Diet and Medical Therapy Versus Bariatric Surgery in Type 2 Diabetes (DIBASY)
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|ClinicalTrials.gov Identifier: NCT00888836|
Recruitment Status : Completed
First Posted : April 28, 2009
Last Update Posted : July 29, 2014
|First Submitted Date ICMJE||April 27, 2009|
|First Posted Date ICMJE||April 28, 2009|
|Last Update Posted Date||July 29, 2014|
|Study Start Date ICMJE||April 2009|
|Actual Primary Completion Date||October 2011 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||To assess the efficacy of bariatric surgery in inducing partial or total remission of type 2 diabetes mellitus, as compared to standard medical anti-diabetic care (STC). [ Time Frame: 5 years ]|
|Original Primary Outcome Measures ICMJE
||To assess the efficacy of bariatric surgery in inducing partial or total remission of type 2 diabetes mellitus, as compared to standard medical anti-diabetic care (STC). [ Time Frame: 2 years ]|
|Change History||Complete list of historical versions of study NCT00888836 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
||Secondary endpoints include percentage change of fasting plasma glucose levels, glycated hemoglobin, weight, waist circumference, blood pressure, cholesterol, HDL-cholesterol and triglycerides, hard cardiovascular risk and quality of life. [ Time Frame: 5 years ]
We aim at measuring in the long term (5 years after enrollment) by the glycemic holter the degree of glucose control in the patients belonging to the 3 arms of our randomized, controlled study comparing conventional medical therapy with bilio-pancreatic diversion and Roux-en-Y gastric bypass. To this end, the patients will wear the glycemic holter over 24-48 hours and the results recorded. The patients are already recording periodical 7 points glucose self monitoring.
Quality of life will be investigated at 5 years from enrollment by the RAND 36-Item Health Survey. It taps 8 health concepts: physical functioning, bodily pain, role of limitations deriving from physical health problems, limitations due to physical or emotional problems, emotional well being, social functioning, energy/fatigue, and general health perception. It also includes a single item that provides an indication of perceived change in health. The questionnaire will be administered by the physician.
|Original Secondary Outcome Measures ICMJE
||To compare the efficacy of GBP and BPD in diabetes control vs. STC To assess weight changes, and early or late morbidity To evaluate the effect of surgery on diabetes complications To assess changes of ß-cell function and insulin sensitivity [ Time Frame: 10 years ]|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Diet and Medical Therapy Versus Bariatric Surgery in Type 2 Diabetes|
|Official Title ICMJE||Prospective Randomized Controlled Trial on the Effect of Gastric Bypass and Biliopancreatic Diversion on Type 2 Diabetes Mellitus in Patients With BMI > 35 vs. Medical Therapy|
It is generally held that ß-cell function is irreversibly lost already at the time the disease manifests itself and thereafter continues to decline linearly with time. Several studies, however, have documented the possibility that ß-cell function may be restored, at least partially, in type 2 diabetes. Of major relevance to the issue of ß-cell recovery in diabetes are the following findings:
The principal aim of this study is to verify the effect on type 2 diabetes mellitus (T2DM) of GBP and BPD, the two operations which have shown specific actions on glucose homeostasis control, in type 2 diabetic patients with BMI > 35 kg/m2, and to compare this effect with matched T2DM control patients receiving the standard of medical care.
ß-cell dysfunction and insulin resistance are the main pathophysiological defects responsible for the development of hyperglycaemia . Both these defects predict incident diabetes in high-risk subjects . Insulin resistance per se is not sufficient to cause hyperglycaemia; mild degrees of ß-cell dysfunction, on the other hand, may not result in diabetic hyperglycaemia in insulin sensitive individuals. It is only when impaired ß-cell function occurs in the background of insulin resistance that plasma glucose levels begin to rise (as is the case of individuals with impaired glucose tolerance ). The occurrence of postprandial, or day-long, hyperglycaemia further compromises both ß-cell function and insulin action, a phenomenon called glucose toxicity [4-6]. As a consequence, the vast majority of patients with established type 2 diabetes present, in addition to marked insulin resistance, a clear defect in ß-cell function, which is generally proportional to the severity of the hyperglycaemia . Of note is that the extent of ß-cell dysfunction in type 2 patients may be misjudged when ß-cell function is inferred from simple measurements of fasting or postprandial plasma insulin concentrations. In fact, insulin secretion increases (in non-linear manner ) in insulin resistant individuals, a compensatory response aimed at maintaining glucose tolerance. As a consequence, the absolute insulin hypersecretion (particularly in the fasting state) commonly found in patients with IGT or diabetes masks the underlying defect in the ability of the ß-cell to cope with nutrient stimulation.
It is generally held that ß-cell function is irreversibly lost already at the time the disease manifests itself and thereafter continues to decline linearly with time. Several studies, however, have documented the possibility that ß-cell function may be restored, at least partially, in type 2 diabetes [9-13]. Of major relevance to the issue of ß-cell recovery in diabetes are the following findings: (a) bariatric surgery in morbidly obese patients with type 2 diabetes can restore euglycaemia, the acute insulin response to glucose [14-17] and insulin sensitivity [18,19]; (b) recent studies have reported that diabetic subjects return to euglycaemia and normal insulin levels within days after surgery, long before a significant weight loss has occurred ; and (c) whereas RYGB improves insulin sensitivity in proportion to weight loss, BPD improves insulin action out of proportion to weight loss, i.e., it normalises it at a time when patients are still markedly obese . Because RYGB is a predominantly restrictive procedure involving the foregut whereas BPD is a predominantly malabsorptive procedure involving the distal GI tract, these findings suggest that the control of both insulin action and ß-cell function is influenced by signals originating from the GI tract.
Some studies have investigated the hormonal changes that follow bariatric surgery. In most cases, however, clinical testing was performed after significant weight reduction, thereby making it difficult to establish whether any observed hormonal effect was the cause or the consequence of weight loss and diabetes resolution. Recently, it has been reported that RYGB induces rapid normalisation of blood glucose and insulin levels in concomitance with significant changes of the levels of hormones involved in the regulation of glucose metabolism (ACTH, leptin and GIP) in the early postoperative period . It has been proposed that the incretins could be one of the key mediators of the anti-diabetic effects of certain types of bariatric surgery. Previous data have shown that the significant weight loss observed after various bariatric procedures was accompanied by improvement of diabetes control and increased GLP-1 levels. However, most studies were cross sectional [23,24], reported fasting  rather than post-prandial GLP-1 levels, and compared various types of surgery such as jejuno-ileal bypass (JIB) [26,27] or bilio-pancreatic diversion (BPD) , often leading to inconclusive results. Data on fasting GIP levels after bariatric surgery are inconsistent, reporting either a decrease [25,28,29] or an increase [23,24]. GLP-1 levels increase after a meal in patients after RY-GBP  or with oral glucose after BPD . Meal-stimulated GIP levels have been reported to increase after JIB , or to decrease after GBP, JIB or BPD surgery [26,29,31,32]. None of these studies, however, measured GLP-1 and GIP simultaneously, reported the incretin levels and effect on insulin secretion (with the exception of the last quoted one, which reported both GIP and insulin response to meal markedly reduced after BPD), or was done in diabetic patients.
Some authors have suggested that an enhanced release of GLP-1, triggered by the earlier presentation of undigested food to lower segments of the bowel, might be involved in the glycaemic improvement consequent to bypass procedures for obesity surgery.
Collectively, these observations clearly suggest that there is a large margin for ß-cell recovery of function in type 2 diabetes and that different segments of the gut participate differentially in such recovery.
The primary end-points of the study are the differences in the proportions of patients reaching partial or complete remission of type 2 diabetes between conventional therapy and BPD or conventional therapy and RYGB.
In particular, according to Buse et al (Diabetes Care 2009; 32:2133-35) partial remission is defined as fasting glucose values of 100-125 mg/dl [5.6-6.9 mmol/l]) and HbA1c<6.5%, of at least 1 year's duration in the absence of active pharmacologic therapy. Complete remission is referred to fasting glucose <100 mg/dl [5.6 mmol/l]) and HbA1c in the normal range of at least 1 year's duration in the absence of active pharmacologic therapy.
Secondary endpoints Secondary endpoints include percentage change of fasting plasma glucose levels, glycated hemoglobin, weight, waist circumference, blood pressure, cholesterol, HDL-cholesterol and triglycerides, and hard cardiovascular risk.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 2
|Study Design ICMJE||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Condition ICMJE||Type 2 Diabetes|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Actual Enrollment ICMJE
|Original Estimated Enrollment ICMJE
|Actual Study Completion Date||November 2011|
|Actual Primary Completion Date||October 2011 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
|Ages||30 Years to 60 Years (Adult)|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||Italy|
|Removed Location Countries|
|NCT Number ICMJE||NCT00888836|
|Other Study ID Numbers ICMJE||UCSC-2009-1|
|Has Data Monitoring Committee||No|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||Not Provided|
|Responsible Party||Geltrude Mingrone, Catholic University of the Sacred Heart|
|Study Sponsor ICMJE||Catholic University of the Sacred Heart|
|Collaborators ICMJE||Not Provided|
|PRS Account||Catholic University of the Sacred Heart|
|Verification Date||July 2014|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP