Diabetes Mellitus, Type 2, Insulin Resistance
Conditions
Keywords
diabetes mellitus, type 2, Insulin resistance, Aging, Incretins, DPP-IV protein, human, Glucagon-Like Peptide 1, Gastric Inhibitory Polypeptide, insulin, glucagon, ghrelin
Brief summary
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.
Interventions
None listed
Sponsors
University of Campinas, Brazil
Study design
Observational model
CASE_CONTROL
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
35 Years to 80 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Homeostasis Model Assessment Insulin Resistance (HOMA-IR) Index | within 1 month from screening visit | 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. |
| Glucose Infusion Rate | within 1 month from screening visit | 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 |
| 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 | within 1 month from screening visit | 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 |
| Distinctive Beta-cell Function From the Arginine Stimulation Test in Normoglycemic Subjects After Sixty-five Years Old in Comparison With Middle-age Normoglycemic Subjects. | within 1 month from screening visit | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Dipeptidyl Peptidase IV (DPP-IV) Concentration | within 1 month from screening visit | measured in fasting serum sample by ELISA kit |
| GLP-1 Area Under the Curve (AUC) | 1 month from screening visit | 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. |
Countries
Brazil
Participant flow
Recruitment details
The recruitment process took place at the Laboratory of Investigation on Metabolism and Diabetes - LIMED, located at the Medical School of the State University of Campinas (UNICAMP).
Pre-assignment details
Cross-sectional study conducted with 24 non-obese patients with normal glucose tolerance. Two groups formed: middle-aged (n=12) and aged(n=12). They were healthy and had no significant illness. None were taking drugs that affect insulin sensitivity/secretion or incretin hormones.
Participants by arm
| Arm | Count |
|---|---|
| Elderly Normal Glucose Tolerance (NGT) Normoglycemic subjects 65-80 years old | 12 |
| Middle-age Normal Glucose Tolerance (NGT) Middle-age normoglycemic subjects 35 to 50 years old. | 12 |
| Total | 24 |
Baseline characteristics
| Characteristic | Elderly Normal Glucose Tolerance (NGT) | Total | Middle-age Normal Glucose Tolerance (NGT) |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants 0 | 0 Participants 0 | 0 Participants 0 |
| Age, Categorical >=65 years | 12 Participants 0 | 12 Participants 0 | 0 Participants 0 |
| Age, Categorical Between 18 and 65 years | 0 Participants 0 | 12 Participants 0 | 12 Participants 0 |
| Age Continuous | 64 years STANDARD_DEVIATION 2 | 54 years STANDARD_DEVIATION 3 | 44 years STANDARD_DEVIATION 4 |
| Region of Enrollment Brazil | 12 participants | 24 participants | 12 participants |
| Sex: Female, Male Female | 9 Participants | 20 Participants | 11 Participants |
| Sex: Female, Male Male | 3 Participants | 4 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 12 | 0 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 |
Outcome results
Primary
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
Time frame: within 1 month from screening visit
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Elderly Normal Glucose Tolerance (NGT) | 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 | 1.7 (μmol∙kg-1min-1) | Standard Deviation 0.9 |
| Middle-age Normal Glucose Tolerance (NGT) | 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 | 3.4 (μmol∙kg-1min-1) | Standard Deviation 1.3 |
p-value: 0.01Wilcoxon (Mann-Whitney)
Primary
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.
Time frame: within 1 month from screening visit
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Elderly Normal Glucose Tolerance (NGT) | Distinctive Beta-cell Function From the Arginine Stimulation Test in Normoglycemic Subjects After Sixty-five Years Old in Comparison With Middle-age Normoglycemic Subjects. | 328.5 (μmol∙kg-1.min-1) | Standard Error 303.4 |
| Middle-age Normal Glucose Tolerance (NGT) | Distinctive Beta-cell Function From the Arginine Stimulation Test in Normoglycemic Subjects After Sixty-five Years Old in Comparison With Middle-age Normoglycemic Subjects. | 223.5 (μmol∙kg-1.min-1) | Standard Error 174.9 |
p-value: >0.05Wilcoxon (Mann-Whitney)
Primary
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
Time frame: within 1 month from screening visit
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Elderly Normal Glucose Tolerance (NGT) | Glucose Infusion Rate | 0.48 mg*[kg(FFM)^-1]*min*10 | Standard Deviation 0.16 |
| Middle-age Normal Glucose Tolerance (NGT) | Glucose Infusion Rate | 1.73 mg*[kg(FFM)^-1]*min*10 | Standard Deviation 0.13 |
p-value: 0.001Wilcoxon (Mann-Whitney)
Primary
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.
Time frame: within 1 month from screening visit
Population: minimum number required to find a significant difference between groups considering the intra-subject variation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Elderly Normal Glucose Tolerance (NGT) | Homeostasis Model Assessment Insulin Resistance (HOMA-IR) Index | 1.91 units on a scale | Standard Deviation 1 |
| Middle-age Normal Glucose Tolerance (NGT) | Homeostasis Model Assessment Insulin Resistance (HOMA-IR) Index | 0.84 units on a scale | Standard Deviation 0.21 |
p-value: 0.001Wilcoxon (Mann-Whitney)
Secondary
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.
Time frame: 1 month from screening visit
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Elderly Normal Glucose Tolerance (NGT) | GLP-1 Area Under the Curve (AUC) | 1061.7 pg/ml/min | Standard Deviation 354.4 |
| Middle-age Normal Glucose Tolerance (NGT) | GLP-1 Area Under the Curve (AUC) | 1027.1 pg/ml/min | Standard Deviation 164.9 |
p-value: >0.05Wilcoxon (Mann-Whitney)
Secondary
Serum Dipeptidyl Peptidase IV (DPP-IV) Concentration
measured in fasting serum sample by ELISA kit
Time frame: within 1 month from screening visit
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Elderly Normal Glucose Tolerance (NGT) | Serum Dipeptidyl Peptidase IV (DPP-IV) Concentration | 1466.6 pg/ml | Standard Deviation 1088.8 |
| Middle-age Normal Glucose Tolerance (NGT) | Serum Dipeptidyl Peptidase IV (DPP-IV) Concentration | 1458.2 pg/ml | Standard Deviation 1006.9 |
p-value: >0.05Wilcoxon (Mann-Whitney)