CLINICAL AND MRI ASSESSMENT OF THE PAROTID GLAND IN DIABETIC PATIENTS: PRELIMINARY STUDY

Ola Mohamed Rehan MSc 1 , Hoda Abdel Kader Saleh PhD 2 , Dr. Ayman Ismail Kamel PhD 3 and Noha Saleh Abu Taleb PhD 4 . 1. Assistant Lecturer of Oral and Maxillofacial Radiology, Faculty of Oral and Dental Medicine, Cairo University. 2. Professor of Oral and Maxillofacial Radiology, Faculty of Oral and Dental Medicine, Cairo University. 3. Professor of Radiology, Faculty of Medicine, Cairo University 4. Assoc. Professor of Oral and Maxillofacial Radiology, Faculty of Oral and Dental Medicine, Cairo University. ...................................................................................................................... Manuscript Info Abstract ......................... ........................................................................ Manuscript History

There are various radiographic techniques used for evaluation of the salivary gland structure such as magnetic resonance imaging (MRI), computed tomography (CT), ultrasonography, and scintigraphy. On the other hand, the ductal system can be evaluated by conventional sialography and recently magnetic resonance (MR) sialography (Kuan et al., 2016).
MRI has several advantages over other diagnostic imaging procedures. It has extremely high contrast resolution between soft tissues. Furthermore, in MRI no ionizing radiation is involved, and therefore do not have the associated harmful effects of ionizing radiation (White and Pharoah, 2014). Advantages of MR sialography are rapid acquisition times, noninvasiveness, and the possibility to visualize all major salivary glands without further positioning of the patient (Kalinowski et al., 2002).
There are various clinical and radiographic techniques used for evaluation of the salivary gland excretory function. The most advocated clinical method for diagnosing salivary gland dysfunction is to quantitate unstimulated and stimulated whole saliva flow rates (SFR) (Diogo Löfgren et al., 2012). The aim of this study is the evaluation of the parotid gland structure, ductal system, and function in diabetic patients.

Patients And Methods:-
Twenty subjects were selected from the outpatient clinic of the Oral Medicine and Diagnosis Department, Faculty of Oral and Dental Medicine, Cairo university. The subjects selected were divided into two groups; ten healthy volunteers (control group) and ten patients with type 2 diabetes mellitus.
Volunteer subjects were selected according to the following criteria, no parotid gland diseases as verified by the history, the clinical examination, and the acquired T1WIs. Also, they were not under any medication for any other disorder or suffering of any systemic disease which may affects salivary gland function. Diabetic subjects did not take any medications except those for diabetic treatment.
A written informed consent was obtained from all the subjects sharing in this study. The subjects were examined clinically for the presence of xerostomia and bad oral hygiene. Next, the salivary flow rate (SFR) was measured for each subject 2 hours after breakfast at 11am. The subject spitted in a cup and saliva was collected for 5 minutes. Then, the gland was stimulated by 5ml lemon juice and the post stimulation saliva was collected for 5 minutes in another cup. The collected saliva was measured by plastic syringe in units of ml/min. MRI examination of left parotid gland for each patient was performed by using a 1.5 T superconductive magnet. The examination was performed at the Radiology Department, Faculty of Medicine, Cairo University. Axial T1WIs were performed using head coil with the following parameters (TSE sequence; TR: 488; TE: 15; NEX: 2; FOV: 230 mm; Image matrix: 232× 185; Slice thickness: 4 mm; Interslice gap: 5 mm; Acquisition time: 2 minutes and 28 seconds). Coronal T1WIs were performed using head coil with the following parameters (TSE sequence; TR: 488; TE: 15; NEX: 2; FOV: 230 mm; Image matrix: 232× 185; Slice thickness: 3 mm; Interslice gap: 3 mm; Acquisition time: 2 minutes and 15 seconds).
MR sialography was performed after stimulation of the gland by 5ml lemon juice to evaluate the ductal morphology, using single shot turbo spin echo sequence (SSTSE) and surface coil with the following parameters (TR: 8000; TE: 900; NEX: 2; FOV: 120 mm; Image matrix: 124×150; Slice thickness: 30 mm; Acquisition time: 16 seconds) Statistical Analysis:-Student's t-test and Mann-Whitney U test were used for comparisons between the two groups. Chi-square (x 2 ) test was used for studying the comparisons and associations between different qualitative variables. Pearson's correlation coefficient was used to determine significant correlations between different quantitative variables. The significance level was set at P ≤ 0.05. Statistical analysis was performed with IBM ® (Corporation, NY, USA). SPSS ® (Inc., an IBM Company). Statistics Version 20 for Windows.

Results:-
Regarding the clinical findings, the diabetic group showed statistically significant higher prevalence of xerostomia than the control group (P-value = 0.001). Similarly, the oral hygiene, the diabetic group showed statistically significant higher prevalence of bad oral hygiene than the control group (P-value = 0.006). Besides, the salivary flow rate (SFR) of the control group showed statistically significant higher mean values in both the pre-and post-stimulation states (P-values = 0.027 and 0.001 respectively) than the diabetic group.
Concerning the imaging results, the ductal changes in the diabetic group showed statistically significant higher prevalence than the control group (P-value = 0.025) (Fig1).
As well, the diabetic group showed statistically significant higher prevalence of enlargement (P-value = 0.001) (Fig2) and statistically significant higher prevalence of parenchymal changes (P-value = 0.019) than the control group (Fig3).
A correlation was found between SFR values and the occurrence of xerostomia in the diabetic group. Patients with no xerostomia showed statistically significant higher mean SFR than patients with xerostomia (P-value = 0.044).

Discussion:-
Diabetes mellitus is a complex metabolic disease described by altered carbohydrate, lipid, and protein metabolism resulting in marked or absolute insulin deficiency or peripheral tissue insulin resistance (Vernillo, 2001).
The oral manifestations of diabetes mellitus include increased accumulation of plaque, higher susceptibility to infections, and pronounced hyperplasia of the attached gingival. All play a significant role in the increased incidence of periodontal disease, oral candidal infections, dental caries, dysgeusia or altered taste, and burning mouth syndrome. Moreover, diffuse non-tender bilateral enlargement of the parotid glands, called diabetic sialosis, may be noted in both types of diabetes. Furthermore, xerostomia may result from an overall diminished flow of saliva (Islam, 2011).
There are various techniques for the evaluation of the salivary gland morphology and function and in this study the parotid glands of diabetic patients were examined using MRI.
Twenty subjects, ten healthy volunteers and ten type 2 diabetic patients were selected for the study. Each subject was asked for the presence of xerostomia. For each subject, pre and post stimulation SFR of the parotid gland was measured by 5ml of lemon juice. Afterward, axial T1WIs and MR sialography were performed to evaluate the parenchyma and the ductal system of the gland respectively. In the present study, the left parotid gland was selected for the MRI examinations for standardization. MR sialography imaging was performed using fast and high resolution SSTSE sequence and a small surface coil is placed on the parotid gland area to obtain high resolution MR sialographic images Takagi et al, 2005).
A single section with a thick imaging slab was performed to obtain a two dimensional image of the curvilinear fluid filled duct similar to conventional radiographs using x-rays. MR sialography examination was performed after the stimulation of the gland by lemon juice to enhance the visibility of the main and branching ducts (Hugill et al., 2008).
Clinical results of this study revealed that the diabetic group had statistically significant (P = 0.001) higher prevalence of xerostomia than the control group (70% and 0% respectively). This finding was parallel to Carda et In the current study the diabetic group showed statistically significant (P = 0.006) higher prevalence of bad oral health than the control group (70% and 10% respectively) and this finding was close to Campus et al 2005. It is well known that patients with diabetes are liable to oral infections that lead to caries, periodontal disorders, and tooth loss due to the poor glycemic control in diabetics (Campus et al., 2005;Taylor and Borgnakke, 2008).
Regarding SFR, the mean unstimulated SFR in the diabetic group was significantly (P=0.027) lower than that in the normal group (0.30ml/min and 0.39ml/min respectively). Similarly, the mean stimulated SFR in the diabetic group was also significantly (P=0.001) lower than that in the control group (1.65ml/min and 2.75ml/min respectively). The impairment of the parotid gland function may be multifactorial. Fatty infiltration or accumulation within parenchymal portion of the gland (Panchbhai et al., 2010). Other theory suggested that salivary hypofunction and xerostomia may be due to diabetic neuropathy and atrophy of the myoepithelial cells, both interfere with the secretion mechanism which is produced by the stimulation of the alpha and beta adrenergic receptors of the acinar cells that physiologically induce exocytosis (Carda et al., 2006). Moreover, the hypofunction was also attributed to polydipsia and polyuria which reduce the extracellular fluid that directly affects the salivary production (Panchbhai et al., 2010).
About the ductal changes observed in this study, the diabetic group showed statistically significant (P = 0.025) higher prevalence of ductal changes in the form of dilatation and other signs of inflammation than control group (40% and 0% respectively).
Diabetic patients are more susceptible to developing oral bacterial infections as they are well known to have an impaired defense mechanism hence considered to be immuno-compromised. Subsequently, retrograde infections may affect the salivary glands especially that cleansing and buffering capacity of the saliva is diminished in those patients (Panchbhai et  Pertaining to the MRI findings in the T1WI, left parotid gland enlargement was observed in 70% of the diabetic patients versus 0% in the control group this parallel to the clinical finding. Moreover, parenchymal changes in the form of high signal intensity areas scattered within the gland parenchyma was observed in 60% of the diabetic patients versus 10 % in the control group, the prevalence of these parenchymal changes between both groups was statistically significant (P = 0.019).
Diabetes mellitus is one of the major etiological causes of sialosis, a pathology generally characterized by a painless bilateral enlargement of the parotid gland (Carda et al., 2006;Chen et al., 2013).
In many studies, the parotid gland enlargement found in diabetic patients was attributed to either a secondary increase of the adipose tissue within the parenchymal portion of the gland or together with the presence of numerous intra-cytoplasmatic fat inclusions in both the acinar and ductal cells of the parotid glands which are caused by modifications in the diabetic fat metabolism (Carda et al., 2006;Carda et al., 2005). Furthermore, the glandular enlargement in diabetics may be the result of acinar hypertrophy and this was also approved by Scully et al., 2008.

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On the other hand, Carda et al., 2005 stated that in parotid sialosis of diabetic origin, the parotid enlargement may be due to the fatty infiltration in glandular stroma only as they observed that the glands had smaller acini than controls and had ductal dilatation with stasis of secretory material.
Dependent on the previous studies, the high signal intensity areas observed in the diabetic patients in this study may be due to fat deposition in the parotid parenchyma.
In the present study, a correlation was found between the unstimulated SFR and the presence of xerostomia in diabetic patients where the xerostomic patients showed statistically significant lower mean unstimulated SFR than non xerostomic ones.

Conclusion:-
Diabetes mellitus may cause the hypofunction of the salivary glands and the MRI and MR sialography are valuable techniques in the examination of the structure and ductal morphology of the salivary glands.