 3 hours: ≤140 mg/dL. The presence of two or more abnormal results establishes the diagnosis of gestational diabetes (Bryan S Quintanilla Rodriguez, 2022; Chloe A Zera, 2021)

Glycosuria is another method to determine glucose intolerance in blood. This is a urine test conducted using a reagent strip. The test needs to be done 2 or more times at a single incidence or more than one time on many occasions (Begum, 2016). It is recommended that the initial test be conducted before 24 weeks gestation, known as early blood glucose screening (Watson, 1990).

Effect of gestational diabetes

Perinatal and offspring are affected by long-term gestational diabetes mellitus (Emily D Szmuilowicz, 2019). Gestational diabetes mellitus confers lifelong risks to both women and their children (Chloe A Zera, 2021). Potential adverse outcomes seen in offspring exposed to gestational diabetes mellitus are listed below (Emily D Szmuilowicz, 2019).

There are a few short-term effects of gestational diabetes mellites, which include excessive birth weight (>4 kg), hypoglycemia, and respiratory distress (Sarah R Murray, 2020).

The increase in glucose in the fetus results in the increased production of fetal insulin. This causes fetal hyperinsulinemia, which leads to excessive fetal growth resulting in forming of a big baby. There are possibilities of birth complications including a high risk of cesarean, slow or difficult labour or birth, or birth injury due to a large baby (Emily D Szmuilowicz, 2019).

Relatively, the oxygen availability to the fetus is disturbed due to the hyperinsulinemia that changes lung surfactant synthesis. This in turn causes distress to the respiratory system causing unavailability of oxygen to the fetus resulting in stillbirth and admission to the neonatal intensive care unit (Emily D Szmuilowicz, 2019; Mayo, 2019).

As gestational diabetes causes increased glucose levels in the blood that is passed to the fetus. This causes increased production of insulin in the fetus. During delivery, the supply of glucose is abruptly stopped. This makes the insulin utilize the available neonatal glucose, resulting in neonatal hypoglycemia (Emily D Szmuilowicz, 2019).

The other complication observed in gestation diabetes mellitus in the fetus and neonatal are malformations, serious infection, preterm birth, jaundice, cardiometabolic risk in both childhood and adulthood, neurodevelopmental impairments, increased adiposity, insulin resistance, and high glucose levels (less than diagnosis range for diabetes) (Cheung, 2009; Sarah R Murray, 2020; Dugan & Ma-Crawford, 2019; Emily D Szmuilowicz, 2019).

The other long-term effect on adults is obesity, insulin resistance, cesarean delivery, high glucose levels (less than the diagnosis range for diabetes), and type 2 diabetes mellitus (Ryan, 2011).

Intervention

Initial diagnosis and prevention are the best practice to keep the glucose level in control. Hence one should have enough knowledge of the various precautions to be taken to prevent getting gestational diabetes (Cheung, 2009; Dugan & Ma-Crawford, 2019).

Dietary and physical activity

As per Aguilera et al., the performance of physical activity and maintenance of gestational diabetes have positive relationships. There is up to 70–85% of gestational diabetes can be managed with adequate physical activity, and dietary, and lifestyle changes (Michelle Lende, 2020; José Alberto Laredo-Aguilera, 2020).

Approximately 80-90% of women’s gestational diabetes can be managed by medical nutritional therapy. The therapy includes the following diet and activities:

·        3 small to moderate-sized meals

·        2 to 3 snacks

·        balanced diet including whole-grain carbohydrates, protein, and unsaturated fats

·        moderate physical activity: 30 mins of moderate-intensity aerobic exercise for at least 5 days per week or a minimum of 150 mins per week (Emily D Szmuilowicz, 2019)

Pharmaceutical intervention

Insulin

In case gestational diabetes is not controlled using diet and physical exercise, then they are recommended to use insulin as first-line therapy. Insulin does not cross the placenta at a significant level. The different types of insulin used are:

·        Fasting hyperglycemia: basal insulin (long or intermediate-acting)

·        Postprandial hyperglycemia: prandial insulin (rapid-acting)

Oral agents

1.      Glyburide (glibenclamide)

This medication has a risk of macrosomia and neonatal hypoglycemia as they are suspected to cross the placenta.

2.      Metformin 

Metformin also freely crosses over the placenta and is determined to have an equal or larger fetal metformin concentration than maternal concentration. It has a mixed outcome of less maternal weight gain, lower postprandial glucose, and less pregnancy-induced hypertension, but higher rates of preterm birth.

 

The ACOG, ADA, and Diabetes Canada insist on to use of insulin as the first-line agent for the treatment of gestational diabetes. Other societies recommend metformin to the patient only when they are unable or unwilling to take insulin (Chloe A Zera, 2021). The list of preferred medications for gestational diabetes mellites by each society is listed in Table 1.

Table 1: Recommendation for treatment of gestational diabetes mellites

Organization	First line	Alternative first line	Second line	Third linear insulin
ADA	Insulin	–	Metformin or glyburide for women who cannot safely take insulin. Do not use in women with hypertension, pre-eclampsia, or at risk for intrauterine growth restriction	–
ACOG	Insulin	–	Metformin for women who decline, cannot safely take, or cannot afford insulin	Glyburide
SMFM	Metformin	Insulin	–	–
NICE	Metformin only if mild fasting hyperglycemia (glucose <108 mg/dL) and no complications	Insulin if fasting glucose ≥126 mg/dL; consider starting with insulin if fasting glucose is 108–125 mg/dL or obstetric complications	–	Glibenclamide
Diabetes Canada	Insulin	Metformin	–	Glyburide
ACOG = American College of Obstetricians and Gynecologists; ADA = America Diabetes Association; N/A = not applicable; NICE = National Institute for Health and Care Excellence; SMFM = Society for Maternal-Fetal Medicine Source: (Chloe A Zera, 2021)

Other oral hypoglycaemic agents for type 2 diabetes are not recommended during pregnancy (Chloe A Zera, 2021).

The treatment for gestational diabetes is preferred by altering lifestyle and pharmacological intervention based on the level of complication. After obtaining positive results on gestational diabetes mellites, one should consult a doctor.

References

Begum, P. R. R. a. J., 2016. Screening and Diagnosis of Gestational Diabetes Mellitus, Where Do We Stand. J Clin Diagn Res, p. 10(4): QE01–QE04.

Bryan S Quintanilla Rodriguez, H. M., 2022. Gestational Diabetes, Treasure Island (FL): StatPearls Publishing.

Caitlin MacGregor, A. F. L. K.-D. W. G. P. W. H. N. S. C. B. A. B., 2020. Maternal perceived discrimination and association with gestational diabetes. Am J Obstet Gynecol MFM, p. 2(4):100222.

Cheung, N. W., 2009. The management of gestational diabetes. Vasc Health Risk Manag, p. 5:153–164.

Chloe A Zera, E. W. S., 2021 . Controversies in Gestational Diabetes. touchREV Endocrinol, p. 17(2):102–107.

Emily D Szmuilowicz, J. L. J. a. B. E. M., 2019 . Gestational Diabetes Mellitus. Endocrinol Metab Clin North Am, p. 48(3):479–493.

Emma C Johns, F. C. D. J. E. N. R. M. R., 2018 . Gestational Diabetes Mellitus: Mechanisms, Treatment, and Complications. Trends Endocrinol Metab, pp. 29(11):743-754.

Irma Silva-Zolezzi, T. M. S. J. S., 2017 . Maternal nutrition: opportunities in the prevention of gestational diabetes. Nutr Rev, pp. 75(suppl 1):32-50.

José Alberto Laredo-Aguilera, M. G.-B. A. R.-S. A. I. C.-C. a. J. M. C.-T., 2020. Physical Activity Programs during Pregnancy Are Effective for the Control of Gestational Diabetes Mellitus. Int. J. Environ. Res. Public Health, pp. 17(17),6151.

Joy A Dugan, J. M. C., 2019 . Managing gestational diabetes. Journal of the American Academy of Physician Assistants, pp. 32:9;21-25.

Mayo, C., 2019. Gestational diabetes - Symptoms and causes. [Online]
Available at: https://www.mayoclinic.org/diseases-conditions/gestational-diabetes/symptoms-causes/syc-20355339

Michelle Lende, A. R., 2020 . Gestational Diabetes: Overview with Emphasis on Medical Management. Int J Environ Res Public Health, p. 21;17(24):9573.

Polina Viktorovna Popova, A. S. T. Y. A. B. A. S. G. K. A. D. E. A. P. L. V. K. E. N. G., 2017. Risk of gestational diabetes mellitus: Which lifestyle parameters should be changed?. Diabetes Mellitus, pp. 20(1),85-92.

Ryan, E. A., 2011. Diagnosing gestational diabetes. Diabetologia , pp. 54,480–486.

Sarah R Murray, R. M. R., 2020. Short- and long-term outcomes of gestational diabetes and its treatment on fetal development. Prenat Diagn, pp. 40(9):1085-1091.

Watson, W. J., 1990. Screening for glycosuria during pregnancy. South Med J, pp. 83(2):156-8.

 

 

 

Does depression lead to stroke?

Depression is the most common condition observed in the present condition. But ‘depression leading to stoke’ terrorizes us all.

Even though this is a commonly occurring disorder, when unattended leads to serious consequences emotionally and physically. It is quite a surprise to know that directly or indirectly the physical body is affected by depression. Yet it is unknown as to why and how there is a connection with the emotion and body.

Brain is an important part of our organ system. When something affects brain such as stroke, it needs the at most attention to avoid risk. Stroke can occur at any age and it is not gender specific. Perhaps it can even occur in an unborn child (inside the womb).

Everyone under goes depression in some point of time, however the severity is very minimal. At the same time, we do observe a lot of people suffering from chronic depression which requires medical attention.

The more we see the illness leading to critical disorder, more is the fear within everyone. So, we must have enough knowledge and awareness to avoid complication. This very question alerts to dig more information on

·       If depression really does have risk of getting stroke?

·       If it does, how?

·       What is the risk factor?

It is generally observed that depression is a common emotional disorder seen post-stroke (post-stroke depression [PSD]). But recent studies were made and observed that patients suffering from stroke had history of depression.

Firstly, lets understand the terms.

Depression

Depression is a medical illness which provide negative impact on emotion that may trigger negative action on oneself or others. It often involves feeling of loneliness, sadness, loss of interest in activities which previously gave happiness, or any negative senses.

Depression is a disorder that affects the mood, body, sleep, eating and thoughts. It is characterized by extent of mood change that intervenes one’s day to day activity.

Symptoms:

·       Loneliness

·       Feeling hopeless or worthless

·       Deprived in energy

·       Irritability

·       Lack of interest in any activity

·       Loss of appetite

·       Suicidal idea

·       Difficulty in sleeping

 

Stroke 

Strokes is caused when there is interruption in the flow of blood to the brain. It is often observed due to blood clot or rupture in the arteries.

There are two types of strokes:

1.    Ischemic stroke: A stroke caused by a clot is called an ischemic stroke (87%).

2.    Haemorrhagic stroke: These are strokes caused by bleeding (13%).

Symptoms:

·       Sudden numbness or weakness in body parts, especially on one side

·       Sudden confusion

·       Sudden trouble talking or understanding speech

·       Sudden issues of vision in one or both eyes

·       Sudden severe headache

·       Inability to balance body, dizziness, or difficulty in walking

Relation between depression and stroke

There are studies stating that about 18-61% of the stroke survivors experienced depression know as post-stroke depression, however the recent studies found out that there were previous episodes of depressions prior to stroke. It is also observed that depression may increase the risk of stroke and fatality due to stroke.

Scientists have found out neurological condition known as pre-stroke depression which enhances the risk of dying from stroke.

There were studies done to prove the link between depression and risk of stroke by performing 4-question test to measure depression levels.

•          “Yes” equals a point

•          “no” equals zero point

•          Values 1 through 4 indicates various degree of depression level

On evaluation for 9 years, the patients who scored above zero had increased risk of stroke by 39% and values of four had 54% higher risk of stroke.

There are a few assumptions and predictions made, which could be the reasons for increasing the risk of stroke due to depression.

1.    Depression causes inflammation throughout the body, due to increase in inflammation markers in the bloodstream. This causes increase in severity of depression, risk of stroke or even lead to fatality.

2.    There are behavioral changes due to depression. When a person under goes depression, they tend to involve in an unhealthy behavior. Such as smoking, reduced healthy eating habits, less exercise, etc. that may lead to increasing the risk of stroke.

When the person fails to take prescribed medication for blood pressure or cholesterol-lowering drugs. The increase in blood pressure and cholesterol are major risk factors for the cause of stroke.

3.    Antidepressant medication used for treating depression may also be the cause

Below is a study showing that depression may leads to stroke and outer outcomes:

·       ‘Depression and risk of stroke: a meta-analysis of prospective studies’ by Jia-Yi Dong, Yong-Hong Zhang, Jian Tong and Li-Qiang Q

 

This study was performed to find the association between depression and risk of stroke.

This study was a meta-analysis study which is community-based or population-based prospective studies. The relevant studies were identified through May 2011

The study was made on 17 prospective studies considering 206,641 participants and 6086 cases confirmed positive association with depression and risk of stroke. Patients with history of depression had 34% higher risk to experience stroke.

To fill the gaps in the meta-analysis, an updated meta-analysis was made by cross referring to medication history of those patients.

In the observational study, it was seen that patients taking medication to treat depression were more likely to have stroke than the once who did not take medication. It was seen that depression medication were prone to have severe depression symptoms and increased risk of stroke.

But we should not be misunderstood to avoid or assume to be unsafe anti-depressants to treat depression. The interaction among some medications and side effects needs close monitoring. And the patient must make sure all the medication details that they take has to be shared to the physician.

Herbal medication for depression should be discussed with physician before trying, since recently one of the scientists discovered that St. John’s wort, over the counter herbal medication for depression was found to be harmful when interaction with other medications.

Antidepressants and stroke

Antidepressant treatment is used to improve stroke outcome; however, it was observed that certain antidepressants (such as selective serotonin reuptake inhibitors [SSRIs]) cause the bleeding by inhibiting aggregation of platelet and increasing the risk of stroke.

There were new studies being conducted to overlook if the antidepressants used by the patients may cause stroke. To know the most common antidepressants prescribed in India, the study conducted was ‘Prescription pattern of antidepressants in five tertiary care psychiatric centres of India’ by Adarsh Tripathi, Ajit Avasthi, Avinash Desousa, Dipesh Bhagabati, Nilesh Shah, Roy Abraham Kallivayalil, Sandeep Grover, J.K. Trivedi, and Naotaka Shinfuku.

The common drugs for depression, fall into the following class of drugs:

•          selective serotonin reuptake inhibitors (SSRIs)

•          serotonin-norepinephrine reuptake inhibitors (SNRIs)

•          tricyclic antidepressants (TCAs)

•          tetracyclic antidepressants

•          dopamine reuptake blockers

•          5-HT1A receptor antagonists

•          5-HT2 receptor antagonists

•          5-HT3 receptor antagonists

•          monoamine oxidase inhibitors (MAOIs)

•          noradrenergic antagonists

The study came up with data for the most used medication for depression. There were about 79.2% of the prescription were SSRI class of drug and escitalopram was the most common prescribed (40%), followed by sertraline (17.6%) and fluoxetine (16.3%).

Since SSRI was the most used class of drugs for depression, many studies were conducted to see the involvement of SSRI drugs in the increase of stroke risk.

The below are the few SSRI drugs prescribed for depression

·       sertraline (Zoloft)

·       fluoxetine (Prozac, Sarafem)

·       citalopram (Celexa)

·       escitalopram (Lexapro)

·       paroxetine (Paxil, Pexeva, Brisdelle)

·       fluvoxamine (Luvox)

Common side effects of SSRIs include:

·       nausea

·       trouble sleeping

·       nervousness

·       tremors

·       sexual problems

Studies were conducted to verify if the antidepressants (SSRI used to treat depressant) increased the risk of stroke are listed below.

1.    ‘Use of Antidepressants and Risk of Incident Stroke: A Systematic Review and Meta-Analysis’ by Trajkova S, D’Errico A, Soffietti R et al.
2.        ‘Risk of first onset stroke in SSRI-exposed adult subjects: Survival analysis and examination of age and time effects’ by Chan C. Huang H, Lin C et al.
3.        ‘Impact of prestroke selective serotonin reuptake inhibitor treatment on stroke severity and mortality’ by Janne Kaergaard Mortensen, Heidi Larsson, Søren Paaske Johnsen, and Grethe Andersen

All these studies observed independent increase in risk of stroke on the use of SSRIs.

In the other hand, one of the studies observed increase in severity and mortality in patients with haemorrhagic stroke within 30 days than ischemic stroke. However, in contradiction the 8-year study observed that SSRI use is more likely to be in ischemic than haemorrhagic.

It is assumed that the mechanism of stroke may be due to cerebral micro bleeding or over correction of haemostasis function.

There are not enough data available to provide a broad view of the mechanism involved in the increase in stroke risk with history of depression. Yet from the available data we can conclude few things. The depression causing inflammation may lead to severity of the condition and lead to risk. Other simple logic is the change in behavior changes that could be the possible reason to increase in risk of stroke.

Other observations were made and found that patients taking antidepressants (especially SSRIS) were more prone to increase in risk of stroke. However, the reason may be depression itself or the antidepressant medication is unclear.

There is inconsistency in the outcome of the study (probability of ischemic or haemorrhagic stroke). This unclear data needs more attention and research.