Randomized Study Comparing Metabolic Surgery With Intensive Medical Therapy to Treat Diabetic Kidney Disease

Diabetes Mellitus, Type 2 Clinical Trial

— OBESE-DKD  

Official title:

Open, Randomized, Unicenter Study Comparing Metabolic Surgery With Intensive Medical Therapy to Treat Diabetic Kidney Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04626323
• Other study ID #: OBESE-DKD
• Secondary ID: CAAE - 370134205
• Status: Recruiting
• Phase: Phase 2
• Start date: May 25, 2021
• Est. completion date: December 2024

Study information

• Verified date: May 2021
• Source: Hospital Alemão Oswaldo Cruz
• Contact: Cristina M Aboud, RN, MSc
• Phone: +551135491187
• Email: cmamedio[@]haoc.com.br
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Proven therapy for DKD is primarily limited to RAAS blockers and SLGT2i. Weight reduction has the potential to become an additional and much needed treatment option. Of all the weight reduction strategies metabolic surgery is suited to be the most effective. Yet no study has of yet compared the effect of metabolic surgery against best medical treatment on the progression of DKD. This pilot trial is designed to be the first determine the efficacy of metabolic surgery in slowing progression of DKD as compared to best medical therapy. The study design will address all the major limitations previously documented, including the major dilemma of estimating versus measuring GFR. Of note, the study's design will allow its sample size to be adjusted upward using an adaptive design if necessary, to achieve statistical significance. It will also inform study design and sample size issues for all future studies in this field. The payoff of establishing metabolic surgery as a new and effective intervention to slow progression to ESRD would be great in terms of reducing patient suffering and societal costs. This will be an open-label, randomized trial involving sixty (60) patients with diabetic kidney disease (DKD) and obesity who will undergo Roux-en-Y gastric bypass (RYGB) in the intervention arm or receive best medical treatment (BMT) in the control arm. The aim of this prospective, open, randomized study is to evaluate the efficacy and safety of RYGB surgery versus best medical treatment on the progression of DKD in patients with type 2 diabetes and obesity.

Description:

This will be an open-label, randomized trial involving sixty (60) patients with DKD and obesity who will undergo RYGB (intervention arm) or receive BMT (control arm). Thirty (30) obese patients with DKD will undergo gastric bypass. Patients will also receive standard of care medical therapy for DKD (ACEI or ARB + SGLT2i) and T2DM (metformin, glitazones, incretin therapy - DPP4 inhibitor and GLP-1 analogs - and insulin, if necessary). Other comorbidities, such as hypertension and dyslipidemia, will be treated according to the latest recommendations of the ADA. The surgical procedure will consist of a laparoscopic surgery performed by an experienced surgeon (approximately 6000 bariatric surgeries), who is accredited as surgeon of excellence by the Brazilian Society of Bariatric and Metabolic Surgery and Surgical Review and Surgical Review Corporation program since 2009. Thirty (30) obese patients with DKD will undergo best medical treatment for DKD (ACEI or ARB + SGLT2i) and T2DM (metformin, glitazones, incretin therapy - DPP4 inhibitor and GLP-1 analogs - and insulin, if necessary). Other comorbidities, such as hypertension and dyslipidemia, will be treated according to the latest recommendations of the ADA. Regarding medication therapy: Metformin will be maintained in the postoperative period while fasting glycemia is above 100 mg/dL unless contraindicated. Anti-antihypertensive drugs and medications for dyslipidemia will be maintained in the postoperative period, unless contraindicated. Micronutrient supplementation (vitamins and mineral salts) will be prescribed to all patients undergoing metabolic surgery. Patients allocated to the control group will receive the same supplementation if necessary.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 70 Years

Eligibility

Inclusion Criteria:

• Female or male aged =30 and =70 years
• Diabetic kidney disease as defined by an estimated glomerular filtration rate (eGFR) (as estimated by CKD-EPI creatinine + cystatin C equation)72 between 45-59l/min/1.73m2 and macroalbuminuria (= 300 mg/g) in a 24 hr urine sample
• BMI =30-40 kg/m2
• Fasting C-peptide over 1 ng/ml
• Negative glutamic acid decarboxylase autoantibodies test
• Patients having received accurate information about the surgery and requesting the procedure
• Patients having understood and accepted the need for long-term medical and surgical follow-up
• Effective method of contraception in women of child-bearing age
• Signed informed consent document

Exclusion Criteria:

• Refusal to participate
• Autoimmune diabetes/type 1 diabetes
• Previous abdominal operations that would complicate a metabolic surgery or increase surgical risk
• Previous malabsorptive and restrictive surgeries
• Malabsorptive syndromes and inflammatory bowel disease
• Significant and/or severe hepatic disease that may complicate metabolic surgery
• Pregnancy or women of childbearing age without effective contraceptive
• Recent history of neoplasia (< 5 years), except for non-melanoma skin neoplasms
• History of liver cirrhosis, active chronic hepatitis, active hepatitis B or hepatitis C
• Major cardiovascular event in the last 6 months
• Current angina
• Pulmonary embolism or severe thrombophlebitis in the last 2 years
• Positive HIV serum testing
• Mental incapacity or severe mental illness
• Severe psychiatric disorders that would complicate follow-up after randomization
• Alcoholism or illicit drug use
• Uncontrolled coagulopathy
• Participation in other clinical trials in the past 30 days
• Inability to tolerate RAAS blockers and/or SGLT2i
• Iodine allergy
• History of acute kidney injury requiring renal replacement therapy
• Dialysis dependency
• Kidney transplantation
• Use of immunosuppressive drugs, chemotherapy and/or radiotherapy
• Any disorder which, in the opinion of the investigator, might jeopardize subject's safety or compliance with the protocol

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Diabetic Nephropathies
• Kidney Disease, Chronic
• Kidney Diseases
• Kidney Injury
• Renal Insufficiency, Chronic

Intervention

Procedure:
• Roux-en-Y gastric bypass
Pneumoperitoneum closed with Veress needle Identification of Treitz angle Measurement of biliary loop (50 cm) Bowel transection with linear stapler (white load) Measurement of the alimentary limb (100 cm) Laterolateral Entero-anastomoses (white load) Construction of gastric pouch distant about 3 cm from the esophageal-gastric junction with stomach section in the small curvature. Linear cutting anastomosis (gastrojejunostomy) from about 1 to 1.2 cm Anastomosis integrity evaluation by methylene blue test and/or perioperative air. Expected surgical time: 60 minutes

Drug:
• Best medical treatment
Patients will also receive standard of care medical therapy for DKD (ACEI or ARB + SGLT2i) and T2DM (metformin, glitazones, incretin therapy - DPP4 inhibitor and GLP-1 analogs - and insulin, if necessary).

Locations

Country	Name	City	State
Brazil	Centro especializado em Obesidade e Diabetes do Hospital Alemão Oswaldo Cruz	Sao Paulo	São Paulo

Sponsors (1)

Lead Sponsor	Collaborator
Hospital Alemão Oswaldo Cruz

Country where clinical trial is conducted

Brazil, 

References & Publications (60)

(IHME) IfHMaE. Findings from the Global Burden of Disease Study 2017. Seattle, WA2018.

Afkarian M, Sachs MC, Kestenbaum B, Hirsch IB, Tuttle KR, Himmelfarb J, de Boer IH. Kidney disease and increased mortality risk in type 2 diabetes. J Am Soc Nephrol. 2013 Feb;24(2):302-8. doi: 10.1681/ASN.2012070718. Epub 2013 Jan 29. — View Citation

Alicic RZ, Rooney MT, Tuttle KR. Diabetic Kidney Disease: Challenges, Progress, and Possibilities. Clin J Am Soc Nephrol. 2017 Dec 7;12(12):2032-2045. doi: 10.2215/CJN.11491116. Epub 2017 May 18. — View Citation

American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2012 Jan;35 Suppl 1:S64-71. doi: 10.2337/dc12-s064. — View Citation

Aminian A, Brethauer SA, Kirwan JP, Kashyap SR, Burguera B, Schauer PR. How safe is metabolic/diabetes surgery? Diabetes Obes Metab. 2015 Feb;17(2):198-201. doi: 10.1111/dom.12405. Epub 2014 Nov 19. — View Citation

Atkins RC, Zimmet P. Diabetic kidney disease: act now or pay later. Kidney Int. 2010 Mar;77(5):375-7. doi: 10.1038/ki.2009.509. — View Citation

Batterham RL, Cummings DE. Mechanisms of Diabetes Improvement Following Bariatric/Metabolic Surgery. Diabetes Care. 2016 Jun;39(6):893-901. doi: 10.2337/dc16-0145. — View Citation

Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH, Remuzzi G, Snapinn SM, Zhang Z, Shahinfar S; RENAAL Study Investigators. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J — View Citation

Canney AL, Cohen RV, Elliott JA, M Aboud C, Martin WP, Docherty NG, le Roux CW. Improvements in diabetic albuminuria and podocyte differentiation following Roux-en-Y gastric bypass surgery. Diab Vasc Dis Res. 2020 Jan-Feb;17(1):1479164119879039. doi: 10.1 — View Citation

Cohen JB, Tewksbury CM, Torres Landa S, Williams NN, Dumon KR. National Postoperative Bariatric Surgery Outcomes in Patients with Chronic Kidney Disease and End-Stage Kidney Disease. Obes Surg. 2019 Mar;29(3):975-982. doi: 10.1007/s11695-018-3604-2. — View Citation

Cohen RV, Pereira TV, Aboud CM, Caravatto PP, Petry TB, Correa JL, Schiavon CA, Correa M, Pompílio CE, Pechy FN, le Roux CW; MOMS Study Investigators. Microvascular Outcomes after Metabolic Surgery (MOMS) in patients with type 2 diabetes mellitus and clas — View Citation

Cohen RV, Pinheiro JC, Schiavon CA, Salles JE, Wajchenberg BL, Cummings DE. Effects of gastric bypass surgery in patients with type 2 diabetes and only mild obesity. Diabetes Care. 2012 Jul;35(7):1420-8. doi: 10.2337/dc11-2289. — View Citation

Cohen RV, Shikora S, Petry T, Caravatto PP, Le Roux CW. The Diabetes Surgery Summit II Guidelines: a Disease-Based Clinical Recommendation. Obes Surg. 2016 Aug;26(8):1989-91. doi: 10.1007/s11695-016-2237-6. — View Citation

Cummings DE, Cohen RV. Bariatric/Metabolic Surgery to Treat Type 2 Diabetes in Patients With a BMI <35 kg/m2. Diabetes Care. 2016 Jun;39(6):924-33. doi: 10.2337/dc16-0350. — View Citation

D'Agati VD, Chagnac A, de Vries AP, Levi M, Porrini E, Herman-Edelstein M, Praga M. Obesity-related glomerulopathy: clinical and pathologic characteristics and pathogenesis. Nat Rev Nephrol. 2016 Aug;12(8):453-71. doi: 10.1038/nrneph.2016.75. Epub 2016 Ju — View Citation

Dansinger ML, Gleason JA, Griffith JL, Selker HP, Schaefer EJ. Comparison of the Atkins, Ornish, Weight Watchers, and Zone diets for weight loss and heart disease risk reduction: a randomized trial. JAMA. 2005 Jan 5;293(1):43-53. — View Citation

de Boer IH, Rue TC, Hall YN, Heagerty PJ, Weiss NS, Himmelfarb J. Temporal trends in the prevalence of diabetic kidney disease in the United States. JAMA. 2011 Jun 22;305(24):2532-9. doi: 10.1001/jama.2011.861. — View Citation

Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004 Aug;240(2):205-13. — View Citation

Eckel RH, Kahn SE, Ferrannini E, Goldfine AB, Nathan DM, Schwartz MW, Smith RJ, Smith SR. Obesity and type 2 diabetes: what can be unified and what needs to be individualized? J Clin Endocrinol Metab. 2011 Jun;96(6):1654-63. doi: 10.1210/jc.2011-0585. — View Citation

Foley RN, Collins AJ. The growing economic burden of diabetic kidney disease. Curr Diab Rep. 2009 Dec;9(6):460-5. — View Citation

Foster MC, Hwang SJ, Porter SA, Massaro JM, Hoffmann U, Fox CS. Fatty kidney, hypertension, and chronic kidney disease: the Framingham Heart Study. Hypertension. 2011 Nov;58(5):784-90. doi: 10.1161/HYPERTENSIONAHA.111.175315. Epub 2011 Sep 19. — View Citation

Friedman AN, Moe S, Fadel WF, Inman M, Mattar SG, Shihabi Z, Quinney SK. Predicting the glomerular filtration rate in bariatric surgery patients. Am J Nephrol. 2014;39(1):8-15. doi: 10.1159/000357231. Epub 2013 Dec 19. — View Citation

Friedman AN, Wahed AS, Wang J, Courcoulas AP, Dakin G, Hinojosa MW, Kimmel PL, Mitchell JE, Pomp A, Pories WJ, Purnell JQ, le Roux C, Spaniolas K, Steffen KJ, Thirlby R, Wolfe B. Effect of Bariatric Surgery on CKD Risk. J Am Soc Nephrol. 2018 Apr;29(4):12 — View Citation

Friedman AN, Wang J, Wahed AS, Docherty NG, Fennern E, Pomp A, Purnell JQ, le Roux CW, Wolfe B. The Association Between Kidney Disease and Diabetes Remission in Bariatric Surgery Patients With Type 2 Diabetes. Am J Kidney Dis. 2019 Dec;74(6):761-770. doi: — View Citation

Friedman AN, Wolfe B. Is Bariatric Surgery an Effective Treatment for Type II Diabetic Kidney Disease? Clin J Am Soc Nephrol. 2016 Mar 7;11(3):528-35. doi: 10.2215/CJN.07670715. Epub 2015 Oct 8. Review. — View Citation

Gloy VL, Briel M, Bhatt DL, Kashyap SR, Schauer PR, Mingrone G, Bucher HC, Nordmann AJ. Bariatric surgery versus non-surgical treatment for obesity: a systematic review and meta-analysis of randomised controlled trials. BMJ. 2013 Oct 22;347:f5934. doi: 10 — View Citation

Gregg EW, Chen H, Wagenknecht LE, Clark JM, Delahanty LM, Bantle J, Pownall HJ, Johnson KC, Safford MM, Kitabchi AE, Pi-Sunyer FX, Wing RR, Bertoni AG; Look AHEAD Research Group. Association of an intensive lifestyle intervention with remission of type 2 — View Citation

Gugliucci A, Kotani K, Taing J, Matsuoka Y, Sano Y, Yoshimura M, Egawa K, Horikawa C, Kitagawa Y, Kiso Y, Kimura S, Sakane N. Short-term low calorie diet intervention reduces serum advanced glycation end products in healthy overweight or obese adults. Ann — View Citation

Heshka S, Anderson JW, Atkinson RL, Greenway FL, Hill JO, Phinney SD, Kolotkin RL, Miller-Kovach K, Pi-Sunyer FX. Weight loss with self-help compared with a structured commercial program: a randomized trial. JAMA. 2003 Apr 9;289(14):1792-8. — View Citation

Imam TH, Fischer H, Jing B, Burchette R, Henry S, DeRose SF, Coleman KJ. Estimated GFR Before and After Bariatric Surgery in CKD. Am J Kidney Dis. 2017 Mar;69(3):380-388. doi: 10.1053/j.ajkd.2016.09.020. Epub 2016 Dec 4. — View Citation

Inge TH, Laffel LM, Jenkins TM, Marcus MD, Leibel NI, Brandt ML, Haymond M, Urbina EM, Dolan LM, Zeitler PS; Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) and Treatment Options of Type 2 Diabetes in Adolescents and Youth (TODAY) Consortia. — View Citation

Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, Nathan DM; Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002 Feb 7;346(6):393-40 — View Citation

Laferrère B, Teixeira J, McGinty J, Tran H, Egger JR, Colarusso A, Kovack B, Bawa B, Koshy N, Lee H, Yapp K, Olivan B. Effect of weight loss by gastric bypass surgery versus hypocaloric diet on glucose and incretin levels in patients with type 2 diabetes. — View Citation

Le Jemtel TH, Samson R, Jaiswal A, Lewine EB, Oparil S. Regression of Left Ventricular Mass After Bariatric Surgery. Curr Hypertens Rep. 2017 Sep;19(9):68. doi: 10.1007/s11906-017-0767-5. Review. — View Citation

Lewis EJ, Hunsicker LG, Clarke WR, Berl T, Pohl MA, Lewis JB, Ritz E, Atkins RC, Rohde R, Raz I; Collaborative Study Group. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl — View Citation

Look AHEAD Research Group, Wing RR. Long-term effects of a lifestyle intervention on weight and cardiovascular risk factors in individuals with type 2 diabetes mellitus: four-year results of the Look AHEAD trial. Arch Intern Med. 2010 Sep 27;170(17):1566- — View Citation

Mann JF, Gerstein HC, Pogue J, Bosch J, Yusuf S. Renal insufficiency as a predictor of cardiovascular outcomes and the impact of ramipril: the HOPE randomized trial. Ann Intern Med. 2001 Apr 17;134(8):629-36. — View Citation

Mingrone G, Panunzi S, De Gaetano A, Guidone C, Iaconelli A, Nanni G, Castagneto M, Bornstein S, Rubino F. Bariatric-metabolic surgery versus conventional medical treatment in obese patients with type 2 diabetes: 5 year follow-up of an open-label, single- — View Citation

Müller-Stich BP, Senft JD, Warschkow R, Kenngott HG, Billeter AT, Vit G, Helfert S, Diener MK, Fischer L, Büchler MW, Nawroth PP. Surgical versus medical treatment of type 2 diabetes mellitus in nonseverely obese patients: a systematic review and meta-ana — View Citation

Nangaku M, Izuhara Y, Usuda N, Inagi R, Shibata T, Sugiyama S, Kurokawa K, van Ypersele de Strihou C, Miyata T. In a type 2 diabetic nephropathy rat model, the improvement of obesity by a low calorie diet reduces oxidative/carbonyl stress and prevents dia — View Citation

Nasr SH, D'Agati VD, Said SM, Stokes MB, Largoza MV, Radhakrishnan J, Markowitz GS. Oxalate nephropathy complicating Roux-en-Y Gastric Bypass: an underrecognized cause of irreversible renal failure. Clin J Am Soc Nephrol. 2008 Nov;3(6):1676-83. doi: 10.22 — View Citation

Navaneethan SD, Yehnert H, Moustarah F, Schreiber MJ, Schauer PR, Beddhu S. Weight loss interventions in chronic kidney disease: a systematic review and meta-analysis. Clin J Am Soc Nephrol. 2009 Oct;4(10):1565-74. doi: 10.2215/CJN.02250409. Epub 2009 Sep — View Citation

Neff KJ, Elliott JA, Corteville C, Abegg K, Boza C, Lutz TA, Docherty NG, le Roux CW. Effect of Roux-en-Y gastric bypass and diet-induced weight loss on diabetic kidney disease in the Zucker diabetic fatty rat. Surg Obes Relat Dis. 2017 Jan;13(1):21-27. d — View Citation

O'Brien R, Johnson E, Haneuse S, Coleman KJ, O'Connor PJ, Fisher DP, Sidney S, Bogart A, Theis MK, Anau J, Schroeder EB, Arterburn D. Microvascular Outcomes in Patients With Diabetes After Bariatric Surgery Versus Usual Care: A Matched Cohort Study. Ann I — View Citation

Ohtomo S, Izuhara Y, Nangaku M, Dan T, Ito S, van Ypersele de Strihou C, Miyata T. Body weight control by a high-carbohydrate/low-fat diet slows the progression of diabetic kidney damage in an obese, hypertensive, type 2 diabetic rat model. J Obes. 2010;2 — View Citation

Perkovic V, Jardine MJ, Neal B, Bompoint S, Heerspink HJL, Charytan DM, Edwards R, Agarwal R, Bakris G, Bull S, Cannon CP, Capuano G, Chu PL, de Zeeuw D, Greene T, Levin A, Pollock C, Wheeler DC, Yavin Y, Zhang H, Zinman B, Meininger G, Brenner BM, Mahaff — View Citation

Peromaa-Haavisto P, Tuomilehto H, Kössi J, Virtanen J, Luostarinen M, Pihlajamäki J, Käkelä P, Victorzon M. Obstructive sleep apnea: the effect of bariatric surgery after 12 months. A prospective multicenter trial. Sleep Med. 2017 Jul;35:85-90. doi: 10.10 — View Citation

Schauer PR, Bhatt DL, Kirwan JP, Wolski K, Aminian A, Brethauer SA, Navaneethan SD, Singh RP, Pothier CE, Nissen SE, Kashyap SR; STAMPEDE Investigators. Bariatric Surgery versus Intensive Medical Therapy for Diabetes - 5-Year Outcomes. N Engl J Med. 2017 — View Citation

Scheurlen KM, Probst P, Kopf S, Nawroth PP, Billeter AT, Müller-Stich BP. Metabolic surgery improves renal injury independent of weight loss: a meta-analysis. Surg Obes Relat Dis. 2019 Jun;15(6):1006-1020. doi: 10.1016/j.soard.2019.03.013. Epub 2019 Mar 2 — View Citation

Schiavon CA, Bersch-Ferreira AC, Santucci EV, Oliveira JD, Torreglosa CR, Bueno PT, Frayha JC, Santos RN, Damiani LP, Noujaim PM, Halpern H, Monteiro FLJ, Cohen RV, Uchoa CH, de Souza MG, Amodeo C, Bortolotto L, Ikeoka D, Drager LF, Cavalcanti AB, Berwang — View Citation

Seshadri P, Iqbal N, Stern L, Williams M, Chicano KL, Daily DA, McGrory J, Gracely EJ, Rader DJ, Samaha FF. A randomized study comparing the effects of a low-carbohydrate diet and a conventional diet on lipoprotein subfractions and C-reactive protein leve — View Citation

Shulman A, Peltonen M, Sjöström CD, Andersson-Assarsson JC, Taube M, Sjöholm K, le Roux CW, Carlsson LMS, Svensson PA. Incidence of end-stage renal disease following bariatric surgery in the Swedish Obese Subjects Study. Int J Obes (Lond). 2018 Jun;42(5): — View Citation

Stern JS, Gades MD, Wheeldon CM, Borchers AT. Calorie restriction in obesity: prevention of kidney disease in rodents. J Nutr. 2001 Mar;131(3):913S-917S. Review. — View Citation

Sundbom M, Näslund E, Vidarsson B, Thorell A, Ottoson J. Low overall mortality during 10 years of bariatric surgery: nationwide study on 63,469 procedures from the Scandinavian Obesity Registry. Surg Obes Relat Dis. 2020 Jan;16(1):65-70. doi: 10.1016/j.so — View Citation

Tuck ML, Sowers J, Dornfeld L, Kledzik G, Maxwell M. The effect of weight reduction on blood pressure, plasma renin activity, and plasma aldosterone levels in obese patients. N Engl J Med. 1981 Apr 16;304(16):930-3. — View Citation

UK Prospective Diabetes Study (UKPDS). X. Urinary albumin excretion over 3 years in diet-treated type 2, (non-insulin-dependent) diabetic patients, and association with hypertension, hyperglycaemia and hypertriglyceridaemia. Diabetologia. 1993 Oct;36(10): — View Citation

Wiggins JE, Goyal M, Sanden SK, Wharram BL, Shedden KA, Misek DE, Kuick RD, Wiggins RC. Podocyte hypertrophy, "adaptation," and "decompensation" associated with glomerular enlargement and glomerulosclerosis in the aging rat: prevention by calorie restrict — View Citation

World Health Organization Diabetes. 2018; https://www.who.int/news-room/fact-sheets/detail/diabetes.

Wycherley TP, Brinkworth GD, Noakes M, Buckley JD, Clifton PM. Effect of caloric restriction with and without exercise training on oxidative stress and endothelial function in obese subjects with type 2 diabetes. Diabetes Obes Metab. 2008 Nov;10(11):1062- — View Citation

Young L, Nor Hanipah Z, Brethauer SA, Schauer PR, Aminian A. Long-term impact of bariatric surgery in diabetic nephropathy. Surg Endosc. 2019 May;33(5):1654-1660. doi: 10.1007/s00464-018-6458-8. Epub 2018 Sep 24. — View Citation

* Note: There are 60 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean differenceGlomerular filtration rate (GFR)	Mean difference in GFR between BMT and RYGB at the pre-specified time points of 12 and 36 months after randomization	At 12 and 36 months after randomization
Secondary	Change in twenty-four hour urinary albumin/protein excretion	Change in 24h urinary albumin/protein excretion	From baseline to 12 and 36 months
Secondary	Improvements in micro- or macroalbuminuria	Proportion of patients who achieve improvements in micro- or macroalbuminuria from baseline to 12 and 36 months	From baseline to 12 and 36 months
Secondary	Change in CKD stage and CKD prognostic risk	Change in CKD stage and CKD prognostic risk from baseline to month 12 and 36	From baseline to 12 and 36 months
Secondary	Change in GFR, eGFR and 24 hr creatinine clearance	Change in GFR, eGFR and 24 hr creatinine clearance from baseline to months 12 and 36	From baseline to 12 and 36 months
Secondary	Proportion of participants with =30%, =40%, and =50% reduction in GFR measurements	Proportion of participants with =30%, =40%, and =50% reduction in GFR measurements (GFR, eGFR and 24 hr creatinine clearance) from baseline to months 12 and 36	From baseline to 12 and 36 months
Secondary	Decline in eGFR, sustained low eGFR, kidney transplantation, maintenance dialysis, and kidney death	Time to occurrence of sustained % decline in eGFR, sustained low eGFR, kidney transplantation, maintenance dialysis, and kidney death	Time to occurrence (from baseline)
Secondary	Maintenance dialysis, kidney transplantation, kidney death, and GFR < 15 ml/min	Individual and composite endpoints of maintenance dialysis, kidney transplantation, kidney death, and GFR < 15 ml/min at 12 and 36 months	At 12 and 36 months after randomization
Secondary	Change in body weight	Change in body weight from baseline to months 12 and 36	From baseline to 12 and 36 months
Secondary	Change in body mass index	Change in body mass index from baseline to months 12 and 36	From baseline to 12 and 36 months
Secondary	Change in waist circumference	Change in waist circumference from baseline to months 12 and 36	From baseline to 12 and 36 months
Secondary	Medications to maintain optimal diabetes and blood pressure control	Number and dose of medications to maintain optimal diabetes and blood pressure control from baseline to months 12 and 36	From baseline to 12 and 36 months
Secondary	Change in fasting glucose	Change in fasting glucose from baseline to months 12 and 36	From baseline to 12 and 36 months
Secondary	Change in HbA1c	Change in HbA1c from baseline to months 12 and 36	From baseline to 12 and 36 months
Secondary	Change in basal insulin	Change in basal insulin from baseline to months 12 and 36	From baseline to 12 and 36 months
Secondary	Change in homeostasis model assessment (HOMA) scores	Change in homeostasis model assessment (HOMA) scores from baseline to months 12 and 36	From baseline to 12 and 36 months
Secondary	Remission in type 2 diabetes	Achievement of partial or complete remission in type 2 diabetes by months 12 and 36	At 12 and 36 months after randomization
Secondary	Change in blood pressure	Change in blood pressure from baseline to months 12 and 36	From baseline to 12 and 36 months
Secondary	Hypoglycemic adverse events	Number of patients with confirmed or symptomatic hypoglycemic adverse events from baseline to months 12 and 36	From baseline to 12 and 36 months
Secondary	Changes in total cholesterol, triglycerides, LDL and HDL levels	Changes in total cholesterol, triglycerides, LDL and HDL levels from baseline to months 12 and 36	From baseline to 12 and 36 months
Secondary	Number of participants achieving LDL < 100 mg/dL and HDL > 40mg/dL	Number of participants achieving LDL < 100 mg/dL and HDL > 40mg/dL from baseline to months 12 and 36	From baseline to 12 and 36 months
Secondary	Changes in serum calcium and phosphorus,	Changes in serum calcium and phosphorus from baseline to months 12 and 36	From baseline to 12 and 36 months
Secondary	Change in parathyroid hormone (PTH)	Change in parathyroid hormone (PTH) from baseline to months 12 and 36	From baseline to 12 and 36 months
Secondary	Change in mineral bone density	Change in mineral bone density from baseline to months 12 and 36	From baseline to 12 and 36 months
Secondary	Change in quality of life	Change in quality of life measured by SF-36 questionnaire from baseline to months 12 and 36	From baseline to 12 and 36 months
Secondary	Adverse events	Number of patients with adverse events from baseline to months 12 and 36	From baseline to 12 and 36 months
Secondary	Acute kidney injury	Number of episodes of acute kidney injury from baseline to months 12 and 36	From baseline to 12 and 36 months
Secondary	Adverse cardiovascular events (nonfatal stroke, nonfatal MI, cardiovascular death)	Composite of major adverse cardiovascular events (nonfatal stroke, nonfatal MI, cardiovascular death) from baseline to months 12 and 36	From baseline to 12 and 36 months
Secondary	Mortality	Total mortality from baseline to months 12 and 36	From baseline to 12 and 36 months
Secondary	Days hospitalized	Number of days hospitalized from baseline to months 12 and 36	From baseline to 12 and 36 months
Secondary	Change in urinary volume	Change in urinary volume from baseline to months 12 and 36	From baseline to 12 and 36 months
Secondary	Change in calcium and oxalate excretion	Change in calcium and oxalate excretion from baseline to months 12 and 36	From baseline to 12 and 36 months
Secondary	High sensitivity c-reactive protein	Change in high sensitivity c-reactive protein from baseline to months 12 and 36	From baseline to 12 and 36 months
Secondary	Change in muscle strength	Change in muscle strength using one repetition maximum (1-RM) from baseline to months12 and 36	From baseline to 12 and 36 months
Secondary	Kidney volumes	Change in kidney volumes from baseline to months 12 and 36	From baseline to 12 and 36 months
Secondary	Change in ventricular mass	Change in left and right ventricular mass from baseline to months 12 and 36	From baseline to 12 and 36 months
Secondary	Change in ejection fraction	Change in left ventricular ejection fraction from baseline to months 12 and 36	From baseline to 12 and 36 months
Secondary	Costs of care and health care utilization	Costs of care and health care utilization from baseline to months 12 and 36	From baseline to 12 and 36 months

External Links

•   Obesity and Diabetes Center
•   Oswaldo Cruz German Hospital