Clinical trial NCT03165812: A Diabetes Improvement in Medical Therapy Versus SADJB Study
Official title: Single Anastomosis Duodeno Jejunal Bypass With Sleeve Gastrectomy (SADJB-SG) Versus Intensive Medical Therapy (IMT) in the Treatment of Type 2 Diabetes Mellitus Among Asian Patients With BMI 23.5 - 30 kg/m2: A Clinical Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Diabetes Mellitus, Type 2
Overweight
Keywords: Sleeve Gastrectomy
Duodeno Jejunal Bypass
Single Anastomosis
Intensive Medical Therapy
Diabetes Mellitus
Lead sponsor: Universiti Putra Malaysia
Sponsor class: OTHER
First posted: 2017-05-24
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The study will involve two groups with equal allocation of patients in the intensive medical therapy (IMT) group and Single Anastomosis Duodeno Jejunal Bypass with Sleeve Gastrectomy (SADJB-SG) group with stratification by use of insulin at screening. All patients who agree to participate in this study will be assigned to one of the treatment groups by the doctor without randomization.
Primary purpose: TREATMENT

Brief summary: The incidence of diabetes mellitus is increasing annually in Asia. It is the leading cause of blindness, chronic renal insufficiency, and amputations, multiplying the risks of heart disease and stroke. Ninety percent of diabetic patients are type 2 diabetes mellitus (T2DM), which is usually associated with overweight and obese. Single Anastomosis Duodeno-Jejunal Bypass with Sleeve Gastrectomy (SADJB-SG) is a type of bariatric surgery whereby food is bypassed into the distal jejunum, and the duodenum is excluded. Sleeve gastrectomy offers the restrictive component by reducing the capacity of the stomach. In short, this combined technique results in food restriction and malabsorption. A total of 84 patients will be recruited in this study. An equal number of patients will be allocated into two groups. There will be an intensive medical therapy group (IMT) and SADJB-SG group. The patients in IMT group will be subjected to strict adherence to diet, optimization of diabetic medications and close monitoring of blood glucose and glycated haemoglobin (HbA1c) level. The SADJB-SG group will be undergoing surgery. The variables that will be studied include body mass index (BMI), fasting blood glucose (FBG), glycated haemoglobin (HbA1c), C- peptide, plasma insulin and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Biochemical markers are important in this research as the development of T2DM involves both multi-organ insulin resistance and inadequate insulin secretion by pancreatic β-cells, leading to high blood sugar during fasting and post meal. Other mechanisms proposed in this study are leptin, adipokines, incretins, amino acids, and diabetic dyslipidaemia. The raw data will be analysed using the SPSS statistical software. At the end of the study, the investigator will evaluate and determine the role of SADJB-SG in glycaemic control and BMI in T2DM patients compared to IMT. The investigator hypothesized that there is an improvement in HbA1c level in T2DM patients in SADJB-SG group compare to IMT group.

Detailed description: Recruitment will be a prospective study in patients with body mass index (BMI) of 23.5-30 kg/m2, aged between 18 and 65 years old. Each patient will be preoperatively screened (including psychologist assessment) and evaluated by the study multidisciplinary team before recruitment. The study will involve two groups with equal allocation of patients in the intensive medical therapy (IMT) group and Single Anastomosis Duodeno Jejunal Bypass with Sleeve Gastrectomy (SADJB-SG) group with stratification by use of insulin at screening. All patients who agree to participate in this study will be assigned to one of the treatment groups by the doctor without randomization. Before making a final decision for treatment, every patient will undergo a detailed and up-to-date evaluation by the doctor regarding the suitability, the pros and cons, risk and benefits, the potential postoperative complications and the likelihood of requiring postoperative nutritional supplementation. Patients that are eligible to take part in this study will be informed, and the final decision will solely be made based on patients' willingness. The patients will also be made aware that this is an experimental trial and both verbal and written informed consent will be taken before treatment. In addition, the patients will be informed regarding the use of the clinical and analytical data for publication purposes. Initial assessment of the patient's social demographic data, history of present illness (duration of diabetes, oral hypoglycemic agent used), medical and surgical history, family history, anthropometric measurements (height, weight, BMI, calculated as weight (kg)/height (m2), waist, hip and neck circumference), history of weight loss attempt, diet and lifestyle assessment, quality of life assessment and biochemical measures including fasting blood glucose (FBG), glycated haemoglobin (HbA1c), C- peptide, plasma insulin and HOMA-IR, assessment for obstructive sleep apnea, depression and sleep quality will be obtained upon approval of participation in the study or before any form of treatment. An additional pre-operation questionnaire will be given to the SADJB-SG group during initial assessment to ensure understanding of the patients towards the surgery. Adverse events will be monitored closely at 1, 2, 3, and 4 weeks after surgery. In any occurrence of an adverse event, it will be documented and reported within 14 days.The study will be terminated if there are life-threatening or severe adverse events associated with SADJB-SG group or IMT group.

Patients will not be given access to the study data however the patients will be informed regarding their progress during every follow-up visit. All medical records and research data will be kept in the investigator's hard disk and web-based storage (i-cloud and i-drive) for two years. Study data will be held even after the study period as there will still be a continuous follow-up with the patients for life. However, all patients' information obtained from this study will be kept and handled in a confidential manner, by applicable laws and regulations. When publishing or presenting the study results, the identity of patients will not be revealed without patient's expressed consent. Participants will also be covered under clinical trial insurance from the institution during the study period. In the case of emergency, all patients will be given the contact number of the investigator as the investigators are contactable throughout the day. This study will begin after receiving the approval of Medical Research \& Ethics Committee, Ministry of Health Malaysia.

Sample size:

The sample size was estimated with the help of PS software (power and sample size calculation software) 3.1.2 with a power of 80% and a significant level of 0.05. The estimation was based on the diabetic remission in a few study done on bariatric surgery on one arm and intensive medical treatment on the other and it was detected a range of 57% to 73% diabetic remission among the bariatric surgery group. Another study by Lee WJ et al., 2014 found a diabetic remission rate of 64% (HbA1C\<6.0%) with the SADJB-SG group one year after surgery. The total estimated sample size is 34 patients in each arm for this study. However, with the inclusion of 20% dropout rate, the total number of patients needed for this study is 42 patients in each arm.

Laboratory investigations:

15 ml of fasting blood samples will be taken early in the morning for the following blood tests stated below in Ethylenediaminetetraacetic acid (EDTA), fluoride oxalate and plain tubes, depending on the respective test. Samples will be further centrifuged for the serum to be stored in 3 aliquots (1 ml each) for batch analysis. This serum will be stored at - 80°C pending further analysis. The analysis will be done at the Chemical Pathology Laboratory, Faculty of Medicine \& Health Sciences, UPM.3.6.1. Baseline preoperative biochemical markers and profiles for all bariatric surgery T2DM candidates, and other nutrients 'at risk' related to medication usage or poor dietary quality include:

Blood investigations on automated analyser:

* Full blood count
* Renal profile (urea, creatinine, sodium, potassium)
* Liver function test (total protein, albumin, bilirubin, alkaline phosphatase, alanine transaminase, aspartate aminotransferase, gamma-glutamyl transferase)
* Thyroid function test (TSH, free T4)
* Cortisol
* Fasting plasma glucose, HbA1c
* Fasting lipid profile (total cholesterol, triglyceride, LDL, HDL)
* Bone profile \[calcium, phosphate, magnesium, parathyroid hormone, 25-OH vitamin D\]
* Iron, ferritin, vitamin B12, folate

Urine investigations

* Urinalysis (dipstick) \& urine FEME (automated analyser)
* Urine microalbumin (automated analyser)

These investigations will be repeated in 24 months but more frequently if clinically indicated. Apart from that, studying the following parameters at baseline, 6 and 12 months post-surgery will allow us to explore the hypothesis that a modulatory effect on incretin production could lead to better glycaemic control independent of weight loss.

* Insulin, C-peptide (automated analyser), HOMA-IR (calculated value)
* Lipoprotein Subfractionation on Lipoprint LDL system.
* Incretins (GLP-1, GIP)
* Adipokines such as leptin
* Adiponectin
* FGF19 (Fibroblast Growth Factor 19)
* Tumor necrosis factor-alpha (TNF-alpha)

Genetic Analysis:

DNA Extraction- Laboratory analyses will be obtained after an overnight fast and the plasma will be separated by centrifugation and storage at -20ºC. The available commercial DNA extraction methods will be utilized to get a good DNA regarding quantity and quality.

DNA Quantification- The quality of the extracted DNA will be evaluated using electrophoresis and the concentration of the extracted DNA will be estimated using the spectrophotometer.

Genotyping analysis-

* Standardization of Polymerase chain reaction (PCR) will be carried out for the respective genes.
* Identification and analysis of candidate genes polymorphisms of GCG, GLP1R, DPP4, GIP, GIPR and PCSK1 genes by conventional PCR, PCR-RFLP, Real time- PCR High Resolution Analysis.

Staining and Visualizing of Genomic DNA- Agarose electrophoresis will be carried out to determine the PCR products by staining with ethidium bromide. The genomic DNA, PCR amplified products and the restricted fragments will be visualized under ultraviolet light and the image will be captured by Alpha Imager.

Validation- Nearly 10% of the samples will be randomly chosen and the samples will be genotyped on the same assay for the second time and the results will be scored by the other researcher.

Positive and Negative Controls PCR amplified products from the respective gene will be sequenced to identify the genotypes. Those samples will be used as a positive control for the respective genes and the PCR grade water lacking the DNA template will be used as a negative control.

DNA Sequencing methods-

* DNA sequencing will be done to confirm the polymorphism of the respective genes.
* The sequencing results will be subjected to BLAST (www.ncbi.nlm.nig.gov/BLAST) and it has been verified against the published gene sequence for the respective gene.

Data Analysis:

Statistical calculations will be performed using the standard statistical software package, IBM SPSS Statistics for Windows, Version 23.0. Armonk, NY: IBM Corp. Results will be expressed as mean values and standard deviation for normally distributed variables. Median and interquartile range (IQR) will be calculated for all not normally distributed continuous variables. Non-parametric tests such as Mann-Whitney U test and/or Kruskall-Wallis test will be used for non-normal distribution of variables. Associations between qualitative variables will be determined by Chi-square test, Fisher's exact test and SAS Exact Contingency Table. In all statistical analyses, p-value of \< 0.05 (95% confidence interval) was considered to be statistically significant.

Analysis of variance (ANOVA) will be used to test for significant differences between means.

* Univariate logistic regression analysis will be used to determine the synergistic effect of the genetic variants
* The Hardy-Weinberg equilibrium for genotypic distribution will be evaluated using the Hardy-Weinberg equilibrium exact test.
* Rotor-Gene 6000 software (software version 1.7, built 87) will be used for the HRM analysis for certain gene polymorphisms by generating a normalized melting curve, a difference graph and a derivative plot.

The categorical variables from this study such as Body Mass Index (BMI), fasting glucose, HbA1c, C- peptide levels, Plasma insulin and HOMA-IR will be reported as counts and percent and compared between SADJB-SG group and IMT group by SPSS method.

Study Ethics:

Ethical clearance will be obtained from the Ethics Committee for Research Involving Human Subjects Universiti Putra Malaysia (JKEUPM) and Kuala Lumpur General Hospital. This study will be submitted to National Medical Research Register (NMRR) for Medical Research and Ethics Committee, Ministry of Health Malaysia (MREC) clearance. Informed consent will be obtained from each participant of the study.

Conflict of Interest:

There is no conflict of interest among the investigators.

Eligibility criteria: Inclusion Criteria:

* Age 18-65 years.
* BMI 23.5 - 30 kg/m2.
* Diabetes more than two years and less than ten years.
* American Society of Anesthesiologists (ASA) classification \< 4
* Able to give informed consent

Exclusion Criteria:

* Age: below 18 and above 65.
* Inability to informed consent.
* Patients on GLP-1 agonist and insulin two weeks before admission into the trial.
* Diabetes more than ten years or less than two years.
* C-Peptide level \< 2.0 ng/mL
* American Society of Anesthesiologists (ASA) classification \> 3
* Logistic issue where patient come from rural area and has difficulty in complying with the post-operation close monitoring and follow-up
* Patient who has psychiatric disorder (depression, substance abuse, eating disorder, alcoholism, dementia etc.)

Primary outcomes:
measure: Type 2 Diabetes Mellitus (T2DM) patients in SADJB-SG group achieving glycated hemoglobin (HbA1c) level of less than 7% (with or without diabetes medications) in 2 years as compare to patients in IMT group.
timeFrame: 24 months
Secondary outcomes:
measure: T2DM patients in SADJB-SG group achieving mean fasting blood glucose level of 4.4-7.0 mmol/l in 2 years as compare to patients in IMT group.
timeFrame: 24 months
measure: T2DM patients in SADJB-SG group achieving lower body mass index (BMI) in 2 years as compare to IMT group.
timeFrame: 24 months
measure: Changes in serum level of lipids.
timeFrame: 24 months
measure: Assessment of NAFLD associated morbidities by detecting the metabolic changes after SADJB-SG.
timeFrame: 24 months
measure: Identification of proposed mechanism for improvement in glycemic control following SADJB-SG.
timeFrame: 24 months
measure: Identification of genetic biomarkers.
timeFrame: Baseline
Other outcomes:
Locations:
city: Kajang
country: Malaysia
facility: Hospital Serdang
state: Selangor
city: Kuala Lumpur
country: Malaysia
facility: Hospital Kuala Lumpur
state: Wilayah Persekutuan Kuala Lumpur
Study officials:
affiliation: Universiti Putra Malaysia
name: Tikfu Gee, MBBS, MS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zimmet P, Alberti KG, Shaw J. Global and societal implications of the diabetes epidemic. Nature. 2001 Dec 13;414(6865):782-7. doi: 10.1038/414782a.
citation: Greenway SE, Greenway FL 3rd, Klein S. Effects of obesity surgery on non-insulin-dependent diabetes mellitus. Arch Surg. 2002 Oct;137(10):1109-17. doi: 10.1001/archsurg.137.10.1109.
citation: Guh DP, Zhang W, Bansback N, Amarsi Z, Birmingham CL, Anis AH. The incidence of co-morbidities related to obesity and overweight: a systematic review and meta-analysis. BMC Public Health. 2009 Mar 25;9:88. doi: 10.1186/1471-2458-9-88.
citation: Prospective Studies Collaboration; Whitlock G, Lewington S, Sherliker P, Clarke R, Emberson J, Halsey J, Qizilbash N, Collins R, Peto R. Body-mass index and cause-specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies. Lancet. 2009 Mar 28;373(9669):1083-96. doi: 10.1016/S0140-6736(09)60318-4. Epub 2009 Mar 18.
citation: Bradley D, Magkos F, Klein S. Effects of bariatric surgery on glucose homeostasis and type 2 diabetes. Gastroenterology. 2012 Oct;143(4):897-912. doi: 10.1053/j.gastro.2012.07.114. Epub 2012 Aug 8.
citation: Pories WJ, MacDonald KG Jr, Flickinger EG, Dohm GL, Sinha MK, Barakat HA, May HJ, Khazanie P, Swanson MS, Morgan E, et al. Is type II diabetes mellitus (NIDDM) a surgical disease? Ann Surg. 1992 Jun;215(6):633-42; discussion 643. doi: 10.1097/00000658-199206000-00010.
citation: Pories WJ, Swanson MS, MacDonald KG, Long SB, Morris PG, Brown BM, Barakat HA, deRamon RA, Israel G, Dolezal JM, et al. Who would have thought it? An operation proves to be the most effective therapy for adult-onset diabetes mellitus. Ann Surg. 1995 Sep;222(3):339-50; discussion 350-2. doi: 10.1097/00000658-199509000-00011.
citation: Lee WJ, Huang MT, Wang W, Lin CM, Chen TC, Lai IR. Effects of obesity surgery on the metabolic syndrome. Arch Surg. 2004 Oct;139(10):1088-92. doi: 10.1001/archsurg.139.10.1088.
citation: Madan AK, Orth W, Ternovits CA, Tichansky DS. Metabolic syndrome: yet another co-morbidity gastric bypass helps cure. Surg Obes Relat Dis. 2006 Jan-Feb;2(1):48-51; discussion 51. doi: 10.1016/j.soard.2005.09.014.
citation: Mottin CC, Vontobel Padoin A, Schroer CE, Barancelli FT, Glock L, Repetto G. Behavior of type 2 diabetes mellitus in morbid obese patients submitted to gastric bypass. Obes Surg. 2008 Feb;18(2):179-81. doi: 10.1007/s11695-007-9249-1. Epub 2008 Jan 4.
citation: Rubino F, Marescaux J. Effect of duodenal-jejunal exclusion in a non-obese animal model of type 2 diabetes: a new perspective for an old disease. Ann Surg. 2004 Jan;239(1):1-11. doi: 10.1097/01.sla.0000102989.54824.fc.
citation: Rubino F, Forgione A, Cummings DE, Vix M, Gnuli D, Mingrone G, Castagneto M, Marescaux J. The mechanism of diabetes control after gastrointestinal bypass surgery reveals a role of the proximal small intestine in the pathophysiology of type 2 diabetes. Ann Surg. 2006 Nov;244(5):741-9. doi: 10.1097/01.sla.0000224726.61448.1b.
citation: Dixon JB, O'Brien PE, Playfair J, Chapman L, Schachter LM, Skinner S, Proietto J, Bailey M, Anderson M. Adjustable gastric banding and conventional therapy for type 2 diabetes: a randomized controlled trial. JAMA. 2008 Jan 23;299(3):316-23. doi: 10.1001/jama.299.3.316.
citation: O'Brien PE, Dixon JB, Laurie C, Skinner S, Proietto J, McNeil J, Strauss B, Marks S, Schachter L, Chapman L, Anderson M. Treatment of mild to moderate obesity with laparoscopic adjustable gastric banding or an intensive medical program: a randomized trial. Ann Intern Med. 2006 May 2;144(9):625-33. doi: 10.7326/0003-4819-144-9-200605020-00005.
citation: Corsini DA, Simoneti CA, Moreira G, Lima SE Jr, Garrido AB. Cancer in the excluded stomach 4 years after gastric bypass. Obes Surg. 2006 Jul;16(7):932-4. doi: 10.1381/096089206777822313.
citation: Harper JL, Beech D, Tichansky DS, Madan AK. Cancer in the bypassed stomach presenting early after gastric bypass. Obes Surg. 2007 Sep;17(9):1268-71. doi: 10.1007/s11695-007-9216-x.
citation: Buchwald H, Oien DM. Metabolic/bariatric surgery worldwide 2011. Obes Surg. 2013 Apr;23(4):427-36. doi: 10.1007/s11695-012-0864-0.
citation: Lovshin JA, Drucker DJ. Incretin-based therapies for type 2 diabetes mellitus. Nat Rev Endocrinol. 2009 May;5(5):262-9. doi: 10.1038/nrendo.2009.48.
citation: Cohen RV, Neto MG, Correa JL, Sakai P, Martins B, Schiavon CA, Petry T, Salles JE, Mamedio C, Sorli C. A pilot study of the duodenal-jejunal bypass liner in low body mass index type 2 diabetes. J Clin Endocrinol Metab. 2013 Feb;98(2):E279-82. doi: 10.1210/jc.2012-2814. Epub 2013 Jan 21.
citation: Cohen R, Pinheiro JS, Correa JL, Schiavon CA. Laparoscopic Roux-en-Y gastric bypass for BMI < 35 kg/m(2): a tailored approach. Surg Obes Relat Dis. 2006 May-Jun;2(3):401-4, discussion 404. doi: 10.1016/j.soard.2006.02.011.
citation: Schauer PR, Bhatt DL, Kirwan JP, Wolski K, Brethauer SA, Navaneethan SD, Aminian A, Pothier CE, Kim ES, Nissen SE, Kashyap SR; STAMPEDE Investigators. Bariatric surgery versus intensive medical therapy for diabetes--3-year outcomes. N Engl J Med. 2014 May 22;370(21):2002-13. doi: 10.1056/NEJMoa1401329. Epub 2014 Mar 31.
citation: Schauer PR, Kashyap SR, Wolski K, Brethauer SA, Kirwan JP, Pothier CE, Thomas S, Abood B, Nissen SE, Bhatt DL. Bariatric surgery versus intensive medical therapy in obese patients with diabetes. N Engl J Med. 2012 Apr 26;366(17):1567-76. doi: 10.1056/NEJMoa1200225. Epub 2012 Mar 26.
citation: Lee WJ, Chong K, Ser KH, Lee YC, Chen SC, Chen JC, Tsai MH, Chuang LM. Gastric bypass vs sleeve gastrectomy for type 2 diabetes mellitus: a randomized controlled trial. Arch Surg. 2011 Feb;146(2):143-8. doi: 10.1001/archsurg.2010.326.
citation: Lee WJ, Lee KT, Kasama K, Seiki Y, Ser KH, Chun SC, Chen JC, Lee YC. Laparoscopic single-anastomosis duodenal-jejunal bypass with sleeve gastrectomy (SADJB-SG): short-term result and comparison with gastric bypass. Obes Surg. 2014 Jan;24(1):109-13. doi: 10.1007/s11695-013-1067-z.
citation: Sanchez-Pernaute A, Herrera MA, Perez-Aguirre ME, Talavera P, Cabrerizo L, Matia P, Diez-Valladares L, Barabash A, Martin-Antona E, Garcia-Botella A, Garcia-Almenta EM, Torres A. Single anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S). One to three-year follow-up. Obes Surg. 2010 Dec;20(12):1720-6. doi: 10.1007/s11695-010-0247-3.
citation: Buchwald H, Estok R, Fahrbach K, Banel D, Jensen MD, Pories WJ, Bantle JP, Sledge I. Weight and type 2 diabetes after bariatric surgery: systematic review and meta-analysis. Am J Med. 2009 Mar;122(3):248-256.e5. doi: 10.1016/j.amjmed.2008.09.041.
citation: Lee WJ, Almulaifi AM, Tsou JJ, Ser KH, Lee YC, Chen SC. Duodenal-jejunal bypass with sleeve gastrectomy versus the sleeve gastrectomy procedure alone: the role of duodenal exclusion. Surg Obes Relat Dis. 2015 Jul-Aug;11(4):765-70. doi: 10.1016/j.soard.2014.12.017. Epub 2014 Dec 24.
citation: Garcia-Caballero M, Valle M, Martinez-Moreno JM, Miralles F, Toval JA, Mata JM, Osorio D, Minguez A. Resolution of diabetes mellitus and metabolic syndrome in normal weight 24-29 BMI patients with One Anastomosis Gastric Bypass. Nutr Hosp. 2012 Mar-Apr;27(2):623-31. doi: 10.1590/S0212-16112012000200041.
citation: Bose M, Olivan B, Teixeira J, Pi-Sunyer FX, Laferrere B. Do Incretins play a role in the remission of type 2 diabetes after gastric bypass surgery: What are the evidence? Obes Surg. 2009 Feb;19(2):217-229. doi: 10.1007/s11695-008-9696-3. Epub 2008 Sep 27.
citation: Laferrere B. Diabetes remission after bariatric surgery: is it just the incretins? Int J Obes (Lond). 2011 Sep;35 Suppl 3(0 3):S22-5. doi: 10.1038/ijo.2011.143.
citation: Chronaiou A, Tsoli M, Kehagias I, Leotsinidis M, Kalfarentzos F, Alexandrides TK. Lower ghrelin levels and exaggerated postprandial peptide-YY, glucagon-like peptide-1, and insulin responses, after gastric fundus resection, in patients undergoing Roux-en-Y gastric bypass: a randomized clinical trial. Obes Surg. 2012 Nov;22(11):1761-70. doi: 10.1007/s11695-012-0738-5.
citation: Geloneze B, Geloneze SR, Chaim E, Hirsch FF, Felici AC, Lambert G, Tambascia MA, Pareja JC. Metabolic surgery for non-obese type 2 diabetes: incretins, adipocytokines, and insulin secretion/resistance changes in a 1-year interventional clinical controlled study. Ann Surg. 2012 Jul;256(1):72-8. doi: 10.1097/SLA.0b013e3182592c62.
citation: Goktas Z, Moustaid-Moussa N, Shen CL, Boylan M, Mo H, Wang S. Effects of bariatric surgery on adipokine-induced inflammation and insulin resistance. Front Endocrinol (Lausanne). 2013 Jun 10;4:69. doi: 10.3389/fendo.2013.00069. eCollection 2013.
citation: Enkhmaa B, Shiwaku K, Anuurad E, Nogi A, Kitajima K, Yamasaki M, Oyunsuren T, Yamane Y. Prevalence of the metabolic syndrome using the Third Report of the National Cholesterol Educational Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATP III) and the modified ATP III definitions for Japanese and Mongolians. Clin Chim Acta. 2005 Feb;352(1-2):105-13. doi: 10.1016/j.cccn.2004.08.012.
citation: Pyorala K, Pedersen TR, Kjekshus J, Faergeman O, Olsson AG, Thorgeirsson G. Cholesterol lowering with simvastatin improves prognosis of diabetic patients with coronary heart disease. A subgroup analysis of the Scandinavian Simvastatin Survival Study (4S). Diabetes Care. 1997 Apr;20(4):614-20. doi: 10.2337/diacare.20.4.614.
citation: Foger B. Lipid lowering therapy in type 2 diabetes. Wien Med Wochenschr. 2011 Jun;161(11-12):289-96. doi: 10.1007/s10354-011-0908-4.
citation: Inukai T, Yamamoto R, Suetsugu M, Matsumoto S, Wakabayashi S, Inukai Y, Matsutomo R, Takebayashi K, Aso Y. Small low-density lipoprotein and small low-density lipoprotein/total low-density lipoprotein are closely associated with intima-media thickness of the carotid artery in Type 2 diabetic patients. J Diabetes Complications. 2005 Sep-Oct;19(5):269-75. doi: 10.1016/j.jdiacomp.2005.03.002.
citation: Superko HR, Gadesam RR. Is it LDL particle size or number that correlates with risk for cardiovascular disease? Curr Atheroscler Rep. 2008 Oct;10(5):377-85. doi: 10.1007/s11883-008-0059-2.
citation: Syvanne M, Ahola M, Lahdenpera S, Kahri J, Kuusi T, Virtanen KS, Taskinen MR. High density lipoprotein subfractions in non-insulin-dependent diabetes mellitus and coronary artery disease. J Lipid Res. 1995 Mar;36(3):573-82.
citation: Asztalos BF, Cupples LA, Demissie S, Horvath KV, Cox CE, Batista MC, Schaefer EJ. High-density lipoprotein subpopulation profile and coronary heart disease prevalence in male participants of the Framingham Offspring Study. Arterioscler Thromb Vasc Biol. 2004 Nov;24(11):2181-7. doi: 10.1161/01.ATV.0000146325.93749.a8. Epub 2004 Sep 23.
citation: Soran H, Hama S, Yadav R, Durrington PN. HDL functionality. Curr Opin Lipidol. 2012 Aug;23(4):353-66. doi: 10.1097/MOL.0b013e328355ca25.
citation: Krauss RM, Siri PW. Metabolic abnormalities: triglyceride and low-density lipoprotein. Endocrinol Metab Clin North Am. 2004 Jun;33(2):405-15. doi: 10.1016/j.ecl.2004.03.016.
citation: Nassif AT, Nagano TA, Okayama S, Nassif LS, Branco Filho A, Sampaio Neto J. Performance of the Bard Scoring System in Bariatric Surgery Patients with Nonalcoholic Fatty Liver Disease. Obes Surg. 2017 Feb;27(2):394-398. doi: 10.1007/s11695-016-2284-z.
citation: Frantzides CT, Carlson MA, Moore RE, Zografakis JG, Madan AK, Puumala S, Keshavarzian A. Effect of body mass index on nonalcoholic fatty liver disease in patients undergoing minimally invasive bariatric surgery. J Gastrointest Surg. 2004 Nov;8(7):849-55. doi: 10.1016/j.gassur.2004.07.001.
citation: Taitano AA, Markow M, Finan JE, Wheeler DE, Gonzalvo JP, Murr MM. Bariatric surgery improves histological features of nonalcoholic fatty liver disease and liver fibrosis. J Gastrointest Surg. 2015 Mar;19(3):429-36; discussion 436-7. doi: 10.1007/s11605-014-2678-y. Epub 2014 Dec 24.
citation: Furuya CK Jr, de Oliveira CP, de Mello ES, Faintuch J, Raskovski A, Matsuda M, Vezozzo DC, Halpern A, Garrido AB Jr, Alves VA, Carrilho FJ. Effects of bariatric surgery on nonalcoholic fatty liver disease: preliminary findings after 2 years. J Gastroenterol Hepatol. 2007 Apr;22(4):510-4. doi: 10.1111/j.1440-1746.2007.04833.x.
citation: van Dijk SJ, Molloy PL, Varinli H, Morrison JL, Muhlhausler BS; Members of EpiSCOPE. Epigenetics and human obesity. Int J Obes (Lond). 2015 Jan;39(1):85-97. doi: 10.1038/ijo.2014.34. Epub 2014 Feb 25.
citation: Prasadan K, Koizumi M, Tulachan S, Shiota C, Lath N, Paredes J, Guo P, El-Gohary Y, Malek M, Shah S, Gittes GK. The expression and function of glucose-dependent insulinotropic polypeptide in the embryonic mouse pancreas. Diabetes. 2011 Feb;60(2):548-54. doi: 10.2337/db09-0035.
citation: Miyawaki K, Yamada Y, Ban N, Ihara Y, Tsukiyama K, Zhou H, Fujimoto S, Oku A, Tsuda K, Toyokuni S, Hiai H, Mizunoya W, Fushiki T, Holst JJ, Makino M, Tashita A, Kobara Y, Tsubamoto Y, Jinnouchi T, Jomori T, Seino Y. Inhibition of gastric inhibitory polypeptide signaling prevents obesity. Nat Med. 2002 Jul;8(7):738-42. doi: 10.1038/nm727. Epub 2002 Jun 17.
citation: Choquet H, Kasberger J, Hamidovic A, Jorgenson E. Contribution of common PCSK1 genetic variants to obesity in 8,359 subjects from multi-ethnic American population. PLoS One. 2013;8(2):e57857. doi: 10.1371/journal.pone.0057857. Epub 2013 Feb 25.
citation: Chang YC, Chiu YF, Shih KC, Lin MW, Sheu WH, Donlon T, Curb JD, Jou YS, Chang TJ, Li HY, Chuang LM. Common PCSK1 haplotypes are associated with obesity in the Chinese population. Obesity (Silver Spring). 2010 Jul;18(7):1404-9. doi: 10.1038/oby.2009.390. Epub 2009 Oct 29.
citation: Heo YS, Park JM, Kim YJ, Kim SM, Park DJ, Lee SK, Han SM, Shim KW, Lee YJ, Lee JY, Kwon JW. Bariatric surgery versus conventional therapy in obese Korea patients: a multicenter retrospective cohort study. J Korean Surg Soc. 2012 Dec;83(6):335-42. doi: 10.4174/jkss.2012.83.6.335. Epub 2012 Nov 27.
citation: Cummings DE, Arterburn DE, Westbrook EO, Kuzma JN, Stewart SD, Chan CP, Bock SN, Landers JT, Kratz M, Foster-Schubert KE, Flum DR. Gastric bypass surgery vs intensive lifestyle and medical intervention for type 2 diabetes: the CROSSROADS randomised controlled trial. Diabetologia. 2016 May;59(5):945-53. doi: 10.1007/s00125-016-3903-x. Epub 2016 Mar 17.
citation: Ikramuddin S, Korner J, Lee WJ, Bantle JP, Thomas AJ, Connett JE, Leslie DB, Inabnet WB 3rd, Wang Q, Jeffery RW, Chong K, Chuang LM, Jensen MD, Vella A, Ahmed L, Belani K, Olofson AE, Bainbridge HA, Billington CJ. Durability of Addition of Roux-en-Y Gastric Bypass to Lifestyle Intervention and Medical Management in Achieving Primary Treatment Goals for Uncontrolled Type 2 Diabetes in Mild to Moderate Obesity: A Randomized Control Trial. Diabetes Care. 2016 Sep;39(9):1510-8. doi: 10.2337/dc15-2481. Epub 2016 Jun 16.