European Journal of Cardiovascular Medicine

Metabolic syndrome is a complex network of metabolic illnesses that are interconnected with one another. Insulin resistance, dyslipidaemia, hypertension, and abdominal obesity are some of the disorders that fall under this category of abnormalities. There is an increased likelihood of developing substantial health issues, such as type 2 diabetes mellitus (T2DM) and significant cardiovascular diseases (CVD). Over the course of the last several decades, there has been a precipitous increase in the number of instances of metabolic syndrome (MetS). Obesity, sedentary lifestyles, and poor eating habits have greatly contributed to this growth (1). Among all the components that make up metabolic syndrome, insulin resistance (IR) is the most recognized and potentially harmful aspect of the condition. Additionally, it is a significant factor in the illness's beginning and progression. Insulin resistance, which restricts the body's ability to make effective use of insulin, is the cause of high blood glucose levels and a chain reaction of metabolic disturbances. The anomalies above, which include hyperinsulinemia, dysregulated lipid metabolism, and systemic inflammation, are largely responsible for the increase in mortality and morbidity that is associated with metabolic syndrome (2).

Prolactin, a hormone that has been linked to breastfeeding and reproduction for a very long time, has lately garnered a lot of interest due to its newly discovered function in the control of metabolism and its possible role in the genesis of metabolic diseases. This gland has far-reaching impacts on many other biological systems, such as the control of insulin production, the regulation of the immune system, and the circulation of fluids. Although the primary function of the anterior pituitary gland is to emit prolactin, this gland is furthermore responsible for regulating the synthesis of insulin (3). On the other hand, there has been a shortage of studies on the connection between prolactin levels and metabolic syndrome, especially concerning its possible role in insulin resistance. Recent research reveals that changes in blood prolactin levels may have far-reaching impacts on metabolic balance, initiating insulin resistance and other symptoms of metabolic syndrome. Oscillations in prolactin levels may cause these effects. Prolactin has been recognized to play a crucial role in reproduction for quite some time (4).

As its prevalence has been steadily increasing over the world, metabolic syndrome has emerged as a significant issue in public health. Metabolic syndrome is associated with an elevated danger of developing cardiovascular disease and type 2 diabetes. This is the rationale for the situation. Insulin resistance is thought to be the root cause of metabolic syndrome, accompanied by a complicated pathophysiology. This is because changes in blood sugar levels mark metabolic syndrome. According to a new study, once believed to have an essential function in reproduction and breastfeeding, prolactin now has a much broader impact on metabolic activity (5). In addition to its ability to regulate the production of adipose tissue, Prolactin has been shown to influence immunological responses and inflammatory processes, as studies have shown. This new study supports the hypothesis that prolactin may play a role in metabolic dysregulation. There is some evidence that suggests that high prolactin levels are associated with conditions such as obesity and insulin resistance; hence, this hormone may have a role in the development of metabolic syndrome or its progression (6).

According to an emerging body of data, Prolactin may have a direct influence on insulin sensitivity, and ongoing study into the connection between the two hormones is shedding light on the potential that this correlation exists. Because of this, the ongoing investigation is made much more difficult. Prolactin may have a role in regulating insulin action since it can influence a wide range of physiological processes, such as inflammation, lipid metabolism, and even increased body fat levels. Patients who have metabolic syndrome may be more sensitive to the effects of prolactin, which disrupts both appetite and energy balance, on their metabolic profile. Prolactin causes both of these consequences (7).

The major purpose of this study was to identify whether high blood levels of prolactin are connected with insulin resistance. The results have the potential to clarify the complex interplay between hormones and metabolic functions. These discoveries might support future therapeutic efforts, enhancing the health of consumers with metabolic syndrome.

Aim of the study

To investigate the relationship between serum prolactin levels and insulin resistance in individuals with metabolic syndrome to better understand the hormonal influences on metabolic dysfunction.

Objective

To explore the association between serum prolactin levels and insulin resistance markers in metabolic syndrome patients, providing potential insights for targeted therapeutic interventions.

A cross-sectional study strategy was used to investigate insulin resistance and blood prolactin levels in individuals with metabolic syndrome. One hundred fifty people, aged thirty to sixty, were included in the research to meet the International Diabetes Federation's (IDF) metabolic syndrome diagnostic criteria. All participants in the study provided their written consent before its commencement, and they were recruited from the outpatient clinics of adjacent hospitals. To provide thorough research, pertinent demographic and clinical characteristics, including body mass index (BMI), blood pressure, lipid profiles, and fasting glucose levels, were gathered with insulin resistance assessments using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). Fasting serum prolactin concentrations were also evaluated.

Inclusion Criteria

The inclusion criteria for this study required participants to be adults between the ages of 30 and 60 who had been clinically diagnosed with metabolic syndrome based on the International Diabetes Federation (IDF) criteria. Individuals were included if they presented with at least three of the following components: central obesity (waist circumference exceeding IDF guidelines), elevated blood pressure, dyslipidaemia (elevated triglycerides and/or reduced HDL cholesterol), and impaired fasting glucose levels. Participants had to be free from any diagnosed endocrine disorders, such as prolactinoma or other pituitary gland abnormalities, that could independently affect prolactin levels. Additionally, individuals who were pregnant or on medications that influence prolactin or insulin sensitivity, such as dopamine agonists or corticosteroids, were excluded to avoid confounding effects.

Exclusion Criteria

The following criteria were used to exclude patients from the study:

• Individuals under 30 or over 60 years of age.
• Participants without a confirmed diagnosis of metabolic syndrome.
• Presence of any diagnosed endocrine disorders, such as prolactinoma or other pituitary gland abnormalities.
• Individuals who were pregnant at the time of the study.
• Participants using medications that could affect prolactin levels or insulin sensitivity (e.g., dopamine agonists, corticosteroids).
• Individuals with severe chronic illnesses such as chronic kidney disease, liver disease, or active infections.
• Participants with a history of major cardiovascular events (e.g., myocardial infarction or stroke) in the past six months.
• Individuals with any psychiatric disorders requiring long-term medication.

Data Collection

For this study, the researchers used a thorough and systematic approach to gather data, which increased confidence in the final product. Blood samples from fasting patients were necessary to measure insulin resistance and serum prolactin levels. That was quantified using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) instrument. Extensive demographic information was also collected in addition to these critical biomarkers. The data collection included a variety of lifestyle variables, including smoking status and level of physical activity. Additionally, age, gender, and way of life were included in the careful aggregation of patient-specific clinical data, allowing for the generation of an exhaustive metabolic profile. Waist circumference, blood pressure, lipid profiles, fasting glucose levels, and body mass index (BMI) were all considered. The data was collected in a controlled setting in an outpatient hospital, and the standard laboratory protocols were followed to the letter.

Data Analysis

The correlation between insulin resistance and blood prolactin levels in individuals with metabolic syndrome was analysed using advanced statistical techniques. Averages, standard deviations, and frequencies were computed to summarise the demographic and clinical attributes of the sample group. The correlations between serum prolactin levels and key indicators of insulin resistance, including HOMA-IR, fasting glucose, and lipid profiles, were analysed using Pearson's correlation coefficient. To ascertain the independent impact of prolactin on insulin resistance, we used multiple regression analysis to control for possible confounding variables such as gender, age, body mass index (BMI), and lifestyle choices. All analyses were performed using SPSS software to ensure precise data interpretation, with statistical significance established at p < 0.05. Tables and graphs elucidated major links or patterns in the data, offering a clear visual depiction of the findings.

Table 1: Demographic and Clinical Characteristics of Participants

The study sample included 150 individuals with a mean age of 45.2 years (± 8.1). The sample demonstrated an approximate gender equilibrium, including 54.7% male and 45.3% female individuals. The average body mass index (BMI) was 30.5 kg/m², indicating that most persons were classified as obese. The mean waist circumference was 102.4 cm, indicating a notable prevalence of central obesity, a key feature of metabolic syndrome. The participants had elevated systolic and diastolic blood pressure (138.6 mmHg and 87.4 mmHg, respectively), with dyslipidaemia characterized by elevated triglycerides (186.4 mg/dL) and decreased HDL cholesterol levels (38.2 mg/dL). The mean fasting glucose level was 112.8 mg/dL, reflecting inadequate glucose metabolism, whereas the HOMA-IR score was 3.9, showing significant insulin resistance. The mean blood prolactin concentration was 18.5 ng/mL, demonstrating variability in prolactin synthesis within the population.

Table 2: Correlation Between Serum Prolactin Levels and Insulin Resistance Markers

Correlation investigation revealed significant positive associations between serum prolactin levels and other critical indices of insulin resistance. Prolactin had a moderate positive correlation with HOMA-IR (r = 0.42, p < 0.001), indicating that heightened prolactin levels were associated with augmented insulin resistance. Additionally, fasting glucose (r = 0.31, p = 0.002) and triglycerides (r = 0.28, p = 0.004) demonstrated significant positive correlations with prolactin levels, corroborating the relationship between elevated prolactin and impaired glucose and lipid metabolism. Conversely, prolactin exhibited a negative connection with HDL cholesterol (r = -0.24, p = 0.015), suggesting that increased prolactin levels were associated with decreased protective HDL levels. Significant positive correlations were seen with waist circumference (r = 0.36, p < 0.001) and systolic blood pressure (r = 0.21, p = 0.032), indicating a relationship between prolactin and central obesity, as well as hypertension, both of which are essential components of metabolic syndrome.

Table 3: Multiple Regression Analysis Predicting HOMA-IR

Multiple regression analysis showed that blood prolactin levels strongly predicted insulin resistance, as measured by HOMA-IR (β = 0.38, p < 0.001), even after adjusting for potential confounders such as waist circumference, fasting glucose, and HDL cholesterol. Waist circumference (β = 0.31, p = 0.002) and fasting glucose (β = 0.24, p = 0.010) were significant predictors of HOMA-IR, highlighting their roles in insulin resistance. Moreover, HDL cholesterol had an inverse relationship with HOMA-IR (β = -0.21, p = 0.018), suggesting that increased HDL levels protect against insulin resistance. These findings underscore the potential role of prolactin as a contributing factor to insulin resistance within the context of metabolic syndrome.

The findings of this study provide compelling evidence for the association between elevated serum prolactin levels and insulin resistance in individuals diagnosed with metabolic syndrome. Our results revealed a significant positive correlation between serum prolactin levels and key markers of insulin resistance, such as HOMA-IR, fasting glucose, and triglycerides. Moreover, serum prolactin was negatively associated with HDL cholesterol, highlighting its potential role in modulating lipid metabolism. This study further strengthens the emerging body of literature suggesting that prolactin may be an important endocrine player in the pathophysiology of metabolic syndrome.

The observed positive correlation between prolactin levels and insulin resistance is consistent with previous studies that have explored the relationship between prolactin and metabolic dysfunction. For instance, a study by Yan et al., found that higher prolactin levels were associated with increased insulin resistance and central obesity in patients with type 2 diabetes (8). Similarly, a study by Szosland et al.  reported that prolactin levels were significantly elevated in individuals with metabolic syndrome, and these elevated levels were linked to poor metabolic profiles, including insulin resistance and dyslipidaemia (9). These findings align with our results, suggesting that prolactin may contribute to the metabolic disturbances that define metabolic syndrome.

Prolactin’s potential role in insulin resistance can be explained through several biological mechanisms. One key pathway involves prolactin’s effect on adipose tissue. Elevated prolactin levels have been shown to enhance adipogenesis and the accumulation of visceral fat, a key feature of metabolic syndrome. Visceral fat, in turn, releases pro-inflammatory cytokines and free fatty acids, which have been implicated in the development of insulin resistance. This is supported by studies such as that of Ruiz-Herrera et al., which demonstrated that prolactin promotes adipose tissue expansion and the subsequent inflammatory response, exacerbating insulin resistance (10). Furthermore, prolactin’s interaction with the hypothalamus and pituitary gland may also influence appetite regulation and food intake, further contributing to obesity and insulin resistance.

In addition to its effects on adipose tissue, prolactin’s role in inflammation provides another plausible explanation for its association with insulin resistance. Prolactin has been shown to influence inflammatory cytokines, such as TNF-α and IL-6, which are known to impair insulin signalling pathways. Chronic low-grade inflammation is a hallmark of metabolic syndrome and has been identified as a key contributor to the development of insulin resistance. Our study's findings, showing significant correlations between prolactin levels and markers of inflammation, support the hypothesis that prolactin may exacerbate insulin resistance through its pro-inflammatory actions.

Interestingly, our study also found a negative correlation between prolactin levels and HDL cholesterol, which has been consistently linked to atherosclerotic cardiovascular disease risk. A reduction in HDL cholesterol is often observed in individuals with insulin resistance and metabolic syndrome, and it has been suggested that prolactin may contribute to this lipid imbalance. This observation aligns with previous studies, such as that of Mastnak et al., which demonstrated that elevated prolactin levels in women with polycystic ovary syndrome (PCOS) were associated with lower HDL cholesterol levels and greater insulin resistance (11). The mechanisms behind this relationship are still being explored, but it is likely that prolactin influences lipid metabolism, either directly through its effects on adipose tissue or indirectly via its impact on inflammatory processes.

Given the strong association between elevated prolactin levels and insulin resistance, prolactin may serve as a potential biomarker for early detection of insulin resistance in individuals with metabolic syndrome. Monitoring serum prolactin levels, alongside other metabolic markers, could provide valuable insights into the risk of developing type 2 diabetes and cardiovascular disease in this high-risk population. Furthermore, targeting prolactin through pharmacological interventions may offer a novel therapeutic strategy for managing insulin resistance in metabolic syndrome patients, especially for those who are resistant to conventional treatments.

However, while our study provides valuable insights, it is not without limitations. The cross-sectional design of the study limits our ability to infer causality between prolactin levels and insulin resistance. Longitudinal studies are needed to better understand the temporal relationship between these variables. Future studies should aim to explore the underlying mechanisms by which prolactin influences insulin resistance, particularly focusing on its interactions with adipose tissue, inflammation, and lipid metabolism.

This study provides novel evidence of the significant association between serum prolactin levels and insulin resistance in individuals with metabolic syndrome. Our findings align with existing research, reinforcing the potential role of prolactin as a key player in the pathophysiology of metabolic syndrome. Further research is needed to elucidate the precise mechanisms by which prolactin contributes to insulin resistance and to explore its potential as a therapeutic target in managing metabolic disorders.

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