2
to the uterus and a pregnancy can begin. In the current study, researchers found that at the time the uterus is most receptive to the embryo, women with infertility because of endometriosis have very low levels of an enzyme that is involved in synthesizing the lig- and for L-selectin. The ligand is a rubberband- like molecule that tethers L-selectin to the wall of the uterus. Because the women lack the enzyme that makes the L-selectin ligand, the embryo may not be able to attach to the uter- ine wall, and a pregnancy cannot begin. The scientists in this study used a new tech- nology called microarray analysis, which makes it possible to screen a large number of genes at one time. The researchers measured gene expression—the turning on or off of a particu- lar gene, like a light switch turns a light on or off. They analyzed more than 12,000 genes. They found 91 genes that had more than a twofold increase in gene expression in women with endometriosis, compared to those with- out the disease, and 115 genes that had more than a twofold decrease in expression in women with endometriosis compared to those without. These genes are likely to play a role in the development of endometriosis in the pelvis and its associated infertility. In addition, the researchers found three groups of genes that appear to play a role in endometriosis. One group of genes increased in expression during the window of implanta- tion in women without endometriosis, but sig- nificantly decreased at this time in women with the disease. The gene for the enzyme needed to synthesize the ligand for L-selectin appeared in this group. The second group of genes normal- ly decreased, but instead increased in women with endometriosis. The third group of genes consisted of only one gene, which normally decreased during the window of implantation, but in women with endometriosis, it decreased even further. The researchers’ data support the theory that having certain genes present in the incor- rect amount contributes to the development of endometriosis. It may also create an inhos- pitable environment for an embryo to attach to the uterus. The findings also add weight to the hypothesis that the endometrium of women with endometriosis is abnormal. The study’s findings might lead to a new way to screen women for the disease. Currently, diagnosis requires a laparoscopy (a procedure in which a small incision is made in the abdomen) or laparotomy (a larger incision is made), usually with a general anesthetic. This new research may one day enable scien- tists to develop a less invasive test, based on the detection of abnormal gene activity. More information about endometriosis is available from the NICHD publication Endometriosis, at www.nichd.nih.gov/ publications/pubs/endometriosis.pdf. Oral Insulin Doesn’t Prevent Type 1 Diabetes I nsulin taken orally doesn’t delay or prevent type 1 diabetes in people at moderate risk (25 to 50 percent likelihood) of developing type 1 diabetes in five years, researchers report- ed at the annual meeting of the American Dia- betes Association. The finding emerged from the second trial conducted as part of the Dia- betes Prevention Trial-Type 1 (DPT-1), which ended last month. The findings affirm the other DPT-1 trial, completed two years ago, which found that low-dose insulin injections failed to prevent or delay type 1 diabetes in people at high risk (50 percent or greater chance) of developing the disease in five years. The oral insulin study was based on the hypothesis that insulin taken orally might sup- press the immune system’s destructive attack on beta cells. Studies in the nonobese diabetic (NOD) mouse, an animal model of type 1 dia- betes, had shown that oral insulin given before diabetes development could reduce or delay onset of the disease. By “feeding” a person insulin, the immune cells in the digestive tract might learn to recognize insulin in a different way and favor the development of immune responses that delay the onset or progression of diabetes or prevent its occurrence altogether. The oral insulin trial is the third large study that failed to prevent type 1 diabetes in at-risk people. The European Nicotinamide Diabetes Intervention Trial (ENDIT) also failed to pre- vent or delay type 1 diabetes with nicoti- namide, a vitamin present in small amounts. 310 AWHONN Lifelines Volume 7 Issue 4 Carolyn Davis Cockey, MLS, is executive editor of AWHONN Lifelines and associate director of publications for AWHONN.

Oral Insulin Doesn't Prevent Type 1 Diabetes

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to the uterus and a pregnancy can begin. In the

current study, researchers found that at the

time the uterus is most receptive to the

embryo, women with infertility because of

endometriosis have very low levels of an

enzyme that is involved in synthesizing the lig-

and for L-selectin. The ligand is a rubberband-

like molecule that tethers L-selectin to the wall

of the uterus. Because the women lack the

enzyme that makes the L-selectin ligand, the

embryo may not be able to attach to the uter-

ine wall, and a pregnancy cannot begin.

The scientists in this study used a new tech-

nology called microarray analysis, which makes

it possible to screen a large number of genes at

one time. The researchers measured gene

expression—the turning on or off of a particu-

lar gene, like a light switch turns a light on or

off. They analyzed more than 12,000 genes.

They found 91 genes that had more than a

twofold increase in gene expression in women

with endometriosis, compared to those with-

out the disease, and 115 genes that had more

than a twofold decrease in expression in

women with endometriosis compared to those

without. These genes are likely to play a role in

the development of endometriosis in the pelvis

and its associated infertility.

In addition, the researchers found three

groups of genes that appear to play a role in

endometriosis. One group of genes increased

in expression during the window of implanta-

tion in women without endometriosis, but sig-

nificantly decreased at this time in women with

the disease. The gene for the enzyme needed to

synthesize the ligand for L-selectin appeared in

this group. The second group of genes normal-

ly decreased, but instead increased in women

with endometriosis. The third group of genes

consisted of only one gene, which normally

decreased during the window of implantation,

but in women with endometriosis, it decreased

even further.

The researchers’ data support the theory

that having certain genes present in the incor-

rect amount contributes to the development of

endometriosis. It may also create an inhos-

pitable environment for an embryo to attach to

the uterus. The findings also add weight to the

hypothesis that the endometrium of women

with endometriosis is abnormal.

The study’s findings might lead to a new

way to screen women for the disease.

Currently, diagnosis requires a laparoscopy (a

procedure in which a small incision is made in

the abdomen) or laparotomy (a larger incision

is made), usually with a general anesthetic.

This new research may one day enable scien-

tists to develop a less invasive test, based on the

detection of abnormal gene activity.

More information about endometriosis is

available from the NICHD publication

Endometriosis, at www.nichd.nih.gov/

publications/pubs/endometriosis.pdf.

Oral Insulin Doesn’t PreventType 1 Diabetes

Insulin taken orally doesn’t delay or prevent

type 1 diabetes in people at moderate risk

(25 to 50 percent likelihood) of developing

type 1 diabetes in five years, researchers report-

ed at the annual meeting of the American Dia-

betes Association. The finding emerged from

the second trial conducted as part of the Dia-

betes Prevention Trial-Type 1 (DPT-1), which

ended last month.

The findings affirm the other DPT-1 trial,

completed two years ago, which found that

low-dose insulin injections failed to prevent or

delay type 1 diabetes in people at high risk (50

percent or greater chance) of developing the

disease in five years.

The oral insulin study was based on the

hypothesis that insulin taken orally might sup-

press the immune system’s destructive attack

on beta cells. Studies in the nonobese diabetic

(NOD) mouse, an animal model of type 1 dia-

betes, had shown that oral insulin given before

diabetes development could reduce or delay

onset of the disease. By “feeding” a person

insulin, the immune cells in the digestive tract

might learn to recognize insulin in a different

way and favor the development of immune

responses that delay the onset or progression of

diabetes or prevent its occurrence altogether.

The oral insulin trial is the third large study

that failed to prevent type 1 diabetes in at-risk

people. The European Nicotinamide Diabetes

Intervention Trial (ENDIT) also failed to pre-

vent or delay type 1 diabetes with nicoti-

namide, a vitamin present in small amounts.

310 AWHONN Lifelines Volume 7 Issue 4

Carolyn Davis Cockey,

MLS, is executive editor

of AWHONN Lifelines

and associate director

of publications for

AWHONN.

Page 2: Oral Insulin Doesn't Prevent Type 1 Diabetes

Upcoming clinical trials will be con-

ducted under Type 1 Diabetes

TrialNet, a collaborative network of

clinical centers dedicated to preventing

type 1 diabetes and preserving insulin

production in new-onset patients. The

first trials are scheduled to begin

enrolling patients in the fall of 2003.

About 17 million people in the U.S.

have diabetes, the most common cause

of blindness, kidney failure and ampu-

tations in adults and a major cause of

heart disease and stroke. About 1 mil-

lion have type 1 diabetes. Formerly

known as juvenile onset or insulin-

dependent diabetes, type 1 diabetes

usually begins in children and adults

under age 30. It develops when the body’s

immune system attacks the insulin-

producing cells of the pancreas.

Glucose Control Lowers AtherosclerosisRisk

In other diabetes news, strict glucosecontrol in type 1 diabetes reduces

the risk of atherosclerosis, a benefitthat persists for years, according to astudy published in the June 5, 2003,issue of the New England Journal ofMedicine.

August | September 2003 AWHONN Lifelines 311

Aspirin EffectiveAmong Blacksfor SecondStrokePrevention

Aspirin is as

effective as

ticlopidine for pre-

vention of a second

stroke among blacks,

according to the recently

reported results from the

African American Anti-

platelet Stroke Prevention

Study (AAASPS), a large multi-

center trial of 1,809 African Ameri-

can stroke patients from more than 60

sites in the U.S.

The study, sponsored by the National

Institute of Neurological Disorders and Stroke (NINDS)

was published in the June 11, 2003, issue of the Journal of

the American Medical Association. Originally scheduled to

run until October 2003, the AAASPS was stopped in July

2002, after analyses suggested that there was less than a 1

percent chance that ticlopidine would be shown to be

superior to aspirin if the study were carried to completion.

Looking at the results of previous trials of ticlopidine, a

type of clot inhibitor, investigators thought that there was

a strong possibility that this agent would be safer and

more effective than aspirin in African Americans with a

history of stroke. The NINDS funded the AAASPS in

order to study this possibility.

“The study shows that aspirin is probably a better

choice than ticlopidine for recurrent stroke prevention in

African Americans. For those who can tolerate it, aspirin is

readily available, inexpensive, and easy to administer.

Ticlopidine, on the other hand, is more expensive, more

difficult to use, and has the potential for serious side

effects,” said John R. Marler, MD, Associate Director for

Clinical Trials research at the NINDS.

African Americans are at about twice the risk of experi-

encing a stroke or dying from a stroke, compared to

whites, and have a higher prevalence of stroke and cardio-

vascular disease risk factors such as hypertension, diabetes

mellitus, obesity, and cigarette smoking.

In other stroke news, researchers have found that African

Americans are more likely to suffer strokes and recover

from them at a slower rate than whites, and these differ-

ences are not simply the result of greater stroke severity.

According to Ronnie D. Horner, PhD, program director

at the National Institute of Neurological Disorders and

Stroke (NINDS), and leader of a recently published study,

research has found that African Americans who delay their

poststroke rehabilitation recover at a significantly slower

rate than whites who experience the same rehabilitation

delay. Recovery rates are even lower among low-income

African Americans. The findings appear in the April 2003

edition of the journal Stroke.

Previous studies have shown that patients who receive

prompt care (within three days of the stroke) in hospital

stroke rehabilitation units, experience lower mortality and

better recovery of physical function.

The study examined racial differences in timely access

to rehabilitation services following a stroke with patients

at nine Veterans Affairs medical centers nationwide.

Patients were treated within the VA health care system,

which provides equal access for its patients, and were fol-

lowed for one year following the onset of hemorrhagic or

ischemic stroke.

The patients essentially received the same in-hospital

treatment, but the pace of recovery from stroke was most

likely inhibited for blacks due to a lack of social resources,

such as transportation or supplemental in-home care that

can otherwise enhance recovery over time.