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Black stool, why is that happened? Let me tell you

Black stool, in medicine we call it melena. melena or melæna refers to the black, "tarry" feces that are associated with gastrointestinal hemorrhage.[1] The black color is caused by oxidation of the iron in hemoglobin during its passage through the ileum and colon.

Bleeding originating from the lower GI tract (such as the sigmoid colon and rectum) is generally associated with the passage of bright red blood, or hematochezia, particularly when brisk. Blood acts as a cathartic agent in the intestine, promoting its prompt passage. Only blood that originates from a high source (such as the small intestine), or bleeding from a lower source that occurs slowly enough to allow for enzymatic breakdown is associated with melena. For this reason, melena is often associated with blood in the stomach or duodenum (upper gastrointestinal tract), for example by a peptic ulcer. A rough estimate is that it takes about 14 hours for blood to be broken down within the intestinal lumen; therefore if transit time is less than 14 hours the patient will have hematochezia, and if greater than 14 hours the patient will exhibit melena. One often-stated rule of thumb is that melena only occurs if the source of bleeding is above the ligament of Treitz although, as noted below, exceptions occur with enough frequency to render it unreliable. Blood in the stool may come from anywhere along your digestive tract, from mouth to anus. It may be present in such small amounts that you cannot actually see it, and it is only detectable by a fecal occult blood test. When there is enough blood to change the appearance of your stools, the doctor will want to know the exact color to help find the site of bleeding. To make a diagnosis, your doctor may use endoscopy or special x-ray studies. Black stool usually means that the blood is coming from the upper part of the gastrointestinal (GI) tract. This includes the esophagus, stomach, and the first part of the small intestine. Blood will typically look like tar after it has been exposed to the body's digestive juices as it passes through the intestines. Maroon-colored stools or bright red blood usually suggests that the blood is coming from the lower part of the GI tract (large bowel, rectum, or anus). However, sometimes massive or rapid bleeding in the stomach causes bright red stools. Eating black licorice, lead, iron pills, bismuth medicines like Pepto-Bismol, or blueberries can also cause black stools. Beets and tomatoes can sometimes make stools appear reddish. In these cases, your doctor can test the stool with a chemical to rule out the presence of blood. Bleeding in the esophagus or stomach (such as with peptic ulcer disease) can also cause you to vomit blood. In some patients bleeding can be black and "tarry" (sticky) and foul smelling. The black, smelly and tarry stool is called melena. Melena occurs when the blood is in the colon long enough for the bacteria in the colon to break it down into chemicals (hematin) that are black. Therefore, melena usually signifies bleeding is from the upper gastrointestinal tract (for example: bleeding from ulcers in the stomach or the duodenum or from the small intestine) because the blood usually is in the gastrointestinal tract for a longer period of time before it exits the body. Sometimes melena may occur with bleeding from the right colon. On the other hand, blood from the sigmoid colon and the rectum usually does not stay in the colon long enough for the bacteria to turn it black. Rarely, massive bleeding from the right colon, from the small intestine, or from ulcers of the stomach or duodenal can cause rapid transit of the blood through the gastrointestinal tract and result in bright red rectal bleeding. In these situations, the blood is moving through the colon so rapidly that there is not enough time for the bacteria to turn the blood black. Symptoms Patients sometimes present with signs of anemia or those due to low blood pressure. Very often, however, aside from the melena itself, there are no other symptoms. The presence of blood must be confirmed with either a positive hemoccult slide on rectal exam, frank blood on the examining finger, or a positive stool guaiac from the lab. If a source in the upper GI tract is suspected, an upper endoscopy can be performed to diagnose the cause. Lower GI bleeding sources usually present with hematochezia or frank blood. A test with poor sensitivity/specificity that may detect the source of bleeding is the tagged red blood cell scan. This is especially used for slow bleeding (<0.5 ml/min). However, for rapid bleeding (>0.5 ml/min), mesenteric angiogram ± embolization is the gold standard. Note: As iron is the source of the black color, consumption of black pudding may cause asymptomatic melena. Why is that happened? The most common cause of melena is peptic ulcer disease. Any other cause of bleeding from the upper gastro-intestinal tract, or even the ascending colon, can also cause melena. Melena may also be a sign of drug overdose if a patient is taking anti-coagulants, such as warfarin. It is also caused by tumours, especially malignant tumors affecting the esophagous, more commonly the stomach & less commonly the small intestine due to their bleeding surface. However,the most prominent and helpful sign in these cases of malignant tumours is haematemesis. It may also accompany hemorrhagic blood diseases (e.g. purpura & hemophilia). Other medical causes of melena include bleeding ulcers, gastritis, esophageal varices, and Mallory-Weiss syndrome. Some causes of "false" melena include Iron supplements, Pepto-Bismol, Maalox, and lead, blood swallowed as a result of a nose bleed (epistaxis), and blood ingested as part of the diet, as with the traditional African Maasai diet, which includes much blood drained from cattle. Melena is usually not a medical emergency because the bleeding is slow. Urgent care however is required to rule out serious causes and prevent potentially life-threatening emergencies. A less serious, self-limiting case of melena can occur in newborns two to three days after delivery, due to swallowed maternal blood. The upper part of the GI tract will usually cause black stools due to: Abnormal blood vessels (vascular malformation) A tear in the esophagus from violent vomiting (Mallory-Weiss tear) Bleeding stomach or duodenal ulcer Inflammation of the stomach lining (gastritis) Lack of proper blood flow to the intestines (bowel ischemia) Trauma or foreign body Widened, overgrown veins (called varices) in the esophagus and stomach The lower part of the GI tract will usually cause maroon or bright red, bloody stools due to: Anal fissures Bowel ischemia (when blood supply is cut off to part of the intestines) Colon polyps or colon cancer Diverticulosis (abnormal pouches in the colon) Hemorrhoids (common cause) Inflammatory bowel disease (such as Crohn's disease or ulcerative colitis) Intestinal infection (such as bacterial enterocolitis) Small bowel tumor Trauma or foreign body Vascular malformation (abnormal collections of blood vessels called arteriovenous malformations or AVMs) How to treat this? If you have passed a lot of blood, you may need emergency treatment, which can include: Blood transfusions Fluids through a vein Interventional radiography embolization (a procedure to block the blood vessels that may be bleeding) Medications to decrease stomach acid Possible surgery if bleeding does not stop

It's really hard to urinate, maybe you have BPH or worst cancer

Benign prostatic hyperplasia (BPH), also known as benign prostatic hypertrophy, is a histologic diagnosis characterized by proliferation of the cellular elements of the prostate. Cellular accumulation and gland enlargement may result from epithelial and stromal proliferation, impaired preprogrammed cell death (apoptosis), or both.

BPH involves the stromal and epithelial elements of the prostate arising in the periurethral and transition zones of the gland (see Pathophysiology). The hyperplasia presumably results in enlargement of the prostate that may restrict the flow of urine from the bladder.

BPH is considered a normal part of the aging process in men and is hormonally dependent on testosterone and dihydrotestosterone (DHT) production. An estimated 50% of men demonstrate histopathologic BPH by age 60 years. This number increases to 90% by age 85 years.

The voiding dysfunction that results from prostate gland enlargement and bladder outlet obstruction (BOO) is termed lower urinary tract symptoms (LUTS). It has also been commonly referred to as prostatism, although this term has decreased in popularity. These entities overlap; not all men with BPH have LUTS, and likewise, not all men with LUTS have BPH. Approximately half of men diagnosed with histopathologic BPH demonstrate moderate-to-severe LUTS.

Clinical manifestations of LUTS include urinary frequency, urgency, nocturia (awakening at night to urinate), decreased or intermittent force of stream, or a sensation of incomplete emptying. Complications occur less commonly but may include acute urinary retention (AUR), impaired bladder emptying, the need for corrective surgery, renal failure, recurrent urinary tract infections, bladder stones, or gross hematuria. (See Clinical Presentation.)

Prostate volume may increase over time in men with BPH. In addition, peak urinary flow, voided volume, and symptoms may worsen over time in men with untreated BPH (see Workup). The risk of AUR and the need for corrective surgery increases with age.

Patients who are not bothered by their symptoms and are not experiencing complications of BPH should be managed with a strategy of watchful waiting. Patients with mild LUTS can be treated initially with medical therapy. Transurethral resection of the prostate (TURP) is considered the criterion standard for relieving bladder outlet obstruction (BOO) secondary to BPH. However, there is considerable interest in the development of minimally invasive therapies to accomplish the goal of TURP while avoiding its adverse effects (see Treatment and Management).

Anatomy

The prostate is a walnut-sized gland that forms part of the male reproductive system. It is located anterior to the rectum and just distal to the urinary bladder. It is in continuum with the urinary tract and connects directly with the penile urethra. It is therefore a conduit between the bladder and the urethra. (See the image below.)

Normal prostate anatomy. The prostate is located at the apex of the bladder and surrounds the proximal urethra.

The gland is composed of several zones or lobes that are enclosed by an outer layer of tissue (capsule). These include the peripheral, central, anterior fibromuscular stroma, and transition zones. BPH originates in the transition zone, which surrounds the urethra.

Pathophysiology

Prostatic enlargement depends on the potent androgen dihydrotestosterone (DHT). In the prostate gland, type II 5-alpha-reductase metabolizes circulating testosterone into DHT, which works locally, not systemically. DHT binds to androgen receptors in the cell nuclei, potentially resulting in BPH.

In vitro studies have shown that large numbers of alpha-1-adrenergic receptors are located in the smooth muscle of the stroma and capsule of the prostate, as well as in the bladder neck. Stimulation of these receptors causes an increase in smooth-muscle tone, which can worsen LUTS. Conversely, blockade of these receptors (see Treatment and Management) can reversibly relax these muscles, with subsequent relief of LUTS.

Microscopically, BPH is characterized as a hyperplastic process. The hyperplasia results in enlargement of the prostate that may restrict the flow of urine from the bladder, resulting in clinical manifestations of BPH. The prostate enlarges with age in a hormonally dependent manner. Notably, castrated males (ie, who are unable to make testosterone) do not develop BPH.

The traditional theory behind BPH is that, as the prostate enlarges, the surrounding capsule prevents it from radially expanding, potentially resulting in urethral compression. However, obstruction-induced bladder dysfunction contributes significantly to LUTS. The bladder wall becomes thickened, trabeculated, and irritable when it is forced to hypertrophy and increase its own contractile force.

This increased sensitivity (detrusor overactivity [DO]), even with small volumes of urine in the bladder, is believed to contribute to urinary frequency and LUTS. The bladder may gradually weaken and lose the ability to empty completely, leading to increased residual urine volume and, possibly, acute or chronic urinary retention.

In the bladder, obstruction leads to smooth-muscle-cell hypertrophy. Biopsy specimens of trabeculated bladders demonstrate evidence of scarce smooth-muscle fibers with an increase in collagen. The collagen fibers limit compliance, leading to higher bladder pressures upon filling. In addition, their presence limits shortening of adjacent smooth muscle cells, leading to impaired emptying and the development of residual urine.

The main function of the prostate gland is to secrete an alkaline fluid that comprises approximately 70% of the seminal volume. The secretions produce lubrication and nutrition for the sperm. The alkaline fluid in the ejaculate results in liquefaction of the seminal plug and helps to neutralize the acidic vaginal environment.

The prostatic urethra is a conduit for semen and prevents retrograde ejaculation (ie, ejaculation resulting in semen being forced backwards into the bladder) by closing off the bladder neck during sexual climax. Ejaculation involves a coordinated contraction of many different components, including the smooth muscles of the seminal vesicles, vasa deferentia, ejaculatory ducts, and the ischiocavernosus and bulbocavernosus muscles.

Epidemiology

BPH is a common problem that affects the quality of life in approximately one third of men older than 50 years. BPH is histologically evident in up to 90% of men by age 85 years. As many as 14 million men in the United States have symptoms of BPH. Worldwide, approximately 30 million men have symptoms related to BPH.

The prevalence of BPH in white and African-American men is similar. However, BPH tends to be more severe and progressive in African-American men, possibly because of the higher testosterone levels, 5-alpha-reductase activity, androgen receptor expression, and growth factor activity in this population. The increased activity leads to an increased rate of prostatic hyperplasia and subsequent enlargement and its sequelae.

Prognosis

In the past, chronic end-stage BOO often led to renal failure and uremia. Although this complication has become much less common, chronic BOO secondary to BPH may lead to urinary retention, renal insufficiency, recurrent urinary tract infections, gross hematuria, and bladder calculi.

Carcinoma of the penis is rare in developed countries. By contrast, it accounts for up to 20 percent of cancers in men some parts of Africa, Asia, and South America. (See "Carcinoma of the penis: Epidemiology, risk factors, and clinical presentation", section on 'Epidemiology'.)

The rarity of this condition, its variable clinical appearance, men's frequent hesitation to seek treatment, and inconsistency in follow-up often lead to long delays in diagnosis and treatment. Furthermore, the data on treatment outcomes are derived primarily from retrospective studies. Number of patients are small and there are no randomized trials and to define the optimal treatment.

Key areas of controversy in the management of penile cancers include:

• The role of penile-sparing treatments versus more aggressive surgery (partial or total penile amputation)
• The need for prophylactic inguinal lymphadenectomy in men without palpable inguinal nodes
• Optimal management of men with locally advanced or metastatic disease

The diagnosis, treatment, and prognosis of penile carcinoma are presented here. The epidemiology, risk factors, and clinical presentation are discussed separately.

How to treat sunburn without going to a doctor

Do you ever have sunburn in your life? me too. And its really hurt.

If you have sunburn, you should avoid direct sunlight by covering up the affected areas of skin and staying in the shade until the sunburn has healed.

Protecting your skin from the sun with sunscreen is better than treating it. Read information about sun protection for eyes and skin including more advice about sunscreen and how to apply it.

Most cases of sunburn can be treated at home. Advice for treating sunburn is outlined below.

Water

Cool the skin by sponging it with lukewarm water or by having a cool shower or bath. Applying a cold compress, such as a cold flannel, to the affected area will also cool your skin.

Drinking plenty of fluids will help you to cool down and will replace water that is lost through sweating. It will also help to prevent dehydration (when the normal water content in your body is reduced, causing thirst and light-headedness).

Avoid drinking alcohol because it will dehydrate you even more.

Moisturiser

For mild sunburn, apply a moisturising lotion or aftersun cream, available at pharmacies. Aftersun cream will cool your skin and moisturise it, helping to relieve the feeling of tightness.

Moisturisers that contain aloe vera will also help to soothe your skin. Calamine lotion can relieve any itching or soreness.

Hydrocortisone cream

Sunburn may also be treated by applying 1% hydrocortisone cream to the affected area. This type of cream contains a corticosteroid and is rubbed directly onto the sunburned area of skin to reduce pain and inflammation (swelling).

Hydrocortisone cream should not be used on children who are under two years old.

Do not apply it to certain parts of the body, including:

• the face
• genitals
• broken or infected skin

Seek advice from your pharmacist before you start using hydrocortisone cream to treat sunburn.

Painkillers

Painkillers can help to relieve the pain and reduce the inflammation that is caused by sunburn.

Paracetamol can be used to treat pain and control fever. Ibuprofen is a type of non-steroidal anti-inflammatory drug(NSAID), which can relieve pain, reduce inflammation and lower a high temperature.

Aspirin should not be given to children who are under 16 years old. 

Severe sunburn

Severe cases of sunburn may require special burn cream and burn dressings. Ask your pharmacist for advice. You may need to have your burns dressed by a nurse at your GP surgery.

Very severe sunburn cases may require treatment at your localaccident and emergency (A&E) department.

Seeking medical help

If a baby or small child has been sunburned, or if blisters or a fever develop, seek medical advice from your GP

A sunburn is a burn to living tissue, such as skin, which is produced by overexposure to ultraviolet (UV) radiation, commonly from the sun's rays. Usually, normal symptoms in humans and other animals consist of red or reddish skin that is hot to the touch, general fatigue, and mild dizziness. An excess of UV radiation can be life-threatening in extreme cases. Exposure of the skin to lesser amounts of UV radiation will often produce a suntan.

Excessive UV radiation is the leading cause of primarily non-malignant skin tumors.[1][2] Sunscreen is widely agreed to prevent sunburn, although some scientists argue that it may not effectively protect against malignant melanoma, which either is caused by a different part of the ultraviolet spectrum or is not caused by sun exposure at all.[3][4] Clothing, including hats, is considered the preferred skin protection method. Moderate sun tanning without burning can also prevent subsequent sunburn, as it increases the amount of melanin, a skin photoprotectant pigment that is the skin's natural defense against overexposure. Importantly, both sunburn and the increase in melanin production are triggered by direct DNA damage. When the skin cells' DNA is damaged by UV radiation, type I cell-death is triggered and the skin is replaced.[5] Malignant melanoma may occur as a result of indirect DNA damage if the damage is not properly repaired. Proper repair occurs in the majority of DNA damage. The only cure for sunburn is slow healing, although some skin creams can help with the symptoms.

Sunburn is caused by UV radiation, either from the sun or from artificial sources, such as welding arcs, the lamps used in sunbeds, and ultraviolet germicidal irradiation. It is a reaction of the body to the direct DNA damage, which can result from the excitation of DNA by UV-B light. This damage is mainly the formation of a thymine dimer. The damage is recognized by the body, which then triggers several defense mechanisms, including DNA repair to revert the damage and increased melanin production to prevent future damage. Melanin transforms UV-photons quickly into harmless amounts of heat without generating free radicals, and is therefore an excellent photoprotectant against direct and indirect DNA damage.

The pain may be caused by overproduction of a protein called CXCL5, which activates nerve fibres^[6].

Experiments with mice found that protection against sunburn by chemical sunscreens does not necessarily provide protection against other damaging effects of UV radiation such as enhanced melanoma growth.^[7]

Ultraviolet B (UVB) radiation causes dangerous sunburns and increases the risk of two types of skin cancer: basal-cell carcinomaand squamous cell carcinoma.^[1][2]

Some exposure to sunlight is not only harmless but positively necessary to health. Humans need vitamin D; most is synthesised in the body by exposure of the skin to sunlight, with some from the diet. People with darker skins need more sunlight to maintain vitamin D levels. The widespread concern about over-exposure to the sun causing cancer has led some people to go too far in avoiding exposure and using sunscreen; this can lead to vitamin D deficiency and the condition of rickets due to this deficiency, particularly in children, and particularly in climates with less sunshine. Cases of rickets are, indeed, on the increase. Twenty to thirty minutes of unimpeded exposure to the sun two to three times a week are recommended. ^[8]

The statement sunburn causes skin cancer is accurate when it refers to either basal-cell carcinoma, the mildest form of cancer, or squamous cell carcinoma. But the statement is false when it comes to malignant melanoma (see picture: UVR sunburn melanoma)^{[citation needed]}. The statistical correlation between sunburn and melanoma is due to a common cause — UV radiation. However, they are generated via two different mechanisms: Direct DNA damage is ascribed by many medical doctors to a change in behaviour of the sunscreen user due to a false sense of security afforded by the sunscreen. Other researchers blame insufficient correction for confounding factors: light-skinned individuals versus indirect DNA damage.^{[clarification needed]}

Topically applied sunscreen blocks UV rays as long as it does not penetrate into the skin. This prevents sunburn, suntanning, and skin cancer. If the sunscreen filter is absorbed into the skin, it prevents sunburn, but increases the amount of free radicals, which in turn increases the risk for malignant melanoma. The harmful effect of photo-excited sunscreen filters on living tissue has been shown in many photo-biological studies.^{[9][10][11][12]} Whether sunscreen prevents or promotes the development of melanoma depends on the relative importance of the protective effect from the topical sunscreen versus the harmful effects of the absorbedsunscreen.

The use of sunscreen is known to prevent the direct DNA damage that causes sunburn and the two most common forms of skin cancer, basal-cell carcinoma and squamous cell carcinoma.^[13] However, if sunscreen penetrates into the skin, it promotes indirect DNA damage, which causes the most lethal form of skin cancer, malignant melanoma.^[14] This form of skin cancer is rare, but it causes 75% of all skin cancer-related deaths. Increased risk of malignant melanoma in sunscreen users has been the subject of many epidemiological studies.

One of the most effective ways to prevent sunburn is to reduce the amount of UV radiation reaching the skin. The strength of sunlight is published in many locations as a UV index. The World Health Organization recommends to limit time in the midday sun (between 10 a.m. and 4 p.m.), to watch the UV index, to seek shade, to wear protective clothing and a wide-brim hat, and to use sunscreen.^[28]Sunlight is generally strongest when the sun is close to the highest point in the sky. Due to time zones and daylight saving time, this is not necessarily at 12 p.m., but often one to two hours later.

Commercial preparations are available that block UV light, known as sunscreens or sunblocks. They have a sunburn protection factor (SPF) rating, based on the sunblock's ability to suppress sunburn: The higher the SPF rating the lower the amount of direct DNA damage.

A sunscreen rated as SPF 10 blocks 90% of the sunburn-causing UVB radiation; an SPF20-rated sunscreen blocks 95%^{[citation needed]}. Modern sunscreens contain filters for UVA radiation as well as UVB. The stated protection factors are correct only if 2 μl of sunscreen is applied per square cm of exposed skin. This translates into about 28 ml (1 oz) to cover the whole body of an adult male, which is much more than many people use in practice. Although UVA radiation does not cause sunburn, it does contribute to skin aging and an increased risk of skin cancer. Many sunscreens provide broad-spectrum protection, meaning that they protect against both UVA and UVB radiation.

Research has shown that the best protection is achieved by application 15 to 30 minutes before exposure, followed by one reapplication 15 to 30 minutes after exposure begins. Further reapplication is necessary only after activities such as swimming, sweating, and rubbing.^[29] This varies based on the indications and protection shown on the label — from as little as 80 minutes in water to a few hours, depending on the product selected.

When one is exposed to any artificial source of occupational UV, special protective clothing (for example, welding helmets/shields) should be worn.

There is also evidence that common foods may have some protective ability against sunburn if taken for a period before the exposure.^[30] Beta-carotene and lycopene, chemicals found in tomatoes and other fruit, have been found to increase the skin's ability to resist the effects of UV light. In a 2007 study, after about 10–12 weeks of eating tomato-derived products, a decrease in sensitivity toward UV was observed in volunteers. Ketchup and tomato puree are both high in lycopene.^[31] Dark chocolate rich inflavonoids has also been found to have a similar effect if eaten for long periods before exposure.

The most important aspects of sunburn care are to avoid exposure to the sun while healing and to take precautions to prevent future burns. The best treatment for most sunburns is time. Most sunburns heal completely within a few weeks. Home treatments that help manage the discomfort or facilitate the healing process include using cool and wet cloths on the sunburned areas, taking frequent cold showers or baths, and applying soothing lotions that contain aloe vera^{[dubious – discuss]} to the sunburn areas. Topical steroids (such as 1% hydrocortisone cream) may also help with sunburn pain and swelling. The peeling that comes after some sunburn is inevitable. However, there are lotions that may relieve the itching. Acetaminophen (such as Tylenol), Nonsteroidal anti-inflammatory drugs (such as Ibuprofen or Naproxen), and Aspirin have all shown to reduce the pain of sunburns

[edit]

You could get Diabetes Mellitus when you are pregnant

well, I found this almost all the time in the hospital.

Gestational diabetes (or gestational diabetes mellitus, GDM) is a condition in which women without previously diagnoseddiabetes exhibit high blood glucose levels during pregnancy (especially during third trimester). There is some question whether the condition is natural during pregnancy. Gestational diabetes is caused when the body of a pregnant woman does not secrete enough insulin required during pregnancy, leading to increased blood sugar levels.

Gestational diabetes generally has few symptoms and it is most commonly diagnosed by screening during pregnancy. Diagnostic tests detect inappropriately high levels of glucose in blood samples. Gestational diabetes affects 3-10% of pregnancies, depending on the population studied,^[2] so may be a natural phenomenon.

As with diabetes mellitus in pregnancy in general, babies born to mothers with gestational diabetes are typically at increased risk of problems such as being large for gestational age (which may lead to delivery complications), low blood sugar, and jaundice. If untreated, it can also cause seizures or still birth. Gestational diabetes is a treatable condition and women who have adequatecontrol of glucose levels can effectively decrease these risks.

Women with gestational diabetes are at increased risk of developing type 2 diabetes mellitus (or, very rarely, latent autoimmune diabetes or Type 1)^{[citation needed]} after pregnancy, as well as having a higher incidence of pre-eclampsia and Caesarean section;^[3] their offspring are prone to developing childhood obesity,^{[citation needed]} with type 2 diabetes later in life.^{[citation needed]}Most patients are treated only with diet modification and moderate exercise, but some take antidiabetic drugs, includinginsulin.^[3]

Women treated for gestational diabetes generally have smaller birthweight babies, leading to other problems, such as survival rate of premature and early births, particularly male babies.

Classification

Gestational diabetes is formally defined as "any degree of glucose intolerance with onset or first recognition during pregnancy".^[4] This definition acknowledges the possibility that patients may have previously undiagnosed diabetes mellitus, or may have developed diabetes coincidentally with pregnancy. Whether symptoms subside after pregnancy is also irrelevant to the diagnosis.^[5]

The White classification, named after Priscilla White,^[6] who pioneered in research on the effect of diabetes types on perinatal outcome, is widely used to assess maternal and fetal risk. It distinguishes between gestational diabetes (type A) and diabetes that existed prior to pregnancy (pregestational diabetes). These two groups are further subdivided according to their associated risks and management.^[7]

The two subtypes of gestational diabetes (diabetes which began during pregnancy) are:

• Type A1: abnormal oral glucose tolerance test (OGTT), but normal blood glucose levels during fasting and two hours after meals; diet modification is sufficient to control glucose levels
• Type A2: abnormal OGTT compounded by abnormal glucose levels during fasting and/or after meals; additional therapy with insulin or other medications is required

The second group of diabetes which existed prior to pregnancy is also split up into several subtypes.

Type B: onset at age 20 or older or duration of less than 10 years.

Type C: onset at age 10-19 or duration of 10–19 years.

Type D: onset before age 10 or duration greater than 20 years.

Type E: overt diabetes mellitus with calcified pelvic vessels.

Type F: diabetic nephropathy.

Type R: proliferative retinopathy.

Type RF: retinopathy and nephropathy.

Type H: ischemic heart disease.

Type T: prior kidney transplant.

An early age of onset or long-standing disease comes with greater risks, hence the first three subtypes.

[edit]Risk factors

Classical risk factors for developing gestational diabetes are:^[8]

• A previous diagnosis of gestational diabetes or prediabetes, impaired glucose tolerance, or impaired fasting glycaemia
• A family history revealing a first-degree relative with type 2 diabetes
• Maternal age - a woman's risk factor increases as she gets older (especially for women over 35 years of age).
• Ethnic background (those with higher risk factors include African-Americans, Afro-Caribbeans, Native Americans, Hispanics, Pacific Islanders, and people originating from South Asia)
• Being overweight, obese or severely obese increases the risk by a factor 2.1, 3.6 and 8.6, respectively.^[9]
• a previous pregnancy which resulted in a child with a high birth weight (>90th centile, or >4000 g (8 lbs 12.8 oz))
• Previous poor obstetric history

In addition to this, statistics show a double risk of GDM in smokers.^[10] Polycystic ovarian syndrome is also a risk factor,^[8] although relevant evidence remains controversial.^[11] Some studies have looked at more controversial potential risk factors, such as short stature.^[12]

About 40-60% of women with GDM have no demonstrable risk factor; for this reason many advocate to screen all women.^[13] Typically, women with GDM exhibit no symptoms (another reason for universal screening), but some women may demonstrate increased thirst, increased urination, fatigue, nausea and vomiting, bladder infection,yeast infections and blurred vision.

[edit]Pathophysiology

Effect of insulin on glucose uptake and metabolism. Insulin binds to its receptor (1) on the cell membrane which in turn starts many protein activation cascades (2). These include: translocation of Glut-4 transporter to the plasma membrane and influx of glucose (3), glycogen synthesis (4),glycolysis (5) and fatty acid synthesis (6).

The precise mechanisms underlying gestational diabetes remain unknown. The hallmark of GDM is increased insulin resistance. Pregnancy hormones and other factors are thought to interfere with the action of insulin as it binds to the insulin receptor. The interference probably occurs at the level of the cell signaling pathway behind the insulin receptor.^[14] Since insulin promotes the entry of glucose into most cells, insulin resistance prevents glucose from entering the cells properly. As a result, glucose remains in the bloodstream, where glucose levels rise. More insulin is needed to overcome this resistance; about 1.5-2.5 times more insulin is produced than in a normal pregnancy.^[14]

Insulin resistance is a normal phenomenon emerging in the second trimester of pregnancy, which progresses thereafter to levels seen in non-pregnant patients with type 2 diabetes. It is thought to secure glucose supply to the growing fetus. Women with GDM have an insulin resistance they cannot compensate with increased production in the β-cells of the pancreas. Placental hormones, and to a lesser extent increased fat deposits during pregnancy, seem to mediate insulin resistance during pregnancy. Cortisol andprogesterone are the main culprits, but human placental lactogen, prolactin and estradiol contribute, too.^[14]

It is unclear why some patients are unable to balance insulin needs and develop GDM; however, a number of explanations have been given, similar to those in type 2 diabetes: autoimmunity, single gene mutations, obesity, and other mechanisms.^[15]

Because glucose travels across the placenta (through diffusion facilitated by GLUT3 carriers), the fetus is exposed to higher glucose levels. This leads to increased fetal levels of insulin (insulin itself cannot cross the placenta). The growth-stimulating effects of insulin can lead to excessive growth and a large body (macrosomia). After birth, the high glucose environment disappears, leaving these newborns with ongoing high insulin production and susceptibility to low blood glucose levels (hypoglycemia).^[16]

[edit]Screening

Diabetes diagnostic criteria^[17][18]  edit

Condition	2 hour glucose	Fasting glucose	HbA1c
	mmol/l(mg/dl)	mmol/l(mg/dl)	%
Normal	<7.8 (<140)	<6.1 (<110)	<6.0
Impaired fasting glycaemia	<7.8 (<140)	≥ 6.1(≥110) & <7.0(<126)	6.0–6.4
Impaired glucose tolerance	≥7.8 (≥140)	<7.0 (<126)	6.0–6.4
Diabetes mellitus	≥11.1 (≥200)	≥7.0 (≥126)	≥6.5

A number of screening and diagnostic tests have been used to look for high levels ofglucose in plasma or serum in defined circumstances. One method is a stepwise approach where a suspicious result on a screening test is followed by diagnostic test. Alternatively, a more involved diagnostic test can be used directly at the first antenatal visit in high-risk patients (for example in those with polycystic ovarian syndrome oracanthosis nigricans).^[16]

Tests for gestational diabetes

Non-challenge blood glucose test Fasting glucose test 2-hour postprandial (after a meal) glucose test Random glucose test

Screening glucose challenge test

Oral glucose tolerance test (OGTT)

Non-challenge blood glucose tests involve measuring glucose levels in blood samples without challenging the subject with glucose solutions. A blood glucose level is determined when fasting, 2 hours after a meal, or simply at any random time. In contrast, challenge tests involve drinking a glucose solution and measuring glucose concentration thereafter in the blood; in diabetes, they tend to remain high. The glucose solution has a very sweet taste which some women find unpleasant; sometimes, therefore, artificial flavours are added. Some women may experience nausea during the test, and more so with higher glucose levels.^[19][20]

[edit]Pathways

Opinions differ about optimal screening and diagnostic measures, in part due to differences in population risks, cost-effectiveness considerations, and lack of an evidence base to support large national screening programs.^[21] The most elaborate regimen entails a random blood glucose test during a booking visit, a screening glucose challenge test around 24–28 weeks' gestation, followed by an OGTT if the tests are outside normal limits. If there is a high suspicion, a woman may be tested earlier.^[5]

In the United States, most obstetricians prefer universal screening with a screening glucose challenge test.^[22] In the United Kingdom, obstetric units often rely on risk factors and a random blood glucose test.^[16][23] The American Diabetes Association and the Society of Obstetricians and Gynaecologists of Canada recommend routine screening unless the patient is low risk (this means the woman must be younger than 25 years and have a body mass index less than 27, with no personal, ethnic or family risk factors)^[5][21] The Canadian Diabetes Association and the American College of Obstetricians and Gynecologists recommend universal screening.^[24][25] The U.S. Preventive Services Task Force found there is insufficient evidence to recommend for or against routine screening.^[26]

[edit]Non-challenge blood glucose tests

When a plasma glucose level is found to be higher than 126 mg/dl (7.0 mmol/l) after fasting, or over 200 mg/dl (11.1 mmol/l) on any occasion, and if this is confirmed on a subsequent day, the diagnosis of GDM is made, and no further testing is required.^[5] These tests are typically performed at the first antenatal visit. They are patient-friendly and inexpensive, but have a lower test performance compared to the other tests, with moderate sensitivity, low specificity and high false positive rates.^[27][28][29]

[edit]Screening glucose challenge test

The screening glucose challenge test (sometimes called the O'Sullivan test) is performed between 24–28 weeks, and can be seen as a simplified version of the oral glucose tolerance test (OGTT). It involves drinking a solution containing 50 grams of glucose, and measuring blood levels 1 hour later.^[30]

If the cut-off point is set at 140 mg/dl (7.8 mmol/l), 80% of women with GDM will be detected.^[5] If this threshold for further testing is lowered to 130 mg/dl, 90% of GDM cases will be detected, but there will also be more women who will be subjected to a consequent OGTT unnecessarily.

[edit]Oral glucose tolerance test

Main article: Oral glucose tolerance test

The OGTT^[31] should be done in the morning after an overnight fast of between 8 and 14 hours. During the three previous days the subject must have an unrestricted diet (containing at least 150 g carbohydrate per day) and unlimited physical activity. The subject should remain seated during the test and should not smoke throughout the test.

The test involves drinking a solution containing a certain amount of glucose, and drawing blood to measure glucose levels at the start and on set time intervals thereafter.

The diagnostic criteria from the National Diabetes Data Group (NDDG) have been used most often, but some centers rely on the Carpenter and Coustan criteria, which set the cutoff for normal at lower values. Compared with the NDDG criteria, the Carpenter and Coustan criteria lead to a diagnosis of gestational diabetes in 54 percent more pregnant women, with an increased cost and no compelling evidence of improved perinatal outcomes.^[32]

The following are the values which the American Diabetes Association considers to be abnormal during the 100 g of glucose OGTT:

• Fasting blood glucose level ≥95 mg/dl (5.33 mmol/L)
• 1 hour blood glucose level ≥180 mg/dl (10 mmol/L)
• 2 hour blood glucose level ≥155 mg/dl (8.6 mmol/L)
• 3 hour blood glucose level ≥140 mg/dl (7.8 mmol/L)

An alternative test uses a 75 g glucose load and measures the blood glucose levels before and after 1 and 2 hours, using the same reference values. This test will identify fewer women who are at risk, and there is only a weak concordance (agreement rate) between this test and a 3 hour 100 g test.^[33]

The glucose values used to detect gestational diabetes were first determined by O'Sullivan and Mahan (1964) in a retrospective cohort study (using a 100 grams of glucose OGTT) designed to detect risk of developing type 2 diabetes in the future. The values were set using whole blood and required two values reaching or exceeding the value to be positive.^[34] Subsequent information led to alterations in O'Sullivan's criteria. When methods for blood glucose determination changed from the use of whole blood to venous plasma samples, the criteria for GDM were also changed.

[edit]Urinary glucose testing

Women with GDM may have high glucose levels in their urine (glucosuria). Although dipstick testing is widely practiced, it performs poorly, and discontinuing routine dipstick testing has not been shown to cause underdiagnosis where universal screening is performed.^[35] Increased glomerular filtration rates during pregnancy contribute to some 50% of women having glucose in their urine on dipstick tests at some point during their pregnancy. The sensitivity of glucosuria for GDM in the first 2 trimesters is only around 10% and the positive predictive value is around 20%.^[36][37]

[edit]Management

Main article: Diabetes management

A kit with a glucose meter and diary used by a woman with gestational diabetes.

The goal of treatment is to reduce the risks of GDM for mother and child. Scientific evidence is beginning to show that controlling glucose levels can result in less serious fetal complications (such as macrosomia) and increased maternal quality of life. Unfortunately, treatment of GDM is also accompanied by more infants admitted to neonatal wards and more inductions of labour, with no proven decrease in cesarean section rates or perinatal mortality.^[38][39] These findings are still recent and controversial.^[40]

A repeat OGTT should be carried out 2–4 months after delivery, to confirm the diabetes has disappeared. Afterwards, regular screening for type 2 diabetes is advised.^[8]

If a diabetic diet or G.I. Diet, exercise, and oral medication are inadequate to control glucose levels, insulin therapy may become necessary.

The development of macrosomia can be evaluated during pregnancy by using sonography. Women who use insulin, with a history of stillbirth, or with hypertension are managed like women with overt diabetes.^[13]

[edit]Lifestyle

Counselling before pregnancy (for example, about preventive folic acid supplements) and multidisciplinary management are important for good pregnancy outcomes.^[41] Most women can manage their GDM with dietary changes and exercise. Self monitoring of blood glucose levels can guide therapy. Some women will need antidiabetic drugs, most commonly insulin therapy.

Any diet needs to provide sufficient calories for pregnancy, typically 2,000 - 2,500 kcal with the exclusion of simple carbohydrates.^[13] The main goal of dietary modifications is to avoid peaks in blood sugar levels. This can be done by spreading carbohydrate intake over meals and snacks throughout the day, and using slow-release carbohydrate sources—known as the G.I. Diet. Since insulin resistance is highest in mornings, breakfast carbohydrates need to be restricted more.^[8] Ingesting more fiber in foods with whole grains, or fruit and vegetables can also reduce the risk of gestational diabetes.^[42]

Regular moderately intense physical exercise is advised, although there is no consensus on the specific structure of exercise programs for GDM.^[8][43]

Self monitoring can be accomplished using a handheld capillary glucose dosage system. Compliance with these glucometer systems can be low.^[44] Target ranges advised by the Australasian Diabetes in Pregnancy Society are as follows:^[8]

• fasting capillary blood glucose levels <5.5 mmol/L
• 1 hour postprandial capillary blood glucose levels <8.0 mmol/L
• 2 hour postprandial blood glucose levels <6.7 mmol/L

Regular blood samples can be used to determine HbA1c levels, which give an idea of glucose control over a longer time period.^[8]

Research suggests a possible benefit of breastfeeding to reduce the risk of diabetes and related risks for both mother and child.^[45]

[edit]Medication

If monitoring reveals failing control of glucose levels with these measures, or if there is evidence of complications like excessive fetal growth, treatment with insulin might become necessary. The most common therapeutic regime involves premeal fast-acting insulin to blunt sharp glucose rises after meals.^[8] Care needs to be taken to avoid low blood sugar levels (hypoglycemia) due to excessive insulin injections. Insulin therapy can be normal or very tight; more injections can result in better control but requires more effort, and there is no consensus that it has large benefits.^[16][46][47]

There is some evidence that certain oral glycemic agents might be safe in pregnancy, or at least, are significantly less dangerous to the developing fetus than poorly controlled diabetes. Glyburide, a second generation sulfonylurea, has been shown to be an effective alternative to insulin therapy.^[48][49] In one study, 4% of women needed supplemental insulin to reach blood sugar targets.^[49] Metformin has shown promising results, with its oral format being much more popular than insulin injections.^[3]Treatment of polycystic ovarian syndrome with metformin during pregnancy has been noted to decrease GDM levels.^[50] A recent randomized controlled trial of metformin versus insulin showed that women preferred metformin tablets to insulin injections, and that metformin is safe and equally effective as insulin.^[51] Severe neonatal hypoglycemia was less common in insulin-treated women, but preterm delivery was more common. Almost half of patients did not reach sufficient control with metformin alone and needed supplemental therapy with insulin; compared to those treated with insulin alone, they required less insulin, and they gained less weight.^[51] With no long-term studies into children of women treated with the drug, here remains a possibility of long-term complications from metformin therapy,^[3] although follow-up at the age of 18 months of children born to women with polycystic ovarian syndrome and treated with metformin revealed no developmental abnormalities.^[52]

[edit]Prognosis

Gestational diabetes generally resolves once the baby is born. Based on different studies, the chances of developing GDM in a second pregnancy are between 30 and 84%, depending on ethnic background. A second pregnancy within 1 year of the previous pregnancy has a high rate of recurrence.^[53]

Women diagnosed with gestational diabetes have an increased risk of developing diabetes mellitus in the future. The risk is highest in women who needed insulin treatment, had antibodies associated with diabetes (such as antibodies against glutamate decarboxylase, islet cell antibodies and/or insulinoma antigen-2), women with more than two previous pregnancies, and women who were obese (in order of importance).^[54][55] Women requiring insulin to manage gestational diabetes have a 50% risk of developing diabetes within the next five years.^[34] Depending on the population studied, the diagnostic criteria and the length of follow-up, the risk can vary enormously.^[56] The risk appears to be highest in the first 5 years, reaching a plateau thereafter.^[56] One of the longest studies followed a group of women from Boston, Massachusetts; half of them developed diabetes after 6 years, and more than 70% had diabetes after 28 years.^[56] In a retrospective study in Navajo women, the risk of diabetes after GDM was estimated to be 50 to 70% after 11 years.^[57] Another study found a risk of diabetes after GDM of more than 25% after 15 years.^[58] In populations with a low risk for type 2 diabetes, in lean subjects and in patients with auto-antibodies, there is a higher rate of women developing type 1 diabetes.^[55]

Children of women with GDM have an increased risk for childhood and adult obesity and an increased risk of glucose intolerance and type 2 diabetes later in life.^[59] This risk relates to increased maternal glucose values.^[60] It is currently unclear how much genetic susceptibility and environmental factors each contribute to this risk, and if treatment of GDM can influence this outcome.^[61]

There are scarce statistical data on the risk of other conditions in women with GDM; in the Jerusalem Perinatal study, 410 out of 37962 patients were reported to have GDM, and there was a tendency towards more breast and pancreatic cancer, but more research is needed to confirm this finding.^[62][63]

[edit]Complications

GDM poses a risk to mother and child. This risk is largely related to high blood glucose levels and its consequences. The risk increases with higher blood glucose levels.^[64]Treatment resulting in better control of these levels can reduce some of the risks of GDM considerably.^[44]

The two main risks GDM imposes on the baby are growth abnormalities and chemical imbalances after birth, which may require admission to a neonatal intensive care unit. Infants born to mothers with GDM are at risk of being both large for gestational age (macrosomic)^[64] and small for gestational age^{[citation needed]}. Macrosomia in turn increases the risk of instrumental deliveries (e.g. forceps, ventouse and caesarean section) or problems during vaginal delivery (such as shoulder dystocia). Macrosomia may affect 12% of normal women compared to 20% of patients with GDM.^[16] However, the evidence for each of these complications is not equally strong; in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study for example, there was an increased risk for babies to be large but not small for gestational age.^[64]Research into complications for GDM is difficult because of the many confounding factors (such as obesity). Labelling a woman as having GDM may in itself increase the risk of having a caesarean section.^[65][66]

Neonates are also at an increased risk of low blood glucose (hypoglycemia), jaundice, high red blood cell mass (polycythemia) and low blood calcium (hypocalcemia) and magnesium (hypomagnesemia).^[67] GDM also interferes with maturation, causing dysmature babies prone to respiratory distress syndrome due to incomplete lung maturation and impaired surfactant synthesis.^[67]

Unlike pre-gestational diabetes, gestational diabetes has not been clearly shown to be an independent risk factor for birth defects. Birth defects usually originate sometime during the first trimester (before the 13th week) of pregnancy, whereas GDM gradually develops and is least pronounced during the first trimester. Studies have shown that the offspring of women with GDM are at a higher risk for congenital malformations.^[68][69][70] A large case-control study found that gestational diabetes was linked with a limited group of birth defects, and that this association was generally limited to women with a higher body mass index (≥ 25 kg/m²).^[71] It is difficult to make sure that this is not partially due to the inclusion of women with pre-existent type 2 diabetes who were not diagnosed before pregnancy.

Because of conflicting studies, it is unclear at the moment whether women with GDM have a higher risk of preeclampsia.^[72] In the HAPO study, the risk of preeclampsia was between 13% and 37% higher, although not all possible confounding factors were corrected.^[64]

[edit]Epidemiology

Gestational diabetes affects 3-10% of pregnancies, depending on the population studied.^[2]