Background and aims. Metabolic syndrome or insulin-resistance syndrome is an obesity related condition that

increases the risk of developing type 2 diabetes mellitus over time. In this prospective study, overweight and obese

individuals were assessed for insulin-resistance status by the HOMA indexes.

Material and methods. 48 bariatric patients associating metabolic syndrome were assessed before and 6 months

after the surgery procedure (gastric sleeve, gastric by-pass). The assessment included the following laboratory

blood tests: glucose, insulin, HOMA1 index and HOMA2 index before meal.

Results. There was a significant improvement of insulin resistance status in obese patients who underwent

bariatric surgery.

Conclusions. Insulin resistance status in obese individuals improves significantly after bariatric treatment

Danut Dejeu

Marius Bembea

Paula Dejeu

Viorel Dejeu

Romanian Medical Journal

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Revista Medicală RoMână – VoluMul lXVi, Nr. 4, An 2019400STUDII CLINICEBariatric surgery metaBolic effects in oBese individuals associating insulin resistance statusPaula dejeu1, md, viorel dejeu2,4, md, Phd, danut dejeu2,4, md, Phd,  Prof. marius Bembea3,5, md, Phd1 Medical Laboratory, Bethany Medical Clinic Oradea, Bihor County, Romania 2 General Surgery, “Dr. Gavril Curteanu” City Hospital, Oradea, Romania  3 Pediatrics and Clinical Genetics, “Dr. Gavril Curteanu” City Hospital, Oradea, Romania 4 General Surgery, MedLife Genesys Hospital, Arad, Romania 5 Faculty of Medicine and Pharmacy, University of Oradea, RomaniaCorresponding author:Paula Elisa DejeuE-mail: pauladejeu@yahoo.com ABSTRACTBackground and aims. Metabolic syndrome or insulin-resistance syndrome is an obesity related condition that increases the risk of developing type 2 diabetes mellitus over time. In this prospective study, overweight and obese individuals were assessed for insulin-resistance status by the HOMA indexes. Material and methods. 48 bariatric patients associating metabolic syndrome were assessed before and 6 months after the surgery procedure (gastric sleeve, gastric by-pass). The assessment included the following laboratory blood tests: glucose, insulin, HOMA1 index and HOMA2 index before meal. Results. There was a significant improvement of insulin resistance status in obese patients who underwent bariatric surgery. Conclusions. Insulin resistance status in obese individuals improves significantly after bariatric treatment. Keywords: insulin resistance, HOMA index, obesity, bariatric surgeryBACKgRound And AimSObesity is a pathological condition character-ized by a mixed disorder of metabolic processes of the organism with a change in its energy balance. In some genetic syndromes, obesity is the phenotypi-cal manifestation of a single gene, but in more than 90% of cases this disease is the result of a multiple pathogenic factors which mainly disrupt the bal-ance between energy intake and energy consump-tion. Bariatric surgery is a modern approach in obesi-ty treatment with proven results in rapid and sus-tained body weight loss. The weight loss itself in-duces beneficial metabolic effects and improves intestinal hormone secretion [1], but surgical treat-ment of obesity appears to provide suitabe circum-stances for maintaining a long-term downward trend in body weight. Currently, the body size of an individual is most frequently evaluated by BMI (body mass index or Quetelet index) [2], the ratio between weight (kg) and square of height (m2). Therefore, considering BMI values, World Health Organization (WHO) classifies obesity in four categories as follows: – Overweight: BMI = 25-29.9 kg/m2, with a mildly increased comorbidity risk associat-ed; – Obesity Class I: BMI = 30-34.9 kg/m2, with a moderately increased comorbidity risk; – Obesity Class II: BMI = 35-39.9 kg/m2, with an increased comorbidity risk; – Obesity Class III or morbid obesity: BMI over 40 kg/m2, associating a very high co-morbidity risk [3].Insulin resistance syndrome or metabolic syn-dromeInsulin resistance is a condition of the organism in which a certain amount of insulin concentration induces a suboptimal response in the peripheral tis-Ref: Ro Med J. 2019;66(4) DOI: 10.37897/RMJ.2019.4.19Revista Medicală RoMână – VoluMul lXVI, Nr. 4, An 2019 401sues [4]. Insulin resistance manifests primarily in tissues that are insulin-dependent for intracellular glucose transport, namely hepatic, muscular and adipose tissues [5].The pathophysiological mechanisms involved in insulin resistance syndrome include genetic or primary defects of target cells, anti-insulin antibod-ies and accelerated insulin catabolism [6]. Mito-chondrial dysfunctions also have a significant role in the development of insulin resistance and associ-ated complications [7]. Insulin resistance plays a major role in the pathogenetic development of met-abolic syndrome, which may include at least one of the following: hyperinsulinemia, glucose intoler-ance, type 2 diabetes mellitus, hypertension, ele-vated levels of serum triglycerides, low HDL-cho-lesterol, central obesity [8] and pro-coagulant status characterized by elevated PAI-1 levels.In 2009, the International Diabetes Federation, the International Society of Atherosclerosis, the World Federation of Cardiology and the American Society of Cardiology defined metabolic syndrome by meeting at least three of the following criteria [9]:– abdominal obesity (abdominal circumfer-ence > 80 cm in women and > 94 cm in Eu-ropean males);– serum triglycerides > 150 mg/dl or patient following a lipid-lowering medication;– HDL-serum cholesterol < 40 mg/dl in men, < 50 mg/dl in women or patient following a treatment for increasing HDL-cholesterol values;–	 systolic	blood	pressure	≥	130	mmHg	and/or	diastolic	blood	pressure	≥	85	mmHg	or	pa-tient following blood presure treatment;– baseline blood glucose levels > 100 mg/dl or patient previously diagnosed with diabetes mellitus.Therefore, metabolic syndrome is not a disease in itself, but a combination of metabolic disorders that can identify individuals at high risk for cardio-vascular events and/or type 2 diabetes mellitus. The risk of sudden death is estimated to be five times higher in patients with type 2 diabetes mellitus and three times higher in patients with metabolic syn-drome. If type 2 diabetes mellitus is not present, metabolic syndrome increases over time the risk of its occurrence up to five times [10].HOMA indexMatthews et al. described in 1985 a method which easily evaluates the insulin resistance status of an organism, namely HOMA index („Homeosta-sis model assessment”) [11]. Under basal condi-tions, the relationship between glucose and insulin serum levels reflects the balance between liver glu-cose synthesis	and	insulin	secretion	of	β	pancreatic	cells maintained through a feed-back loop estab-lished between the liver and endocrine pancreas. HOMA1 index, the initial model, was calibrated to give a normal 100% pancreatic cell function and a normal insulin resistance of 1. Increased insulin resistance associates increased basal blood insulin level	and	suboptimal	secretion	of	pancreatic	β	cells	by increasing blood sugar levels. Considering this glucose-insulin interrelation, any pair of basal sug-ar and insulin blood levels can be used to quantify insulin	resistance	(IR)	and	pancreatic	β	cell	 func-tion (% B) using the following formula:HOMA1-IR	=	(IB	(μU/l)	x	GB	(mmol/l))	/	22.5,	where IB represents basal blood insulin levels before meal,	and	GB	basal	blood	glucose	levels	before	meal.	For basal glucose in mg/dL, the denominator is 405.HOMA index is considered a lab test which has a predictive value in the cardiovascular risk [12]. Furthermore, detection of insulin resistance in non-diabetic subjects using HOMA index test was associated with an increased risk of stroke [13].Recommendations to determine HOMA index include the following: assessment of patients with BMI over 28 kg/m2; suspicion of insulin resistance status (metabolic syndrome, type 2 diabetes melli-tus); polycystic ovary syndrome [14].HOMA1 index does not take into account the differences between insulin and hepatic sensitivity, increased insulin secretion and decreased hepatic gluconeogenesis to blood glucose levels above 180 mg/dl, glycosuria and circulating proinsulin. There-fore, the improved model index HOMA 2 was also calculated in the present study by accessing the website https://www.dtu.ox.ac.uk/homacalculator/download.php. HOMA2 calculator automatically calculates the insulin resistance after introducing glucose and insulin serum levels, and also reveals the	percentage	of	functional	β-pancreatic	cells.	Insulin levels were determined using chemilu-minescence detection method (CLIA) and as for glucose, the spectrophotometric method [15].HOMA index reference values are [16]:< 2 – normal;> 2 – possible resistance to insulin;> 2.5 – increased probability of insulin resistance;> 5 – the mean value in type 2 diabetes mellitus.mATeRiAl And meThodThe present prospective clinical trial was con-ducted from January 2017 to September 2018, at the Laboratory Department of Bethany Medical Revista Medicală RoMână – VoluMul lXVI, Nr. 4, An 2019402Clinic Oradea over the patients who underwent bariatric	surgery	at	MedLife	Genesys	Hyperclinic	Arad, Bariatric Surgery Department. Study design and patientsThe laboratory blood tests for the eligible sub-jects were performed in Oradea at Bethany Private Medical Center. The patients included in the study were overweight and obese individuals associating metabolic syndrome assessed in order to receive a bariatric treatment, namely gastric sleeve or gastric by-pass. The following flowchart (Figure 1) presents the selection algorithm for the eligible patients.FIGURE 1. The selection algorithm of eligible patientsLaboratory, anthropometric and clinical data collectionBefore bariatric surgery and 6 months thereaf-ter, the patients enrolled in the study were assessed for the following laboratory tests: insulin, glucose serum levels and HOMA indexes before meal.The clinical evaluation included the following: weight, height, body mass index (BMI), abdominal circumference, blood pressure, family history of overweight/obesity and comorbidities.Statistical analysisIn terms of followed trend in time, comparison of mean values was performed using the Student pair test for normal distribution variables and the Wilcoxon test for those with asymmetric distribu-tion. The statistical significance limit was 0.05.ReSulTSdistribution by gender109 patients were enrolled in the study, of which 83 (76.1%) were female and 26 (23.9%) male: p < 0.0001, Chi-Square test (Figure 2).FIGURE 2. Distribution by gender of the enrolled group (percentage%)Considering only the patients who came for the 6th month follow-up assessment, the ratio becomes even more unequal: out of 48 patients, 41 (85.4%) were women and only 7 (14.6%) men (p < 0.0001, Chi-Square test). By comparing these data with the gender distri-bution in the group that didn’t show up at the post-operative assessment, we obtain the following data:TABLE 1. Gender distribution in the lost group and the enrolled groupGender Lost group(n = 61)Enrolled group(n = 48)Female nr. (%) 42 (68.9) 41 (85.4)Male nr. (%) 19 (31.1) 7 (14.6)There is a higher ratio in women among controls, but the difference does not reach the statistical sig-nificance: p = 0.0738, Yates correction (Figure 3).FIGURE 3. Distribution of the lost group and the enrolled group by gender (percentage%)M = male, F = femaleRevista Medicală RoMână – VoluMul lXVI, Nr. 4, An 2019 403glucose serum levels pre- and postoperativeGlucose	levels	before	meal	registered	a	decreas-ing trend of marked significance: the median pre-operative value was 98 mg/dl and postoperatively 89 mg/dl (p < 0.0001, Wilcoxon test) (Figure 4).insulin serum levels pre- and postoperativeThe insulin level also registered a significant de-crease:	from	the	mean	value	of	20.6	μU/ml	(±	14.0)	to	mean	values	of	6.64	μU/ml	(±	3.8)	(p	<	0.0001,	the Student test for dependent batches) (Figure 5).homA 1 and homA 2 indexes pre- and postoperative The following table reveals the geometrical mean values for HOMA 1 and HOMA 2 risk indexes.FIGURE 4. Glucose serum levels before bariatric surgery and at 6 months thereafterFIGURE 5. Insulin serum levels before bariatric surgery and at 6 months thereafterRevista Medicală RoMână – VoluMul lXVI, Nr. 4, An 2019404TABLE 2. Geometrical mean values for HOMA 1 and HOMA 2 risk indexesIndex Preoperative(n=48)Postoperative(n=48)Statisticsignificance (p)HOMA 1 – geometrical mean value 4.3 (3.2-5.6) 1.2 (1.0-1.5) < 0.0001HOMA 2 – geometrical mean value 2.3 (1.8-3.0) 0.76 (0.65-0.85)< 0.0001After studying the results shown in this table, the decrease of HOMA indexes after bariatric sur-gery becomes obvious. The Figure 6 and Figure 7 further emphasizes these differences.Percentage of functional β pancreatic cells  pre- and postoperativeAs	for	the	percentage	of	functional	β	pancreatic	cells, we noticed a statistically significant decrease: the	preoperative	arithmetic	mean	is	144.2	(±	74.9)	and	 the	postoperative,	86.0	 (±	34.9)	 (p	<	0.0001,	Student test for dependent batches) (Figure 8).FIGURE 6. HOMA1 index values before and after bariatric surgeryFIGURE 7. HOMA2 index values before and after bariatric surgeryRevista Medicală RoMână – VoluMul lXVI, Nr. 4, An 2019 405diSCuSSionSThe gender distribution results of this study fall within the limits observed in the literature [17]. Thus, the ratio between genders, clear-cut suitable for the feminine gender, follows the trend observed in similar studies. Both the percentage of preopera-tive group (76.1%) and study group (85.4%) re-main in the range of these studies indicating a fe-male percentage of 60 to 90%. The results regarding the levels of serum insulin and blood glucose obtained in this study are con-sistent with other similar studies [18,19].The inci-dence of elevated blood glucose levels before meal decreased significantly 6 months after the bariatric procedures (gastric sleeve, gastric by-pass). For the patients with a short history of diabetes, insulin re-sistance may be the major cause of the disease and not	β	pancreatic	cell	dysfunction	[20,21].	Thus,	in-creasing insulin sensitivity is an effective treatment for type 2 diabetes mellitus. The decrease trend of HOMA1 and HOMA2 indexes along with the opti-FIGURE 8. Percentage of functional b pancreatic cells  pre- and postoperativemized	functionality	of	β	pancreatic	cells	indicates	an improvement in insulin resistance status with a good long-term prognosis for the individual. Post-operative HOMA1 index is considered an inde-pendent predictor factor for the complete remission response of diabetes mellitus [22]. The results of our study regarding the decrease of HOMA1 index fall within the variability observed in the specialty literature. ConCluSionSExcess adipose tissue has a baneful effect on carbohydrate and lipid metabolisms. One of the bariatric surgery beneficial effects is a quick signif-icant improvement in the insulin resistance status in obese individuals, registering a decreasing risk of developing type 2 diabetes mellitus over time. 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Pathophysiology of insulin resistance in human disease. Physiol Rev. 1995 Jul. 75(3):473-86.7. Kim JA, Wei Y, Sowers JR. Role of mitochondrial dysfunction in insulin resistance. Circ Res. 2008 Feb 29. 102(4):401-14.8. Reaven G, Abbasi F, McLaughlin T. Obesity, insulin resistance, and cardiovascular disease. Recent Prog Horm Res. 2004. 59:207-23. 9. Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, Fruchart JC, James WP, Loria CM, Smith SC Jr; International Diabetes Federation Task Force on Epidemiology and Prevention; Hational Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; International Association for the Study of Obesity. 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Dardzinska JA, Malgorzewicz S, Kaska L, Proczko M, Stefaniak T, Stankiewicz M, Sledzinski Z: Fasting and postprandial acyl and desacyl ghrelin levels in obese and non-obese subjects. Endokrynologia Polska 2014; 65(5), 377-381.19. Zhu Y, Sun Z, Du Y, Xu G, Gong K et al. Evaluation of insulin resistance improvement after laparoscopic sleeve gastrectomy or gastric bypass surgery with HOMA-IR. Biosci Trends 2017; 11(6): 675-681.20. McEvoy CT, Cardwell CR, Woodside JV, Young IS, Hunter SJ, McKinley MC. A posteriori dietary patterns are related to risk of type 2 diabetes: Findings from a systematic review and meta-analysis.  J Acad Nutr Diet 2014; 114:1759-1775.21. Kotani K, Imazato T, Anzai K, Kyushu Diabetes Testing Study G. Expected role of medical technologists in diabetes mellitus education teams. Biosci Trends. 2015; 9:205-206.22. Schauer PR, Kashyap SR, Wolski K, Brethauer SA, Kirwan JP, Pothier CE et al. 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BARIATRIC SURGERY METABOLIC EFFECTS IN OBESE INDIVIDUALS ASSOCIATING INSULIN RESISTANCE STATUS

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BARIATRIC SURGERY METABOLIC EFFECTS IN OBESE INDIVIDUALS ASSOCIATING INSULIN RESISTANCE STATUS

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