Effects of Fats on Blood Glucose in People With and Without Type 2 Diabetes Mellitus

Overview[ - collapse ][ - ]

Purpose People with type 2 diabetes mellitus (earlier known as maturity onset diabetes mellitus) have high blood levels of sugar and fat. This study is being done to determine if excessive sugar entering the blood in people with type 2 diabetes mellitus is caused by excessive fat. We will also evaluate how the anti-diabetic medications, pioglitazone and metformin taken by mouth work to control blood sugar in people with diabetes.
ConditionDiabetes Mellitus, Type 2
InterventionDrug: Metformin vs Thiazolidinedione (Pioglitazone)
PhaseN/A
SponsorMayo Clinic
Responsible PartyMayo Clinic
ClinicalTrials.gov IdentifierNCT00308373
First ReceivedMarch 27, 2006
Last UpdatedJanuary 19, 2010
Last verifiedJanuary 2010

Tracking Information[ + expand ][ + ]

First Received DateMarch 27, 2006
Last Updated DateJanuary 19, 2010
Start DateJuly 2004
Estimated Primary Completion DateNovember 2005
Current Primary Outcome MeasuresNot Provided
Current Secondary Outcome MeasuresNot Provided

Descriptive Information[ + expand ][ + ]

Brief TitleEffects of Fats on Blood Glucose in People With and Without Type 2 Diabetes Mellitus
Official TitleEffects of Elevated Free Fatty Acids on Endogenous Glucose Production in People With and Without Type 2 Diabetes Mellitus
Brief Summary
People with type 2 diabetes mellitus (earlier known as maturity onset diabetes mellitus)
have high blood levels of sugar and fat. This study is being done to determine if excessive
sugar entering the blood in people with type 2 diabetes mellitus is caused by excessive fat.
We will also evaluate how the anti-diabetic medications, pioglitazone and metformin taken
by mouth work to control blood sugar in people with diabetes.
Detailed Description
The ultimate goal of this application is to determine the cause(s) of type 2 diabetes
mellitus. The role of the liver in the evolution of type 2 diabetes has not been as
extensively studied as that of muscle. This has been, in part, due to the inherent
difficulty of measuring hepatic insulin action in humans under physiologic conditions.
Plasma free fatty acids (FFA) can cause insulin resistance in non-diabetic humans and are
commonly elevated in people with type 2 diabetes. We will re-examine the mechanism(s) by
which elevated FFA cause hepatic insulin resistance in non-diabetic humans, will determine
whether elevated FFA alter insulin induced suppression of endogenous glucose production
(EGP) in diabetic humans and if so, whether this is due to changes in glycogenolysis and/or
gluconeogenesis. We will also seek to determine whether treatment with a pioglitazone (a
thiazolidinedione) blunts or prevents FFA induced hepatic (and extrahepatic) insulin
resistance in people with type 2 diabetes and whether the effects of FFA on insulin action
are influenced by gender. We will examine if use of thiazolidinediones reduces cortisol
production by changing the overall activity of 11 beta hydroxysteroid dehydrogenase type 1.
We will also investigate whether use of thiazolidinediones alters objectively measured
breathing or sleepiness in people with type 2 diabetes.
Study TypeInterventional
Study PhaseN/A
Study DesignAllocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment
ConditionDiabetes Mellitus, Type 2
InterventionDrug: Metformin vs Thiazolidinedione (Pioglitazone)
Study Arm (s)Not Provided

Recruitment Information[ + expand ][ + ]

Recruitment StatusCompleted
Estimated Enrollment73
Estimated Completion DateNovember 2005
Estimated Primary Completion DateNovember 2005
Eligibility Criteria
Forty-two (21 women, 21 men) diabetic and 31 (16 women, 15 men) matched non-diabetic
volunteers will be recruited. Diabetic volunteers whose HbA1c is 7-9% if managed with diet
alone or 6.5-8.5% if on either a sulfonylurea or metformin will be eligible for the study.
Diabetic and non-diabetic subjects will be healthy and matched for age, gender, and body
mass index. Individuals with a body mass index less than 19 or greater than 44 kg/m2 will
be excluded from study to avoid potential confounding effects that may result from extreme
leanness or obesity. Subjects greater than age 35 years of age will be eligible for study.
Subjects less than 35 years will not be studied in order to minimize the possibility of
type 1 diabetes. Healthy diabetic subjects will mean that the participant has no history
of a) proliferate retinopathy; b) significant nephropathy, (i.e., plasma creatinine > 1.4
mg/dl in women and 1.5 mg/dl in men, and/or proteinuria); c) symptomatic autonomic
neuropathy; d) clinically significant atherosclerotic vascular disease (e.g., history of
MI or angina); e) a known systemic illness. To ensure subjects are healthy, following
informed written consent, subjects will undergo a history and physical examination; blood
will be collected for a complete blood count and chemistry group; urine will be collected
to insure there is no evidence of infection or clinically significant proteinuria. Body
composition (including percent fat, visceral fat, hepatic fat, and lean body mass) will be
measured in eligible subjects in the GCRC body composition core using DEXA and a multiple
cut CT scan. (Diabetic volunteers will again undergo body composition studies in Part 2 of
the protocol, after about 4 months of therapy. Please see below)
GenderBoth
Ages35 Years
Accepts Healthy VolunteersAccepts Healthy Volunteers
ContactsNot Provided
Location CountriesUnited States

Administrative Information[ + expand ][ + ]

NCT Number NCT00308373
Other Study ID Numbers1104-04
Has Data Monitoring CommitteeNot Provided
Information Provided ByMayo Clinic
Study SponsorMayo Clinic
CollaboratorsNational Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators Principal Investigator: Robert A. Rizza, M.D. Mayo Clinic
Verification DateJanuary 2010

Locations[ + expand ][ + ]

Mayo Clinic
Rochester, Minnesota, United States, 55905