Paget's disease of bone is a chronic disease of bone remodeling in which areas of the skeleton have increased rates of bone resorption and bone formation. For years, it has been felt that the abnormality in this disease is in the osteoclasts. Over the last year, our group has identified 3 families with evidence of Paget's disease of bone in multiple generations. We wish to study as many family members of each kindred as possible to diagnose the presence or absence of Paget's disease of bone and then begin doing chromosome mapping to localize the gene for Paget s disease of bone. At a recent meeting of the American Society for Bone and Mineral Research, a group has reported that the gene for Paget's disease of bone localizes to the long arm of chromosome 18. In his laboratory, Dr. Michael Econs will perform studies to further localize the gene. We will use the GCRC to characterize the phenotypic manifestations of Paget's disease and determine which family members are affected. We will also obtain blood samples for DNA analysis. A karyotype (fine banding) from one member of each family will be obtained to determine if there are cytogenetic abnormalities. While these abnormalities are rare, the presence of such an abnormality will markedly speed up the search for the diseased gene. M01RR000300672 The purpose of this study is to evaluate the benefits of combined Glucotrol XL and acarbose therapy in patients with type II diabetes mellitus who cannot achieve adequate glycemic control with Glucotrol alone. The comparison of treatments will include evaluation of: fasting plasma glucose, post-prandial glucose excursions, incidence and frequency of hypoglycemia, free insulin, lipids, and overall metabolic control. We hypothesize that significant post-prandial hyperglycemia contributes to fasting hyperglycemia by impacting residual insulin secretory capacity. In a previous study, we used the ultra-short acting insulin Lispro to specifically target the post-prandial glucose rise in patients who were hypoglycemic on maximum doses of sulfonylurea. With this therapy, fasting blood sugar levels were significantly lowered without the addition of an overnight treatment. The availability of the oral hypoglycemic agent acarbose now allows us to explore this effect without the addition of exogenous insulin. Acarbose (""""""""Precose"""""""") is an alpha-glucosidase inhibitor which works locally, in the small intestine, to partially inhibit disaccharidase enzymes, therefore lowering post prandial glucose excursions by delaying glucose absorption into the bloodstream. Acarbose is available with a prescription, and is approved for use alone or in combination with sulfonylureas. Glucotrol XL is the long-acting formulation of the sulfonylurea glipizide, which has been shown to lower fasting blood glucose more effectively than short-acting formulations. In addition, glipizide is associated with a lower rate of hypoglycemia than other sulfonylureas. Therefore, Glucotrol XL is an attractive agent to use in combination with acarbose. Although acarbose has been studied in combination with sulfonylureas, no specific analysis of combination with Glucotrol has been performed.
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