Beta Cell Function : A Useful Measure of Insulin Resistance in Adolescent with Polycystic Ovarian Disease

Polycystic ovarian syndrome (PCOS) is the universal endocrine disarray in premenopausal women, These women are prone to insulin resistance as well as altered beta cell function. Study was designed to find out the relationship of insulin resistance and beta-cell function in adolescent with PCOS. Material and Methods: Study included 50 female patients, aged range 16-20 years from Obstetrics and Gynaecology department in Lahore. All subjects were already diagnosed and documented as patients of polycystic ovarian syndrome on the basis of pelvic ultrasonic findings. Level of serum insulin was estimated by ELISA technique using standard kit. Level of fasting glucose was estimated by glucose oxidase 1 Department of Physiology Fatima Jinnah Medical University, Lahore 2 Department of Physiology Sharif Medical and Dental College, Lahore 3 Department of Pathology Akhtar Saeed Medical and Dental College, Lahore 4 Department of Biochemistry Fatima Jinnah Medical University, Lahore 5 Department of Physiology Fatima Jinnah Medical University, Lahore Date of Submission 22-12-2015 Date of Revision Received 30-03-2016 Date of Acceptance for Publication 24-07-2016 Conflict of Interest: None Funding Source: None


Introduction
Polycystic ovarian syndrome (PCOS) is one of the most-widespread endocrine disarray in premenopausal women with 4 -12% prevalence rate. 1 PCOS is characterized by menstrual irregularity, infertility, an ovulation, hyperandrogenism, and insulin resistance. 2 Insulin upholds glucose homeostasis in association with both glucose uptake gluconeogenesis states.
ANNALS VOL 22, ISSUE 3, JUL.-SEP.2016   Moreover, other roles of insulin are related to renal, neural and cardiovascular function.This showed the association of insulin resistance with risk of hypertension, heart problems and nephropathy etc. 3 Insulin signaling by different metabolites and crosstalk with some other signaling pathways directs to insulin resistance.Increase insulin level also increased insulin resistance.Insulin resistance is typified by a decreased cell or tissue ability to counter the level of insulin.According to studies up to 90% of PCOS women have insulin resistance. 4,1hanges in release of insulin due to changes in insulin sensitivity cause the changes in the secretory capacity of the beta cell. 5,6In response to increasing insulin resistance, beta cell secretes more insulin in normal physiological state.However in susceptible individuals beta-cell function begins to decline and in case of severe but stable insulin resistance leads to hyperglycemia which may results an increase in demand for insulin.There is also a change in function of beta cells causing hyperplasia of beta cells.The malfunction of the beta cell to insulin resistance is responsible for increase in the risk of type 2 diabetes in women with PCOS. 5 Pathogenesis of beta-cell failure is based on increased influx of glucose and fatty acids due to increased response.The increase in metabolism of glucose and fatty acids may causes insulin resistance and disruption in the function of beta cell. 7,8It is postulated that cells of the body shows resistance to insulin effect as the insulin receptors become less responsive to insulin resulting in an increase release of insulin from beta cells and cause hyperinsulinemia 9 .Insulin resistance can be assessed with fasting insulin, fasting glucose: insulin (G/I) ratio, beta cell function and HOMA IR . 10,11s the abnormalities in insulin level are poorly detected by simple determination of either glucose or insulin.There is a need to find out not only the insulin resistance but also study the beta cell function in PC-OS.

Patients and Method
Study included 50 female patients from Obstetrics and Gynaecology Department in Lahore.Females between the ages 16 -20 year were registered.All subjects were at their reproductive age and already diagnosed and documented as patients of polycystic ovarian syndrome on the basis of pelvic ultrasonic findings.Subjects with hyperthyroidism, hypothyroidism, con-genital adrenal hyperplasia and diabetes mellitus were not included in the study.Normal subjects with no disease were taken as controls.Letter of consent was taken from each subject.This study has been endorsed by Ethical Committee.About 5.00 ml blood was drawn after overnight fasting of both patients and normal subjects.For estimation of blood glucose, about 2.00 ml of blood was taken in anticoagulant coated tube and estimated by glucose oxidase method using standard kit of Merck.Remaining 3.00 ml of blood was allowed to clot and centrifuge.Serum was separated and used for estimation of insulin level using ELISA technique kit Human insulin Norvex (cat no: KAQ1251).The value of insulin resistance and glucose insulin ratio were calculated using the formula.
Glucose:insulin ratio = [glucose (mg/dl)/insulin (uU/ml)]. 12eta cell function was found using formula of Homa -% B 1 = [Fasting insulin/fasting glucose × 0.0555] -3.5. 13ata is shown as means ± SD.Variations in the parameters of patients were compared by student t-test using SPSS 16.P value < 0.05 was taken as statistically significant.Correlation between serum insulin, insulin resistance and beta cell function was find by Pearson's correlation coefficient.

Results
Age and Biochemical characteristics of adolescent are tabulated.Mean age of subjects with PCOS and of control was 18.9 ± 1.14 and 18.6 ± 1.12 year respectively.Fasting glucose of PCOS subject was non-significantly decreased when compared to normal subjects.Serum insulin level was significantly increased (P < 0.001) in patients as compared normal subjects.Glucose insulin (GIR) ratio was decreased significantly (P < 0.001) when compared with the ratio of normal subjects.Insulin resistance was non-significantly increased in subjects compared to the insulin resistance of normal subjects.Beta cell function was increased in subjects with PCOS compared to beta cell function.
The Pearson's correlation showed that there was significant positive correlation between HOMA -IR and fasting insulin (r = 0.5828).A weak negative correlation (r = -0.335)was noted between level of insulin and beta cell function (Table 2).

Discussion
Polycystic ovary syndrome accounts for the vast majority of an ovulatory symptoms and hyperandrogenism in women.Chief complaint of adolescent girl was hirsutism, menstrual irregularity, treatment-resistant acne as well as obesity may be a signal of PCOS 14 .
Mean age of subjects with PC-OS and of control was 18.9 ± 1.14 and 18.6 ± 1.12 year respectively.However a study found that average age was of women with PCOS was 26.3 ± 5.4 years ranged 17 to 36 years. 14asting glucose of subject with PCOS was non-significantly decreased when compared to glucose level of normal subjects.Our study is in line with a study showed that  15 It is stated that glucose levels are not a predictor of insulin resistance, however it may be related with dyslipidemia and coronary artery disease (CAD). 16vel of serum insulin was increased in subjects compared to the level of insulin in normal subject and showed a highly significant difference (t = 2.67, P < 0.001).An increased level of fasting insulin was also reported by a group of workers. 15,17Number of studies have shown that there is a imperfection in glucosestimulated insulin secretion. 18,19However according to some studies patients with PCOS have an increased insulin response, maybe for compensation of insulin resistance. 20,21Nevertheless some researchers have reported normal insulin secretion in patients with PC-OS. 22,23e Pearson's correlation was shown that there was a significant positive correlation between insulin resistance and fasting insulin (r = 0.5828).However, number of studies does not found any correlation between insulin secretion and insulin resistance.Studies reported that although the insulin response may be increased, it may not be suitably increased to relate with the degree of insulin resistance. 24lucose insulin ratio (GIR) was decreased significantly (t = 2.81, P < 0.001) in subjects when compared to their controls.According to a study the fasting glucose/insulin ratio is a valuable screening test for insulin resistance in the age of adolescent. 25Another study also found that GIR was found to be the highly discriminative of glucose disposal rate, upright degree of insulin sensitivity and has highly sensitive for detection of insulin resistance in PCOS patient. 26It is found by a group of workers that GIR are sensitive measure of insulin resistance in patients with PCOS.They concluded that these are the patients who need insulin lowering agents and not ovulation induction therapy alone. 17nsulin resistance was non-significantly increased in subjects as compared to their controls.It is reported that mitochondrial dysfunction may be responsible for metabolic disturbances related to insulinresistant states. 27A study found that due to insulin resistance, an increase secretion of insulin from β-cell of pancreas in a compensatory mode. 18Another study stated that a small number of PCOS women with insulin resistance ANNALS VOL 22, ISSUE 3, JUL.-SEP.2016 may develop diabetes.This suggests that such patients may also have primary defects in insulin secretion. 2dditionally it is reported that both disturbed beta cell function and defect in insulin levels are related with impaired glucose metabolism. 28resent study found an increased function of beta cell in PCOS adolescent compared to normal subjects.It is reported that due to the increased function of beta cell, secretion of insulin decreased progressively so that these individuals may have a high risk of developing diabetes. 5According to a study insulin response to glucose is not linked with a change of insulin sensitivity.Thus, there may be a defect in β-cell women with PCOS. 24ccording to our study significant correlation was observed between fasting insulin level and insulin resistance.Our study is in line with that of Laasko who found a significant correlation between fasting insulin and insulin resistance.Study concluded that the increases in fasting insulin levels appear to be compensatory attempts to overcome the resistance to glucose uptake. 27e also observed a weak correlation between level of serum insulin and beta cell function.According to a study, β-cell function changes with variation in insulin sensitivity.Study also found that the relationship is a hyperbola i.e. with increase insulin sensitivity there is small alteration in insulin levels and responses, whereas a decrease in insulin sensitivity causes a big change in level of insulin and responses 29 .Another study concluded that conserving beta cell function, signaling of insulin in beta cells and signaling of insulin in the glucose beneficiary tissues uphold glucose homeostasis. 30

Conclusion
It is therefore concluded that function of beta cell failure to reimburse insulin resistance increases the diabetes risk in adolescent with PCOS.More research is needed to define the degree of beta cell effect.

Table 1 :
Age and Biochemical characteristics of adolescent with age range 16 -20 years.

Table 2 :
Pearson Coefficient Correlation between Variables.