記住我
ORIGINAL ARTICLE
Year : 2022 | Volume
: 49
| Issue : 3 | Page : 260-264
Evaluation of insulin resistance and beta-cell dysfunctions in newly diagnosed polycystic ovarian syndrome patients
Vikrant Ghatnatti1, Shwetha Patil2, Harpreet Kour3
1 Department of Endocrinology, Jawaharlal Nehru Medical College, KLE Academy of Higher Education and Research, Belagavi, Karnataka, India
2 Department of Obstetrics and Gynecology, Jawaharlal Nehru Medical College, KLE Academy of Higher Education and Research, Belagavi, Karnataka, India
3 Department of Physiology, Jawaharlal Nehru Medical College, KLE Academy of Higher Education and Research, Belagavi, Karnataka, India
Correspondence Address:
Dr. Harpreet Kour
Department of Physiology, Jawaharlal Nehru Medical College, KLE Academy of Higher Education and Research, Nehru Nagar, Belagavi - 590 010, Karnataka
India
Source of Support: None, Conflict of Interest: None
CheckDOI: 10.4103/jss.jss_4_21
Introduction: Women with polycystic ovary syndrome (PCOS) are at increased risk of developing glucose intolerance and diabetes attributed to increased insulin resistance (IR). However, it is not clear whether β-cell dysfunction has a central role in pathogenesis. The distinction has important implications for the prevention of type 2 diabetes in PCOS with interventions that ameliorate IR. This study aimed to find if IR differs among the various phenotypes of PCOS and perform a quantitative estimation of β-cell dysfunction versus IR in patients of PCOS participants. Materials and Methods: This case–control study was conducted for 1 year in the Endocrinology and Gynaecology outpatient departments at Gauhati Medical College. Fifty women newly diagnosed with PCOS, as per the Rotterdam criteria, were considered cases. Fifty, age- and body mass index-matched healthy females were taken as controls. Fasting and postprandial blood glucose, serum insulin, testosterone, and oral glucose tolerance test values were taken. Impaired fasting glucose, impaired glucose tolerance (IGT), and type 2 diabetes mellitus T2DM were diagnosed according to ADA 2011 criteria. IR and β-cell function were determined by “homeostasis model assessment (HOMA)”. Results: We observed an altered relationship between IR and insulin secretion, consistent with an intrinsic β-cell defect, wherein IR led to a decreased amount of compensatory insulin secretion in PCOS compared with normal women. The correlation coefficients relating HOMA%B to HOMA-IR were lower in PCOS, indicating less compensatory insulin secretion for a given increment in IR. Conclusion: PCOS patients are at increased risk of developing glucose intolerance and diabetes.
Keywords: Dysglycemia, glucose tolerance, insulin sensitivity, polycystic ovary syndrome, type 2 diabetes mellitus, β-cell function
Polycystic ovary syndrome (PCOS) accounts for up to 7%–10% of prevalence globally and is the most common endocrine disorder found in the reproductive age group of women.[1] Increased impaired blood glucose levels, obesity, and insulin resistance (IR) are documented as the root cause of PCOS in the majority of papers.[2],[3],[4] More than 50% of women with PCOS are insulin resistant, and it is estimated that they have a 5–8-fold increased risk of type 2 diabetes mellitus (T2DM) when compared with age- and weight-matched controls.[5],[6] Factors associated with increased risk of PCOS include lack of physical activity, obesity, epigenetics, endocrine disruptors due to industries, and a family history of PCOS. This may affect the value of the life of women due to its multiform signs and symptoms. Furthermore, many women show impaired glucose tolerance (IGT) and are at risk of developing diabetes mellitus. Indeed, many PCOS women are insulin resistant, partly due to genetic tendency and partly due to obesity.[7],[8],[9] The resistance to the action of insulin in PCOS primarily refers to the impaired action of this hormone on glucose transport and antilipolytic in adipocytes, in the presence of normal insulin binding. In turn, the resulting compensatory hyperinsulinemia leads to an exaggerated effect of insulin in other less traditionally responsive tissues, including stimulated androgen secretion by the ovarian theca cells.[10],[11] Although there are many studies on IR in PCOS, literature is scant regarding the β-cell function in women with PCOS from India, where the disease burden is huge. Therefore, this study was planned to evaluate the IR and beta-cell dysfunctions in newly diagnosed PCOS patients.
Materials and MethodsSubjects
This cross-sectional study was conducted for 1 year in the Department of Endocrinology Gauhati Medical College and Hospital, Guwahati. A total of 78 patients were enrolled for 1 year. After screening, 23 patients were excluded after primary evaluation as per exclusion criteria and 5 patients refused to participate in the study. Hence, a total of 50 female patients newly diagnosed to have PCOS by the Rotterdam criteria 2003 were enrolled in the study. Written informed consent was obtained from all patients involved in the study, and Institutional Ethical Clearance was obtained before the conduct of the study from the Institutional Ethical Committee of Gauhati Medical College and Hospital via Ref. no 233/2013/222 dated 05-04-2014. Age and body mass index (BMI) matched 50 participants were also included as controls.
Inclusion criteria
PCOS was diagnosed using the Rotterdam 2003 criteria, which defines PCOS as having any two features among oligoovulation or anovulation, clinical and or biochemical signs of hyperandrogenism or polycystic ovaries by ultrasonography.
Exclusion criteria
Patients with known medical illnesses such as diabetes, impaired fasting glucose, or IGTPatients on medications such as corticosteroids, oral contraceptives, or metformin-like drugs could alter the endocrine and metabolic parameters under investigationPatients with disorders, namely 21-hydroxylase-deficient nonclassic adrenal hyperplasia, thyroid dysfunction, hyperprolactinemia, neoplastic androgen secretion, drug-induced androgen excess, the syndromes of severe IR, Cushing's syndrome, and glucocorticoid resistance.Methods
Height and weight were measured for all participants, and BMI was calculated as weight (kg)/height (m2). Waist circumference (WC in centimeters) was measured in a standing position midway between the lower costal margin and the iliac crest. Blood pressure was calculated as the mean of two manual sphygmomanometer readings with the patient in a seated position.[12]Biochemical parameters:The oral glucose tolerance test (OGTT)[13] was performed at 800 h after an overnight fast of 10–12 h in both cases and controls. An oral glucose load with 75 g of anhydrous glucose dissolved in 250–300 ml of water was administered over 3–5 min immediately after the fasting sample, and a postprandial blood sample was collected at 120 min. Glucose levels were estimated by the glucose oxidase peroxidase method. The interpretation of OGTT is:
An ideal normal-weight individual aged <35 years has a HOMA-IR of 1.0 mol × U/L2 and a HOMA-% B function of 100%. HOMA values of PCOS subjects were compared with age- and BMI-matched controls.
Statistical analysis
Data are presented as mean + standard deviation. Chi-square and Fisher's exact tests were used to make categorical comparisons. A value of P < 0.05 was considered statistically significant. Regression analyses were carried out to find the relationship between HOMA-%B, HOMA-IR, age, BMI, and total testosterone. All data were analyzed with commercial software IBM SPSS Statistics for Windows, Version 19.0. Armonk, NY, USA: IBM Corp. IBM Corp. Released 2010.
ResultsPostprandial blood glucose, fasting plasma insulin, and HOMA-IR were significantly higher in PCOS compared to controls [Table 1].
Table 1: Clinical and hormonal profile of polycystic ovary syndrome patientsPCOS women with dysglycemia were significantly older in age and had a significantly higher BMI and WC in centimeters than the PCOS women who had normal glucose levels. Fasting serum insulin levels and IR, as determined by HOMA-IR, were significantly higher in PCOS women with abnormal glucose in comparison with those who had normal glucose levels [Table 2] and [Table 3].
Table 2: Categorization of glucose abnormalities in polycystic ovary syndrome women
Table 3: Clinical and hormonal profile of euglycemic polycystic ovary syndrome patients versus dysglycemic polycystic ovary syndromeThe highly significant correlation (r = 0.68; P < 0.001) between HOMA-IR and HOMA-% B indicates increasing (compensatory) insulin secretion with increasing IR. Obesity is known to correlate with IR. As expected, in PCOS, there was a significant positive correlation between BMI and HOMA-IR (r = 0.38; P < 0.001). BMI was also positively correlated with HOMA-%B (r = 0.45; P = 0.006). Age was not significantly correlated with HOMA-IR (r = 0.49; P = 0.85) or HOMA-%B (r = 0.32; P = 0.43). Total testosterone was not significantly correlated with IR, insulin secretion, age, or BMI [Table 4].
Table 4: Correlation of variables in euglycemic polycystic ovary syndrome patients by using multiple regression analysisIn women with PCOS, regression of age, BMI, HOMA-IR, and testosterone on HOMA-% B showed that testosterone, age, and BMI were not significant predictors of HOMA-%B (P = 0.12, 0.55, and 0.16). The only predictor of HOMA-%B as judged by regression coefficient was HOMA-IR (Regression Coefficient (RC) = 0.65; P < 0.05) [Table 5].
Table 5: Multiple regression analyses in euglycemic women with polycystic ovary syndrome to find Independent factors influencing β-cell function and insulin resistance in patients with polycystic ovary syndromeMultiple regression of HOMA-IR on age, BMI, HOMA-%B, and testosterone revealed that the most important predictors of IR (HOMA-IR) were BMI (Regression Coefficient (RC) = 0.54; P = 0.01) and HOMA-%B (RC = 1.18; P < 0.05). Age and testosterone were not significant predictors of HOMA-IR in this analysis.
To illustrate the differential relationship of HOMA-%B and HOMA-IR, overlaid regression plots for HOMA-%B versus HOMA-IR for PCOS and controls were made. These plots depict the effect of incremental increases in HOMA-IR on HOMA-%B. The lesser effect of HOMA-IR on HOMA-%B in PCOS is reflected in the decreased slope of the regression line for PCOS, indicating that a given increase in HOMA-IR results in a lesser increment in HOMA-%B in women with PCOS than in those without [Figure 1].
Figure 1: Regression plot of HOMA-IR on HOMA-%B among cases and controls. HOMA: homeostasis model assessment, IR: Insulin resistance Discussion The findings of this study included significant differences in fasting insulin levels, IR, and HOMA-IR among women newly diagnosed with PCOS. The anthropometric parameters, blood pressure, and fasting blood glucose levels, were within normal limits. In our study, 68% of the PCOS women were insulin resistant (as defined by HOMA IR >2). IR has been documented as an underlying cause of PCOS. IR is directly related to obesity; however, Many physicians do not prefer to use the term “insulin resistance” in the absence of obesity; however, studies have reported higher levels of plasma insulin in thin women with PCOS. On the contrary, a study by Sharma and Majumdar reported that overweight females with PCOS have a higher prevalence of metabolic syndrome.[10],[11],[12],[13]
Dysglycemia was found in 24% of the cases in our study as compared to most other studies, probably because we had recruited newly diagnosed cases of PCOS in contrast to already diagnosed cases of PCOS in other studies. Furthermore, the mean age of our patients was less compared to the other studies. We excluded newly diagnosed PCOS cases with a history of diabetes. Another reason is the use of Rotterdam criteria, unlike other studies. A long-term prospective population-based study reported that women with PCOS are likely to have 1.7 times higher risk of developing prediabetes and diabetes as compared to the general female population.[14] These findings are supported by other studies also.[15],[16],[17] Postprandial dysglycemia has been documented to be a commonly seen feature in women with PCOS, suggesting IR. Therefore, 2-h post-challenge glucose values are optimal for the diagnosis of IGT and T2DM in PCOS.[18],[19],[20]
This study also tried to characterize the most important independent determinants of β-cell function and IR in PCOS, demonstrating a disproportionate decrease in β-cell function compared with IR in PCOS compared with normal women. This dramatic finding is given that the two groups had similar mean values of these insulin-related traits is consistent with the concept of compensatory insulin hypersecretion in response to IR. As the patients were selected to have normal fasting glucose levels, so they had an adequate β-cell function. When compared to controls, these PCOS patients had β-cells secreting insulin at relatively lower levels which increases the risk of developing T2DM.[19],[20]
In contrast to IR in PCOS, there have been comparatively few studies examining β-cell function/insulin secretion in PCOS. Several studies demonstrated increased insulin secretion in PCOS compared with normal, although other studies demonstrated decreased insulin secretion in PCOS.[21],[22],[22] Another possible confounding factor is that many studies quantified insulin secretion without accounting for the prevailing level of IR; this is essential for accurate interpretation of indices of β-cell function because insulin secretion and insulin sensitivity have been shown to have a hyperbolic relationship.[22] Insulin secretion may be adjusted for IR using statistical means or by employing the disposition index, the product of an index of insulin secretion with an index of insulin sensitivity. Nevertheless, even among careful studies making this adjustment, conflicting results regarding insulin secretion in PCOS are found in the literature.[19],[20],[21],[22] We avoided this problem by examining the relationship between insulin secretion and IR, rather than comparing mean values.
ConclusionOwing to the inadequate compensation of insulin secretion by β cells, these PCOS patients are at increased risk of developing glucose intolerance and diabetes. The demonstration that β-cell function is a central pathogenic defect in PCOS is relevant from a clinical point of view while planning both preventive and therapeutic strategies.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References
留言 (0)