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
Study Type
OBSERVATIONAL
Test is used to assess insulin effects on hepatic glucose production.
Test of beta-cell function and insulin secretion. Involves increasing and maintaining blood glucose concentration with IV variable infusion of dextrose.
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.
Yale New Haven Hospital
New Haven, Connecticut, United States
Glucose tolerance status
An oral glucose tolerance test will be performed to assess glucose tolerance status to determine if subjects have pre-IGT, IGT or diabetes
Time frame: Baseline
Insulin sensitivity
This primary outcome will be obtained from the oral glucose tolerance test
Time frame: Baseline
Insulin secretion
This primary outcome will be obtained from the hyperglycemic clamp
Time frame: Baseline
Beta cell capacity
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.
Time frame: Baseline
Hepatic glucose fluxes (gluconeogenesis and glycogenolysis)
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
Time frame: At least 2 weeks post baseline testing
Islet cell antibodies (ICA),
Peripheral blood draw before the start of oral glucose tolerance test
Time frame: Baseline
Glutamic acid decarboxylase antibodies (GAD65)
Peripheral blood draw before the start of oral glucose tolerance test
Time frame: Baseline
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Islet antigen-2 antibodies (IA-2A)
Peripheral blood draw before the start of oral glucose tolerance test
Time frame: Baseline
Zinc transporter 8 (ZnT8)
Peripheral blood draw before the start of oral glucose tolerance test
Time frame: Baseline
Fasting lipid panel
Peripheral blood draw before the start of oral glucose tolerance test
Time frame: Baseline
Fasting incretins
Peripheral blood draw before the start of oral glucose tolerance test
Time frame: Baseline
Prandial incretins
Peripheral blood draw at the end of the oral glucose tolerance test
Time frame: Baseline
Free fatty acids
Peripheral blood draw before the start of oral glucose tolerance test
Time frame: Baseline
Growth hormone
Peripheral blood draw before the start of oral glucose tolerance test
Time frame: Baseline
Insulin-like growth factor-1 (IGF-1)
Peripheral blood draw before the start of oral glucose tolerance test
Time frame: Baseline
Renal function (BUN and creatinine)
Peripheral blood draw before the start of oral glucose tolerance test
Time frame: Baseline
Hemoglobin A1c
Peripheral blood draw before the start of oral glucose tolerance test
Time frame: Baseline
Urinalysis
Will be obtained at baseline before the start of oral glucose tolerance test to look for albuminuria
Time frame: Baseline
Glycerol
Peripheral blood draw before the start of oral glucose tolerance test
Time frame: Baseline
Leptin
Peripheral blood draw before the start of oral glucose tolerance test
Time frame: Baseline
Adiponectin
Peripheral blood draw before the start of oral glucose tolerance test
Time frame: Baseline
Liver function tests (AST and ALT)
Peripheral blood draw before the start of oral glucose tolerance test
Time frame: Baseline
C-reactive protein (CRP)
Peripheral blood draw before the start of oral glucose tolerance test
Time frame: Baseline
Interleukin 6 (IL-6)
Peripheral blood draw before the start of oral glucose tolerance test
Time frame: Baseline
Tumor necrosis factor alpha (TNF-alpha)
Peripheral blood draw before the start of oral glucose tolerance test
Time frame: Baseline