still wondering about the type

[clearprop]

its about a year since diagnosis and i cant still find out the type.
i am 19 and my dad is diabetic as well,but he was dx at 55 type 2.initially,docs believed i am type 1 due to age,but did my best and finally lowered this ****ing **** without needles.had antibodies GAD tests and were all negative.. c-pept was 1.3 in a normal range of 1.0-5.0..my numbers are between 70-200,depending on my pancreas mood :banghead: and last Hb1ac was 6.5
currently switched from 1000 to 1700 metformin after 8 months
maybe am mody,maybe type 2..maybe mody with insulin resistance.wtf,all these are so confusing
can someone help ?

my apology for the english

[foxl]

Have you read the blood sugar 101 website yet? She's a MODY! And has much info on different types!

Good luck ... it took me a lot to get testing.

[MODY-RN]

Sounds like MODY to me... that is what we have in my family. My Mom and her sister (both lean), my brother and myself (just over 40 and lean), and my 17 year old athlete daughter! There is more than T1, T2 or even T 1.5 out there... does it really matter in the end? Seems like it is just more about living with the disease, eating well, staying active and trying to achieve as normal numbers (BS and A1C) as we can.

[Subby]

Sounds like MODY to me... that is what we have in my family. My Mom and her sister (both lean), my brother and myself (just over 40 and lean), and my 17 year old athlete daughter! There is more than T1, T2 or even T 1.5 out there... does it really matter in the end? Seems like it is just more about living with the disease, eating well, staying active and trying to achieve as normal numbers (BS and A1C) as we can.

I agree in that if you strike on the correct treatment, and get clear results of great success, with lifestyle-conducive control, without knowing your type, then knowing type can go jump in a lake.

I disagree too, though, in that if there is not clear success, if there is confusion as to what mechanical issues are going on in your body, and if there is confusion as to what approaches and meds do or will actually help you achieve your goals of control and good health. Then, knowing type could be very valuable.

Clearprop, as Linda says, a definite must read for you from top to bottom is MODY - It's Not Type 1 and Not Type 2, but Something Else (http://www.phlaunt.com/diabetes/14047009.php)

I hope this link stays, as it's not all that easy to find, but if not, search for bloodsugars101 and look around for "diagnosing diabetes".

[MODY-RN]

Getting a true diagnosis is difficult sometimes. The MD's don't know of the other types, insurance won't pay for genetic testing, etc... the list goes on and on. Finding an Endo who has knowledge about the other types is key.

[Rekarb]

I show no antibodies and my c-peptide is 1.5. The term that I've seen used is Ketosis prone type 2. It presents initially like a type 1 with hyperglycemia then once it gets settled down it can be handled like a type 2. Some researchers view it as a type of mody others don't. Here's one of the better citations for it.

Sobngwi E, Gautier JF: Adult-onset idiopathic type I or ketosis-prone type
II diabetes: evidence to revisit diabetes classification. Diabetologia 45:283–
285, 2002

It does make a difference how you treat this type. Oral meds perform poorly initially. The patient should be stablized with insulin first. If they show no GAD antibodies and have normal c-peptides, they tend to move to near normal blood sugars. The theory is that this types beta cells react badly to glucose toxicity. Once that gets handled beta cell activity greatly increases. Just one more weird diabetes thing!

Hopes this helps

Mike

[sarahspins]

I agree in that if you strike on the correct treatment, and get clear results of great success, with lifestyle-conducive control, without knowing your type, then knowing type can go jump in a lake.

I agree with this - it only matters if you are being treated based on the incorrect assumption of the *wrong* type... and that treatment isn't working. I spent a few miserable months on oral meds as an early T1 and it was torture.. I wouldn't wish it on anyone. It only took me a few weeks to realize I needed a different doctor, but it took a few months to actually get an appointment.

To a point what type you are doesn't matter, as long as you can find a course of treatment/management that works.

[tealas]

I'm a sequenced MODY3, and it has made a big difference in my own perception of my diabetes and ability to communicate (and argue) with my doctors for better treatment.

I paid for Exeter University to sequence for MODY3 in 2002 out of pocket. But with a biochemstry background, I was able to target the test pretty much to the correct form of MODY. I knew my family was either MODY3 or MODY5 based on case histories. Once I knew my mutation, (then later) I only had to pay them about $150 to sequence my son to see if he inherited it. It was all very worth it to me - all the years I spent being an "atypical" or "borderline" diabetic. Some doctors telling me I was Type 1 and needed insulin immediately and others telling me I wasn't diabetic at all when my avg blood sugar was about 180-200mgl/dl and I was spilling ketones! My mother (MODY3) died of renal failure at 63about one year after I was sequenced - I sure wish the MODY information and some of the newer drugs (Byetta, Amylin) had come sooner to helped spare her that fate. She was old school and only wanted to take one shot of NPH insulin in the morning :(

MODY3 is pretty easy to screen for if you can use a chart that tracks your blood sugars and your urine glucose readings. If you can catch your urine readings next trip to the loo after a rise to only about 140-160mg/dl and you see glucose, then you are almost certainly a MODY3. Currently MODY3 is considered the most common form of MODY.

MODY3's also have increased insulin sensitivity. My uncle almost certainly is a MODY3 (can't get him to send in a test for sure :( ) - and his doctor had him on Actos (increases insulin sensitivity). This drug seemed to trigger some very negative side-effects for him. when I found out he was on it I immediately told them I doubted it was appropriate for MODY3's. MODY3's are not insulin resistant Type 2's - therefore I wouldn't take any insulin resistance based medication.

Given my biochemistry background, I have tried to keep up somewhat with the research on MODY's. Especially all the HNF* forms of MODY are really *NOT* just diabetes. I hate it when my doctor looks at me just as a diabetic. HNF-1alpha (the regulatory protein that is mutated in MODY3) performs functions in at least the liver, pancreas, small intestine and the kidneys. The reason that MODY3's are sulfa sensitive is because our livers don't process drugs as quickly! Liver lipid metabolism is also affected (esp Apolipids). The reason MODY3's have a lower renal threshold is that HNF-1alpha is responsible for glucose reuptake mechanisms in the kidneys - but it is also responsible for some other number of cotransport mechanisms (I think potassium is one of them). When all is said and done 30-50 years from now, they will likely view some of the MODY's not as "diabetes" but as a metabolic syndrome and the affects on the other organs will potentially be treated as well.

So when my Endo tells me I should take statins, I ask him where the MODY3 specific data is, and does he know my liver is going to process them the same way the average diabetic does? ;)

FYI - they are getting smarter testing for MODY here in the States. There are three labs that I have been able to find (Esoterix, Athena and Ambry). Ambry says they run the sequencing in order of frequency of the conditions (MODY3, MODY2, MODY1):
This has turned into a bit of a rant - thanks for reading....

[foxl]

MODY, LADA, Flatbush ... if you ever had Ketoacidosis, look up Ketoacidosis-prone Diabetes, or KPD.

Just to muddy the waters, my Endo, along with many, still uses the presence or absence of insulin production to define type and only those producing NO INSULIN are T1D.

I have consciously elected to sidestep that, and refer to insulin resistance and autoimmune D in discussing with her ... :evil: BWAH HAH HAH.

[Rekarb]

Tealas

This was my kind of rant. A lot of good information there. Unfortunately most of us don't have enough background to tease out enough info to get to something specific.

I've been researching all manner of info and I seem to match the KPD A-B+ type. What has been mystifying to me is the spilling of glucose in the urine now that my spikes are getting consistently below 160. Some where in all my reading I fell across some discussion of MODY and this type. I also remember that it quickly descended into a mishmash of RNA sequences that threw me off the trail.

Keep an eye out, if you see something give me a holler.

Mike

[tealas]

Mike if you are spilling glucose in your urine around 160mg/dl, then you are almost certainly a MODY3. Do you want me to email you some of the Exeter research articles that document this?

[tealas]

(tried to edit above post, but ran over 10 minute window!)

Mike,

If you are spilling glucose in your urine lower than 160mg/dl, then you are almost certainly a MODY3! I think Exeter documented that MODY3's can spill as low as about 130mg/dl.

Do you want me to email you some of the Exeter research articles? I'm not sure if they are available online any longer (for free).

What I have noticed is that if my blood sugars are high over a longer period of time (weeks/months), then my renal threshold goes lower. Kind of makes sense from a metabolic standpoint, doesn't it? Blood sugar too high, tell kidneys to bail glucose? As blood sugars stabilize back to normal levels, my renal threshold seems to slowly go back up. I've certainly seen my renal threshold down around 140 or 150mg/dl. But now that my HbA1c's are ~5.8, I've seen my BS go up around 160 mg/dl and not spilled. I think this means that like the beta cells, there is a potential recovery in the expression of the good copy of the HNF-1alpha gene when your average blood sugars go down over a period of weeks and months. The glucose reuptake is directly related to levels of HNF-1alpha. Metabolic feedback loops start going the right direction as you lower blood sugars over time - especially post-meal spikes. I read a very obscure article suggesting that the good copy of the HNF-1alpha gene can get "shut-off" by certain feedback loops. Hard to pin down 100%, but I really believe there is some type of feedback loop process like this, and that recovery can take place over many months.

Also from a Chinese Medicine (TCM) standpoint, spilling sugar in your urine is not "free". I typically have many "low kidney energy" kind of symptoms when I am spilling sugar everyday. This was so noticeable to me that even though my Endo told me it was no problem to be spilling sugar all the time, I tightened up my own post-meal goals to below renal threshold in 2006. Within a few months many of the TCM symptoms of low kidney function had eased up.

If you start reading much in the journal articles about HNF-1alpha, you quickly see it is a busy beaver. Involved with all kinds of metabolic loops in the kidneys, small intestines, pancreas and liver. I'm certain that restoring as much expression of HNF-1alpha is very important for MODY3's. If we could measure it more tangibly, it would be as important as your HbA1c. But we don't... yet. However, we can use rough indicators like the renal threshold to get a fuzzy picture of what might be going on with levels of HNF-1alpha expression.

FYI - green smoothies. They might sound and look sort of unappealing, but I can drink one of these first thing in the morning and have my blood sugar go down to 78 mg/dl, even though it has 20-30 grams of fresh fruit carbs in it! There is something about the raw greens (enzymes, cholorphyll?) that seems to restore these feedback loops.

[Rekarb]

Tealas
I would very much appreciate any information that you could send me.

[tealas]

Tealas
I would very much appreciate any information that you could send me.


For anyone else reading this in the future, these are the three articles I'm sending to Rekarb:

Exeter's article about genetic testing of MODY3 (goes over some of the key diagnositic differences between known forms of MODY back in 2000): Wiley InterScience :: Genetic testing in maturity onset diabetes of the young (MODY): a new challenge for the diabetic clinic (http://www3.interscience.wiley.com/journal/78502957/abstract?CRETRY=1&SRETRY=0)

This article documents relationship of glycosuria and developement of MODY3 in genetic carriers: Beta-cell dysfunction, insulin sensitivity, and glycosuria precede diabetes in hepatocyte nuclear factor-1alpha mutation carriers (http://www.ncbi.nlm.nih.gov/pubmed/15983330)
This is the Objective for the above article which lists the key features of MODY3: OBJECTIVE: Patients with diabetes due to hepatocyte nuclear factor (HNF)-1alpha mutations have beta-cell deficiency, insulin sensitivity, altered proinsulin levels, and a low renal threshold for glucose. It is uncertain how many of these features precede the development of diabetes. The aim of our study was to test for these characteristics in young nondiabetic HNF-1alpha mutation carriers.

This article documents some parent of origin impacts for MODY3: Determinants of the development of diabetes (maturity-onset diabetes of the young-3) in carriers of HNF-1alpha mutations: evidence for parent-of-origin effect. (http://www.ncbi.nlm.nih.gov/pubmed/12453976)


If you start searching on PubMed, there are many articles on MODY3. Some of them are only animal studies, but these document how HNF-1alpha plays an important role in many organs. For instance this article: Biochem Pharmacol. 2006 Aug 14;72(4):512-22. Epub 2006 Mar 30.

Alterations in transporter expression in liver, kidney, and duodenum after targeted disruption of the transcription factor HNF1alpha.
Maher JM, Slitt AL, Callaghan TN, Cheng X, Cheung C, Gonzalez FJ, Klaassen CD.
Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, KS 66160, USA.

The transcription factor hepatocyte nuclear factor 1alpha (HNF1alpha) is involved in regulation of glucose metabolism and transport, and in the expression of several drug and bile acid metabolizing enzymes.


The more interesting articles get into Apolipoprotein issues for MODY3's. My pattern for lipids is that I have low triglycerides, high HDL and LDL. My risk ratio is usually right around 2.0. However the kind folks at Exeter informed me via email that high HDL may not be as protective in MODY3's - this is premlinary research by them and needs to be taken with a grain of salt. Almost certainly this pattern of HDL and LDL is primarily due to the Apolipoprotein changes stemming from reduced levels of HNF-1alpha. We basically don't metabolize lipids quite right due to these regulatory protein changes.