Realizing I fit the MODY profile well, any MODYers or others have insights to share?

I'm a pretty unusual diabetic, been called almost every label in the book over the years, including Type 2, Type 1.5, Type 1, LADA, and MODY. The labels never seemed terribly important, but it occurs to me that I may actually fit the MODY label quite well. I'm not sure how much this matters, but even if it has minimal treatment implications it's nice to try to get some clarity on what's going on with my body.

I was diagnosed in 2002 with a high end of pre-diabetic range fasting BG of 120 or a few points higher and a solidly diabetic, but not crazy high, oral glucose tolerance peaking in the mid-200s, and A1c of 5.6, no symptoms, got picked up in a random physical. I subsequently had an oral glucose tolerance test with insulin levels monitored, and my endogenous insulin production was clearly deficient, with no indication of meaningful insulin resistance. My phase 1 post-prandial insulin response, i.e. my body's ability to marshal insulin to cover carbs, was very poor, but my phase 2 response was pretty robust, keeping my fasting and average BGs in check. If it's relevant, I was (and remain) pretty lean and athletic.

I was briefly put on a sulfonylurea, to which I was somewhat responsive, then within a few months basal insulin and a few months after that bolus insulin. I switched to insulin because my doctor (a leading diabetes researcher) and I agreed that a fairly aggressive approach to preserve beta cells and extend the honeymoon was warranted, and I had no qualms about starting insulin. Oddly, I don't recall the question of underlying mechanism, i.e. MODY vs LADA, being central, the gist was that whatever the cause, insulin would keep my BGs as normal as possible.

Over twelve years since, my endogenous insulin production capacity has gradually declined, though I still make a little insulin. My c-peptide results demonstrate impaired endogenous insulin production, as expected (though no one told me not to fast for those so I'm not even sure how meaningful they are). When doing intense physical activity like alpine climbing or trekking or road biking, I do just fine with zero basal or bolus insulin, except for some bolus insulin in the evening with dinner. During everyday life, I was on multiple daily injections until recently taking 12 units of basal evenings and a little more than that of bolus over the course of the day, on a moderate carb diet. I just started a pump, where I'm currently running a basal rate of 0.375 per hour (which equates to only 9 units/day), I really had to reduce my basal rate on the pump, as many do. Eventually I'll start running different rates at different times of day. My insulin/carb ratio seems to be between 1/15 and 1/20 at different times of day, my correction factor maybe 1/75, but I still need to do some work to dial these in. My most recent A1c was 6.2, my highest ever, these days I'm between 5.8 and 6.2.

I haven't had antibody screening, I vaguely recall perhaps one was tested many years ago and came back negative but I could be wrong about that. My sense is it's probably worthwhile to screen for the various antibodies at this point, though the treatment ramifications of those results would be modest at best. Is gene screening also accessible?

This sounds like MODY, right, i.e. significantly impaired insulin production as a result of genetic mutations rather than an autoimmune attack on the beta cells? Obviously antibody (and gene?) testing would be the more definitive way to diagnose this, but everything else--initial presentation with only modest hyperglycemia, no DKA, twelve-year honeymoon so far that looks set to continue with only gradual decline in endogenous insulin production--seems to be consistent with MODY. Does this have any treatment ramifications, besides making it easier to sustain good BGs? I suppose it means if I were to have kids I'd be fairly likely to pass it on to them (it turns out I have several family members diagnosed with Type 2, I think that also fits the MODY profile of a gene defect that runs in the family). Is there any reason not to have antibody (and gene?) testing done? My impression is in the UK and perhaps other places that might limit my treatment options, though I'm not sure it's an issue in the US, at least with good health insurance.

Insights welcome, joining the forum recently has really been a wonderful opportunity to better understand this condition and find a community of fellow travelers.

paying 100 us dollars for the 23andme test, i found out i have the risk allele T for the most well-studied gene whose risk alleles have been found to predict diabetes-. aka the T alleles in the TCF7L2 gene. 23andme also tests for other diabetic genes, both type 1 and 2, but i don't think it tests for MODY. the fda shut 23andme down for giving health reports, but i believe, but am not 100% sure, that you could pay the 100, get ancestry info, and then go over to the website, search for any of a number of health topics/genes which are then linked to a lot of sites including 23andme. snpedia tells you what the risk alleles are (for TCF7L2, CC is the good combo. TT greatly increases the risk of Type 2 and some LADA people have it. I have CT, which still gives me increasing high bg on a low carb diet. the T allele is associated with deficient insulin production.) there are forums at 23ndme too. using genome wide association studies to predict risk is still an emerging science, but my results did not surprise me since i have diabetes in both parents. the thing that surprised me is that i am not insulin resistant like most type 2's. also, my gene is involved in a cellular signalling pathway and my risk allele is also associated with colon cancer, aggressive prostate cancer, and breast cancer. my mom died of breast cance and my father and grandfather both had colon cancer. i had polpys removed at 42, which is supposedly young to have them. some people don't want to test with 23andme because there are lots of people with conditions that weren't caught by this gene test. some people have type 1 and their 23andme results never turned up that possibility. like i said, it is still an emerging science. but for me it has helped me be more motivated to go low carb since i know i just don't have the insulin to eat like regular people. my OGTT results reinforce this for me. also i have colonoscopy screenings every 5 years. plus i am aware that i need to watch out for breast cancer, although i would rather have an mri done for it. finally, i just love science, so it may sound like i am a hypochondriac to you, but i love to delve into the research of it all.

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My endo acknowledged that I very well could be a “MODY 3” but elected not to order the tests for them-- he said that they are outrageously expensive labs and he was virtually certain that no insurance would pay for them… He also said that regardless of how the labs came back it wouldn’t change his treatment protocol with me a bit, so while it was worthwhile to mention it really wasn’t worthwhile pursuing s definitive answer… I took his word for it. It still crosses my mind from time to time but I have reached a point where I dont really care about the acronyms or the type 1 vs 2, LADA vs MODY etc alphabet soup anymore-- I just care about effective management…

Yep, given how you described your condition, it occurred to me you were an even stronger candidate for MODY than I am. And I've gotten the same response re the tests, and I'm sympathetic to that answer. At the same time, I don't think it's totally irrelevant. For one thing, it has a huge effect on the prognosis for any kids I might have in future. While the genetic testing to confirm MODY is apparently very expensive, I don't think the antibody testing to rule out LADA is nearly so expensive, I'm kind of surprised the antibody testing isn't a standard part of the diagnostic workup when we first present as diabetic.

It's too bad that FDA clamped down on this, though I can understand why. Low carb makes sense, but you could also eat a more moderate carb diet controlled with exogenous insulin (not sure whether you're doing that already). And agreed it's fascinating to understand this curious condition further!

i don't qualify for exogenous insulin yet based on a1c and ogtt, although if i ate real food like a bowl of unsweetenend oatmeal or a slice of pumpkin pie, i would hit 200 at one hour and beyond no problem. but they don't have the pie test approved yet :(

“I dont really care about the acronyms or the type 1 vs 2, LADA vs MODY etc alphabet soup anymore-- I just care about effective management…”

i care because i have found comorbid conditions to watch out for. plus the curiosity factor.

also, we might find out certain things unique to our type of diabetes that would be helpful in treatment of it and/or other health conditions. more knowledge is always better (if it doesn't break the bank that is). i will find a way to pay out of pocket for anything related to my health if it isn't too expensive. the 100 dollars for 23 and me was less than a pair of leather boots (i bought the fakey leather ones at macy's for 65).

re MODY, i forget which version jenny ruhl says she has, but you might look into her story for clues to your own present and future. you can find her websites by googling diabetesupdate and bloodsugar101.
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OGTT is a pretty significant carb load, you stay below 200 for that?

A big bowl of oatmeal is a pretty killer carb load, I'm not convinced it deserves its "healthy" moniker for anyone, even non-diabetics.

Sometimes doctors can be very by-the-book, if you're willing to use insulin and it would help you manage your BGs better, you're much better off starting it earlier and thereby going more easy on your body. That, anyway, is my take, and thankfully it was my physicians', too, when I was first diagnosed.

last december my OGTT test was 90 fasting, 165: 30 min, 128 one hour, 128 two hours.

i don't think i am high enough for insulin yet although since september my fasting has gone up by about 15 pts. also, anyone reading this who thinks i should zip it cuz i have such good numbers, sorry...i know what diabetes does watching my parents and my goal is to enjoy life for a long time minus the kind of suffering they went/are going thru. and then drop dead. so i will get out way way ahead of this. plus as i said it is my interest.

I believe he was talking more like 5,000+ out of pocket for legit MODY genetic testing

Yeah, those are almost normal numbers, it does seem premature for you to go on insulin, and frankly you're probably better served keeping your carb consumption in check.

I was diagnosed by a primary care doc I saw away from home. He initially said type 2 but then called me back like the same day after consulting with someone and said he believed I was actually type 1 and I started insulin the next day. When I got home here my family doc here ordered the antibody tests. I showed tiny levels of GAD antibody, but they aren’t convinved that it was conclusive proof of good old fashioned T1

that is a bank breaker. i could get a fairly good used car for that.

So does anyone know of a place where MODY can be tested for at a reasonable price? This would seem like valuable information.

You sound just like me. My basal during the afternoon/early evening is 0.05 - I would set it to 0 but I can't on my pump. If I don't suspend for 2-3 hours before working out, I will drop quickly and severely. My ratios are the same as yours and my A1C varies in the same range as yours. I had the autoimmune tests and my GAD65 numbers were extremely high. I'm not really sure why you think this sounds like MODY, but I don't know much about that variant.

FYI - my antibody testing was around $350, paid for by me, and I've heard MODY testing is in the thousands.

Pretty much? No. Because you're in the US, you could potentially get tested for free by the Kovler diabetes center in Chicago, but you need to fit their criteria. I fit every, single MODY criterion except that my C-peptide is high and they won't test me. I understand that because it's a weird thing to have for MODY, but I fit all the criteria. If you do, you're welcome to try it with them. They, however, are the only ones who are anywhere near a "reasonable" price unless you're running the gels in the lab yourself.

MODY means that you have a genetic defect that impairs your ability to produce insulin, as opposed to the classic Type 1 where your immune system attacks the beta cells. In my case, twelve years after being diagnosed, I still make a fair bit of insulin, so my basal rates are very low and c-peptide confirms remaining endogenous insulin production. What insulin I do make, or inject, my body uses extremely efficiently (as both my I:C ratio and OGTT w insulin levels both make clear), so I definitely don't have the mechanism for Type 2. It's possible I have very slow onset LADA, i.e. a very gradual immune attack on the beta cells, but it would be oddly slow. So MODY strikes me as a plausible alternative.

My doctor just ordered two of the antibody screens, GAD and one other. Depending on how those come back, we may do MODY gene testing if we can get insurance to cover it, but I have no idea whether they might, since it's very expensive.

We have a MODY group which discusses many of these topics. The best resource worldwide for MODY is Exeter which still offers a lot of information and affordable testing. You can check out their website DiabetesGenes.

I'm signed up for the TuD group. Interesting re Exeter.

Hi v_prediabetic.

I know this thread is old, and I hope you reply. :slight_smile:

I have the same TCF7L2 CT allele. I have no insulin resistance (fasting insulin is low), fasting C-peptide is lowish, indicating weak first-phase (post-meal) insulin output. I eat to my meter… 25g cargs will send me to 130s. Fasting is in the 80s when I’m good. I tested negative for LADA antibodies. No MODY gene testing; too expensive, and 23andme don’t test them.

I’m curious about how a slice of pie will send you to 200 but OGTT is only 165 at 30 mins and 128 @ 1 and 2 hrs. My OGTT is 210 @ 1 hr and 110 @ 2 hrs.

Do you know of other TCF7L2 resources?

BTW regarding colon cancer, a lot of studies show that soluble fiber intake reduces that risk, and stool testing will tell you stool pH and flora composition. Low pH is associated with lower risk of colon cancer.