Department of Veterans Affairs publishes Diabetes Rule

The Department of Veterans Affairs on January 11, 2001 published proposed rules in the Federal Register for Type 2 Diabetes. Please read the document carefully and send your comments in to the VA no later than March 12, 2001

DEPARTMENT OF VETERANS AFFAIRS
38 CFR Part 3 RIN 2900-AK63
Proposed Rule - January 11, 2001

Disease Associated With Exposure to Certain Herbicide Agents:

Type 2 Diabetes

AGENCY: Department of Veterans Affairs.

ACTION: Proposed rule.

SUMMARY:

The Department of Veterans Affairs (VA) is proposing to amend
its adjudication regulations concerning presumptive service connection for
certain diseases for which there is no record during service. This proposed
amendment is necessary to implement a decision of the Secretary of
Veterans Affairs under the authority granted by the Agent Orange Act of 1991
that there is a positive association between exposure to herbicides used in
the Republic of Vietnam during the Vietnam era and the subsequent
development of Type 2 diabetes. The intended effect of this proposed
amendment is to establish presumptive service connection for that condition
based on herbicide exposure.

DATES: Comments must be received on or before March 12, 2001.

ADDRESSES: Mail or hand-deliver written comments to: Director, Office
of Regulations Management (02D), Department of Veterans Affairs, 810
Vermont Ave., NW., Room 1154, Washington, DC 20420; or fax comments
to (202) 273-9289; or e-mail comments to OGCRegulations@mail.va.gov.
Comments should indicate that they are submitted in response to ``RIN 2900-
AK63.'' All comments received will be available for public inspection in the
Office of Regulations Management, Room 1158, between the hours of 8:00
a.m. and 4:30 p.m., Monday through Friday (except holidays).

FOR FURTHER INFORMATION CONTACT:

 Bill Russo, Regulations Staff,
Compensation and Pension Service, Veterans Benefits Administration,
Department of Veterans Affairs, 810 Vermont Avenue, NW., Washington, DC
20420, telephone (202) 273-7210.

SUPPLEMENTARY INFORMATION:

 Section 3 of the Agent Orange Act of
1991, Pub. L. 102-4, 105 Stat. 11, directed the Secretary to seek to enter
into an agreement with the National Academy of Sciences (NAS) to review
and summarize the scientific evidence concerning the association between
exposure to herbicides used in support of military operations in the Republic
of Vietnam during the Vietnam era and each disease suspected to be
associated with such exposure. Congress mandated that NAS determine, to
the extent possible: (1) Whether there is a statistical association between the
suspect diseases and herbicide exposure, taking into account the strength of
the scientific evidence and the appropriateness of the methods used to
detect the association; (2) the increased risk of disease among individuals
exposed to herbicides during service in the Republic of Vietnam during the
Vietnam era; and (3) whether there is a plausible biological mechanism or
other evidence of a causal relationship between herbicide exposure and the
suspect disease. Section 3 of Pub. L. 102-4 also required that NAS submit
reports on its activities every two years (as measured from the date of the
first report) for a ten-year period.

Section 2 of Pub. L. 102-4 provides that whenever the Secretary
determines, based on sound medical and scientific evidence, that a positive
association (i.e., the credible evidence for the association is equal to or
outweighs the credible evidence against the association) exists between
exposure of humans to an herbicide agent (i.e., a chemical in an herbicide
used in support of the United States and allied military operations in the
Republic of Vietnam during the Vietnam era) and a disease, the Secretary
will publish regulations establishing a presumptive service connection for that
disease. Presumptive service connection relaxes the evidentiary burden, so
that the claimant need not provide direct evidence of a link between his or
her disease and the claimant's exposure to Agent Orange. Instead, such a
link is presumed and may be rebutted only if there is affirmative evidence to
the contrary.

If the Secretary determines that a presumption of service connection is not
warranted, he is to publish a notice of that determination, including an
explanation of the scientific basis for that determination. The Secretary's
determination must be based on consideration of the NAS reports and all
other sound medical and scientific information and analysis available to the
Secretary.

(Under Section 2 of Pub. L. 102-4, any veteran who served in Vietnam
during the Vietnam Era and has one of the diseases on the presumptive list
codified at 38 CFR 3.309(e), is presumed to have been exposed to
herbicides. Under current law, the Vietnam Era is defined as January 9, 1962
through May 7, 1975, for the purposes of such presumptions. 38 U.S.C.
1116.)

Although Pub. L. 102-4 does not define ``credible,'' it does instruct the
Secretary to ``take into consideration whether the results [of any study] are
statistically significant, are capable of replication, and withstand peer
review.'' Simply comparing the number of studies which report a positive
relative risk to the number of studies which report a negative relative risk for
a particular condition is not a valid method for determining whether the
weight of evidence overall supports a finding that there is or is not a positive
association between herbicide exposure and the subsequent development of
the particular condition. Because of differences in statistical significance,
confidence levels, control for confounding factors, bias, and other pertinent
characteristics, some studies are clearly more credible than others, and the
Secretary has given the more credible studies more weight in evaluating the
overall weight of the evidence concerning specific diseases.

I. History of Agent Orange Presumptions

NAS issued its initial report, entitled ``Veterans and Agent Orange: Health
Effects of Herbicides Used in Vietnam,'' (VAO) on July 27, 1993. The
Secretary subsequently determined that a positive association exists
between exposure to herbicides used in the Republic of Vietnam and the
subsequent development of Hodgkin's disease, porphyria cutanea tarda,
multiple myeloma, and certain respiratory cancers; and that there was no
positive association between herbicide exposure and any other condition,
other than chloracne, non-Hodgkin's lymphoma, and soft-tissue sarcomas, for
which presumptions already existed. A notice of the diseases that the
Secretary determined were not associated with exposure to herbicide
agents was published on January 4, 1994 (see 59 FR 341-46).

NAS issued its second report, entitled ``Veterans and Agent Orange:
Update 1996'' (Update 1996), on March 14, 1996. The Secretary
subsequently determined that a positive association exists between
exposure to herbicides used in the Republic of Vietnam and the subsequent
development of prostate cancer and acute and subacute peripheral
neuropathy in exposed persons. The Secretary further determined that there
was no positive association between herbicide exposure and any other
condition, other than those for which presumptions already existed. A notice
of the diseases that the Secretary determined were not associated with
exposure to herbicide agents was published on August 8, 1996 (see 61 FR
41442-49).

NAS issued a third report, entitled ``Veterans and Agent Orange: Update
1998'' (Update 1998), on February 11, 1999. The focus of this updated
review was on new scientific studies published since the release of Update
1996 and updates of scientific studies previously reviewed. The Secretary
determined that there was no positive association between herbicide
exposure and any condition other than those for which presumptions already
existed. A notice of this determination was published on November 2, 1999
(see 64 FR 59232-59243).

II. History of NAS Review of Type 2 Diabetes

In VAO, Update 1996, and Update 1998, NAS placed metabolic and
digestive disorders (including Type 2 diabetes) in the category labeled
``Inadequate/Insufficient Evidence to Determine Whether an Association
Exists.'' According to NAS, this means that the available studies are of
insufficient quality, consistency, or statistical power to permit a conclusion
regarding the presence or absence of an association. For example, studies
fail tocontrol for confounding factors, have inadequate exposure
assessments, or fail to address latency.

However, after NAS released Update 1998 the National Institute of
Occupational Safety and Health (NIOSH) published a report that detects an
association, though not a strong association, between Type 2 diabetes and
dioxin exposure. The study does suggest a dose response relationship
because of excess cases of Type 2 diabetes found in workers having the
highest serum-lipid levels of dioxin (Calvert GM, Sweeney MH, Deddens J,
Wall DK. 1999. Evaluation of Type 2 diabetes, Serum Glucose and Thyroid
Function Among U.S. Workers Exposed to 2,3,7,8 tetrachlorodibenzo-p-
dioxin. Occupational and Environmental Medicine 56:270-276). The
Secretary concluded that the NIOSH study was potentially important enough
that it warranted a full review by NAS as soon as possible, and he directed
VA to amend its contract with NAS for the third biennial update to require a
special report on herbicide exposure and Type 2 diabetes, as a separate
deliverable.

In February 2000, before NAS released its report on herbicide exposure
and Type 2 diabetes, the U.S. Air Force released data from its study of
participants in operation Ranch Hand (the crews assigned to spray Agent
Orange from aircraft in Vietnam) (AFHS. 2000. Air Force Health Study: An
Epidemiologic Investigation of Health Effects in Air Force Personnel
Following Exposure to Herbicides. 1997 Follow-up Examination Results.
Brook AFB, TX: Air Force Research Laboratory. AFRL-HE-BR-TR-2000-
02.) On April 10, 2000, VA asked NAS to include an analysis of the new
Ranch Hand data in its report on Type 2 diabetes. NAS agreed to do so.
III. October 2000 NAS Review of Type 2 Diabetes
NAS issued its report, ``Veterans and Agent Orange: Herbicide/ Dioxin
Exposure and Type 2 Diabetes'' (VAO: Diabetes) on October 11, 2000. NAS
concluded that ``there is limited/suggestive evidence of an association
between exposure to the herbicides used in Vietnam or the contaminant
dioxin and Type 2 diabetes.'' (``Type 2 diabetes'' is also referred to as ``Type
II diabetes mellitus'' or ``adult-onset diabetes.'') The term ``limited/suggestive
evidence'' means ``evidence is suggestive of an association between
herbicides and the outcome, but limited because chance, bias, and
confounding could not be ruled out with confidence.'' NAS based its
conclusion on the totality of the scientific evidence on this issue, not one
particular study. (VAO: Diabetes).

Mortality Studies on Type 2 Diabetes

In VAO: Diabetes, NAS noted that positive associations between
herbicides and Type 2 diabetes are reported in many mortality studies. NAS
stated that these may underestimate the incidence of Type 2 diabetes
because: (1) It is not typically fatal; (2) its known complications, as opposed
to Type 2 diabetes itself, may be more likely to be listed as the cause of
death on the death certificate; and (3) contributory causes of death are not
routinely recorded on death certificates. In one mortality study reviewed by
NAS, people living near the site of a 1976 industrial accident involving dioxin
were found to have a higher risk of death from Type 2 diabetes than a
reference population, in all exposure zones in which deaths were recorded.
(Pesatori AC, Zocchetti C, Guercilena S, Consonni D, Turrini D, Bertazzi,
PA. 1998. Dioxin exposure and non-malignant health effects: a mortality
study. Occupational and Environmental Medicine. 55:126-131.) Two studies
of a group of workers exposed to TCDD at 12 U.S. plants found positive, but
non-statistically significant associations between measures of exposure and
notations of Type 2 diabetes on death certificates, although the later paper
also found a significant negative trend between Type 2 diabetes mortality
and cumulative TCDD exposure. (Steenland K, Nowlin S, Ryan B, Adams S.
1992. Use of multiple-cause mortality data in epidemiological analyses: US
rate and proportion files developed by the National Institute for Occupational
Safety and Health and the National Cancer Institute. American Journal of
Epidemiology 136(7):855-862; Steenland K, Piacetelli L, Deddens J,
Fingerhut M, Chang LI. 1999. Cancer, heart disease and diabetes in workers
exposed to 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin. Journal of the National
Cancer Institute 91(9):779-786.) Another study, which examined workers who
produced or sprayed phenoxy herbicides and chlorophenols, reported an
elevated relative risk of mortality from Type 2 diabetes in exposed workers
versus non-exposed referents. (Vena J, Boffetta P, Becher H, Benn T, Bueno-
de-Mesquita HB, Coggon D, Colin D, Flesch-Janys D, Green L, Kauppinen
T, Littorin M, Lynge E, Mathews JD, Neuberger M, Pearce N, Pesatori AC,
Saracci R, Steenland K, Kogevinas M. 1998. Exposure to dioxin and
nonneoplastic mortality in the expanded IARC international cohort study of
phenoxy herbicide and chlorophenol production workers and sprayers.
Environmental Health Perspectives 106 (Supplement 2):645-653.) In
addition, earlier studies previously reviewed by NAS in and VAO, Update
1996, and Update 1998 showed an inconsistent but weakly positive
association between exposure measures and Type 2 diabetes.
Morbidity Studies on Type 2 Diabetes

In VAO: Diabetes, NAS noted that, ``Positive associations are reported in
most of the morbidity studies identified by the [NAS Committee to Review
the Evidence Regarding the Link Between Exposure to Agent Orange and
Diabetes].'' NAS discussed a number of epidemiological studies. In a study
of a population near an Arkansas plant that manufactured pesticides,
researchers found that insulin levels were significantly higher in the group with
high dioxin levels. The study authors concluded that this was evidence that
dioxin may cause insulin resistance. (Cranmer M, Louie S, Kennedy RH,
Kern PA, Fonseca VA. 2000. Exposure to 2,3,7,8-tetrachlorodibenzo-p-
dioxin (TCDD) is associated with hyperinsulinemia and insulin resistance.
Toxicological Sciences 56(2): 431-436.) A survey of Australian Vietnam
veterans found a statistically significant excess of self-reported Type 2
diabetes--2,391 cases were reported when 1,780 were expected.
(Commonwealth Department of Veterans Affairs. 1998a. Morbidity of
Vietnam Veterans: A Study of the Health of Australia's Vietnam Veteran
Community. Volume 1: Male Vietnam Veterans Survey and Community
Comparison Outcomes. Canberra: Commonwealth Department of Veterans
Affairs.)

The 1999 NIOSH study (Calvert et al., 1999) reported an elevated
incidence of Type 2 diabetes in individuals who had high levels of serum
dioxin relative to others examined in that study. A study of the Ranch Hand
comparison group, reported in 1999 and published in 2000, showed similar
findings. (Longnecker MP, Michalek JE. 2000. Serum dioxin level in relation
to Type 2 diabetes among Air Force veterans with background levels of
exposure. Epidemiology 11(1):44-48.) The Air Force's subsequent analysis
of Ranch Hand data (AFHS, 2000) showed almost identical Type 2 diabetes
incidence in Ranch Hand and the matched comparison group. However, this
study did show significant dose-response relationships between dioxin levels
and Type 2 diabetes incidence, controlling for confounding variables.

Biological Plausibility

Regarding biologic plausibility, NAS concluded in VAO: Diabetes that
animal, laboratory, and human studies constitute ``reasonable evidence that
TCDD exposure could affect Type 2 diabetes risk in humans.'' This
conclusion is based mainly on three studies. (Michalek JE. 1999. Oral
presentation: Workshop on the Evidence Regarding a Link Between
Exposure to Agent Orange and Diabetes. Washington, DC: Institute of
Medicine, July 23; Longnecker MP and Michalek JE. 2000. Serum Dioxin
Level in relation to Type 2 diabetes among Air Force veterans with
background levels of exposure. Epidemiology 11(1):44-48; Cranmer M,
Louie S, Kennedy RH, Kern PA, Fonseca VA. 2000. Exposure to 2,3,7,8-
tetrachlorodibenzo-p-dioxin (TCDD) is associated with hyperinsulinemia and
insulin resistance. Toxicological Sciences 56(2): 431-436.)
IV. The Secretary's Determination on Diabetes

NAS reviewed all known relevant scientific and medical articles published
since Update 1998, and prior studies, as an integral part of the process that
resulted in VAO: Diabetes. In VAO: Diabetes, NAS observed that, ``Although
some of the risk estimates in the studies examined by the committee are not
statistically significant and, individually, studies can be faulted for various
methodological reasons, the accumulation of positive evidence is suggestive.''

After considering all of the evidence, the Secretary has determined that
there is a positive association between exposure to herbicides and Type 2
diabetes and, therefore, a presumption of service connection is warranted.
V. Compliance With the Congressional Review Act, the Regulatory
Flexibility Act, and Executive Order 12866

We estimate that the five-year cost of this proposed rule from appropriated
funds would be $3.3 billion in benefits costs and $62 million in government
operating expenses. Since it is likely that the adoption of the proposed rule
may have an annual effect on the economy of $100 million or more, the Office
of Management and Budget has designated this proposed rule as a major
rule under the Congressional Review Act, 5 U.S.C. 802, and a significant
regulatory action under Executive Order 12866, Regulatory Planning and
Review. The following information is provided pursuant to E.O. 12866.
This proposed rule is necessary to comply with the Agent Orange Act of
1991, which requires VA to establish a presumption of service connection if
the Secretary finds that there is a positive association between exposure to
herbicides used in the Republic of Vietnam during the Vietnam era and the
subsequent development of any particular disease. As explained above, the
Acting Secretary has found that there is such an association regarding Type
2 diabetes. There are no feasible alternatives to this proposed rule, since the
Agent Orange Act of 1991 requires the Secretary to promulgate it once he
finds the positive association described above. The adoption of the
proposed rule would not interfere with state, local or tribal governments in the
exercise of their governmental functions.

Benefits Costs

Historical statistics indicate that the total number of veterans who served in
the Republic of Vietnam or its surrounding waters was about 2.6 million. We
estimate that about 2.3 million of these veterans are alive today. Using
information gained from VAO: Diabetes and VA's Office of Planning and
Analysis, VA applied a prevalence rate of 9% to the current population to
determine the number of veterans who might have Type 2 diabetes today.
VA assumes that over five years, about 90% of these same veterans would
file a diabetes-related claim. We expect that 8 out of 10 claims will be made
by first time applicants (original) and that 2 out of 10 will come from veterans
already service connected for some other issue (reopened). The average
monthly award made on account of diabetes or its ancillary conditions for
original and reopened claims is estimated to be $462 and $786,
respectively. These figures are based on average benefits to current
beneficiaries for all conditions and include dependents' benefits and
unemployability benefits where applicable. A moderate number of DIC and
burial claims have also been factored into this estimate.

VA estimates the cumulative totals of benefits awards to claimants for
years 2001-2005 as follows: 10,199, 80,526, 129,988, 159,198 and
178,356. Benefits costs (in $ million) for years 2001-2005 are as follows:
$16.6, $303, $720.1, $1,010.7, and $1,205.3, for a total cost of $3.3 billion
over five years. This cost estimate also provides for a nominal number of DIC
payments and burial awards. Anticipated cost-of-living allowances (COLA's),
per current economic assumptions, were factored into this estimate;
however, no retroactive payments were considered.

Administrative Costs.

The administrative workload caused by this proposed rule is expected to
be 13,361 claims filed in 2001 and more than 220,000 over five years. Full
time employee resources devoted to processing claims in years one through
five would be 128, 378, 311, 185, and 123, respectively. Administrative
workloads assume that not all claims would be granted; it is probable that
diabetes related claims will be received from veterans who never served in
the Republic of Vietnam. GOE costs (in $ million) for years 2001-2005 are as
follows: $6.4, $18.6, $16.5, $11.9, and $8.2, for a total GOE cost of $62
million over five years.

The Secretary hereby certifies that this regulatory amendment will not have
a significant economic impact on a substantial number of small entities as
they are defined in the Regulatory Flexibility Act, 5 U.S.C. 601-612. The
reason for this certification is that these amendments would not directly affect
any small entities. Only VA beneficiaries could be directly affected.

Therefore, pursuant to 5 U.S.C. 605(b), these amendments are exempt from
the initial and final regulatory flexibility analysis requirements of sections 603
and 604.

The Catalog of Federal Domestic Assistance program numbers are
64.100, 64.101, 64.104, 64.105, 64.106, 64.109, and 64.110.
List of Subjects in 38 CFR Part 3

Administrative practice and procedure, Claims, Disability benefits, Health
care, Pensions, Veterans, Vietnam.
Approved: December 6, 2000.
Hershel W. Gober,
Acting Secretary of Veterans Affairs.

For the reasons set forth in the preamble, 38 CFR part 3 is proposed to be
amended as follows:

PART 3--ADJUDICATION

Subpart A--Pension, Compensation, and Dependency and Indemnity Compensation

1. The authority citation for part 3, subpart A continues to read as
follows:

Authority: 38 U.S.C. 501(a), unless otherwise noted.

2. In Sec. 3.309, paragraph (e), the listing of diseases is amended by
adding ``Type 2 diabetes (also known as Type II diabetes mellitus or adult-
onset diabetes)'' between ``Chloracne or other acneform disease consistent
with chloracne'' and ``Hodgkin's disease'' to read as follows:
Sec. 3.309 Diseases subject to presumptive service connection.