THE MEASUREMENT OF THE CHOROIDAL THICKNESS DURING ORAL GLUCOSE TOLERANCE TESTS IN PREDIABETIC SUBJECTS: A SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY STUDY/PREDIYABETIK HASTALARDA YAPILAN ORAL GLIKOZ TOLERANS TESTI ESNASINDA KOROID KALINLIGININ OLCULMESI: SPEKTRAL DOMAIN OPTIK KOHERENS TOMOGRAFI CALISMASI.
Diabetes mellitus (DM) is characterized by chronic hyperglycaemia and fluctuations in blood glucose levels (1). The current methods to identify DM include the fasting plasma glucose (FPG) level test, the 2 hours plasma glucose value after 75-g oral glucose tolerance test (OGTT) and glycosylated hemoglobin (HbA1c) level test. The previous stage of DM is prediabetes known as impaired glucose tolerance (IGT) or impaired fasting glucose (IFG), which indicate an increased risk for the future development of DM (2). IFG has identified as an FPG level of between 110 to 125 mg/dL and IGT identified as a 2 hours plasma glucose level of 140-200 mg/dL after 75 g oral glucose load (3).
Investigating how acute hyperglycaemic changes affect the choroid in patients with prediabetes may allow us to interpret physiological responses to metabolic changes in the eye.
Measuring choroidal thickness (ChT) in vivo has been enabled with new generation spectral domain optical coherence tomography (SD-OCT) devices. Many researchers have used the SD-OCT to investigate the pathologic and normal processes in the choroidal layer. It enables in vivo measurement of ChT and cross-sectional choroidal imaging. There are many studies investigating the role of the choroid in the pathogenesis of many ocular diseases such as degenerative myopia, age-related macular degeneration, central serous chorioretinopathy, diabetic retinopathy (DR), macular hole and retinitis pigmentosa (4-8).
Our hypothesis was that the response of the choroidal layer for hyperglycemia could be more dynamic and would differ between healthy individuals and prediabetic subjects. In this study, we aimed to investigate the effect of OGTT on ChT changes using OCT in prediabetics with no signs and symptoms of the ocular disease.
MATERIAL AND METHOD
This observational and prospective study was performed between April 2015 and August 2016 at the Ophthalmology Department of the Izmir Katip Celebi University Ataturk Training and Research Hospital. It was conducted according to the principles of the Declaration of Helsinki and approved by the institutional ethics committee ((GATA Ethics Committee 5.5.2015/8 (218)), and informed consent was obtained from each patient. The OGTT group included 50 eyes of 50 patients with prediabetes whose FPG was 110 to 125 mg/dL and/or 2 h OGTT plasma glucose was 140-200 mg/dL, followed by the Endocrinology and Metabolism department. These patients underwent OGTT and were referred to the ophthalmology clinic before and during the OGTT for ophthalmological examinations. The control group included 50 eyes of 50 healthy age and sex-matched volunteers who were recruited from the healthy individuals visiting the outpatient clinic of ophthalmology. The control group received the same amount of glucose-free water. The control subjects did not have a diagnosis of any ocular or other systemic diseases. Only the right eyes of the participants were included in the study.
The inclusion criteria for both groups were: best-corrected visual acuity of at least 20/20, nonsmoking, no drug and alcohol abuse, no medication, less than 2 diopters (D) of cylindrical and/or 3 D of spherical refractive error, and without any glaucomatous findings such as glaucomatous optic disk changes, such as excavation, notching, or focal thinning of the neuroretinal rim, peripapillary hemorrhage and glaucomatous retinal nerve fiber layer loss. Exclusion criteria included any history of retinal diseases, intraocular pressure (IOP) readings higher than 21 mmHg, any systemic abnormalities (e.g., vascular disease, hypertension, or chronic inflammatory disease), history of previous intraocular surgery or laser therapy, smoking and poor image quality because of unstable fixation or cataract.
All patients and controls underwent complete ophthalmologic examinations, including visual acuity and refraction, slit-lamp biomicroscopy, applanation tonometry, axial length (AL) by ultrasonography (OcuScan; Alcon, TX, USA) and dilated funduscopy with a 90-D lens. Systolic and diastolic blood pressures were measured using a digital automatic device (Omron Healthcare Co., Ltd. Kyoto, Japan) after participants rested for at least 10 min. Blood pressure values of both groups were within the normal range (systolic <120 mm Hg, diastolic <80 mm Hg).
Each subject underwent an OGTT (75 g glucose) after overnight fasting. Blood glucose levels were measured with a blood glucose analyzer (HemoCue Diagnostics BV, Oisterwijk, the Netherlands). Endogenous insulin levels were measured by means of immunometric assays (Lu minescence, Bayer Diagnostics, Mijdrecht, Netherlands) in the Endocrinology Laboratory at the Department of Clinical Chemistry.
Body mass index (BMI) was calculated as BMI=weight (kg)/height [(m).sup.2].
Spectral-domain optical coherence tomography scans
All participants were examined with SD-OCT (Nidek, RS3000, Gamagori, Japan) after pupillary dilation with tropicamide 1% (Tropamid 1%; Bilim ilac, Istanbul, Turkey). Three images were performed for each individual and the highest signal strength (at least 7) was enrolled. Macula Line Raster scan protocol was used to assess the ChT. The ChT was measured as the perpendicular distance between the hyperreflective outer border of the retinal pigment epithelium-Bruch's membrane and choroidal-scleral interface. Two experienced physicians (F.A and M.A) who were blinded to the diagnosis of the participants who underwent the OCT scans and ChT evaluations. The ChT was measured at 7 different points: at the subfovea; at 500 [micro]m, 1000 [micro]m, and 1500 [micro]m temporal to the fovea; and at 500 [micro]m, 1000 [micro]m, and 1500 [micro]m nasal to the fovea (Figure 1). The SD-OCT measurements were performed between 9:00 and 12:00 AM due to diurnal effect. The built-in follow-up feature was used to acquire scans at the same retinal position in subsequent imaging sessions.
All statistical data was analyzed using SPSS version 21.0 (SPSS Inc., Chicago, IL, USA). Values were expressed as mean [+ or -] standard deviation. The normality of the values was analyzed by using the Shapiro-Wilk test and baseline differences between groups were analysed using unpaired t-tests or Mann-Whitney U test according to distribution pattern. Categorical data was compared using the [chi square]-test or Fisher's exact test. The results of the OGTT were analysed by repeated measures analysis of variance test (rANOVA). Bonferroni adjustment for multiple testing was applied. Differences were accepted significant at p<0.05. Correlations between the variables were analysed by Pearson or Spearman correlation coefficient.
A total of 50 prediabetic patients (31 male and 19 female) and 50 healthy subjects (26 male and 24 female) were enrolled in this study. The mean age of the prediabetic patients was 41.26[+ or -]6.49 years. There were no differences in sex, age, spherical equivalent (SE), IOP, BMI or AL between the two groups (p>0.05). The mean HbA1c level was higher in prediabetic group as 5.98[+ or -]0.33% in the prediabetic group, 5.68[+ or -]0.15% in the healthy group (p<0.001). The remaining demographic, along with clinical and ophthalmologic characteristics are summarized in Table 1.
Fasting Plasma Glucose (FPG) levels of the patients with only isolated Impaired Fasting Glucose (IGT) patients are higher than non-diabetic patients (all p<0.0001). In patients with prediabetes, mean PG increased from 114.38[+ or -]5.64 mg/dl to 187.94[+ or -]33.47 mg/dl at 60 min (p<0.001) and to the 146.6[+ or -]44.53 mg/dl at 120 min (Table 2).
Mean insulin levels were also higher in patients with prediabetes than in healthy volunteers during the entire experiment (all p<0.0001, Table 3).
Changes in ChT differed between the groups. There was a significant difference between repeated measures in prediabetes group, whereas no changes occurred in healthy volunteers. Post hoc tests showed that this significant difference was caused in the first hour of OGTT measurement. So a transient increase was observed in the mean ChT as well as subfoveal, nasal and temporal locations at the 500 [micro]m distance to fovea in prediabetes individuals. While subfoveal ChT difference was 1.52[+ or -]4.11 [micro]m (range, -11.00/24.00 [micro]m) in prediabetes, -0.22[+ or -]1.74 [micro]m (range -2.00/8.00 [micro]m) in the control group at the first hour of the OGTT.
The ChT at 1.500 [micro]m nasal distance to fovea was significantly lower in prediabetic individuals at the beginning and after 2 hours from glucose loading. Table 4 summarizes ChT measurements during OGTT.
There was no correlation between basal ChT with both HbA1c and BMI in any groups.
Hyperglycemia is a condition that has various effects on the organism as well as on the eye. There have been some debates about hyperglycemia that need to be clarified. In this regard some questions such as the difference between acute or chronic effect of hyperglycemia, the levels at which begins to damage the eye, the earliest affected tissue in the eye, correlation between hyperglycemia exposure time and its effect, retinal neurodegeneration is a primary and independent change or, instead, a consequence of retinal vascular impairment, how retinal and choroidal blood flow were affected have been investigated (9).
Some models have been used to study the various forms of hyperglycemia. To evaluate the acute hyperglycemic episodes, OGTT or a glucose clamp attachment; or to investigate the 3-months hyperglycemic condition, HbA1c levels have been widely used (10). While it was suggested that an OGTT may provide a more similar approach to daily metabolism we used this method in this study (11).
In the present study, in the cases of healthy individuals and prediabetes, the choroidal response was evaluated in an OGTT-induced acute hyperglycemic episode. A transient choroidal thickening occurred in the prediabetes group, while there was no change in the healthy volunteers.
Changes in ChT after an acute hyperglycemic episode has only been investigated in one study to the best of our knowledge (12). Klefter et al. reported reduced ChT of healthy subjects without significant changes in DM patients contrary to our results. They claimed that this finding was probably due to a transient reduction in choroi dal blood flow in healthy individuals. However, they did not analyze insulin levels and the number of the participants enrolled in the study was relatively small. In addition diabetic patients were included in that study unlike prediabetes patients in our study. In the present study we suggest that the ChT may temporarily increase in prediabetes patients unlike in healthy individuals, probably due to the fact that both insulin and glucose levels increase more than the control group. In this regard we would like to discuss the acute, subacute and chronic effect of hyperglycaemia on the choroid in this study.
DM--in addition to chronic hyperglycaemia--is a chronic disease characterized by fluctuations in glucose levels (1). For that reason, detecting acute hyperglycemic changes with instant measurements may help us to better understand the effect of the disease on ocular structures.
As a matter of fact to understand the effects of acute hyperglycaemia on the eye, systemic metabolic changes should be analyzed. There is an increase in insulin levels and glucose levels and plasma osmolality after glucose uptake via OGTT.
Two opposite hemodynamic effects of insulin have been reported: sympathetic vasoconstriction and vasodilation with direct effect via adenosine and endothelial nitric oxide (13, 14). In a previous study, it was shown that mild hyperinsulinemia induces an effect on pulsatile choroidal blood flow partially mediated by nitric oxide (15). Polak et al. have found increased pulsatile choroidal blood flow whereas retinal blood flow was not significantly changed (16). The different effects of insulin on the choroidal and retinal circulation attributed to the differences in sympathetic innervation in the retina and choroid that the retinal vessels do not have sympathetic innervation (17). Compatible with these findings insulin levels were higher in prediabetes patients in our study and this may contribute to the choroidal thickening.
However it was reported that glucose has potent vasodilator properties (18). Studies have not found any changes in retinal structure during acute hyperglycaemia (19, 20) but there is an agreement about the issue that acute hyperglycaemia increased retinal oxygen extraction (12, 21) and retinal arterial oxygen saturation (12, 22-24). Concomitantly, studies in this area have shown that hyperglycemia either increases (25, 26) or at least does not alter (27-29) retinal blood flow. Considering all these factors, glucose may also increase the ChT in the present study. On the other hand, whether the changes depend only on the increase in insulin levels or are caused by hyperglycemia is not clear. Hence somatostatin was given before OGTT and the insulin levels were suppressed and normoinsulinemic hyperglycemia was provided in some studies (20).
Furthermore it was suggested that serum osmolarity may be positively correlated with ChT (30, 31). Depending on the increase in osmolality; ocular hypotension, lens thickening, shallowing of the anterior chamber and a myopic shift in refractive index have been reported (32). There is no quantitative data associated with osmolality as a deficiency in our work, but this may be another factor that increases ChT.
Since the choroid receives 95% of all ocular blood flow and is the only blood supply of avascular fovea, choroid has been a possible target for vascular-related studies in diabetic patients and was identified an entity--diabetic choroidopathy which was associated with increased vascular tortuosity, microaneurysms, nonperfusion areas, either vascular dilations or narrowing in the choroid (3335) But the relationship between the natural course of DR and diabetic choroidopathy is still unclear. There are current studies trying to find answers to the question of if there is any predictive value in choroidal changes before developing DR.
The studies reported conflicting results. The majority of the authors reported choroidal thinning in diabetic patients without DR (9, 36-39). They postulated that choroidal thinning may be the earliest sign in the diabetic patients with no clinical DR and suggested that microvascular changes might occur earlier than structural changes in DM. Some OCT angiography studies supported this finding that vessel density already decreased in patients with DM before the clinical signs of DR occur (40, 41). Authors attributed the choroidal thinning to choriocapillaris dropout caused by hyperglycemia and hypoinsulinemia (42, 43). Regarding this Nagaoka et al. demonstrated decreased choroidal blood flow in diabetic patients, even before visible DR was present (8).
In contrast to these findings choroidal thickening was also reported in DM patients with no DR (38, 44). It was attributed to choroidal vasodilation and increase of blood flow by increased vascular endothelial growth factor (45).
The studies performed after retinopathy had developed are also controversial. In a recent study of Horvath et al. with swept source OCT, ChT was thinner in cases with more advanced DR (46). Controversially ChT increased in eyes with severe NPDR and PDR in another study (47). It has also been reported that there is no relationship between the duration of DM and ChT (48).
The possible cause of these conflicting results may be the involvement of heterogeneous and relatively small samples in the studies. A recent study provided an idea of these contradictory outcomes, Ferreira et al. reported that mean ChT increased in the first 77 months of DM, then decreased until 150 months, after which, it tended to be stabilized (38). They postulated there may be three phases of choroid during DM, early choroidal thickening, choroidal thinning--due to atrophy- and vascular stabilization phases where resistance and remodeling of vessels were seen.
One other reason for the conflicting results could be the number of the scoring physicians. At least two scorers must rate the results.
There was no correlation between HbA1c and ChT in our study, in agreement with other studies (38). No change in ChT values with different HbA1c levels may be related to an increase in resistance index in diabetic patients developed during the chronic period (49).
Our study had some limitations. ChT measurements were done manually. However, this manual technique already showed a high intraobserver and interobserver reproducibility (50). The values for intraclass correlation coefficient (ICC) between raters as well as the mean inter-observer difference should have been provided.
Also, the magnitude of the choroidal increase is relatively small. Variability in ChT measurements can arise from factors related to the observer, image quality or exact location of the measurement.
There is a much larger dispersion in the prediabetic group than in the control group as expressed by SD and min-max values. This finding could be due to clinicians diagnosing prediabetes which should be treated; emphasizing life style changes effect on the patient and the patients perception and motivation, adopting these changes which is a crutial point at the management of type two diabetes. The time between the start of the life style changes and OGTT could also be a determining factor.
This study may give an opinion that hyperglycemia and/ or hyperinsulinemia can cause different effects in the acute or chronic process in the choroid and it may have a predictive value about DR progression. Future studies were needed to clarify the exact mechanism between hyperglycemia and ocular structures as well as choroid.
Ethics Committee Approval: This study was approved by the GATA Ethics Committee (5.5.2015/8 (218)).
Informed Consent: Written consent was obtained from the participants.
Peer Review: Externally peer-reviewed.
Author Contributions: Conception/Design of Study-E.C., M.A., N.D., F.A.; Data Acquisition-E.C., F.A.; Data Analysis/Interpretation-E.C., M.A., S.P, N.D., F.A.; Drafting Manuscript-E.C., M.A.,
S.P, N.D., F.A.; Critical Revision of Manuscript-E.C., M.A., S.P, N.D., F.A.; Final Approval and Accountability-E.C., M.A., S.P, N.D., F.A.; Technical or Material Support-M.A., N.D., F.A.; Supervision-E.C., M.A., S.P, FA.
Conflict of Interest: Authors declared no conflict of interest.
Financial Disclosure: Authors declared no financial support.
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Eylem CAGILTAY  [ID], Muhammed ALTINISIK  [ID], Sjaak POUWELS , Nur DEMIR  [ID], Fahrettin AKAY  [ID]
University of Medical Sciences, Sultan Abdulhamid Han Training and Research Hospital,  Department of Internal Medicine, Division Endocrinology and Metabolic Diseases,  Department of Opthalmology, Istanbul, Turkey  Celal Bayar University, Faculty of Medicine, Department of Opthalmology, Manisa, Turkey  Haaglanden Medical Center, Department of Surgery, the Hague, Netherlands  Katip Celebi University, Ataturk Training and Research Hospital, Department of Opthalmology, Izmir, Turkey
ORCID IDs of the authors: E.C. 0000-0003-3901-4015; M.A. 0000-0003-0239-0180; S.P. 0000-0002-6390-7692; N.D. 0000-0003- 4764-1131; FA 00000001-9679-9379
Corresponding author/Iletisim kurulacak yazar: firstname.lastname@example.org
Submitted/Basvuru: 29.11.2019 * Revision Requested/Revizyon Talebi: 20.01.2020 * Last Revision Received/Son Revizyon: 20.01.2020 * Accepted/Kabul: 30.01.2020 * Published Online/Online Yayin: 10.03.2020
Caption: Figure 1: A sample of 7 different points measurement of ChT.
Table 1: Demographic characteristics of the patients Prediabetic group (Mean [+ or -] SD, min-max) Age (years) 41.26 [+ or -] 6.49 (30-50) Sex (Male/female) 31/19 (62%/38%) SE (D) -0.41 [+ or -] 0.79 (-2.00/1.00) IOP (mmHg) 14.94 [+ or -] 2.82 (10-25) AL (mm) 23.30 [+ or -] 0.56 (22.0-24.5) HbA1c (%) 5.98 [+ or -] 0.33 (5.50-6.90) BMI (kg/[m.sup.2]) 26.32 [+ or -] 1.34 (23.65-29.10) Healthy group (Mean [+ or -] p SD, min-max) Age (years) 41.20 [+ or -] 6.22 0.963 Sex (Male/female) 26/24 (52%/48%) 0.313 SE (D) -0.25 [+ or -] 1.14 (-2.50/2.25) 0.417 IOP (mmHg) 14.82 [+ or -] 2.26 (11-19) 0.815 AL (mm) 23.10 [+ or -] 0.52 (22.0-24.5) 0.06 HbA1c (%) 5.18 [+ or -] 0.46 (4.10-5.70) <0.001 BMI (kg/[m.sup.2]) 25.94 [+ or -] 1.31 (23.70-29.10) 0.149 SE: Spherical equivalente, IOP: Intraocular pressure, AL: Axial length, BMI: Body mass index, SD: Standard deviation, p: Statistical significance Table 2: PG levels during OGTT PG levels Prediabetes (mg/dl) p (within group) Basal 114.38 [+ or -] 5.64 1 hour after glucose 187.94 [+ or -] 33.47 <0.001 loading 2 hour after glucose 146.6 [+ or -] 44.53 loading PG levels Healthy volunteers p (within group) (mg/dl) Basal 83.98 [+ or -] 9.65 1 hour after glucose 147.46 [+ or -] 28.54 <0.001 loading 2 hour after glucose 96.45 [+ or -] 23.54 loading PG levels p (between groups) Basal <0.001 1 hour after glucose <0.001 loading 2 hour after glucose <0.001 loading OGTT: Oral glucose tolerance test, PG: Plasma glucose Table 3: Insulin levels during OGTT Insulin levels Prediabetes patients P (within group) ([micro]U/mL) Basal 14.5 [+ or -] 8.55 1 hour after glucose 100.14 [+ or -] 42.61 <0.001 loading 2 hour after glucose 76 [+ or -] 53.01 loading Insulin levels Healthy volunteers p (within group) ([micro]U/mL) Basal 11.32 [+ or -] 3.46 1 hour after glucose 73.56 [+ or -] 26.45 <0.001 loading 2 hour after glucose 41.56 [+ or -] 15.65 loading Insulin levels p (between groups) Basal <0.001 1 hour after glucose <0.001 loading 2 hour after glucose <0.001 loading OGTT: Oral glucose tolerance test Table 4: ChT measurements during OGTT ChT Measurements Prediabetes patients P (within ([micro]m) group) Average 0 260.81 [+ or -] 29.71 Average 1 262.25 [+ or -] 29.98 0.022 Average 2 261.14 [+ or -] 29.22 Subfoveal 0 267.46 [+ or -] 29.004 Subfoveal 1 268.98 [+ or -] 30.15 0.021 Subfoveal 2 267.82 [+ or -] 28.872 Nazal 500 [micro]m 0 262.04 [+ or -] 30.15 Nazal 500 [micro]m 1 264.1 [+ or -] 30.3 0.001 Nazal 500 [micro]m 2 263.5 [+ or -] 29.78 Nazal 1000 [micro]m 0 250.8 [+ or -] 29.73 Nazal 1000 [micro]m 1 252.66 [+ or -] 29.24 0.104 Nazal 1000 [micro]m 2 251.68 [+ or -] 28.26 Nazal 1500 [micro]m 0 235.26 [+ or -] 33.01 Nazal 1500 [micro]m 1 236.36 [+ or -] 32.53 0.242 Nazal 1500 [micro]m 2 235.76 [+ or -] 31.32 Temporal 500 [micro]m 0 270.76 [+ or -] 30.63 Temporal 500 [micro]m 1 272.68 [+ or -] 30.69 0.018 Temporal 500 [micro]m 2 270.66 [+ or -] 30.08 Temporal 1000 [micro]m 0 271.24 [+ or -] 32.24 Temporal 1000 [micro]m 1 272.32 [+ or -] 32.15 0.276 Temporal 1000 [micro]m 2 271.34 [+ or -] 31.64 Temporal 1500 [micro]m 0 268.16 [+ or -] 32.72 Temporal 1500 [micro]m 1 268.62 [+ or -] 33.06 0.205 Temporal 1500 [micro]m 2 267.16 [+ or -] 32.19 ChT Measurements Healthy volunteers p (within ([micro]m) group) Average 0 264.18 [+ or -] 27.01 Average 1 263.97 [+ or -] 26.95 0.094 Average 2 264.58 [+ or -] 26.45 Subfoveal 0 271.04 [+ or -] 27.939 Subfoveal 1 270.82 [+ or -] 28.31 0.685 Subfoveal 2 270.98 [+ or -] 27.27 Nazal 500 [micro]m 0 265.96 [+ or -] 27.7 Nazal 500 [micro]m 1 265.64 [+ or -] 27.47 0.69 Nazal 500 [micro]m 2 266 [+ or -] 27.3 Nazal 1000 [micro]m 0 257.7 [+ or -] 26.63 Nazal 1000 [micro]m 1 257.62 [+ or -] 26.2 0.527 Nazal 1000 [micro]m 2 258.12 [+ or -] 26.65 Nazal 1500 [micro]m 0 247.46 [+ or -] 26.9 Nazal 1500 [micro]m 1 247.38 [+ or -] 26.87 0.251 Nazal 1500 [micro]m 2 249.64 [+ or -] 28.63 Temporal 500 [micro]m 0 270.6 [+ or -] 29.1 Temporal 500 [micro]m 1 270.4 [+ or -] 29.27 0.228 Temporal 500 [micro]m 2 270.7 [+ or -] 28.76 Temporal 1000 [micro]m 0 270.54 [+ or -] 29.32 Temporal 1000 [micro]m 1 270.34 [+ or -] 29.27 0.427 Temporal 1000 [micro]m 2 270.6 [+ or -] 28.83 Temporal 1500 [micro]m 0 265.9 [+ or -] 28.93 Temporal 1500 [micro]m 1 265.64 [+ or -] 28.77 0.26 Temporal 1500 [micro]m 2 266 [+ or -] 28.37 ChT Measurements p (between groups) Average 0 0.555 Average 1 0.764 Average 2 0.538 Subfoveal 0 0.531 Subfoveal 1 0.754 Subfoveal 2 0.575 Nazal 500 [micro]m 0 0.5 Nazal 500 [micro]m 1 0.791 Nazal 500 [micro]m 2 0.663 Nazal 1000 [micro]m 0 0.225 Nazal 1000 [micro]m 1 0.374 Nazal 1000 [micro]m 2 0.244 Nazal 1500 [micro]m 0 0.045 Nazal 1500 [micro]m 1 0.068 Nazal 1500 [micro]m 2 0.023 Temporal 500 [micro]m 0 0.979 Temporal 500 [micro]m 1 0.705 Temporal 500 [micro]m 2 0.995 Temporal 1000 [micro]m 0 0.91 Temporal 1000 [micro]m 1 0.748 Temporal 1000 [micro]m 2 0.903 Temporal 1500 [micro]m 0 0.715 Temporal 1500 [micro]m 1 0.632 Temporal 1500 [micro]m 2 0.849 Results are expressed as mean [+ or -] SD. 0: Befoloading 1: One hour after glucose loading 2: Two loading
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|Author:||Cagiltay, Eylem; Altinisik, Muhammed; Pouwels, Sjaak; Demir, Nur; Akay, Fahrettin|
|Publication:||Journal of Istanbul Faculty of Medicine|
|Date:||Jul 28, 2020|
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