Diabetes and Hepatitis C

Summary: My endo thinks that my D is caused by hepatitis C. I think that this is possible but not certain. I've searched TU carefully (with Google), and this topic hasn't been covered, so I thought it would be useful to post about it. The longwinded version:

I haven't posted much since mid-May, when many of you were very helpful in replying to my initial post. There are several reasons for this. One is that once I got traction with Novolog, I've had excellent control. At the same time, the hard core of experienced posters here are so good that it wasn't clear I had anything unique to say in discussions, so I decided to spend a lot of time reading old posts (a treasure chest, from Funny Hypo Stories to The Good Wifeabetes?)

The main reason, though, was that I was digesting a hepatitis C Dx. I found out about this as a consequence of asking my internist for pancreatic CT scan the day I was Dx'ed, as I explained elsewhere. The scan showed that my pancreas had a few calcifications, kidneys had a cyst or two, and 'mild nodularity of the hepatic contour'. I now understand that nodularity is associated with scarring and cirrhoses. In any case, during the same dramatic initial 90 minute visit with my endo where I first got my hands on some Novolog, he persuaded me to take a hepC antibody test, which came out positive. This was followed by a PCR test for the virus: positive. DNA sequencing revealed I have genotype 1b. Finally, as a substitute for liver biopsies, current practice is to test for a panel of markers for liver damage. Unfortunately these tests unequivocally show only 'normal liver' and 'cirrhosis'. Intermediate results showing damage short of cirrhosis--I had a FibroSpect score of 59--are uninterpretable in terms of safety margin. At this point I will interrupt this narrative for a few words about hepatitis C.

hepC is caused by an RNA virus, so-called because the viral genes are encoded in RNA not DNA. HepC is not caused by a retrovirus. Retroviruses, such as HIV, also have an RNA genome, but they transcribe DNA from it which becomes permanently inserted in the host's chomosome. HepC virus replicates in the cytoplasm and has no DNA stage in its life cycle. HepC is blood borne through contaminated needles, transfusion sets, etc. It's existence began to be suspected in the 1970s, but the virus was not conclusively identified until 1989. The typical type of infection is chronic, and people may be asymptomatic for decades. Sometimes the latency is so long that an infected person dies of other causes; sometimes a chronically infected person develops cirrhoses, which frequently progresses to hepatic cancer. End stage disease can sometimes be cured by a transplant; one prominent hepC/hepatic cancer survivor is former Grateful Dead bassist Phil Lesh, who now gives a little rap about organ donation before the encore at all his shows.

Before 2011, the treatment prospects were pretty grim. The major treatment was PEGylated interferon and ribivarin. This had a 50% success rate and usually took 24 weeks, during which the interferon caused fever, diarrhea, and exhaustion characterized by sleeping 14hrs/day. Since 2011, however, new treatments have become available that are 99% effective and have no side effects except photosensitivity. The 'official medical guidelines' are here. These treatments appear to be safe and highly effective, but they are currently new and very expensive and will require heavy advocacy with your insurance company/medicare/medicaid.

This is not a hepC board; what about the D? My endo believes that I have type 2, and I am about 95% certain I agree with him. Let's recap:

Arguments in favor of slow onset type 1: Never obese, loss of weight prior to Dx, BMI 20-21, TDD 40U at 60kg--high but not impossible for type 1. No auto-antibodies, but as Melitta points out, 5% of bona fide Type 1's don't have them.

Arguments in favor of type 2: I show signs of insulin resistance. My I:C has varied from 2.5:1 recovering from major periodontal surgery to 1:5 after regular aerobic exercise. The TDD of 20U basal / 20U bolus only applies to days with low carb breakfast and lunch, 70carb total. At 100carb/day bolus total more like 30, and on a carby day (130-140carb) 40. That's a TDD of 40-60U with basal always 20U. Finally, C-peptide is 3.4 ng/ml, normal for this lab given as 1.1-4.4. This test was given in late April, when I was testing a lot but had levemir only with good fasting BG and ugly post-meal spikes. My log says I tested BG at 84 right before the C-peptide test late in the afternoon and hadn't had lunch. This seems high for fasting at this BG at (then) 23U/day basal.

My endo, like me, thought for for sure I had type 1 at first. He thought that in part because I'd be 'among the 10% of non-obese type 2's and probably among the 5% without metabolic syndrome'. After the hepC Dx, his opinion shifted to type 2 from hepC caused insulin resistance. My hepatologist thinks the evidence is only epidemiological and pooh-poohs the whole notion. I had intended to make this post only after doing thorough research, but the day job takes a lot of time, so I'll share what I know.

I just got the 14th edition of "Joslin's Diabetes Mellitus", which seems to be a top textbook but this edition dates from 2005. It makes no mention of hepatitis C in Chapter 27 "Secondary causes of diabetes", which is where it would be mentioned. I have found numerous (low quality) papers that are, in fact, epidemiological, and show a higher frequency of type 2 among hepC patients. One review that has a useful paragraph about diabetes and is open access is here. Unfotunately, some interesting references therein are behind paywalls. One paper that isn't is this one by Milner at al.. The authors used a euglycemic clamp to measure insulin resistance in a group of uninfected and hepC infected non-diabetic subjects. They found significant insulin resisrance in the hepC subjects, and by indirect means concluded that it was in muscle and not in liver. Maybe this is why metformin does nothing for me?

In any case, this post is now WAY too long. I'm interested in any comments, experiences, about this here at TU. If you'd like to correspond privately with me about hepC, please send a friend request. I'll try to do more reading and report what i find. Should I actually get treated (not clear at this point), the effects of treatment on my D will be useful data. Apologies for the length of this post.

-ZZ

This is the first I've heard of it, but diabetes is just very complex. Unfortunately the diagnosis of the "types" such as 1 and 2 is just murky. There is no "bona fide" type 1 and type 2 really just means "Diabetes of unknown causes." In the end all that really matters is that you get the right treatment.

I've done some poking at the paper you cited and can provide some of the referenced papers. I'm doing this publicly because there are others out there with both diabetes and Hep C such as here.

Here are some of the citations from the paper.

I. M. Jacobson, P. Cacoub, L. Dal Maso, S. A. Harrison, and Z. M. Younossi, “Manifestations of chronic hepatitis C virus infection beyond the liver,” Clinical Gastroenterology and Hepatology, vol. 8, no. 12, pp. 1017–1029, 2010.

J. M. Petit, J. B. Bour, C. Galland-Jos et al., “Risk factors for diabetes mellitus and early insulin resistance in chronic hepatitis C,” Journal of Hepatology, vol. 35, no. 2, pp. 279–283, 2001. (attached)

I've also found some other papers which I put into a zip file that is attached

680-Riskfactorsfordiabetesmellitus.pdf (94.3 KB) 681-HepCpapers.zipx (997 KB)

Not too long ago, “T1” and “T2” terms didn’t exist. Regardless of what “caused diabetes” if you respond to insulin treatment well, I see nothing wrong with keeping your treatment goals and techniques well in the “insulin dependent diabetes” camp.

TDD 40U at 60kg--high but not impossible for type 1

I think you have a somewhat distorted view of what the range of TDD's for T1's is. The early onset LADA's who profusely post here typically have tiny tiny doses. What you have is entirely typical of T1.

One rule of thumb I remember from the 70's: TDD is very often close to one unit per kg. Of course actual range can be a lot bigger than this, and back in the 70's the thought of "control" is ludicrous by today's standards. Maybe with better control (good average bg, fewer swings) helps keep the TDD down a bit below this for many of us.


Arguments in favor of type 2: I show signs of insulin resistance. My I:C has varied from 2.5:1 recovering from major periodontal surgery to 1:5 after regular aerobic exercise.

I can guarantee you that T1's show huge swings in insulin needs in response to exercise and/or infections too!

Yeah, I'm gonna agree with you here Tim. 40 units a day isn't all that unusual for a type 1 , but seems rather low for a type 2 to me? I mean I'm a person with type 1 who's diagnosed as an adult and 40 seems a lot for me but I'm also small and from my various calculations I should be using somewhere around 20 units a day and that's around what I use. (I find I use 19-21 total every day) .

I'm IDDM through and through,
whether the type be 1 or 2
Some may like their metformin
For me the best is insulin
I know my meter cannot lie
I keep it straight with MDI

Uh...but seriously--
Tim and Sensorium, what are your I:C ratios? 'Insulin resistance' is a bit of a slippery concept. My endo, who I have reason to believe is clueful about D (heh...and claims he sometimes reads TU), says I'm resistant. I thought part of the reason was my I:C ratios.

I have passed as a type 1 at a JRDF event. Do you think there is such a thing as 'glydar' (like gaydar)? At this event I congratulated and shook hands with a t1 Dxed in 1962..he said "Are you really a T1?" It reminded me of being outed as a heterosexual at the 1991 NYC gay pride parade...very funny really...I didn't have good taste in decoration :)

ZZ

Brian, Thank you for the excellent refs. So far I've only fully read the first...hardly surprising the interferon-ribivirin regimen produces depression!

So with regard to the doasage/resistance dicussion below--you and (probably) me are IDDM type 2's. You've probably mentioned it elsewhere, but what is your I:C ratio and do you see patterns in your insulin use/glycemic regulation that differ from T1?

ZZ

Personally, I think there are too many debates on T1 and T2 based on outward appearances because it does not discriminate. So just what is the phenotype of T2? UGH! My medical alert just indicates 'On Insulin'.
This is from this article for anyone who wishes to read further. It is interesting and thank you for presenting this topic.

http://care.diabetesjournals.org/content/29/5/1140.full
'The prevalence of type 2 diabetes in people living in the developed world ranges from 2.0 to 9.4% (8), rising to 12.3% in U.S. adults between 40 and 74 years of age (9). The decline in mortality of people with diabetes, together with the rapidly increasing frequency of obesity and the sedentary lifestyle of the population portends a dramatic increase in the prevalence rates of type 2 diabetes (10–11). Therefore, both HCV liver disease and type 2 diabetes are two already prevalent diseases that will probably continue to increase in the next decades.'

My I:C ratio is a bit variable depending on time of day and exercise but I would usually simplify it to average out to "1:10". I was kinda wondering if you got the top and bottom of your I:C ratio mixed up!

There was a different T1 discussion board, where one of the most vocal members actually insisted that everyone who wanted to post, had to send their C-peptide numbers and antibody tests to her before she would believe they were T1 :-).

If you eventually equated my use of the word "most vocal" to something between "loudmouth" or "busybody" you would be getting there!

I consider myself insulin resistant. But I can't really answer your question about I:C because I don't really dose that way. I eat a very low carb diet and my problem is chronically elevated fasting blood sugars. I have a TDD of 80-90 units and take about 80% of that as basal. My mealtime dosing is a combination of correction and then a bolus for my meal which combines the carbs, protein and size of the meal. The dominant part of my bolus is the correction. I'll often bolus 5-10 units for a meal, the vast majority which is to correct my fasting blood sugar.

We are all different. Even those of us with exactly the same "diagnosis" are different. I am particularly strange. You can ask my wife and you can ask my endo and they will both tell you I am strange. My endo currently assigns me an ICD-9 diagnostic code of 250.01 - Type 1 controlled. She says she considers me an "ideopathic T1" and my treatment is basically like any other T1 would get. But I still consider myself a T2. In the end I had to let go of trying to answer the question of what kind of diabetes I have and how did it happen. My goal is now to make sure I can effectively treat and manage my condition. And as Tim notes, I can do that with insulin so that is really all that matters.

I was kinda wondering if you got the top and bottom of your I:C ratio mixed up!

Oops. My other half and I have endless confusion because of the oddity
that you multiply by a sensitivity factor and divide by the I:C
ratio. I meant 1:2.5 to 1:5. Very obvious when actually dosing...

ZZ

My I:C is 1:15, sometimes though if I'm running low or sick or something is making me slightly lower than average I'll use 1:20 . I usually average about 4-5 units per meal past breakfast.

Lol glydar that's funny but I would be confused too and I don't even think it's impossible for slim people to have type 2.

Do you have a family history of diabetes? Like does it run in your family? If it does, I'd honestly consider MODY into play even though you use insulin and most people with MODY actually use type 2 drugs?