Gebka. 2014. Effect of ALA On Diabetic Patients
Gebka. 2014. Effect of ALA On Diabetic Patients
Gebka. 2014. Effect of ALA On Diabetic Patients
Mediators of Inflammation
Volume 2014, Article ID 131538, 7 pages
http://dx.doi.org/10.1155/2014/131538
Clinical Study
Effect of the Administration of Alpha-Lipoic Acid on Contrast
Sensitivity in Patients with Type 1 and Type 2 Diabetes
Received 16 August 2013; Revised 28 November 2013; Accepted 24 December 2013; Published 10 February 2014
Copyright © 2014 Anna Gębka et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
The aim of this study was to estimate the effects of oral supplementation of alpha-lipoic acid (ALA) on contrast sensitivity (CS) in
patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). The study included 12 patients with T1DM aged
43 ± 12 years, 48 patients with T2DM aged 59 ± 10 years, and 20 control subjects aged 33 ± 8 years. Patients from each studied group,
including the control group, were randomly assigned to receive 300 mg of ALA orally once daily for 3 months. CS was evaluated
with the Functional Acuity Contrast Test (FACT, Stereo Optical). In the group of patients with T1DM receiving ALA for 3 months
CS remained stable and improved in those with T2DM. Reduction of CS in both T1DM and T2DM patients without alpha-lipoic
acid supplementation was observed. In the control group on alpha-lipoic acid supplementation, CS improvement was noticed at
one spatial frequency. Changes in the CS were observed, despite stable visual acuity and eye fundus image in all studied subjects.
Our study demonstrated that oral administration of alpha-lipoic acid had influence on CS in both T1DM and T2DM patients.
Table 1: Clinical characteristics of patients with T1DM, T2DM, and healthy control subjects.
Oral Without
Oral ALA
Age (years) Duration of HbA1c (%) Insulin hypoglycemic diabetic Complications
supplementation
diabetes (years) therapy (%) medications treatment (𝑁)
(𝑁)
(%) (𝑁)
T1DM patients 43 ± 12 7.4 ± 1.1
19 ± 12 100 — — 5 6 with NPDR
𝑁 = 12
7 NPDR
4 ischemic heart
disease
T2DM patients 59 ± 10 7.2 ± 4.8
7±8 19 77 4 28 10 hypertension
𝑁 = 48
4 cataract
2 glaucoma
2 pseudophakia
Healthy control
subjects 33 ± 8 — — — — — 14 —
𝑁 = 20
T1DM: diabetes mellitus type 1; T2DM: diabetes mellitus type 2; 𝑁: the number of patients.
an eight-carbon disulphide and contains two thiol groups. with nonproliferative DR), 48 patients with type 2 diabetes
ALA, also known as thioctic acid, in vivo may be oxidized mellitus (29 male, 19 female; mean age 59±10 years; 7±8 years
or reduced. Its reduced form, dihydrolipoic acid (DHLA), is since diagnosis; HbA1c 7.2 ± 4.8; 71 eyes without DR, 12 eyes
also biologically active [23]. ALA has an asymmetric carbon, with nonproliferative DR), and the control group represented
thus resulting in two isomers: R-enantiomer (R-ALA) and by 20 healthy people (5 male, 15 female; mean age 33 ± 8
S-enantiomer (S-ALA). Lipoic acid supplements contain R- years; 38 eyes) participated in this prospective study. Diabetes
ALA or a racemic mixture of R-ALA and S-ALA. R-ALA is was diagnosed according to the Polish Diabetes Association
endogenously synthesized and covalently bound in proteins guidelines which correspond with the guidelines of the
to the amino group of lysine, a cofactor for mitochon- American Diabetes Association [28, 29]. All studied patients
drial dehydrogenase enzyme complex (pyruvate dehydroge- underwent a complete ophthalmologic examination, includ-
nase and alpha-ketoglutarate dehydrogenase mitochondrial ing ETDRS chart visual acuity evaluation, slit-lamp biomi-
enzyme complexes) [24]. Since pyruvate dehydrogenase cat- croscopy, and contrast sensitivity (CS) examination. Exclu-
alyzes the oxidative decarboxylation of pyruvate to acetyl- sion criterion was visual acuity lower than 20/25. All patients
CoA, ALA plays an essential role in pathways generating with type 1 diabetes mellitus (T1DM) had negative medical
energy from glucose in mitochondria [25]. history of cardiovascular disease, diabetic neuropathy, and
As mentioned before, oxidative stress plays an important nephropathy, and then no other DR eye complications were
role in the etiology of DR and antioxidants may have a great observed during ophthalmoscopic examinations. Among the
contribution in its prophylaxis and treatment. ALA fulfills ones with type 2 diabetes mellitus (T2DM), 3 patients had
criteria for an ideal antioxidant stated by Packer et al. [26]: it is positive medical history of cardiovascular disease and 10
absorbed from the diet, then becomes converted in cells into of hypertension. All T2DM patients had negative medical
a usable form, and has a low toxicity and both hydrophilic and history of renal disease and diabetic neuropathy. Moreover,
hydrophobic properties. Because of amphiphilic character of in the T2DM group, 4 patients had early stages of cataract, 2
ALA, its antioxidant action takes place in the cytosol, in patients had glaucoma, and two of them had pseudophakia.
the plasma membrane, and in the serum and lipoproteins 77% of T2DM patients were receiving oral hypoglycemic
[24]. As an antioxidant, ALA scavenges ROS and is also medications, 19% were on insulin therapy, and 4% were
able to regenerate endogenous oxidized antioxidants, such as without diabetic treatment. Clinical characteristics of the
glutathione, vitamin C, E, and coenzyme Q10. DHLA has the studied patients with T1DM and T2DM as well as the control
capacity to reduce the oxidized forms of these antioxidants subjects are presented in Table 1.
and thus activates them [27]. Patients with T1DM and T2DM from each studied group,
In light of the above insights, we attempted to investigate including the control group, were randomly assigned to
the potential influence of oral supplementation with ALA on receive 300 mg of ALA orally once daily for 3 months. Five of
contrast sensitivity in patients with T1DM and T2DM. the 12 patients with T1DM (3 patients with nonproliferative
DR, 2 patients without DR) received 300 mg of ALA orally
2. Materials and Methods once daily for 3 months. Twenty-eight patients with T2DM
(2 patients with nonproliferative DR, 26 patients without DR)
2.1. Studied Subjects. Twelve patients with type 1 diabetes received 300 mg of ALA orally once daily for 3 months. In
mellitus (8 male, 4 female; mean age 43±12 years; 19±12 years addition, fourteen of the twenty studied healthy subjects also
since diagnosis; HbA1c 7.4 ± 1.1; 11 eyes without DR, 11 eyes received 300 mg of ALA orally once daily for 3 months.
Mediators of Inflammation 3
Table 2: Characteristics of contrast sensitivity examinations in T1DM patients with and without ALA supplementation at baseline and after
3 months.
T1DM patients without T1DM patients with
Spatial frequencies ALA supplementation ALA supplementation
CS × LC = 48 measurements CS × LC = 40 measurements
Baseline After 3 months 𝑃 value Baseline After 3 months 𝑃 value
A-1.5 cpd
Mean. ± SD 6.5 ± 1.5 6.0 ± 1.6 5.6 ± 1.1 5.6 ± 1.2
Range 3.0–9.0 3.0–9.0 𝑃 = 0.009∗∗ 4.0–8.0 3.0–8.0 𝑃 = 0.614
Median 7.0 6.0 5.0 5.0
95% CI [6.1; 7.0] [5.5; 6.4] [5.3; 6.0] [5.2; 5.9]
B-3 cpd
Mean. ± SD 6.0 ± 1.4 5.5 ± 1.6 5.1 ± 1.7 5.0 ± 1.6
∗∗
Range 2.0–8.0 1.0–9.0 𝑃 = 0.010 2.0–8.0 1.0–9.0 𝑃 = 0.770
Median 6.0 6.0 5.0 5.0
95% CI [5.6; 6.5] [5.1; 6.0] [4.5; 5.6] [4.5; 5.5]
C-6 cpd
Mean. ± SD 5.3 ± 2.2 4.8 ± 2.0 4.2 ± 2.2 4.2 ± 2.2
Range 0.0–8.0 0.0–8.0 𝑃 = 0.005∗∗ 0.0–8.0 0.0–8.0 𝑃 = 0.947
Median 6.0 5.0 4.0 4.0
95% CI [4.6; 5.9] [4.2; 5.3] [3.5; 4.9] [3.5; 4.9]
D-12 cpd
Mean. ± SD 3.6 ± 2.6 3.1 ± 2.4 2.9 ± 2.3 2.7 ± 2.3
Range 0.0–8.0 0.0–8.0 𝑃 = 0.020∗∗ 0.0–7.0 0.0–7.0 𝑃 = 0.626
Median 4.0 4.0 3.0 2.0
95% CI [2.8; 4.4] [2.4; 3.8] [2.1; 3.6] [2.0; 3.5]
E-18 cpd
Mean. ± SD 2.1 ± 2.2 2.0 ± 2.0 1.7 ± 1.9 1.5 ± 1.9
Range 0.0–7.0 0.0–5.0 𝑃 = 0.530 0.0–5.0 0.0–6.0 𝑃 = 0.365
Median 1.0 1.5 0.5 0.0
95% CI [1.4; 2.7] [1.4; 2.5] [1.1; 2.3] [0.8; 2.1]
CS × LC: the number of contrast sensitivity measurements of each eye in 4 luminance conditions and under 5 spatial frequencies.
A-1.5, B-3, C-6, D-12, and E-18 cpd: spatial frequencies.
∗∗
Statistically significant differences between the baseline examination of T1DM patients without ALA supplementation versus after 3 months.
This study was approved by the Ethics Committee of the CS was analyzed first at the photopic level (85.0 cd/m2 ) and
Medical University of Gdańsk (NKBBN/250/2013). then under the mesopic level (3.0 cd/m2 ).
Table 3: Characteristics of contrast sensitivity examinations in T2DM patients with and without ALA supplementation at baseline and after
3 months.
T2DM patients without T2DM patients with
Spatial frequencies ALA supplementation ALA supplementation
CS × LC = 132 measurements CS × LC = 200 measurements
Baseline After 3 months 𝑃 value Baseline After 3 months 𝑃 value
A-1.5 cpd
Mean. ± SD 5.7 ± 1.7 5.3 ± 1.7 5.8 ± 1.6 5.7 ± 1.5
Range 1.0–9.0 0.0–9.0 𝑃 = 0.000∗∗ 0.0–9.0 1.0–9.0 𝑃 = 0.451
Median 6.0 5.0 6.0 6.0
95% CI [5.4; 6.0] [5.0; 5.5] [5.6; 6.0] [5.5; 5.9]
B-3 cpd
Mean. ± SD 5.0 ± 1.8 4.7 ± 1.9 5.2 ± 1.7 5.3 ± 1.6
∗∗
Range 0.0–8.0 0.0–9.0 𝑃 = 0.001 0.0–8.0 0.0–9.0 𝑃 = 0.7371
Median 5.0 5.0 5.0 5.0
95% CI [4.7; 5.4] [4.3; 5.0] [5.0; 5.5] [5.0; 5.5]
C-6 cpd
Mean. ± SD 3.9 ± 2.3 3.5 ± 2.2 4.3 ± 2.3 4.4 ± 2.1
Range 0.0–9.0 0.0–8.0 𝑃 = 0.001∗∗ 0.0–9.0 0.0–9.0 𝑃 = 0.377
Median 4.0 4.0 5.0 4.5
95% CI [3.5; 4.3] [3.1; 3.9] [3.9; 4.6] [4.1; 4.7]
D-12 cpd
Mean. ± SD 2.1 ± 2.3 2.1 ± 2.1 2.7 ± 2.2 3.0 ± 2.2
Range 0.0–7.0 0.0–7.0 𝑃 = 0.866 0.0–8.0 0.0–9.0 𝑃 = 0.001∗
Median 1.0 2.0 3.0 3.0
95% CI [1.7; 2.5] [1.7; 2.5] [2.3; 3.0] [2.7; 3.3]
E-18 cpd
Mean. ± SD 1.2 ± 1.9 1.1 ± 1.8 1.3 ± 2.0 1.6 ± 2.0
Range 0.0–7.0 0.0–7.0 𝑃 = 0.329 0.0–9.0 0.0–8.0 𝑃 = 0.013∗
Median 0.0 0.0 0.0 0.0
95% CI [0.9; 1.5] [0.8; 1.4] [1.0; 1.6] [1.3; 1.9]
CS × LC: the number of contrast sensitivity measurements of each eye in 4 luminance conditions and under 5 spatial frequencies.
A-1.5, B-3, C-6, D-12, and E-18 cpd: spatial frequencies.
∗
Statistically significant differences between the baseline examination of T2DM patients with ALA supplementation versus after 3 months.
∗∗
Statistically significant differences between the baseline examination of T2DM patients without ALA supplementation versus after 3 months.
12 T1DM patients aged 43±12 years and the mean duration of significantly lower contrast sensitivity reported (6.5 ± 1.5
the disease was 19 ± 12 years. In this study group, there were versus 6.0±1.6, 𝑃 = 0.009; 6.0±1.4 versus 5.5±1.6, 𝑃 = 0.010;
12 eyes without DR and 12 eyes with nonproliferative DR. In 5.3 ± 2.2 versus 4.8 ± 2.0, 𝑃 = 0.005; 3.6 ± 2.6 versus 3.1 ± 2.4,
addition, we also examined 48 patients with type 2 diabetes 𝑃 = 0.020) with spatial frequencies A-1.5, B-3, C-6, and
mellitus aged 59 ± 10 years, 7 ± 8 years since diagnosis. In D-12 cpd, respectively. However, no statistically significant
this group, there were 71 eyes without DR and 12 eyes with difference in contrast sensitivity (5.6 ± 1.1 versus 5.6 ± 1.2,
nonproliferative DR and the control group was represented 𝑃 = 0.614; 5.1 ± 1.7 versus 5.0 ± 1.6, 𝑃 = 0.77; 4.2 ± 2.2 versus
by 20 healthy people aged 33 ± 8 years; 38 eyes participated 4.2±2.2, 𝑃 = 0.947; 2.9±2.3 versus 2.7±2.3, 𝑃 = 0.626; 1.7±1.9
in this prospective study. In the tested group, 5 patients with versus 1.5 ± 1.9, 𝑃 = 0.365) at the tested spatial frequencies of
T1DM were receiving ALA supplementation in the dose of A-1.5, B-3, C-6, D-12, and E-16 cpd was seen in T1DM patients
300 mg once daily for 3 months. 28 patients with T2DM as who had received ALA supplementation for three months as
well as 14 healthy controls were also receiving 300 mg of ALA compared with the baseline (Table 2).
orally once daily for 3 months (Table 1).
3.3. Effect of Oral Supplementation ALA on CS in Patients
3.2. Effect of Oral Supplementation ALA on CS in Patients with T2DM. In the study group of patients with T2DM, who
with T1DM. In patients with T1DM who in the tested group were not supplemented with ALA at the dose of 300 mg once
did not receive ALA supplementation, there was statistically daily, the reported contrast sensitivity was significantly lower
Mediators of Inflammation 5
Table 4: Characteristics of contrast sensitivity examinations in the control group with and without ALA supplementation at baseline and
after 3 months.
Control group without Control group with
ALA supplementation ALA supplementation
Spatial frequencies CS × LC = 44 measurements CS × LC = 108 measurements
After 3 After 3
Baseline 𝑃 value Baseline 𝑃 value
months months
A-1.5 cpd
Mean. ± SD 6.9 ± 1.6 6.7 ± 1.3 6.7 ± 1.6 6.8 ± 1.2
Range 4.0–9.0 5.0–9.0 𝑃 = 0.318 0.0–9.0 5.0–9.0 𝑃 = 0.465
Median 7.0 7.0 7.0 7.0
95% CI [6.4; 7.4] [6.3; 7.1] [6.4; 7.0] [6.6; 7.1]
B-3 cpd
Mean. ± SD 6.8 ± 1.6 6.7 ± 1.6 6.1 ± 1.5 6.4 ± 1.2
Range 3.0–9.0 3.0–9.0 𝑃 = 0.423 0.0–9.0 3.0–9.0 𝑃 = 0.027∗
Median 6.5 7.0 6.0 7.0
95% CI [6.3; 7.3] [6.2; 7.2] [5.8; 6.4] [6.2; 6.7]
C-6 cpd
Mean. ± SD 5.9 ± 1.8 6.0 ± 1.5 5.4 ± 1.9 5.5 ± 1.7
Range 1.0–9.0 2.0–8.0 𝑃 = 0.414 0.0–8.0 0.0–8.0 𝑃 = 0.399
Median 6.0 6.0 5.0 6.0
95% CI [5.3; 6.4] [5.5; 6.4] [5.1; 5.8] [5.2; 5.8]
D-12 cpd
Mean. ± SD 4.4 ± 2.3 4.5 ± 2.2 4.3 ± 1.9 4.2 ± 1.9
Range 0.0–9.0 0.0–9.0 𝑃 = 0.648 0.0–8.0 0.0–8.0 𝑃 = 0.446
Median 4.0 4.5 4.0 4.0
95% CI [3.7; 5.1] [3.8; 5.2] [3.9; 4.7] [3.8; 4.5]
E-18 cpd
Mean. ± SD 2.9 ± 2.6 2.5 ± 2.4 2.9 ± 2.2 2.6 ± 1.9
Range 0.0–9.0 0.0–8.0 𝑃 = 0.127 0.0–9.0 0.0–7.0 𝑃 = 0.234
Median 3.0 2.0 3.0 2.0
95% CI [2.1; 3.7] [1.8; 3.3] [2.5; 3.3] [2.3; 3.0]
CS × LC: the number of contrast sensitivity measurements of each eye in 4 luminance conditions and under 5 spatial frequencies.
Spatial frequencies: A-1.5, B-3, C-6, D-12, and E-18 cpd.
∗
Statistically significant differences between the baseline examination of control group with ALA supplementation versus after 3 months.
(5.7 ± 1.7 versus 5.3 ± 1.7, 𝑃 = 0.000; 5.0 ± 1.8 versus 4.7 ± 1.9, contrast sensitivity (5.8 ± 1.6 versus 5.7 ± 1.5, 𝑃 = 0.451,
𝑃 = 0.001; 3.9 ± 2.3 versus 3.5 ± 2.2, 𝑃 = 0.001) at the spatial 5.2 ± 1.7 versus 5.3 ± 1.6, 𝑃 = 0.737, and 4.3 ± 2.3 versus
frequency of A-1.5, B-3, and C-6 cpd, respectively. However, 4.4 ± 2.1, 𝑃 = 0.377) respectively, at the frequencies of A-1.5,
no statistically significant difference in contrast sensitivity B-3, and C-6 cpd, as compared with the baseline (Table 3).
was shown (2.1 ± 2.3 versus 2.1 ± 2.1, 𝑃 = 0.866, and 1.2 ± 1.9
versus 1.1 ± 1.8, 𝑃 = 0.329) at the tested spatial frequencies 3.4. Effect of Oral Supplementation ALA on CS in Healthy
of D-12 and E-16 cpd, respectively, in T2DM patients who Control Subjects. In the control group of healthy volunteers
had not received ALA supplementation in the dose of 300 mg who had received ALA supplementation in the dose of
once daily for three months, as compared with the baseline. 300 mg once daily for three months, a statistically significant
On the other hand, in T2DM patients who had received contrast sensitivity improvement had been observed only at
ALA supplementation in the dose of 300 mg once daily for the spatial frequency B-3 (6.1 ± 1.5 versus 6.4 ± 1.2, 𝑃 =
three months, contrast sensitivity had improved significantly 0.027) as compared with the baseline. However, in the healthy
(2.7 ± 2.2 versus 3.0 ± 2.2, 𝑃 = 0.001, and 1.3 ± 2.0 versus control group, no statistical significance had been obtained
1.6 ± 2.0, 𝑃 = 0.013), respectively, at the spatial frequencies at other tested frequencies after three months as compared
of D-12 and E-16 cpd. While examining T2DM patients who with the baseline, regardless of whether the participants had
had received ALA supplementation for three months, we have received ALA supplementation in the dose of 300 mg once
not though observed any statistically significant difference in daily (Table 4).
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