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In the last three weeks I have been diagnosed with

complications which I believe are directly related to

PSC. I was diagnosed 3 weeks ago with osteopenia and

finally gave in to taking the fosamax after I was sure

it was ok. This past week, I have been diagnosed with

diabetes and most recently elevated creatinine in my

blood indicating poor kidney function Although I

refuse to let this disease define me; I can't help but

believe this is related to 13 years of PSC. I am

concerned about the relationship of Diabetes to PSC

and its potential harm or detriment to future

treatments, i.e. transplants, ercps. I would

appreciate any thoughts from those who may have

similar issues.

Thanks

Phil

50 Psc/uc: 93

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>

> In the last three weeks I have been diagnosed with

> complications which I believe are directly related to

> PSC... This past week, I have been diagnosed with

> diabetes and most recently elevated creatinine in my

> blood indicating poor kidney function Although I

> refuse to let this disease define me; I can't help but

> believe this is related to 13 years of PSC. I am

> concerned about the relationship of Diabetes to PSC

> and its potential harm or detriment to future

> treatments, i.e. transplants, ercps.

Hello to and Barb and others who do research for us so well and

seemingly efficiently (I'm sure faster and better than I do!)... I

have had the same questions as Phil. Is there a higher prevalence of

diabetes among PSC'ers? If so, any ideas why (other than potential

higher prednisone use due to history of UC... or quiescent chronic

pancreatitis... or....???).

If there is higher incidence, I wonder if there is a protective

benefit by careful diet, with low concentrated sweets (which I think

many do by watching their fat intake and pie, cake, candy, ice cream,

etc are all high sugar and high fat!).

I'd be curious if there is any literature on incidence of diabetes

with PSC and/or more general liver disease.

Thanks for your time.

Joanne

(, Ca, mom of , 16, PSC/UC 2-06; JRA 2-98)

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Hi Joanne;

I've read that there seems to be a higher incidence of autoimmune

diseases in PSCers, and this may be in part be a genetic

predisposition:

Am J Gastroenterol. 2000 Nov;95(11):3195-9.

Increased frequency of autoimmune diseases in patients with primary

sclerosing cholangitis.

Saarinen S, Olerup O, Broome U

Department of Gastroenterology and Hepatology, Karolinska Institute

at Huddinge University Hospital, Stockholm, Sweden.

OBJECTIVES: Primary sclerosing cholangitis (PSC) is a chronic

cholestatic liver disease of unknown origin that mostly affects male

patients with inflammatory bowel disease (IBD). The immune system is

believed to be involved in the etiology/pathogenesis as these

patients present with several immunological disturbances.

Susceptibility to develop primary sclerosing cholangitis is partly

determined by genes in the HLA complex. The aim of this study was to

compare the prevalence of autoimmune disorders in IBD patients with

and without PSC and to correlate the presence of autoimmune disorders

in PSC to outcome and HLA association. METHODS: One hundred nineteen

PSC patients were included in the study. Each PSC patient with IBD

was matched to a IBD patient without PSC. The presence of autoimmune

disorders was carefully evaluated in each group. Moreover,

comparisons between PSC patients with and without autoimmune

disorders were performed. RESULTS: Twenty-five percent of the PSC

patients had at least one autoimmune disorder outside the liver and

colon compared to 9% in the IBD group without PSC (p < 0.005). Nine

of the PSC patients had two or more autoimmune diseases compared to

only one patient in the IBD group (p < 0.02). The PSC patients with

and without associated autoimmune disease did not differ in clinical

presentation, outcome of PSC or HLA alleles. A significant

overrepresentation of DRB1*03 was still present after excluding PSC

patients with concomitant autoimmune diseases outside the liver and

colon compared to a healthy Swedish control group. CONCLUSIONS:

Autoimmune disorders are more frequent among PSC patients compared to

IBD patients without liver disease. Associated autoimmune diseases in

PSC patients does not influence the outcome or clinical presentation

of PSC. PMID: 11095341.

I can't access the full manuscript of this paper right now to find

out which autoimmune diseases they considered. But I'll try to get

the details for you tomorrow.

Potincasa lists the diseases most commonly associated with PSC:

Table 1 Diseases most commonly associated with PSC

Celiac disease

Rheumatoid arthritis

Thyroiditis

Sjogren's syndrome

Lupus erythematosus

Lupic nephritis

Chronic pancreatitis

Retroperitoneal fibrosis

Systemic sclerosis

Peyronie's disease

Autoimmune hemolytic anemia

Immune thrombocytopenic purpura

Membranous nephropathy

Histiocytosis X

Cystic fibrosis

Angioblastic lymphadenopathy

Intra-abdominal adenopathy

Vasculitis

Pseudotumor of the orbit

Gallbladder disease

(Portincasa P, Vacca M, Moschetta A, Petruzzelli M, Palasciano G, van

Erpecum KJ, van Berge-Henegouwen GP. Primary sclerosing cholangitis:

updates in diagnosis and therapy. World J Gastroenterol. 2005 Jan 7;11

(1):7-16. PMID: 15609388)

Suprisingly diabetes is not on this list, suggesting that it may be

relatively rare? The following paper suggests that the " unusual "

combination of PSC, UC and diabetes might be associated with

specific genes/alleles in the human leukocyte antigen (HLA) complex:

J Intern Med. 1993 Mar;233(3):281-6.

HLA-DR3, DQ2 homozygosity in two patients with insulin-dependent

diabetes mellitus superimposed with ulcerative colitis and primary

sclerosing cholangitis.

Ivarsson SA, sson S, Kockum I, Lernmark A, Lindgren S, Nilsson

KO, Sundkvist G, Wassmuth R

Department of Paediatrics, University of Lund, Malmo General

Hospital, Sweden.

Two unrelated young males with the unusual simultaneous presence of

insulin-dependent diabetes mellitus, ulcerative colitis and primary

sclerosing cholangitis are reported. Both patients manifested

homozygosity for the DR3-DQw2 (DQB*0201) HLA genotypes. We believe

that homozygosity for this genotype may predispose for this type of

multi-organ autoimmune disease. PMID: 8450297.

Best regards,

Dave

(father of (21); PSC 07/03; UC 08/03)

> I'd be curious if there is any literature on incidence of diabetes

> with PSC and/or more general liver disease.

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This is interesting.

My mother has hyperthyroidism, my sister

has UC (no PSC) and I have PSC (no IBD).

Chaim Boermeester, Israel

From:

[mailto: ] On Behalf Of

Sent: Sunday, March 18, 2007 9:09

AM

To:

Subject: Re: psc

complications

Hi Joanne;

I've read that there seems to be a higher incidence of autoimmune

diseases in PSCers, and this may be in part be a genetic

predisposition:

Am J Gastroenterol. 2000 Nov;95(11):3195-9.

Increased frequency of autoimmune diseases in patients with primary

sclerosing cholangitis.

Saarinen S, Olerup O, Broome U

Department of Gastroenterology and Hepatology, Karolinska Institute

at Huddinge University

Hospital, Stockholm, Sweden.

OBJECTIVES: Primary sclerosing cholangitis (PSC) is a chronic

cholestatic liver disease of unknown origin that mostly affects male

patients with inflammatory bowel disease (IBD). The immune system is

believed to be involved in the etiology/pathogenesis as these

patients present with several immunological disturbances.

Susceptibility to develop primary sclerosing cholangitis is partly

determined by genes in the HLA complex. The aim of this study was to

compare the prevalence of autoimmune disorders in IBD patients with

and without PSC and to correlate the presence of autoimmune disorders

in PSC to outcome and HLA association. METHODS: One hundred nineteen

PSC patients were included in the study. Each PSC patient with IBD

was matched to a IBD patient without PSC. The presence of autoimmune

disorders was carefully evaluated in each group. Moreover,

comparisons between PSC patients with and without autoimmune

disorders were performed. RESULTS: Twenty-five percent of the PSC

patients had at least one autoimmune disorder outside the liver and

colon compared to 9% in the IBD group without PSC (p < 0.005). Nine

of the PSC patients had two or more autoimmune diseases compared to

only one patient in the IBD group (p < 0.02). The PSC patients with

and without associated autoimmune disease did not differ in clinical

presentation, outcome of PSC or HLA alleles. A significant

overrepresentation of DRB1*03 was still present after excluding PSC

patients with concomitant autoimmune diseases outside the liver and

colon compared to a healthy Swedish control group. CONCLUSIONS:

Autoimmune disorders are more frequent among PSC patients compared to

IBD patients without liver disease. Associated autoimmune diseases in

PSC patients does not influence the outcome or clinical presentation

of PSC. PMID: 11095341.

I can't access the full manuscript of this paper right now to find

out which autoimmune diseases they considered. But I'll try to get

the details for you tomorrow.

Potincasa lists the diseases most commonly associated with PSC:

Table 1 Diseases most commonly associated with PSC

Celiac disease

Rheumatoid arthritis

Thyroiditis

Sjogren's syndrome

Lupus erythematosus

Lupic nephritis

Chronic pancreatitis

Retroperitoneal fibrosis

Systemic sclerosis

Peyronie's disease

Autoimmune hemolytic anemia

Immune thrombocytopenic purpura

Membranous nephropathy

Histiocytosis X

Cystic fibrosis

Angioblastic lymphadenopathy

Intra-abdominal adenopathy

Vasculitis

Pseudotumor of the orbit

Gallbladder disease

(Portincasa P, Vacca M, Moschetta A, Petruzzelli M, Palasciano G, van

Erpecum KJ, van Berge-Henegouwen GP. Primary sclerosing cholangitis:

updates in diagnosis and therapy. World J Gastroenterol. 2005 Jan 7;11

(1):7-16. PMID: 15609388)

Suprisingly diabetes is not on this list, suggesting that it may be

relatively rare? The following paper suggests that the " unusual "

combination of PSC, UC and diabetes might be associated with

specific genes/alleles in the human leukocyte antigen (HLA) complex:

J Intern Med. 1993 Mar;233(3):281-6.

HLA-DR3, DQ2 homozygosity in two patients with insulin-dependent

diabetes mellitus superimposed with ulcerative colitis and primary

sclerosing cholangitis.

Ivarsson SA, sson S, Kockum I, Lernmark A, Lindgren S, Nilsson

KO, Sundkvist G, Wassmuth R

Department of Paediatrics, University

of Lund, Malmo General

Hospital, Sweden.

Two unrelated young males with the unusual simultaneous presence of

insulin-dependent diabetes mellitus, ulcerative colitis and primary

sclerosing cholangitis are reported. Both patients manifested

homozygosity for the DR3-DQw2 (DQB*0201) HLA genotypes. We believe

that homozygosity for this genotype may predispose for this type of

multi-organ autoimmune disease. PMID: 8450297.

Best regards,

Dave

(father of (21); PSC 07/03; UC 08/03)

> I'd be curious if there is any literature on incidence of diabetes

> with PSC and/or more general liver disease.

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> I can't access the full manuscript of this paper right now to find

> out which autoimmune diseases they considered. But I'll try to get

> the details for you tomorrow.

Hi Joanne;

I've uploaded the Saarinen paper to the files/research folder. Looking

at the details presented in this paper it appears that PSC with

diabetes is not that rare [at least in Scandinavia]! My apologies for

jumping to a false conclusion in my earlier post!

Best regards

Dave

(father of (21); PSC 07/03; UC 08/03)

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Dave -

Thanks for both of your responses. I copied the article you sent. I

have seen other lists of autoimmune diseases which do include

diabetes. We actually saw the elevated LFT's on blood work for

done 7 years prior to his PSC diagnosis. He was having acute abdominal

pain, with symptoms so similar to GERD (GI reflux). On work-up, all

that showed was non-functional gallbladder and elevated LFT's.

Prilosec and diet changes helped somewhat for all those years.

The original lab work was done for his medications for Juvenile

Rheumatoid Arthritis (which I felt so pleased that it was the

pausi-articular arthritis which kids typically grew out of!). His

knees still bother him and unfortunately, when his PSC/UC are bad, his

entire spinal column hurts him.

has a first cousin with juvenile diabetes (on my dad's side).

His grandmother (my mom) was diagnosed last year with ulcerative

colitis, age 74. Nearly all of my aunts, uncles and grandparents on

both sides of family have diabetes! Our family is a mix of paternal

Jewish Belarus and English/Irish/French!

One other interesting thing - I recently read (but heaven knows where)

that someone believes that nearly 100% of PSC patients will eventually

demonstrate symptoms of UC or Crohns. Wish I could remember where I

read that.

As always, thank you SO Much for your research and time and thoughts.

Joanne

(, Ca., mom of , 16, UC/PSC 2-06; JRA 2-98)

>

> Table 1 Diseases most commonly associated with PSC

>

> Celiac disease

> Rheumatoid arthritis

> Thyroiditis

> Sjogren's syndrome

> Lupus erythematosus

> Lupic nephritis

> Chronic pancreatitis

> Retroperitoneal fibrosis

> Systemic sclerosis

> Peyronie's disease

> Autoimmune hemolytic anemia

> Immune thrombocytopenic purpura

> Membranous nephropathy

> Histiocytosis X

> Cystic fibrosis

> Angioblastic lymphadenopathy

> Intra-abdominal adenopathy

> Vasculitis

> Pseudotumor of the orbit

> Gallbladder disease

>

> Suprisingly diabetes is not on this list, suggesting that it may be

> relatively rare? The following paper suggests that the " unusual "

> combination of PSC, UC and diabetes might be associated with

> specific genes/alleles in the human leukocyte antigen (HLA) complex:

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-----Original Message-----

has a first cousin with juvenile diabetes (on my dad's

side). Nearly all of my aunts,

uncles and grandparents on

both sides of family have diabetes!

Joanne,

I found – literally

- dozens of studies that say diabetes can lead to liver disease. Also found one article that said, in some

cases they actually couldn’t figure out which came first – diabetes

or liver disease.

Barb in Texas

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> Joanne,

> I found - literally - dozens of studies that say diabetes can lead to

> liver disease. Also found one article that said, in some cases they

> actually couldn't figure out which came first - diabetes or liver

> disease.

Pretty fascinating - the functions of liver and pancreas are so

complex... it just makes you wonder if we could figure out the

relationships, where would that lead in looking for treatments and cure.

Joanne

(, Ca)

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