Re: Ashley's Story

Charles,

It sounds like you do not yet have all the pieces to solve the puzzle, but
with time you will.

I don't want to interfere with what your docs are doing, and it sounds like
they are giving you good advice. I don't have all the facts that they do, so
if anything here conflicts with what they are telling you, I would go with
what they say.

In interest of time, I'll comment on some but not all the issues.

>
> ·         It is said that exercise does not have any impact on type II
> diabetic patients. However, exercise (walking, swimming, and yoga) reduced
> Ashley's sugar level noticeably.

Whoever said this is wrong. Exercise impact both types.

>
> ·         Ashley's beta cell test (anti islet cell test) performed after
> the diagnosis was negative indicating Ashley was not loosing any beta
> cells. The endocrinologist theorized that Ashley was not loosing any beta
> cells when the test was actually administered. Further, he concluded that
> there is 95% chance that Ashley was Type II diabetic, meaning there is a
> 5% chance Ashley is not diabetic.

You need to be careful with the some of the commercially available tests for
islet cells, as you can see false negative results. IMHO, the best tests in
this family are the Anti-GAD and IA2 antibodies. Negative Anti-GAD and IA2
would suggest no type 1 (see below).

>
> ·         No one from Ashley's family (from both of her parents' sides) is
> diabetic. Ashley's illness cannot be hereditary.

It can still be hereditary. Most children with type 1 have no family
history, just like Ashley. But when you carefully look at the families, many
of them have other autoimmune diseases such as thyroid disease. And if you
wait a while, it is very common to see more autoimmune disease sprout up in
family members.

>
> ·         Ashley's siblings are perfectly healthy.

That's good news. But if Ashley is positive for Anti-Gad or IA2, you should
consider checking the siblings for antibodies too. They can be positive for
several years BEFORE the diagnosis.


> ·         Ashley did not exhibit any type II diabetic symptoms including:
> ketone in blood, excessive thirst, and urinate frequently.

Reminds me of the 17yr old I saw Friday who claimed no symptoms with his 550
mg/dl glucose. We diagnosed him that day with type 1.

>
> My Questions
>

> Naturally, we have a number of questions regarding Ashley's health. The
> staff at THSC has been more than helpful and courteous and I don't intend
> disregard or disrespect their assessment of Ashley's conditions. I just
> have some unanswered questions and was hoping to get some answers from a
> wider forum, while conveying Ashley's story. My questions are:
>
> ·         How can Ashley go from being perfectly healthy (on Feb 24th) and
> Type II diabetic in a week (Mar 03rd)? Can the sugar level increase that
> rapidly over such a short period of time? Wouldn't you expect the sugar
> level to gradually rise if you are diabetic?

No, this is the way children often present.

>
> ·         Is it possible that Ashley's diabetes was triggered by
> Prednisolone (please see my research in Appendix A)? If so, was Ashley
> given a heavier dose that she needed?

Prednisolone unmasked a previously occuring glucose intolerance, but likely
made it look even worse.

> ·         Since Ashley did not show most of the symptoms of a type II
> diabetic patient, except for a temporary short sprout in blood sugar
> level, is it possible that she was rashly misdiagnosed? Are there any more
> tests that we can perform to confirm her diagnosis with a higher degree of
> accuracy?

>
> ·         If there is 5% (according to endocrinologist) chance that Ashley
> is not diabetic, what could explain the whole episode?

There is the entity of childhood "transient hyperglycemia".

Four of my former teachers at Joslin Clinic published a paper on this in
1993. The reference is
J Pediatr. 1993 Sep;123(3):347-54.

"Distinction between transient hyperglycemia and early insulin-dependent
diabetes mellitus in childhood: a prospective study of incidence and
prognostic factors." by Herskowitz-Dumont R, Wolfsdorf JI, Jackson RA,
Eisenbarth GS. .  Joslin Diabetes Center, New England Deaconess Hospital,
Boston, Massachusetts.  (These are some of the foremost researchers in the
cause of type 1 diabetes)

Here is the abstract

"We prospectively studied 63 children with transient hyperglycemia to
determine their risk of acquiring insulin-dependent diabetes mellitus (IDDM)
and to evaluate the predictive value of immunologic markers of prediabetes
and of the intravenous glucose tolerance test. Children with transient
hyperglycemia were identified by a prospective systematic review of the
laboratory reports of a large children's hospital and an office-based
pediatric practice and by referral from pediatricians. Transient
hyperglycemia occurred in 0.46% of children seen in the children's hospital
and in 0.013% of children attending a pediatric office practice.
Insulin-dependent diabetes mellitus developed within 18 months of
identification in 32% of children in whom transient hyperglycemia was
discovered in the absence of a serious illness, compared with 2.3% of
children identified during a serious illness (relative risk, 13.9; 95%
confidence interval, 1.56 to 123.5). Islet cell antibodies and competitive
insulin autoantibodies each had a 100% positive predictive value for IDDM;
the negative predictive value of islet cell antibodies and competitive
insulin autoantibodies was 96% and 98%, respectively. The stimulated insulin
release during an intravenous glucose tolerance test, adjusted for age, had
the highest overall accuracy of prediction. All children less than 6 years
of age with stimulated insulin release levels < 85 pmol/L (12 microU/ml)
subsequently had IDDM, as did an 11-year-old child whose stimulated insulin
release level was below the 1st percentile of 170 pmol/L (24 microU/ml). To
date, no child whose stimulated insulin release level was above the 5th
percentile has had IDDM. We conclude that when transient hyperglycemia
occurs during a serious intercurrent illness, the risk of progression to
IDDM is low. In contrast, one third of children in whom transient
hyperglycemia is identified without a serious illness can be expected to
have IDDM within 1 year. A combination of islet cell antibodies, competitive
insulin autoantibodies, and stimulated insulin release levels during an
intravenous glucose tolerance test can accurately distinguish children with
prediabetes from those with presumed benign transient increases in plasma
glucose concentrations."

Thus, you could consider doing an IV glucose tolerance test to measure the
insulin output. These authors are still working in the field, and your endo
could call them to see if they would have an updated recommendation. Rich
Jackson is still at Joslin Diabetes Center in Boston, Joseph Wolfsorf is at
Children's Hospital in Boston, and George Eisenbarth is at the Barbara Davis
Center at Univ of Colorado in Denver. They are all extremely nice & helpful
docs, and I bet they would be willing to talk to your endo on the phone if
he/she were to call.



> ·         Assuming Ashley is in her honeymoon period, is there a way to
> extend it? Are her conditions reversible?

If this is a honeymoon, you can actually extend it with insulin. I realize
this sounds odd, but insulin seems to reduce the immune attack from the
islet cells, and reduces the stress on the islets.


> ·         Should Ashley's siblings be worried? Are there any precautions
> that they can take?

If Ashley has type 1, they have a small ~5% risk themselves.

>
> ·         How did exercise help with Ashley's blood sugar level when she
> is diagnosed with type II diabetes?

It helps everyone's BG.

>
> ·         Is there an alternative treatment method to reduce/control Type
> II diabetes?

In early Type 1 there are preventative treatments being developed with
TrialNet.

If you mean alternative, such as health foods, etc, don't waste your time.


> ·         Is there an alternative method to administer insulin than
> injections?

Inhaled insulin is being released in the US next month.


> ·         Can the beta cells be harvested from Ashley's twin sister and
> transplanted to Ashley?

Twin ??!?

Is this an identical twin?

At this point, islet cell transplantation is promising, but not yet 'there'.

Since Ashley's glucose is back to normal, this is a moot issue. She would
not be needing islets if her BG is normal, and the risks to your daughters
are too great.

Summary:

Ashley could have transient hyperglycemia of childhood triggered by her
respiratory illness. The magnitude of the BG elevation was made worse by the
prednisolone.  The issue that you have hit upon is how to identify whether
this is early type 1 diabetes vs. transient hyperglycemia.

You may want to consider checking anti-GAD and IA2 antibodies if they were
not the ones already done. Negative antibodies are about 96- 98% predicitive
that she does not have type 1. If negative, you can either wait and continue
to monitor Ashley, or consider doing the IV glucose tolerance test which
would have even more predictive value.

For what it is worth, I have had one similar case in the last 20 years. A 14
year old with a BG of 250 (13.8 mmol/l) , trace ketones, & repeatedly
negative antibodies. I watched her for about 6 years before she moved away,
and still had no recurrence of any glucose intolerance. We discussed doing
an IV glucose tolerance test, but decided not to.

Good luck. Let us know how it goes for you & Ashley.


William C Biggs MD FACE
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