Characterization of Diabetes Mellitus in Fibrous Dysplasia/McCune-Albright Syndrome
- Conditions
- Diabetes MellitusIntraductal Papillary Mucinous NeoplasmMcCune-Albright SyndromeFibrous Dysplasia
- Registration Number
- NCT03520153
- Lead Sponsor
- Yale University
- 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
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
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
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
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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
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.
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
Insulin secretion Baseline This primary outcome will be obtained from the hyperglycemic clamp
- Secondary Outcome Measures
Name Time Method 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
Growth hormone 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
Renal function (BUN and creatinine) 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
Glutamic acid decarboxylase antibodies (GAD65) 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
Insulin-like growth factor-1 (IGF-1) 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
Tumor necrosis factor alpha (TNF-alpha) 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
Adiponectin 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
C-reactive protein (CRP) Baseline Peripheral blood draw before the start of oral glucose tolerance test
Related Research Topics
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Trial Locations
- Locations (1)
Yale New Haven Hospital
🇺🇸New Haven, Connecticut, United States
Yale New Haven Hospital🇺🇸New Haven, Connecticut, United States