Nutritional and Metabolic Diseases

Gland and Hormone Related Diseases

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Symptoms and General Pathology

Musculoskeletal Diseases

Neoplasms

Diseases and Abnormalities at or Before Birth

Skin and Connective Tissue Diseases

Rare Diseases

Diabetes Mellitus

Syndrome

Fibrous Dysplasia of Bone

Neoplasms, Cystic, Mucinous, and Serous

Fibrous Dysplasia, Polyostotic

Metabolic Diseases

Glucose Metabolism Disorders

Endocrine System Diseases

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Osteochondrodysplasias

Mucopolysaccharidosis IV

Bone Diseases

Bone Diseases, Developmental

Fibrous Dysplasia

McCune-Albright Syndrome

Mucopolysaccharidosis Type IV

Hypoglycemic Agents

All Drugs and Chemicals

Insulin

Insulin, Globin Zinc

Fibrous Dysplasia/McCune-Albright Syndrome with diabetes mellitus.

Participants will receive the following interventions: Hyperinsulinemic Euglycemic Clamp and 2H20; Hyperglycemic Clamp; and Oral Glucose Tolerance Test.

Fibrous Dysplasia/McCune-Albright Syndrome without diabetes mellitus.

Participants will receive the following interventions: Hyperinsulinemic Euglycemic Clamp and 2H20; Hyperglycemic Clamp; and Oral Glucose Tolerance Test.

Fibrous Dysplasia/McCune-Albright Syndrome without diabetes mellitus and without intraductal papillary mucinous neoplasms.

Participants will receive the following interventions: Hyperinsulinemic Euglycemic Clamp and 2H20; Hyperglycemic Clamp; and Oral Glucose Tolerance Test.

Fibrous Dysplasia/McCune-Albright Syndrome without diabetes mellitus and with intraductal papillary mucinous neoplasms.

Participants will receive the following interventions: Hyperinsulinemic Euglycemic Clamp and 2H20; Hyperglycemic Clamp; and Oral Glucose Tolerance Test.

Participants will receive the following interventions: Hyperinsulinemic Euglycemic Clamp and 2H20; Hyperglycemic Clamp; and Oral Glucose Tolerance Test.

Test is used to assess insulin effects on hepatic glucose production.

Hyperinsulinemic Euglycemic Clamp and 2H20

Test of beta-cell function and insulin secretion. Involves increasing and maintaining blood glucose concentration with IV variable infusion of dextrose.

Hyperglycemic Clamp

The oral glucose tolerance test (OGTT) measures the body's ability to use a type of sugar, called glucose, that is the body's main source of energy. An OGTT can be used to diagnose prediabetes and diabetes.

Oral Glucose Tolerance Test

Cemre Robinson, MD

The investigators' objective is to understand the pathogenesis of diabetes mellitus in Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) by: 1) establishing the contributions of insulin resistance versus impaired insulin secretion, 2) investigating presence of excess glucagon signaling by measuring gluconeogenesis and glycogenolysis, and 3) investigating a potential interaction between diabetes and intraductal papillary mucinous neoplasms (IPMNs).

Specific project aims include:

Aim 1: Determine insulin secretion and sensitivity in subjects with MAS-associated diabetes.

Aim 2: Measure gluconeogenesis and glycogenolysis in MAS-associated diabetes to investigate a potential role for excess glucagon signaling.

Aim 3: Determine if IPMN development is associated with impairment of insulin secretion prior to development of overt diabetes.

The authors expect that this study will:

1. Establish the etiology of diabetes in FD/MAS
2. Increase understanding of the role of IPMNs in pathogenesis of diabetes
3. Provide critical insights into the pathogenesis of diabetes in FD/MAS

Characterization of Diabetes Mellitus in Fibrous Dysplasia/McCune-Albright Syndrome

The test detects deletions in the HNF4A, GCK, HNF1A, HNF1B genes and mutations in the HNF4A, GCK, HNF1A, HNF1B and IPF1. Will be obtained at baseline before the start of oral glucose tolerance test only in those subjects with an existing diagnosis of diabetes mellitus.

An oral glucose tolerance test will be performed to assess glucose tolerance status to determine if subjects have pre-IGT, IGT or diabetes

This primary outcome will be obtained from the oral glucose tolerance test

This primary outcome will be obtained from the hyperglycemic clamp

AIRmax stimulation test during the hyperglycemic clamp to ascertain the maximal acute insulin response (AIR) to arginine, which is a measure of functional beta cell capacity.

Measurements from the Hyperinsulinemic Euglycemic Clamp/ 2H20 Study will be used to assess insulin effects on hepatic glucose production and glycerol kinetics isotopes and the deuterium enrichment at carbons 2 and 5 (C2 and C5) of plasma glucose providing information on glucose fluxes

Peripheral blood draw before the start of oral glucose tolerance test

Peripheral blood draw at the end of the oral glucose tolerance test

Will be obtained at baseline before the start of oral glucose tolerance test to look for albuminuria

Spots Global Cancer Trial Database for hyperinsulinemic euglycemic clamp and 2h20