The Aging Endocrine Pancreas: Characterization of the Entero-insular Axis Physiology in the Elderly

Study Overview
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Brief Summary
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Like most endocrine axes, the entero-insular axis is expected to go through an age-related physiological deterioration, what might contribute to special features of the elderly onset type 2 diabetes in comparison to middle-age. Twenty four NGT volunteers will be evaluated by a meal tolerance test (MTT) for incretin hormone measurements, and by the hyperglycemic clamp followed by an arginine test for assessing the beta-cell function and the acute insulin response. Others parameters as body composition and basic biochemistry will be also evaluated at Laboratory of Investigation on Metabolism and Diabetes - LIMED / State university of Campinas, Brazil. The characterization of the glucagon-like peptide-1 (GLP-1) production, dipeptidyl peptidase IV (DPP-IV) activity and/or endocrine pancreas incretin-response at aging, might be an interesting evidence to reinforce an incretin-based therapeutic approach for elderly onset type 2 diabetes.

Official Title
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The Aging Endocrine Pancreas: Characterization of the Entero-insular Axis Physiology in the Elderly.

Conditions
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Diabetes Mellitus, Type 2, Insulin Resistance

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Stable weight (< 5% variation) within the last three months Age: 35 to 50 years old for middle-age group, and 65 to 80 years old for elderly group. BMI: 20 to 29.9 kg/m2 Normal glucose tolerance (NGT) for groups Elderly and Middle-age Exclusion Criteria: Use of estrogen, progestogen or systemic corticosteroids. Hepatic cirrhosis, renal failure or any clinical condition with impaired insulin sensitivity Smoking Obesity Uncontrolled systemic or debilitating diseases

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Elderly NGT<br>Normoglycemic subjects 65-80 years old | |
| Middle-age NGT<br>Middle-age normoglycemic subjects 35 to 50 years old. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Homeostasis Model Assessment Insulin Resistance (HOMA-IR) Index | Insulin sensitivity index calculated as HOMA-IR = (Glucose * Insulin) / 22.5, where glucose is mmol/L and insulin is mili-units (mU)/L. Higher values indicate lower insulin sensitivity. | within 1 month from screening visit | 
| Glucose Infusion Rate | Whole-body insulin sensitivity, as estimated by the mean glucose infusion rate corrected for fat-free mass(FFM){mg*[kg(FFM)^-1]*min*10} at last 60 min of 180-min hyperglycemic clamp | within 1 month from screening visit | 
| Adaptive Beta-cell Insulin Production. The Product of Meal Tolerance Test-derived Insulinogenic Index (IGI) for Clamp-derived Insulin Sensitivity Index (ISI) in Normoglycemic Subjects After 65 Years Old in Comparison With Middle-age Normoglycemic Subjects | Beta-cell function was determinated as the beta-cell secretion measured by meal tolerance test adjusted by insulin sensitivity assessed by the hyperglycemic clamp test:Insulinogenic Index/Insulin Sensitivity Index adjusted by free fat mass | within 1 month from screening visit | 
| Distinctive Beta-cell Function From the Arginine Stimulation Test in Normoglycemic Subjects After Sixty-five Years Old in Comparison With Middle-age Normoglycemic Subjects. | Distinctive beta-cell function as measured by the disposition index - based on the acute insulin response from the arginine stimulation test versus glucose infusion rate adjusted by free fat mass from hyperglycemic clamp - in normoglycemic subjects after sixty-five years old in comparison with middle-age normoglycemic subjects. | within 1 month from screening visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Dipeptidyl Peptidase IV (DPP-IV) Concentration | measured in fasting serum sample by ELISA kit | within 1 month from screening visit | 
| GLP-1 Area Under the Curve (AUC) | Area under the curve of glucagon-like peptide (GLP-1) concentrations (measured by ELISA kit) from time 0 to 180 min during a standard meal tolerance test, calculated by the trapezoidal rule. | 1 month from screening visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diabetes mellitus, type 2, Insulin resistance, Aging, Incretins, DPP-IV protein, human, Glucagon-Like Peptide 1, Gastric Inhibitory Polypeptide, insulin, glucagon, ghrelin