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Filip Teodor

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3407

Genetic Component Underlying Eosinophilic Esophagitis

New advances are  made in treating a rare form of esophagitis, that is eosinophilic esophagitis. According to the study  published in the Journal of Allergy and Clinical Immunology, researchers have discovered a genetic component underlying the disease.

Eosinophilic esophagitis is a disease that occurs mainly in children, but it has also been described in adults. It occurs in the context of food allergy and is actually an inflammation of the esophagus wall which is infiltrated with eosinophils, a type of white blood cells normally present in blood. It is possible that the disease is underdiagnosed, as is sometimes confused with reflux esophagitis.

Esophagitis

Eosinophilic Esophagitis

In the past 20 years the disease has become increasingly common. According to Rothenberg and his laboratory team, the incidence of disease is at least 1,000 cases. The cause of esophagitis if often acid reflux, which is manifested by heartburn, especially after eating. Other causes include viruses such as herpes simplex, radiation, certain drugs (antibiotics such as tetracycline). It is believed that the cause of eosinophilic esophagitis is allergy because, on the one hand, the esophagus is infiltrated with eosinophils, cells that appear in other allergies, and on the other hand, eosinophilic esophagitis usually occurs due to a food allergy. Most commonly, eosinophilic esophagitis is manifested by dysphagia, but it can be accompanied by weight loss, heartburn, vomiting.

Recently, researchers from Cincinnati Children’s Hospital at the Medical Center have identified a genetic component underlying the disease. They found an anomaly of microRNAs, which is reversed by administration of steroids. The study’s senior investigator, Marc E. Rothenberg, MD, PhD, director of Allergy and Immunology and the Center for Eosinophilic Disorders at Cincinnati Children’s, points out that this finding is extremely valuable because it can be a step forward in diagnosing and treating this disease little known until now.

The research conducted by researchers at Cincinnati Children’s Hospital from Medical Center, facilitates the diagnosis of eosinophilic esophagitis, particularly in children. Until now, children with this disease needed to be diagnosed using a rather invasive method, that is endoscopy. Thanks to the study, patients suffering from this disease can now be diagnosed by a simple blood test that measures microRNAs.

Researchers analyzed the cases of patients with active  eosinophilic esophagitis,  esophagitis that responded to steroid treatment, non-chronic eosinophilic esophagitis and healthy patients. Thus, scientists have found that eosinophilic esophagitis is associated with increased microRNAs blood levels, specifically miR-21 and miR-223. Also, what the researchers noted was that these high levels of microRNAs return to normal after administering steroids.

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A new study that has been published in the journal Biological Psychiatry shows that the cells that are involved in the fight against infections (T cells) are also involved in the increase of blood pressure. Tests were conducted on laboratory mice and have shown that after being subjected to psychological stress, the rise of blood pressure is affected by T cells. Test results also show that the effects that chronic stress has on the cardiovascular health of patients be caused by the presence of our immune system.

“Chronic stress has long been known to have harmful effects on the immune system as well as being a risk factor for hypertension,” says lead author Paul Marvar from the Emory University School of Medicine from the United States of America. Marvar also said that the main goal of the study was to determine whether or not T cells have an important role in stress-dependent hypertension. Marvar worked in collaboration with Dr. David Harrison, who later moved from the Emory University and with Dr. Kerry Ressler, professor of psychiatry and behavioral sciences.

BP

For the current research, scientists used laboratory mice that were subjected to psychological stress through the confinement in an enclosed space for one hour. This was done two times a day for a week and resulted in the increase of blood pressure with almost  10 mm Hg, from around 115 to 125 mm Hg.

Along with normal mice, another batch of mice were tested. This second batch only included mice that genetically lacked T cells. Researchers observed that the second batch of mice did not show an increase in blood pressure after being subjected to the same tests. However, after injecting T cells into the mice, scientists observed that blood pressure became sensitive to stress.

In an earlier study, Dr. David Harrison and his team revealed the fact that the process involved in the increase of blood pressure requires T cells and the blood pressure regulating hormone, angiotensin.

The lead author of the study also notes that there are numerous recent studies which suggest that current medication used in the treatment and control of blood pressure could also help reduce stress and anxiety.

“Further understanding the mechanisms underlying these observations and determining whether they may benefit people with anxiety disorders, for example post-traumatic stress disorder (PTSD) is a current goal of my research”, says Marvar.

High blood pressure is known to be an important risk factor for strokes and heart attacks. There are various drugs on the market, and many patients take them but experience little to no effect afterwards. Therefore many current studies are trying to find a new alternative to these drugs.

3638

Breast Cancer Treatment

A new study, conducted by researchers from the Friedrich Miescher Institute for Biomedical Research shows that a group of proteins called phosphatase SHP2 are involved in growth and dissemination of breast cancers with poor prognosis. This study was published in the latest issue of nature Medicine and highlights the important role of SHP 2 in breast cancer development,  being able to maintain viable and active tumor initiating cells which are responsible for tumor development, metastasis and cancer relapse.

Tumor initiating cells represent a group of cells that can initiate cancer growth, make some cancer types to become resistant to therapies or can cause relapse. In latest years this family of cells are extensively studied by researchers because they are thought to be responsible for resistance to chemotherapy in some types of cancer and for early relapse after targeted therapy. It was also observed that tumor initiating cells predominate in aggressive and refractory forms of cancer. Until now, knowledge about the way how this cells promote cancer growth and inter-cellular pathways used by this cells to determine metastasis and relapse was not available and studies in this direction are only at the beginning.

Breast CancerWith this study, scientists were able to demonstrate that in the developing of aggressive forms of breast cancer  a series of signaling proteins that are holding the capacity to activate tumor initiating cells are involved. This signaling proteins called phosphatase SHP2 are involved in breast cancer proliferation, invasion and metastasis. The discovery was made after researchers depleted SHP2 from malignant cells using small RNA sequences when proliferation and invasion of breast cancer cells has decreased and the tumor growth was blocked, thus reducing metastasis. It was also observed that SHP2 depletion lowers the number of tumor initiating cells .

“We believe that one should not only target the bulk of the tumor but also the tumor initiating cells. By better understanding the signaling events governing tumor initiating cells, we hope to develop new, more efficacious, therapeutic approaches.”, researchers said.

After depleting SHP2 proteins, researchers noticed that this phosphatase is actually using intracellular pathways that activate transcription factors associated with stem cells proliferation. SHP2 proteins are encoded by a series of genes called “signature genes” that are over-expressed in breast cancer with poor prognosis and invasive behavior.

The discovery of signature genes which are over-expressed by SHP2 proteins has an important clinical impact as it allows scientists to identify breast cancers with high levels of SHP2 proteins, tumors which can be treated with SHP2 targeted therapy.

This study highlights the critical role of SHP2 proteins in activation of tumor initiating cells which are associated with rapid growth, early invasion and metastasis of breast cancers with poor prognosis. In the near future, scientists hope be able to develop tests which can detect aggressive forms of cancers in its early stages and also develop SHP2-targeted therapies.

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Study Finds Link Between Sleeping Pills And Higher Death Risk

A new study led by scientists at Scripps Clinic suggests that the use of sleeping pills increases the risk of death by over 4 times, while also increasing the numbers of cancer cases. The study was funded by the Scripps Health Foundation and other philanthropic sources.

Published in the journal BMJ Open, the study has a major impact on a fast growing pharmaceutical segment. Only in the past few years, the pharmaceutical segment that deals with sleeping pills generated almost $2 billion in annual sales in the United States alone.

“What our study shows is that sleeping pills are hazardous to your health and might cause death by contributing to the occurrence of cancer, heart disease and other diseases”, said Daniel F. Kripke, the main author of the study.

Dr. Kripke also says that this study has shown for the first time that most of the commonly used sleeping pills are associated with increased cancer risk and higher mortality rates. Tested medication included the commonly prescribed Ambien and Restoril, believed to be safer than other drugs until now.

Insomina

Insomina

The study was conducted on two groups of patients. The first group was made from patients that received sleeping pills while the second group had patients that were not receiving any hypnotic drugs. Both groups contained patients of similar age, gender and health, thus removing any possible external influence.

The current research also shows that patients that were prescribed up to only 18 pills per year had a death risk of over 3 times higher than patients that weren’t taking any pills. Patients that participated in the study were all 18 years of age or older. Increased risk was discovered in all age groups. Cancer rates were discovered to be almost 35 percent higher in patients that were prescribed more than 132 sleeping pills over the entire year, compared to patients that did not take any hypnotic medication.

Approximately 40,000 patients were studied using data that has been stored into electronic medical records in the past decade. The records belonging to 10,531 patients that were taking prescribed hypnotic medication were compared to a control group formed by 23,674 patients that weren’t taking any sleeping pills. Information was collected from the clinical visits conducted between Jan. 1, 2002 and Sept. 30, 2006.

It is important to note that our results are based on observational data, so even though we did everything we could to ensure their validity, it’s still possible that other factors explain the associations”, added co-author and medical director of the Viterbi Family Sleep Center, Lawrence E. Kline. He also believes that their new work will spur further research in this domain, whilst inciting physicians to consider other medication instead of sleeping pills.

Scientists at the Viterbi Family Sleep Center use cognitive therapy instead of hypnotic medication in order to treat different sleep disorders. One of their studies suggests that patients who suffer from insomnia could require less than the normally suggested eight hours of nightly sleep.

“Understanding how to use the circadian rhythm is a very powerful tool that doesn’t require a prescription”, concluded Dr. Kline.

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Study Sheds Light On The Link Between Bisphenol A Exposure And Heart Disease

One of the most used chemical compounds in the plastic industry is Bisphenol A or BPA. According to a prospective study conducted on a significant batch of people, higher urine concentration of bisphenol are seemingly linked to a greater risk of developing heart disease at some point in the future. Currently people are exposed to Bisphenol A mainly after consuming packaged food and bottled beverages but also by coming into contact with household dust or after dental procedures that imply the use of sealants.

BPA

BPA

This study was published online in the American Heart Association Circulation Journal and was undertook by several scientists from the Peninsula College of Medicine and Dentistry and European Centre for the Environment and Human Health in partnership with Cambridge University.

The above mentioned scientists had already been in possession of data showing a connection between BPA and an increased risk of cardiovascular disease, but were unable to asses the exact long-term effects of BPA exposure on health.

The newest study that breaks ground in the former mentioned field was conducted by the University of Cambridge using data from the European Prospective Investigation of Cancer in Norfolk, United Kingdom. In this study the 758 participants who developed one sort of cardiovascular disease although they had initially been healthy  were compared against 861 other people who continued to be healthy at the end of the study. The comparison showed that those in the first batch (the 758 participants) presented higher levels of urinary BPA at the start of the 10-year study. We have to point out that the relevance of this outcome is somehow questionable due to the fact that each study participant only had one urine sample tested at the onset of the study.

Study leader, Professor David Melzer stated that this particular study results cast light on an existing correlation between Bisphenol A and heart disease but its causative nature is not set in stone. At this point there is very little information about the exact effects and dynamics of BPA in humans and additional safety trials are required in order to asses its long-term effects.

We all know the major risk factors of heart disease like dyslipidemia, hypertension and cigarette smoke and it is very hard to say if BPA alone could be a one of them and even if so, to quantify the extent at which it causes heart disease would be nearly impossible.

3476

Mitochondria Could Represent A New Target For Cancer Therapy, According To New Study

A new breakthrough in cancer therapy suggests that the mitochondria may be targeted by future cancer therapies. Scientists from Chicago University were able to regulate the number of mitochondria in cancerous cells by manipulating two biochemical signals, thus obtaining a size reduction of human lung cancer transplanted into lab mice. Mitochondria represent the most important energetic structure of the cell, being involved in cellular metabolism.

When the cells begin to divide, mitochondria separate in two individual parts, process called fission. Once the division has ended, mitochondria will merge back into piece, process called fusion. Therefore, the dividing process requires one cell  to increase its number of mitochondria by fission, resulting two parts of one mitochondria which will later on be included into two daughter cells.

Scientists were able to control molecular signals that regulate the process of fission and fusion in malignant cells, thus reducing cell division and stopping cancerous cell proliferation (the most important characteristic of cancer development). By increasing the signals that stimulate fusion, researchers were able to achieve tumor reduction by one-third of the original size. Using molecular signals that inhibit fission the tumor was reduced with more than a half of its original size.

“We found that human lung cancer cell lines have an imbalance of signals that tilts them towards mitochondrial fission. By boosting the fusion signal or blocking the fission signal we were able to tip the balance the other way, reducing cancer cell growth and increasing cell death. We believe this provides a promising new approach to cancer treatment.”, according to researchers.

Mitochondria

Mitochondria

With this study scientists proved that a huge step forward in cancer treatment can be achieved by targeting mitochondrial division. Stopping the division process of mitochondria stops the entire cell division. Until now, drugs used in cancer treatments interfere with the whole cell division process. This new therapy interferes only with mitochondrial division and will probably prove to be very useful for treating patients suffering from types of cancers that become resistant to drugs that are targeting the cellular cycle.

Researchers observed that malignant cells present an fragmented mitochondrial internal network compared to normal cells. It was noticed that cancerous cells also present low leveles of one protein that stimulates fusion, called mitofusin-2 (Mfn-2) and high levels of a protein that promotes fission, called dynamin-related protein (Drp-1).  Drp-1 has a very important role in mitochondrial division at the beginning of the fission process. High levels of this protein are surrounding mitochondria causing their separation into two fragments.

Scientists used gene therapy to inhibit fission by increasing the activity of Mfn-2 and inhibit Drp-1 both by  altering the production  and injecting a molecule that interferes with its activity. After these interventions, researchers concluded that inhibiting Drp-1 does not represent a cancer cure. Although tumor size does decrease, the treatment fails in making it disappear altogether.

“Inhibiting mitochondrial fission did not show any significant toxicity in mice or rats, so we are quite optimistic that our findings can lead to the development of novel, clinically feasible therapies.”, researchers added.

These therapies which promote the activity of Mfn-2 and inhibit the activity of Drp-1 are only available for laboratory studies and have not yet been tested on humans. Perhaps clinical trials will evaluate these treatment options in the near future.

16958

Genital Herpes Symptoms And Manifestations In Women

Genital herpes is a disease, once contacted you wear with you for the rest of your life . The condition causes painful eczemas and a blistering rash in the genital area. The herpes simplex virus infection can occur both in women and men equally, but infection means can differ.

Transmission Of Genital Herpes

Genital herpes virus is transmitted through sexual contact, namely through exchange of saliva, semen, cervical or vesicular fluid that enter the body through open wounds. Generally the virus does not infect dead epidermis keratinized cells. For the virus to act and to multiply, it must come into contact with mucosal cells or living tissues.

Female Genital Herpes

Women have a four times greater risk of becoming infected with genital herpes than men. If a uninfected man and a healthy woman have  unprotected sex with an infected partner, the woman is more likely to contract dangerous herpes simplex type 2.

Why does this happen?

The genital area of female body has a greater surface of mucoid secreting cells. Menstrual cycle hormonal fluctuations affect the immune system that becomes unable to fight with full force against herpes simplex infection. In woman genital herpes can be accompanied by swelling of the labia major. Genital herpes located on the urethra will cause urination important dysuria, sometimes urine retention. Genital herpes may also be manifested as an urethritis with mucous discharge. Often is accompanied by chills, fever, fatigue, headaches and generalized adenopathy (enlargement of lymph nodes) or locoregional adenopathy. Extra-genital herpes lesions may appear especially on the thighs, buttocks and groin.

BV Symptoms Quiz

Factors that can reactivate infection include local trauma (especially sexual intercourse), other infectious diseases, fever, menstruation, emotional stress, etc.. Generally (except immunocompromised patients), due to the host prompt immune response the viral replication si slow, evolution is less severe and shorter than in the case of primary infection (many cases are asymptomatic recurrences).

Genital Herpes Symptoms

The first outbreak of genital herpes in women is more painful and lasts longer than recurrent herpes. Women develop a more severe disease and  present more complications during the first manifestation of the disease. Lesions may occur anywhere on the genital area, including the vulva, vagina, cervix and urethra. In addition, herpes can spread to other anatomical parts, such as the buttocks and thighs. These early eruptions are infectious for about three weeks, due to the blisters that contain large numbers of infectious viral particles.

Besides the eruptions described above, the woman’s womb lymph nodes may swell and become painful during urination. Meningitis is a serious complication that can occur in 10-15% of cases.

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Misleading Symptoms

There are cases in which the symptoms that the patient presents can be misleading and are not actually signs of infection with genital herpes.

A woman who presents to the doctor with rash or blisters in the vagina or on the cervix may actually be the symptoms of other disorders like  candidiasis, cervicitis or pelvic inflammatory disease. Also, if injuries of the urethra occur, they could designate a urinary tract infection or a bladder dysfunction.

For a correct diagnosis is necessary to carry out medical tests immediately after the lesions appear and start the required treatment. Local antiseptic is sufficient for drying and minimal prevent suprainfectin, but to prevent recurrences (especially genital and anorectal) an antiviral treatment will be prescribed with acyclovir, a drug highly active against herpes simplex virus type I,  varicella zoster virus and herpes simplex type II.

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Sources

1. https://getridofherpes.net

2. https://www.nhs.uk/conditions/Genital-herpes/Pages/Introduction.aspx

3. https://umm.edu/health/medical/altmed/condition/herpes-simplex-virus

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Dermatitis Herpetiformis

Dermatitis herpetiformis is a chronic, extremely pruritic disease that is characterized by clusters of vesicles distributed symmetrically over the extensor surfaces of the knees and elbows, scalp, and the back of the neck. The face is affected infrequently and the oral mucosa only rarely. The disease responds dramatically to sulfones and sulfapyridine. The illness may begin at any age, but it most frequently appears in the second to fourth decades. Although the disease appears to be lifelong in the most individuals, it tends to become milder after it has been present for about 10 years. Spontaneous remissions persisting for several years or spontaneous cures have been recorded.

Dermatitis Herpetiformis on the Back

Dermatitis Herpetiformis on the Back

The histology of the skin lesions in the earliest phase is characterized by collections of neutrophils at the tips of the dermal papillae (microabscesses), often in association with separation of the papillary tips from overlying epidermis. Most patients with dermatitis herpetiformis diagnosed on the basis of clinical and histologic features and their response to therapy have granular deposits of IgA identified by direct immunofluorescence in the dermal papilae of their cutaneous lesions, in a 3-5 mm perilesional zone, and sometimes in more distant normal skin. It is now possible to make the diagnosis on formalin-fixed tissue with the use of an avidin-biotin-peroxidase technique that is more convenient than direct immunofluorescence on fresh tissue. Immunofluorescent markers of IgA deposition are neccessary for the diagnosis of dermatitis herpetiformis.

Dermatitis Herpetiformis Patient

Picture of a patient suffering from dermatitis herpetiformis. Picture showing an affected elbow

Dermatitis herpetiformis is associatted with mucosal changes in the small bowel that are indistinguishable from those of celiac sprue. The atrophic villous pattern in dermatitis herpetiformis ranges from mild to severe. It is more prominent in the proximal small bowel than in the distal portion as observed in celiac sprue, but the atrophy occurs  in a spotty fashion as opposed to more universal involvement in sprue. The differences in extent and degree of mucosal involvement in dermatitis herpetiformis have been proposed as the reason for the rarity of clinical signs of malabsorption.

Data from several series have shown that chemical evidence of steatorrhea was present in 22 of 69 patients, but in only 6 were there clinical signs and symptoms of malabsoption. Katz and Strober found only 2 of 51 patients had symptoms of malabsoption. Dermatitis herpetiformis preceded or followed malabsoption by as long as 3 to 8 years. Ten percent to 33% of patients have had abnormalities of D-xylose excretion, and anemia secondary to iron and folate deficiencies. Abnormalities in glucose, bicarbonate and water absorption similar to those found in sprue also have been present.

Sulfones can produce remission of the skin lesions but have no effect on the enteropathy. However, a gluten-free diet in dermatitis herpetiformis will not only cause the intestinal lesions to revert to normal as in sprue, but in most patients it will induce a remission in the skin lesions or significantly reduce the dose of sulfones necessary to keep the skin clear. It requires 6 to 12 months to achieve these cutaneous effects with a gluten-free diet. Return to a gluten-containing diet is followed by a relapse of skin disease in 1 to 3 weeks. Some patients with dermatitis herpetiformis do not respond to a gluten-free diet. Curiously, IgA and C3 still can be found in the normal skin of patients who have responed to a gluten-free diet.

The pathogenesis of dermatitis herpetiformis is belived to involve the deposition of IgA at the dermal-epidermal jonction of the skin with subsequent activation of complement by the alternative pathway. Neutrophils are attracted to the site and the histologic lesion is generated. However, the presence of IgA alone is insufficient to initiate the formation of the lesions, and other factors are necessary although they still are undefined. It has been established that patch tests with anionic I, Cl, Br, F and SCN will initiate local lesions within 24 to 48 hours. Oral potassium iodide also can induce lesions and exacerbate the disease. It is not understood how the halogens bring this about. The significance of IgA deposition in the skin is likewise unclear. It has been proposed that the IgA is directed against gluten protein or cross-reacting antigens, and that it originates in the gastrointestinal tract. There is no evidence that circulating immune complexes, which are detectable in some patients, play a pathogenetic role in this disease.

Other evidence links dermatitis herpetiformis to sprue. Relatives of patients with dermatitis herpetiformis have been shown to have a high prevalence of villous artrophy assumed to be caused by celiac sprue. HLA-B8/DRw3/DQw2 are present with increased frequency in both sprue and dermatitis herpetiformis.

Fry. et al. and Doran et al. have reported that absorption studies with D-xylose and folic acid yielded false-positive results for malabsoption in patients with extensive eczema and psoriasis. The abnormal results from D-xylose testing have been attributed to decreased renal clearance, not malabsoption. The reason for the decreased renal clearance has not been studied. . Serum folate and D-xylose levels, which are common screening tests for malabsoption, cannot be used for this purpose in patients with extensive skin disease. Correction of the serum folate levels has not benefited the eruptions in these patients.

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What Is Diabetes

Diabetes is a metabolism disturbance (metabolism is defined as the processes through which our body uses the food we eat for obtaining energy, basically all the chemical reactions that occur in any living cell to sustain life). Many aliments we eat are decomposed to glucose, which is the formula of sugar in the blood stream. Glucose is the main fuel¯ of our body.

After digestion, the glucose passes into the blood stream and is delivered to the whole body, to every living cell where is used for energy purposes and growth. For glucose to enter the cell, presence of insulinis needed. Insulin is a hormone produced by the pancreas, a large size gland situated posterior to the stomach.

When we eat, the pancreas automatically produces the required amount of insulin for moving the large quantity of glucose from the blood stream inside the cells. For persons who suffer from diabetes, the pancreas produces less insulin than needed or not at all, or the cells do not respond adequately to the insulin produced by the pancreas. This way, the body loses its primary source of fuel¯, even though the blood contains high levels of glucose (sugar).

What is Diabetes and their types.

What is Diabetes and their types.

What are the types of diabetes?

  1. Diabetes type 1
  2. Diabetes type 2
  3. Gestational Diabetes

Diabetes type 1 is an autoimmune disease and occurs when the immune system of the body which main role normally is the anti-infectious one, turns against your own structures. In diabetes the immune system attacks the beta producing cells situated in the pancreas and destroys them. Therefore the pancreas produces insulin in small quantities or not at all. A person with type 1 diabetes must receive insulin every day to survive. Till present scientists don't know exactly what triggers the immune system to attack the beta cells, but genetic, auto immune, environmental and viral factors are suspicioned.

Diabetes type 1 occurs at approximately 5 to 10 % from all cases of diabetes. It is diagnosed frequently at children and young adults, but may occur at any age.

Types of Diabetes

Types of Diabetes

Diabetes type 2 is the most frequent type, approximately 89-95% from the total number of diabetes cases are type 2. This form is associated with older people, obesity, family cases of diabetes, lack of physical activity. Approximately 80% of diabetes type 2 patients are obese. When is diagnosed in the type 2 diabetes case, the pancreas produces enough insulin but due to still unknown causes the organism cannot use it effectively, situation named insulin resistance. After several years the production of insulin drops, resulting in type 1 diabetes. The quantity of glucose elevates in the blood stream and the body cannot use it as an energy source.

Gestational Diabetes occurs obviously  during pregnancy and just like type 2 diabetes, appears more frequently at Afro Americans, Indians, Hispanics, and at women with family cases of diabetes.Woman who had gestational diabetes are prone to type 2 diabetes, with a 20 to 50 %probability factor in the next 5 to 10 years.