Relationship between Ghrelin and Leptin with Insulin Resistance in Obese Patients and Non-Obese Individuals

 

Doaa Mahdi Omran¹, Saad Merza Alaraji², Ali Hussein Albayati³, Wathiq Essam⁴

¹Iraqi Ministry of Health, Babylon University, Iraq

²Babylon University, Iraq

³Babylon University, Iraq

⁴Iraqi Ministry of Health, Babylon University, Iraq

 

ABSTRACT:

Experimental studies have suggested that Ghrelin and Leptin play a role in glucose homeostasis, and thus any disturbance to their action might lead to Insulin resistance, Obesity and type II Diabetes Mellitus, thus we assess the hypothesis that low Ghrelin concentration and high Leptin concentration are a risk factor for obesity and Insulin resistance. The materials and methods: One hundred people were included in this study: fifty obese patients and fifty non-obese. The mean age for the study group was (34.00±9.43) years old while that of the control group was (34.00±9.43) year's old respectively, they were classified according to their Body Mass Index after measuring their height and weight, the mean BMI of case patients was (39.23±6.71kg/m²) and (23.08±1.19 kg/m²) for the control individuals, exclusion Criteria included: history of diabetes mellitus; finding of high blood glucose on biochemical examination, history of taking drugs that cause obesity or increase in body weight such as steroids, patients with diseases of high growth hormone level such as acromegaly, pregnant women, while the investigations that were done including: Fasting blood sugar, fasting serum Ghrelin, fasting serum Leptin and fasting serum Insulin, Insulin resistance was measured using HOMA-IR module. Results showed that there is association between insulin resistance and obesity as it well known and a significant relation between fasting serum Leptin with Obesity/Insulin resistance (p value>0.05) but a non-significant relation between fasting serum Ghrelin and Obesity/Insulin Resistance (p value>0.05). Conclusion: Obesity is associated with insulin resistance with high level of fasting serum Leptin but with not high level of fasting serum Ghrelin.

 

 

 

INTRODUCTION:

Obesity is a condition manifested by abnormal distribution of adipose or fatty tissue or excessive accumulation of fat in the body that may lead to impairment of health [1].

 

Accumulation of fatty tissue results from a disturbance in balance between energy intake and expenditure which is too big to be regulated by the hypothalamic regulatory mechanism represented by Basal Metabolic Rate (BMR) [2].

 

The causes for obesity are usually related to many factors such as genetic factors, consumption of high calorie food and/or poor or lack of practicing of physical exercise, diseases of endocrine system, medications, or psychological disorders [3]. Globally, the adult proportion with a body-mass index (BMI) of 25 kg/m² or greater had amplified from 28.8% to 36.9% between 1980 and 2013 in males and from 29.8% to 38.0% in females [1]. Obesity leads to many serious health problems such as type 2 diabetes mellitus, cardiac disease, cancers, and joint problems, respiratory and neurological problems [4].

 

Many hormones play a role in regulating the feelings of hunger and satiety; most important of these hormones are Ghrelin and Leptin. Ghrelin plays an important role in appetite and feeding behaviors, it is called as the hunger hormone, and it is a peptide hormone formed by Ghrelinergic cells in the gastro-intestinal tract [5], which besides regulating appetite, Ghrelin also plays an important role in regulating the rate and distribution of energy expenditure [6].

 

Ghrelin leads to increase in the body weight by activating receptors in the arcuate nucleus; these neurons are both Ghrelin-Leptin and insulin-sensitive. Circulatory ghrelin level is highest directly before meal and lowest directly after meal [7].

 

Leptin is a hormone produced by adipose cells [8]. Leptin regulate body weight by inhibiting hunger and is opposed by the work of the other energy regulatory hormone (Ghrelin) that stimulate hunger hormone. Leptin, as Ghrelin; acts on receptors in the arcuate nucleus in the hypothalamus [9].

 

In obese individuals, a decreased sensitivity to Leptin occurs, which results in an inability to detect the feeling of fullness or satiety although high energy stores are present [10].

 

Insulin resistance (IR) is a state in which cells fail to respond normally to the actions of insulin. The pancreas makes insulin when glucose level is raised in the bloodstream after the digestion of the carbohydrates from food. In normal condition, insulin makes glucose to be being taken into the cells, to be used for energy utilization, and inhibits cells from utilizing fat as a source of energy. When the cells produce insulin in patients with insulin resistance; the cells are not responding normally to its action and are unable to use it in effective way, leading to high level of glucose in the circulation. Beta cells subsequently raise their release of insulin, further increasing the blood insulin concentration. Usually this remains undetected and can help the diagnosis of Type 2 diabetes. The result of the study showed that Insulin Resistance is clearly present with the obese patients in comparison to non-obese individuals P value 0.002, Leptin level is higher with obese patients P value <0.001 while there is no difference between the two groups with Ghrelin level P value 0.55.

 

MATERIALS AND METHODS:

Inclusion Criteria

A convenient sample of one-hundred individuals is included in this study (50 individuals were classified obese and 50 individuals with normal BMI), with age range from 20-50 years old. Individuals with BMI above 30 kg/m² are considered as obese patients. Individuals with BMI of less than 25 kg/m² are considered normal.

 

Exclusion criteria:

The study excludes any participant with history of diabetes mellitus, finding of high blood glucose on biochemical examination, history of taking drugs that cause obesity or increase in body weight such as antiepileptic drugs, steroids, chemotherapy also excluded, patients with diseases of high growth hormone level such as acromegaly plus any congenital abnormality and post-menopause women and or pregnant women.

Individuals with BMI between 25-30 were excluded.

 

Lab Analysis:

Fasting Ghrelin and Leptin were both measured with ELISA.

Insulin Resistance was measured with HOMA-IR model:

IR = FBS × Fasting Insulin Concentration / 22.5

Insulin was measured by ELISA.

A result above 2.5 is considered as IR

 

RESULTS:

P value ≤ 0.05 is significant

 

DISCUSSION:

Insulin Resistance:

There is a significant difference in percent between cases and controls, and the resulted data show that 32% of cases having Insulin resistance with mean of 3.54 ± 5.508 and 10% of the subjects in the control group having Insulin Resistance with mean of 1.47 ± 2.660; P= 0.022, this relation has been long established such as with Jean-Philippe Bastard, et al; 2006 [11], whom asserted that obesity is associated with a low-grade inflammation of white adipose tissue (WAT) resulting from chronic activation of the innate immune system and which can subsequently lead to insulin resistance, impaired glucose tolerance and even diabetes mellitus. It is established that this link might also lead to CV disease [12].

 

Fasting Serum Ghrelin:

There is no significant difference in percent between cases and controls, and the resulted data show that 100% of cases have normal fasting serum Ghrelin with mean of 5.3744 ± 3.24639 ng/ml and 97.5% of the subjects in the control group have normal level of fasting Ghrelin with mean of 5.8007 ± 3.47018 ng/ml; P= 0.55 this agrees with Tracey McLaughlin. et al, 2009[13], whom they confirmed that IR in obese patients with similar age group with our study is associated with low to normal Ghrelin levels. This can be explained by which IR and its associated metabolic abnormalities are part of the body counter- regulatory mechanisms to counter the effect of Ghrelin in obese patients [13].

 

This is also shown with Seppo, et al; 2003[14] and published in the same year by the American diabetes association in which they confirmed that low or normal Ghrelin levels are associated with Insulin resistance in obese non-diabetic individuals in comparison to non-obese non-diabetic individuals. A similar result was reached by (Waleed, Mohammed, Hassanien and Khalid EL Sayed Abokhosheim; 2014) [15]. As for gender differentiation Ghrelin levels were similar in men and women as cited by Purnell, Weigle, Breen, and Cummings; 2003 [16].

 

Fasting Leptin:

There is a significant difference in percent between cases and controls, and the resulted data show that 78% of cases have abnormal fasting serum Leptin with mean of 4420.48 ± 1697.81261pg/ml and 17.5% of the subjects in the control group have abnormal level of fasting Leptin with mean of 1709.255 ± 1819.35831 pg/ml; P= 0.0001, this agrees with the Miriam, et al; 2002 [17], which show a higher concentrations of Leptin in obese patients with IR in comparison with non-obese individual, both groups non-diabetic, this can be simply explained because Leptin is produced by fatty tissue which is present in higher amount in obese people.

 

CONCLUSIONS:

Obese people are high risk to insulin resistance, Type 2 diabetes mellitus and CV diseases. Many hormones play an important role in regulation of BMI such as Ghrelin and Leptin, Leptin is clearly elevated in obese patients while Ghrelin still despite being the hunger hormone is not firmly associated with obesity but definitely these hormones needs more investigations to learn more about their effects on body weight and IR.

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Received on 12.12.2017             Modified on 24.12.2017

Accepted on 20.01.2018           © RJPT All right reserved