Type 1 diabetes prevention

Type 1 Diabetes

Type 1 diabetes (previously called insulin-dependent or juvenile diabetes) is usually diagnosed in children, teens, and young adults, but it can develop at any age.

If you have type 1 diabetes, your pancreas isn’t making insulin or is making very little. Insulin is a hormone that enables blood sugar to enter the cells in your body where it can be used for energy. Without insulin, blood sugar can’t get into cells and builds up in the bloodstream. High blood sugar is damaging to the body and causes many of the symptoms and complications of diabetes.

Type 1 diabetes is less common than type 2—about 5% of people with diabetes have type 1. Currently, no one knows how to prevent type 1 diabetes, but it can be managed by following your doctor’s recommendations for living a healthy lifestyle, controlling your blood sugar, getting regular health checkups, and getting diabetes self-management education.

Hypoglycemia

Hypoglycemia symptoms can include:

  • Shakiness
  • Nervousness or anxiety
  • Sweating, chills, or clamminess
  • Irritability or impatience
  • Dizziness and difficulty concentrating
  • Hunger or nausea
  • Blurred vision
  • Weakness or fatigue
  • Anger, stubbornness, or sadness

For Parents

If your child has type 1 diabetes, you’ll be involved in diabetes care on a day-to-day basis, from serving healthy foods to giving insulin injections to watching for and treating hypoglycemia (low blood sugar; see below). You’ll also need to stay in close contact with your child’s health care team; they will help you understand the treatment plan and how to help your child stay healthy.

Much of the information that follows applies to children as well as adults, and you can also

Causes

Type 1 diabetes is caused by an autoimmune reaction (the body attacks itself by mistake) that destroys the cells in the pancreas that make insulin, called beta cells. This process can go on for months or years before any symptoms appear.

Some people have certain genes (traits passed on from parent to child) that make them more likely to develop type 1 diabetes, though many won’t go on to have type 1 diabetes even if they have the genes. Being exposed to a trigger in the environment, such as a virus, is also thought to play a part in developing type 1 diabetes. Diet and lifestyle habits don’t cause type 1 diabetes.

Symptoms & Risk Factors

It can take months or years for enough beta cells to be destroyed before symptoms of type 1 diabetes are noticed. Type 1 diabetes symptoms can develop in just a few weeks or months. Once symptoms appear, they can be severe.

Some type 1 diabetes symptoms are similar to symptoms of other health conditions. Don’t guess—if you think you could have type 1 diabetes, see your doctor right away to get your blood sugar tested. Untreated diabetes can lead to very serious—even fatal—health problems.

Risk factors for type 1 diabetes are not as clear as for prediabetes and type 2 diabetes, though family history is known to play a part.

Getting Tested

A simple blood test will let you know if you have diabetes. If you’ve gotten your blood sugar tested at a health fair or pharmacy, follow up at a clinic or doctor’s office to make sure the results are accurate.

If your doctor thinks you have type 1 diabetes, your blood may also tested for autoantibodies (substances that indicate your body is attacking itself) that are often present with type 1 diabetes but not with type 2. You may have your urine tested for ketones (produced when your body burns fat for energy), which also indicate type 1 diabetes instead of type 2.

Management

Unlike many health conditions, diabetes is managed mostly by you, with support from your health care team (including your primary care doctor, foot doctor, dentist, eye doctor, registered dietitian nutritionist, diabetes educator, and pharmacist), family, teachers, and other important people in your life. Managing diabetes can be challenging, but everything you do to improve your health is worth it!

If you have type 1 diabetes, you’ll need to take insulin shots (or wear an insulin pump) every day to manage your blood sugar levels and get the energy your body needs. Insulin can’t be taken as a pill because the acid in your stomach would destroy it before it could get into your bloodstream. Your doctor will work with you to figure out the most effective type and dosage of insulin for you.

You’ll also need to check your blood sugar regularly. Ask your doctor how often you should check it and what your target blood sugar levels should be. Keeping your blood sugar levels as close to target as possible will help you prevent or delay diabetes-related complications.

Stress is a part of life, but it can make managing diabetes harder, including controlling your blood sugar levels and dealing with daily diabetes care. Regular physical activity, getting enough sleep, and relaxation exercises can help. Talk to your doctor and diabetes educator about these and other ways you can manage stress.

Healthy lifestyle habits are really important, too:

  • Making healthy food choices
  • Being physically active
  • Controlling your blood pressure
  • Controlling your cholesterol

Make regular appointments with your health care team to be sure you’re on track with your treatment plan and to get help with new ideas and strategies if needed.

Whether you just got diagnosed with type 1 diabetes or have had it for some time, meeting with a diabetes educator is a great way to get support and guidance, including how to:

  • Develop and stick to a healthy eating and activity plan
  • Test your blood sugar and keep a record of the results
  • Recognize the signs of high or low blood sugar and what to do about it
  • Give yourself insulin by syringe, pen, or pump
  • Monitor your feet, skin, and eyes to catch problems early
  • Buy diabetes supplies and store them properly
  • Manage stress and deal with daily diabetes care

Ask your doctor about diabetes self-management education and to recommend a diabetes educator. You can also search the American Association of Diabetes Educators’ nationwide directoryexternal icon for a list of educators in your community.

Hypoglycemia

Hypoglycemia pdf icon (low blood sugar) can happen quickly and needs to be treatedexternal icon immediately. It’s most often caused by too much insulin, waiting too long for a meal or snack, not eating enough, or getting extra physical activity. Hypoglycemia symptoms are different from person to person; make sure you know your specific symptoms, which could include:

  • Shakiness
  • Nervousness or anxiety
  • Sweating, chills, or clamminess
  • Irritability or impatience
  • Dizziness and difficulty concentrating
  • Hunger or nausea
  • Blurred vision
  • Weakness or fatigue
  • Anger, stubbornness, or sadness

If you have hypoglycemia several times a week, talk to your doctor to see if your treatment needs to be adjusted.

Connect with Others

Tap into online diabetes communities for encouragement, insights, and support. The American Diabetes Association’s Community pageexternal icon and the American Association of Diabetes Educators’ Peer Support Resourcesexternal icon are great ways to connect with others who share your experience.

Complications

Complications are most commonly linked to high blood glucose levels over a long period of time, so the best protection against developing anything is to keep your levels in range.

Common complications

The most common complications can be classified broadly as:

  • Damage to the large blood vessels of the heart, brain and legs (called macrovascular complications)
  • Damage to the small blood vessels (microvascular complications) causing problems in the eyes, kidneys, feet and nerves

The parts of the body that can be most affected by diabetes complications are heart and blood vessels, kidneys, eyes, nerves, gums and feet.

Once you have had type 1 for a couple of years you’re at risk of developing some subtle changes to the organs containing non-insulin requiring cells. Many type 1 related complications don’t show up until you’ve had the condition for many years, sometimes decades.

Check ups

Complications usually develop silently and gradually over time, which means that regular check ups are a must to catch the signs early.

If these changes to your organs are found early, there are strategies to stop or delay the progression of type 1-related complications. For this reason, it is recommended that you are screened for complications two to five years after being diagnosed, then annually thereafter.

Type 1 Diabetes Complications

Nerve damage, blindness, and kidney disease are common complications of type 1 diabetes.

People with type 1 diabetes lack the hormone insulin, which regulates the body’s use of glucose for energy.

This results in high blood glucose, or hyperglycemia, as glucose builds up in the bloodstream.

The main treatment for type 1 diabetes is lifelong insulin therapy, which lowers blood glucose and allows the body to use glucose as fuel.

High blood glucose is associated with a number of symptoms, such as increased urination, extreme thirst or hunger, and slow-healing sores.

Over time, elevated blood glucose levels can also lead to various complications in different areas of the body, since hyperglycemia damages many different types of tissue.

Diabetic Neuropathy

Neuropathy is a type of nerve damage, or nerve dysfunction.

In people with diabetes, neuropathy may develop when high blood glucose levels damage blood vessels that supply oxygen to nerves.

As many as 60 to 70 percent of all people with diabetes have some form of neuropathy, according the National Institute of Diabetes and Digestive and Kidney Diseases.

A common form of diabetic neuropathy is peripheral neuropathy, which causes numbness, pain, and weakness in the toes, feet, legs, hands, or arms.

Because of this widespread complication, people with diabetes must take special care of their feet.

Nerve damage may cause people to lose feeling in their feet, leading to unnoticed injuries that may become infected (poor blood flow can also lead to slower healing).

What’s more, nerve damage may cause foot deformations that lead to additional pressure at certain points on the feet — and these pressure points may develop into blisters, sores, or ulcers.

Diabetic neuropathy may also affect various other areas of the body, including the digestive tract, heart, sex organs, facial muscles, buttocks, and urinary tract.

Diabetic Retinopathy

By affecting the blood vessels in the retina, diabetes may cause retinopathy, a type of eye disease.

In some people, diabetic retinopathy causes blood vessels in the eye to swell and leak fluid, while in others, there is abnormal growth of new blood vessels on the retina.

Diabetic retinopathy often leads to blurred vision, and sometimes blindness.

In fact, it’s the leading cause of blindness among adults 20 to 74 years old, according to a 2010 report in the journal Endocrinology and Metabolism Clinics of North America.

People with diabetes are also more likely to develop cataracts (cloudiness of the eye lens) and glaucoma (optic nerve damage).

Diabetic Nephropathy

About 20 to 40 percent of people with diabetes develop nephropathy, a form of kidney disease, according to the 2010 report.

The kidneys work to filter blood, keeping it clean of waste products.

Diabetic nephropathy develops when high blood glucose levels damage blood vessels in the kidneys, causing them to gradually lose their filtering ability — and allowing waste products to build up in the body.

The first symptom of nephropathy is often swelling in certain areas of the body. In many cases, however, nephropathy doesn’t cause any symptoms until almost all kidney function is gone.

Dialysis is often necessary if kidney function drops below a certain level. If the kidneys fail completely, a kidney transplant may be necessary.

Other Diabetes Complications

Type 1 diabetes can also lead to other complications, including:

  • High blood pressure
  • Cardiovascular disease
  • Stroke
  • Skin and mouth infections
  • Gastroparesis (delayed gastric emptying), a type of neuropathy
  • Sexual dysfunction
  • Depression

Diabetes can also cause pregnancy complications — such as an increased risk of stillbirth, miscarriages, and birth defects — if blood glucose is not controlled properly.

Why Can’t We Prevent Type 1 Diabetes?

Type 1 diabetes is potentially preventable

Both the name and that notion emerged in the mid-1970s, when it became clear that this form of diabetes has an autoimmune basis. Studies in identical twins showed that two of three initially unaffected cotwins would remain nondiabetic, an experiment of nature implying that type 1 diabetes was a disease involving a dose of happenstance, not solely of genetic predestination. Knowledge that the immune system was involved raised therapeutic possibilities because immunity had been successfully manipulated to our own advantage (e.g., vaccines). Proof of principle for disease prevention emerged from rodent models of type 1 diabetes, and trials of immunosuppression with cyclosporin at disease onset showed that this could prolong β-cell function in humans, if only transiently. Join this to the discovery that islet autoantibodies appeared in the circulation many years before clinical onset and could be used to predict disease development and one has a condition for which screening and intervention are justified, if such an intervention could be identified (1,2).

The emerging therapeutic possibility has been matched to a growing need. The incidence of childhood diabetes continues to rise steadily, and the ever-increasing push toward more intensive management is limited by rising costs and the unremitting demand this form of therapy places on its recipients. It has been clearly demonstrated that improved clinical management can make an enormous difference, but there is at present little evidence to suggest that its impact extends much beyond well-motivated patients attending specialized centers. Meanwhile, the burden of long-term complications continues to rise, and it has been estimated that this increase will continue for at least 20 years after an effective means of prevention becomes available (3).

This combination of need, scientific rationale, and strong backing by public and private sources prompted the launch of three major diabetes prevention trials in the early to mid-1990s. All set out to determine whether progression to type 1 diabetes could be modified in high-risk individuals, in this case, islet autoantibody-positive relatives of an affected proband. Three different agents (nicotinamide, subcutaneous insulin, and oral insulin) and two huge study groups (the European Nicotinamide Diabetes Intervention Trial and the Diabetes Prevention Trial-Type 1), led to but one common result—failure to prevent type 1 diabetes (4,5).

What went wrong?

Success evaded us, it seems, because of both unrealistic expectations and failed assumptions. Failure can, however, be highly educational. The experience gained from these trials, when joined to other recent advances in knowledge (6), provides useful clues and recommendations for the future (Table 1).

The paradox that has emerged is that individuals at very high risk of progression, convenient though they are for trial design and power calculations, may not be the best people in whom to intervene, precisely because their risk is so high. The immune system is a formidable adversary, with an extensive range of weaponry at its disposal (7,8), and it is not easily diverted from its purpose once fully mobilized against any particular set of antigens. The markers that we use to identify risk do so because they represent collateral damage from an assault on the target tissue that is already entering its final stages. Prevention studies with nonobese diabetic mice confirm that it is much easier to intervene early in the disease process than at the stage of overt hyperglycemia (9,10). The literary analogy that springs to mind is that of the little Dutch boy who prevented a flood by putting his finger in a hole in the dyke and thus prevented it from enlarging (11). We may have been waving one finger ineffectually at a much larger breach in the defenses.

Other lines of argument support this inference. Clinical onset of type 1 diabetes is the outcome of a smoldering disease process typically ignited many years earlier, probably soon after birth. Therefore, early disease onset most likely reflects a particularly aggressive and already well-advanced variant of the condition. Clinical trials are largely based around recruitment of children, however, and these have a disproportionate effect on the outcome because most progressors fall into this category. Young though they are, they represent end-stage pre-diabetes. This line of reasoning suggests that we should shift our focus toward intervention much earlier in life. The problem here is that recruitment should logically be based on susceptibility (high-risk HLA combinations, family history, or both) rather than the far more potent markers of disease activation (islet autoantibodies) or progression (early signs of β-cell failure) that have been used so effectively later in the disease process. Trials in early infancy—when intervention is likely to prove most effective—will run into the practical limitations of low-screening efficiency, massive size with corresponding cost, safety considerations, and the longevity of investigators. At a more fundamental level, we need to inquire whether we truly understand enough about the interplay of genes, environment, and the developing immune system to be able to intervene intelligently and effectively in healthy infants. The honest answer to this has to be “no.” In the absence of such understanding, it makes sense to limit our efforts to interventions that are unquestionably safe.

Proposal for the road ahead

Are we truly impaled upon the horns of a dilemma? Is there no middle road between the alternatives of intervening too early or too late? One practical option has been to sidestep this whole issue and focus intervention on the newly diagnosed patient. The rationale here is relatively simple: all newly diagnosed subjects have the disease, so there are no false positives. They are all on a path leading to near-total β-cell failure, so any preservation of β-cell function, even transient, could be beneficial. The knowledge that study entrants are already condemned to lose most of their residual β-cells adds a useful “comfort factor” to the equation when the theoretical possibility that some interventions might inadvertently accelerate β-cell destruction is under consideration. This approach, using endogenous insulin secretion as its end point, allows a number of interventions to be screened in parallel and within a relatively short time frame. The disease process may be too advanced for there to be much prospect of lasting clinical benefit, let alone a cure, but any hint of efficacy could provide a basis for future endeavors. What form should these take?

As we lack insight into the precise immune effector mechanisms, we believe it may be time to learn a lesson from successful therapeutic approaches used in other complex diseases (e.g., cancer, AIDS, and systemic lupus erythematosus). Combination or “cocktail” therapy for these disorders shows that multiple agents in combination are often markedly superior to the use of a single drug. Why should type 1 diabetes be any different? Combined immunosuppression has certainly demonstrated its value in the treatment of islet grafts, and it stands to reason that the reversal of autoimmunity requires a similar approach. Indeed, the experience of Bosi et al. (12) suggests that reactivation of autoimmunity following islet transplantation may be harder to treat than the alloimmune rejection process. Should potential therapeutic agents that are potentially efficacious and acceptably safe be used in combination to limit inflammation and β-cell destruction? These might include, but would not be limited to, nutritional interventions, antigen-based therapies, monoclonal antibodies, and other immunoregulatory and immunosuppressive agents. Single agents that show any promise of efficacy after disease onset—a “flick on the dial” may suffice—could be tested in successive cohorts of newly diagnosed patients in combination with other measures, and in this way, it may prove possible to painfully inch our way forward. This at least is how success was achieved in the examples of effective combination therapy cited above.

Need for optimistic realism

There is a Romanian joke that defines a pessimist as a well-informed optimist. The easy optimism of the early days of attempted diabetes prevention may have evaporated, but pessimism is not yet warranted (13,14). For one thing, and despite their negative outcomes, the large-scale prevention trials mentioned have shown beyond doubt that diabetes can be predicted and that interventions can be tested in the context of controlled trials. This in itself, to our thinking, represents one of the major success stories of diabetes research over the last decades. In addition, the trials have instilled a new sense of discipline and purpose into the diabetes research community, backed by proposed guidelines for further intervention trials (15), including outcome measurements, standardization, safety, efficacy, mechanistic studies, and statistics. Rumors of the death of diabetes prevention may have been exaggerated, but there are no easy victories in sight.

What to know about type 1 diabetes

The physical effects of type 1 diabetes include:

  • increased hunger and thirst
  • frequent urination
  • blurred or unclear vision and problems with sight
  • tiredness and fatigue
  • weight loss without an apparent trigger or cause

Refer any clear signs of diabetes to a primary care physician, who will administer tests to confirm that these are a result of diabetes.

The honeymoon phase

After receiving a diagnosis of type 1 diabetes, the islet cells responsible for insulin secretion may continue to produce the hormone for a while before ceasing.

During this time, a person will need fewer insulin shots to maintain healthy levels of blood glucose.

Doctors refer to this as the “honeymoon phase” or honeymooning.

This phase can lead to a person with type 1 diabetes mistakenly thinking that they are getting better. The honeymoon phase, while giving the impression of recovering symptoms, still requires close monitoring and regular adjustments of insulin dosage.

Sticking to the recommended treatment plan is essential while honeymooning.

If a person does not manage these symptoms, a range of dangerous complications might develop.

These include:

Diabetic retinopathy: Excess glucose leads to a weakening of the walls of the retina, the part of the eye that detects light and color. As retinopathy progresses, small blood vessels may form behind the eyes that might bulge and rupture, causing vision problems.

Diabetes is one of the leading causes of blindness among working-age adults.

Diabetic neuropathy: High blood sugar reduces circulation, damaging nerves in the hands and feet and leading to a loss of sensation or abnormal sensations such as burning, tingling, and pain.

As diabetes can also reduce the body’s ability to heal, minor cuts and injuries can lead to more permanent damage, especially as a person may not immediately notice them.

Diabetic nephropathy, or diabetic kidney disease: The kidneys filter glucose from the blood. Too much glucose can overwork them, and progressively cause kidney failure, which may progress to needing dialysis.

Cardiovascular disease: Diabetes can lead to a range of abnormalities that impair the function of the heart and arteries, including heart attack, stroke, and peripheral vascular disease.

As a result of poor circulation, diabetes can also increase the risk of amputations.

Gum disease: Type 1 diabetes can increase the risk of gum disease and tooth loss, meaning that a person with this type should be very careful to maintain dental health.

Depression: Diabetes has strong links with depression.

Diabetic ketoacidosis (DKA) is an acute complication of diabetes that occurs when a person does not meet the requirement for insulin, and the body undergoes extreme stress.

Diabetic ketoacidosis leads to very high blood sugars. The body experiences a shift in metabolism and starts breaking down fat instead of sugar, producing ketones as a waste product.

Ketones can be harmful to the body and cause acidosis. DKA is a medical emergency that requires hospitalization and treatment with intravenous insulin etc.

Carefully managing type 1 diabetes can dramatically reduce the risk of these complications. A landmark study called the Diabetes Care and Control Trial (DCCT) has shown that good blood sugar control can significantly reduce the risk of microvascular complications.

Many of the initial blood tests indicate the presence of diabetes but do not specify which type of diabetes is present

Doctors use clinical and laboratory clues to differentiate between the two types of diabetes.

While exceptions can occur, people with type 1 diabetes tend to present at a much younger age and are lean. Individuals with type 2 diabetes are typically older and overweight.

The doctor will then test for autoantibodies against pancreatic cells in the blood. While antibodies would help the immune system combat diseases and infections, autoantibodies occur when the immune system is attacking healthy tissues incorrectly.

The doctor can also measure C-peptide, an indicator of how much insulin the body produces. They expect it to be lower in type 1 diabetes, as this relates to the destruction of the insulin-producing cells.

Foods to limit or avoid with type 1 diabetes

It is important to know which foods to limit or avoid to keep your blood sugar in a healthy range.

The usual blood sugar target ranges for children of all ages are:

  • Before meals: 70 to 150
  • 2 to 3 hours after meals: less than 180
  • Bedtime and during the night: 90 to 150

Foods to limit

Sugar and processed carbohydrates make blood sugar rise and fall quickly.

Limit how much and how often you eat foods high in sugar and processed carbohydrate, such as:

  • Chips
  • Crackers
  • Candy
  • Cookies
  • Ice cream
  • Cakes/cupcakes
  • Pies

Foods to avoid

Do not drink drinks sweetened with sugar, such as:

  • Energy drinks
  • Flavored milk
  • Egg nog
  • Fruit juice
  • Regular soda
  • Sports drinks
  • Lemonade
  • Sweet tea

You can drink these to treat a low blood sugar.

Do not eat breakfast foods with a lot of sugar and simple carbohydrate, such as:

  • Breakfast pastries
  • Doughnuts
  • Flavored oatmeal
  • Pop-Tarts
  • Toaster pastries

Instead try:

  • Fruit for a sweet treat
  • Raw veggies and dip for a crunchy treat
  • Drinks sweetened with artificial sweeteners, such as:
    • Crystal Light
    • MiO
    • Diet soda
    • Powerade Zero
  • Breakfast cereal and flavored oatmeal with:
    • Less than 10 grams of sugar per cup
    • 3 or more grams of fiber per serving

Is It Possible to Prevent or Delay Type 1 Diabetes?

What if there was a way to determine exactly who would develop type 1 diabetes (T1D) and doctors could intervene to prevent it altogether or at least delay the onset by years?
JDRF, a leading research advocacy organization, and the Disease Interception Accelerator (DIA) group of Janssen Pharmaceuticals announced a joint venture earlier this year to take on this challenge.1 The goal is to identify the root cause of T1D and intercept its progression to disease before symptoms arise.
There have been many questions about the actual cause of T1D. Work in recent years suggests there is a window of opportunity to stop or delay the disease before the onset of clinical symptoms of the disease.2,3 The autoimmune response directed against beta cells is suggested to be secondary to tissue damage and unrelated to disease pathogenesis.4 The presence of antibodies against the islets of Langerhans that were detected in the serum of patients diagnosed with T1D, but not in healthy individuals, led to the suggestion of the autoimmune etiology of T1D.4
Although T1D has been referred to by many names, such as juvenile diabetes or insulin-dependent diabetes, the treatment has always been the same: insulin. T1D is a pancreatic beta cell specific disease that results in absolute insulin deficiency.4,5 Data from the United Kingdom suggest life expectancy of adults with T1D is reduced by up to 13 years.6,7 The symptoms of T1D are similar to type 2 diabetes, including frequent urination and feeling thirsty, hungry, or tired. Additionally, with T1D, there is the possibility of sudden weight loss, nausea and vomiting from the build-up of ketones in the body, and diabetic ketoacidosis.8
Although only about 5% of patients with diabetes have T1D,9 the effect can be more devastating since children and young adults are the ones most commonly given a diagnosis of T1D. These individuals live with the disease for many more years, thus prolonging the time for cellular damage, which increases the potential for complications of diabetes that include blindness and kidney damage and, in extreme cases, loss of toes or lower limbs.8 The goal of intensive insulin therapy is to reduce long-term complications while avoiding acute emergencies, such as hypoglycemia, to optimize quality of life for patients.2,6
DISEASE PATHOLOGY
T1D is mainly related to an autoimmune response through which the action of T cells and/or T lymphocytes results in destruction of pancreatic cells.10 The most commonly identified islet autoantibodies associated with progression to T1D are insulin autoantibodies), glutamic acid decarboxylase 65 autoantibodies, insulinoma antigen 2 autoantibodies, and zinc transporter 8 autoantibodies.11 However, T1D can also be triggered by different factors such as obesity, viruses, and chronic or acute inflammations that affect the cells of the pancreas that produce insulin.10 Although there are no physical symptoms, there is data that suggests T1D is commonly preceded by early symptoms including seroconversion to islet autoantibody and metabolic disturbances.11
The mechanism of how metabolic syndrome and autoimmune factors affect the progression of T1D is not yet clear, however.
POTENTIAL PREVENTION STRATEGIES
About 50% of patients with T1D are overweight or obese.12 Whereas insulin therapy can achieve optimal glucose control, it can also cause patients to gain weight. This makes insulin less effective, which then requires more insulin—and a vicious cycle begins. Traditional treatment options for T1D include pancreas transplantation and transplant of islet and embryonic stem cells.
Pancreas transplantation10 is still a useful treatment for some patients; however, it might not be an optimal option for all patients. Transplant of islet cells is an option, safer than transplantation, but still an invasive procedure.10 Finally, embryonic stem cells are still in the research phase due to costs and standardization concerns.10 These options are viable, but they should probably be used in patients with extreme disease progression or reserved as a last resort.
Adjunct therapies may be necessary to help better manage glucose levels and optimize insulin therapy,12 thereby reducing T1D complications, preserving beta cells, and improving insulin secretion.10 There is ongoing research for alternative treatments for continuous glycemic control and for slowing down the damage caused by T1D.10 Studies have looked at the use of immunosuppressive agents, including cyclosporine, prednisone, and azathioprine, for initiating the remission of T1D.4 Results suggest the preservation of residual beta cells, with adjunct immunosuppressants, was able to produce sufficient insulin and subsequently improve glycated hemoglobin. However, when treatment ended, T1D rapidly relapsed.4,10 The big concern with using immunosuppressive agents is the toxicity associated with their use.4
JDRF’s chief scientific officer, Richard Insel, MD, and his team are eager to work with Janssen’s DIA group to advance an innovative scientific initiative.1 Insel and JDRF are big advocates for preventive intervention; at the launch of the venture, Insel said it provides an exciting opportunity.1
“The studies are all still in the research setting,” Insel said in an interview with Evidence-Based Diabetes Management. He shared the 2 main ways of identifying patients at risk of developing T1D. One involves screening relatives of patients with T1D for an autoimmune response, specifically identifying antibodies that would attack islets of pancreas cells. Several antibodies have previously been identified, and individuals who produce 2 or more islet autoantibodies are at a higher risk for developing T1D.11 The progression to T1D, he said, could take years or even decades, however.
The second method of identifying patients at risk for developing T1D requires screening all children younger than 18 years. This would include a genetic-risk screening of children once a year, perhaps at the annual medical visit. This is already being done in Germany for all 3- and 4-year-olds. Insel referred to TrialNet, a T1D study conducted by an international network of researchers who are exploring ways to prevent, delay, and reverse the progression of disease.13 The study presented by Alberto Pugliese, MD, in June 2014 at the 74th Scientific Sessions of the American Diabetes Association, was a 5-year study that followed relatives of patients who have T1D. In the study, researcher looked at the risk of developing T1D with human leukocyte antigen influence, in addition to having positive autoantibodies. The results showed that having several high-risk haplotypes/genotypes indicated a high risk for 5-year T1D incidence. Relatives with a single antibody had an increased risk of developing additional autoantibodies, without progression to T1D.14
Another article pooled data from several prospective cohort studies that examined children who were genetically at risk for developing T1D. The results showed an almost 70% risk of progression to T1D at a 10-year follow-up when patients had multiple islet autoantibodies compared with 15% for patients with a single autoantibody. Children who lacked islet autoantibodies had a less than 1% risk to progression.15
The Pre-POINT study, funded by JDRF, was conducted in Germany, Austria, the United States, and the United Kingdom. The study enrolled 25 children aged 2 to 7 years with a family history of T1D and who were islet autoantibodies–negative. The children were randomized to receive either oral insulin or placebo once daily. The study results showed there was an immune response without hypoglycemia at high doses; however, there were almost twice as many adverse events—67 versus 35, respectively—in the insulin-treated compared with the placebo group.3 This might be an interesting treatment option, but larger trials are necessary for further study.
“Currently, there are multiple ongoing studies and over 150,000 patients have been screened to determine predisposition of developing T1D,” said Insel. JDRF is funding multiple trials along with National Institutes of Health’s TrialNet trials. “Some of the trials are looking to arrest the progression to T1D.” Although this is currently in the research setting, there are high expectations from the results of these studies.
SUMMARY
Postponing or preventing T1D is an exciting concept. Although extensive groundwork is necessary to identify the right precursors, determine the correct agents, and maintain optimal glucose control, the focus on this patient population will have a huge impact. Additionally, looking at adjunct therapy to help optimize insulin therapy in patients with T1D needs ongoing research.
There is some excitement in the identification of the mechanism and management of T1D, which is long overdue. Ongoing trials are evaluating ways to arrest progression, perhaps using some of the newer agents to help improve the response to insulin or to prevent the rapid breakdown of insulin.

1. Janssen sets a course to intercept type 1 diabetes together with JDRF . Raritan, NJ: Janssen Research and Development; February 11, 2015.
https://www.jnj.com/news/all/Janssen-Sets-A-Course-To-Intercept-Type-1-Diabetes-Together-With-JDRF. Accessed September 25, 2015.
2. Beauchamp G, Haller MJ. Can we prevent type 1 diabetes? Curr Diab Rep. 2015;15(11):86.
3. Bonifacio E, Ziegler AG, Klingensmith G, et al; Pre-POINT Study Group. Effects of high-dose oral insulin on immune responses in children at high risk for type 1 diabetes: the Pre-POINT randomized clinical trial. JAMA. 2015;313(15):1541-1549.
4. Mannering SI, Pathiraja V, Kay TWH. The case for an autoimmune etiology of type 1 diabetes . Clin Exp Immunol. doi:10.1111/cei.12699.
5. Campbell-Thompson M, Rodriques-Calvo T, Battaglia M. Abnormalities of the exocrine pancreas in type 1 diabetes. Curr Diab Rep. 2015;15(10):653.
6. Amiel SA, Pursey N, Higgins B, Dawoud D; Guideline Development Group. Diagnosis and management of type 1 diabetes in adults: summary of updated NICE guidance. BMJ.2015;351:h4188.
7. Livingstone SJ, Levin D, Looker HC, et al; Scottish Diabetes Research Network epidemiology group; Scottish Renal Registry. Estimated life expectancy in a Scottish cohort with type 1 diabetes, 2008-2010. JAMA. 2015;313(1)37-44.
8. The diabetes advisor. American Diabetes Association website. http://professional.diabetes.org/PatientEducationLibraryDetail. aspx?pmlPath=Symptoms_18afd79d-5335-430b-a951-87c547003035&pmlName=Symptoms.pdf&pmlId=270&pmlTitle=Diabetes%20Symptoms. Accessed September 25, 2015.
9. Type 1 diabetes. American Diabetes Association website. http://www.diabetes.org/diabetes-basics/type-1/?loc=utilheader_type1. Accessed September 25, 2015.
10. Mancio RD, Minatel E, de Almeida Cardoso M, Ali Khan B, José Caldeira E. The immunomodulation to diabetes control:new proposals for the reversion of this disease. Diab Metab Syndr. 2015; 9(4):210-212.
11. Marinkovic T, Oresic M. Modeling strategies to study metabolic pathways in progression to type 1 diabetes – challenges and opportunities . Arch Biochem Biophys. 2015; pii: S0003-9861(15)30037-0. doi: 10.1016/j.abb.2015.08.011.
12. Schechter R, Reutrakul S. Management of severe insulin resistance in patients with type 1 diabetes. Curr Diab Rep 2015;15(77):1-12.
13. TrialNet studies. Type 1 Diabetes TrialNet website. http://www.diabetestrialnet.org/studies/. Accessed September 29, 2015.
14. Pugliese A. HLA influence progression to type 1 diabetes (T1D) in autoantibody-positive relatives. Presented at: the 74th Scientific Sessions of the American Diabetes Association; San Francisco, CA; June 13-17, 2014. Accessed September 25, 2015.
15. Ziegler AG, Rewers MD, Simell O, et al. Seroconversion to multiple islet autoantibodies and risk of progression to diabetes in children. JAMA 2013;309(23):2473-2479.

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