Microvascular Blood Flow and Metabolic Flexibility in Hispanics
| Status: | Recruiting |
|---|---|
| Conditions: | Diabetes, Diabetes |
| Therapuetic Areas: | Endocrinology |
| Healthy: | No |
| Age Range: | 18 - 65 |
| Updated: | 5/5/2018 |
| Start Date: | June 1, 2018 |
| End Date: | December 30, 2020 |
| Contact: | Ryan D Russell, PhD |
| Email: | ryan.russell@utrgv.edu |
| Phone: | 9568826509 |
Cardiometabolic Health in Adult Latinos in the Rio Grande Valley With and Without Specific Gene Mutations
Microvascular insulin resistance has been shown to precede myocyte insulin resistance and
impairments in metabolic function. However, there is no convincing data showing the
relationship between impaired microvascular flow and impaired metabolic flexibility. Recent
evidence exists that impaired microvascular blood flow in Caucasians directly contributes to
impaired metabolic flexibility in Caucasians (under review), however there is no such
evidence in Hispanics. Since there is a large disparity in cardiometabolic disease in
Hispanics, this study aims to determine the role of impaired microvascular blood flow on
impaired substrate oxidation switching (metabolic flexibility) in healthy people at risk for
developing type 2 diabetes.
impairments in metabolic function. However, there is no convincing data showing the
relationship between impaired microvascular flow and impaired metabolic flexibility. Recent
evidence exists that impaired microvascular blood flow in Caucasians directly contributes to
impaired metabolic flexibility in Caucasians (under review), however there is no such
evidence in Hispanics. Since there is a large disparity in cardiometabolic disease in
Hispanics, this study aims to determine the role of impaired microvascular blood flow on
impaired substrate oxidation switching (metabolic flexibility) in healthy people at risk for
developing type 2 diabetes.
Metabolic disease, including type 2 diabetes (T2D) and pre-diabetes is a significant health
issue globally, particularly in the Hispanic population. The impact of this disease on
morbidity and mortality is unquestionable, as it is associated with various aspects of neural
and cardiovascular disease. The incidence of T2D is continually increasing, which threatens
the health of future generations and poses a significant financial burden to the health care
system. Early detection of "at-risk" patients could lead to more targeted treatments and
improved outcomes.
The oral glucose tolerance test (GTT) is the gold standard for assessing pre-diabetes, and is
used world-wide. Recent work has uncovered an important finding demonstrating that
hyperglycemia from the GTT causes acute microvascular insulin resistance of skeletal muscle
in healthy Caucasians, even with normal insulin response and blood glucose. It is likely that
the GTT causes acute glucotoxicity which impairs normal vascular function. These findings
have a significant clinical impact as they imply that the GTT does not have the sensitivity
to identify people with vascular-derived insulin resistance, one of the earliest events in
the development of T2D. Therefore, people with vascular-derived insulin resistance cannot be
identified or diagnosed with the GTT.
An alternative test exists that has greater sensitivity to identify vascular-derived
pre-diabetes than the GTT or by measuring HbA1c levels in otherwise healthy Caucasians. Using
a mixed meal challenge (MMC - liquid drink comprising carbohydrate, protein and lipid) in
combination with specific microvascular blood flow (MBF) and metabolic tests, MBF and
metabolic abnormalities can be detected with greater sensitivity than traditional testing.
However, no work in this area has been conducted in the Hispanic population. Therefore, it is
important to determine if, like Caucasians, Hispanics display microvascular insulin
resistance as the first step towards developing pre-diabetes.
Respiratory exchange ratio (RER) is a non-invasive test for measuring whole body fuel
(carbohydrate or fat) utilization by measuring the amount of CO2 expired and the amount of O2
consumed. The ratio of these gases (or RER) gives an indication of whether a person is
burning predominately fat (RER = 0.7) or carbohydrate (RER = 1.0). RER in healthy people
under fasting conditions is typically ~0.75. Metabolic flexibility is the ability to switch
from fat oxidation during fasting conditions to carbohydrate oxidation.
There are preliminary data showing that healthy people, who have normal glucose responses to
an GTT and normal HbA1c levels , but are metabolically inflexible (MI) have a higher blood
glucose excursion post-MMC when compared those who are metabolically flexible (MF) despite a
similar plasma insulin excursion. Importantly, healthy MI have lower muscle microvascular
perfusion post-MMC when compared to MF.
Also, the MMC distinguishes differences in carbohydrate use between these groups. The healthy
MI population had a delayed switch from utilising fat to carbohydrate despite having a
similar fasting respiratory exchange ratio (RER, ~0.77). This inability to switch to
carbohydrate oxidation is more pronounced when expressed as the change in the RER area under
the curve (AUC).
Thus, the lack of microvascular blood flow in skeletal muscle in the MI in response to the
MMC is linked to the delayed ability to metabolize glucose (or carbohydrate), but not with
changes in blood glucose levels. Therefore, the MMC is an alternative and more sensitive test
for detecting early stages of microvascular insulin resistance that would otherwise go
undetected with the GTT. However, the lack of correlation between impaired MBF in skeletal
muscle during the GTT and blood glucose in some people suggest an alternate destination for
glucose delivery, such as liver.
In addition, there are several genes that are associated with metabolic disease in adults and
children. Lipid infusion is known to acutely impair MBF. As such, SNPs regulating lipid
transport and storage are also likely to impact local MBF, though thus far remain untested.
Therefore, in addition to the gold-standard MBF and metabolic assessments, genetic analysis
of targeted SNPs known to affect lipid transport and storage. Cardiometabolic and genetic
data will be correlated with additional lifestyle and physiological factors using
non-invasive techniques to assess: a) habitual physical activity levels, b) central blood
pressure and arterial stiffness, and c) skeletal muscle fiber type. These data will help
explain mechanisms whereby specific genes and lifestyle combine to affect early
pathophysiology of vascular-derived insulin resistance and metabolic syndrome.
issue globally, particularly in the Hispanic population. The impact of this disease on
morbidity and mortality is unquestionable, as it is associated with various aspects of neural
and cardiovascular disease. The incidence of T2D is continually increasing, which threatens
the health of future generations and poses a significant financial burden to the health care
system. Early detection of "at-risk" patients could lead to more targeted treatments and
improved outcomes.
The oral glucose tolerance test (GTT) is the gold standard for assessing pre-diabetes, and is
used world-wide. Recent work has uncovered an important finding demonstrating that
hyperglycemia from the GTT causes acute microvascular insulin resistance of skeletal muscle
in healthy Caucasians, even with normal insulin response and blood glucose. It is likely that
the GTT causes acute glucotoxicity which impairs normal vascular function. These findings
have a significant clinical impact as they imply that the GTT does not have the sensitivity
to identify people with vascular-derived insulin resistance, one of the earliest events in
the development of T2D. Therefore, people with vascular-derived insulin resistance cannot be
identified or diagnosed with the GTT.
An alternative test exists that has greater sensitivity to identify vascular-derived
pre-diabetes than the GTT or by measuring HbA1c levels in otherwise healthy Caucasians. Using
a mixed meal challenge (MMC - liquid drink comprising carbohydrate, protein and lipid) in
combination with specific microvascular blood flow (MBF) and metabolic tests, MBF and
metabolic abnormalities can be detected with greater sensitivity than traditional testing.
However, no work in this area has been conducted in the Hispanic population. Therefore, it is
important to determine if, like Caucasians, Hispanics display microvascular insulin
resistance as the first step towards developing pre-diabetes.
Respiratory exchange ratio (RER) is a non-invasive test for measuring whole body fuel
(carbohydrate or fat) utilization by measuring the amount of CO2 expired and the amount of O2
consumed. The ratio of these gases (or RER) gives an indication of whether a person is
burning predominately fat (RER = 0.7) or carbohydrate (RER = 1.0). RER in healthy people
under fasting conditions is typically ~0.75. Metabolic flexibility is the ability to switch
from fat oxidation during fasting conditions to carbohydrate oxidation.
There are preliminary data showing that healthy people, who have normal glucose responses to
an GTT and normal HbA1c levels , but are metabolically inflexible (MI) have a higher blood
glucose excursion post-MMC when compared those who are metabolically flexible (MF) despite a
similar plasma insulin excursion. Importantly, healthy MI have lower muscle microvascular
perfusion post-MMC when compared to MF.
Also, the MMC distinguishes differences in carbohydrate use between these groups. The healthy
MI population had a delayed switch from utilising fat to carbohydrate despite having a
similar fasting respiratory exchange ratio (RER, ~0.77). This inability to switch to
carbohydrate oxidation is more pronounced when expressed as the change in the RER area under
the curve (AUC).
Thus, the lack of microvascular blood flow in skeletal muscle in the MI in response to the
MMC is linked to the delayed ability to metabolize glucose (or carbohydrate), but not with
changes in blood glucose levels. Therefore, the MMC is an alternative and more sensitive test
for detecting early stages of microvascular insulin resistance that would otherwise go
undetected with the GTT. However, the lack of correlation between impaired MBF in skeletal
muscle during the GTT and blood glucose in some people suggest an alternate destination for
glucose delivery, such as liver.
In addition, there are several genes that are associated with metabolic disease in adults and
children. Lipid infusion is known to acutely impair MBF. As such, SNPs regulating lipid
transport and storage are also likely to impact local MBF, though thus far remain untested.
Therefore, in addition to the gold-standard MBF and metabolic assessments, genetic analysis
of targeted SNPs known to affect lipid transport and storage. Cardiometabolic and genetic
data will be correlated with additional lifestyle and physiological factors using
non-invasive techniques to assess: a) habitual physical activity levels, b) central blood
pressure and arterial stiffness, and c) skeletal muscle fiber type. These data will help
explain mechanisms whereby specific genes and lifestyle combine to affect early
pathophysiology of vascular-derived insulin resistance and metabolic syndrome.
Inclusion Criteria:
- 18-65 years
- having either a parent with type 2 diabetes, or no history for 2 generations
- non-smoking, weight-stable
Exclusion Criteria:
- presence of microvascular disease
- smoking
- having gained or lost more than 5lbs in the last 3 months
- pregnancy
- having cancer, liver, or kidney disease within 5 years
We found this trial at
1
site
1 West University Boulevard
Brownsville, Texas 78520
Brownsville, Texas 78520
Phone: 956-882-6509
Click here to add this to my saved trials
