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Re: [IP] Autoimmune disease-Type 1

Hello All,
Here is the article I mentioned - it talks about "Types"


----- Diabetes Interview article - - - - - - - - - - - - -
This is a very complex topic, pri-marily because there is no agreement on
how to classify people who don't meet the classic description of  type 1 and
type 2. Now that we have new and better ways to determine diabetes etiology,
I suspect it will get better over time.

The child who presents with ketoacidosis and the 50-year-old obese woman who
presents with type 2 diabetes after having gestational diabetes during her
last pregnancy are easy diabetes types to classify. We are learning that not
everyone is "classic," however over the past few years, two terms have
entered the literature: "type 1.5" diabetes and latent autoimmune Diabetes
of adults (LADA). The medical literature on these two types suggests they
are one and the same. However, even though there is no consensus on this
point, I look at these two groups of patients as very different. As LADA was
initially described in1994, the adult patients were relative-ly thin and
really looked more like the classic type 1 patients than the obese type 2s.
Clinically, we have learned that they are very insulin-sensitive and make
insulin for many -years-much longer than the typical -"honeymoon" period we
see in children. In the Diabetes Control and -Complications Trial (DCCT),
which -was mostly young adults, many were still making a bit of insulin at
the -beginning of the study. C-peptide lev-els remained higher in those in

intensive therapy group (A1C about 7%) compared to standard therapy (A1C
about 9%). This is the best evidence that tight control preserves insulin
secretion in these adults with newly diagnosed type 1 diabetes.

It is also critical to appreciate that LADA is just a subtype of type 1
diabetes, meaning that LADA patients I also have a high frequency of the I
same autoimmune markers we see in -children. These include islet cell
anti- -body (ICA), glutamic acid decarboxy-lase (GAD), islet cell
antibody-512, and insulin autoantibody. So patients with LADA may make
C-peptide for a very long time and have at least one of these antibodies in
their blood. Unfortunately, over lime these antibodies often tend to go

My favorite story con-cerns a lady in her 50s on only 15 units of insulin.
Her doctor started her on insulin the day she was diagnosed with diabetes.
Her GAD antibody was positive when I saw her, but her diabetes had been
diagnosed 31 years previously So measuring C-peptide may not be the best way
to under-stand the type of diabetes. Really, the entire picture needs to be
looked at.

I see "type 1.5" diabetes as being very different. These are people who look
like type 2 patients (obese, often with high blood pressure, high
triglycerides low HDL cholesterol), yet when the antibodies mentioned above
are measured, one comes back as pos-itive, suggesting that there is also
an -autoimmune process going on leading to insulin deficiency. We don't yet
know the best way to treat these folks, -but they appear to require insulin
much sooner than the type 2s without the antibody Still, for a while they do
I respond to insulin sensitizers such as Glucophage (metformin), Actos
(pio-glitazone) and Avandia (rosiglitazone). This confusing picture can be
sum-marized as follows: LADAs look like type is (generally thin) and are
insulin-sensitive, whereas "type 1.5s" look like type 2s and are
insulin-resistant. Both have one or more anti-bodies that are positive. This
is, of course, my interpretation of what I -see in my clinic; but to be
fair, there isn't enough published research for everyone to agree with what
I see. To take it one step further, we also  see classic type is from
childhood who later develop insulin resistance, usually from an inherited
defect (family history of type 2 diabetes) but occasionally from polycystic
ovary syndrome (PCOS) in women who are insulin resistentSo here, the type 1
starts first, and then they develop obesity and insulin resistance. I say
that those folks have "type 3" diabetes, although others refer to them as
people with "double double" diabetes or "hybrid" diabetes. As for the
question about C-pep-tide tests, it is good to know the glu-cose level when
measuring the C- peptide. With a low glucose reading, however, we would
expect a low C--peptide, so the high C-peptide seen with the glucose reading
of 56 makes me wonder how good the assay for C-peptide was. We've learned
over the years that not all labs do a good job in measuring this.

IRE B. Hirsch, MD

Professor of Medicine, University of Washington School of Medicine
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