| How
does Low birth weight cause Diabetes? -Recent Advances
in Assessment of Energy Expenditure and Body Composition |
This
is a basic science study being done at Christian Medical College
Hospital, Vellore in coordination with Copenhagen University,
Copenhagen, Denmark and Steno Diabetes Centre, Copenhagen, Denmark.
It
involves determining the baseline characteristics and the
prospective impact of exercise in young South Indian males
on –
1.
Insulin Resistance assessed by hyperinsulinemic euglycemic
clamp technique
2.
Body Composition as assessed by DEXA scanning.
3. Skeletal
Muscle and Hepatic Triglyceride Content as assessed by ¹H
Nuclear Magnetic
Resonance Spectroscopy.
4.
Energy Expenditure as assessed by Indirect Calorimetry.
It
is well established that South Asians, who comprise more than
one-fifth of the worlds population are more likely to develop
insulin resistance, type 2 diabetes, hyperlipidemia and coronary
artery disease (the metabolic syndrome x) when compared with
the Western population.
What is the initial trigger for the development of
metabolic syndrome in South Asians?
- Several studies have shown epidemiological associations
between poor foetal growth and subsequent development of
Type 2 diabetes mellitus and the metabolic syndrome.
- Low birth weight and malnutrition in the intrauterine
environment has been hypothesized to be an important factor
in the development of metabolic syndrome.
- The study has two cohorts of subjects aged 18-22 years,
one cohort being previously normal birth weight and the
other cohort having previously low birth weight subjects
from a rural part of Tamil Nadu.
- The aim of this study is to characterize metabolic differences
between young Indian men born with low birth weight and
born with normal birth weight with focus on Insulin secretion,
Insulin resistance and body fat distribution. If an impaired
secretion or action or a defect in energy expenditure is
proven in Indians with low birth weight compared to normal
birth weight Indians, then it may provide a better understanding
of the biology of metabolic programming in utero. This is
vital in preventing the epidemic of insulin resistance,
obesity and type 2 diabetes mellitus in the vulnerable Indian
phenotype and may warrant preventive health care strategies
targeting such population at an earlier age.
Hyperinsulinemic Euglycemic Clamp technique:
This
is considered as the gold standard for quantifying Insulin
sensitivity. The duration of the procedure is 2 hours during
which the patient receives an Insulin infusion so as to acutely
raise the plasma Insulin and then maintain at 100 micro units/ml.
Simultaneously a variable glucose infusion to maintain euglycemia
is given. Blood Glucose estimation by glucometer is done every
five minutes to assist making changes in glucose infusion
rate. A steady state is reached during which the glucose infusion
rate is equal to the rate at which glucose is disposed by
Insulin (maximal insulin stimulated glucose uptake by tissues).
It thus gives us a measure of tissue sensitivity to Insulin.
High levels of glucose infusion needed during the steady state
to maintain euglycemia mean tissue sensitivity to Insulin
and low infusion rates signify resistance to the action of
Insulin. The M value or the Insulin sensitivity is calculated
as average of the glucose infusion rates (mg/min) during the
last half hour of the clamp divided by the fat free mass (kg)
as determined by DEXA scan.
Indirect Caloriemeter
Actiheart:
The
Actiheart logger consists of a larger, round, main sensor
and a lead to the positive electrode lead typically worn on
the left side of the chest. Both sensor leads affix to electrodes
attached on to the chest wall at specific locations and pick
up the ECG signal. The details of the subject are entered
in to the actiheart’s database. The subject is sent
home with the device and the data from the actiheart is downloaded
after 3 days.
The
actiheart correlates heart rate and activity level (activity
counts) data which it senses, and converts it in to energy
units (calories) through an inbuilt program. It is thus a
very useful device which provides us with a solid base to
determine energy expenditure in a simple way.
Bicycle Ergometry:
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The
test uses an exercise bicycle which provides a graded increase
in resistance over specified time periods. There is a 5 minute
reference phase during which the patient cycles with a load
of 10 watts and warms up. The test proper starts with a load
of 50 watts and increases by 30 watts with every passing minute.
The test goes on until the patient tires. It gives us an index
of the subject’s exercise capacity.
A
heart rate sensor worn around the chest gives information
about the subject’s ability to reach maximal heart rate
over the period of exercise. It is coupled with a breath by
breath ergo-spirometry to determine energy expenditure by
indirect Calorimetry. Blood lactate levels are measured immediately
after the test. Measuring lactate during moderate exercise
is a useful tool in the diagnosis of mitochondrial disorders.
Thus we are looking to determine any defect with energy expenditure
in our subjects. |