The purpose of this study is to investigate the effects of Chromium on glucose tolerance and
endothelial function in people at risk for type II diabetes.
Impaired glucose tolerance (IGT), impaired fasting glucose (IFG), and insulin resistance
(IR) are precursors to type II diabetes mellitus (DM) and its sequelae, and are cardiac risk
factors in their own right. The worsening epidemic of DM in the US, along with the
increasing prevalence of obesity, insulin resistance, and IGT, render the identification of
promising interventions for these states a matter of some urgency. While lifestyle
interventions based on dietary pattern and physical activity can delay or prevent the onset
of diabetes, and reduce cardiovascular risk, adherence at the population level is severely
limiting. Pharmacotherapy offers promise for diabetes prevention, but with associated high
costs, unacceptability to many patients, and potential toxicity. In this context, the
potential role of chromium (Cr), an insulin co-factor, in IGT is of great interest.
Chromium use is widespread, but evidence of any therapeutic effect is limited.
Proposed, therefore, is a randomized, double-blind, placebo controlled pilot trial conducted
at the Yale Prevention Research Center, to investigate the effects of daily Cr for 6 months
at two dose levels on serum measures of glucose tolerance, and on endothelial function, in
adults with IGT, IFG, and IR. A modified crossover design will allow for paired and
unpaired analyses including comparison of both 500 mcg and 1,000 mcg of Cr daily to placebo;
comparison between 500 mcg and 1000 mcg of chromium; and evaluation of Cr washout time. The
study is powered to detect a clinically meaningful effect of Cr supplementation at either
dose on glucose control, and to compare the two doses for equivalence. The study will
investigate effects of Cr on both measures of glucose tolerance (glucose, insulin, OGTT) and
brachial artery endothelial function, thus combining serum measures with a physiologic test
of Cr effects on the vasculature.
The proposed study will generate much needed data regarding the efficacy of Cr in those at
risk for type II diabetes and offers the promise of guiding practice, as well as directing
future study. By contributing to knowledge related to potential diabetes prevention
strategies, this study addresses one of the more pressing public health issues in the US
today. Risk to human subjects in this study is a minor increment over minimal due to the
administration of nitroglycerin as a control in BARS testing.
- 18 years of age or older
- Identified to have impaired glucose tolerance (IGT), impaired fasting glucose (IFG),
or insulin resistance.
According to the 1999 World Health Organization (WHO) report, IGT is diagnosed if the
following two criteria are met: 1) Plasma glucose two hours after consuming 75g glucose
(OGTT) is at least 7.8 mmol/l (140 mg/dl) but below 11.1 mmol/l (200 mg/dl) and 2) Fasting
plasma glucose level is less than 7.0 mmol/l (126 mg/dl). IFG is diagnosed by a fasting
plasma glucose concentration of 5.6 mmol/l (100 mg dl/l) or greater, but less than 7.0
mmol/l (126 mg dl/l). NCEP ATP III guidelines define 5 components of insulin resistance.
At least 3 of the 5 criteria are required for the diagnosis. These components are:
Abdominal obesity determined by waist circumference >102cm(>40in) in men or >88cm(>35in)
in women; triglyceride level ≥150mg/dL; HDL-C <40mg/dL in men or <50mg/dL in women; blood
pressure ≥ 130/≥85mm Hg; and fasting glucose ≥ 100mg/dL.
-Connecticut residents willing to travel to Griffin Hospital in Derby, CT
- Known diabetes (Fasting Plasma Glucose > 126 mg/dl; 2-hour 75-g OGTT plasma glucose >
- Diabetes diagnosed by a physician and confirmed by other clinical data);
- Self-reported hospitalization for treatment of heart disease in past 6 months;
- Impaired renal function as measured by labwork at initial screening (serum creatinine
greater than 2.0 Serum creatinine and urine albumin excretion will be tested every
six months throughout the study). Significant changes from baseline or to outside of
threshold will be reported to the DSMB for appropriate action, including removal from
- Self-reported pancreatitis. In the instance that potential subjects report that they
are unsure whether they have been diagnosed with this condition, a primary medical
doctor's note will be obtained confirming non-diagnosis before inclusion in the
- Self-reported recent or significant abdominal surgery;
- Self-reported pregnancy and/or intention become pregnancy during the study. Women of
child-bearing age will consent to pregnancy testing at baseline, and will agree to
avoiding pregnancy by reliable means throughout the duration of the study.
- Self-reported polycystic ovarian syndrome or irregular menses will be excluded from
the study. (In the future, people with self-reported polycystic ovarian syndrome or
irregular menses may be allowed in the study, however, because their conditions have
the potential of affecting the outcome of BARS testing (a secondary outcome), they
will be treated as a subset of the population during data analysis).