Diabetes Treatments

people with diabetes by approximately 1 year. diabetes now had a treatment for their condition. longest, largest diabetes study ever undertaken, …

PRELIMINARY COMMUNICATION

Adjustable Gastric Banding and Conventional Therapy for Type 2 Diabetes
A Randomized Controlled Trial
John B Dixon, MBBS, PhD Paul E OBrien, MD Julie Playfair, RN Leon Chapman, MBBS Linda M Schachter, MBBS, PhD Stewart Skinner, MBBS, PhD Joseph Proietto, MBBS, PhD Michael Bailey, PhD, MScstats Margaret Anderson, BHealthMan loss achieved using bariatric surgery has never been formally investigated as a treatment for type 2 diabetes in obese participants Several observational studies suggest substantial benefit, but these have generally been restricted to severely obese participants; to our knowledge, there have been no published randomized controlled trials Obesity and type 2 diabetes are likely to be the 2 greatest public health problems of the coming decades1 The conditions are strongly linked, with the increased prevalence of diabetes correlating with the increased prevalence of obesity2 The adjusted relative risk of developing type 2 diabetes in participants with a body mass index BMI greater than 35 calculated as weight in kilograms divided by height in meters squared is 93 95 confidence interval [CI], 81-107 for women3 and 42 95 CI, 22-81 for men,4
compared
For editorial comment see p 341 Context Observational studies suggest that surgically induced loss of weight may be effective therapy for type 2 diabetes Objective To determine if surgically induced weight loss results in better glycemic control and less need for diabetes medications than conventional approaches to weight loss and diabetes control Design, Setting, and Participants Unblinded randomized controlled trial conducted from December 2002 through December 2006 at the University Obesity Research Center in Australia, with general community recruitment to established treatment programs Participants were 60 obese patients BMI 30 and 40 with recently diagnosed 2 years type 2 diabetes Interventions Conventional diabetes therapy with a focus on weight loss by lifestyle change vs laparoscopic adjustable gastric banding with conventional diabetes care Main Outcome Measures Remission of type 2 diabetes fasting glucose level 126 mg/dL [70 mmol/L] and glycated hemoglobin [HbA1c] value 62 while taking no glycemic therapy Secondary measures included weight and components of the metabolic syndrome Analysis was by intention-to-treat Results Of the 60 patients enrolled, 55 92
completed the 2-year follow-up Remission of type 2 diabetes was achieved by 22 73 in the surgical group and 4 13 in the conventional-therapy group Relative risk of remission for the surgical group was 55 95 confidence interval, 22-140 Surgical and conventional-therapy groups lost a mean SD of 207 86 and 17 52 of weight, respectively, at 2 years P 001 Remission of type 2 diabetes was related to weight loss R2 046, P 001 and lower baseline HbA1c levels combined R2 052, P 001 There were no serious complications in either group Conclusions Participants randomized to surgical therapy were more likely to achieve remission of type 2 diabetes through greater weight loss These results need to be confirmed in a larger, more diverse population and have long-term efficacy assessed Trial Registration actrorg Identifier: ACTRN012605000159651
JAMA 2008;2993:316-323 wwwjamacom Author Affiliations: Centre for Obesity Research and Education Drs Dixon, OBrien, Chapman, Schachter, and Skinner and Mss Playfair and Anderson and Department of Epidemiology and Preventive Medicine Dr Bailey, Monash University, Melbourne, Australia; and Department of Medicine AH/NH, University of Melbourne, Melbourne Dr
Proietto Corresponding Author: John B Dixon, MBBS, PhD, FRACGP, Centre for Obesity Research and Education, Monash University Medical School, The Alfred Hospital, Melbourne, Victoria, 3004, Australia john dixon@medmonasheduau

S

IGNIFICANT SUSTAINED WEIGHT

with participants with a BMI less than 22 and less than 23, respectively Approximately half of those diagnosed with type 2 diabetes are obese5 Early and intensive treatment of type 2 diabetes is known to improve health outcomes and quality of life6-9 Weight control comprises perhaps the most im-

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ADJUSTABLE GASTRIC BANDING AND CONVENTIONAL THERAPY FOR TYPE 2 DIABETES

portant aspect of type 2 diabetes management, with weight loss reducing morbidity and mortality10 Recent evidence indicates that improvement in blood glucose control is related to degree of weight loss11 Unfortunately, currently available lifestyle and pharmacological strategies provide only small to modest levels of weight loss, a problem compounded by patients with diabetes experiencing
greater difficulty in losing weight than those without diabetes12-14 The costs associated with medical weight loss therapies for obese patients with type 2 diabetes are high and ongoing15 Despite observational evidence suggesting that weight-loss surgery is associated with a 60 to 80 diabetes remission rate in severely obese persons and that earlier interventions are more likely to provide remission,16 bariatric procedures fail to generate significant attention in diabetes guidelines17 Concerns exist regarding the lack of randomized controlled evidence, as well as the safety, invasiveness, and cost-effectiveness of surgical weight loss procedures Providing appropriate evidence has previously proved problematic, because the invasive nature of the surgery makes participant recruitment difficult However, with the advent of safer, less invasive surgical weight-loss procedures, randomized controlled trials are now feasible, and studies examining mild to moderate obesity, which is responsible for much of the diabetes burden, are possible Multiple case series have demonstrated that laparoscopic adjustable gastric banding LAGB results in significant weight loss,18-20 with mediumterm weight
loss of approximately 20 of body weight21; perioperative mortality is approximately 005 for LAGB21 Using the LAGB intervention, we conducted a 2-year randomized controlled trial involving 60 obese participants BMI 30 and 40 to compare surgically induced weight loss with conventional therapy for the management of recently diagnosed type 2 diabetes 2 years

STUDY DESIGN
Patient Recruitment

Patients were recruited via newspaper advertisement and were not paid to participate, nor did they pay any medical costs The study was reviewed and approved by the human ethics committees of The Alfred Hospital, The Avenue Hospital, and Monash University in accordance with the guidelines of the National Health and Medical Research Council and the Helsinki Declaration, as revised in 2000 Recruitment commenced in December 2002, the last participant was randomized in November 2004, and all data were available for analysis in December 2006 All participants provided written informed consent to participate in the study Additional written informed consent was obtained prior to any surgical procedure
Inclusion Criteria

changes required to maximize current management A run-in period of at least 3 months
was undertaken in which further alterations to eating, exercise, glucose self-monitoring, and medications were suggested During this time, study compliance was assessed using attendance at appointments and completion of questionnaires The endocrinologist independently determined when a patient was ready for randomization Baseline weight, blood pressure, anthropometric measures, and biochemical data levels of fasting plasma glucose, glycated hemoglobin [HbA1c], C-peptide, and serum insulin, and a lipid profile were measured immediately prior to randomization
Randomization Process

Patients were eligible if they were aged between 20 and 60 years, had a body mass index of 30 to 40, had been diagnosed with clearly documented type 2 diabetes within the previous 2 years, had no evidence of renal impairment or diabetic retinopathy, and were able to understand and comply with the study process
Exclusion Criteria

Randomization was computer derived, with blocking into 3 groups to allow for orderly recruitment into both study groups and to reduce the risk of uneven recruitment late in the series The study was not blinded
Treatment Groups

Candidates were excluded if they had a history of
type 1 diabetes, diabetes secondary to a specific disease, or previous bariatric surgery; a history of medical problems such as mental impairment, drug or alcohol addiction, recent major vascular event, internal malignancy, or portal hypertension; or a contraindication for either study group Participants were excluded if they did not attend 2 initial information visits
Assessment and Run-in Period

In addition to any assessments required for inclusion, each potential participant was assessed by a dietitian, a general physician, and a consultant endocrinologist specializing in diabetes LC to suggest any

Conventional-Therapy Program This program delivered best available medical practice for the treatment, education, and follow-up of patients with type 2 diabetes Patients had open access to a general physician, dietitian, nurse, and diabetes educator and had visits with at least 1 team member every 6 weeks throughout the 2 years Medical therapies, including pharmaceutical agents, were determined by an experienced diabetologist on an individual basis Lifestyle modification programs were individually structured to reduce energy intake, to reduce intake of fat 30 and saturated fats,
and to encourage intake of low glycemic index and high-fiber foods Physical activity advice encouraged 10 000 steps per day and 200 minutes per week of structured activity, including moderateintensity aerobic activity and resistance exercise Lifestyle was the primary approach to weight loss, but very low317

2008 American Medical Association All rights reserved

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ADJUSTABLE GASTRIC BANDING AND CONVENTIONAL THERAPY FOR TYPE 2 DIABETES Primary and Secondary Outcomes

Figure 1 Participant Recruitment, Assessment, and Participation Throughout the Study
158 Individuals assessed for eligibility by telephone 25 Excluded after a brief explanation of the study 133 Underwent clinical assessment 73 Excluded after clinical assessment 10 BMI too high 1 BMI too low 7 Medical exclusions 3 Surgical exclusions 4 Diabetes diagnosed 2 years before presentation 18 No diabetes 1 Outside age range 14 Did not return for second clinical interview 12 Refused randomization 3 Geographical distance precluded involvement 60 Randomized 30 Randomized to receive surgical treatment 1 Withdrew
preoperatively 30 Randomized to receive conventional treatment 4 Withdrew 3 Withdrew within first month after randomization 1 Withdrew 4 months after randomization 26 Completed the study 30 Included in analysis

29 Completed the study 30 Included in analysis

BMI indicates body mass index

calorie diets and medications were discussed with all patients and used after consultation with the dietitian or general physician if the patient expressed a desire to use additional measures Surgical Program In addition to all aspects of the conventional-therapy program, the surgical group underwent placement of a laparoscopic adjustable gastric band via the pars flaccida technique by 1 of 2 experienced surgeons within 1 month of randomization22 Progress was reviewed by the bariatric surgical team every 4 to 6 weeks throughout the study, and adjustments to band volume were made using standard clinical criteria23

The primary end points of the study related to glycemic control at 2 years after randomization These were assessed as the proportion of participants achieving remission exceptional glycemic control of type 2 diabetes, defined as fasting plasma glucose levels less than 126 mg/dL to
convert to mmol/L, multiply by 00555 in addition to HbA1c values less than 62 without the use of oral hypoglycemics or insulin The use of metformin posed a dilemma, because it may be recommended in the remitted diabetic state Our protocol recommended cessation of metformin, if prescribed, when the fasting insulin concentration was normal 170 uIU/mL [to convert to pmol/L, multiply by 6945] and the HbA1c value was less than 62 with a normal fasting plasma glucose level less than 1080 mg/dL Secondary outcome measures included percentage change in HbA1C levels, weight, blood pressure, waist circumference, and levels of fasting lipids, including total cholesterol, triglycerides, and high-density lipoprotein cholesterol Changes in medication use, changes in the proportion of participants with the metabolic syndrome as defined by the National Cholesterol Education Program Adult Treatment Panel III criteria,24 and changes in indirect measures of insulin resistance using the homeostatic model assessment method were assessed Adverse events and effects were recorded
Statistical Analysis

Data Analysis Univariate statistical analysis was performed using SPSS version 1201 SPSS Inc, Chicago,
Illinois, with baseline comparisons made using 2 tests for equal proportion, t tests for normally distributed outcomes, or Mann-Whitney U tests otherwise Multivariate longitudinal analysis was performed to assess weight and biochemical changes with time using the PROC Mixed procedure in SAS version 82 SAS Institute Inc, Cary, North Carolina All data were analyzed using a true intention-to-treat analysis for all 60 patients Continuous variables were expressed as mean standard deviation, with differences expressed as mean 95 CI Binary logistic regression was used to examine the associates of diabetes remission A 2-sided P value of 05 was considered statistically significant RESULTS
Study Participants

Sample Size Sample size was selected to provide a statistical power of 80 to detect a 1 difference in HbA1c values between the groups at 2 years group mean, 65 vs 75 [SD, 13] P 0525 The study was also powered for diabetes remission rates on the basis that we expected approximately 60 remission in the surgical group and 20 in the conventional-therapy group25 To allow for these scenarios, a minimum of 27 patients were required in each study group Recruitment size was therefore set at
60

The flow of participants through the study is shown in FIGURE 1 One patient randomized to surgery withdrew from the study on the evening prior to scheduled operation and did not agree to be further followed up The remaining 29 surgically treated patients 97 completed the 2-year program Of the conventionally treated patients, 26 87 completed the 2-year assessment The baseline characteristics of the groups are shown in TABLE 1 There were no statistically significant differences in demographics or values contributing to study outcomes between the groups There were only 13 participants with a baseline BMI less than 35–6 randomized to surgery and 7 to the conventional-therapy group The mean BMI of those recruited to the study was 371 All bands were placed laparoscopically, with a mean procedure time of 54 minutes SD, 108; range, 40-74, and hospital admissions lengths were 1 day 23 [80], 2 days 5 [17], and 4 days 1 [3] The patient who stayed 4 days had the band removed on day 15 due to band intolerance This patient underwent

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follow-up for 2 years, in accordance with the intention-to-treat analysis Sixteen of the 26 completers in the conventional-therapy group elected to use a very low-calorie diet n 11 or sibutramine n 7 at some stage during the 2 years None elected to use orlistat
Diabetes Remission

Table 1 Baseline Characteristics of Participants a
Characteristic Age, mean SD, y Men, No Hypertension, No Metabolic syndrome, No Coronary artery disease, No BMI, mean SD b Weight, mean SD, kg Waist circumference, mean SD, cm Waist to hip ratio, mean SD Neck circumference, mean SD, cm Blood pressure, mean SD, mm Hg Systolic Diastolic HbA1c, mean SD, Plasma glucose, mean SD, mg/dL Plasma insulin, median IQR, IU/mL Lipids, mean SD, mg/dL Total cholesterol Triglycerides HDL-C Total cholesterol to HDL-C ratio Surgery n 30 466 74 15 50 28 93 29 97 0 370 27 1056 138 1141 102 096 009 418 40 1364 156 866 94 78 12 1567 385 197 165-275 2018 327 1906 1066 471 101 441 087 Conventional Therapy n 30 471 87 13 43 27 90 29 97 1 3 372 25 1059 142 1160 100 096 010 424 45 1353 144 845 98 76 14 1580 487 187 137-307 1982 567
1887 1118 481 111 423 111

Remission of type 2 diabetes was achieved by 26 study participants 43 at 2 years 22/30 [73] randomized to the surgical program and 4/30 [13] to the conventionaltherapy program P 001 This represented 76 and 15 remission rates among completers in the surgery and conventional-therapy groups, respectively A most conservative analysis using the assumption that all 4 noncompleters in the conventionaltherapy group achieved remission and that the only noncompleter in the surgical group did not indicates significantly greater remission in the surgically treated group 22/30 [73] for surgery vs 8/30 [27] for conventional therapy, P 001 Greater percentage of weight loss at 2 years and lower baseline HbA1c values were independently associated with remission Cox-Snell R2 050, P 001, but percentage of weight loss alone explained most of the variance Cox-Snell R2 046, P 001 The patients sex, age, baseline BMI, C-peptide level, time spent engaged in planned physical activity, and the group to which they were randomized were not predictive of remission after controlling for percentage of weight loss FIGURE 2 shows individual percentage weight loss as well as baseline and
2-year measures of weight for patients randomized to each group Only 4 of 34 patients 12 who lost less than 10 of body weight were in remission at 2 years Figure 2 This group was characterized by significantly lower baseline HbA1c levels when compared with others who lost 10 or more All were below 69, with the median 645, compared with me-

Abbreviations: BMI, body mass index; HbA1c, glycated hemoglobin; HDL-C, high-density lipoprotein cholesterol; IQR, interquartile range SI conversion factors: To convert glucose values to mmol/L, multiply by 00555; insulin to pmol/L, by 6945; total cholesterol and HDL-C to mmol/L, by 00259; and triglycerides to mmol/L, by 00113 a There were no statistically significant differences between the groups b Calculated as weight in kilograms divided by height in meters squared

dian 76 for the remaining 30 P02 by Mann-Whitney U test Only 4 of 26 15 losing more than 10 body weight did not achieve remission There were no significant baseline predictors of this small group
Weight Loss

Physical Activity

The surgical group achieved a mean 200 SD, 94 body weight loss at 2 years, compared with 14 SD, 49 among the conventional-therapy group P 001 Figure 2
This represents a loss of 625 of excess weight using BMI of 25 as ideal weight in the surgical group compared with 43 in the conventional-therapy group and a reduction of BMI from 369 to 295 compared with a reduction from 371 to 366 Individual and grouped mean SD weight changes for both groups are shown in Figure 2 The surgical group had a greater weight loss P 001, and the difference between the groups increased with time P 001

There was a positive correlation between average times participants reported performing planned physical activity each week throughout the study and weight loss Spearman r 039, P003 Participants n29 who reported more than 3 periods of physical activity of greater than 30 minutes per week median reported had better mean weight loss 139 [SD, 109] kg compared with 78 [SD, 123] kg, P046 and a higher likelihood of diabetes remission odds ratio, 34; 95 CI, 12101; P02 However, reported physical activity was not an independent predictor of diabetes remission
Glycemic Control

Mean levels of HbA 1 c and fasting plasma glucose were significantly lower in the surgical group at 2 years P 001 for both At baseline there were 2 7 surgically treated and 4 13
conventionally treated participants with HbA 1c levels less than
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Figure 2 Percentage of Weight Loss Achieved Over the 2-Year Study Period n 60 and Individual Weight Measures at Baseline and at 2 Years
Surgical group Achieved remission of type 2 diabetes Did not achieve remission of type 2 diabetes Percent Weight Change 10 0 160 140 120 Conventional group Achieved remission of type 2 diabetes Did not achieve remission of type 2 diabetes Change in Weight

Weight Change

cant P 005 reduction in use of antihypertensive agents in the surgical group 20/29 at baseline and 6/29 at 2 years, P 001 compared with the conventional-therapy group 15/26 at baseline and at 2 years There also was a reduction in the use of lipidlowering medications in the surgical group 12/29 at baseline and 4/29 at 2 years, P02 but no significant change in the conventional-therapy group 8/26 at baseline and 7/26 at 2 years
Adverse Events

10 20 30 40 50 Surgical Group
Conventional Group

Weight, kg

100 80 60 40 Baseline 2 Years Baseline 2 Years

Surgical Group

Conventional Group

Remission indicates those achieving remission of type 2 diabetes see Methods at 2 years Data markers with error bars indicate mean SD

62; at 2 years, the numbers were 24 80 and 6 20, respectively The proportion with HbA1c levels less than 62 improved significantly P 001 in the surgical group but not in the conventional-therapy group
Use of Diabetes Medication

Other Health Outcomes

There was a significant reduction in the use of pharmacotherapy for glycemic control in the surgical group at 2 years At baseline, 2 surgically treated and 4 conventionally treated patients were not using pharmacotherapy; at 2 years, the numbers were 26 and 8, respectively In the surgical group at 2 years there were fewer using metformin 3 vs 28, P 001 and other hypoglycemic therapy 1 vs 9, P 006 The 1 surgical patient using insulin at baseline was in remission at 2 years There were no significant changes in the use of therapy in the group randomized to receive conventional therapy Metformin was used by 26 and 18, other oral hypoglycemic agents by 8 and 7, and insulin by 0 and 3, at
baseline and 2 years, respectively

TABLE 2 shows changes in some clinical and laboratory measures of health at 24 months The surgical group had a significantly greater improvement at 2 years in insulin resistance and in levels of triglycerides and high-density lipoprotein cholesterol The metabolic syndrome was present in 29 patients 97 in each group prior to commencement of treatment, and 21 70 of surgically treated and 4 13 conventionally treated participants did not fulfill the National Cholesterol Education Program Adult Treatment Panel III criteria at 2 years P 001 The reduction in the metabolic syndrome was significant in the surgical group P 001 but not in the conventionaltherapy group P 23 Caution is required in interpreting these results, as the study was not powered to assess multiple outcome measures
Use of Nondiabetes Medication

Surgical Group One patient developed a superficial wound infection over the access port site 2 weeks postplacement, which resolved with intravenous antibiotics Two patients developed gastric pouch enlargement, both at 10 months after placement, and were treated with nonurgent laparoscopic revisional surgery to remove and replace the band One
patient experienced eating difficulties and persistent regurgitation with no saline in the band and no impedance of flow on contrast study The band was removed 15 days after placement Hospital stay for each revisional procedure was less than 1 day, and there were no complications Other adverse events reported were postoperative febrile episodes in 1 patient No cause was found, and the fever resolved A minor hypoglycemic episode occurred in 1 patient and gastrointestinal tract intolerance to metformin in another Conventional-Therapy Group Two patients had minor gastrointestinal tract adverse effects, and 1 had persistent diarrhea with metformin One patient developed vasculitic rash, possibly related to rosiglitazone All problems resolved when the medications were discontinued One patient had multiple hypoglycemic episodes, and another was admitted to hospital with angina and a transient cerebral ischemic episode Two patients were intolerant of very low-calorie meal replacement COMMENT This study, to our knowledge the first randomized trial comparing surgically induced loss of weight with con-

Although there was no significant blood pressure difference between completers in the
surgical and conventionaltherapy groups, there was a signifi-

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ventional therapy for management of type 2 diabetes in obese participants, demonstrates superior glycemic control and diabetes remission rates with adjustable gastric banding After 2 years, the surgical group displayed a 5 times higher remission rate and 4 times greater reduction in HbA1c values than the conventional-therapy group This study confirms the findings of several observational studies,25,27-30 including the case-controlled Swedish Obese Subjects Study,31 that found heightened diabetes remission rates among 2000 patients undergoing gastric stapling with follow-up for 10 years In addition to superior glycemic control, this study also demonstrates higher rates of resolution of the metabolic syndrome, confirming the finding of an earlier randomized controlled trial,32 as well as improvements in insulin sensitivity and concentrations of triglycerides and high-density
lipoprotein cholesterol in the surgical group These changes in secondary outcome measures need to be examined with caution and are hypothesis-generating only, as the study was not powered for an examination of multiple secondary outcome measures There also appeared to be significant reductions in the use of oral hypoglycemic, antihypertensive, and lipid-lowering medications in patients randomized to surgery Although the physician responsible for altering medications was not blinded to treatment group, blood pressure and biochemical data indicate that decisionmaking was determined by clinical need An important finding of this study is that degree of weight loss, not the method, appears to be the major driver of glycemic improvement and diabetes remission in obese participants This has important implications, as it suggests that intensive weight-loss therapy may be a more effective first step in the management of diabetes than simple lifestyle change This study shows that few participants achieved remission with a body weight loss of less than 10, a level expected to produce important health benefits33

The aim of this current trial was to compare 2 established treatment programs
that involve widely available and accepted therapies The use of bariatric surgery is rapidly increasing, and more than 90 of procedures performed in Australia are LAGB At the time this study was carried out, early intensive use of insulin was unusual practice in Australia, and access to thiozoladinedione medications was restricted for patients with poor glycemic control The hypo-

glycemic agent exenatide was also unavailable The results achieved by the surgical group in this study closely resemble those now being targeted by experimental intensive medical therapies using multiple hypoglycemic strategies, including exenatide and early insulin use34 It is worth noting that the results achieved by weight-loss surgery come without the risks of hypoglycemia and weight gain often associated with medical therapies

Table 2 Primary and Secondary Outcomes at 2 Years a
Mean SD Variable Remission of diabetes, No Surgery Conventional n 30 Therapy n 30 Primary Outcome, No 22 73 4 13 Between-Group Difference, Mean 95 CI RR for surgical remission, 55 22 to 140 P Value 001

Weight, kg Change, kg Waist circumference, cm Change, cm Waist to hip ratio Change Blood pressure, mm Hg Systolic Change
Diastolic Change HbA1c, Change Plasma glucose, mg/dL Change Plasma insulin, IU/mL Change HOMA IR b Change, Total cholesterol, mg/dL Change Triglycerides, mg/dL Change HDL-C, mg/dL Change Total cholesterol to HDL-C ratio Change

Secondary Outcomes 846 158 1048 153 -211 105 -15 54 958 103 1127 103 -179 108 -40 91 090 006 095 008 -006 006 -001 006 1304 190 -60 179 854 70 -07 111 600 082 -181 124 1056 303 -512 376 98 47 -124 84 190 073 -455 190 2054 466 36 516 1189 797 -717 929 597 136 126 98 358 100 -082 19 1326 177 -17 142 831 85 -09 111 721 139 -038 126 1396 381 -184 412 241 136 10 148 350 097 -33 354 1978 593 -04 314 1867 1272 -21 1206 507 121 26 61 41 14 -014 104

-196 -238 to -152 -139 -190 to -87 -005 -007 to -0007

001 001 02

-43 -136 to 51 02 -54 to 60 -143 -21 to -080 -328 -531 to -123 -134 -196 to -73 -422 -57 to -268 c 40 -188 to 260 -696 -1253 to -136 100 58 to 142

37 92 001 002 001 001 72 02 001

-068 -124 to -014

02

Abbreviations: CI, confidence interval; HbA1c, glycated hemoglobin; HDL-C, high-density lipoprotein cholesterol; HOMA IR, insulin resistance by homeostatic model assessment; LDL-C, low-density lipoprotein cholesterol; RR, relative risk SI conversion
factors: see Table 1 footnote a Mean SD percentage change for participants with baseline values carried forward for those who dropped out of the study A comparison of the actual change from baseline is also presented Data include all 60 participants with baseline data carried forward for missing data b An indirect measure of insulin resistance calculated from levels of fasting plasma glucose and fasting C-peptide26 cP 05 calculated using independent t test

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Importantly, this study is the first, to our knowledge, to formally document change in glycemic control in patients with diabetes and BMI of 30 to 35 following surgically induced weight loss Bariatric surgical guidelines include only BMI greater than 35 with comorbid type 2 diabetes as an indication for weight loss surgery35,36 In this study we found the benefits of weight loss as efficacious for participants with BMI in the 30 to 35 range as for those with BMI in the 35 to 40 range;
however, analysis and conclusions are limited, as there were only 13 participants 22 in this BMI category Our study did not include participants with a BMI greater that 40 We believed it inappropriate to recruit those with a BMI greater than 40 into the study, because a number of observational studies have shown effectiveness of bariatric surgery in these patients The adverse events observed in this trial were in line with expectations Among patients undergoing LAGB surgery, rates of postoperative wound infection around the port were approximately 1 to 2, and reoperation rates for gastric pouch enlargement were approximately 5 Several limitations of our study need to be recognized First, we restricted the study to participants with a recent diagnosis 2 years of type 2 diabetes, and therefore results may not apply to those with a longer history of disease due to deterioration of -cell function with time Second, the experience of our bariatric surgical team with the LAGB procedure is extensive Systematic review shows inverse correlation between the experience of the LAGB surgical team and incidence of early and late complications21 Third, our study was not powered for safety or to
detect differences in hard end points, such as mortality or cardiovascular events Such studies would require many more participants followed up over a much longer period Our study only followed up participants for 2 years, and results cannot be readily extrapolated for longer periods Clearly, weight re-

gain or simply the passage of time puts those achieving remission of type 2 diabetes at risk of relapsing back into diabetic status One patient from the surgical group and 4 from the conventional-therapy group did not complete the 2-year follow-up To account for this missing information, the most conservative case scenario was considered, with the 4 noncompleters from the conventionaltherapy group assumed to have achieved diabetic remission and the noncompleter from the surgical group assumed to have not achieved remission Under this scenario, the difference between the surgical and the conventional-therapy groups for those achieving remission still remained highly significant 22/30 [73] for surgery vs 8/30 [27] for conventional therapy, P 001 In conclusion, this randomized trial demonstrates that weight loss associated with adjustable gastric banding results in diabetes remission
in the majority of obese participants recently diagnosed as having diabetes and was associated with greater improvements in features of the metabolic syndrome and use of related medications While caution is required in interpreting the longer-term benefits of surgery and weight loss, this study presents strong evidence to support the early consideration of surgically induced loss of weight in the treatment of obese patients with type 2 diabetes
Author Contributions: Drs Dixon and Bailey and Ms Anderson had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis Study concept and design: Dixon, OBrien, Schachter, Proietto Acquisition of data: Dixon, OBrien, Playfair, Chapman, Schachter, Skinner, Anderson Analysis and interpretation of data: Dixon, OBrien, Playfair, Bailey, Anderson Drafting of the manuscript: Dixon, OBrien Critical revision of the manuscript for important intellectual content: Dixon, OBrien, Playfair, Chapman, Schachter, Skinner, Proietto, Bailey, Anderson Statistical analysis: Dixon, Bailey, Anderson Obtained funding: Dixon, OBrien Administrative, technical, or material support: Dixon,
OBrien, Playfair, Schachter, Skinner, Proietto, Anderson Study supervision: Dixon, OBrien, Schachter, Anderson Financial Disclosures: Dr Dixon reported having received research grants from the National Health and

Medical Research Council, Allergan Health, and Novartis Australia; having received compensation for serving on the speakers panel of Novartis Australia and Allergan Health; and serving on the medical advisory board of Novartis Australia and Allergan Health Dr OBrien reported receiving research grants from the National Health and Medical Research Council, Allergan Health, and Novartis Australia; having received compensation for serving on the speakers panel of Allergan Health; and serving on the medical advisory board of Allergan Health Dr Chapman reported receiving travel grants and honoraria from Eli Lilly, Novo Nordisc, Sanofi Aventis, and Alphapharm Dr Proietto reported serving on the medical advisory boards of Novartis Australia, Eli Lilly Australia, Abbott Australia, and Sanofi-Aventis Australia No other disclosures were reported Funding/Support: This study was funded by Monash University, which has received an unrestricted grant from Allergan Health The laparoscopic
adjustable gastric bands Allergan Health and the laparoscopic ports Applied Medical were provided without charge by the manufacturers Role of the Sponsors: Allergan Health and Applied Medical had no role in the design and conduct of the study; the collection, analysis, and interpretation of the data; or the preparation, review, or approval of the manuscript

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GA, Hartley GG, Ves-

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ADJUSTABLE GASTRIC BANDING AND CONVENTIONAL THERAPY FOR TYPE 2 DIABETES
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[The medical career] is one in which it is possible for people–men or women–to pursue the dying ideal that an occupation for adults should allow of intellectual freedom, should give character as much chance as cleverness, and should be subject to the tonic and difficulty and the spice of danger
–Wilfred Trotter 1872-1939

2008 American Medical Association All rights reserved

Reprinted JAMA, January 23, 2008–Vol 299, No 3

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