Healthy
Conditions
Brief summary
Researchers are trying to determine how changes in fasting glucose and free fatty acids (products released from fat) affect insulin secretion.
Detailed description
Non-invasive measurement of β-cell health is a long-hoped for tool in diabetes research. The observation that Type 2 Diabetes Mellitus (T2DM), and acute insulin resistance increase proinsulin concentrations led to the suggestion that a proinsulin/insulin ratio is a marker of β-cell integrity. However, proinsulin has a longer half-life (20-30min) than insulin (5min) and, unlike insulin, is not extracted by the liver. This limitation can only be overcome by direct and simultaneous measurement of insulin and proinsulin secretion. This experiment will measure in vivo proinsulin clearance so that proinsulin secretion can be calculated in people with differing degrees of glucose tolerance. It is also notable that subgroups of prediabetes differ in their fasting glucose and free fatty acid (FFA) concentrations. Whether short-term alteration of fasting glucose and FFA can alter subsequent prandial glucose metabolism is unknown. The loss of 1st phase insulin secretion(thought to represent release of pre-formed insulin granules) in T2DM can be partly restored by improved glycemic control although 2nd phase insulin secretion (thought to represent de novo synthesis of insulin) is unchanged. This experiment we will ascertain if changes in fasting FFA and glucose alter 1st and 2nd phase insulin secretion in people without diabetes.
Interventions
DRUGSomatostatin
Somatostatin will be used to inhibit endogenous insulin secretion on either study day in both arms of the study
OTHERDextrose
intravenous glucose will be used to raise fasting glucose in people with NFG / NGT
DRUGInsulin
insulin will be used to lower fasting FFA and glucose in people with IFG / IGT
OTHERIntralipid
intravenous intralipid (Fat Emulsion) will be used to raise fasting FFA in people with NFG / NGT
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Mayo Clinic
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
25 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Weight-stable, non-diabetic subjects from Biobank participants at Mayo Clinic, Rochester
Exclusion criteria
* Age \< 25 or \> 65 years (to avoid studying subjects who could have latent type 1 diabetes, or the effects of age extremes in subjects with normal or impaired fasting glucose). * HbA1c ≥ 6.5% * Use of glucose-lowering agents. * For female subjects: positive pregnancy test at the time of enrollment or study * History of prior upper abdominal surgery such as adjustable gastric banding, pyloroplasty and vagotomy. * Active systemic illness or malignancy. * Symptomatic macrovascular or microvascular disease. * Hormone replacement therapy \>0.625 mg premarin daily
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| First phase of Insulin secretion in response to manipulation of fasting FFA and glucose | First 120 minutes of study | 1st phase of insulin secretion (Phi 1) - physiologic parameter |
| Second phase of Insulin secretion in response to manipulation of fasting FFA and glucose | First 120 minutes of study | 2nd phase of insulin secretion (Phi 2) - physiologic parameter |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| proinsulin secretion in response to manipulation of fasting FFA and glucose | 2nd 120 minutes of the study | proinsulin secretion - physiologic parameter |
| proinsulin clearance in response to manipulation of fasting FFA and glucose | 2nd 120 minutes of the study | proinsulin clearance - physiologic parameter |
Countries
United States
Outcome results
None listed