Cardiovascular Journal of Africa: Vol 31 No 1 (January/February 2020)

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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 31, No 1, January/February 2020 AFRICA 7
the cases (66 vs 75 ml/min, p = 0.001), but there was no difference
in urine ACR. On univariate analysis (Table 3), the odds ratio
for DKD was 1.74 (p = 0.029), DPN was 0.92 (p = 0.7) and
DR was 2.2 (p = 0.1). Because of baseline differences between
the groups, a multivariate analysis was performed to adjust for
confounders (Tables 4, 5, 6). The differences between the groups
were no longer significant. The most important predictor of
microvascular complications was a five-year increase in age,
especially for DKD (OR 1.63, p < 0.001) and DPN (OR 1.19,
p = 0.008).
There was a trend towards a higher incidence of CVD in
the hypothyroid group (OR 1.76, p = 0.06) that was still present
in the multivariate analysis (OR 1.97, p = 0.07) (Table 7). The
most important predictor of CVD was age, and female gender
appeared protective. Amputations due to diabetes were 3.1% in
the controls and 3.0% in the cases (p = 0.725)
Discussion
This was a cross-sectional, retrospective study comparing
primarily micro- and macrovascular complications in type 2
diabetes subjects with and without hypothyroidism. It was done
in a single-physician practice in South Africa in a predominantly
white population, and results must be interpreted in this context.
The major findings of the study were the following:
hypothyroid subjects were significantly more likely to be female,
older, with a longer duration of diabetes and less likely to be
black; diabetic control, defined by HbA 1c level, was better in
hypothyroid subjects than in the controls despite less use of
hypoglycaemic agents; hypothyroid subjects had higher HDL
cholesterol and lower triglyceride levels; lower eGFR and greater
prevalence of CKD; there was a trend to increased DR with no
differences in amputations or DPN; and a trend to increased
CV events. However after adjustment for baseline differences,
the association of hypothyroidism with DKD and DR was no
longer apparent using multivariate analysis. However the trend
for CVD remained.
The increased prevalence of hypothyroidism in women in this
study probably reflects underlying gender differences, previously
reported.1,8 Similarly, the increased age in the cases probably
reflects the higher prevalence in older people.8 The lower
prevalence of hypothyroidism in black people was also reported
in previous studies, 1 but our results need to be interpreted with
caution in view of the skewed nature of the population.
Hypothyroidism has previously been reported in a systematic
review and meta-analysis to be associated with microvascular
complications that included DR, DKD and DPN. Although on
univariate analysis, an association with DKD was demonstrated,
this was not confirmed on multivariate analysis. The most
important predictor of microvascular complications in our
study was found to be increasing age, especially in relation to
DKD and DPN. Unfortunately only 24.2% of our subjects went
for formal retinal examination and this could have masked an
association between DR due to a type 1 statistical error.
The relationship between hypothyroidism, including SCH
and CVD, has been well established, 9 and treatment with
thyroxine may reduce this risk.10 In our study there was a trend
for increased CVD in both univariate and multivariate analysis.
The reason for not showing a clear association with CVD
was probably mitigated by the fact that all the cases received
thyroxine and statins to control LDL cholesterol. There was no
difference in LDL cholesterol between the cases and controls
as a result. Raised LDL cholesterol due to hypothyroidism is
probably one of the major mechanisms for CVD.
Table 7. Associations between CVD and patient characteristics
on uni- and multivariate analysis
Variable
Univariate Multivariate
OR (95% CI) p-value OR (95% CI) p-value
Age, 5-year increase 1.35 (1.18–1.56) < 0.001 1.41 (1.17–1.70) < 0.001
Gender, female 0.25 (0.13–0.48) < 0.001 0.16 (0.07–0.36) < 0.001
Race, non-black 1.10 (0.48–2.49) 0.826 0.63 (0.24–1.62) 0.336
Obese 0.74 (0.39–1.42) 0.371 0.87 (0.41–1.84) 0.713
Hypothyroid 1.76 (0.97–3.19) 0.064 1.97 (0.94–4.13) 0.073
HBA1c 0.90 (0.26–3.13) 0.872 1.48 (0.33–6.71) 0.613
HDL-C 0.43 (0.15–1.27) 0.127 0.63 (0.18–2.23) 0.472
Duration of T2DM 1.70 (1.11–2.60) 0.014 1.19 (0.71–2.01) 0.512
Table 6. Associations between DR and patient characteristics
on uni- and multivariate analysis
Variable
Univariate
(n = 75)
Multivariate
(n = 75)
OR (95% CI) p-value OR (95% CI) p-value
Age, 5-year increase 1.26 (1.02–1.54) 0.029 1.19 (0.89–1.60) 0.235
Hypothyroid 2.2 (0.86–5.65) 0.102 1.61 (0.55–4.68) 0.386
CKD present 1.59 (0.62–4.06) 0.334 0.89 (0.29–2.75) 0.838
HBA1c 5.67 (0.64–50.13) 0.118 6.52 (0.56–75.22) 0.133
Duration of DM 1.98 (0.97–4.07) 0.061 1.24 (0.52–2.99) 0.624
Table 5. Associations between DPN and patient characteristics
on uni- and multivariate analysis
Variable
Univariate Multivariate
OR (95% CI) p-value OR (95% CI) p-value
Age, 5-year increase 1.21 (1.10–1.34) < 0.001 1.19 (1.05–1.35) 0.008
Gender, female 1.10 (0.70–1.71) 0.698 1.07 (0.65–1.77) 0.789
Race, non-black 2.11 (1.11–4.02) 0.023 1.66 (0.83–3.31) 0.152
Hypothyroid 0.92 (0.59–1.43) 0.706 0.63 (0.37–1.08) 0.094
CKD present 1.76 (1.06–2.90) 0.028 1.22 (0.70–2.16) 0.486
HBA1c 1.37 (0.54–3.52) 0.507 1.47 (0.51–4.23) 0.480
Duration of DM 1.63 (1.21–2.20) 0.001 1.37 (0.97–1.93) 0.075
Table 4. Associations between DKD and patient characteristics
on uni- and multivariate analysis
Variable
Univariate Multivariate
OR (95% CI) p-value OR (95% CI) p-value
Age, 5-year increase 1.57 (1.37–1.79) < 0.001 1.63 (1.39–1.91) < 0.001
Gender, female 1.05 (0.64–1.72) 0.854 0.77 (0.43–1.38) 0.382
Race, non-black 1.16 (0.58–2.33) 0.668 0.67 (0.30–1.48) 0.322
Hypothyroid 1.74 (1.06–2.88) 0.029 1.25 (0.68–2.29) 0.467
HBA1c 0.91 (0.32–2.58) 0.854 2.07 (0.60–7.19) 0.250
Duration of T2DM 1.60 (1.14–2.24) 0.007 0.90 (0.60–1.33) 0.592
Table 3. Micro- and macrovascular outcomes between cases
and controls on univariate analysis
Outcome (n, %)
Total group
n = 310
Controls
n = 162
Cases
n = 148 p-value
Amputation, 8 (2.6) 5 (3.1) 3 (2.0) 0.725
CKD (n = 297) 90 (30.3) 38 (24.7) 52 (36.4) 0.029
CVD 54 (17.4) 22 (13.6) 32 (21.6) 0.062
Neuropathy 148 (47.7) 79 (48.8) 69 (46.6) 0.706
Retinopathy (n = 75) 33/75 (44.0) 11/33 (33.3) 22/42 (52.4) 0.099