Nutritional Regulation of Wound Inflammation: Part II

Fermented Papaya Preparation (FPP) possesses antioxidant properties, which provide benefit
against age-related complications. FPP is also known to protect red blood cells (RBCs)
against oxidative damage and to help protect against severe forms of thalassemia. Several
independent observations convergently point toward the hypothesis that treatment with papaya
preparations may facilitate wound healing responses. Chronic wounds in patients with diabetes
represent a major public health problem. Previous studies from the investigators have
demonstrated that wound-site macrophages from patients with diabetes are compromised in their
ability to support wound healing. Recently, our laboratory reported the first evidence
demonstrating that FPP may improve diabetic wound outcomes by specifically influencing the
response of wound-site macrophages and the subsequent angiogenic response. FPP has a long
track record of safe human consumption.

The objective of the current study is to determine whether FPP is able to improve inducible
respiratory burst outcomes in peripheral blood mononuclear cells (PBMC) of participants with
diabetes. Our investigators have recently reported that supplementation with standardized
fermented papaya preparation (FPP) in adult diabetic mice improves dermal wound healing
outcomes. The production of reactive oxygen species (ROS) by type 2 diabetics (T2DM) PBMC is
markedly inhibited compared to that of the PBMC from non-diabetic donors. We observed that ex
vivo FPP supplementation corrected such inhibition in ROS production by PBMC from T2DM
donors. Therefore, based on these observations, the investigators propose to study the
outcome that FPP supplementation has in patients with diabetes.

Inclusion Criteria:

- Adult patients 30 to 80 years old with clinically defined type II diabetes and HbA1c ≤
9.0 and BMI between 22 and 42

- Diabetic subjects selected for the study will meet one or more of the following
criteria as recommended by American Diabetes Association:

- 1) Symptoms of diabetes and casual plasma glucose 200 mg/dl (11.1 mmol/l) (casual is
defined as any time of day without regard to time since last meal. The classic
symptoms of diabetes include polyuria, polydipsia, and unexplained weight loss); OR

- 2) Fasting plasma glucose (FPG) 126 mg/dl (7.0 mmol/l) (fasting is defined as no
caloric intake for at least 8 h); OR

- 3) 2-hr plasma glucose 200 mg/dl (11.1 mmol/l) during an oral glucose tolerance test
(OGTT) (this test should be performed as described by the World Health Organization,
using a glucose load containing the equivalent of 75g anhydrous glucose dissolved in
water)

Exclusion Criteria:

- Individuals who are deemed unable to understand the procedures, risks and benefits of
the study (i.e., informed consent) will be excluded

- T2DM with HbA1c = 9.1 or above

- BMI less than 22 and over 42

- Clinically significant kidney or liver disease

- Severe neurologic dysfunction

- Females who are pregnant as well as individuals who are therapeutically
immuno-compromised will also be excluded in order to minimize the risk to such
individuals (and fetus) and to decrease statistical variability and to minimize the
potential of confounders

- Candidates for inclusion into the study will not include individuals as defined in 45
CFR 46 Subparts B, C and D, nor from any other population which may be considered
vulnerable

- Pregnant women are excluded to minimize the risk to such individuals (and fetus) and
to decrease statistical variability and to minimize the potential of confounders