This blog post, originally posted on Tu Diabetes, is so important, I asked Melitta if she would guest post here with the same article…. Susi

We Need a Detective in the House: Medical Misdiagnosis of Insulin-Deficient Diabetes

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. Please leave a comment here.

Credit: I’d like to thank April (Anni), BSC (Brian), Brande, and Natalie for their assistance with this blog.
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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 $471.
(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.

Are you asking what a rage bolus is?

In case you are, it’s the act of giving insulin, often much more than you need, when you’re really angry at a high glucose reading that you can’t immediately explain, or one that refuses to come down.

If you read any diabetes blog or forum enough, or have it yourself, you’ll know that for many people with diabetes, in all its incarnations, it’s a 24 hour job to look after it. Yes, even when you’re sleeping you have to make sure before you rest your weary head, that you have calculated and mashed together, to the best of your ability, food, insulin, activity, stress and more, so that your blood glucose won’t go low or high overnight.

There are very few things in life that you can’t take a break from – even for one day, let alone a week or two of blissful holiday. Diabetes is with you 24 hours a day and it has to be managed 24 hours a day.

So now and then I get cranky with it. Even though I know a lot of the science, on occasion, diabetes doesn’t behave as expected.

I probably under report every last bit of the bad stuff here on this blog, but tonight I’m sorely tempted to put some very raw feelings on the screen.

It’s more than annoyance and less than outright anger – somewhere in between. Let’s see if I can contain myself.

Here’s the scenario:

Dinner: BBQ
Food: Hungarian cabbage salad (oil, vinegar and a tiny bit of Splenda – a scant teaspoon for a whole cabbage), steak, tomato, cucumber, avocado – just with salt, half a corn cob (as a treat) with some butter.
Drink: Water and some diet mineral water.

Easy to bolus for? Supposedly! On paper, other than the corn, it’s lowish carb. I’ve bolused for this kind of dinner a gazillion times and been fine. Hadn’t eaten for many hours before.

I calculated about 30gr carbs, figuring that I would probably have maybe 1.5 loosely packed cups of cabbage salad (I could eat that stuff all day long!), half a tomato, the half cob of corn (definitely not low-carb), 3 slices cucumber, plus I also bolus for protein and fat and a few extra carbs for the diet soda (the one I drink has 3g carbs per glass). It would easily be way less “carbs” if I didn’t add in 50% of the protein and 10% of the fat (TAG bolusing).

My BG was were I expect it to be when I’m not eating – perfect. Total already bolused for today 20gr carbs. Am happy with that.

I entered the carbs into my pump, went for a combo bolus of 2 hours (very thick steak with fat) and thoroughly enjoyed my dinner, with the steak rested well before I started eating.

I really thought I did everything right. Apparently not…

At 2 hours I checked my BG and it was fine – just inside normal and the combo bolus was just ending so the insulin should still be working and keep working for another 2-3 hours as the rest of my dinner hit my bloodstream.

At 4 hours I should have stayed within normal range yet I was way higher, totally on the wrong side of normal. Not too much but enough to make me cranky. Diabetes you are not behaving tonight!

Did I underestimate the carbs? I didn’t think so but I probably did – it was probably the steak that I didn’t calculate properly. I thought I did a small overestimate on the total I should bolus for, but thinking about it and checking some nutrition info, I’ve probably under-bolused for the steak.

Insert expletives, because I don’t want more fat-promoting insulin. More expletives because I must have screwed up. More expletives because I don’t want to be dealing with this right now. Rage bolus coming up!

At midnight, my angry fingers dialled up more than what my pump suggested.

Two hours later (2am) and I was back inside normal but not where I usually am. Technically I should have gone low.

Hmmm… more expletives. Another rage bolus, but this time more rage than bolus. It’s now 3am and I’ve stayed exactly what I was at 2am! What the bleep?

So what is it? Insulin not working? Pump site not behaving (it’s behaved fine the last 48 hours)? Total screw up on the carbs and how long they would take to hit my bloodstream?

It’s easily 7 hours since I’ve eaten. Seven hours for a steak to keep working? I’m not so sure about that but in case it is… holy cow (pun intended)!

So now I’m faced with changing out my pump site and going to bed. Never a good idea! It’s much better if you hang around awake to make sure the site is working and that you have a stable blood glucose before you hit the pillow. Or do I have another rage bolus? Maybe it was all that swearing that caused the stress that caused the BG to stay up. We all know how the just the tiniest amount of stress sets me off.

Don’t know what I’m going to do yet. I still have hope that all the insulin I’ve taken will do its job or the dinner I had won’t keep repeating the BGs I don’t want!

In Ginger Vieira’s dLife vlog today, she talks about treating hypos – low blood glucose.

There are a wide range of symptoms that signal a hypo and also a wide range of what people use to treat. The goal, of course, is to bring your blood glucose back into normal range. That can sometimes be tricky.

Some people have early warning of a hypo, some don’t. It waxes and wanes for some people, as it does for me. Sometimes I can feel a hypo coming on, sometimes I just have vague feeling I should test, and sometimes, I don’t know until my blood glucose numbers have gone way below the threshold.

Lately, the only warning I get is that my eyes go strange – almost exactly like the beginning of a classic migraine with aura, just before the aura starts properly. They both start the same way for me. You’d think after all this time, I’d recognise the difference, and there is one.

The migraine takes only a minute or three to go into full-blown aura with technicolour snakes and quivering harbour bridges in all colours of the rainbow. It’s unmistakeable! I get that for exactly 25 minutes (that has never varied in 35 yrs) and then sometimes if I’m lucky and treat with some caffeine or aspirin, I just get a vague headache, or sometimes it’s a bad headache. It’s no big deal, I’ve had them all my life, and the really brain-crashing headaches I had when I was younger, are extremely rare these days. But the start of a migraine… the aura… I get often.

The hypo just stays as large blind spots for me, which get bigger.

Often I sit there waiting for a migraine aura to develop. Often it doesn’t and I wonder whether I’ve just caught the migraine really early. I’m learning that these are tricks my brain is playing on me and that I should test.

I sat there for a full 10 minutes the other day, blind and blurry spots all over the place and it didn’t occur to me to test! I just sat there like a goose, waiting!

When I finally did test and I was 3.1 mmoL/l (55 mg/dl) – no shaking, no hunger, no other symptoms. Not too bad, but imagine if I’d have sat there for another 10 or 20 minutes!

Something Ginger talks about is not over-trating a low. Quite rightly, she points out how difficult it is sometimes not to listen to your brain that is often screaming for you to eat everything in sight. That doesn’t happen to me often, but it has happened a few times… a few times too many with not unexpected results which I have to treat with more insulin.

The experts say that if you no longer have hypo symptoms, that you should run your blood glucose a little higher for a few days. How high, I’m not sure, but I’m not altogether convinced it’s sage advice if you’re supposed to run them way above normal. And doing that, apparently (from the blogs and forums I read), doesn’t work all the time.

I guess one answer is to test, test. We’re told to do that anyway. The other way to minimise hypos is not to contribute to wild swings in blood glucose. Dr Richard Bernstein alludes to this in his advice that if you’re not loading yourself up with tons of carbs, you’re not having to inject huge doses of insulin. Bernstein talks about ‘the Law of Insulin Absorption” too.

It goes like this: “When you inject insulin, not all of it reaches your bloodstream. Research has shown that there’s a level of uncertainty as to just how much absorption of insulin takes place. The more insulin you use, the greater the level of uncertainty.” And this, ” Say you do inject 20 units of insulin at one time. Each unit lowers the blood sugar of a typical 150-pound adult by 40 mg/dl. A 29 percent variability will create a 7-unit discrepancy in your 20-unit injection, which means a 280 mg/dl blood sugar uncertainty (40 mg/dl x 7 units). The result is totally haphazard blood sugars and complete unpredictability, just by virtue of the different amounts of insulin absorption.” ¹

It also makes sense that if you have lots of hypos and you are eating lots of carbs but injecting the supposedly right amount of insulin, lowering your carb intake is one step to getting more predictability. If you eat less carbs, you’re injecting less insulin. Less room for error too. I certainly subscribe to this notion and have proven it works for me. I get much better predictability of insulin and less high/low swings if I keep to lower carbs. Certainly I get hypos, but about 80-90% of them are from activity I didn’t anticipate. The rest are mostly from bad carb guessing when I’m eating out or when the carbs on the packet are either wrong or don’t exist at all. The occasional one happens when I don’t eat as much as I’ve put on the plate and I haven’t eaten quite enough for the insulin I’ve taken.

When it comes to hypos, not over-treating them is the key to normalising your blood glucose rather than having a huge swing to high.

Here are a few things I’ve learned…

How I treat my hypo totally depends on what else is going on. If I have some bolus insulin still working, I will look how much (my pump will tell me) and work out how much further it will drop me. Then I have a fast acting carb – glucose tabs, juice, or jelly beans, plus maybe half a sandwich or a 10 gram cracker, without bolusing for either.

The big tip that Ginger talks about is using food or drinks that you don’t particularly love, so you help remove the temptation to over treat. I really hate those sour glucose tablets. I can barely get through one of them. So, that’s what I keep in my bag. I do love the orange flavoured BD Glucose tabs you can get in Australia, but really, I can eat 2 (10g) or 3 (15g) and I can’t love yet one more.

If I have no bolus insulin working and I have done no exercise that would keep dropping me (and don’t anticipate any immediate activity), I take only enough fast acting hypo remedy to put me back to about the middle range of normal. That’s often not the 15 grams of carb recommended. It might just be 10.

The temptation to do more than this is overpowering. When your brain tells you to eat everything you can find, it’s powerful. You win some, you lose some. If  I’ve over-treated (and I’m sure everyone does this from time to time), I will have some bolus insulin, even though I’ve begun low. Any carb that will take me over where I want to be with blood glucose, gets some insulin for just that part.

I’ve had that feeling – eat or you’ll die. No amount of trying to be logical makes the feeling go away, but using food/drink that you don’t usually crave can help.

So often when you’re going hypo, your brain doesn’t cooperate! I’ve had hypos where I didn’t remember what I was supposed to do! Eventually it clicks, but that initial feeling can be very disconcerting. I’ve heard stories where people have continued not to know what to do – it’s quite common. Famous last words, that it hasn’t happened to me… yet.

What’s right for me, isn’t right for everyone else, but what we all try to aim for is not to over treat. The longer I’ve been on insulin, the less nervous it makes me treating hypos and I can somewhat curb the feeling that I have to eat like mad or something bad will happen. There’s some confidence that came for me with treating hypos successfully. The more I did it, the more my brain told me that ‘this much’ is all I need to consume. The earlier you catch a hypo, the better, I believe. Your brain is still functioning reasonably well at that level.

It’s a bit like ‘feel the fear and do it anyway’ – not consuming more than you need to get your blood glucose back into normal range. Very hard sometimes! Easy other times!