Tag: Diabetes mellitus type 1

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Diabetics

Definition:
Diabetes mellitus, or simply diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the pancreas does not produce enough insulin, or because cells do not respond to the insulin that is produced.  This high blood sugar produces the classical symptoms of polyuria (frequent urination), polydipsia (increased thirst), and polyphagia (increased hunger).

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There are three main types of diabetes mellitus (DM).

*Type 1 DM results from the body’s failure to produce insulin, and currently requires the person to inject insulin or wear an insulin pump. This form was previously referred to as “insulin-dependent diabetes mellitus” (IDDM) or “juvenile diabetes”.

*Type 2 DM results from insulin resistance, a condition in which cells fail to use insulin properly, sometimes combined with an absolute insulin deficiency. This form was previously referred to as non insulin-dependent diabetes mellitus (NIDDM) or “adult-onset diabetes”.

*The third main form, gestational diabetes, occurs when pregnant women without a previous diagnosis of diabetes develop a high blood glucose level. It may precede development of type 2 DM.

Other forms of diabetes mellitus include congenital diabetes, which is due to genetic defects of insulin secretion, cystic fibrosis-related diabetes, steroid diabetes induced by high doses of glucocorticoids, and several forms of monogenic diabetes.
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Diabetes has no age bar. It can appear in a newborn, children, young adults, during pregnancy or in older people. If there are suspicious symptoms, tests should be done.

Some families have a tendency to develop diabetes, with many members being affected. This is because it is a genetic disease that an be inherited from both parents. Type 1 and 2 diabetes are inherited from multiple genes. In type 2 diabetes particularly, the environment and family’s dietary and exercise habits also influence these genes. Families that eat “well” and are sedentary with snacking and excessive TV viewing are more likely to develop type 2 diabetes. Sometimes type 1 diabetes can develop in persons without a family history or genetic predisposition. It may follow viral infections, especially with the mumps and coxsackie group of viruses. The virus attacks and destroys the cells in the pancreas responsible for manufacturing insulin.

There is now a third type of diabetes, where the mutation occurs in a single gene. This gene is dominant, so that if either parent carries it, then half the children (male and female) will be affected. It was called MODY (maturity onset diabetes of youth). The diabetes affecting newborn children is of this type.

Initially, MODY was called type 1.5 diabetes and it was presumed that it was caused by only one type of genetic defect. Recent research has shown that there are 13 defects that lead to MODY.

*It is likely to be present in people who have been diagnosed with diabetes before the age of 30.

*It is present in every generation of the family.

*It can be managed with diet, exercise and tablets. Insulin is usually not required (even in children).

*MODY (depending on the type) can result in the affected woman having small or large babies.

* There may be cysts in the kidney.

* Malabsorption can occur.

* Patients may be infertile.

The incidence of MODY is higher in areas where there is a great deal of consanguinity (marrying a close relative) and when people marry generation after generation from the same community.

It is now possible to test for MODY genes in many centres and identify high-risk individuals and families.

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Symptoms:
The classic symptoms of untreated diabetes are loss of weight, polyuria (frequent urination), polydipsia (increased thirst), and polyphagia (increased hunger). Symptoms may develop rapidly (weeks or months) in type 1 diabetes, while they usually develop much more slowly and may be subtle or absent in type 2 diabetes.

Prolonged high blood glucose can cause glucose absorption in the lens of the eye, which leads to changes in its shape, resulting in vision changes. Blurred vision is a common complaint leading to a diabetes diagnosis. A number of skin rashes that can occur in diabetes are collectively known as diabetic dermadromes.

Causes:
The cause of diabetes depends on the type.

Type 1

Type 1 diabetes is partly inherited, and then triggered by certain infections, with some evidence pointing at Coxsackie B4 virus. A genetic element in individual susceptibility to some of these triggers has been traced to particular HLA genotypes (i.e., the genetic “self” identifiers relied upon by the immune system). However, even in those who have inherited the susceptibility, type 1 DM seems to require an environmental trigger. The onset of type 1 diabetes is unrelated to lifestyle.

Type 2

Type 2 diabetes is due primarily to lifestyle factors and genetics.[16] A number of lifestyle factors are known to be important to the development of type 2 diabetes, including obesity (defined by a body mass index of greater than thirty), lack of physical activity, poor diet, stress, and urbanization.[4] Excess body fat is associated with 30% of cases in those of Chinese and Japanese descent, 60-80% of cases in those of European and African descent, and 100% of Pima Indians and Pacific Islanders. Those who are not obese often have a high waist–hip ratio.

Dietary factors also influence the risk of developing type 2 diabetes. Consumption of sugar-sweetened drinks in excess is associated with an increased risk.  The type of fats in the diet is also important, with saturated fats and trans fatty acids increasing the risk and polyunsaturated and monounsaturated fat decreasing the risk.  Eating lots of white rice appears to also play a role in increasing risk.  A lack of exercise is believed to cause 7% of cases.

The following is a comprehensive list of other causes of diabetes:

*Genetic defects of ?-cell function
*Maturity onset diabetes of the young
*Mitochondrial DNA mutations

*Genetic defects in insulin processing or insulin action
*Defects in proinsulin conversion
*Insulin gene mutations
*Insulin receptor mutations

*Exocrine pancreatic defects
*Chronic pancreatitis
*Pancreatectomy
*Pancreatic neoplasia
*Cystic fibrosis
*Hemochromatosis
*Fibrocalculous pancreatopathy

Diabetes has no age bar. It can appear in a newborn, children, young adults, during pregnancy or in older people. If there are suspicious symptoms, tests should be done.

Some families have a tendency to develop diabetes, with many members being affected. This is because it is a genetic disease that an be inherited from both parents. Type 1 and 2 diabetes are inherited from multiple genes. In type 2 diabetes particularly, the environment and family’s dietary and exercise habits also influence these genes. Families that eat “well” and are sedentary with snacking and excessive TV viewing are more likely to develop type 2 diabetes. Sometimes type 1 diabetes can develop in persons without a family history or genetic predisposition. It may follow viral infections, especially with the mumps and coxsackie group of viruses. The virus attacks and destroys the cells in the pancreas responsible for manufacturing insulin.

Diagnosis:
Diabetes is diagnosed with blood tests. Blood sugar count after a 12 hour fast should be less than 100mg/dl and two hours after a full meal less than 140 mg/. Glycosolated haemoglobin (HbA1 c) should be 5.6.

A GTT (glucose tolerance test) can be done in suspect cases. In this the fasting blood glucose level is checked and 75gm glucose given. The blood is checked every 30 to 60 minutes after that. One hour later the blood glucose level should be lower than 180 mg/dL, two hours later less than 155 mg/dL, and three hours later lower than 140 mg/dL.

Complications:
Uncontrolled, untreated, neglected diabetes of all types causes complications with the nervous system, heart, kidneys, eyes and muscles affected.

All forms of diabetes increase the risk of long-term complications. These typically develop after many years (10–20), but may be the first symptom in those who have otherwise not received a diagnosis before that time. The major long-term complications relate to damage to blood vessels. Diabetes doubles the risk of cardiovascular disease. The main “macrovascular” diseases (related to atherosclerosis of larger arteries) are ischemic heart disease (angina and myocardial infarction), stroke, and peripheral vascular disease.

Diabetes also damages the capillaries (causes microangiopathy). Diabetic retinopathy, which affects blood vessel formation in the retina of the eye, can lead to visual symptoms including reduced vision and potentially blindness. Diabetic nephropathy, the impact of diabetes on the kidneys, can lead to scarring changes in the kidney tissue, loss of small or progressively larger amounts of protein in the urine, and eventually chronic kidney disease requiring dialysis.

Another risk is diabetic neuropathy, the impact of diabetes on the nervous system — most commonly causing numbness, tingling, and pain in the feet, and also increasing the risk of skin damage due to altered sensation. Together with vascular disease in the legs, neuropathy contributes to the risk of diabetes-related foot problems (such as diabetic foot ulcers) that can be difficult to treat and occasionally require amputation. Additionally, proximal diabetic neuropathy causes painful muscle wasting and weakness.

Several studies suggest a link between cognitive deficit and diabetes. Compared to those without diabetes, the research showed that those with the disease have a 1.2 to 1.5-fold greater rate of decline in cognitive function, and are at greater risk.

Treatment:
The major goal in treating diabetes is to minimize any elevation of blood sugar (glucose) without causing abnormally low levels of blood sugar. Type 1 diabetes is treated with insulin, exercise, and a diabetic diet. Type 2 diabetes is treated first with weight reduction, a diabetic diet, and exercise. When these measures fail to control the elevated blood sugars, oral medications are used. If oral medications are still insufficient, treatment with insulin is considered.

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A change in lifestyle goes a long way in preventing the onset of diabetes and controlling it after it sets in. These guidelines are particularly important if you have MODY or feel that you or your family members are in danger of developing it.

Prevention:
To prevent development of the disease as an adult, it is our children who need to be targeted for intervention. Lifestyle changes — a healthy diet and regular exercise — should be implemented at the school level.

Disclaimer: This information is not meant to be a substitute for professional medical advise or help. It is always best to consult with a Physician about serious health concerns. This information is in no way intended to diagnose or prescribe remedies.This is purely for educational purpose.

Resources:
http://en.wikipedia.org/wiki/Diabetes_mellitus
http://www.medicinenet.com/diabetes_treatment/article.htm
http://www.telegraphindia.com/1131118/jsp/knowhow/story_17579340.jsp#.UolfgL4o52Y

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Freedom From the Daily JAB

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Indian scientists are using tissue engineering to give diabetes patients new insulin-making cells……...CLICK & SEE

Biomaterials scientist Prabha Nair is pitting her expertise of polymers to hold out a new line of hope for patients with diabetes who are dependent on insulin shots. In her laboratory, she has used two structures fashioned out of polymer materials to normalise blood sugar in rats with diabetes for up to 90 days. One of the polymer structures is designed to make insulin-secreting cells function properly, while the other is intended to protect such cells from threats that might emerge from the body’s immune system.

Nair and her colleagues at the government-funded Sree Chitra Tirunal Institute of Medical Sciences and Technology (SCTIMST), Thiruvananthapuram have combined two applications of polymers to tackle two major obstacles that have held back a promising but experimental treatment for diabetes from widespread use. The treatment, called islet cell transplantation, involves the removal of insulin-secreting cells from the pancreas of a deceased organ donor and their implantation into a patient with diabetes.

It is nearly a decade since researchers at the University of Alberta in Edmonton, Canada, demonstrated that islet cell transplantation may help patients with diabetes acquire normal blood sugar levels and achieve some level of freedom from the need for insulin.

A review of islet transplantation on 225 patients between 1999 and 2006 had revealed several benefits — including reduced need for insulin, improved blood glucose control, and lowered risk of hypoglycemia, according to the National Institute of Diabetes and Digestive and Kidney Disorders in the US. Two years after the islet transplantation, about one-third of the recipients were free of the need for insulin shots, the review suggested.

Islet cell transplantation, however, is not standard therapy yet. “There is a critical shortage of islet cells because of a shortage of organ donors,” says Nair, a scientist in the division of tissue engineering and regeneration technologies at the SCTIMST.

Patients who receive islet cells need to take immunosuppressive drugs throughout their lives to prevent their immune systems from destroying the implanted cells. These drugs have side effects including an increased risk of cancer.

The SCTIMST researchers harvested a class of cells known as pancreatic progenitor cells from mice and placed them in a cocktail of appropriate biochemicals where they turn into insulin-secreting islet-like cells.

The scientists then loaded these islet-like cells into three-dimensional scaffolds constructed out of a gelatin, a natural polymer, and polyvinylpyrrolidone, a synthetic polymer. The islet-like cells proliferate on the scaffolds and serve as a potential source of insulin.

In experiments, the scientists observed that rats with diabetes that received these islet cell-bearing scaffolds alone died within 20 days. Their scaffold cells had been attacked by the rats’ immune systems, leading to the destruction of tissue and the failure of the implantation.

“We also designed a polymer capsule to shield the implanted islet cells from the immune system,” Nair told KnowHow. When the scientists combined the scaffolding, also called tissue engineering, with encapsulation, the rats survived for up to 90 days.

The rats were models for type-I, or insulin-dependent diabetes, but researchers say the tissue engineering and encapsulation strategy may also be considered as a possible option for patients with adult-onset diabetes who need insulin injections. Given the differences in the lifespans of rats and humans, some researchers believe the 90-day freedom from insulin observed in the laboratory animals may be equivalent to several years in humans — although exactly how long is still a subject of debate.

“These results are really exciting,” says Aroop Dutta, a tissue engineering specialist and founder of ExCel Matrix Biologicals, a Hyderabad-based start-up in biomaterials and tissue engineering, who was not connected with the research in Thiruvananthapuram.

“There just aren’t enough human-derived islet cells for the large numbers of diabetes patients dependent on insulin. Animal cells or stem cell-based approaches are the only viable options as sustained sources of islet cells,” he adds.

The results of the SCTIMST’s experiments were published last Friday in the journal Acta Biomaterialia. The researchers say their use of islet cells from mice in rats with diabetes suggests that the polymer capsule that keeps the immune system at bay may facilitate xenotransplants — the use of cells or organs across species — as an option for reversing diabetes. “But there is still much work to be done,” Nair cautions.

“We’ll need to establish that this also works in large animals,” she said. The SCTIMST group plans to initiate studies in pigs with diabetes. If the technique is indeed shown to work in large animals too, it could be ready for human clinical trials within two or three years.

Source : The Telegraph ( kolkata, India)

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Sperm Stems Sugar

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Scientists have developed a novel cure for diabetes by which male patients can grow insulin-producing cells from their own testes.

Stem cells hatched from human testes may offer a cure for diabetes in the near future. A team of US researchers, including a young Indian American student, has shown that men suffering from Type-1 diabetes may be able to grow their insulin-producing cells from their testicular tissue.

The scientists, led by G. Ian Gallicano of the Georgetown University Medical Center (GUMC) in the US, have found that when these bio-engineered cells are grafted into diabetic mice, they function quite like beta-islet cells, the insulin-secreting cells normally found in the pancreas.

By decreasing the animals’ blood glucose levels, the human derived islet cells demonstrated their potential to counter diabetic hyperglycemia in humans, Gallicano told scientists at an annual meeting of the American Society of Cell Biology (ASCB) in Philadelphia yesterday.

Anirudh Saraswathula, an undergraduate student at Duke University, is a co-author of the work. Under a mentoring programme, Saraswathula — who was a student at the Thomas Jefferson High School for Science and Technology in Alexandria — worked in Gallicano’s lab last year. His contribution to the work won Saraswathula — whose parents hail from Hyderabad — several prizes at national level innovation competitions in the US earlier this year.

The current work draws from an earlier breakthrough by GUMC researchers, including Gallicano. The scientists had shown that spermatogonial stem cells (SSCs) — that produce sperm — can be converted back into pluripotent embryonic-like stem cells that are capable of morphing into any cell type that a body needs, from brain neurons to pancreatic tissue. Embryonic stem cells — as the name suggests — are derived from human embryos. Their use in clinical application is mired in ethical issues.

“No stem cells, adult or embryonic, have been yet induced to secrete enough insulin to cure diabetes in humans, but we know SSCs have the potential to do what we want them to, and we know how to improve their yield,” Gallicano said in a release issued by the ASCB.

This could work in certain types of Type-2 diabetes as well, particularly in those patients whose beta cells are shut down. “Actually our hope is for it to serve as a cure, not just a treatment. Previous attempts at curing or treating diabetes have not quite panned out,” Gallicano told KnowHow.

Despite the rising tide of diabetes patients and dire predictions of worse to come, diabetes treatment has advanced little for decades beyond blood testing and insulin replacement. The only radically new approach to Type-I diabetes in recent years has been the Edmonton Protocol, named after the Canadian city where the technique was standardised, for transplanting insulin-producing beta-islet cells from deceased donors into the pancreas of diabetic patients who can no longer survive on insulin injections. Islet cell transplantation is plagued by problems of donor shortage and death of these cells in the body because of immune-mediated rejection.

Researchers have also cured diabetes in mice using induced pluripotent stem (IPS) cells — adult stem cells that have been reprogrammed with other genes to behave like their embryonic counterparts. The technique, however, has its downside because it can give rise to tumours since the procedure requires the use of cancer genes.

However, to date, numerous barriers surround and prevent stem cell therapies from treating diabetes. With respect to embryonic stem cells, immune rejection, risk of teratoma (tumour) formation, and ethical dilemmas remain at the forefront of their delay in clinical application. Conventional adult stem cells have not lived up to their billing either as they are difficult to generate in the quantities necessary, and they, too, can face immune rejection, explains Gallicano.

As a result, the search has gone on to find a stem / progenitor cell that is deemed “suitable” by the Food and Drug Administration for use in the clinic. “In light of this, we believe our preliminary data using SSCs show significant promise in addressing these critical barriers. Our cells do not need external genes to become pluripotent. There are no ethical dilemmas we are aware of. Our cells do form teratomas — but it takes 10 times more cells to do so when compared to IPS or ES cells, and they secrete very high levels of insulin once we differentiate them,” says Gallicano. For the present experiment, the scientists used SSCs harvested from deceased human organ donors.

Another advantage of the procedure, according to Gallicano, is that there is no chance of immune rejection, a major bottleneck of most organ transplants. That’s because these beta-islet cells are obtained from the patient’s own testes.

“If pluripotent stem cells could be derived from a patient’s own testes, problems of organ shortage and immune rejection could be bypassed. This research holds great promise for Type-1 diabetes patients,” says Anoop Misra, head of the department of diabetes, obesity and metabolic diseases at Fortis Hospital, New Delhi.

The scientists are hopeful that a similar methodology may yield a potential cure for female diabetics as well. “The fundamental approach of transforming male gametes (male sperm cells) into pluripotent stem cells might be applicable to the female counterpart — that is, oocytes,” Gallicano observes.

Source: The Telegraph ( Kolkata, India)

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This Simple Habit May Actually Reduce Cancer and Diabetes by 50%

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It is Vitamin D that influences more than 200 genes. This includes genes related to cancer and autoimmune diseases like multiple sclerosis.

Vitamin D affects your DNA through the vitamin D receptors (VDRs), which bind to specific locations of the human genome.

Reuters reports:

“Vitamin D deficiency is a well-known risk factor for rickets, and some evidence suggests it may increase susceptibility to autoimmune diseases such as multiple sclerosis (MS), rheumatoid arthritis and type 1 diabetes, as well as certain cancers and even dementia.”

Resources:
Reuters August 23, 2010

Genome Research August 23, 2010; [Epub ahead of print]

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Sweet remedy

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A protein, a by-product of natural insulin production, reduces heart complications in diabetics.  Reports on the outcome of a new study :-

Doctors have known for a long time that diabetes is one of the major risk factors for heart disease. If uncontrolled sugar levels persist for long, the blood vessels can become leaky. Such a condition allows cholesterol to seep in. And when cholesterol builds up inside the arterial blood vessels, they thicken from inside, reducing and eventually blocking the blood flow, leading to atherosclerosis.

Thanks to sustained campaigning over the years, most people now know that diabetes is also bad for the heart.

However, what many people do not know is that an inadvertent fallout of certain treatment methods can be detrimental to the heart’s functioning. A case in point is insulin therapy. One of the last resorts in diabetes management, the hormone insulin is administered either through a subcutaneous injection or by using a self-controlling pump attached to the body.

But this externally supplied insulin, for reasons not yet known, causes some cells in the blood vessels to grow more than they should, leading to a narrowing of their passageway to the heart.

A consequence of this, as some studies have shown, is that diabetics on insulin who have undergone bypass surgery are likely to have their newly grafted veins blocked earlier than non-diabetic heart patients.

But now a team of vascular biologists at the University of Leeds in the UK has found that a small protein, which was long thought to have been a useless by-product of natural insulin production in the pancreas, can ameliorate this undesirable side effect of insulin treatment.

Led by Karen Porter of the Leeds Institute of Genetics, Health and Therapeutics (Light), the researchers found that C-peptide, a natural by-product of insulin production, has a role to play in nature’s scheme of things and hence is not as “useless” as it is made out to be.

When C-peptide was given along with insulin, as happens in normal people who are not diabetic, the excessive growth and movement of cells was completely stopped, they report in the latest issue of the journal Diabetologia. “We found that administering insulin with C-peptide — which is released naturally in partnership with insulin in healthy people — appears to protect blood vessels from this damage,” says Porter.

Though insulin has been in use as medication since the 1930s, research till very recently failed to ascribe any role to C-peptide, insulin’s natural “partner”.

As a result, it was never incorporated in externally supplied insulin. In the 1970s though, some scientists briefly wondered if diabetics might be suffering from a lack of C-peptide. Subsequent studies, however, didn’t help much as they failed to ascertain any beneficial effect.

For instance, a study in 1993 by Julio Santiago of the Washington University who injected diabetic patients with low levels of the protein — just enough to match normal levels — saw no effect.

“Patients with diabetes are known to have higher cardiovascular risk and some will require coronary artery bypass grafting, using a vein from the leg. Patients donated these veins, left over after their operations, for research and we found that insulin on its own caused the cells lining these veins to go into an overdrive, with increased growth and movement that we know contribute to blockages. We were really surprised as to how powerful C-peptide was — it completely took away this insulin effect,” explains Porter.

“The study shows us a new path, wherein thickening of arteries — which is sometimes induced by insulin itself — could be decreased by giving C-peptide. This has huge relevance for the treatment of heart disease in patients with diabetes,” says Anoop Misra, head of internal medicine at New Delhi’s Fortis Hospital.

However, Nihal Thomas, an endocrinologist at the Christian Medical College, Vellore, says the idea that an additional peptide may augment the action of insulin is not entirely new. Previous studies with peptides such as IGF1 (insulin-like growth factor-1) and GLP-1 (glucagon-like peptide- type 1) have shown similar benefits.

Moreover, the mechanism works at a cellular level in laboratory studies. “It needs to be established over a period of time through extensive human clinical trials to assess its clinical viability,” he adds.

But if the trials were to become successful in the next few years, a large number of diabetics all over the world will benefit from it.

It will be especially welcome in India, which is home to more than 40 million Type 2 diabetic patients.

This more common form of diabetes, associated with obesity and a sedentary lifestyle, results in the pancreas overworking and eventually failing. These patients will require insulin therapy over time. For instance, some 5 per cent of Indian diabetics are on insulin. Those suffering from Type 1 diabetes need insulin therapy at a much earlier stage.

“The number of people affected by diabetes each year indicates the problem is here to stay. Patients can generally learn to manage and live with their diabetes but heart disease is a complication that kills,” says Porter.

As has been shown by the Light researchers, a combination of insulin and C-peptide may provide a more effective treatment than insulin alone in controlling some of the cardiovascular complications associated with diabetes.

Source: The Telegraph ( Kolkata, India)

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