Metabolic Outcomes in Obese Patients after Bariatric Embolization of the Left Gastric Vessel

Abstract

The prevalence of overweight and obesity is growing rapidly in the modern world. Currently more than 600 million people are obese, over 2 billion people are overweight. By 2025, according to World Health Organization experts (WHO), the number of people with obesity will increase almost twofold and will make from 30 to 50 percent of the population in economically developed countries. Embolization of the left gastric artery is an innovative, minimally invasive method of treating obesity, which allows to reduce body weight six months after its implementation by 17–18% on average. This technique, long used in emergency medicine as a method to stop gastric bleeding, has a new potential in the treatment of obesity. In this manuscript we present a pilot study examining the effects of bariatric embolization of the left gastric artery on the parameters of fat and carbohydrate metabolism in obese patients. We also present a case report illustrating the weight loss and the metabolic benefits of the left gastric artery embolization.

1. Introduction

Obesity has become the modern day epidemic affecting both developed and developing countries.

Data from numerous studies indicate that obesity has adverse metabolic effects on human health and is major cause for the development of diabetes mellitus, malignant neoplasms, cardiovascular diseases, as well as degenerative joint diseases, infertility, fatty liver disease, among others [1].

Obesity treatment comprises lifestyle interventions, including diet therapy, increased physical activity, psychotherapy as well as pharmacotherapy, and traditional bariatric surgery. It should be noted that the effectiveness of the conservative methods of treating obesity is quite limited compared to the results of bariatric surgery aimed at weight loss.

Bariatric surgery is by far the most effective strategy for achieving long-term weight loss. The use of bariatric surgery is justified in persons suffering from morbid obesity (body mass index above 40 kg/m²), and in persons suffering from type 2 diabetes or other obesity-associated diseases - with an index over 35 kg/m². These surgical indications are particularly important given the lack of efficacy of conservative methods of treatment [2], Currently, the following types of bariatric surgery are most commonly used: gastric banding, sleeve gastroplasty, biliopancreatic bypass surgery and gastric bypass surgery [3].

Despite the fact that there is irrefutable evidence of the effectiveness of bariatric surgery over conservative methods of treating obesity, such operations like any surgical intervention, has many potential complications, and other health risks for patients and, moreover, surgical interventions do not always provide the desired results. These limitations of the current surgical interventions led to the emergence of new approaches in the fight against obesity, which would occupy their niche between standard bariatric surgery and conservative methods of treatment [4].

Bariatric embolization of the left gastric artery (ELGA), used for more than 40 years in emergency surgery to stop gastrointestinal bleeding, now is used as an innovative intervention of obesity management. During ELGA manipulation polyvinyl alcohol microspheres are introduced through the radial or femoral artery with a microcatheter, which subsequently creates ischemia of the gastric fundus that leads to the desired outcome: a decrease in the level of the hunger hormone ghrelin and a subsequent decrease in appetite [5].

The ghrelin hormone, the structure and function of which was first described by Kojima et al. in 1999, the 28th amino acid peptide that is produced by the endocrine cells lining the fundus of the stomach, remains today one of the known hormones that stimulates appetite. It is known that the level of ghrelin increases significantly during fasting and decreases after eating [6].

Ghrelin, having a powerful orexigenic effect and playing an important role in weight regulation, is a promising therapeutic target in bariatric surgery. Several studies [7, 8, 9, 10, 11] have demonstrated a significant decrease in weight as well as in ghrelin level after left gastric artery embolization [3, 12]. Thus, the definitive role of ghrelin in weight loss in obese patients after bariatric embolization is evident [3, 12, 13].

However, such studies have only examined the effect of bariatric embolization on body weight and ghrelin levels in obese patients. In this study we aim to evaluate not only weight reduction and ghrelin level after ELGA, but also to assess how changes in the level of the hunger hormone affect other hormones that regulate energy homeostasis and how to achieve weight stabilization after the initial weight loss with ELGA.

The aim of the current study is to evaluate the effect of bariatric embolization of the left gastric artery on the parameters of fat and carbohydrate metabolism in obese patients.

2. Materials and methods

A pilot study was conducted in the City Clinical Hospital n.a. S.P. Botkin in the Department of Endocrinology No. 59, which included 23 patients (10 men and 13 women, mean age 40.2 ± 10.6 years) with a diagnosis of morbid obesity (BMI > 40 kg/m²) and obesity of the 2nd degree (BMI > 35 kg/m²). In order to reduce body weight all the patients underwent surgical intervention in the form of bariatric embolization of the left gastric artery with polyvinyl alcohol microparticles 300–500 microns. Preoperative preparation included computed tomography of the aorta and its branches with contrast and administration of proton pump inhibitors.

During ELGA that is performed without anesthesia by transradial or transfemoral access, catheterization and angiography of the celiac trunk and left gastric artery were performed, followed by slow introduction of polyvinyl alcohol spherical particles with a diameter of 300–500 microns into the artery which led to the embolization of the left gastric artery. The duration of surgery is from 20 minutes to 1 hour.

The research work was approved at a meeting of the ethics committee of the Federal State Budgetary Educational Institution of Higher Education, Russian Medical Academy of Continuous Professional Education of the Ministry of Health of Russia dated on January 16, 2018 No 1.

Prior to the initiation of the study, each patient signed a written informed consent to participate in the study. All the patients before and after the bariatric embolization underwent an anthropometric examination including measurement of height, body weight, calculation of BMI, waist circumference (WC) as well as laboratory work including the determination of adiponectin, ghrelin and leptin. To assess carbohydrate metabolism, fasting plasma glucose, glycated hemoglobin, insulin, and HOMA-ir were also determined.

The severity of insulin resistance was determined using the HOMA-ir index, which was calculated using the formula HOMA-ir = (fasting glycemia (mmol/l) × IRI (immunoreactive insulin) (μU/ml))/22.5. The duration of the observation was 6 months, after which a follow up examination was carried out.

SPSS® statistical software version 21 was used to analyze our study data. The Wilcoxon test was used to assess the difference between the indicators before and after ELGA. Paired interrelations of indicators were determined by Pearson’s rank correlation coefficient. The critical significance level (p) in the study was taken equal to 0.01. The results of the study are presented as M ± m, where M is the average value and m is the error of the mean.

3. Results

Preliminary results showed that 6 months after the bariatric embolization of the left gastric artery, a statistically significant decreases in all anthropometric parameters were observed: body weight decreased from 138 ± 33.2 kg to 114 ± 26 kg (18.5%, p < 0.001), BMI from 47.4 ± 9.3 kg/m² to 38.1 ± 7.4 kg/m² (19.6%, p < 0.001), WC index from 130.4 ± 9.7 cm to 115 ± 10.3 cm (9%, p = 0.01).

After ELGA, patients experienced a decrease in the hunger hormone and changes in the secretion of adipose tissue hormones. Previous studies have noted a decrease in weight and ghrelin level after ELGA [5, 6, 12]. Thus, the level of ghrelin decreased from 20.23 ± 4.6 to 2.09 ± 0.93 femtomol/μl (90% p < 0.001). The level of leptin, which is secreted in proportion to adipose tissue, decreased from 23.3 ± 4.9 ng/ml to 10.5 ± 3.7 ng/ml. (54% p < 0.001). At the same time, a correlation analysis was carried out between the change of body weight and the level of ghrelin, which has a positive correlation with the weight of patients after bariatric embolization (r = 0.329, p < 0.01).

In this study, the level of adiponectin was determined, which, according to the literature, is a key and universal marker of metabolic health [14]. It is known that the level of adiponectin is reduced in patients with visceral obesity and tends to increase with decreasing body weight [15]. The results of our study confirm these literature data: for example, 6 months after bariatric embolization, patients showed a statistically significant increase in the average level of adiponectin from 22.5 ± 8.1 μg/ml to 42.4 ± 11 μg/ml (88.4%, p < 0.001).

As an example, we performed a correlation analysis between the change of adiponectin and body weight. Adiponectin negatively correlated with body weight of patients, the correlation coefficient after 6 months was (r = −0.389, p < 0.01). After ELGA, a positive change of carbohydrate metabolism was revealed.

The mean fasting glucose level initially before ELGA was 6.7 ± 0.9 mmol/l and by the sixth month it decreased to 5.3 ± 0.7 mmol/l (p < 0.001), the mean HbA1 level with an initial value of 6.2 ± 0.85% 6 months after the intervention showed a significant decrease to 5.5 ± 0.56% (p < 0.001), insulin initially −15.6 ± 7.7 μU/ml, after six months it decreased to 8.1 ± 0.7 μU/ml (p < 0.001), HOMA-IR index initially −4.5 ± 1.2, after 6 months of observation: −1.9 ± 0.32 (p < 0.001). The dynamics of the studied parameters of patients is presented in Table 1.

Parameter	Baseline	6 months	P-value
Body weight, kg	138.1 ± 33.2	113 ± 26	<0.001
BMI, kg/m^2	47.4 ± 9.3	38.1 ± 7.4	<0.001
WC, cm	130.4 ± 9.7	115 ± 10.3	<0.001
Fasting glycemia, mmol/l	6.9 ± 1.5	5.1 ± 0.7	<0.001
HbA1C, %	6.2 ± 1	5.3 ± 0.6	<0.001
Insulin, mcU/ml	15.6 ± 7.7	8.1 ± 0.7	<0.001
Adiponectin, mcg/ml	22.5 ± 8.1	20.1 ± 7.6	<0.001
Leptin, ng/ml	23.3 ± 4.9	21.2 ± 5.6	<0.001
HOMA-ir	4.5 ± 1.2	1.9 ± 0.32	<0.001
Ghrelin, femtomol/μl	20.23 ± 4.8	15.9 ± 5.2	<0.001

Table 1.

The dynamics of the studied parameters in patients with obesity before and after ELGA.

BMI, body mass index; WC, waist circumference etc.; HbA1C, glycated hemoglobin; Homa-ir, homeostasis model assessment of insulin resistance.

4. Discussion

Currently, the available therapeutic options as well as the surgical interventions to combat obesity are not fully effective. Several emerging therapeutic alternatives, are being evaluated in search of new, highly effective, yet safe methods of treating obesity.

Bariatric embolization of the left gastric artery appears to be an attractive therapeutic alternative that might become one of the most successful strategies in the fight against obesity while allowing control of energy consumption, affecting fat metabolism and significantly reducing the level of ghrelin, the hunger hormone.

The preliminary results of our pilot study, despite a small cohort of patients and the absence of a control group, showed that subjects who underwent bariatric embolization demonstrated a statistically significant weight loss 6 months after it was carried out by an average of 18–19%, a decrease in BMI, which was accompanied by a decrease in ghrelin by 90% and leptin by 54%, which are secreted in proportion to body fat mass.

It should be noted that previous studies evaluated only the changes of body weight measured in kg, BMI and ghrelin levels, but in our work we further evaluated other metabolic parameters and demonstrated how the level of ghrelin, which is the main underlying cause of weight loss in bariatric embolization, is associated with changes in other hormones that regulate energy homeostasis such as leptin, adiponectin [3, 12, 13, 14].

We also demonstrated at 6th month of observation, patients had a statistically significant increase in the average values of adiponectin by 84%, which has a negative correlation with body weight. An increase in the level of adiponectin was accompanied by a regression of metabolic changes in obese patients six months after the bariatric embolization, a decrease in body weight, an improvement in the sensitivity of peripheral tissues to insulin with the restoration of all parameters of carbohydrate metabolism and the prevention of many metabolic diseases, one of which is type 2 diabetes mellitus.

After the embolization of the left gastric artery in obese patients by 6 month, we demonstrated significant improvements in all indicators of carbohydrate metabolism: fasting glucose, HbA1c, insulin, HOMA-ir index.

While, future studies with long-term patients’ follow-up will be required, our piolt data showed that bariatric embolization can become the very effective therapeutic intervention for obesity management in the short term, allowing not only to reduce body weight, but also to normalize carbohydrate metabolism and restore the hormonal function of adipose tissue.

Finally, we would like to present a clinical case of a patient who underwent embolization of the left gastric artery in order to reduce body weight.

Clinical case №1. Patient X., aged 48, was admitted to the Department of Endocrinology No 59 of the City Clinical Hospital n.a. S.P. Botkin with complaints of overweight, general weakness, fatigue, severe thirst, dry mouth and shortness of breath after walking a distance of less than 500 m.

Patient reported significant weight gain in 2011 after an accident resulting in left leg fracture which limited his physical activity. Subsequently, the patient noted an increase in weight of 10 kg per year. In 2016 he was diagnosed type 2 diabetes mellitus and oral hypoglycemic therapy with vildagliptin at a dosage of 50 mg was prescribed, followed by the addition of metformin at a dosage of 1000 mg twice a day. Also, the patient’s condition was aggravated by arterial hypertension with an episodic increase to 220/120 mmHg, which he has been suffering from for 25 years.

On examination: height 178 cm, body weight 136 kg, BMI 42.9 kg/m².

On auscultation of the heart, the tones were muffled, rhythmic, no murmurs were heard, blood pressure was 140/85 mm Hg, the heart rate was 76 beats per minute. The frequency of respiratory movements was 16 per minute, with auscultation of the lungs, vesicular breathing was carried out in all parts of the lungs, there was no wheezing. The abdomen was enlarged due to subcutaneous fat, on the lateral surfaces of which striae were noted.

Biochemical profile revealed an increase in fasting glucose to 9.58 mmol/ml, glycated hemoglobin – 7.5%; insulin – 23.2 mU/l; C-peptide was 1642 pmol/l; HOMA-IR index (Homeostasis Model Assessment of Insulin Resistance) = 9.8; HOMA-β = 160.5. There were also high levels of uric acid up to 470 μmol/l, triglycerides up to 5.8 mmol/l, total cholesterol up to 6.7 mmol/l, LDL up to 3.5 mmol/l.

Ultrasound examination of the hepatobiliary system showed hepatomegaly, diffuse changes in the liver and pancreas of a lipomatous-fibrous nature.

The patient also underwent esophagogastroscopy, which revealed no contraindications to bariatric embolization of the left gastric artery.

Preoperative workup included ECG, echocardiography, radiography of the chest organs, ultrasound of the arteries and veins of the lower extremities, ultrasound examination of the kidneys and adrenal glands.

The patient was diagnosed with morbid obesity (BMI = 42.9 Kg/m²). Diabetes mellitus type 2. The target level of glycated hemoglobin was less than 7%. Arterial hypertension of stage 3, a very high risk of cardiovascular complications. Dyslipidemia IIb. Hyperuricemia. Non-alcoholic fatty liver disease.

The indications for surgical treatment were determined for the patient, and subsequently, computed tomography of the aorta and its branches with contrast was performed to determine the anatomical variant of the gastric blood supply. Preparation for bariatric embolization also included the administration of the proton pump inhibitor drugs omeprozole 20 mg twice a day and sucralfate 1 g four times a day for a week before surgery.

In a planned manner in December 2017 in order to reduce body weight, the patient underwent surgical intervention in the form of X-ray endovascular bariatric embolization of the left gastric artery. The duration of the operation was 1 hour 10 minutes.

On the third day after the intervention, gastroscopy was performed, according to which no possible ischemic complications from the gastric mucosa were detected.

The examination of the patient before bariatric embolization, and after three days, 1 month, 3 and 6 months included the determination of body weight, BMI (Kg/m²), fasting glucose, glycated hemoglobin, insulin, C-peptide, HOMA-IR, HOMA-β, as well as the level of ghrelin, leptin and high molecular weight adiponectin.

The results of the study showed that by the end of the first month after ELGA, the patient’s weight decreased by 8% and amounted to 125 kg, by 3 months - by 11.7% (120 kg), by 6 months - by 17% (112 kg), and after a year body weight compared with baseline data decreased by 20.5% and amounted to 108 kg against 136 kg of initial weight. By the end of the 6th month of observation, BMI decreased to 35.3 kg/m² (−18.4% of the initial), and a year later decreased to 34 kg/m² (−20.7% of the initial).

It should be noted that we observed a decrease in the level of ghrelin and leptin by 6 months after ELGA and also should be especially emphasized, the significant increase in the level of high-molecular-weight adiponectin, which is a recognized universal marker of metabolic health (Table 2).

Date	Weight (kg)	BMI (kg/m^2)	Ghrelin (femtomol/μl)	Leptin (ng/ml)	Adiponectin (μg/ml)
At the time of admission	136	42.9	3.4	8.2	7.85
3 days after ELGA	134	42.2	2.55	7.7	11.59
1 month after ELGA	125	39.4	1.93	7.1	16.14
3 months after ELGA	120	37.8	1.5	4.7	16.92
3 months after ELGA	112	35.3	0.7	4.6	58.5
Δ % of the initial	−17.6%	−20.7%	- 73%	−43.9	+ 645%!!!

Table 2.

Changes in weight and hormonal profile in a patient with morbid obesity after ELGA.

The analysis of the parameters of carbohydrate metabolism after surgery showed a stable positive trend in the form of a stable decrease in fasting glycemia after 6 months to 4.8 mmol/l (−49.4% of the initial), the level of glycated hemoglobin to 6.1% (−18.6% of baseline), decrease in insulin to 7.5 μIU/ml (−67.6% of baseline) and C-peptide to 3.2 ng/ml34% of baseline), decrease in HOMA-IR to 1.6 (−75, 3% of the initial) and HOMA-β up to 115(+51%) (Table 3).

Date	Fasting glucose (mmol/l)	HbA1c (%)	Insulin (μU/ml)	C-peptide (ng/ml)	HOMA-IR	HOMA-β
At the time of admission	9.58	7.5	23.2	4.9	9.8	76
3 days after ELGA	7.8	7.4	23.0	4.7	7.9	106
1 month after ELGA	5.17	6.9	15.6	4.1	3.5	186.8
3 months after ELGA	4.9	6.4	7.74	3.44	1.68	110.5
6 months after ELGA	4.8	6.1	7.5	3.2	1.6	115
Δ % of the initial	−49.4%	−18.6%	−67.6%	−34%	−75.3%	+51%

Table 3.

Changes of carbohydrate metabolism parameters in a patient with morbid obesity after bariatric embolization.

By the end of the sixth month of follow-up after surgery, we also obtained a significant decrease in the patient’s uric acid level to 367 μmol/l (−21.9% of the baseline), a decrease in total cholesterol to 3.17 mmol/l (−52.5% of the baseline), as well as LDL up to 1.86 (−46.8%) and triglycerides up to 2.13 mmol/l (−63% of the baseline) (Table 4).

Date	Total cholesterol (mmol/l)	LDL (mmol/l)	HDL (mmol/l)	Triglycerides (mmol/l)	Uric acid (μmol/l)
At the time of admission	6.7	3.5	0.88	5.8	470
6 months after ELGA	3.17	1.86	1.4	2.13	367
Δ% of the initial	−52.5%	−46.8%	+93%	−63%	−21.9%

Table 4.

The dynamics of lipid profile parameters in an obese patient before and after ELGA.