Exeter and Kovler are wholly on the same page that MODY2 doesn't warrant treatment, full stop. MODY2ers can of course develop classic Type 2 diabetes, or for that matter Type 1, just like anyone else, though oddly MODY2 doesn't necessarily increase the risk of developing Type 2, which is counterintuitive. But absent that, Exeter and Kovler, on the basis of a fair bit of empirical work, currently think you're wasting your time trying to treat MODY2 (in part because it's not very treatable, i.e. good luck budging your A1Cs in any meaningful way if you're actually MODY2).
I'm really sympathizing with the psychological situation advice like this must be putting you in. It's a bit like having walked around with a colostomy bag for 10 years then having a doctor tell you, "meh.. you don't really need that, never really did... put it away and you'll be fine."
Not sure what I'd be thinking if I were you. If I could live a close to normal life, and have mildly elevated BG levels without much risk of it spiraling out of control I'd be the first to jump at that opportunity. RE complications--- I don't know. Neither does anyone else. I think if my A1C would stay in a normal range without meds, I'd just stop taking meds and get on with my life. There is so much more to life than worrying about blood sugar all the time. I'd have to assume having modestly elevated levels would likely ultimately shorten your life... but I'd take 75 years of actually living life to the fullest over 80 years of babysitting my BG all day every day. I'd take that choice every time if it were available to me.
I'm glad you're confident in the advice you are getting. What was your initial diagnosis and the decision to put you on insulin like for you? For me, my BG levels were wildly out of control when first discovered. I can't logically convince myself that I could stop taking insulin and not end up wildly out of control again. If you can convince yourself of that, then it sounds like it may be up to you... do you want to live the life of a diabetic, or not?
Please keep us posted in how the transition to not taking insulin goes I am very interested.
Thanks! The adjustment is hard, but even if this pans out the way I think it will, I don't regret the last dozen years at all. I especially don't regret the hard stuff. Almost dying while going severely hypoglycemic in the middle of a snowstorm on the biggest glacier in the Alps is a big part of who I am today (less so if I hadn't survived, of course--though arguably it would define me even more in that case! :)).
If I thought my decisions would shorten my life, I probably would change my mind. Keep in mind that exogenous insulin has obvious risks and almost certainly complications associated with it, too. We're doing something very crude and artificial with a delicately balanced system, it's almost implausible exogenous insulin, particularly larger doses of it, wouldn't have serious consequences.
I was randomly diagnosed, had to check my immunizations for grad school, GP ordered a physical, fasting was low-120s, glucose tolerance peaked mid-200s, A1c of 5.6 (these days it's been 5.8-6.2, it'll be fascinating to see what it is off insulin, I'm guessing low to mid-6s). Fairly soon after that I got sent to one of the top diabetes researchers in the world (architect of several of the longitudinal diabetes studies, e.g. DCCT, DPP, and others), and he was on board with aggressive treatment, so I started insulin, first basal, then bolus. We basically thought of me as LADA. He eventually handed me off to another endo because I "didn't need him anymore," and I've had various endos in various cities since, of varying quality.
Will definitely keep engaging here!
So they never antibody tested you early on? I am not sure when antibody testing arrived on the scene actually... Generally I've been dismissive of the value of antibody testing... but in your particular case it seems that a negative antibody panel 12 years ago might have changed your story quite a bit...
I'm not sure, which sounds crazy. I think there might have been one antibody test, but not a panel. The thinking was, I think, that it didn't matter much, i.e. we treated symptoms, not causes. Given how well I fit MODY-2--the Kovler people called it immediately when I contacted them--it does seem a bit odd, especially from a leading researcher. My current endo agreed antibody testing was worth it--after a dozen years my honeymoon seemed to be dragging on awfully long--I tested negative. He then agreed to pursue MODY testing, the insurance sent me a letter saying it was their policy not to cover it, but since the doctor said I needed it, no problem (very odd letter), and that's how we ended up here.
Niccolo, congratulations on your determination getting you to a correct diagnosis. I know that it doesn't answer all the questions, but good for you for perseverance. And I am sure that your journey will help others.
Thanks! Only took 13 years. :)
The degree to which we have to take responsibility for our own medical care is pretty crazy. I just emailed my endo to let him know how I was interpreting the "inconclusive" results he'd shared with me and that I'd gone off my pump. Will be interesting to see what reaction that gets.
How long have you been off your pump now? What is your BG doing? Were you diagnosed as Type 1 before? I could see a lot of endos freaking out if they got an e-mail from a "Type 1" saying they went off their pump! I hope everything works out for you - and I agree with Brian, I'd say you still belong!
12 hours off all exogenous insulin now. Ate a low-carb lunch (15g carbs) at 100, peaked at 150, stabilized at 125, ate a moderately high-carb dinner (56g carbs), peaked at 240, now dropping back down slowly. It's weird watching this on the CGM and not doing anything about it, goes against 12 years of well-honed instincts.
At this point I'm just gathering data. Even in the unlikely event that I go back on insulin, a period with these kinds of excursions shouldn't matter.
I suspect going forward I'll eat a low-ish carb diet, work daily exercise into my routine, and keep getting regular A1Cs. But for now I'm in full-blown data-gathering mode.
I've been called a type 1, 2, 1.5, and 3 over the years. I doubt the doctor will freak out, unless he forgets about my history. I'm actually new to him, so it's not totally implausible.
So what do you think would happen if you had a real major carb load? Like 200g in a meal like a âtypicalâ American. How about a supersized McValue meal with a 40oz coke? Not to imply that anyone who values their life should ever eat like that-- Iâm just curious what do you think would happen?
It's a good question to which I don't know the answer. My highest documented high ever was 325, it was not too long after diagnosis, and I tried to bolus for a small/medium bag of candy in a movie, which in retrospect was just silly. In college, I used to drink a ton of orange juice in the cafeteria, it was just something the guys all did, a row of OJ glasses across the tray. We were all super active and lean, so I guess we needed the calories, but it seems insane to me in retrospect. And by definition I've had this gene mutation since birth (and before), so I must have been hitting some pretty impressive numbers back then.
I have a feeling I have a natural ceiling in the high-200s/low-300s. If I understand the glucokinase gene mutation correctly, it basically recalibrates the glucose "thermostat" upwards, but I'm not clear on whether it also impairs it above that new threshold, my guess is yes, because it's not like after I cross the 140 or 180 thresholds my body rapidly brings me back down, it takes a while.
I suppose a stack of pancakes with syrup would be a way to test this. But I'm not particularly inclined to run the test. It does raise an interesting question, though, which is if I'm leery to spike to 300, then at what lower levels am I not leery? Because I do have the deeply ingrained idea that almost any excursion is bad.
My understanding is that the primary blood sugar regulation feature of MODY-2 is chronically high fastings which are 120-160 mg/dl and rise with age. I have also seen a number of references to an increment or delay on OGTTs as a feature which suggests that there is a different "threshold" for the response to high blood sugars. So on an OGTT (or carby meal) you would have a 2 hour that is high, but not super high. Personally, if I eat something with more than 30g of simple carbs I can see highs at 2 hours of over 200 and I've seen a few 300s. But I've never seen a blood sugar higher than that, even at 1 hour after a meal.
These characteristics of MODY-2 make me think that the SGLT-2 drugs like Invokana may be quite effective for treatment since they can act both on fasting blood sugars and cut the renal threshold and get you to bring down after meal highs quicker.
I would place little value on body of work on clinical treatment of MODY-2. The majority of efforts both at Kovler and Exeter have been a "race" to identify all the genetic variations of MODY-2 (and all forms of MODY). They are focused on diagnosis and establishing the hereditary nature of the condition rather than treatment. Both sites have what I would term "case study" evidence on treatment. I have never seen empirical evidence of a controlled study of treatment which looks at outcomes (such as blood sugar biomarkers, complications or mortality). Unfortunately we are on our own right now which has led me to conclude that the best evidence suggests that high blood sugars no matter what the cause are harmful and I hence I should seek to normalize my blood sugars.
ps. I don't know if you mentioned it, but did you see a genetic counselor or did your endo order and interpret the results?
I would also note that in one of my contacts with Kovler, I applied for a study and was rejected. The reason was that I had successfully used basal insulin to reduce my fasting blood sugars (albeit from 140-160 mg/dl down to 100-120 mg/dl). They informed me that MODY-2 absolutely does not respond to insulin and this belief has been repeated to me by several sources. My current endo refuses to test me for MODY-2 based on this same belief. I suspect this belief is actually wrong. I have interacted with other MODY-2s that have had some success with insulin
As to whether this result in harmful hyperinsulimia argument, I am not so clear. Due to the nature of MODY-2 your body actually downregulates insulin production as a way of establishing the higher "setpoint." It isn't clear to me that reasonable levels of exogenous basal insulin doesn't simply restore what should be normal levels of insulin. It isn't like you were using high levels of insulin.
ps. And my last c-peptide, where I bolused to have my blood sugar "normal," showed a value of 0.4 mg/dl. This either suggests my pancreas is nearly totally pooped out or that my body had downregulated endogenous insulin production.
Hmmm. Studies showing that undiagnosed MODY2 family members have no higher complication rates than non-MODY2 ones would seem to speak rather directly to the consequences of non-treatment. Same for studies that show treatment does not meaningfully change MODY2ersâ A1cs. Sorry if I missed it earlier, how much have you been able to budge your A1c with treatment?
Endo ordered, no genetic counseling. Of course, Kovler effectively provided that.
If youâre MODY2, down-regulated is much more plausible than pooped. My c-peptide was the same, fyi.
They didnât seem fazed that my fasting was readily susceptible to insulin. Note also that I have a novel MODY2 variant, but they said 1/3 of people they see do.
But effective at lowering BGs isnât necessarily the same as effective at warding off complications. Still, itâs worth thinking about for sure.
niccolo,
Do those "complications" include heart attacks?
Though it may be anecdotal, I have heard from enough people with diagnoses of MODY-2 and strong family histories of young heart attacks to take this seriously.
And with my own family history, 5 uncles and aunts on the diabetes side all dropping from heart attacks, two of them in their mid-50s, thin and fit, I'm not willing to gamble that the doctors have this right.
These are the same doctors who were telling us to eat margerine and eat bananas, pasta, and oatmeal just a few years ago. Also based on lots of published research. Extremely poorly conducted, poorly analyzed research, polluted by religiously held assumptions, but peer reviewed and published in respected journals.
Niccolo! What a ride you have going on now. You sound good, and your excellent brain is keeping you safe. So wonderful to hear you have something somewhat tangible to work with now. You are most definitely a member of this family! I suspect that the information you are sharing and continue to share will help others as well.
Brian,
I have heard from people who were diagnosed by Athena with MODY-2 who found that cutting carbs DID lower their fasting blood sugar, despite assurances that it wouldn't.
Ironically, I don't have MODY-2 (according to Chicago) but I find lowering my fasting blood sugar almost impossible no matter what I try. Even Low carb dieting makes my fbg go up slightly. I tried every possible insulin combination without avail, and pretty much live with the fact that my FBG is going to be 108 for the rest of my life. It goes higher if I get sloppy, but rarely lower.