Matrix Metalloproteinases and Diabetic Nephropathy

Matrix metalloproteinases (MMPs) are a family of protein-degrading enzymes that are involved
in the breakdown and remodeling of many tissues and organs. Abnormal activity of these
enzymes has been implicated in many disease processes including rheumatoid arthritis, dental
disease and metastatic cancer. Recent studies also suggest that elevations in blood sugar
may abnormally effect MMP enzyme activity. Decreased activity of some of these MMP enzymes
may be a partial cause of the abnormal enlargement of the kidney (renal hypertrophy) seen at
the start of diabetic kidney disease (nephropathy). Preliminary clinical data from our
laboratory confirm that children with newly diagnosed type 1 diabetes mellitus (DM) have
lower blood levels of some of these enzymes at the time of very high blood sugar readings.
However, these enzyme levels become normal again as blood sugar levels improve with insulin
treatment. In the present study, we propose to investigate the hypothesis that MMPs are
involved in the cause of diabetic kidney disease by measuring concentrations of specific
MMPs and some related proteins in the blood and urine of patients with type 1 DM who are
between the ages of 14-40 years. We will enroll some patients who are recently diagnosed
with diabetes, some who have had diabetes for several years, but without signs of kidney
disease, and some with long-term diabetes and various degrees of kidney disease. Continuous
Subcutaneous Glucose Monitoring, conducted for 3-4 days, will also be provided as a part of
this study, to determine how different levels of blood sugar control might relate to
different levels of MMP enzyme activity in the blood. We anticipate that this study will
help to establish a link between abnormal MMP activity and the cause of nephropathy in type
1 DM, allowing scientists to design better therapies for the prevention and treatment of
diabetes-related kidney problems.