Introduction

Type II diabetes mellitus (DM), characterized by insulin resistance (IR), impaired insulin secretion and increased glucose production1 is estimated to affect 65.1 million people in India according to IDF (International Diabetes Federation) in 2013.2 Asian countries have reported the diabetes burden to be disproportionately high in young to middle-aged adults3 and Asian Indians are known to be at a greater risk of developing diabetes.4

Urbanization is to be blamed for the rising prevalence of diabetes in India and other developing countries.5 If diagnosed diabetes early, it is highly likely that complications could be prevented3 thus emphasizing the need for primary prevention of diabetes and its complications.

There is a known association between diabetes mellitus and altered salivary composition and function. Vascular complications develop as a result of changes in the metabolism of lipids and proteins.9 Glucose moves through membranes of blood vessels, passes from the blood plasma via gingival sulcus to the gingival fluid, and reaches the saliva.10

Salivary glucose levels are known to be raised in diabetics6 and increased blood glucose may cause higher levels of salivary glucose.4 In a certain study, a decrease in fasting salivary glucose levels was seen in the experimental group.8

If diabetes is left undiagnosed and untreated, it can cause progressive microvascular and macrovascular damage and eventually result in a lower life expectancy. Therefore, innovative methods of testing for the disease is essential to overcome this disease burden.

Contradictory results have been obtained from studies that evaluate glucose concentration in saliva, however if a correlation exists, estimating salivary glucose levels could be used as a non-invasive method for determining glucose levels in diabetics.

Insulin resistance, body composition, and energy balance have different effects on men when compared to women because adipose tissue distribution plays the main role in developing insulin resistance and other complications that develop as a result of obesity.11 Type II diabetics show an increased cardiovascular morbidity and mortality. It has been seen that postprandial blood glucose is an independent risk factor for cardiovascular events, with a stronger predictive power in women.12 This study was done to examine effects of gender on salivary and blood glucose in type II diabetics and healthy adults.

Materials and Methods

80 adults in the age group of 30 – 50 years were recruited for the study from outpatients attending KIMS Hospital outpatient department, Bangalore, to determine and compare salivary glucose levels in diabetics and healthy adults and to assess the relationship between blood glucose and salivary glucose levels using the method of colorimetry. They were divided into 2 groups – diabetics and healthy adults. Both groups were further divided into 2 groups based on gender – male and female.

All subjects underwent anthropometric assessment (recording of height using a stadiometer and also weight to the nearest 100gms). BMI was also calculated. The blood and saliva samples were assessed in the lab in the Department of Biochemistry, Kempegowda Institute of Medical Sciences, Bangalore.

Blood and saliva samples were obtained from subjects after an overnight fast and 2 hours postprandial. Blood samples were analysed with hexokinase enzyme (automated analyser) and saliva samples with glucose oxidase enzyme (colorimeter).

Salivary glucose levels were compared between diabetics and healthy adults by t – test. Relationship between salivary and blood glucose was assessed by correlation test. Difference in salivary and blood glucose levels between diabetic and healthy males and females was determined by t – test.

The results were presented as mean ± SD and the significance of any difference was tested with t-test and Mann-Whitney test wherever appropriate. Differences with P values < 0.05 were considered statistically significant. Spearman’s rank correlation test was used to determine the correlation between blood and salivary glucose values.

Results

Salivary glucose is significantly higher in diabetics. The mean salivary glucose concentration in the fasting state was 9.77 ± 5.34 mg/dl for the study group and 5.77 ± 2.01 mg/dl in the control group, a statistically significant difference (P <0.001), as shown in Table 2 (Figures 1 & 2). The mean salivary glucose level in the postprandial state for the diabetic group was 13.65 ± 5.92 mg/dl and in healthy adults, 10.57 ± 3.07 mg/dl and this difference was statistically significant (P <0.001).

Blood glucose is higher in female diabetics and salivary glucose is higher in male diabetics. The mean salivary glucose concentration in the fasting state in diabetic men was 10.30 ± 7.02 mg/dl and 4.71 ± 1.25 mg/dl in the control group, a statistically significant difference (P = 0.001), as shown in Table 3 (Figure 3). The mean salivary glucose level in the postprandial state in diabetic men was 13.76 ± 7.53 mg/dl and in healthy men, 9.56 ± 1.56 mg/dl and this difference was statistically significant (P = 0.015). The mean salivary glucose concentration in the fasting state in diabetic women was 9.38 ± 3.80 mg/dl and 6.23 ± 2.12 mg/dl in the control group, a statistically significant difference (P<0.001), as shown in Table 3 (Figure 3). The mean salivary glucose level in the postprandial state in diabetic women was 13.57 ± 4.57 mg/dl and in healthy men, 11.01 ± 3.46 mg/dl and this difference was statistically significant (P = 0.015).

Correlation flanked by salivary and blood glucose is not seen.

Discussion

The onset of diabetes mellitus, a constellation of abnormalities caused by insulin resistance and deficiency, in Asia is at lower BMI levels and younger ages when compared to the Western population.13 However, the average BMI in Asian populations is still relatively low. In the present study, the mean BMI of the study group was 25.37 ± 2.57 kg/m2 and that of the control group was 24.46 ± 3.33 kg/m2 and there was no significant difference between them (P=0.204) (Table 1).

Asians are possibly more genetically susceptible to insulin resistance and diabetes than Whites. A few factors that contribute to the rise in the diabetes epidemic in Asians are “normal-weight metabolically obese” phenotype, high prevalence of smoking, excessive alcohol intake, high intake of refined carbohydrates and dramatically decreased physical activity levels. It has also been seen that poor nutrition during intrauterine and in early life followed by overnutrition later in life may also play a role in Asia’s diabetes epidemic.15

Alterations in the oral mucosa in diabetes mellitus has been observed in experimental studies and clinical practice.28-30 The elevated glucose levels in saliva observed by Murrah, Crusson and Sauk also confirms the effect of diabetic membranopathy, which leads to an increased percolation of glucose from blood to saliva, thus affecting the salivary composition in these patients 31 which could explain the increased levels of salivary glucose in diabetics. The higher level of salivary glucose in diabetics in postprandial state suggests the effects of metabolism on simple and complex carbohydrates which form the major portion of the diet of South Indians.

There was no correlation seen in the relation between blood glucose and salivary glucose. A similar result was observed by Sashikumar et al24 for blood and saliva samples collected in the fasting state and Panchbai et al.6 for postprandial and random blood and saliva samples. There is no correlation probably because separate mechanisms are involved in the metabolism of salivary and blood glucose.

Our results are supported by some studies but differ from those obtained by other researchers probably due to diversity in the selection criteria of the samples and the type of design of each study, differences in the methods employed in collection of saliva and variation in age of the subjects studied, and varying levels of metabolic control in diabetic patients. In order to prevent progression from prediabetes to frank diabetes and its complications, early identification of people at risk of developing type II diabetes will help in preventing. Also if non–invasive methods are employed, greater number of people will participate in the screening of diseases.

Geer et al reported that for a given body mass index, men we have more lean mass while women have higher adiposity. Women had more peripheral or subcutaneous adipose tissue compared to men, who, in turn, were found to have more visceral and hepatic adipose tissue. Along with these differences, differences in sex hormones and adipokines, may explain a more insulin-sensitive environment in women than in men.11

In a 5 year follow up study, Cavalot et al, observed that postprandial blood glucose predicts the occurrence of cardiovascular events in type 2 diabetic patients when compared to fasting blood glucose, this effect being stronger in women than in men after correction for cardiovascular risk factors and type of therapy.12 Another study done by Haas et al noted that fatality rates are higher for women compared with men with diabetes even though women have lower rates of obstructive coronary artery disease (CAD).36

In our study, blood glucose is higher in female diabetics and salivary glucose is higher in male diabetics. The differences in fasting and postprandial blood glucose and salivary glucose in male and female diabetics suggest that differences in clinical signs, development of complications, preventative approach, prognosis and gender responses to therapy should be considered to achieve better and continuous glycaemic control in type II diabetics. The field of gender medicine focuses on such differences and considers gender a significant variable in research.

Limitation

The small sample size is a limitation of our study and the study of larger populations in the future can provide more information about the relationship between blood glucose and salivary glucose levels.

Conclusion

Salivary glucose levels are significantly higher in diabetics in fasting and postprandial states in our study therefore, estimation of salivary glucose levels can be used as a mass screening method for diabetes in large populations. Sex differences in fasting and postprandial blood glucose and salivary glucose suggest that differences in gender responses to therapy should be considered to achieve better and continuous glycaemic control in type II diabetics.

Acknowlegements

We thank all the participants, who volunteered for this study.1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38

Table 1 Characteristics of subjects
Diabetic group Control group Male (n) 17 12Female (n) 23 28Age (year ) 42.03 ± 5.77 39.95 ± 6.43 BMI (kg/m2) 25.37 ± 2.57 24.46 ± 3.33

Table 2 Blood glucose and salivary glucose levels of the groups
Diabetic group Control group value
Fasting blood glucose (FBG)(mg/dl) 147.93 ± 65.50 88.00 ± 12.48 <0.001*
Postprandial blood glucose (PPBG)(mg/dl) 224.40 ± 90.25 126.73 ± 30.85 <0.001*
Fasting salivary glucose (FSG)(mg/dl) 9.77 ± 5.34 5.77 ± 2.01 <0.001*
Postprandial salivary glucose (PPSG)(mg/dl) 13.65 ± 5.92 10.57 ± 3.07 0.001*

Table 3 Blood glucose and salivary glucose levels of males
Diabetic men Men in control group value
Fasting blood glucose (FBG)(mg/dl) 122.94 ± 57.55 88.00 ± 15.46 0.008*
Postprandial blood glucose (PPBG)(mg/dl) 205.06 ± 100.08 132.42 ± 37.24 0.010*
Fasting salivary glucose (FSG)(mg/dl) 10.30 ± 7.02 4.71 ± 1.25 0.001*
Postprandial salivary glucose (PPSG)(mg/dl) 13.76 ± 7.53 9.56 ± 1.56 0.015*

Table 4 Blood glucose and salivary glucose levels of females
Diabetic group Control group value
Fasting blood glucose (FBG)(mg/dl) 166.39 ± 66.02 88.00 ± 11.30 <0.001*
Postprandial blood glucose (PPBG)(mg/dl) 238.70 ± 81.55 124.29 ± 28.09 <0.001*
Fasting salivary glucose (FSG)(mg/dl) 9.38 ± 3.80 6.23 ± 2.12 <0.001*
Postprandial salivary glucose (PPSG)(mg/dl) 13.57 ± 4.57 11.01 ± 3.46 0.015*

Figure 1 Mean Fasting blood glucose (FBG) and Fasting salivary glucose (FSG) in the groups

Figure 2 Mean Postprandial blood glucose (PPBG) and Postprandial salivary glucose (PPSG) in the groups

Figure 3 Mean Fasting salivary glucose (FSG) and Postprandial salivary glucose (PPSG) in males

Figure 4 Mean Fasting salivary glucose(FSG) and Postprandial salivary glucose (PPSG) in females

References

  1. Retrospective study among primary care Type 2 diabetes mellitus patients within the city of Zliten, Libya, represented high incidence of early onset of disease diagnosis Ahmed AbdulrzagF, Fayed MohamedS, Yasser MajdaH, Lincz LisaF. Libyan Journal of Medical Sciences.2019;3(1):13-13.
  2. High prevalence of diabetes and impaired glucose tolerance in India: National Urban Diabetes Survey Ramachandran A., Snehalatha C., Kapur A., Vijay V., Mohan V., Das A. K., Rao P. V., Yajnik C. S., Prasanna Kumar K. M., Nair Jyotsna D.. Diabetologia.2001;44(9):1094-1101.
  3. Update on diabetes mellitus and related oral diseases Manfredi M, McCullough MJ, Vescovi P, Al-Kaarawi ZM, Porter SR. Oral Diseases.2004;10(4):187-200.
  4. Health benefits of saliva: a review Dodds Michael W.J., Johnson Dorthea A., Yeh Chih-Ko. Journal of Dentistry.2005;33(3):223-233.
  5. Parotid gland basement membrane variation in diabetes mellitus Murrah V. A., Crosson J. T., Sauk J. J.. Journal of Oral Pathology and Medicine.1985;14(3):236-246.
  6. A new method to evaluate fasting plasma glucose by salivary glucose measurement Mahdavi S O, Hasheni S, Boostani N S, Zokaee H. IJDO.2012;4(3):127-133.
  7. Evaluation of salivary glucose, IgA and flow rate in diabetic patients: a case-control study Vaziri P B, Vahedi M, Mortazavi H, Abdollahzadeh S, Hajilooi M. Journal of dentistry.2010;7(1):13-21.
  8. Expanding role of the Madras Diabetes Research Foundation - Indian Diabetes Risk Score in clinical practice Mohan Viswanathan, Anbalagan VikneshPrabu. Indian Journal of Endocrinology and Metabolism.2013;17(1):31-31.
  9. Alternations in salivary glucose during ramadan fasting Sariri Reyhaneh, Varasteh Abdolali, Erfani Ali. Health.2010;02(07):769-772.
  10. Some salivary factors in insulin-dependent diabetics Thorstensson Helene, Falk Hanne, Hugoson Anders, Olsson Jadwiga. Acta Odontologica Scandinavica.1989;47(3):175-183.
  11. Comparison of Self-reported and Measured BMI as Correlates of Disease Markers in U.S. Adults* McAdams Mara A., Van Dam Rob M., Hu Frank B.. Obesity.2007;15(1):188-188.
  12. Salivary alterations in insulin‐dependent diabetes mellitus Belazi Maria A., Galli‐Tsinopoulou Assimina, Drakoulakos Drakoulis, Fleva Alexandra, Papanayiotou Panayiotis H.. International Journal of Paediatric Dentistry.1998;8(1):29-33.
  13. Harrison’s principles of internal medicine Powers A C, Fauci A, Braunwald E, Kasper D. New York: McGraw-Hill; 2008.
  14. Alterations in Whole Saliva Constituents in Patients with Diabetes Mellitus and Periodontal Disease Navalkar Amita, Bhoweer Anilkumar. Journal of Indian Academy of Oral Medicine and Radiology.2011;23(4):498-501.
  15. High Prevalence of Diabetes and Cardiovascular Risk Factors Associated With Urbanization in India Ramachandran A., Mary S., Yamuna A., Murugesan N., Snehalatha C.. Diabetes Care.2008;31:893-898.
  16. Estimation of salivary glucose, salivary amylase, salivary total protein and salivary flow rate in diabetics in India Panchbhai Arati S., Degwekar Shirish S., Bhowte Rahul R.. Journal of Oral Science.2010;52(3):359-368.
  17. Mixed salivary glucose levels and candidal carriage in patients with diabetes mellitus Darwazeh A. M. G., MacFarlane T. W., McCuish A., Lamey P.-J.. Journal of Oral Pathology and Medicine.1991;20(6):280-283.
  18. Comparative study of the concentration of salivary and blood glucose in type 2 diabetic patients Vasconcelos Ana Carolina U., Soares Maria Sueli M., Almeida Paulo C., Soares Teresa C.. Journal of Oral Science.2010;52(2):293-298.
  19. Postprandial Hyperglycemia and Insulin Sensitivity Differ among Lean Young Adults of Different Ethnicities Dickinson S., Colagiuri S., Faramus E., Petocz P., Brand-Miller J. C.. The Journal of Nutrition.2002;132(9):2574-2579.
  20. Saliva: A tool in assessing glucose levels in Diabetes Mellitus Satish B N, Srikala P, Maharudrappa B, Awanti S M, Kumar P, Hugar D. J Int Oral Health.2014;6(2):114-117.
  21. Postprandial Blood Glucose Is a Stronger Predictor of Cardiovascular Events Than Fasting Blood Glucose in Type 2 Diabetes Mellitus, Particularly in Women: Lessons from the San Luigi Gonzaga Diabetes Study Cavalot F., Petrelli A., Traversa M., Bonomo K., Fiora E., Conti M., Anfossi G., Costa G., Trovati M.. The Journal of Clinical Endocrinology & Metabolism.2006;91(3):813-819.
  22. Mobile smart device infrared light measuring apparatus, pimethod, and system for analyzing substances. United States patent 20140027641 Mucci D A, Clark R G, Fox J S. 2014.
  23. inventors; Northeastern University., assignee. Saliva glucose monitoring system. United States patent 20140197042 Zhang W, Wang M L. .
  24. Salivary glucose levels and oral candidal carriage in type II diabetics Sashikumar Radhika, Kannan Ranganathan. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology.2010;109:706-711.
  25. Saliva: A tool in assessing glucose levels in Diabetes Mellitus Satish B N, Srikala P, Maharudrappa B, Awanti S M, Kumar P, Hugar D. J Int Oral Health.2014;6(2):114-117.
  26. Saliva-the key regulator of oral changes in diabetes patients Babu N A, Masthan K M, Bhattacharjee T, Elumalai M. IJPSR.2014;5(7):2579-2583.
  27. Salivary glucose concentration in patients with diabetes mellitus - a minimally invasive technique for monitoring blood glucose levels Amer S, Yousuf M, Siddiqiui P Q, Alam J. Pak J of Pharm Sci.2001;14(1):33-40.
  28. A simplified Indian Diabetes Risk Score for screening for undiagnosed diabetic subjects Mohan V, Deepa R, Deepa M, Somannavar S, Datta M. Journal of the Association of Physicians of India.2005;53:759-763.
  29. Sex Differences in Coronary Microvascular Function in Individuals With Type 2 Diabetes Haas Andrea V., Rosner Bernard A., Kwong Raymond Y., Rao Ajay D., Garg Rajesh, Di Carli Marcelo F., Adler Gail K.. Diabetes.2019;68(3):631-636.
  30. Globalization of Diabetes: The role of diet, lifestyle, and genes Hu F. B.. Diabetes Care.2011;34:1249-1257.
  31. Endocrine functions of the pancreas and regulation of carbohydrate metabolism Ganong W F, Barrett KE, Barman SM, Boitano S, Brooks HL. Review of Medical Physiology.2012;:449-450.
  32. Epidemiology of type 2 diabetes: Indian scenario. The Indian journal of medical research Mohan V, Sandeep S, Deepa R, Shah B, Varghese C. 2007.
  33. Xerostomia and salivary levels of glucose and urea in patients with diabetes Ivanovskik Naumovski V, Kostadinova M, Pesevska S, Drijanska K, Filipce V. Prilozi Macedonian Academy of Sciences and Arts, Section of Biological and Medical Sciences.2012;33(2):219-219.
  34. Global Prevalence of Diabetes: Estimates for the year 2000 and projections for 2030 Wild S., Roglic G., Green A., Sicree R., King H.. Diabetes Care.2004;27(5):1047-1053.
  35. Gender differences in insulin resistance, body composition, and energy balance Geer Eliza B., Shen Wei. Gender Medicine.2009;6:60-75.
  36. Diabetes in Asia: epidemiology, risk factors and pathophysiology Chan J C, Malik V, Jia W, Kadowaki T, Yajnik C S, Yoon K H. JAMA.2009;301(20):2129-2140.
  37. Saliva specimen: A new laboratory tool for diagnostic and basic investigation Chiappin Silvia, Antonelli Giorgia, Gatti Rosalba, De Palo Elio F.. Clinica Chimica Acta.2007;383(1-2):30-40.