Type 2 diabetes remission 2 years post Roux-en-Y gastric bypass and sleeve gastrectomy: the role of the weight loss and comparison of DiaRem and DiaBetter scores.

AIMS: The comparative efficacy of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy on Type 2 diabetes remission and the role of weight loss are unclear. The DiaRem diabetes remission prediction score uses HbA1c , age and diabetes medications but not diabetes duration. The aim of this study was to compare the DiaRem with the DiaBetter score that includes diabetes duration, upon combined (complete plus partial) 2-year post-surgery diabetes remission in people following RYGB and sleeve gastrectomy, and to investigate the relationship between weight loss and diabetes remission. METHODS: A retrospective single-centre cohort study of obese people with diabetes who underwent RYGB (107) or sleeve gastrectomy (103) and a validation cohort study (173) were undertaken. Diabetes remission, % weight loss, DiaRem, DiaBetter scores and areas under receiving operator characteristic (ROC) curves were calculated. The relationship between % weight loss and diabetes remission was investigated using logistic regression. RESULTS: The proportion of people achieving diabetes remission was highest for those with the lowest DiaBetter and DiaRem scores. Areas under the ROC curves were comparable [DiaBetter: 0.867 (95%CI: 0.817-0.916); DiaRem: 0.865 (95%CI: 0.814-0.915), P=0.856]. Two-year % weight loss was higher post RYGB [26.6 (95%CI: 24.8-28.4)] vs post-sleeve gastrectomy [20.6 (95%CI: 18.3-22.8), P<0.001]. RYGB had 151% higher odds of diabetes remission [OR 2.51 (95%CI: 1.12-5.60), P=0.025]. This association became non-significant when adjusted for % weight loss. CONCLUSION: DiaBetter and DiaRem scores predict diabetes remission following both procedures. Two-year % weight loss plays a key role in determining diabetes remission.

Psychological characteristics, eating behavior, and quality of life assessment of obese patients undergoing weight loss interventions.

BACKGROUND AND AIMS: Bariatric surgery is the most effective treatment for obesity. However, not all patients have similar weight loss following surgery and many researchers have attributed this to different pre-operative psychological, eating behavior, or quality-of-life factors. The aim of this study was to determine whether there are any differences in these factors between patients electing to have bariatric surgery compared to less invasive non-surgical weight loss treatments, between patients choosing a particular bariatric surgery procedure, and to identify whether these factors predict weight loss after bariatric surgery. MATERIAL AND METHODS: This was a prospective study of 90 patients undergoing gastric bypass, vertical sleeve gastrectomy, or adjustable gastric banding and 36 patients undergoing pharmacotherapy or lifestyle interventions. All patients completed seven multi-factorial psychological, eating behavior, and quality-of-life questionnaires prior to choosing their weight loss treatment. Questionnaire scores, baseline body mass index, and percent weight loss at 1 year after surgical interventions were recorded. RESULTS AND CONCLUSIONS: Surgical patients were younger, had a higher body mass index, and obesity had a higher impact on their quality of life than on non-surgical patients, but they did not differ in the majority of eating behavior and psychological parameters studied. Patients opting for adjustable gastric banding surgery were more anxious, depressed, and had more problems with energy levels than those choosing vertical sleeve gastrectomy, and more work problems compared to those undergoing gastric bypass. Weight loss after bariatric surgery was predicted by pre-operative scores of dietary restraint, disinhibition, and pre-surgery energy levels. The results of this study generate a number of hypotheses that can be explored in future studies and accelerate the development of personalized weight loss treatments.

Modifying an immunogenic epitope on a therapeutic protein: a step towards an improved system for antibody-directed enzyme prodrug therapy (ADEPT).

Carboxypeptidase G2 (CP) is a bacterial enzyme, which is targeted to tumours by an antitumour antibody for local prodrug activation in antibody-directed enzyme prodrug therapy (ADEPT). Repeated cycles of ADEPT are desirable but are hampered by human antibody response to CP (HACA). To address this, we aimed to identify and modify clinically important immunogenic sites on MFECP, a recombinant fusion protein of CP with MFE-23, a single chain Fv (scFv) antibody. A discontinuous conformational epitope at the C-terminus of the CP previously identified by the CM79 scFv antibody (CM79-identified epitope) was chosen for study. Modification of MFECP was achieved by mutations of the CM79-identified epitope or by addition of a hexahistidine tag (His-tag) to the C-terminus of MFECP, which forms part of the epitope. Murine immunisation experiments with modified MFECP showed no significant antibody response to the CM79-identified epitope compared to A5CP, an unmodified version of CP chemically conjugated to an F(ab)(2) antibody. Success of modification was also demonstrated in humans because patients treated with His-tagged MFECP had a significantly reduced antibody response to the CM79-identified epitope, compared to patients given A5CP. Moreover, the polyclonal antibody response to CP was delayed in both mice and patients given modified MFECP. This increases the prospect of repeated treatment with ADEPT for effective cancer treatment.