Diabetes Lab Tests


#1

Continuing the discussion from C-peptide results help:

I’m going to preface this with … I don’t know nearly enough and I’d like to know more. I also don’t know, if what I know, is accurate.

It’s wonderful that people who want too, can order their own labs and pay for them out of pocket (OOP). One website is linked the post this discussion is continuing from.

While I was reading the thread above, it dawned on me, when we (the collective body) order our own lab tests, do we know what we’re doing?

It would be great if those with more knowledge could help us (again the collective body) put together a list of what goes with what and why.

Take the c-peptide for example. In reading and listening I see where you should also have a blood glucose drawn at the same time. It matters. If the blood glucose is normal/high and the c-peptide is low/low normal, it points more to Type 1. Where if the blood glucose is high and the c-peptide is on the high side of normal or high, it points more to Type 2. I’ve read where a person with Type 1 can also have insulin resistance (Type 2). Is there a special way to read/perform a c-peptide for that occurrence? With a c-peptide test exogenous insulin (that which we inject/pump) as opposed to endogenous insulin (that which our body’s [should] produce) appears to matter as well. I’ve heard the test is best done without exogenous insulin on board.

With other tests, such as the antibody tests, I’ve read where some are done only when you have not begun to use exogenous insulin. I’ve read where some only show up during the initial period of diagnosis, but if your diagnosis is old (I don’t know - 1+ years), it does not show. I’ve read where a person can be Type 1/LADA without testing positive for any antibodies.

I’m sure there are other lab tests relevant to diabetes, but what are they and how do they work?

If you can help wade through this with us (again, the collective us), please do.


#2

I don’t think this particular test can work in that circumstance. Anyone with Type 1 sufficiently “advanced” to be insulin dependent (so, almost every Type 1 not extremely early in a slow-building LADA type presentation) will have a very low c-peptide score, because the body’s ability to produce insulin has been seriously harmed. Insulin resistance (which is not the same as Type 2) certainly can happen in Type 1s using exogenous insulin. The c-peptide test won’t actually help, in this case.

I’m not a medical doctor, but I do read a lot of research on this topic (and others about diabetes). Below is a bit of what I’ve gathered if you want to further research this question.

What would help in this case is a set of other tests and inferences from data:

  • Fasting Insulin at the same time as Fasting Glucose–Insulin levels can be measured directly, and have the advantage of being generally cheaper than c-pep tests and reflecting both endogenous and exogenous insulin. A high fasting insulin and high fasting blood glucose could very well indicate insulin resistance in Type 1 (and definitely in Type 2). Fasting Insulin and Blood Glucose can be combined in various indexes (HOMA-IR and QUICKI) to give a quantitative indicator of insulin resistance. These aren’t perfectly accurate, but they’re the best quantitative tools available at this time.

  • Dyslipidemia is associated with insulin resistance in Type 1s, Type 2s (including pre-diabetic), and non-diabetics (one can be insulin resistant and not diabetic). Higher than normal LDL, triglycerides, and low HDL along with persistent hyperglycemia are a pretty good indicator of insulin resistance.

  • A significant change in the amount of insulin needed to control BG can be a sign of either temporary or chronic insulin resistance. Most of us are aware of how stress (whether it be from social, emotional, sleep-disorder, or other cause) can make BGs much harder to control in the short run, and this is due to temporary changes in insulin resistance. Longer-term changes (over the course of months and associated with other indicators) could very well be a sign of insulin-resistance.

And, finally, just a note: Type 1s can be insulin resistant, and insulin resistance is not the same thing as Type 2. As far as we know, there isn’t such a thing as “double diabetes,” in the sense that people are diagnosed with both Type 1 and Type 2.


#3

Thank you, @David49! This is great information. I don’t recall seeing/hearing anyone talk about a fasting insulin test, probably because more people are concerned with type, not necessarily with are they insulin resistant or not. The same with lipid tests; I didn’t realize they were an indicator for insulin resistance. Although, I do know that lipids improve greatly with a low/no carb approach.

This is new to me, that Type 2 and insulin resistance are not one and the same. I’ve always heard Type 1 is deficient and Type 2 is resistant.

I’ve heard of people being/having both primary types of diabetes, but as with LADA/1.5, I don’t think there is a diagnostic code for that, yet. Any LADA, from what I know, is diagnosed as Type 1. This could be the same with “double diabetes”; there just isn’t the code yet?

Thank you for shedding some light :slight_smile:


#4

Glad to help! I’m a research scientist by profession, and although I’m not a medical researcher I do work in the biological sciences. I try to stay abreast of the most recent research, and I often try to help interpret it for wider (non-scientific) audiences.

That’s because we love to simplify complex topics, and also because science/news writers are often writing about things outside their competence. And then add in social media, and… well, lots of bad information out there.

So, the thing about Type 2 is that recent (not even that recent) clinical and research results indicate that beta-cell dysfunction precedes onset of insulin resistance, which precedes (typical) weight gain, which precedes hyperglycemia. There is also increasing evidence that Type 2 has both genetic and environmental causes/triggers/conditions. The “common conception” that obesity causes insulin resistance, which causes Type 2 seems to be getting the typical progression backwards. And I’m sure there are exceptions to the rule, but this is one of the reasons why there are far more obese people without Type 2 than with Type 2. Obesity can be caused by multiple factors, but Type 2 seems to have a very particular progression.

Part of that progression is the eventual loss of beta-cell function to produce insulin in many (maybe most?) Type 2s if they live long enough. This is one of the reasons why otherwise-healthy, normal weight Type 2s can and do end up insulin-dependent later in life. They may not present signs or symptoms of insulin resistance (often due to successful treatment), but they progressively lose ability to produce endogenous insulin. We have several members of tudiabetes that fit this particular “profile.”

So, at the very earliest stages of diagnosis of diabetes, Type 1s usually present as insulin deficient, and Type 2s often present as insulin resistant. But that’s not the same as causation. For example, we know that Type 1 is caused by various types of autoimmune attack on pancreatic tissues or physical damage to pancreatic tissues. This presents as insulin deficiency, which then causes the various symptoms that are used to identify the disorder. In the slow-onset presentation of LADA (not all LADA is slow-onset, some people are diagnosed during DKA), the loss of beta-cell function can be so slow that the patient is diagnosed as Type 2 based on “population statistics.” This was true for me, and I still have significant endogenous production three years after diagnosis. Some LADA (and likely even some childhood Type 1 cases) have insulin resistance, but that doesn’t change the fact that the cause of their primary disorder is autoimmune attack or physical damage.

Similarly, Type 2 is very complex and has multiple presentations. It’s just easy shorthand to equate insulin resistance with Type 2, but even “metabolic syndrome” doesn’t always progress to Type 2 untreated. That seems (to me at least and various researchers) to indicate that Type 2 isn’t as simple as “insulin resistance leads to Type 2 diabetes.”


#5

I was dx’d T1 n 1983, and I guess an antibody test existed but was expensive and not routine for diagnosis. My presentation was sudden and acute and there wasn’t any question, so by the time it became more of a thing it never occurred to me to have it done. Then a couple of years ago I happened to mention it when I started with a new endo, and I ended up getting the standard test–GAD65. It came up negative, but she said that that result wasn’t particularly meaningful after >30 years. She said something might turn up on one of the other antibody tests, but we both kinda decided what’s the point?


#6

Thank you again, @David49! What an interesting career you must have! Your explanations are very helpful and … understandable.

As for simplifying complex topics … you’ve explained it very well; it makes sense! That’s the thing with diabetes, it is so utterly complex, to reduce it to a few sub-types doesn’t seem to work, yet to identify, with any clarity, all of the (read majority/more than identified now) sub-types, doesn’t seem possible.

I like the word, the premise, causation. Also, I believe there is more that unites us than divides us, between diabetes types that is, especially as it relates to symptoms and complications. I wouldn’t want to be a physician and need to diagnose anyone, with anything, in our ever changing world; their job cannot be an easy one. Recently, I’ve heard, there is an autoimmune component to Type 2. I know a lot of Type 2 individuals who are of normal weight and those who are not. And, as you pointed out, many obese individuals who do not have any signs of even developing diabetes. My husband’s father was Type 2 and of normal weight throughout his lifetime - perhaps he was LADA? He did have and died from Alzheimer’s complications. I’ve been told Alzheimer’s is a form of diabetes - some call it Type 3. My husband is Type 2 and has lost a lot of the weight. His family is all of normal weight; my husband’s weight came on because of an accident in childhood - long story. I mentioned to our family doctor recently that I was amazed at how much less insulin he (my husband) is now using. He (the doctor) said it was because of my husband’s weight loss. We’ve learned first hand, weight loss does help with insulin resistance. And, taking less insulin helped him to lose more weight … a win-win.

@DrBB I’ve heard this a lot, that the antibody tests, although helpful, aren’t always definitive. It seems to me, as I read of others journeys with diabetes, the early 1980’s was a time of great change, on the diabetes front … major advancements in treatment options.

To all … would there be any benefit to having a list of various lab tests and what can/should go along with each, such as a blood glucose test should be done in conjunction with a c-peptide test? Fasting insulin and glucose tests? Which antibody tests are run, when? Do they need to be? Would this list help the community at large, who, in many instances, need to be their own advocate and seek answers (via lab tests) because their doctor’s resist ordering them?


#7

David,
When you say you still have significant endogenous insulin production, do you mind clarifying what you generally define as significant (based on c peptide results)? I’m curious because though my c peptide level has never measured within the normal range since diagnosis (always below), it is not at absolute zero.
Thank you!


#8

I’m positive for antibodies, but am at the absolute bottom of the c-peptide “normal” range at 0.6 ng/mL. I’ve always had low fasting insulin, low c-peptide, even when I have high BG. I also appear to have the very, very slowly developing type of LADA that some people get in middle-age.


#9

Bernstein said most T1s have some residual insulin production. He once said he’s the only one he’s found without it, but later he said he was producing a tiny bit.


#10

Just a thought, there are definitive tests to determine insulin sensitivity vs insulin resistance in a patient, but they are almost never used outside of laboratories and research studies. One of my doctors has suggested we could try the “practical” version (number 2) in a clinical setting, but it seems expensive and I doubt my insurance would cover it.

  1. The first is to “clamp” insulin and/or carbohydrate. This usually involves IV insulin drips and glucose feeds so that there are quantifiable and precisely controlled levels of glucose and insulin in the body. This doesn’t show whether the body can make insulin (due to the IV), but it can show how well the body uses available insulin to deal with blood glucose. This has been done in studies, but is completely impractical.

  2. The other way to do a test which can indicate insulin resistance or insulin deficiency in a quantitative sense can be used clinically (although I’m not aware of it being done). It is to use the Oral Glucose Tolerance Test (OGTT) commonly used to screen for gestational diabetes with a couple of modifications. BG and Insulin levels are tested before the glucose challenge, and then afterwards:

  • Blood Glucose is tested every 15 minutes for 2-3 hours.
  • Insulin levels are also tested every 15 minutes for 2-3 hours.

What this protocol would produce is a very nice Blood Sugar to Available Insulin curve, and would be similar to fasting BG + fasting insulin but with much more information. A rise in BG with a rise in insulin levels to high levels, and then slowly falling BG would be characteristic of insulin resistance. A rise in BG that stays elevated with little-to-no increase in insulin would indicate insulin deficiency. A rapid rise in BG, with a delay, then a rise in insulin and a rapid decline in BG would be indicative of some kind of signaling disorder (which can also be characteristic of early Type 2).


#11

David,

Your post and analysis are so interesting. I had a test akin (but less comprehensive) to your #2 example performed by my endo after presenting w/ high fbg’s and A1c. Endo tested my bs and insulin levels around OGTT at base, 1,2 and 3 hours; results:

Insulin Bs
fasting 0.8L 83*
1hr 10.5L 199**
2hr 10.8L 126
3hr 2.5L No report

  • Previous fbg’s had been in the 120’s, but by the time of the OGTT, I had gone strict lo carb
    **Interestingly, even a small carb meal will send my bs much higher than the OGTT–near 270+. (I wear the dexcom CGM.)

What do you make of these results?? (I’m secretly always trying to shed the LADA diagnosis! :slight_smile: Thank you!


#12

When looking at those numbers, that curve looks fairly normalish, but hard to say with only hourxhour tests (see below). That was on your own, without exogenous insulin? While shooting up to 199 mg/dL is certainly not great, being back down to 126 mg/dL by two hours is close to a “normal” response. Generally speaking, I know my doctor likes to see the 2 hour mark be “back to the the starting BG,” but she is strict in the Bernstein school of diabetes management :slight_smile:. I.e., may not be achievable for everyone.

The reason why you want 15 minute rather than hour by hour tests is that “normal” insulin response to BG challenge is in two phases. With tests every 15 minutes, and a normal insulin production profile, you should see a huge spike in insulin production immediately after eating (first phase), and then a slow ramp up (second phase). The first phase tends to blunt the rise and “cap” it at some level, and then the second phase of insulin release helps to bring BG back down to pre-meal levels before tapering off. Yours looks like a “square wave” response, but that might be because we don’t see the insulin levels every 15 minutes. The “normal” response would have two peaks, and a fairly normal distribution of BG.


#13

That makes sense, David. Thank you for that. This diabetes thing can be so confusing!

(No, I was not yet on insulin.)
I am still not convinced as to my “correct” diagnosis, though my Dr. classifies me as Lada (despite being antibody negative). His rationale:
-lean and fit
-always below range c peptide (even when fbg is high) and,
-low insulin production (again even w/ hi bg) as shown by that OGTT

I, like you, however find diabetes diagnosis seems a more nuanced game. My endo typically responds when I re-re-revisit (much to his chagrin) the question of what “type” of diabetes I have (or whether I have diabetes:grin:),
“Why do you care? The goal is to keep your numbers in range.”
I know he’s absolutely correct there.
Too bad I like things best when they make sense, tied up in neat little packages of understanding!

Hopefully our continuing convo may help someone else trying to navigate in the hazy Lada realm. Is your Lada experience like mine?

I take only 3U of tresiba daily (5’5", 108lbs), eat pretty lo carb (though not Bernstein low) and bolus primarily only when I cheat. (I do find protein to sometimes require dosing. And sometimes very large amounts of veggies require a small dose too–Bernstein’s “chinese restaurant” effect.) I like afrezza for my infrequent cheats because my cheats are usually sugar-based. I often add additional doses of afrezza over a few hours to keep bs #'s in check. Humalog was difficult for me–hanging around in my body too long–especially because I like to exercise. Afrezza gets out faster and if I need to add small doses based upon CGM, it’s easy. Also, my endo has been kind enough to provide me with afrezza samples, eliminating some of the $$ burden.

Every so often I get it in my mind that I just don’t have Lada or any other diabetes. (My CGM SV is usually pretty darn good.) Then I go wild, eat a piece of See’s candy (or two) without bolusing & watch my bs shoot to 280+/-.
My endo will patiently remind me that I had a paltry (and undesired) weight of 99lbs at diagnosis (not pretty), was extremely thirsty and fatigued and had numbness and tingling in fingers.
Then I capitulate and agree: Why do I care the type??? The goal is to keep my numbers in range. (But really, I’m not that easily mollified.)
My endo also claims that studies show that early Lada’s given exogenous insulin can sometimes preserve remaining beta cell function, extending the honeymoon and making control easier. (I’m not qualified to comment on the validity of this statement.)
Anyone know about this???


#14

Hi Karin! Yeah, I’ve definitely had some weirdness on the diagnosis and progression front. I was diagnosed initially with “mild,” early-stage Type 2. Which was a bit weird, being pretty fit and healthy otherwise. I was re-diagnosed as LADA after a later antibody test, primarily because the “typical” Type 2 treatments weren’t really doing a whole lot.

So, OK, I’m LADA (as of three years ago). However, my c-pep has stabilized, and although I’m always low-production of insulin, I do produce enough to manage eating very low-carb. And, so far, my disease hasn’t seemed to progress too far. The long and the short of it I’m one of those few people that is diagnosed Type 1 but not yet on insulin. My grandmother and younger brother had similar presentations, and it took 10+ years to become insulin dependent.

If it was up to me, I’d probably prescribe myself low-dose basal and use afrezza for cheats, exactly as you are. The science seems to suggest that’s a good deal for slowing beta cell decline. However, my doctors disagree, and I’m a plant doctor rather than a human doctor :slight_smile:

If I were your doctor, which you can be glad I’m not since I’m primarily a plant and microbial biologist, I would interpret those characteristics as being Type 1 as well. You certainly seem closer to that from what you’ve written than Type 2. It could be possible you have one of the rarer MODY disorders (strictly genetic) that require low-dose insulin but are otherwise dissimilar from T1 and T2 and not generally progressive. Ony way to tell, however, is very expensive genetic testing. There are other (more likely) possibilities:

So, Type 1 has seven known autoantibodies associated with it, 5 of which are regularly tested for. If you didn’t get the “full” panel, you could be positive for one of the ones you weren’t tested for. There exists also a rare diagnosis called “idiopathic Type 1” or Type1b, which presents in adulthood normally, is antibody negative, and is highly correlated to certain genotypes. It tends to progress like Type 1, but very slowly. Antibody tests generally never are positive for this group of diabetics, who used to also be called “ketoacidosis-prone Type 2 diabetics.” The long and the short of it is, some people experience the beta-cell decline to zero production typical of Type 1 without ever having tested positive for antibodies.

Big Caveat! Thirty years ago, there were two antibodies known to be associated, and a huge chunk of people tested negative but were Type 1. We keep finding new antibodies to test for, and there is no good scientific reason to think we’ve found them all now! Antibodies are really hard to isolate (I’ve done some work with them in other non-human pathosystems, and they are tough to identify and work with). I would be absolutely gobsmacked if we even know 50% of the antibodies that are characteristic of Type 1 diabetes.

Caveat Two! Many scientists suspect there are far more “types” of diabetes that 1, 2 and MODY. Can’t really get into the literature on that today, but I’ve written about it here in the past. There are British scientists who have suggested reclassification (which has happened before), and it is quite possible that you are suffering from some sort of “version” of diabetes mellitus that has a different cause than “Type 1.” In that sense, your doctor is absolutely right: the goal of treatment, regardless of cause or type, is to minimize BG departures from the desirable range. Period.


#15

Great discussion! My first endo diagnosed me as T2 but no oral meds worked so he put me on sliding scale Novolog. I didn’t like the way he was so controlling so fired him.

My new endo’s first test results were:

A1C 3/29/18 6.3
GAD 65 <5 12.19.17 (Antibodies to the pancreas are negative)
F Insulin Antibodies <5.0 12.19.17 ( Insulin antibodies were negative)
F IA-2 Autoantibodies <1.0 12.19.17 (Antibodies to the pancreas are negative)
C-Peptide, Serum 0.7 12.19.17

He later ran testosterone, tsh and other panels. I have high BP, cholesterol and low testosterone as well btw.

From what I was told, Medicare calls T1 with c peptides 0.9 or lower. (although I’m not on medicare)

I’m already on an insulin pump (630G now Omnipod) and Dexcom but was told that if I had insurance problems he’d be willing to recode me as a T1 since I’m basically being treated as a T1 anyway.

But I like nice labels! Would you say I’m T1 or T2?


#16

Bob,

What was your bs at the time of that c peptide? I understand this info affects c peptide analysis. Here is a link to an article on all of the different antibodies to be checked for type 1:


#17

Thank you @Karin7 this helps!

All, after reading the article, it doesn’t mention doing a c-peptide fasting or non-fasting or with/without a blood glucose level. It’s my understanding that a c-peptide should be done in conjunction with a blood glucose and also that it should be non-fasting. As a matter of fact, I’ve heard it’s best to have a c-peptide done non-fasting, after a carby meal, without any exogenous insulin. This shows then, your body’s insulin response in the presence of food. I’m not sure if no exogenous insulin was basal, bolus, or both. I think there’s potential for a problem (read DKA) with blood glucose going too high - especially if there was no basal.

The article Karin7 shared is dated September 2015. I don’t know all of the currently identified antibody tests, but this list is a start from that list.

Antibody tests:

  1. GADA or Anti-GAD (GAD)

  2. Insulin Autoantibodies (IAA)

  3. Insulinoma-Associated-2 Autoantibodies (IA-2A)

  4. Islet Cell Cytoplasmic Autoantibodies (ICA)

  5. Zinc Transporter 8 (ZnT8Ab)