DO YOU HAVE AUTOIMMUNE DIABETES?

Read in 6 minutes

WHY DO YOU NEED TO KNOW IF YOU HAVE DIABETES AUTOIMMUNITY?

Sonia Kumar (not her real name) a 38 year old mother of two young girls, spent seven frustrating months trying to get her blood sugar under control.She was recommended escalating doses of oral anti-diabetes medications. She was even accused of cheating on her diet!But none of this helped her! It took an astute physician (not me!) to test her for diabetes autoantibodies to find out that she actually had Type 1 Diabetes!

The diagnosis was missed because people often think that Type 1 Diabetes does not develop in adults.

WHAT IS DIABETES?

Diabetes is a group of metabolic diseases with high blood sugar (hyperglycaemia) as the common feature. The high blood sugar results from defects in insulin secretion, defects in insulin action or both. About 20 years ago diabetes was classified into Insulin Dependent (IDDM) or Juvenile and Non-Insulin Dependent (NIDDM) or Adult Onset Diabetes. However, in the last several years it has become apparent that the use of insulin or age at onset could not adequately explain the disease conditions and specify the best treatment plan. Therefore, there is an opinion amongst diabetes researchers that the time has come for a new classification of the disease.

Diabetes develops because of an interaction between genes and the environment. Our genes have not changed in thousands of years,but our environment has.To a great extent this explains the dramatic increase in diabetes over recent years. Some of the influences have originated in the intrauterine environment before a person is born!

Exposure to environmental toxins like BPA have also contributed to the recent epidemic of diabetes.

Developments in the field of precision medicine, ethnicity-specific data and big data along with patient-participatory research will change the management of diabetes for the better.

TYPES OF DIABETES:

(For a medically appropriate classification please check the American Diabetes Association website for “Etiologic classification of diabetes mellitus”).

  • Type 1 Diabetes
  • Type 2 Diabetes (Commonest)
  • Gestational Diabetes (GDM/Pregnancy Diabetes)
  • Maturity Onset Diabetes of the Young (MODY)♣
  • Latent Autoimmune Diabetes of the Adult(LADA)♣
  • Drug Induced Diabetes.♣
TYPE 1 DIABETES

High blood sugar resulting from an absolute deficiency of insulin secretion. Type 1 Diabetes may be

  • Autoimmune or
  • Idiopathic.

Autoimmune Diabetes occurs when the Insulin producing cells in the pancreas are destroyed by an autoimmune process. Autoimmune markers for Type 1 Diabetes, also called Diabetes-Associated Autoantibodies (DAA) are usually present in most of these patients.

Idiopathic—In a small percentage of patients there is Insulin deficiency but no autoimmunity.

Though absolute insulin deficiency is a hallmark of Type 1 Diabetes, about 30 % of people with this condition have insulin resistance as well.

DIABETESASSOCIATED AUTOANTIBODIES (DAA):

  • Glutamic Acid Decarboxylase Autoantibodies (GAD65 or Anti-GAD)
  • Insulin Autoantibodies (IAA)
  • Insulinoma-Associated-2 Autoantibodies (IA-2A)
  • Islet Cell Cytoplasmic Autoantibodies (ICA)
  • Zinc Transporter 8 (ZnT8Ab) Autoantibodies
GESTATIONAL DIABETES (GDM or PREGNANCY DIABETES)

GDM is defined as any degree of glucose intolerance that was first recognized during pregnancy. This definition would include women who had previously undiagnosed Type 2 Diabetes and also those women who developed diabetes for the first time during pregnancy.Asian Indian women are at a very high risk for pregnancy diabetes. Therefore it is very important for them to be screened at the beginning , during mid-trimester as well as in the last trimester.

GDM raises the risk of several complications in both the mother as well the baby. Increased birth defects, increased birth weight, early (preterm) delivery are some of the risks in the babies born of mothers with GDM. The mother is at increased risk of pregnancy high blood pressure and pre-eclampsia and is at a higher risk for developing diabetes later in life. In addition, she is at increased risk for heart disease even if she does not develop diabetes later on in life!

TYPE 2 DIABETES

This is the commonest type of diabetes.Type 2 diabetes includes individuals who have insulin resistance and usually relative insulin deficiency. These individuals may not need insulin treatment to survive. However, use of insulin does not decide the type of the disease. Diabetes Associated Autoantibodies are absent in people with Type 2 Diabetes.

HOW DOES THIS AFFECT YOU?

It is important to keep in mind that adults can develop autoimmune diabetes too! British Prime Minister Theresa May, who was diagnosed with Type 1 Diabetes at age 56 and Sonia Kumar mentioned above were both initially diagnosed as Type 2 Diabetics. However both of them needed insulin therapy to control their blood sugar levels,when they were found to have Diabetes Antibodies.

Sulfonylurea (SU) drugs like chlorpropamide,glyburide,glipizide which work by stimulating the pancreas to release more insulin, are not the right drugs for these people.Use of these drugs in patients with diabetes autoimmunity have shown poor metabolic control and earlier loss of insulin producing beta cells in the pancreas.

A study in apparent long-standing type 2 diabetes found that those with Diabetes Associated Autoantibodies or with low C-peptide did not respond well to glucagon-like peptide 1 (GLP-1) agonist drugs like Liraglutide,Exenatide etc.

People with one autoimmune condition are at a higher risk for other autoimmune conditions as well. Diabetes Autoimmunity has often been associated with thyroid autoimmunity.

NUMBERS TO KNOW

If you have diabetes you obviously know your blood sugar and glycated haemoglobin (HbA1C) levels. In addition the following tests are important for the right treatment:

  • Diabetes Associated Autoantibodies (DAA)
  • C-Peptide ♣ :This  test can indicate how much insulin your body is producing.

(♣ Separate blog posts on these topics later.)

As Dr. Elliott P. Joslin, (who was the first doctor in the United States to specialize in diabetes and the founder of Joslin Diabetes Center) wrote “ . . . unless the physician takes care, he will fall into schematic ways and forget that it is the patient who comes for treatment and not the diabetes. Each is a case unto itself.” 

 

REFERENCES

Mohan V, Usha S, Uma R. Screening for gestational diabetes in India: Where do we stand? Journal of Postgraduate Medicine. 2015;61(3):151-154. doi:10.4103/0022-3859.159302.
Goueslard, Karine, et al. "Early cardiovascular events in women with a history of gestational diabetes mellitus." Cardiovascular diabetology 15.1 (2016): 15.
Leslie, R. David, et al. "Diabetes at the crossroads: relevance of disease classification to pathophysiology and treatment." Diabetologia 59.1 (2016): 13-20.
Brophy S, Davies H, Mannan S, Brunt H, Williams R. Interventions for latent autoimmune diabetes (LADA) in adults. Cochrane Database of Systematic Reviews 2011, Issue 9. Art. No.: CD006165. DOI: 10.1002/14651858.CD006165.pub3.

PREDICTIVE AUTOANTIBODIES—YOU MAY HAVE AN AUTOIMMUNE DISEASE AND NOT KNOW IT!

Read in 5 minutes

Any disease condition is a continuum. This means that you do not move from being well to having a disease overnight. Just as in Type 2 Diabetes, where you may have dysregulated blood sugar levels (Dysglycemia) many years before you develop the disease, so it is with many autoimmune conditions. You may have autoantibodies in your blood many years before developing the disease. Despite recent advances in treatment, there is a large percentage of people in whom long-term remission of the autoimmune disease cannot be achieved. This leads to poor quality of life and sometimes an early death. As this oft-quoted Benjamin Franklin axiom says “an ounce of prevention is worth a pound of cure”. Several scientific studies in the last few years have shown that you may have tell-tale evidence in your body 5-14 years before developing an autoimmune disease. An autoimmune condition develops when there is an interaction between your genes, an environmental trigger, your immune system and intestinal permeability. Your genes are present from birth but you do not develop an autoimmune disease until later. So what happens? In any autoimmune disease like it is in any other disease, it is an interaction between your genes and the environment that decides your health. As Dr. Eric Topol, a world-renowned cardiologist, geneticist, digital health pioneer, and medical innovator, says,“healthy aging is 100 percent due to genetics and 100 percent due to your environment”.

Autoimmune conditions develop when your immune system makes antibodies against your own tissue ( Autoimmunity).  This can lead to your healthy tissue losing their ability to function normally. For example, in Type 1 Diabetes, your own body makes antibodies against your own pancreatic cells which produce insulin. Insulin is the hormone that keeps your blood sugar in balance. The other, commoner diabetes is Type 2 Diabetes, in which antibodies to pancreatic tissue is not usually present. (Incidentally, these autoantibodies to pancreatic tissue have been found in about 5% of people otherwise diagnosed as Type 2 Diabetes.Watch for post on LADA , Latent Autoimmune Diabetes of the Adult).

In fact, a new staging approach is being used in Type 1 Diabetes taking into consideration the number of autoantibodies present. The staging starts well before the disease develops. This approach is used to prevent or delay the onset of the disease. Perhaps you can start prevention in your child when you are pregnant! Studies have shown the connection between vitamin D deficiency in mothers and autoimmunity in children.

Rheumatoid Arthritis (RA): RA is an autoimmune disease affecting joints, which is characterized by chronic inflammation, causing pain and stiffness in the joints and a poor quality of life. Half of the patients with RA already have X-ray evidence of joint damage at the time of diagnosis. Like most diseases, RA can be treated better if diagnosed early. Therefore, the ability to predict the disease before joint damage occurs will contribute to a better quality of life.

WHO SHOULD BE TESTED FOR AUTOANTIBODIES?

  • Anyone who has a diagnosed autoimmune condition. Studies have shown that if you have one autoimmune disease, the chances of your developing another one are much higher than in the general population.
  • To test for disease progression in people with autoimmune diseases.
  • Anyone with hypothyroidism who has never been tested for thyroid antibodies.
  • First degree relatives (a person’s parent, sibling or child) of people with an autoimmune condition.
  • Patients with painful and stiff joints who haven’t received a definitive diagnosis of RA yet.
  • Anyone interested in better health.

WHAT TESTS SHOULD YOU DO?

A complete workup is very important. However, the following must be included.

  • C-Reactive Protein: This is a marker of inflammation.
  • Vitamin D3 levels: Vitamin D has a major role in your immune system. Low levels of this vitamin have been associated with increased risk of autoimmune diseases. (Vitamin D)
  • Antibodies: This list increases by the day. There are some specialized tests available in some countries which I have not listed here. (For those of you interested in the detailed medical information, please read the article in Autoimmunity reviews6 (2015) Damoiseaux, Jan, et al.).

This table has a short list:

                      ANTIBODY              AUTOIMMUNE CONDITION
ANA Lupus, Scleroderma, Autoimmune Hepatitis, Sjogren’s Disease, Polymyositis, Dermatomyositis, Mixed Connective Tissue Disease, Juvenile Arthritis, Drug-induced Lupus.
Anti-Cyclic Citrullinated Peptide (Anti CCP) Rheumatoid Arthritis
Anti TPO & Anti Thyroglobulin Hashimoto’s Thyroiditis
Anti TSH Receptor Graves’ Disease
Anti-tissue transglutaminase (tTG) antibodies

Endomysial antibodies (EMA)

Deamidated gliadin peptide (DGP) antibodies

(IgA & IgG tests)

Celiac Disease

 

 

Islet Cell Cytoplasmic Autoantibodies (ICA) & Glutamic Acid Decarboxylase Autoantibodies (GADA) Type 1 Diabetes, Late Autoimmune Diabetes of the Adult(LADA).

WHAT IS THE DIFFERENT ABOUT THE FUNCTIONAL AND METABOLIC MEDICINE APPROACH?

Fig 1: Functional & Metabolic Medicine approach versus Conventional Approach:Fork in the road.

Slide1
Fig 1

WHAT SHOULD YOU DO?

  • Meet a practitioner who understands the Functional & Metabolic Medicine approach to autoimmunity. There are no pharmaceutical drugs that can be used to prevent autoimmune diseases before they develop.
  • Stop smoking (Easier said than done!). Exposure to cigarette smoke has been associated with higher risk of Rheumatoid Arthritis in those susceptible to it.
  • Reduce toxic exposure.
  • Reduce inflammation.
  • Manage stress.
  • Maintain adequate Vitamin D3 levels (Vitamin D)

REFERENCES

  • Avouac, Jérôme, Laure Gossec, and Maxime Dougados. “Diagnostic and predictive value of anti-cyclic citrullinated protein antibodies in rheumatoid arthritis: a systematic literature review.” Annals of the rheumatic diseases7 (2006): 845-851.
  • Catrina, Anca I., et al. “Lungs, joints and immunity against citrullinated proteins in rheumatoid arthritis.” Nature Reviews Rheumatology 11 (2014): 645-653.
  • Damoiseaux, Jan, et al. “Autoantibodies 2015: From diagnostic biomarkers toward prediction, prognosis and prevention.” Autoimmunity reviews6 (2015): 555-563.
  • Nielen, Markus MJ, et al. “Increased levels of C‐reactive protein in serum from blood donors before the onset of rheumatoid arthritis.” Arthritis & Rheumatism 8 (2004): 2423-2427.
  • Notkins, Abner Louis. “New predictors of disease.” Scientific American3 (2007): 72-79.

VITAMIN D AND AUTOIMMUNITY

Read in 5 minutes

In recent years vitamin D deficiency has become like an epidemic all over the world. Besides autoimmunity, low vitamin D is associated with many diseases like heart disease, diabetes, cancer, hypothyroidism and many more. In fact, almost every cell in your body has vitamin D receptors.

There are 2 forms of vitamin D3 that you need to keep in mind. The one that is usually tested by most practitioners is Vitamin D3. Your body has to convert Vitamin D3 to the active form 1,25 Dihydroxyvitamin D3[1,25(OH)2 D3]. Most of you are familiar with the action of vitamin D in protecting your bones and maintaining blood calcium levels—the “classical” actions of vitamin However, scientific studies in the last several years have shown that vitamin D has several other actions as well—the “non-classical” actions. These are the actions of vitamin D on bone marrow, immune system, breasts, prostate, heart, muscles and intestine. With respect to autoimmune disease, the immunomodulatory (affecting your immune system) actions of Vitamin D are very important.

Vitamin D has the effect of increasing the activity of the innate immune system while restraining the activity of the adaptive immune system. (Chapter 9). This is the reason why adequate vitamin D3 levels are important for treating and perhaps preventing autoimmune diseases. A substantial number of studies have shown an association between low vitamin D and increased incidence of autoimmune diseases like Rheumatoid Arthritis(RA), Multiple Sclerosis(MS), Psoriasis, Inflammatory Bowel Disease (IBD), Type 1 Diabetes, Sjogrens, Lupus and many more. One example that is often cited is the increasing incidence of MS as one moves away from the equator. This is thought to be related to lesser sun exposure at higher latitudes than at the equator.

1,25 DIHYDROXYVITAMIN D3.

In autoimmune conditions sometimes measuring only vitamin D3 levels may not be enough. A few scientific studies have shown that some people with autoimmune disease have high levels of 1,25 Dihydroxyvitamin D3. This is why sometimes we need to measure both the forms of vitamin D. I remember quite a few occasions when my patients (In India) have called me to say that the lab technician has informed them that “no doctor advises this (1,25 OH)2 D) test” so it is unnecessary!

WHY DO PEOPLE BECOME VITAMIN D DEFICIENT?

Humans obtain vitamin D from either food (fortified), supplements or sunlight exposure. Your blood vitamin D levels depend on several factors.

Air quality: Excessive carbon particles in air from burning of fossil fuels may reduce the amount of vitamin D producing UVB rays from reaching your exposed skin.

Skin color: People with dark skin require about 10 fold more exposure to sunlight to produce the same amount of vitamin D as people with lighter skin color.

How much of your skin is exposed? The more bare skin the bigger the surface area of absorption of sunlight.

Use of sunscreens: Though theoretically use of sun screens can block the UVB rays, rarely do people use adequate quantities of sunscreen to bar all UVB from reaching their skin.

Gut Health: If you have unhealthy gut or you have inflammatory bowel disease (IBD), your absorption of vitamin D from supplements is poor.

Liver and Kidney Health: Some types of liver disease may affect bile production. This can affect vitamin D function. In chronic kidney disease (CKD) the vital step of conversion of vitamin D to its active form is affected and this can lead to severe vitamin D deficiency. This is why patients with CKD have their 1,25 Dihydroxyvitamin D3 measured regularly.

Vitamin D receptor (VDR): If you have a genetic variation in VDR you may need a higher dose of vitamin D supplementation.

How much vitamin D3 you take will decide your blood levels of the vitamin. Very low or very high doses, may both be detrimental unless you monitor regularly.

HOW MUCH VITAMIN D SHOULD YOU TAKE AS A SUPPLEMENT?

How much supplementation of vitamin D you need depends on what your blood reports show. It may not be the same dose for everyone because of individual variations. However, it is a much better idea to take a smaller dose (4000-5000 IU) every day rather than a very high dose once a week or once a month. Sometimes a larger dose may be necessary for a short period of time until your blood levels are in the optimal range.

Ideally you should get your vitamin D from sensible sun exposure AND supplementation.

 WHAT IS MOST IMPORTANT ABOUT VITAMIN D AND AUTOIMMUNE CONDITIONS?

Low vitamin D levels have been associated with many autoimmune conditions like

Rheumatoid Arthritis (RA), Multiple Sclerosis(MS), Psoriasis, Inflammatory Bowel Disease (IBD), Type 1 Diabetes, Sjogrens, Lupus and many more. This is because vitamin D affects your immune system function.

Maintaining adequate vitamin D levels may be a major way to prevent developing autoimmune disease. In fact, studies have shown that maintaining adequate vitamin D levels during childhood can prevent the development of Type 1 Diabetes by 29%! This is true for several other autoimmune conditions as well.

If you already have an autoimmune condition maintaining adequate vitamin D levels will make a major difference to how you heal the disease.

Some of you  may need to measure both vitamin D3 and 1,25 Dihydroxyvitamin D3.

AUTOIMMUNITY: A FUNCTIONAL & METABOLIC MEDICINE PERSPECTIVE

Read in 3 minutes

Worldwide there is an unprecedented rise in autoimmune conditions. Did you know that you may have autoimmune antibodies in your blood many years before you develop the disease? Studies have shown that Thyroid Antibodies or Antibodies for Lupus or Rheumatoid Arthritis, Type 1 Diabetes (and many more) may be present in your blood 4 to 15 years before you develop the disease! 

There are about 80 different autoimmune conditions and they are all potentially serious chronic diseases. All of them involve an underlying problem with your immune system. You need your immune system to work well because it protects you from outside invaders. Your immune system tries to protect you by identifying, killing and eliminating invaders that may harm you. Sometimes problems with your immune system can cause it to mistake your own healthy tissue as harmful and attempt to repeatedly attack and destroy them. This is when you develop an autoimmune condition. “Autoimmunity “means immunity against the self.

Your body is combating something-an infection or toxin or allergen or dysregulated stress response and somehow that immune response gets misdirected to your thyroid tissue, nerve layer, skin, kidneys or even the whole body. Your immune system is very highly developed. Therefore, why should it get confused between friend and foe? One possible explanation is molecular mimicry, where your own tissue seems similar to an invader, either structurally or immunologically. Another explanation is “bystander activation”, where your own tissue is destroyed as collateral damage because your immune system is dealing with an infection or inflammation. The underlying dysfunction common to all autoimmune conditions is chronic inflammation.

Different autoimmune conditions affect different organs or organ systems. For example in Hashimoto’s your immune system makes antibodies against your thyroid tissue, in Multiple Sclerosis (MS) your immune system attacks myelin which is a fatty layer that wraps around your nerve fibers ,in Rheumatoid Arthritis (RA) it is the lining of your joints that are attacked. Some conditions like Systemic Lupus Erythematosus (SLE) or lupus, the skin, joints, kidneys or brain may be affected. Depending on which autoimmune condition you have, you will meet different specialists. For example, if you have MS you will meet a Neurologist, RA or SLE a Rheumatologist, Psoriasis a Dermatologist and so on. But as Dr.Yehuda Shoenfeld,Professor of Medicine at Tel Aviv University in Israel, says there should be a separate specialty of Autoimmunology.

Conventional treatment of autoimmune conditions may sometimes make you feel worse. Many of these drugs have serious side effects. However, when used judiciously these drugs can be life changing. But these potentially toxic drugs when used alone, are not a long-term solution. These drugs can temporarily take care of the inflammation while we treat the actual causes of the disease.

WHAT IS DIFFERENT ABOUT THE FUNCTIONAL AND METABOLIC MEDICINE APPROACH?

We know that the following factors influence autoimmune disease:

  • Genes
  • Immune System
  • Environmental Triggers like gluten (Celiac Disease), bacteria, viruses.
  • Intestinal Permeability.
  • Gut Dysbiosis
  • Chronic Inflammation
  • Metal Toxicities like Mercury, Lead, Arsenic.
  • Environmental Pollutants like Persistent Organic Pollutants (POP), Bisphenol-A.
  • Stress (HPA axis Dysfunction)
  • Food Sensitivities
  • Hormonal Imbalance.
  • Vitamin D Deficiency
  • Low Antioxidant Reserve
  • Insufficient Sleep

In the next few posts I will talk about these topics. Meanwhile,

HERE ARE A FEW THINGS THAT YOU CAN DO:

  • Reduce your toxic exposure. Stop using plastic food & water containers. Check your cosmetics & household cleaning products for possible harmful substances. A good place to check is the Environmental Working Group’s website (ewg.org)
  • Eat plenty of fresh vegetables and some fruit.
  • Eat plenty of dark leafy greens.
  • Stop sugar. Sugar causes inflammation.
  • Stop eating processed food.
  • Manage Stress
  • Sleep!