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

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

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2; Insulin Resistance

• Study Type: Observational
• Enrollment (Actual): 24

Contacts and Locations

Study Locations

• Brazil
  • SP
    • Campinas, SP, Brazil
      • LIMED (Laboratory of Investigation of Metabolism and Diabetes)/GASTROCENTRO/Univeristy of Campinas (UNICAMP)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Adult normoglycemic subjects

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Elderly NGT; Normoglycemic subjects 65-80 years old
Middle-age NGT; Middle-age normoglycemic subjects 35 to 50 years old.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Campinas, Brazil
• Investigators: Principal Investigator: Bruno Geloneze, MD, PhD, LIMED (Laboratory of Investigation of Metabolism and Diabetes)/GASTROCENTRO/Univeristy of Campinas (UNICAMP)

Publications and helpful links

General Publications

• Geloneze B, de Oliveira Mda S, Vasques AC, Novaes FS, Pareja JC, Tambascia MA. Impaired incretin secretion and pancreatic dysfunction with older age and diabetes. Metabolism. 2014 Jul;63(7):922-9. doi: 10.1016/j.metabol.2014.04.004. Epub 2014 Apr 12.

Study record dates

Study Major Dates

• Study Start: June 1, 2009
• Primary Completion (Actual): September 1, 2010
• Study Completion (Actual): September 1, 2010

Study Registration Dates

• First Submitted: February 12, 2009
• First Submitted That Met QC Criteria: February 12, 2009
• First Posted (Estimate): February 13, 2009

Study Record Updates

• Last Update Posted (Estimate): April 22, 2013
• Last Update Submitted That Met QC Criteria: March 7, 2013
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Keywords: Insulin resistance; Aging; glucagon; insulin; diabetes mellitus, type 2; Incretins; DPP-IV protein, human; Glucagon-Like Peptide 1; Gastric Inhibitory Polypeptide; ghrelin
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism; Diabetes Mellitus; Diabetes Mellitus, Type 2; Insulin Resistance
• Other Study ID Numbers: LIMED0006

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No