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

Withdrawn
Conditions
Diabetes Mellitus
Intraductal Papillary Mucinous Neoplasm
McCune-Albright Syndrome
Fibrous 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WITHDRAWN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
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

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Glucose tolerance statusBaseline

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

Insulin sensitivityBaseline

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

Beta cell capacityBaseline

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 secretionBaseline

This primary outcome will be obtained from the hyperglycemic clamp

Secondary Outcome Measures
NameTimeMethod
Zinc transporter 8 (ZnT8)Baseline

Peripheral blood draw before the start of oral glucose tolerance test

Fasting lipid panelBaseline

Peripheral blood draw before the start of oral glucose tolerance test

Growth hormoneBaseline

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 incretinsBaseline

Peripheral blood draw before the start of oral glucose tolerance test

Prandial incretinsBaseline

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

Free fatty acidsBaseline

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 A1cBaseline

Peripheral blood draw before the start of oral glucose tolerance test

UrinalysisBaseline

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

GlycerolBaseline

Peripheral blood draw before the start of oral glucose tolerance test

LeptinBaseline

Peripheral blood draw before the start of oral glucose tolerance test

AdiponectinBaseline

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

Trial Locations

Locations (1)

Yale New Haven Hospital

🇺🇸

New Haven, Connecticut, United States

Yale New Haven Hospital
🇺🇸New Haven, Connecticut, United States

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