McCune-Albright Syndrome, Fibrous Dysplasia, Intraductal Papillary Mucinous Neoplasm, Diabetes Mellitus
Conditions
Brief summary
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).
Detailed description
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
Interventions
Test is used to assess insulin effects on hepatic glucose production.
PROCEDUREHyperglycemic Clamp
Test of beta-cell function and insulin secretion. Involves increasing and maintaining blood glucose concentration with IV variable infusion of dextrose.
DIAGNOSTIC_TESTOral Glucose Tolerance Test
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.
Sponsors
Yale University
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) group: * Must be diagnosed based on clinical grounds and/or mutation testing on bone and/or affected tissue Control group: * Must be at least 18 years old
Exclusion criteria
Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) group: * Unwilling to fully cooperate with the evaluation * Unable to provide informed consent Control group: * History of diabetes, insulin resistance, pancreatic disease, pancreatic cysts or amylase/lipase abnormality * Use of any type of oral diabetes medications and/or insulin * Unable to provide informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hepatic glucose fluxes (gluconeogenesis and glycogenolysis) | At least 2 weeks post baseline testing | 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 |
| Glucose tolerance status | Baseline | An oral glucose tolerance test will be performed to assess glucose tolerance status to determine if subjects have pre-IGT, IGT or diabetes |
| Insulin sensitivity | Baseline | This primary outcome will be obtained from the oral glucose tolerance test |
| Insulin secretion | Baseline | This primary outcome will be obtained from the hyperglycemic clamp |
| Beta cell capacity | Baseline | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adiponectin | Baseline | Peripheral blood draw before the start of oral glucose tolerance test |
| Liver function tests (AST and ALT) | Baseline | Peripheral blood draw before the start of oral glucose tolerance test |
| C-reactive protein (CRP) | Baseline | Peripheral blood draw before the start of oral glucose tolerance test |
| Interleukin 6 (IL-6) | Baseline | Peripheral blood draw before the start of oral glucose tolerance test |
| Islet cell antibodies (ICA), | Baseline | Peripheral blood draw before the start of oral glucose tolerance test |
| Tumor necrosis factor alpha (TNF-alpha) | Baseline | Peripheral blood draw before the start of oral glucose tolerance test |
| Renal function (BUN and creatinine) | Baseline | Peripheral blood draw before the start of oral glucose tolerance test |
| Glutamic acid decarboxylase antibodies (GAD65) | Baseline | Peripheral blood draw before the start of oral glucose tolerance test |
| Zinc transporter 8 (ZnT8) | Baseline | Peripheral blood draw before the start of oral glucose tolerance test |
| Fasting lipid panel | Baseline | Peripheral blood draw before the start of oral glucose tolerance test |
| Fasting incretins | Baseline | Peripheral blood draw before the start of oral glucose tolerance test |
| Prandial incretins | Baseline | Peripheral blood draw at the end of the oral glucose tolerance test |
| Free fatty acids | Baseline | Peripheral blood draw before the start of oral glucose tolerance test |
| Growth hormone | Baseline | Peripheral blood draw before the start of oral glucose tolerance test |
| Insulin-like growth factor-1 (IGF-1) | Baseline | Peripheral blood draw before the start of oral glucose tolerance test |
| Islet antigen-2 antibodies (IA-2A) | Baseline | Peripheral blood draw before the start of oral glucose tolerance test |
| Hemoglobin A1c | Baseline | Peripheral blood draw before the start of oral glucose tolerance test |
| Urinalysis | Baseline | Will be obtained at baseline before the start of oral glucose tolerance test to look for albuminuria |
| Glycerol | Baseline | Peripheral blood draw before the start of oral glucose tolerance test |
| Leptin | Baseline | Peripheral blood draw before the start of oral glucose tolerance test |
Other
| Measure | Time frame | Description |
|---|---|---|
| Maturity-Onset Diabetes of Young (MODY) genetic testing | Baseline | 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. |
Countries
United States
Outcome results
None listed