Pre-diabetes
Conditions
Brief summary
People with high fasting glucose can develop type 2 diabetes with the passage of time. This study is being done to determine the effect of a novel medication in people with this elevated fasting glucose. Sitagliptin is a substance that raises levels of a hormone normally found in the blood. This hormone, called glucagon-like peptide-1 (GLP-1), is normally released by the intestine in response to the presence of food. This hormone acts like a messenger between the intestine and the pancreas to raise insulin levels, and therefore, lower blood sugars. Sitagliptin is effective in people with diabetes, however, this study is being done to determine if Sitagliptin is effective in people with high fasting glucose who do not yet have diabetes.
Detailed description
Impaired fasting glucose (IFG) confers a high risk of progression to diabetes. Its pathogenesis has been an area of active investigation, with defects in insulin and glucagon secretion as well as insulin action likely to play a role. Several studies have suggested that the prediabetic and diabetic state are associated with alterations in circulating incretin concentrations. More recently, a large study of non-diabetic individuals demonstrated decreased GLP-1 concentrations after a glucose challenge in individuals with prediabetes but concluded that defects in GLP-1 secretion were unrelated to insulin secretion. In impaired glucose tolerance (IGT), defects in incretin-induced insulin secretion coexist with defects in glucose induced insulin secretion. Worsening degrees of glucose tolerance are associated with decreased insulin secretion for the prevailing insulin action. Moreover early glucagon suppression is impaired in IGT. Since GLP-1 is an insulin secretagogue and suppresses glucagon, it is conceivable that defects in GLP-1 secretion could contribute to the pathogenesis of pre-diabetes. Inhibition of Dipeptidyl Peptidase-4 (DPP-4), an enzyme which rapidly degrades the incretin hormones, has been shown to be a useful therapeutic strategy in type 2 diabetes. DPP-4 inhibitors increase (model-calculated) insulin secretion and decrease glucagon concentrations resulting in a lowering of fasting (and postprandial) glucose concentrations in people with type 2 diabetes. Their effects in people with IFG are less certain. However, DPP-4 inhibitors provide an opportunity to directly examine the contribution of abnormal incretin concentrations to the pathogenesis of IFG, by raising concentrations of endogenous incretin hormones. The current experiments tested this hypothesis by measuring insulin secretion and action and fasting and postprandial glucose turnover before and after 8 weeks of therapy with a DPP-4 inhibitor.
Interventions
DRUGSitagliptin
100 mg once daily
OTHERPlacebo
once daily for duration of the study
Sponsors
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
35 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
Twenty four participants aged 35 to 70 years with impaired fasting glucose (100mg/dl-125 mg/dl) will be studied. Inclusion Criteria: * Males and females between the ages of 35-70. * Good health as determined by past medical history,physical examination, vital signs, electrocardiogram and laboratory tests at the time of screening. * Patients on diuretics or thyroid hormone therapy must be on a stable dose (at least 3 months prior to screening) and the maintenance dose may not be adjusted during the study.
Exclusion criteria
* Individuals with a body mass index less than 19 or greater than 40 kg/m\^2, or a total weight \> 130 kg, will be excluded from study. * Subjects less than 35 years will not be studied in order to minimize the possibility of studying subjects with type 1 diabetes. * No history of a) significant nephropathy, (i.e., plasma creatinine \> 1.4 mg/dl in women and 1.5 mg/dl in men, and/or proteinuria); b) clinically significant atherosclerotic vascular disease (e.g., history of heart attack or angina); c) a known systemic illness. * Pregnant or lactating females.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Lowering of Fasting Glucose | 8 weeks | fasting glucose taken as the mean of blood glucose measured at -30, -20, -10 and 0 minutes prior to each inpatient meal study |
Countries
United States
Participant flow
Recruitment details
Impaired Fasting Glucose (IFG) not on treatment with glucose-lowering medication
Participants by arm
| Arm | Count |
|---|---|
| Sitagliptin People with impaired fasting glucose treated with sitagliptin 100mg once daily. | 11 |
| Placebo People with impaired fasting glucose treated with placebo once daily. | 11 |
| Total | 22 |
Baseline characteristics
| Characteristic | Sitagliptin | Placebo | Total |
|---|---|---|---|
| Age Continuous | 55.2 years STANDARD_DEVIATION 2.5 | 54.1 years STANDARD_DEVIATION 2.4 | 54.7 years STANDARD_DEVIATION 1.8 |
| Region of Enrollment United States | 11 participants | 11 participants | 22 participants |
| Sex: Female, Male Female | 10 Participants | 8 Participants | 18 Participants |
| Sex: Female, Male Male | 1 Participants | 3 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 11 | 0 / 11 |
| serious Total, serious adverse events | 0 / 11 | 0 / 11 |
Outcome results
Primary
Lowering of Fasting Glucose
fasting glucose taken as the mean of blood glucose measured at -30, -20, -10 and 0 minutes prior to each inpatient meal study
Time frame: 8 weeks
Population: Analysis was per protocol - all participants completed the intervention
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Lowering of Fasting Glucose | 5.78 mmol/l | Standard Error 0.12 |
| Placebo | Lowering of Fasting Glucose | 5.83 mmol/l | Standard Error 0.12 |
Comparison: Paired comparisons (within groups) to examine differences between the baseline study and after 8-weeks of treatment were made using Student's two-tailed t-test for paired samples. Between-group comparisons were made using Student's two-tailed t-test for unpaired samples. Given the previously observed variation in fasting glucosep-value: >0.05t-test, 2 sided