I was always fond of Miss Marple, mystery writer Agatha Christie’s intuitive and no-nonsense sleuth. I loved the Nancy Drew and Hardy Boys series when I was growing up. Where are they when we need them? Oh, right, they were fictional characters. What we diabetics(Footnote 1) need, especially those of us who don’t fit the big two obvious categories (rapid onset in childhood = Type 1 diabetes; insulin resistance in adulthood = Type 2 diabetes), is a ruthless detective medical doctor, who investigates and will not stop until the doctor-detective has the patient’s correct diagnosis. In this blog, I address insulin-deficient diabetes, and I want to point out that the disease is the enemy, not the person with diabetes. Fundamentally, people with diabetes deserve a correct diagnosis and treatment.
Sixteen years ago, in 1995, I was misdiagnosed as having Type 2 diabetes, when I actually have Type 1 autoimmune diabetes. As a 35-year-old adult at diagnosis, I didn’t fit the myth/profile of childhood diabetes—it is amazing that I survived the near-death experience of misdiagnosis. Sadly, not much has changed since 1995 and misdiagnosis is still extremely common today, in spite of having diagnostic tests available that can assist with obtaining a correct diagnosis.
Here I will address three categories of insulin-deficient diabetes: 1) autoimmune diabetes, 2) idiopathic Type 1 diabetes (including Type 1b), and 3) monogenic diabetes or MODY. These can occur at any age, from early childhood to elderly adulthood.
Autoimmune Diabetes: Type 1 autoimmune diabetes is actually a no-brainer diagnosis, which makes it even more shocking that misdiagnosis happens so frequently—if a person meets the criteria for a diagnosis of diabetes (fasting blood glucose greater than 125 mg/dl) and is antibody positive (glutamic acid decarboxylase antibodies (GADA), islet cell antibodies (ICA), and/or insulinoma-associated (IA-2) autoantibodies), he/she has Type 1a diabetes. Type 1 autoimmune diabetes is more common in Caucasians, particularly those of Scandinavian descent. About 10% of Caucasian women who are diagnosed with gestational diabetes have autoimmune gestational diabetes, or Type 1 diabetes that is “unmasked” by pregnancy(Footnote 2). Although the myth that Type 1 diabetes is a childhood disease persists, in fact adult-onset Type 1 diabetes represents more than 75% of all Type 1 diabetes(Footnote 3). In populations of people who have been given the diagnosis of Type 2 diabetes, between 10 and 20% of those “Type 2” diabetics are antibody-positive, have been misdiagnosed, and in fact have Type 1 autoimmune diabetes(Footnote 4). The problem is that too few physicians are willing to perform the antibody testing, despite its low cost(Footnote 5). Very recently, the expert panel on diabetes mellitus laboratory testing stated that islet cell autoantibody testing may be used for classification of diabetes in adults(Footnote 6) (for example, differentiating between Type 1 autoimmune diabetes and Type 2 diabetes). Although rare, some people with adult-onset Type 1 diabetes who were misdiagnosed as having Type 2 diabetes have died because they were denied insulin and given treatment for the wrong disease. A far more common outcome of misdiagnosis is earlier onset of complications, which could be avoided if all people with Type 1 autoimmune diabetes are correctly diagnosed and put on exogenous insulin/tight control as soon as possible. Dr. David Bell suggests that islet cell autoantibody testing assists with identifying the type of diabetes, guiding the clinician to appropriate treatment with insulin, avoiding a period of poor glycemic control when oral therapy is failing, optimizing the potential for preservation of beta cell function, and maximizing the prevention of long-term complications of diabetes(Footnote 7).
Idiopathic Type 1 Diabetes: About 10-15% of people diagnosed with Type 1 diabetes are antibody negative (GAD, ICA, IA-2), and they are labeled “idiopathic Type 1 diabetes.” A relatively new form of testing, islet reactive T-cell responses using cellular immunoblotting, identifies some of these cases of idiopathic Type 1 diabetes. Once again, doctors make a diagnosis based on age not etiology—children who are islet reactive T cell positive have “idiopathic Type 1 diabetes” but adults who are islet reactive T cell positive are given the label “Type 2 diabetes.” “Diagnosis” is based on age not etiology or use of evidence-based medicine. Finally, some subjects in a recent study documenting the presence of islet reactive T-cell responses were both antibody positive (islet cell antibody, GADA, insulin autoantibody, insulinoma-associated protein-2 autoantibody, and/or zinc transporter autoantibody) and islet reactive T cell positive(Footnote 8).
Also included in the category of “idiopathic Type 1 diabetes” is Type 1b diabetes. The Children with Diabetes website describes Type 1b as follows: “Some of these patients have permanent insulin deficiency and are prone to ketoacidosis but have no evidence of autoimmunity. Although only a minority of patients with Type 1 diabetes fall into this category, of those who do, most are of African, Hispanic, or Asian origin. Individuals with this form of diabetes suffer from episodic ketoacidosis and exhibit varying degrees of insulin deficiency between episodes. This form of diabetes is strongly inherited, lacks immunological evidence for beta cell autoimmunity, and is not HLA associated. An absolute requirement for insulin replacement therapy in affected patients may come and go.” Michael Barker here on TuDiabetes writes about Type 1b diabetes as ketosis-prone Type 2 diabetes or rapid-onset Type 2 diabetes with remission.
MODY: So in this medical mystery of “what is not insulin-resistant diabetes,” autoimmune diabetes is the easy case to solve. More difficult is monogenic diabetes or Maturity Onset Diabetes of the Young (MODY), which is diabetes caused by genetic mutation. MODY represents about 5% of all cases of diabetes; however, that may be an underestimate because testing for MODY is so rarely performed. The University of Chicago Kovler Diabetes Center says, “MODY can be caused by mutations in at least six (Footnote 9) different genes and each mutated gene results in a slightly different type of diabetes. MODY can occur in childhood or adulthood and can be misdiagnosed as type 1 or type 2 diabetes. However, there may be clues that suggest someone has MODY-type diabetes rather than type 1 or type 2 diabetes. These include a lack of autoantibodies in a presumed diagnosis of type 1 diabetes or a diagnosis of type 2 diabetes in someone who is not overweight or three or more consecutive generations of family members with a diagnosis of diabetes.” From the Athena Diagnostics website (Footnote 10): “An estimated 5% of all cases of diabetes mellitus in the United States are due to autosomal dominant loss-of-function mutations in any one of at least six different genes. Such autosomal dominant diabetes is generally known as MODY, or maturity-onset diabetes of the young, because differential diagnosis based on clinical presentation is only possible in young, non-obese individuals. However, MODY can occur at any age and results in a limited capacity of the pancreas to release insulin, rather than by the insulin resistance typical of type 2 diabetes. Treatment and clinical outlook for MODY depends on the exact genetic cause and may differ greatly from those of type 1 and type 2 diabetes. While one subtype (MODY2) can generally be managed by diet and exercise alone, others (MODY1, 3, and 4) are highly responsive to sulfonylurea therapy; yet another (MODY5) may require treatment for multiple organ abnormalities. Genetic testing for MODY helps diagnose the exact subtype in about 85% of all cases.” MODY information and testing is also available at the Diabetes Research department and the Centre for Molecular Genetics at the Peninsula Medical School and Royal Devon and Exeter Hospital, Exeter, United Kingdom (www.diabetesgenes.org). Many TuDiabetes members who may have MODY have found that a low-carbohydrate diet is essential to good blood sugar control.
In the United States, a medical doctor faces no repercussions if he/she misdiagnoses an insulin-deficient diabetic and gives inappropriate or substandard treatment. The governing bodies (the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus; the American Association of Clinical Endocrinologists) describe the different diseases that fall under the umbrella term “diabetes,” but they do not identify any protocols for differentiating amongst the different diseases. So there is no requirement to diagnose, classify, and appropriately treat the different diseases that fall under the term “diabetes.” If there were a standard or guideline, doctors would be held accountable to the minimum standard of care: anything less would be malpractice. From my perspective, the lack of guidelines appears to be about limiting medical liability, not about enhancing patient care.
In closing, I hope this helps shed light on insulin-deficient diabetes, and I truly hope that this helps those who may have been misdiagnosed. Finally, I would be grateful for input and feedback.
Credit: I’d like to thank April (Anni), BSC (Brian), Brande, and Natalie for their assistance with this blog.
FOOTNOTES
(1)Or persons with diabetes (PWDs)
(2)See my blog, Autoimmune Gestational Diabetes. TuD member Kelly, who was diagnosed with GDM and later found to have Type 1 autoimmune diabetes, suggests signs of autoimmune GDM are being diagnosed under the age of 30, having no or little family history of Type 2 diabetes, and being diagnosed (or testing positive for sugar in urine tests) before 25 weeks gestation.
(3)Adult-onset Type 1 diabetes can be rapid-onset, which is what I experienced, or slow-onset, sometimes called Latent Autoimmune Diabetes in Adults (LADA). It’s all autoimmune diabetes, or diabetes caused by immune-mediated destruction of the pancreatic beta cells. Adult-onset Type 1 diabetes is two to three times more common than childhood-onset Type 1 diabetes (Type 1 Diabetes in Adults: Principles and Practice (Informa Healthcare, 2008, p. 27).
(4)Irl Hirsch M.D., “Type 1-and-Change Diabetes,” Clinical Diabetes, 1999.
(5)The out-of-pocket maximum cost is approximately $750.
(6)“Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus” (Diabetes Care, June 2011) (link to Diabetes Care).
(7)Endocrine Practice, March/April 2000.
(8)Identification of Autoantibody-Negative Autoimmune Type 2 Diabetic Patients (Diabetes Care, January 2011).
(9)Eight, according to “Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus” (Diabetes Care, June 2011).
(10)Athena is a division of Quest Diagnostics. Athena’s (test #844) discounted cost of MODY genetic testing is $1700.
Hi Melitta! As you know, I have a vested interest in this subject. In my humble opinion, your blog is exceptionally well written, easy to read, you have references (and no wild claims), and clearly, it addresses the issues of misdiagnosis along with its implications of inadequate care.
I hope this problem, and particularly your blog makes a wider round than just on TuDiabetes. Thank you for being so proactive in the cause! Your story mirrors so many of ours, yet I shudder to think how many more are out there who have no idea and are being strung along by an inadequate system.
I wholeheartedly encourage you to do more articles/blog posts. If you make just one more patient and just one more doctor aware, it can surely save one life if not many more!
Great article. Now if all doctors could be on board!
Great write-up Melitta. I think this is an important topic. Often as patients, our doctors jump to conclusions, assuming that a patient is type 2. Every adult in the US over 30 years of age who arrives at their doctors office with an elevated blood sugar is probably carrying a few extra pounds. Assuming they are type 2 is fine, but all to often no effort is made to confirm the diagnosis and if treatment fails, doctors are all too quick to “blame” the patient for not following their diet or exercising. That is just wrong.
What you didn’t mention is that often type 2 patients are insulin deficient. DeFronzo (1) notes that patients have an impaired glucose tolerance and are > 200 mg/dl 2hrs after a meal, have already list 80% of their beta-cell function. This means that for the most part, it is impossible, without proper tests, for a clinician to differentiate a type 1 from a type 2 until the condition has gotten “really, really bad.” I had one doctor tell me that autoimmune T1 was only diagnosed in the Emergency Room, and in fact talking with her, it was clear that she never ordered the right diagnostic tests or referred patients to an endo, so all her new T1 patients actually did present in the ER.
So as a patient, we have to be careful and demanding. We have a right to ask for proper diagnosis, the right tests. If our treatments do not work, if we do not respond to medications, that is a huge “red flag.” Don’t let a doctor pass of the problem to you as a patient, blaming you for not eating properly or exercising or not taking your medication. Ask the right questions of your doctor and help them understand that proper diagnosis and treatment can make a huge difference in outcomes. .
Melitta:
You have done a terrific job! I thank you for taking on this complex and difficult subject for everyone on this site! I especially appreciate your clarifying the fact that MODY can, indeed, be dx’d at ANY age. Most web-sites incorrectly cite a maximum age (I have seen it as low as25 and as high as 50). In any event…thank you for this great write up!
Hi Melitta. I’ve recently become aware of another “type” of Diabetes, without a name as far as I know. I’m referring to the situation when a person’s beta cells die out because of old age; no autoimmunity or lack of insulin sensitivity involved. I googled Geriatric Diabetes and did not see a description of this problem. My impulse is to think of taking insulin. Does anyone else know anything about this “type” of Diabetes?
Responding to April’s comment, both the Kovler Diabetes Center and the Athena websites make it clear that MODY can be diagnosed at any age. MODY and Type 1 diabetes have similar mythology, that they are childhood diseases. Not true! Those myths lead to a lot of misdiagnoses.
Trudy, in all my reading I have not heard of the situation when a person’s beta cells die out due to old age, but I will see if I can find anything for you.
Thank you for your very interesting article. It makes me very sad that there is such a huuuuuuuge lag between the research and what some doctors do to “treat” their diabetic patients.
I had to fight to get Novolog and it’s the only way I got down from an A1C of 10.6 to an A1C of 7.4 (and dropping) – along with carb restriction and walking. I’d probably still be in the 9 - 10 range without the wise counsel I’ve received from other diabetics on TuD.
We shouldn’t have to fight our doctors to get them to help us figure all this out.
Wow, I feel so lucky that I was correctly diagnosed with LADA right away - partly because I asked for antibody testing after reading Melitta’s previous posts (and my dr readily agreed). Because of your posts, I knew to push for insulin when my blood sugar started to rise, rather than take the amaryl my dr wanted to prescribe (starting insulin on Fri!). Thank you for taking the time to research and share this information; taking control before my blood sugar gets way out of hand will make all the difference in maintaining my good health for years to come. You’re a lifesaver!
What an excellent post. Great job, Melitta!
Great job!! I was also misdiagnosed in the E.R. at 36 years old (Oct.2010). Thankfully I followed up with a great Endo the next day and he knew this was wrong and started me on insulin that day. Great information!!
Very informative! Thanks, Melitta!
I agree whole-heartedly with the othere posters Melitta, job terrifically well-done!! Clearly written & easy to follow, reading it was like food for my soul. 
Thank you so much for taking the time!!
We, my wife the RN and I had to FORCE the Endo to do antibody testing, then to save face, he sent me the results in a LETTER. This is how I found out in the first 5 weeks that I was a type 1. Now the Endo has compounded his original misdiagnosis by NOT starting me on Insulin for 15 months. Thank goodness I finally stumbled across TU, my wife and I have made an appointment to get a second opinion with a younger Endo in the next town over. The more of the blogs comments and forums I read here the madder I become. I feel awful and am swinging from high to low all day as I am still making some insulin. I am eating like a bird and constantly exercising because this is the only thing that keeps my BG's in check. I am fed up and wish that I would have been prescribed Insulin right away instead of Metformin and Byetta, perhaps I would have been able to protect/prolong the life of a few more of the few Beta cells I have left.
Michael
Thanks for another wonderful and informative blog Melitta!