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SA JOURNAL OF DIABETES & VASCULAR DISEASE
RESEARCH ARTICLE
VOLUME 16 NUMBER 2 • NOVEMBER 2019
53
A cross-sectional cohort study with microvascular
complications in patients with type 2 diabetes with and
without hypothyroidism
LOUISE JOHNSON, BRIAN RAYNER
Correspondence to: Brian Rayner
Division of Nephrology and Hypertension, and Kidney and Hypertension
Research Unit, University of Cape Town, South Africa
e-mail:
brian.rayner@uct.ac.zaLouise Johnson
Montana Hospital, Pretoria, South Africa
Previously published online in
Cardiovasc J Afr:
2/8/19
S Afr J Diabetes Vasc Dis
2019;
16
: 53–56
Abstract
Objectives:
Previous reports have suggested an association
between hypothyroidism and macrovascular complications
in type 2 diabetes (T2DM) but the association with
microvascular complications is not well documented. This
study aimed to determine whether there were significant
differences in these complications in patients with T2DM
with and without hypothyroidism.
Methods:
This was a retrospective, cross-sectional, case–
control study from a single centre specialising in diabetes
in South Africa. T2DM was defined by American Diabetes
Association criteria. The cases were all patients treated
for hypothyroidism and the controls were clinically and
biochemically confirmed euthyroid, who were under follow
up between 1 January and 1 July 2016. Chronic kidney
disease (CKD) was defined as an estimated glomerular
filtration rate (eGFR) of < 60 ml/min, determined by the
CKD-epidemiology collaboration equation (CKD-EPI) and/or
albumin/creatinine ratio > 3 mg/mmol. Diabetic retinopathy
(DR) was defined as the presence of aneurysms, bleeds,
exudates and new vessel formation on the retina examined
by an ophthalmologist. Diabetic peripheral neuropathy
(DPN) was defined as the presence of symptoms, loss of
128-Hz sensation and abnormal 10-gm monofilament.
Cardiovascular disease (CVD) was defined as the presence of
major adverse cardiovascular events (MACE).
Results:
There were 148 cases and 162 controls. Compared
to the controls, the cases were older (65.6 vs 59.4 years,
p
<
0.00001), more likely to be female (67.6 vs 39.5%,
p
< 0.0001)
and white (89.2 vs 79.6%,
p
= 0.02), have a lower HbA
1c
level
(7.5 vs 8.2%,
p
= 0.0001), eGFR (64.4 vs 72.7 ml/min,
p
=
0.0006) and triglyceride level (2.18 vs 2.55 mmol/l,
p
= 0.04),
have a higher high-density lipoprotein cholesterol level (1.13
vs 1.02 mmol/l,
p
= 0.001), a longer duration of diabetes (14.8
vs 11.6 years,
p
= 0.001) and using fewer antidiabetic agents
(1.82 vs 2.19,
p
= 0.001). There was a higher prevalence of
CKD (44 vs 57.8%,
p
= 0.03) and CVD (59.3 vs 45.3,
p
= 0.06),
and a trend towards higher DR (66.7 vs 47.6,
p
= 0.09). There
was no difference in body mass index, hypertension, low-
density lipoprotein cholesterol level (all patients received
statin therapy), DPN and amputations. After adjusting for
confounding factors, there was no association between CKD
and DR, and hypothyroidism, but the trend to association
with CVD persisted (OR 1.97.
p
= 0.07).
Conclusions:
Hypothyroidism in T2DM was not associated
with microvascular disease after adjusting for confounding
factors. There was a nearly two-fold risk of CVD. The study is
limited by the retrospective and observational design.
Keywords:
hypothyroidism, type 2 diabetes, microvascular and
macrovascular complications
The National Health and Nutritional Examination Survey III showed
a prevalence of overt and subclinical hypothyroidism (SCH) of 0.3
and 4.3%, respectively.
1
Insulin resistance, type 2 diabetes mellitus
(T2DM) and hypothyroidism are reported to occur more commonly
than by chance, although the exact aetiology is uncertain.
2
Both
T2DM and hypothyroidism are associated with cardiovascular
disease (CVD), often through complex mechanisms, and the
concurrence of hypothyroidism and diabetes may further amplify
endothelial dysfunction, insulin resistance, poorer diabetic control
and microvascular complications.
3
In a systematic review and meta-analysis of SCH in T2DM, the
prevalence was 10.2%, and T2DM was associated with a 1.93-
fold increase in risk for SCH. Furthermore, SCH was associated
with an overall odds ratio of 1.74 for diabetic nephropathy, 1.42
for diabetic retinopathy (DR), 1.85 for peripheral arterial disease,
and 1.87 for diabetic peripheral neuropathy (DPN).
4
However data
from individual studies have not always been consistent with these
associations.
5,6
Given the paucity of data and the contradictory findings of
studies, we aimed to investigate the association of T2DM and
hypothyroidism with micro- and macrovascular complications in
South Africa.
Methods
This was a retrospective, observational, cross-sectional study
of patients with T2DM performed in a large private practice
specialising in diabetes. The cases were all patients treated for
hypothyroidism including those with SCH, and the controls were
clinically and biochemically confirmed euthyroid under follow up
between 1 January and 1 July 2016. The aim of the study was to
compare the prevalence and severity of micro- and macrovascular
complications, and indices of glycaemic control between the cases
and controls.