INTRODUCTION
The thyroid gland is a small, butterfly-shaped gland located
near the throat or is simply a gland located in the neck. Its function is to
take iodine from the blood and combine it with an amino acid (one of the
building blocks of protein) to form thyroid hormones. These hormones made by
the thyroid functions in regulating energy use by the body. They also play
important roles in regulating weight, body temperature, muscle strength and
mood. One of the hormones, thyroxine is responsible
for metabolism.1
Thyroid stimulating hormone (TSH), a progenitor of thyroxine and other thyroid-associated hormones, is made in
a gland in the brain called the pituitary gland. When thyroid levels in the
body are low, the pituitary gland makes more TSH. When thyroid levels are high,
the pituitary gland makes less TSH. TSH levels that are too high or too low can
indicate the thyroid is malfunctionin.2 A TSH test is used to find
out how well the thyroid is functioning1.
Thyroid function tests help to determine if the thyroid is
functioning effectively. Such tests include hyperthyroid (over-working thyroid)
function and hypothyroid (poor thyroid) function3.
High TSH levels can mean the thyroid is not making enough
thyroid hormones, a condition called hypothyroidism. Low TSH levels can mean
the thyroid is making too much of the hormones, often called hyperthyroidism. A
TSH test may be needed if there are symptoms of too much thyroid hormone in the
blood (hyperthyroidism), or too little thyroid hormone (hypothyroidism)3.
Symptoms of hyperthyroidism, also known as overactive
thyroid, include: feeling too hot, increased sweating, muscle weakness,
fatigue, weight loss, tremors in the hands, increased heart rate, diarrhoea, irritability and anxiety, puffiness, bulging of
the eyes, menstrual irregularities, and difficulty sleeping, while symptoms of
hypothyroidism, also known as underactive thyroid are non-specific, but
include: mild to moderate weight gain, tiredness, poor concentration,
depression, hair loss, low tolerance for cold temperatures, irregular menstrual
periods, and constipation4.
Abnormal thyroid function is common. It is seen in two to
three percent of the entire population4.When the thyroid is not
functioning effectively, it can cause changes in other blood tests as well. The
normal range of TSH for an adult is 0.4–5.5 mU/ml5.
Glycated
Haemoglobin (HbA1c)is a
blood test which does not require fasting, and indicates the average blood
sugar level for the past two to three months. It measures the percentage of
blood sugar attached to haemoglobin (Hb), the oxygen-carrying protein in red blood cells6.
The higher the blood sugar levels, the more Hb will
be present with sugar attached to it. A HbA1c level of
>6.5 percent separate tests indicates diabetes. A
HbA1c between 5.7 and 6.4 percent indicates pre-diabetes, and ˂5.7 percent
is considered normal7.
If the HbA1c test results are not consistent, the test is
not available, or one has certain conditions that can make the HbA1c test
inaccurate – as in pregnancy or uncommon form of haemoglobin
(known as haemoglobin variant)6:
In addition to daily blood sugar monitoring, a doctor will
likely recommend regular HbA1c testing to measure average blood sugar level for
the past two to three months6. Compared with repeated daily blood
sugar tests, HbA1c testing better indicates how well diabetes treatment plan is
working overall. An elevated HbA1c level may signal the need for a change in
oral medication, insulin regimen or meal plan8.
The target HbA1c goal may vary depending on age and various
other factors, such as other medical conditions that may be present. However,
for most people with diabetes, the American Diabetes Association (ADA)
recommends an HbA1c of below 7 percent9.
Insulin is a hormone with strong association to diabetes.
People with type 2 diabetes need insulin therapy to survive. Many types of
insulin are available, including rapid-acting, long-acting and intermediate
options. Depending on the needs, a doctor may prescribe a mixture of insulin
types to use throughout the day and night7. Thus includes;
Insulin cannot be taken orally to lower blood sugar because
stomach enzymes interfere with its action10. Often, insulin is
injected using a fine needle and syringe or an insulin pen – a device that
looks like a large ink pen11. An insulin pump also may be an option.
The pump is a device about the size of a cell phone worn on the outside of the
body. A tube connects the reservoir of insulin to a catheter that is inserted
under the skin of the abdomen12. A tubeless pump that works
wirelessly also is now available. The pump is programmed to dispense specific
amounts of insulin. It can be adjusted to deliver more or less insulin
depending on meals, level of activity and blood sugar level13. An
emerging treatment approach is closed loop insulin delivery, also known as the
artificial pancreas. It links a continuous glucose monitor to an insulin pump,
and automatically delivers the correct amount of insulin when needed14.There
are a number of versions of the artificial pancreas, and clinical trials have
had encouraging results. More research needs to be done before a fully
functional artificial pancreas receives regulatory approval15.
However, progress has been made towards an artificial
pancreas. In 2016, an insulin pump combined with a continuous glucose monitor
and a computer algorithm was approved by the Food and Drug Administration (FDA)8. Its shortcoming remains that the user still
needs to tell the machine how many carbohydrates will be eaten10.
ii. Oral or other medications: occasionally, other oral or
injected medications, such as Glimepiride, Gliclazide,
Glipizide, and Glyburide are prescribed. Some
diabetes medications such as Glyburide, glipizide and
glimepiride (sulfonylureas) stimulate the pancreas to produce and release more
insulin, while others, such as metformin undertake inhibitory role, indicating the
need for less insulin to transport sugar into the cells7.Other
medications block the action of stomach or intestinal enzymes that catabolize
carbohydrates or make the tissues more sensitive to insulin. Metformin (glucophage) is generally the first medication prescribed
for type 2 diabetes6.
iii. Fasting blood sugar (FBS) test: A blood sample is taken
after an overnight fast. An FBS level <5.6mmol/l (100mg/dl) is normal, 5.6
to 6.9mmol/l (100 to 125mg/dl) is pre-diabetes and ≥7mmol/l (126mg/dl) on
two separate tests, is diabetes9.
The study was
conducted to evaluate thyroid function in normal, pre-diabetic and diabetic
subjects attending University of Port Harcourt Teaching Hospital (UPTH), Port
Harcourt. It was conducted on the premise that it could provide base-line data for physicians in the management of diabetes. It
will, therefore, make available some scientific information on HbA1c, FBS and
thyroid function (TSH, fT3, and fT4) statuses of normal, pre-diabetic and
diabetic subjects, with the target population being normal individuals,
pre-diabetic and diabetic human subjects designated for investigation
of Thyroid Function (TSH, fT3, fT4), HbA1c, and FBS.
METHODOLOGY
This
study was conducted in the UPTH, in Obio/Akpor Local Government Area of Rivers State, Nigeria. The
study area is located in the Niger Delta region, bordering the Atlantic Ocean.
It is a cosmopolitan environment with people of diverse culture and occupation.
It is an experimental design and employed the following approach in grouping
the human subjects.
GROUP A: The
control group consisting of forty (40) normal (non-diabetic) subjects.
GROUP B: The
test group consisting of 40 pre-diabetic subjects.
GROUP C: The
test group consisting of 40 diabetic subjects.
The
inclusion criteria is being aged between thirty six (36) to seventy six (76)
years who agreed to participate, while the exclusion is co-infection with other
metabolic disorders.
The
sample size was by calculating the minimum sample size, employing the formula below:
N =
Z2(pq) / e216
Where
N = minimum sample size,Z =
1.96 at 95% confidence limits, so that z2 = 3.8416, p = prevalence
of increased normal and diabetic subjects’ percentage average, q = 1-p and e =
error margin tolerated at 5% = 0.05 (e2 = 0.0025)
6.80%
as the prevalence of increased normal subjects
10.20%
as the prevalence of increased diabetic subjects
((6.80
+ 10.20)/2)% = (17.00/2)% = 8.50%
8.50%
as the prevalence of increased mean of normal and diabetic subjects
p =
8.50% = 0.0850
q =
1-p
= 1-0.0850
= 0.9150
N =
((3.8416(0.0850 x 0.9150))/0.0025 = 119.51 = approximately 120.
Before commencing sample collection (blood sample), the subjects
were issued or given the informed consent form to complete or fill out after listening
to a detailed explanation from the researcher. This was followed by taking five
(5) ml of blood from the phlebotomy department of UPTH using 5 ml syringe for
each subject. Two (2) ml was put into Lithium heparin bottle, 2 ml into plain
bottle and one (1) ml into Fluoride oxalate bottle.
The samples were placed in sample racks and left to stand
for at least thirty (30) minutes at room temperature. The sample was then
centrifuged for 5 minutes at 320 rpm (Hettich
Universal) at room temperature and a completely cell free non-haemolysed sample was obtained. The samples were then
separated into a 1 ml sample container which was labeled with the serial number
of the subject, and left to refrigerate before use.
Whole blood sample was also collected from the subjects by intravenous
means (collected intravenously) and the samples were collected into plain and
heparinized bottles respectively, which were allowed to stand for 30 minutes to
clot, centrifuged at 3,000 rpm for 10min for proper separation, separated into
plain bottles and labeled accordingly. This was stored frozen, until when
needed for biochemical analysis.
Published studies that evaluate thyroid function, HbA1c, and
FBS in normal, pre-diabetic and diabetic subjects (especially type 2 diabetes mellitus
[T2DM]) were searched in MEDLINE, EMBASE and Pub Med databases covering the
period from year 2000 to 2018. Literature search was then carried out using the
combination of terms “thyroid”, “thyroid function”, “HbA1c”,“Blood sugar”, "FBS",
"diabetes", "diabetes mellitus", "type 2
diabetes","T2DM", "type 2 DM", "epidemiology",
and "review". The reference lists of the retrieved articles and
reviews of this field17,18,19, were also
searched. The search was limited to human studies and English
publications.
In the course of the study, collecting information about
normal subjects and persons suffering from diabetes was difficult. Two issues
were addressed at the outset: the kind of data collection instrument that would
be used and the unit of measurement that would be employed. Generally, the
instruments used for collecting information about normal and diabetic subjects
were: sample surveys(general social surveys/specific health
surveys) and administrative collections and registries. Each of these tools was
used to measure aspects of diabetes in the study population.
Sample surveys are
shorter surveys designed to be administered to the study sub-population
selected by some other instrument (often a census) that focus on specific
issues; normal and diabetic subjects in this case. They were put into the field
to answer specific questions about the study population. As such, they were
provided the opportunity to ask more detailed questions about being normal and
being diabetic. More detailed information was useful in itself, of course, and
it helped to reduce the number of false positive and negative responses,
therefore offering a more accurate prevalence measure of being normal and being
diabetic. The sample survey was an independent survey focusing entirely on
normal and diabetic subjects.
Administrative collections and registries are composed of information that is collected as part of the
normal operation of some service or programme. In
this case, it is the information found on the participant’s informed consent
form. These collections provided useful information on the characteristics of
people accessing normal routine and diabetes services as well as details about
the services provided. They do not guarantee an accurate measure of
non-diabetes and diabetes prevalence since there would be no coverage of
events. The quality of this type of administrative register information is
closely related to the quality of administrative system, in particular, how
well it has been maintained and how closely the concepts align with the normal
and diabetic subjects’ concept of interest. In this work, most of the diabetic
subjects were drawn from members of the Diabetic Society of Nigeria (DAN), who
already have established meeting days and documented records.
The second preliminary issue that was addressed was the unit
for which the diagnostic parameters were measured. The selection unit was a
collection of normal and diabetic subjects. The measurement unit was mmol/l for the blood sugar and percent (%) for HbA1c.
For the analysis, the diabetic indices comprising the FBS
were analyzed using Randox Kits (RANDOX, USA) while HbA1c
test was analyzed using Wondfo Finecare
System (WONDFO, CHINA). Thyroid Function was analyzed using Accubind
Elisa Kits (ACCUBIND, USA).
The quantitative determination of TSH concentration in human
serum was done by a Microplate Immunoenzymometric
assay20.
The quantitative determination of fT3 concentration in human
serum was done by a Microplate Enzyme Immunoassay21.
The quantitative determination of fT4 concentration in human
serum was done by a Microplate Enzyme Immunoassay22.
HbA1c was determined using the Fine careTM
HbA1c Rapid Quantitative Test which is a fluorescence immunoassay used for
quantitative determination of HbA1c in human blood23.
The quantitative in
vitro determination of FBS in serum and/or plasma was done on the Randox (Rx) Monza analyser.
All data were subjected to statistical analyses. Statistical
analysis was performed using SPSS version 21 (IBM, U.S.A). The data was
analyzed using one-way analysis of variance (ANOVA) and significant differences
were determined using post Hoc Duncan multiple comparison test (p<0.05). The
results were considered significant at 95% confidence level. The values were
represented as mean ± standard deviation (SD) and data obtained was analyzed
using the SPSS. Data was shown as mean + SD and displayed in figures.
Qualitative variables of gender categories were summarized as proportions.
Quantitative variables such as age were summarized as mean. Difference in mean
of parameters was compared using analysis of variance (ANOVA).
RESULTS
Glycemic indices and thyroid function of subjects
The results obtained for the
glycemic indices and thyroid function levels are shown in Table 1.
FBS and HbA1c
(Glycemic indices), and Thyroid Function profile (TSH, fT3, and fT4) of the
subjects are shown in Table 1.
The FBS and HbA1c
showed a significantly increasing trend with values of 4.49±0.08 mmol/l, 6.00±0.11 mmol/l, and
10.84±0.96 mmol/l for FBS; and 4.75±0.05 mmol/l, 5.73±0.08 mmol/l, and
9.74±0.47 mmol/l for HbA1c, for the non-diabetics,
pre-diabetics, and diabetics respectively. All values were significantly higher
(p<0.05)across the
groups for both FBS and HbA1c. The
fT3 and fT4 showed progressive decrease in values having values
of3.22±0.11pmol/L, 3.0±0.12pmol/L, and 2.61±0.09pmol/L for fT3; and 1.11±0.05ng/dL, 1.07±0.06ng/dL, and
0.97±0.05ng/dL for fT4; respectively for the
non-diabetics, pre-diabetics, and the diabetics while the TSH values increased
significantly when compared to the normal. TSH for the pre-diabetic group was
however slightly higher than that for the diabetics as shown in Table 1 below.
DISCUSSION
Analysis of thyroid function (TSH, fT3 and fT4) in the subjects
showed that the thyroid function of pre-diabetics and diabetics differed
significantly from that of the normal non-diabetic subjects. There was a
significant increase in the TSH of the pre-diabetic and diabetic subjects and
this increase was highest in the pre-diabetic subjects which suggest that the
diabetic subjects may have already taken intervention measures. On the other
hand, fT3 and fT4 were decreased in the pre-diabetic and diabetic state. The
decrease in fT3 and fT4 followed the glycaemic state
as indicated by the FBS and HbA1c levels and was lowest in the diabetic subjects.
Thyroid dysfunction is widely reported in diabetes24.
Diabetes mellitus and thyroid dysfunctions are
two commonly encountered endocrine disorders encountered in the hospital
clinic. In a hospital-based study in India, 20% of diabetic subjects were found
to have hypothyroidism24,25.
Our study was in agreement with this as we found
fT3 and fT4 to be lower in the diabetic compared to the pre-diabetic and normal
groups with increased Glycaemia as represented by the FBS and HbA1c
concentrations.
CONCLUSION
This
study assessed thyroid hormone levels and the findings largely corroborated
previous studies. The study revealed that thyroid function
is altered in diabetic subjects.
RECOMMENDATIONS
It is recommended that the thyroid function
levels of subjects attending clinics for diabetic care should be checked
routinely. This research should be further carried out using larger population
of subjects. The research should also be conducted in various geographical
locations as variations in different locations affect the genetic factor and
limit the generalization of the research findings.
CONTRIBUTION
TO KNOWLEDGE
The return of some diabetic markers assayed
through the administration of varying doses of the standard drug shelped in the
control of diabetes mellitus by ameliorating its effect.
REFERENCES
1
National
Heartand Blood Institute. Bethesda (MD).U.S. Department of Health & Human
Services; What To Expect with Blood Tests; (about 4 screens).2012. Retrieved
from https://www.nhlbi.nih.gov/health/health-topics/topics/bdt/with
3 Hinkle J,
Cheever K. Brunner & Suddarth’s Handbook of Laboratory & Diagnostic
Tests. 2nd edition, Kindle. Philadelphia: Wolters Kluwer Health, Lippincott
Williams & Wilkins. 2014. Thyroid-Stimulating Hormone, Serum.
4
Cooper
D,. McDermott M, Wartofsky L. Hyperthyroidism. The Journal of
ClinicalEndocrinology & Metabolism, 2006. 91(7), E2.
5 American
Thyroid Association.Falls Church (VA): American Thyroid Association, Thyroid
Disease & Pregnancy (about 2 screens). 2014. Retrieved from http://www.thyroid.org/thyroid-disease-pregnancy
6
Ferri
FF.Diabetes mellitus. In: Ferri’s Clinical Advisor. Philadelphia, 2018. Pa
Elsevier. https://www.clinicalkey.com.
7 Standards
of medical care in diabetes. Diabetes Care, 2018. 41, s1.
8 Papadakis
MA, McPhee SJ, Rabow MW..Editors: Maxine, A. & Papadakis, M. Diabetes
mellitus & hypoglycemia. In: Current Medical Diagnosis & Treatment.
57th edition. 2018. New York, N. Y: McGraw-Hill Education. http://accessmedicine.mhmedical.com.
9 Gabbe SG,
Holzman GB, Quilligan EJ. Diabetes mellitus complicating normal pregnancy. In:
Obstetrics: Normal & Problem Pregnancies. 7th edition. 2017. Philadelphia,
Pa: Saunders Elsevier. https://www.clinicalkey.com.
10
Cunningham
FG, Nelson DB, Casey BM. Diabetes mellitus. In: Williams Obstetrics. 24th
edition. 2014. New York: The McGraw-Hill Companies. http://accessmedicine.mhmedical.com.
11Artificial
Pancreas. (2018). Juvenile Diabetes Research Foundation (JDRF). Retrieved from http://www.jdrf.org/research/artificial-pancreas/.
12 Natural
medicines in the clinical management of diabetes. Natural Medicines. 2018.
Retrieved from https://naturalmedicines.therapeuticresearch.com.
13 Morrow ES. Allscripts EPSi. Mayo Clinic, Rochester, Minnesota. 2018.
14
Dietary
supplements. American Diabetes Association. 2018. Retrieved from http://www.diabetes.org/living-with-diabetes/treatment-and-care/medication/other-treatments/herbs-supplements-and-alternative-medicines/talking-to-your-health-care-provider.html
15 Kasper
DL, Fauci AS, Hauser SL. Diabetes mellitus: Diagnosis,classification &
pathophysiology. In: Harrison’s Principles of Internal Medicine. 19th edition.
2015. New York, N.Y: McGraw-Hill Education. http://accessmedicine.mhmedical.com.
16 Anderson
DR, Sweeny DJ, Williams TA.Sampling & Sampling Distribution; Determining
the Size of Sample. In: Introduction to Statistics, Concepts & Application.
2nd Edition. 1991. New York: West Publishing Company.
17
Negro
F. Insulin resistance & HCV: will new knowledge modify clinical management?
Journal of Hepatology, 2006. 45,
514-519.
18 White DL,
Ratziu V, El-Serag HB. Hepatitis C infection & risk of diabetes: a
systematic review & meta-analysis. Journal of Hepatology, 2008/ 49, 831-844.
19
Negro
F, Alaei M. Hepatitis C virus & type 2 diabetes. World Journal of
Gastroenterology, 2009. 15,
1537-1547.
20 Spencer
CA, Takeuchi M, Kazarosyan M..Interlaboratory/intermethod differences in
functional sensitivity of immunometric assays of thyrotropin (TSH) & impact
on reliability of measurement of subnormal concentrations of TSH. Clinical
Chemistry, 1995. 41, 367.
21 Kozwich
D, Davis G., Sockol, C. Development of total triiodothyronine enzyme
immunoassay in microtiter plate format. Clinical Chemistry, 1991. 37, 1040.
22 Rae P,
Farrar J, Beckett G..Assessment of thyroid status in elderly people. British
Medical Journal, 2010. 307, 177-180.
23
Jeppsson
JO, Kobold U, Barr J, Finke A, Hoelzel W. Approved IFCC reference system for
measurement of hemoglobin A1c in human blood. Clinical Chemistry &
Laboratory Medicine, 2002. 40(1),
78-89.
24 Ogbonna SU.
Ezeani IU. Risk Factors of Thyroid Dysfunction in Patients With Type 2 Diabetes Mellitus. Frontiers in
Endocrinology (Lausanne), 2019. 10,
440.
25 Chutia H,
Bhattacharyya H, Ruram AA. Evaluation of thyroid function in type 2 diabetes in
north-eastern part of India: A hospital-based study. Journal of Family Medicine
& Primary Care, 2018. 7(4),
752–755.
