Re: GAD65 and a question on C-peptide c

[Guest guest]

If your doctor is typical, he won't do the GAD65. I had to carry on for

over 3 years before I got a repeat of the C-peptide that was done upon dx.

The C-peptide and the lipid panel have to be done fasting. Don't know about

the GAD since I never had one done.

BTW, the C-peptide is a molecule that is produced with endogenous insulin

(that your body produces). Insulin that you shoot does not have C-peptides.

So even if you are taking exogenous insulin (synthetic), they can still

measure the amount of insulin your body is producing by counting the

C-peptides. They haven't found a purpose for C-peptide. I hope they find

out soon because our bodies never manufacture anything that has no purpose

and it just might be important.

I have a question myself: There seem to be 2 kinds of C-peptide tests that

are done... one is called a C-peptide and the normal range is described in

very low numbers (don't know in what unit scale); the other was a

*C-peptide c* whose lab normal range are numbers in the hundreds. I asked

my endo but he didn't know either. ;o) Does anyone here have the answer?

Nora

At 10:50 AM 1/11/06 -0500, you wrote:

>Is the C-peptide the same as the GAD antibody? I did request the GAD

>antibody from him just recently to be done at the same time as the A1c I

>already had scheduled (haven't received an answer from him yet) but if he

>says yes, I should reschedule to the first thing a.m. ? I guess he isn't

>doing a lipid panel but I am sorta curious about it.

>

>Sandy

[Guest guest]

GAD isn't the same as the C-Peptide test. And if I remember correctly,

it doesn't have to be done fasting.

Sandy, don't let your doctor give you a " no " on this. If he says no, I

have at least one article in my archives that might help convince him.

OTOH...maybe I should send it/them to you now?

Vicki

Re: GAD65 and a question on C-peptide c

> If your doctor is typical, he won't do the GAD65. I had to carry on

> for

> over 3 years before I got a repeat of the C-peptide that was done upon

> dx.

> The C-peptide and the lipid panel have to be done fasting. Don't know

> about

> the GAD since I never had one done.

>

> BTW, the C-peptide is a molecule that is produced with endogenous

> insulin

> (that your body produces). Insulin that you shoot does not have

> C-peptides.

> So even if you are taking exogenous insulin (synthetic), they can

> still

> measure the amount of insulin your body is producing by counting the

> C-peptides. They haven't found a purpose for C-peptide. I hope they

> find

> out soon because our bodies never manufacture anything that has no

> purpose

> and it just might be important.

>

> I have a question myself: There seem to be 2 kinds of C-peptide tests

> that

> are done... one is called a C-peptide and the normal range is

> described in

> very low numbers (don't know in what unit scale); the other was a

> *C-peptide c* whose lab normal range are numbers in the hundreds. I

> asked

> my endo but he didn't know either. ;o) Does anyone here have the

> answer?

>

> Nora

>

> At 10:50 AM 1/11/06 -0500, you wrote:

>>Is the C-peptide the same as the GAD antibody? I did request the GAD

>>antibody from him just recently to be done at the same time as the A1c

>>I

>>already had scheduled (haven't received an answer from him yet) but if

>>he

>>says yes, I should reschedule to the first thing a.m. ? I guess he

>>isn't

>>doing a lipid panel but I am sorta curious about it.

>>

>>Sandy

[Guest guest]

Can you post it please Vicki? I would be interested it in as I would like my

mom to get tested with this.

Shauna :-)

OTOH...maybe I should send it/them to you now?

Vicki

[Guest guest]

Sandy, don't let your doctor give you a " no " on this. If he says no, I

have at least one article in my archives that might help convince him.

OTOH...maybe I should send it/them to you now?

Vicki

---------

Yes Vicki - please do!

Sandy

[Guest guest]

Well...here's the SHORT one ...

I'll send the longer one to Sandy offlist.

Vicki

<<

LATENT AUTOIMMUNE DIABETES IN ADULTS (LADA) ­

OVERVIEW,EPIDEMIOLOGY, CURRENT ISSUESJerry P. Palmer, MD, University

ofWashington, Seattle, Washington, USA

When islets cell antibodies (ICA) and the association of this antibody

with type 1 diabetes was discovered over 25 years ago, patients with

type 2 diabetes were also found to be positive forICA more commonly than

normal controls. Of the four autoantibodies found in classical childhood

type 1 diabetes (T1DM) only ICA and GAD antibodies are prevalent in type

2 diabetes(T2DM); insulin

autoantibodies and IA2 antibodies are much less prevalent.

Subsequently, many populations of T2DM around the world have been

screened for ICA and GAD antibodies andthose found to be positive have

been called LADA, antibody positive type 2 diabetes, type 1.5diabetes,

slowly progressive insulin dependent diabetes (SPIDDM), youth onset

diabetes ofmaturity (YODM) and progressive insulin dependent diabetes

mellitus (PIDDM).

Although the frequency varies from 5% or less to 30% in some Caucasian

populations, there is general agreement that LADA patients lose beta

cell

function more rapidly, fail sulfonylurea therapymore quickly, and

require insulin earlier than antibody negative type 2 diabetic patients.

LADA patients also have T cells reactive with islet antigens similar to

T1DM but there is a suggestion that there also may be antigenic

differences in T-cell reactivity between classical childhood T1DM and

LADA, similar to the antibody differences.

Current questions being investigated in LADA patients include: Is LADA a

phenotypic variant of type 1 diabetes or is it a separate typeof

autoimmune diabetes, is LADA one disease, and are specific forms of

treatment preferred in LADA patients? Because LADA is much more common

than T1DM and because the insulin resistance present in LADA patients

causes them to present with clinical diabetes with much more residual

beta cell function than T1DM, there is considerable interest in

determining whether there are specific

therapeutic interventions which will preserve beta cell function in this

subset ofT2DM.

If ENDIT, the DPT1, or one of the other immunomodulatory interventions

being tested in T1DM are found to be successful, we will immediately

need to determine whether this intervention is also efficacious in LADA

patients.

ANTIBODY PROFILE AND EPITOPE MAPPING IN LADA PATIENTS

A.Falorni , University of Perugia, Italy

Latent autoimmune diabetes of the adult (LADA) is identified by the

presence of GAD65autoantibodies (GAD65Ab) in adult diabetic subjects not

requiring insulin therapy at the time of clinical diagnosis. The

presence of GAD65Ab, in LADA subjects, is highly predictive for the

future development of insulin dependency, but not all GAD65Ab-positive

LADA subjects will require insulin therapy at follow-up.

We have studied the GAD65Ab epitope pattern of LADAsubjects and

demonstrated the occurrence of autoantibodies to both the middle

(GAD65-MAb)and the COOH-terminal (GAD65-CAb) region of the autoantigen.

However, only the presence of GAD65-CAb was associated with high risk of

progression towards insulin dependency and low C-peptide values at

follow-up, while the exclusive presence of GAD65-MAb identified

a subgroup of LADA subjects with clinical and metabolic characteristics

indistinguishable from those of typical Type 2 diabetic individuals.

We have also studied the occurrence of other organ-specific

autoantibodies,

such as those directed to thyroid peroxidase (TPOAb),

21-hydroxylase(21OHAb), side-chain cleavage enzyme (P450sccAb),

17-hydroxylase (17OHAb) and tissuetransglutaminase (IgG-TTGAb) and

demonstrated that LADA subjects with GAD65C-Ab, butnot those with only

GAD65-MAb, are characterised by a significantly higher frequency of

markers of organ-specific autoimmunity as compared to typical,

GAD65Ab-negative, type 2diabetic subjects.

We conclude that LADA, as identified by GAD65C-Ab, must be considered a

component of the autoimmune polyendocrine syndromes of the adult.

GENETICS OF LADA

C.B.Sanjeevi, Karolinska Institute, Stockholm, Sweden

The slowly progressing Type 1 diabetes or Latent autoimmune diabetes in

adults (LADA) is associated with HLA class II genes like classical Type

1

diabetes (T1DM). T1DM is positively associated with HLA DR4-DQ8 and or

DR3-DQ2 while DR15-DQ6 (B*0602) is negative associated. The studies done

in Caucasians and other ethnic groups show that DR3-DQ2 is associated in

LADA patients than DR4-DQ8. We recently demonstrated that the

polymorphic alleles of MHC class I chain related A (MICA) gene, located

telomeric to the TNFa gene between the B-associated transcript (BAT-1)

and the HLA-B genes, influences the risk forT1DM. In addition, other

studies have observed an association between MICA genepolymorphism and

T1DM in other ethnic groups. MICA5 was significantly associated withT1DM

only in the age group 1-25 yrs at diagnosis and allele 5.1 of MICA is

associated withadult onset T1DM (>25 years age at onset).

It is still unclear whether LADA is under the control of distinct

genetic markers or is only theconsequence of the action of protective

environmental factors

on a genetic backgroundpredisposing for autoimmune diabetes. Our studies

on MICA shows that allele 5.1 is associated.

LADA patients in European Caucasians. Our study provides the

demonstration of the existence of distinct genetic markers for

childhood/young-onset T1DM and for adult onset T1DM/LADA,namely MICA5

and MICA5.1, respectively.

LATENT AUTOIMMUNE DIABETES IN ADULTS Mona Landin Olsson, Associate

Professor, Dept of Diabetology and Endocrinology, University Hospital,

Lund, Sweden.

After diagnosis of Type 2 diabetes, many patients fail on oral

hypoglycemic

agents and become insulin requiring. Since it is unclear to which extent

undiagnosed autoimmune diabetes contribute to this, we determined

pancreatic autoantibodies in newly diagnosed adult diabetic patients.

Blood samples were collected from 1037 consequtively diagnosed

adult patients (range15-90 years) with diabetes in our district during

four years (Sept 1995-Aug 1999). ICA, GADAand C-peptide were analysed in

1037 patients We found that 159 (15.3%) were positive for any of these

autoantibodies (17.1% of men and 14.6% among women, ns). GADA was the

most frequently occuring antibody (13.6%), followed by ICA (12.9%). Of

all antibody positivepatients (n=159), 55% were classified as Type 1.

About 7% of patients diagnosed as Type 2diabetes were positive for a

pancreatic autoantibody.

The frequency of autoimmune diabetes in the age group 18-30 yrs was

62.0% , in 31-40 yrs 30.2%, in 41-50 yrs 18.5%, in 51-60 yrs 8.7%,in

61-70 yrs 6.4%, in 71-80 yrs 7.0% and among patients older than 80 yrs

it was 2.6%. The absolute number was equal in the group of patients over

and below 40 yrs of age. BMI and C-peptide levels increased

significantly with age, although these levels were lower than in

patients without autoantibodies.

In conclusion, we found that the frequency of autoimmune diabetes was

clinically underestimated among adult diabetic patients. Autoimmune

diabetes occurred in all ages. Since BMI and C-peptide increased with

age, also in autoimmune diabetes, these parameters were less useful in

the differentiation between Type 1 and Type 2 diabetes.

We therefore propose that at least GADAshould be analysed in adult onset

diabetes mellitus.

MULTICENTER INTERVENTION TRIAL OF SLOWLY PROGRESSIVE IDDM WITHSMALL DOSE

OF INSULIN (THE TOKYO STUDY)T.

Kobayashi, T. Maruyama, A. Shimada, A. Kasuga, A. Kanatsuka, I. Takei

and J. Yokoyama,Tokyo, Saitama, Japan

Background:Intervention effect of small dose of insulin (SDI) was

observed on progressivebeta-cell dysfunction in islet cell antibody

(ICA) positive patients with apparent NIDDM (slowly progressive IDDM:

SPIDDM) (Diabetes 45: 622-626, 1996).

Aim :To access the effect of SDI on beta-cell failure in SPIDDM on

multicenter randomized bases.

Materials and Methods:Non-insulin requiring diabetic patients were

selected if they were positive for GADAb and ICA.

The target of glycemic control was as follows: fasting blood glucose

(FBG) less than 120 mg/dl and/or HbA1c less than 7.0%. The criteria for

determining failure of SU included: FBG became more than 200 mg/dl

and/or

HbA1c value more than 9%with the maximal daily dose of glibenclamide

(7.5 mg). All patients received 75g oral glucosetest (OGTT).

Insulin-dependent stage was defined that integrated value of serum

C-peptide levels to OGTT (sigma CPR) becomes less than 4 ng/ml.

Fifty-one

GADAb+ subjects [M/F:30/21, age: 54+/-14 years (M+/-SD), duration: 2.5

+/-3.2 years] were recuited from 3056 non-insulin requiring diabetic

patients. These patients were randomely devided into 2 groups:

Insulin group (n=23) and sulfonylurea (SU) group (n=28).

Results: Sigma CPR value in SU group decreased progressively from

21.3+/-8.3 to 17.3 +/-7.6ng/ml during 2 years, (p < 0.05 vs. baseline).

The value in

Insulin group remain unchanged. Among SU group, 14% (4/28) of subjects

progressed to IDDM stage, while 9% (2/23) of subjects in Insulin group

progressed IDDM stage (N.S.).

With regard to the subjects who had preserved CPR during OGTT (>sigma

CPR 10 ng/ml), SU group subjects progressed to IDDM(4/28) more

frequently than Insulin group subjects (0/21) (p < 0.02).

Conclusion: SDI treatment is effective mean to prevent beta-cell failure

in SPIDDM, especiallyin the patients who initially have preserved

insulin response.

PEPTIDE THERAPY AND PREVENTION OF BETA CELL DETERIORATION IN LADA

P. Pozzilli, University Campus Bio-Medico, Rome, Italy

Prevention of progression towards full exhaustion of beta cells and

consequent dependency frominsulin could be ideally applied to LADA

patients. Assuming the disease process in LADA is similar to that of

young onset Type 1 diabetes although less destructive, protection of

beta cells from complete destruction might be attempted. Clinical

trials are therefore needed in patients with LADA.

Careful selection of patients taking into account duration of overt

hyperglycaemia, presence of one or more islet cell autoantibodies,and

age are critical. The calculation of the required sample size would not

be easy. depending onwhat the end points of the study are. Monitoring

of

C-peptide secretion is an ideal option as to determine the effect of a

given therapeutic approach on the residual beta cell function.

Insulin requirement as an end point would be difficult to assess in a

context of such a trial.Antigen specific suppression using Diapep 277 is

a new and interesting preventive approach to stop progression towards

beta cell destruction. The strategy underlying the Diapep 277 approach

in

LADA is that of antigen specific suppression. Hsp60- specific

autoimmunity precedes the onset of clinical hyperglycemia in the NOD

mouse and the low-dose streptozotocin (STZ)model. The autoimmune

response to hsp60 is not just an epiphenomenona, but probably plays

a role in the pathogenesis of beta cell destruction.The diabetogenic

T-cells recognize an hsp60 peptide epitope corresponding to the

positions 437-460, called p277. This peptide contains two cystein

residues that are highly sensitive to oxidation. The peptide is fully

cross-reactive with the original p277 and has the same

biological activity.

Phase II trials have begun in recent-onset type 1 patients (children and

adults) and early data has shown that stimulated C-peptide can be

preserved at 1 year after diagnosis compared to control patients. For

the LADA trial the end points of a Diapep 277 trial include:a)

progression of beta cell destruction as measured by fasting and

stimulated C-peptide secretion; improvement of metabolic control, as

measured by glycosylated haemoglobin; c) prevention or delay in

progression to insulin therapy using defined criteria for such therapy;

d) modification of immune changes associated with beta cell destruction

by determining cytokine secretion andfluctuation of islet cell antigens

related

antibodies.lications.

RE: GAD65 and a question on C-peptide c

> Can you post it please Vicki? I would be interested it in as I would

> like my

> mom to get tested with this.

>

>

>

> Shauna :-)

>

>

>

>

> OTOH...maybe I should send it/them to you now?

> Vicki

>

[Guest guest]

> >>Is the C-peptide the same as the GAD antibody? I did request the

GAD

> >>antibody from him just recently to be done at the same time as

the A1c

> >>I

> >>already had scheduled (haven't received an answer from him yet)

but if

> >>he

> >>says yes, I should reschedule to the first thing a.m. ? I guess

he

> >>isn't

> >>doing a lipid panel but I am sorta curious about it.

> >>

> >>Sandy

>

[Guest guest]

Vickie,

Please include me when you send out the GAD info.

hanks in advance.

> GAD isn't the same as the C-Peptide test. And if I remember

> correctly,

> it doesn't have to be done fasting.

>

> Sandy, don't let your doctor give you a " no " on this. If he says

> no, I

> have at least one article in my archives that might help convince him.

> OTOH...maybe I should send it/them to you now?

> Vicki

>

=+=+=+=+=+=+=

Maurer

Type II diabetic since 4/87

(diet, exercise, & meds)

Insulin dependent Type II since 9/04

(diet, exercise, Lantus, Humalog, & Metformin XR)

=+=+=+=+=+=+=