Gestational Diabetes Mellitus in a Tertiary Care Hospital of Kolkata, India: Prevalence, Pathogenesis and Potential Disease Biomarkers

Abstract

Aims Prevalence of gestational diabetes mellitus (GDM) may vary across a country like India. Risk factors and disease-pathogenesis were also not fully elucidated. This study aimed to examine prevalence of GDM among pregnant women visiting antenatal clinic of a tertiary-care hospital of Kolkata, India; possible mechanism of disease pathogenesis and potency of associated parameters as disease biomarkers were also explored.

Methods 735 pregnant women were screened for GDM according to DIPSI (Diabetes in Pregnancy Study Group India) guideline and risk-factors were analyzed. Case-control study was conducted with 114 GDM and 114 matched non-GDM control. Blood sample was collected before glucose load for complete blood count, measurement of reactive oxygen species (ROS) and assessment of DNA damage.

Results Prevalence of GDM was found to be 17.2%(127/735). Maternal age, diabetic family history and acanthosis nigricans seemed to be important risk factors. Total ROS, lymphocyte DNA damage (measured by comet-assay) and some inflammatory hematological parameters were significantly higher in GDM compared to control. ROS, comet-tail DNA%, WBC, neutrophil-lymphocyte ratio (NLR) and mean platelet volume (MPV) were established as independent determinants of disease condition after adjustment for pre-gestational body mass index. In receiver operating characteristic analysis, ROS>155.7 arbitrary fluorescent unit, NLR>2.12 and MPV>11.05 fL showed 82.5 & 98.2%, 71.9 & 84.2% and 71.9 & 82.5% sensitivity & specificity respectively in disease prediction.

Conclusions Prevalence of GDM seemed to be high in Kolkata on Indian scenario. Oxidative-stress, related DNA-damage and inflammation seemed to have important contribution in pathogenesis of GDM independent of obesity. ROS, NLR and MPV with respective cut-off scores might be used as diagnostic and prognostic biomarkers for better management of the disease.

Key words

gestational diabetes mellitus - prevalence - kolkata - pathogenesis - oxidative stress - inflammatory biomarkers

• References

• 1 American Diabetes Association . Gestational Diabetes Mellitus (Position Statement). Diabetes Care 2004; 27 (Suppl. 02) S88-S90
• 2 Kalra P, Kachhwaha CP, Singh HV. Prevalence of gestational diabetes mellitus and its outcome in western Rajasthan. Ind J Endocrinol and Metabolism 2013; 17: 677-680
• 3 Schmidt MI, Ducan BB, Reichelt AJ. et al. Gestational diabetes mellitus diagnosed with a 2-h 75 gm oral glucose tolerance test and adverse pregnancy outcomes. Diabetes Care 2001; 24: 1151-115
• 4 Watanabe RM. Inherited destiny? Genetics and gestational diabetes mellitus. Genome Med 2011; 3: 18
• 5 Joshi SR, Parikh RM. India - diabetes capital of the world: now heading towards hypertension. J Assoc Physicians India 2007; 55: 323-324
• 6 Seshiah V, Balaji V, Balaji MS. et al. Prevalence of gestational diabetes mellitus in South India (Tamil Nadu) – A community based study. J Assoc Physicians India 2008; 56: 329-333
• 7 Sreekanthan K, Belicita A, Rajendran K. et al. Prevalence of gestational Diabetes Mellitus in a Medical College in South India: A pilot study. Ind J Clin Prac 2014; 25: 342-347
• 8 Vrachnis N, Belitsos P, Sifakis S. et al. Role of adipokines and other inflammatory mediators in gestational diabetes mellitus and previous gestational diabetes mellitus. Int J Endocrinol 2012; 2012: 549748
• 9 Ceriello A, Motz E. Is oxidative stress the pathogenic mechanism underlying insulin resistance, diabetes, and cardiovascular disease? The common soil hypothesis revisited. Arterioscler Thromb Vasc Biol 2004; 24: 816-823
• 10 Maritim C, Sanders RA, Watkins JB. Diabetes, oxidative stress, and antioxidants: A review. J Biochem Mol Toxicol 2003; 17: 24-38
• 11 Zhu C, Yang H, Geng Q. et al. Association of oxidative stress biomarkers with gestational diabetes mellitus in pregnant women: A case-control study. PLoS One 2015; 10: e0126490
• 12 Pitozzi V, Giovannelli L, Bardini G. et al. Oxidative DNA damage in peripheral blood cells in type-2 diabetes mellitus: Higher vulnerability of polymorpho nuclear leukocytes. Mutat Res 2003; 28: 129-133
• 13 Wolf M, Sauk J, Shah A. et al. Inflammation and Glucose Intolerance: A prospective study of gestational diabetes mellitus. Diabetes care 2004; 27: 21-27
• 14 Yilmaz H, Celik HT, Namuslu M. et al. Benefits of the neutrophil-to-lymphocyte ratio for the prediction of gestational diabetes mellitus in pregnant women. Exp Clin Endocrinol Diabetes 2014; 122: 39-43
• 15 Founds SA, Powers RW, Patrick TE. et al. A comparison of circulating TNF-alpha in obese and lean women with and without preeclampsia. Hypertens Pregnancy 2008; 27: 39-48
• 16 Rota S, Yildirim B, Kaleli B. et al. C-reactive protein levels in non-obese pregnant women with gestational diabetes. Tohoku J Exp Med 2005; 206: 341-345
• 17 Seshiah V, Balaji V, Balaji MS. et al. Gestational diabetes mellitus in India. J Assoc Physicians India 2004; 52: 707-711
• 18 Gorstein J, Sullivan KM, Parvanta I et al. Indicators and methods for cross-sectional surveys of vitamin and mineral status of populations. Micronutrient Initiative (Ottawa) and Centers for Disease Control and Prevention (Atlanta) 2007; 29:
• 19 Seshiah V, Das A, Balaji V. et al. Gestational diabets mellitus guidelines. J Assoc Physicians India 2006; 34: 622-628
• 20 Mishra D, Singh HP. Kuppuswamy’s socioeconomic status scale – A revision. Indian J Pediatr 2003; 70: 273-274
• 21 Manea A, Constantinescu E, Popov D. et al. Changes in oxidative balance in rat pericytes exposed to diabetic conditions. J Cell Mol Med 2004; 8: 117-126
• 22 Singh NP, McCoy MT, Tice RR. et al. A simple technique for quantification of low levels of DNA damage in individual cells. Exp Cell Res 1988; 175: 184-191
• 23 Mohan V, Sandeep S, Deepa R. et al. Epidemiology of type 2 diabetes: Indian scenario. Indian J Med Res 2007; 125: 217-230
• 24 Lao TT, Ho LF, Chan BC. et al. Maternal age and prevalence of gestational diabetes mellitus. Diabetes Care 2006; 29: 948-949
• 25 Retnakaran R, Connelly PW. SermerM et al. The impact of family history of diabetes on risk factors for gestational diabetes. Clin Endocrinol 2007; 67: 754-760
• 26 Higgins SP, Freemark M, Prose NS. Acanthosis nigricans: A practical approach to evaluation and management. Dermatol Online J 2008; 14: 2
• 27 Li P, Yin Y, Lin S. et al. Utility of pregestational body mass index and initial fasting plasma glucose in predicting gestational diabetes mellitus. Am J Med Sci 2016; 351: 420-425
• 28 Richardson AC, Carpenter MW. Inflammatory mediators in gestational diabetes mellitus. Obstet Gynecol Clin North Am 2007; 34: 213-224
• 29 Gelaleti RB, Damasceno DC, Lima PH. et al. Oxidative DNA damage in diabetic and mild gestational hyperglycemic pregnant women. Diabetol Metab Syndr 2015; 7: 1
• 30 Winzer C, Wagner O, Festa A. et al. Plasma adiponectin, insulin sensitivity, and subclinical inflammation in women with prior gestational diabetes mellitus. Diabetes Care 2004; 27: 1721-1727
• 31 Sahbaz A, Cicekler H, Aynioglu O. et al. Comparison of the predictive value of plateletcrit with various other blood parameters in gestational diabetes development. J Obstet Gynaecol 2016; 36: 589-593
• 32 Gorar S, Abanonu GB, Uysal A. et al. Comparison of thyroid function tests and blood count in pregnant women with versus without gestational diabetes mellitus. J Obstet Gynaecol Res 2017; 43: 848-854
• 33 Fröhlich M, Imhof A, Berg G. et al. Association between C-reactive protein and features of the metabolic syndrome: a population-based study. Diabetes Care 2000; 23: 1835-1839
• 34 Pannacciulli N, Cantatore FP, Minenna A. et al. C-reactive protein is independently associated with total body fat, and insulin resistance in adult women. Int J Obes Relat Metab Disord 2001; 25: 1416-1420
• 35 Georgiou HM, Lappas M, Georgiou GM. et al. Screening for biomarkers predictive of gestational diabetes mellitus. Acta Diabetol 2008; 45: 157-165
• 36 Nanda S, Savvidou M, Syngelaki A. et al. Prediction of gestational diabetes mellitus by maternal factors and biomarkers at 11 to 13 weeks. Prenat Diagn 2011; 31: 135-141