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Analysis of factors associated with durable remission of diabetes after Roux-en-Y gastric bypass
Surgery for Obesity and Related Diseases 6 (2010) 254 –259
Original article
Analysis of factors associated with durable remission of diabetes after Roux-en-Y gastric bypass Silas M. Chikunguwo, M.D., Ph.D.*, Luke G. Wolfe, B.S., M.S., Patricia Dodson, M.S., Jill G. Meador, B.S.N., Nancy Baugh, B.S.N., John N. Clore, M.D., John M. Kellum, M.D., James W. Maher, M.D. Department Surgery, Virginia Commonwealth University Medical Center, Richmond, Virginia Received May 27, 2009; revised October 31, 2009; accepted November 3, 2009
Abstract
Background: Data on the durability of remission of type 2 diabetes mellitus (T2DM) after gastric bypass are limited. Our purpose was to identify the rate of long-term remission of T2DM and the factors associated with durable remission. Methods: A total of 177 patients with T2DM who had undergone Roux-en-Y gastric bypass from 1993 to 2003 had 5-year follow-up data available. T2DM status was determined by interview and evaluation of the diabetic medications. Patients with complete remission or recurrence of T2DM were identified. Results: Follow-up ranged from 5 to 16 years. Of the 177 patients, 157 (89%) had complete remission of T2DM with a decrease in their mean body mass index from baseline (50.2 ⫾ 8.2 kg/m2) to 31.3 ⫾ 7.2 kg/m2 postoperatively (mean percentage of excess weight loss 70.0% ⫾ 18.6%). However, 20 patients (11.3%) did not have T2DM remission despite a mean percentage of excess weight loss of 58.2% ⫾ 12.3% (P ⬍.0009). Of the 157 patients with initial remission of their T2DM, 68 (43%) subsequently developed T2DM recurrence. Remission of T2DM was durable in 56.9%. Durable (⬎5-year) resolution of T2DM was greatest in the patients who originally had either controlled their T2DM with diet (76%) or oral hypoglycemic agents (66%). The rate of T2DM remission was more likely to be durable in men (P ⫽ .00381). Weight regain was a statistically significant, but weak predictor, of T2DM recurrence. Conclusion: Early remission of T2DM occurred in 89% of patients after Roux-en-Y gastric bypass. T2DM recurred in 43.1%. Durable remission correlated most closely with an early disease stage at gastric bypass. (Surg Obes Relat Dis 2010;6:254 –259.) © 2010 American Society for Metabolic and Bariatric Surgery. All rights reserved.
Keywords:
Bariatric surgery; Diabetes mellitus; Roux-en-Y gastric bypass
A close interrelationship exists between obesity and type 2 diabetes mellitus (T2DM) [1]. Recent epidemiologic studies have shown that the prevalence of obesity has increased by ⬎75% since 1980, with ⬎34% of the U.S. adult population overweight (body mass index [BMI] 25–29.9 kg/m2) and another 30% classified as obese (BMI ⱖ30 kg/m2)
*Correspondence: Silas M. Chikunguwo, M.D., Ph.D., Department of Surgery, Virginia Commonwealth University Medical Center, 1200 East Broad Street, P.O. Box 980519, Richmond, VA 23298-0519. E-mail: [email protected]
[1,2]. T2DM is estimated to affect ⱖ8% of the adult population and 19% of the population ⬎65 years of age, with an estimated 800,000 new cases diagnosed annually [3]. Clinical studies have clearly established that obesity is a critical etiologic factor in the development of T2DM [4] and that weight loss has beneficial effects on T2DM and improves the metabolic pathophysiology that leads to hyperglycemia. Several clinical observational studies have shown that surgically induced weight loss is associated with significant improvement or remission of T2DM, but generally have been reserved for those with a BMI ⬎40 kg/m2 or a BMI
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S. M. Chikunguwo et al. / Surgery for Obesity and Related Diseases 6 (2010) 254 –259
⬎35 kg/m2 if co-morbidities are present [5–10]. Pories et al. [11,12] assessed the effects of gastric bypass in 165 patients with noninsulin-dependent T2DM and 165 others with impaired glucose tolerance. After a mean follow-up of 7.6 years, 83% of patients with T2DM no longer required pharmacologic treatment and 99% of those with impaired glucose tolerance were euglycemic. In another report, the same investigators compared 154 patients with T2DM who had undergone surgery with 78 who had not [12]. The percentage requiring oral medication or insulin increased from 56% to 88% in the control group but decreased from 32% to 9% in the treatment group. The Swedish Obese Subjects study followed up patients after gastric bypass surgery with respect to the effects on T2DM and reported that a mean weight loss of 28 kg at 2 years led to improved glycemic control in 118 patients with T2DM [13]. This weight loss led to withdrawal of oral hypoglycemic drugs or insulin for many patients. In contrast, the need for drugs increased in the 77 nonsurgically treated patients. The proportion treated by diet alone increased from 59% to 73% in the surgical group; however, in the nonsurgical group, it declined from 55% to 34%. Surgery resulted in a 30-fold reduction in the risk of progression from impaired glucose tolerance to diabetes in the study by Pories et al. [11,12]. The prevalence of T2DM was reduced 30-fold at 2 years and 5-fold at 8 years after surgery in the Swedish Obese Subjects study [14,15]. In a series of 2241 patients, biliopancreatic diversion resulted in a mean permanent reduction of 75% of the initial excess weight, with an operative mortality of .5% [16]. In that study, Scopinaro et al. [16,17] showed that biliopancreatic diversion achieved durable normalization of the plasma glucose, plasma insulin, and glycosylated hemoglobin in 80 –100% of severely obese patients with T2DM. Although the remission of T2DM after gastric bypass has been extensively documented, very limited data are available on the recurrence of T2DM. The main goal of our study was to determine the incidence of durable remission of T2DM after gastric bypass and the factors associated with T2DM recurrence. Understanding the clinical factors that influence both the remission and the recurrence of T2DM after bariatric surgery could potentially lead to better strategies to enhance durable remission. Methods Patient selection and data sources The Virginia Commonwealth University institutional review board approved the present study. We identified patients with T2DM who had undergone either open or laparoscopic Roux-en-Y gastric bypass (RYGB) from 1993 to 2003 by retrospective review of our prospectively collected bariatric database. All patients met the criteria from the 1991 National Institutes of Health Consensus Development Conference for Bariatric Surgery [18]. RYGB was per-
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formed by multiple faculty surgeons using multiple techniques during the study period. Open RYGB was initially done without dividing the stomach, and in laparoscopic RYGB, the stomach was divided in all cases. Short-limb RYGB was defined as that with an alimentary limb ⬍100 cm, and long-limb RYGB was defined as that with an alimentary limb of 100 –150 cm. No distal RYGB was done during the study period. We identified patients with T2DM as those who had T2DM listed preoperatively as a comorbidity in their medical record. The diagnosis of the preoperative T2DM status by the primary care physician was determined from the fasting blood glucose concentration according to the criteria established by the American Diabetes Association (ADA) [19 –21]. Patients with a positive history of T2DM who were taking diabetic medications before surgery were also classified as having T2DM. The patient data were collected prospectively, verified retrospectively, and then entered into the Virginia Commonwealth University Bariatric Surgery Clinical Database—a customized computer database. Other data sources included office charts, follow-up notes, hospital charts, and patient follow-up telephone interviews [22–24]. Outcome measures and change in T2DM status The parameters studied included patient demographics, BMI, weight loss, and changes in co-morbidities. The following data were extracted from the database: age, gender, pre- and postoperative weight, BMI, percentage of excess weight loss (%EWL), and type of RYGB (short-limb or long-limb). At the annual clinic visits, nutritional laboratory studies were obtained, and the resolution or persistence of co-morbidities was documented. Patients not participating in annual follow-up visits were telephoned and asked about their T2DM status and medication changes, if we were unable to persuade them to return for in-person follow-up examinations. The patient’s primary care physician was responsible for the preoperative selection of diabetic therapy, dose, and frequency and for reducing, discontinuing, or adding diabetic medications postoperatively. Weight loss or regain was expressed in terms of the %EWL and the change in BMI. T2DM remission was defined as no longer requiring any diabetic medication or dietary management at some point in the patient’s postoperative course. The durable remission of T2DM was defined as the absence of T2DM signs and symptoms and the absence of any dietary, oral hypoglycemic, or insulin therapy at the most recent follow-up visit or telephone interview. Statistical analysis All analyses were performed using Statistical Analysis Systems, version 9.13 (SAS Institute, Cary, NC). The data are presented as the mean and standard deviation. Continuous data were analyzed using Student’s t test or analysis of variance. Categorical data were compared using Fisher’s
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Table 1 Influence of weight regain on T2DM recurrence Variable
Total (n) BMI (kg/m2) Mean Range %EWL Mean Range
Patient status Preoperative T2DM
Postoperative T2DM remission
Postoperative T2DM without remission
Postoperative T2DM recurrence
Postoperative T2DM without recurrence
177
157 (88.7)
20 (11.3)
68 (43.3)
89 (56.7)
50.2 ⫾ 8.1 37.5–87.1 —
31.2 ⫾ 7.2 18.6–63.7
33.5 ⫾ 4.9 26.3–44.2
32.2 ⫾ 7.7 21.5–63.7
30.5 ⫾ 6.6 18.6–56.1
70.1 ⫾ 18.5 24.9–112.1
57.4 ⫾ 12.6 33.3–77.6*
66.4 ⫾ 17.8 24.9–106.5
73.0 ⫾ 18.5 27.6–112.1†
T2DM ⫽ type 2 diabetes mellitus; BMI ⫽ body mass index; %EWL ⫽ percentage of excess weight loss. Data in parentheses are percentages. * Significant compared with T2DM with remission. † Significant compared with T2DM recurrence.
exact test. P ⬍.05 was considered statistically significant. Multiple logistical regression analysis was used to identify independent predictors of T2DM remission. Results A total of 378 morbidly obese patients with T2DM who had undergone bariatric surgery during the same period were identified from our database. Of these 378 patients with T2DM, 177 (follow-up rate 46.8%), who had undergone open or laparoscopic RYGB from 1993 to 2003, were available for the present study (Table 1). Preoperative
T2DM management consisted of dietary management for 34 patients (21.7%), oral hypoglycemic drugs for 76 patients (48.4%), and insulin for 47 patients (29.9%). Of the 177 patients, 30 were men (17%) and 147 were women (83%). The length of postoperative follow-up was 5–16 years. The mean follow-up duration was 8.6 years. The T2DM status was determined by interview and evaluation of the T2DM treatment. Of the 177 patients, 157 (88.7%) had complete remission of their T2DM at some point in their postoperative course (Table 1 and Fig. 1). This was associated with a decrease in the mean BMI from 50.2 ⫾ 8.2 kg/m2 preoperatively to 31.3 ⫾ 7.2 kg/m2 at the postoperative nadir
Fig. 1. Rates of T2DM remission and recurrence after RYGB.
S. M. Chikunguwo et al. / Surgery for Obesity and Related Diseases 6 (2010) 254 –259
(mean %EWL 70% ⫾ 18.6%). Of the 177 patients, 20 (11.3%) did not achieve remission of their T2DM despite a decrease in their BMI to a mean of 33.2 ⫾ 4.9 kg/m2 (mean %EWL 58.2% ⫾ 12.3%; Table 1). The difference in the %EWL between those with T2DM remission and those without remission was significant (P ⬍.0009). Of the 157 patients with initial remission of their T2DM, 68 (43.3%) subsequently developed T2DM recurrence (Table 1). This correlated with a regain of lost weight (mean %EWL 66% ⫾ 17.8% at nadir and 49.1% ⫾ 27% at T2DM recurrence). Of the 157 patients with initial remission, 89 (56.7%) did not have T2DM recurrence (mean %EWL 73% ⫾ 18.63% at nadir and 57.30% ⫾ 21.7% at the most recent follow-up visit (P ⫽ .0365; Table 1). Durable remission of T2DM correlated well with preoperative T2DM therapy (Fig. 1). Patients with diet-controlled T2DM preoperatively had a 97% incidence (34 of 35 patients) of T2DM remission at some point in the postoperative period (Fig. 1). T2DM remission was durable in 76.4% (26 of 34 patients) of those with diet-controlled T2DM. Of the 83 patients who were treated with oral hypoglycemic agents only preoperatively, 76 (92%) had remission of their T2DM at some point postoperatively (Fig. 1). T2DM remission was durable in 50 (65.7%) of the 76 patients. Although 47 (80%) of 59 patients with insulin-dependent T2DM achieved remission (Fig. 1) at some point in the postoperative course, T2DM recurred in 34 (72%) of these 47 patients (Fig. 1). Limited glycosylated hemoglobin (HbA1c) data were available for 59 patients who initially had remission of their T2DM (Table 2). The mean HbA1c for the patients with recurrence of T2DM was 6.3% ⫾ 0.79% and that for patients with durable remission was 5.5% ⫾ 0.79% (P ⬍.0001; Table 2). Of the 36 patients with durable remission, 31 (86%) had a normal HbA1c value but only 10 (43.5%) of 23 patients with recurrence T2DM had a normal HbA1c value. The patients who underwent long-limb RYGB (⬎100-cm alimentary limb) had a greater incidence of initial T2DM remission (94.9%; 75 of 79 patients) compared with those who underwent short-limb RYGB (83.7%; 82 of 98 patients; P ⫽ .0295; Table 3). Nevertheless, the long-term durability of T2DM remission did not differ between the varying limb lengths (57.3%, 43 of 75, long-limb; 56.1%, 46 of 82, short-limb; P ⫽ 1.0; Table 3).
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Table 3 Variability of T2DM remission and recurrence with limb length Limb length
Resolved*
Unresolved
Recurrence
Long limb Short limb
75 (94.9) 82 (83.7)
4 (5.1) 16 (16.3)
32 (42.1) 36 (43.9)
T2DM ⫽ type 2 diabetes mellitus. Data in parentheses are percentages. * P ⫽ .0295.
The rate of T2DM remission did not differ significantly between the female patients (89%) and male patients (83.3%; P ⫽ .3419; Table 4). However, T2DM remission was more durable in the men (80%, 20 of 25) than in the women (52.3%, 69 of 132; P ⫽ .0144; Table 4). T2DM recurrence with weight regain was more prevalent in older patients (mean age 48.7 ⫾ 11.0 years) than in younger patients (mean age 44.0 ⫾ 10.0 years, P ⬍.01; Table 5). Multiple logistical regression analysis (Table 6) showed that the %EWL, gender, age, and disease (T2DM) severity were independent predictors of T2DM recurrence. The strongest predictors, however, were disease stage (oral control versus insulin, odds ratio .165; dietary control versus insulin, odds ratio .092) and female gender (odds ratio 5.058). Weight regain and age were weak predictors (odds ratio .976 and 1.053, respectively). Discussion It is now well established that obesity is an etiologic factor of T2DM. The current wisdom is that T2DM has no definitive medical cure [18,25]. Despite aggressive antidiabetic medical therapies, the natural course of this chronic disease is characterized by progression to microvascular complications such as neuropathy, nephropathy, retinopathy, and cardiovascular disease [26,27]. In the United states alone, T2DM has been implicated as the most common cause of blindness, renal failure, and amputation and is responsible for 70% of diabetic patient deaths from cardiovascular disease [26,27]. Notwithstanding an arsenal of weight loss schemes and products, most weight loss interventions fail to achieve sustained weight reduction [18,25,28]. This has led to considerations of more invasive therapeutic modalities. RYGB has gained popularity as an effective therapeutic option for T2DM [29,30]. The main goal of our retrospec-
Table 2 Hemoglobin A1c serum levels in patients with durable T2DM remission
Table 4 Variability of T2DM remission and recurrence by gender type
Variable
Durable T2DM remission
T2DM recurrence
Gender
Resolved
Unresolved
Recurrence*
Patients (n) Postoperative HbA1c
36 (61) 5.5% ⫾ .79%
23 (39) 6.3% ⫾ .79%*
Women Men
132 (89) 25 (83.3)
15 (10.2) 5 (16.7)
63 (47) 5 (20.1)
T2DM ⫽ type 2 diabetes mellitus; HbA1c ⫽ hemoglobin A1c. * P ⫽ .03 for HbA1c levels for remission versus recurrence.
T2DM ⫽ type 2 diabetes mellitus. Data in parentheses are percentages. * P ⫽ .0144.
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Table 5 Influence of age on rates of T2DM remission and recurrence Diabetic status
Patients (n)
Mean age (yr)
Resolved Unresolved Recurrence No recurrence
157 (88.7) 20 (11.3) 68 (43.3) 89 (56.7)
46.1 ⫾ 11.3 49.3 ⫾ 8.2 48.7 ⫾ 11.9 44.1 ⫾ 10.3
P value .2312 .0107
T2DM ⫽ type 2 diabetes mellitus. Data in parentheses are percentages.
tive study was to determine the rate and durability of T2DM remission after RYGB. The long-term follow-up rate is one of the limiting factors of most clinical observational studies, including ours [7,9,13]. The degree to which this affects the outcome of our study cannot be established with certainty. Most of the patients who were lost to follow-up, ⬎5 years after bariatric surgery, had relocated to different places and could not be located. All the patients in our study were under the care of their primary care physicians, and their T2DM status were diagnosed according to the ADA criteria [20,21]. According to the current ADA guidelines [20,21,31], HbA1c is not recommended for the diagnosis of T2DM. However, it is the most widely accepted laboratory test for the measurement of glycemic control [31]. We had a small group of patients from our study sample who had had HbA1c serum levels measured at their last visit. Patients with remission of T2DM showed statistically and significantly normal and lower HbA1c values than those with T2DM recurrence. HbA1c is not necessarily an absolute criterion for T2DM remission. Patients with well-controlled T2DM using medication can have a normalized HbA1c, indicating tight control of their blood sugar levels and not necessarily T2DM remission. A long-term lack of clinical T2DM symptoms (ADA criteria) [20,21] in the absence of medical therapy, such as was shown in our study, argues in favor of T2DM remission. In 2 meta-analysis studies, Buchwald et al. [29,30] reported rates of complete T2DM remission ⬎82% after bariatric-induced weight loss. These results are in agreement with our data in which we showed that 88.7% of obese patients with T2DM had complete remission of their T2DM after gastric bypass at some point after the surgery. Our results have demonstrated that the durability of T2DM remission correlates with the type of preoperative T2DM medical therapy. Those receiving insulin therapy showed a significantly lower rate of durable remission than the groups that had been treated with oral hypoglycemic or dietary control. Although the mechanism of this phenomenon is not clearly understood, it suggests that the need for insulin therapy might have identified those in whom weight loss would be insufficient to compensate for the decreased insulin secretory capacity. Limited data are available regarding the effect of limb length on the rates of T2DM remission. Polyzogopoulou et al. [32] showed that limb length did not
affect long-term weight loss after gastric bypass surgery. Their study did not address the effect of limb length on the rates of T2DM remission. Our data showed that long-limb RYGB resulted in a greater incidence of initial remission of T2DM compared with short-limb RYGB. Nevertheless, the durability of remission was not affected by the limb length in our experience. A randomized prospective study comparing the effect of short and long limbs on the remission of T2DM (for a ⬎12-year period) would be needed to confirm the findings suggested by our retrospective study. Although many clinical studies have focused on the remission rates of T2DM after bariatric surgery, very limited data are available on the factors that affect the durability of T2DM remission [29,30]. Our results showed that the durability of T2DM remission correlated with sustained weight loss and that recurrence occurred with weight regain, although substantial exceptions to that generalization were also present. None of the patients with weight regain demonstrated clinical or radiologic evidence of gastrogastric fistula or staple line disruption [33,34]. Most patient with significant weight regain underwent upper gastrointestinal contrast radiographic studies to rule out this possibility. Additionally, some patients did not enjoy remission despite a %EWL of ⱕ77.6%. Also, recurrence of T2DM developed in patients with ⱕ106% EWL. Finally, durable remission occurred in patients with a %EWL as low as 27.6%. This variance also suggests that factors other than weight loss are at work. Our regression analysis demonstrated that weight regain is a significant, but weak, predictor. These findings are somewhat in conflict with several studies that have reported the remission of T2DM immediately after gastric bypass and before the patient has lost any weight [32]. Our results suggest that perhaps the early (short-term) T2DM remission that is independent of weight loss is mediated through a different mechanism than the one that mediates long-term T2DM remission. The molecular and cellular mechanisms that mediate T2DM remission after gastric bypass surgery remain speculative, and no consensus has yet been reached on these mechanisms [35–37]. We also found that T2DM remission in patients with preoperative control using either diet or oral hypoglycemic agents was more durable than that of patients who had required insulin Table 6 Stepwise logistical regression analysis to determine independent predictors/variables of T2DM recurrence (model: T2DM recurrence) Variable
Comment
Odds ratio
P value
Age %EWL Disease severity
Older versus younger patients Low versus high Preoperative oral hypoglycemic agent versus insulin control Preoperative dietary versus insulin control Women versus men
1.053 .976 .165
.0057 .0052 ⬍.0001
.092
⬍.0001
5.058
.0053
Gender
Abbreviations as in Table 1.
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therapy preoperatively. Moreover, the results of the present study showed that T2DM remission was less durable in the older patients. Preoperative T2DM requiring insulin therapy indicated more severe diabetic disease than T2DM managed with diet or oral hypoglycemic agents. These data suggest that surgical intervention in the case of early diabetic disease would be more beneficial. Although some questions remain to be answered, it is clear that a high proportion of obese patients with T2DM will derive substantial metabolic benefit from bariatric surgery.
References [1] Flegal KM, Carroll MD, Ogden CL, Johnson CL. Prevalence and trends in obesity among US adults, 1999 –2000. JAMA 2002;288: 1723–7. [2] Flegal KM, Carroll MD, Kuczmarski RJ, Johnson CL. Overweight and obesity in the United States: prevalence and trends, 1960 –1994. Int J Obes Relat Metab Disord 1998;22:39 – 47. [3] Harris MI, Flegal KM, Cowie CC, et al. Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance in U.S. adults: the Third National Health 280 and Nutrition Examination Survey, 1988 –1994. Diabetes Care 1998;21:518 –24. [4] National Task Force on the Prevention and Treatment of Obesity. Overweight, obesity, and health risk. Arch Intern Med 2000;160: 898 –904. [5] Pories WJ, Swanson MS, MacDonald KG, et al. Who would have thought it? An operation proves to be the most effective therapy for adult-onset diabetes mellitus. Ann Surg 1995;222:339 –52. [6] DeMaria EJ, Sugerman HJ, Kellum JM, Meador JG, Wolfe LG. Results of 281 consecutive total laparoscopic Roux-en-Y gastric bypasses to treat morbid obesity. Ann Surg 2002;35:640 – 47. [7] Schauer PR, Ikramuddin S, Gourash W, Ramanathan R, Luketich J. Outcomes after laparoscopic Roux-en-Y gastric bypass for morbid obesity. Ann Surg 2000;232:515–29. [8] Dixon JB, O’Brien PE. Health outcomes of severely obese type 2 diabetic subjects 1 year after laparoscopic adjustable gastric banding. Diabetes Care 2002;25:358 – 63. [9] Sjostrom L, Lindroos AK, Peltonen M, et al. Lifestyle, diabetes, and cardiovascular risk factors 10 years after 295 bariatric surgery. N Engl J Med 2004;351:2683–93. [10] Schauer PR, Burguera B, Ikramuddin S, et al. Effect of laparoscopic Roux-en Y gastric bypass on type 2 diabetes mellitus. Ann Surg 2003;238:467– 85. [11] Pories WJ, MacDonald KG, Flickinger EG, et al. Is type II diabetes mellitus (NIDDM) a surgical disease? Ann Surg 1992;215:633– 43. [12] Pories WJ, Swanson MS, MacDonald KG, et al. Who would have thought it? An operation proves to be the most effective therapy for adult onset diabetes? Ann Surg 1995;222:339 –52. [13] Sjostrom CD, Lissner L, Wedel H, Sjostrom L. Reduction in incidence of diabetes, hypertension and lipid disturbances after intentional weight loss induced by bariatric surgery: the SOS intervention study. Obes Res 1999;7:477– 85. [14] Long SD, O’Brien K, MacDonald KG Jr, et al. Weight loss in severely obese subjects prevents the progression of impaired glucose tolerance to type II diabetes: a longitudinal interventional study. Diabetes Care 1994;17:372–5. [15] Sjöström L. Surgical intervention as a strategy for treatment of obesity. Endocrine 2000;13:213–30. [16] Scopinaro N, Adami GF, Marinari GM, et al. Biliopancreatic diversion. World J Surg 1998;22:936 – 46.
259
[17] Caro JF, Dohm LG, Pories WJ, Sinha MK. Cellular alterations in liver, skeletal muscle, and adipose tissue responsible for insulin resistance in obesity and type II diabetes. Diabetes Metab Rev 1989; 5:665– 89. [18] Consensus development conference panel. NIH conference (1991): gastrointestinal surgery for severe obesity. Ann Intern Med 1991;115: 956 – 61. [19] Saaddine JB, Engelgau MN, Beckles GL, Gregg EW, Thompson TJ, Venkat Narayan KM. A diabetes report card for the United States: quality of care in the 1990s. Ann Surg 2002;136:565–74. [20] American Diabetes Association. Standards of medical care in diabetes. Diabetes Care 2007;30(Suppl 1):S4 – 41. [21] American Diabetes Association. Screening for type 2 diabetes. Diabetes Care 2004;27(Suppl 1):S11– 4. [22] Brustad M, Skeie G, Braaten T, Slimani N, Lund E. Comparison of telephone vs face to face interviews in the assessment of dietary intake by the 24h recall EPIC SOFT program—the Norwegian Calibration Study. Eur J Clin Nutrition 2003;57:107–13. [23] Luepker RV, Pallonen EU, Murray DM, Pirie P. Validity of telephone surveys in assessing cigarette smoking in young adults. Am J Public Health 1989;79:202– 4. [24] Kricker A, Vajdic CM, Armstrong BK, et al. Reliability and validity of a telephone questionnaire for estimating lifetime person sun exposure in epidemiologic studies. Cancer Epidemiol Biomarkers Prev 2005;14:2427–32. [25] Zimmet P, Shaw J, Alberti KG. Preventing type 2 diabetes and the metabolic syndrome in the real world: a realistic view. Diabetic Med 2003;20:693–702. [26] Gu K, Cowie CC, Harris MI. Mortality in adults with and without diabetes in a national cohort of the U.S. population: 1971–1993. Diabetes Care 1998;21:1138 – 45. [27] Daousi C, Pinkney JH. The impact of obesity on the prevalence of cardiovascular disease and diabetic complications in a hospital diabetic population. Diabetes Med 2003;20:102. [28] Leibbrand R, Fichter MM. Maintenance of weight loss after obesity treatment: is continuous support necessary? Behav Res Ther 2002; 40:1275– 89. [29] Buchwald H, Avidor Y, Braunwald E, et al. Bariatric surgery: a systematic review and meta-analysis. JAMA 2004;292:1724 –37. [30] Buchwald H, Estok R, Fahrbach K, et al. Weight and type 2 diabetes after bariatric surgery: systematic review and meta-analysis. Am J Med 2009;122:248 –56. [31] The International Expert Committee. International Expert Committee Report on the role of the A1C assay in the diagnosis of diabetes. Diabetes Care 2009;32:1327–34. [32] Polyzogopoulou EV, Kalfarentzos F, Vagenakis AG. Restoration of euglycemia and normal acute insulin response to glucose in obese subjects with type 2 diabetes following bariatric surgery. Diabetes 2003;52:1098 –103. [33] Roberts KE, Duffy AJ, Bell RL. Laparoscopic transgastric repair of gastrogastric fistula after gastric bypass: a novel technique. Surg Innov 2007;14:18 –23. [34] Cucchi SGD, Pories WJ, MacDonald KG. Gastrogastric fistula: a complication of divided gastric bypass surgery. Ann Surg 1995;221: 387–91. [35] Rubino F, Forgione A, Cummings D, et al. 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;244:741–9. [36] Cummings DE, Overduin J, Foster-Schubert, KE. Gastric bypass for obesity: mechanisms of weight loss and diabetes resolution. J Clin Endocrinol Metab 2009;86:4753– 8. [37] Ferchak V, Meneghini LF. Obesity, bariatric surgery and type 2 diabetes—a systematic review. Diabetes Metab Res Rev 2004;20: 438 – 45.
Original article
Analysis of factors associated with durable remission of diabetes after Roux-en-Y gastric bypass Silas M. Chikunguwo, M.D., Ph.D.*, Luke G. Wolfe, B.S., M.S., Patricia Dodson, M.S., Jill G. Meador, B.S.N., Nancy Baugh, B.S.N., John N. Clore, M.D., John M. Kellum, M.D., James W. Maher, M.D. Department Surgery, Virginia Commonwealth University Medical Center, Richmond, Virginia Received May 27, 2009; revised October 31, 2009; accepted November 3, 2009
Abstract
Background: Data on the durability of remission of type 2 diabetes mellitus (T2DM) after gastric bypass are limited. Our purpose was to identify the rate of long-term remission of T2DM and the factors associated with durable remission. Methods: A total of 177 patients with T2DM who had undergone Roux-en-Y gastric bypass from 1993 to 2003 had 5-year follow-up data available. T2DM status was determined by interview and evaluation of the diabetic medications. Patients with complete remission or recurrence of T2DM were identified. Results: Follow-up ranged from 5 to 16 years. Of the 177 patients, 157 (89%) had complete remission of T2DM with a decrease in their mean body mass index from baseline (50.2 ⫾ 8.2 kg/m2) to 31.3 ⫾ 7.2 kg/m2 postoperatively (mean percentage of excess weight loss 70.0% ⫾ 18.6%). However, 20 patients (11.3%) did not have T2DM remission despite a mean percentage of excess weight loss of 58.2% ⫾ 12.3% (P ⬍.0009). Of the 157 patients with initial remission of their T2DM, 68 (43%) subsequently developed T2DM recurrence. Remission of T2DM was durable in 56.9%. Durable (⬎5-year) resolution of T2DM was greatest in the patients who originally had either controlled their T2DM with diet (76%) or oral hypoglycemic agents (66%). The rate of T2DM remission was more likely to be durable in men (P ⫽ .00381). Weight regain was a statistically significant, but weak predictor, of T2DM recurrence. Conclusion: Early remission of T2DM occurred in 89% of patients after Roux-en-Y gastric bypass. T2DM recurred in 43.1%. Durable remission correlated most closely with an early disease stage at gastric bypass. (Surg Obes Relat Dis 2010;6:254 –259.) © 2010 American Society for Metabolic and Bariatric Surgery. All rights reserved.
Keywords:
Bariatric surgery; Diabetes mellitus; Roux-en-Y gastric bypass
A close interrelationship exists between obesity and type 2 diabetes mellitus (T2DM) [1]. Recent epidemiologic studies have shown that the prevalence of obesity has increased by ⬎75% since 1980, with ⬎34% of the U.S. adult population overweight (body mass index [BMI] 25–29.9 kg/m2) and another 30% classified as obese (BMI ⱖ30 kg/m2)
*Correspondence: Silas M. Chikunguwo, M.D., Ph.D., Department of Surgery, Virginia Commonwealth University Medical Center, 1200 East Broad Street, P.O. Box 980519, Richmond, VA 23298-0519. E-mail: [email protected]
[1,2]. T2DM is estimated to affect ⱖ8% of the adult population and 19% of the population ⬎65 years of age, with an estimated 800,000 new cases diagnosed annually [3]. Clinical studies have clearly established that obesity is a critical etiologic factor in the development of T2DM [4] and that weight loss has beneficial effects on T2DM and improves the metabolic pathophysiology that leads to hyperglycemia. Several clinical observational studies have shown that surgically induced weight loss is associated with significant improvement or remission of T2DM, but generally have been reserved for those with a BMI ⬎40 kg/m2 or a BMI
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⬎35 kg/m2 if co-morbidities are present [5–10]. Pories et al. [11,12] assessed the effects of gastric bypass in 165 patients with noninsulin-dependent T2DM and 165 others with impaired glucose tolerance. After a mean follow-up of 7.6 years, 83% of patients with T2DM no longer required pharmacologic treatment and 99% of those with impaired glucose tolerance were euglycemic. In another report, the same investigators compared 154 patients with T2DM who had undergone surgery with 78 who had not [12]. The percentage requiring oral medication or insulin increased from 56% to 88% in the control group but decreased from 32% to 9% in the treatment group. The Swedish Obese Subjects study followed up patients after gastric bypass surgery with respect to the effects on T2DM and reported that a mean weight loss of 28 kg at 2 years led to improved glycemic control in 118 patients with T2DM [13]. This weight loss led to withdrawal of oral hypoglycemic drugs or insulin for many patients. In contrast, the need for drugs increased in the 77 nonsurgically treated patients. The proportion treated by diet alone increased from 59% to 73% in the surgical group; however, in the nonsurgical group, it declined from 55% to 34%. Surgery resulted in a 30-fold reduction in the risk of progression from impaired glucose tolerance to diabetes in the study by Pories et al. [11,12]. The prevalence of T2DM was reduced 30-fold at 2 years and 5-fold at 8 years after surgery in the Swedish Obese Subjects study [14,15]. In a series of 2241 patients, biliopancreatic diversion resulted in a mean permanent reduction of 75% of the initial excess weight, with an operative mortality of .5% [16]. In that study, Scopinaro et al. [16,17] showed that biliopancreatic diversion achieved durable normalization of the plasma glucose, plasma insulin, and glycosylated hemoglobin in 80 –100% of severely obese patients with T2DM. Although the remission of T2DM after gastric bypass has been extensively documented, very limited data are available on the recurrence of T2DM. The main goal of our study was to determine the incidence of durable remission of T2DM after gastric bypass and the factors associated with T2DM recurrence. Understanding the clinical factors that influence both the remission and the recurrence of T2DM after bariatric surgery could potentially lead to better strategies to enhance durable remission. Methods Patient selection and data sources The Virginia Commonwealth University institutional review board approved the present study. We identified patients with T2DM who had undergone either open or laparoscopic Roux-en-Y gastric bypass (RYGB) from 1993 to 2003 by retrospective review of our prospectively collected bariatric database. All patients met the criteria from the 1991 National Institutes of Health Consensus Development Conference for Bariatric Surgery [18]. RYGB was per-
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formed by multiple faculty surgeons using multiple techniques during the study period. Open RYGB was initially done without dividing the stomach, and in laparoscopic RYGB, the stomach was divided in all cases. Short-limb RYGB was defined as that with an alimentary limb ⬍100 cm, and long-limb RYGB was defined as that with an alimentary limb of 100 –150 cm. No distal RYGB was done during the study period. We identified patients with T2DM as those who had T2DM listed preoperatively as a comorbidity in their medical record. The diagnosis of the preoperative T2DM status by the primary care physician was determined from the fasting blood glucose concentration according to the criteria established by the American Diabetes Association (ADA) [19 –21]. Patients with a positive history of T2DM who were taking diabetic medications before surgery were also classified as having T2DM. The patient data were collected prospectively, verified retrospectively, and then entered into the Virginia Commonwealth University Bariatric Surgery Clinical Database—a customized computer database. Other data sources included office charts, follow-up notes, hospital charts, and patient follow-up telephone interviews [22–24]. Outcome measures and change in T2DM status The parameters studied included patient demographics, BMI, weight loss, and changes in co-morbidities. The following data were extracted from the database: age, gender, pre- and postoperative weight, BMI, percentage of excess weight loss (%EWL), and type of RYGB (short-limb or long-limb). At the annual clinic visits, nutritional laboratory studies were obtained, and the resolution or persistence of co-morbidities was documented. Patients not participating in annual follow-up visits were telephoned and asked about their T2DM status and medication changes, if we were unable to persuade them to return for in-person follow-up examinations. The patient’s primary care physician was responsible for the preoperative selection of diabetic therapy, dose, and frequency and for reducing, discontinuing, or adding diabetic medications postoperatively. Weight loss or regain was expressed in terms of the %EWL and the change in BMI. T2DM remission was defined as no longer requiring any diabetic medication or dietary management at some point in the patient’s postoperative course. The durable remission of T2DM was defined as the absence of T2DM signs and symptoms and the absence of any dietary, oral hypoglycemic, or insulin therapy at the most recent follow-up visit or telephone interview. Statistical analysis All analyses were performed using Statistical Analysis Systems, version 9.13 (SAS Institute, Cary, NC). The data are presented as the mean and standard deviation. Continuous data were analyzed using Student’s t test or analysis of variance. Categorical data were compared using Fisher’s
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Table 1 Influence of weight regain on T2DM recurrence Variable
Total (n) BMI (kg/m2) Mean Range %EWL Mean Range
Patient status Preoperative T2DM
Postoperative T2DM remission
Postoperative T2DM without remission
Postoperative T2DM recurrence
Postoperative T2DM without recurrence
177
157 (88.7)
20 (11.3)
68 (43.3)
89 (56.7)
50.2 ⫾ 8.1 37.5–87.1 —
31.2 ⫾ 7.2 18.6–63.7
33.5 ⫾ 4.9 26.3–44.2
32.2 ⫾ 7.7 21.5–63.7
30.5 ⫾ 6.6 18.6–56.1
70.1 ⫾ 18.5 24.9–112.1
57.4 ⫾ 12.6 33.3–77.6*
66.4 ⫾ 17.8 24.9–106.5
73.0 ⫾ 18.5 27.6–112.1†
T2DM ⫽ type 2 diabetes mellitus; BMI ⫽ body mass index; %EWL ⫽ percentage of excess weight loss. Data in parentheses are percentages. * Significant compared with T2DM with remission. † Significant compared with T2DM recurrence.
exact test. P ⬍.05 was considered statistically significant. Multiple logistical regression analysis was used to identify independent predictors of T2DM remission. Results A total of 378 morbidly obese patients with T2DM who had undergone bariatric surgery during the same period were identified from our database. Of these 378 patients with T2DM, 177 (follow-up rate 46.8%), who had undergone open or laparoscopic RYGB from 1993 to 2003, were available for the present study (Table 1). Preoperative
T2DM management consisted of dietary management for 34 patients (21.7%), oral hypoglycemic drugs for 76 patients (48.4%), and insulin for 47 patients (29.9%). Of the 177 patients, 30 were men (17%) and 147 were women (83%). The length of postoperative follow-up was 5–16 years. The mean follow-up duration was 8.6 years. The T2DM status was determined by interview and evaluation of the T2DM treatment. Of the 177 patients, 157 (88.7%) had complete remission of their T2DM at some point in their postoperative course (Table 1 and Fig. 1). This was associated with a decrease in the mean BMI from 50.2 ⫾ 8.2 kg/m2 preoperatively to 31.3 ⫾ 7.2 kg/m2 at the postoperative nadir
Fig. 1. Rates of T2DM remission and recurrence after RYGB.
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(mean %EWL 70% ⫾ 18.6%). Of the 177 patients, 20 (11.3%) did not achieve remission of their T2DM despite a decrease in their BMI to a mean of 33.2 ⫾ 4.9 kg/m2 (mean %EWL 58.2% ⫾ 12.3%; Table 1). The difference in the %EWL between those with T2DM remission and those without remission was significant (P ⬍.0009). Of the 157 patients with initial remission of their T2DM, 68 (43.3%) subsequently developed T2DM recurrence (Table 1). This correlated with a regain of lost weight (mean %EWL 66% ⫾ 17.8% at nadir and 49.1% ⫾ 27% at T2DM recurrence). Of the 157 patients with initial remission, 89 (56.7%) did not have T2DM recurrence (mean %EWL 73% ⫾ 18.63% at nadir and 57.30% ⫾ 21.7% at the most recent follow-up visit (P ⫽ .0365; Table 1). Durable remission of T2DM correlated well with preoperative T2DM therapy (Fig. 1). Patients with diet-controlled T2DM preoperatively had a 97% incidence (34 of 35 patients) of T2DM remission at some point in the postoperative period (Fig. 1). T2DM remission was durable in 76.4% (26 of 34 patients) of those with diet-controlled T2DM. Of the 83 patients who were treated with oral hypoglycemic agents only preoperatively, 76 (92%) had remission of their T2DM at some point postoperatively (Fig. 1). T2DM remission was durable in 50 (65.7%) of the 76 patients. Although 47 (80%) of 59 patients with insulin-dependent T2DM achieved remission (Fig. 1) at some point in the postoperative course, T2DM recurred in 34 (72%) of these 47 patients (Fig. 1). Limited glycosylated hemoglobin (HbA1c) data were available for 59 patients who initially had remission of their T2DM (Table 2). The mean HbA1c for the patients with recurrence of T2DM was 6.3% ⫾ 0.79% and that for patients with durable remission was 5.5% ⫾ 0.79% (P ⬍.0001; Table 2). Of the 36 patients with durable remission, 31 (86%) had a normal HbA1c value but only 10 (43.5%) of 23 patients with recurrence T2DM had a normal HbA1c value. The patients who underwent long-limb RYGB (⬎100-cm alimentary limb) had a greater incidence of initial T2DM remission (94.9%; 75 of 79 patients) compared with those who underwent short-limb RYGB (83.7%; 82 of 98 patients; P ⫽ .0295; Table 3). Nevertheless, the long-term durability of T2DM remission did not differ between the varying limb lengths (57.3%, 43 of 75, long-limb; 56.1%, 46 of 82, short-limb; P ⫽ 1.0; Table 3).
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Table 3 Variability of T2DM remission and recurrence with limb length Limb length
Resolved*
Unresolved
Recurrence
Long limb Short limb
75 (94.9) 82 (83.7)
4 (5.1) 16 (16.3)
32 (42.1) 36 (43.9)
T2DM ⫽ type 2 diabetes mellitus. Data in parentheses are percentages. * P ⫽ .0295.
The rate of T2DM remission did not differ significantly between the female patients (89%) and male patients (83.3%; P ⫽ .3419; Table 4). However, T2DM remission was more durable in the men (80%, 20 of 25) than in the women (52.3%, 69 of 132; P ⫽ .0144; Table 4). T2DM recurrence with weight regain was more prevalent in older patients (mean age 48.7 ⫾ 11.0 years) than in younger patients (mean age 44.0 ⫾ 10.0 years, P ⬍.01; Table 5). Multiple logistical regression analysis (Table 6) showed that the %EWL, gender, age, and disease (T2DM) severity were independent predictors of T2DM recurrence. The strongest predictors, however, were disease stage (oral control versus insulin, odds ratio .165; dietary control versus insulin, odds ratio .092) and female gender (odds ratio 5.058). Weight regain and age were weak predictors (odds ratio .976 and 1.053, respectively). Discussion It is now well established that obesity is an etiologic factor of T2DM. The current wisdom is that T2DM has no definitive medical cure [18,25]. Despite aggressive antidiabetic medical therapies, the natural course of this chronic disease is characterized by progression to microvascular complications such as neuropathy, nephropathy, retinopathy, and cardiovascular disease [26,27]. In the United states alone, T2DM has been implicated as the most common cause of blindness, renal failure, and amputation and is responsible for 70% of diabetic patient deaths from cardiovascular disease [26,27]. Notwithstanding an arsenal of weight loss schemes and products, most weight loss interventions fail to achieve sustained weight reduction [18,25,28]. This has led to considerations of more invasive therapeutic modalities. RYGB has gained popularity as an effective therapeutic option for T2DM [29,30]. The main goal of our retrospec-
Table 2 Hemoglobin A1c serum levels in patients with durable T2DM remission
Table 4 Variability of T2DM remission and recurrence by gender type
Variable
Durable T2DM remission
T2DM recurrence
Gender
Resolved
Unresolved
Recurrence*
Patients (n) Postoperative HbA1c
36 (61) 5.5% ⫾ .79%
23 (39) 6.3% ⫾ .79%*
Women Men
132 (89) 25 (83.3)
15 (10.2) 5 (16.7)
63 (47) 5 (20.1)
T2DM ⫽ type 2 diabetes mellitus; HbA1c ⫽ hemoglobin A1c. * P ⫽ .03 for HbA1c levels for remission versus recurrence.
T2DM ⫽ type 2 diabetes mellitus. Data in parentheses are percentages. * P ⫽ .0144.
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Table 5 Influence of age on rates of T2DM remission and recurrence Diabetic status
Patients (n)
Mean age (yr)
Resolved Unresolved Recurrence No recurrence
157 (88.7) 20 (11.3) 68 (43.3) 89 (56.7)
46.1 ⫾ 11.3 49.3 ⫾ 8.2 48.7 ⫾ 11.9 44.1 ⫾ 10.3
P value .2312 .0107
T2DM ⫽ type 2 diabetes mellitus. Data in parentheses are percentages.
tive study was to determine the rate and durability of T2DM remission after RYGB. The long-term follow-up rate is one of the limiting factors of most clinical observational studies, including ours [7,9,13]. The degree to which this affects the outcome of our study cannot be established with certainty. Most of the patients who were lost to follow-up, ⬎5 years after bariatric surgery, had relocated to different places and could not be located. All the patients in our study were under the care of their primary care physicians, and their T2DM status were diagnosed according to the ADA criteria [20,21]. According to the current ADA guidelines [20,21,31], HbA1c is not recommended for the diagnosis of T2DM. However, it is the most widely accepted laboratory test for the measurement of glycemic control [31]. We had a small group of patients from our study sample who had had HbA1c serum levels measured at their last visit. Patients with remission of T2DM showed statistically and significantly normal and lower HbA1c values than those with T2DM recurrence. HbA1c is not necessarily an absolute criterion for T2DM remission. Patients with well-controlled T2DM using medication can have a normalized HbA1c, indicating tight control of their blood sugar levels and not necessarily T2DM remission. A long-term lack of clinical T2DM symptoms (ADA criteria) [20,21] in the absence of medical therapy, such as was shown in our study, argues in favor of T2DM remission. In 2 meta-analysis studies, Buchwald et al. [29,30] reported rates of complete T2DM remission ⬎82% after bariatric-induced weight loss. These results are in agreement with our data in which we showed that 88.7% of obese patients with T2DM had complete remission of their T2DM after gastric bypass at some point after the surgery. Our results have demonstrated that the durability of T2DM remission correlates with the type of preoperative T2DM medical therapy. Those receiving insulin therapy showed a significantly lower rate of durable remission than the groups that had been treated with oral hypoglycemic or dietary control. Although the mechanism of this phenomenon is not clearly understood, it suggests that the need for insulin therapy might have identified those in whom weight loss would be insufficient to compensate for the decreased insulin secretory capacity. Limited data are available regarding the effect of limb length on the rates of T2DM remission. Polyzogopoulou et al. [32] showed that limb length did not
affect long-term weight loss after gastric bypass surgery. Their study did not address the effect of limb length on the rates of T2DM remission. Our data showed that long-limb RYGB resulted in a greater incidence of initial remission of T2DM compared with short-limb RYGB. Nevertheless, the durability of remission was not affected by the limb length in our experience. A randomized prospective study comparing the effect of short and long limbs on the remission of T2DM (for a ⬎12-year period) would be needed to confirm the findings suggested by our retrospective study. Although many clinical studies have focused on the remission rates of T2DM after bariatric surgery, very limited data are available on the factors that affect the durability of T2DM remission [29,30]. Our results showed that the durability of T2DM remission correlated with sustained weight loss and that recurrence occurred with weight regain, although substantial exceptions to that generalization were also present. None of the patients with weight regain demonstrated clinical or radiologic evidence of gastrogastric fistula or staple line disruption [33,34]. Most patient with significant weight regain underwent upper gastrointestinal contrast radiographic studies to rule out this possibility. Additionally, some patients did not enjoy remission despite a %EWL of ⱕ77.6%. Also, recurrence of T2DM developed in patients with ⱕ106% EWL. Finally, durable remission occurred in patients with a %EWL as low as 27.6%. This variance also suggests that factors other than weight loss are at work. Our regression analysis demonstrated that weight regain is a significant, but weak, predictor. These findings are somewhat in conflict with several studies that have reported the remission of T2DM immediately after gastric bypass and before the patient has lost any weight [32]. Our results suggest that perhaps the early (short-term) T2DM remission that is independent of weight loss is mediated through a different mechanism than the one that mediates long-term T2DM remission. The molecular and cellular mechanisms that mediate T2DM remission after gastric bypass surgery remain speculative, and no consensus has yet been reached on these mechanisms [35–37]. We also found that T2DM remission in patients with preoperative control using either diet or oral hypoglycemic agents was more durable than that of patients who had required insulin Table 6 Stepwise logistical regression analysis to determine independent predictors/variables of T2DM recurrence (model: T2DM recurrence) Variable
Comment
Odds ratio
P value
Age %EWL Disease severity
Older versus younger patients Low versus high Preoperative oral hypoglycemic agent versus insulin control Preoperative dietary versus insulin control Women versus men
1.053 .976 .165
.0057 .0052 ⬍.0001
.092
⬍.0001
5.058
.0053
Gender
Abbreviations as in Table 1.
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therapy preoperatively. Moreover, the results of the present study showed that T2DM remission was less durable in the older patients. Preoperative T2DM requiring insulin therapy indicated more severe diabetic disease than T2DM managed with diet or oral hypoglycemic agents. These data suggest that surgical intervention in the case of early diabetic disease would be more beneficial. Although some questions remain to be answered, it is clear that a high proportion of obese patients with T2DM will derive substantial metabolic benefit from bariatric surgery.
References [1] Flegal KM, Carroll MD, Ogden CL, Johnson CL. Prevalence and trends in obesity among US adults, 1999 –2000. JAMA 2002;288: 1723–7. [2] Flegal KM, Carroll MD, Kuczmarski RJ, Johnson CL. Overweight and obesity in the United States: prevalence and trends, 1960 –1994. Int J Obes Relat Metab Disord 1998;22:39 – 47. [3] Harris MI, Flegal KM, Cowie CC, et al. Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance in U.S. adults: the Third National Health 280 and Nutrition Examination Survey, 1988 –1994. Diabetes Care 1998;21:518 –24. [4] National Task Force on the Prevention and Treatment of Obesity. Overweight, obesity, and health risk. Arch Intern Med 2000;160: 898 –904. [5] Pories WJ, Swanson MS, MacDonald KG, et al. Who would have thought it? An operation proves to be the most effective therapy for adult-onset diabetes mellitus. Ann Surg 1995;222:339 –52. [6] DeMaria EJ, Sugerman HJ, Kellum JM, Meador JG, Wolfe LG. Results of 281 consecutive total laparoscopic Roux-en-Y gastric bypasses to treat morbid obesity. Ann Surg 2002;35:640 – 47. [7] Schauer PR, Ikramuddin S, Gourash W, Ramanathan R, Luketich J. Outcomes after laparoscopic Roux-en-Y gastric bypass for morbid obesity. Ann Surg 2000;232:515–29. [8] Dixon JB, O’Brien PE. Health outcomes of severely obese type 2 diabetic subjects 1 year after laparoscopic adjustable gastric banding. Diabetes Care 2002;25:358 – 63. [9] Sjostrom L, Lindroos AK, Peltonen M, et al. Lifestyle, diabetes, and cardiovascular risk factors 10 years after 295 bariatric surgery. N Engl J Med 2004;351:2683–93. [10] Schauer PR, Burguera B, Ikramuddin S, et al. Effect of laparoscopic Roux-en Y gastric bypass on type 2 diabetes mellitus. Ann Surg 2003;238:467– 85. [11] Pories WJ, MacDonald KG, Flickinger EG, et al. Is type II diabetes mellitus (NIDDM) a surgical disease? Ann Surg 1992;215:633– 43. [12] Pories WJ, Swanson MS, MacDonald KG, et al. Who would have thought it? An operation proves to be the most effective therapy for adult onset diabetes? Ann Surg 1995;222:339 –52. [13] Sjostrom CD, Lissner L, Wedel H, Sjostrom L. Reduction in incidence of diabetes, hypertension and lipid disturbances after intentional weight loss induced by bariatric surgery: the SOS intervention study. Obes Res 1999;7:477– 85. [14] Long SD, O’Brien K, MacDonald KG Jr, et al. Weight loss in severely obese subjects prevents the progression of impaired glucose tolerance to type II diabetes: a longitudinal interventional study. Diabetes Care 1994;17:372–5. [15] Sjöström L. Surgical intervention as a strategy for treatment of obesity. Endocrine 2000;13:213–30. [16] Scopinaro N, Adami GF, Marinari GM, et al. Biliopancreatic diversion. World J Surg 1998;22:936 – 46.
259
[17] Caro JF, Dohm LG, Pories WJ, Sinha MK. Cellular alterations in liver, skeletal muscle, and adipose tissue responsible for insulin resistance in obesity and type II diabetes. Diabetes Metab Rev 1989; 5:665– 89. [18] Consensus development conference panel. NIH conference (1991): gastrointestinal surgery for severe obesity. Ann Intern Med 1991;115: 956 – 61. [19] Saaddine JB, Engelgau MN, Beckles GL, Gregg EW, Thompson TJ, Venkat Narayan KM. A diabetes report card for the United States: quality of care in the 1990s. Ann Surg 2002;136:565–74. [20] American Diabetes Association. Standards of medical care in diabetes. Diabetes Care 2007;30(Suppl 1):S4 – 41. [21] American Diabetes Association. Screening for type 2 diabetes. Diabetes Care 2004;27(Suppl 1):S11– 4. [22] Brustad M, Skeie G, Braaten T, Slimani N, Lund E. Comparison of telephone vs face to face interviews in the assessment of dietary intake by the 24h recall EPIC SOFT program—the Norwegian Calibration Study. Eur J Clin Nutrition 2003;57:107–13. [23] Luepker RV, Pallonen EU, Murray DM, Pirie P. Validity of telephone surveys in assessing cigarette smoking in young adults. Am J Public Health 1989;79:202– 4. [24] Kricker A, Vajdic CM, Armstrong BK, et al. Reliability and validity of a telephone questionnaire for estimating lifetime person sun exposure in epidemiologic studies. Cancer Epidemiol Biomarkers Prev 2005;14:2427–32. [25] Zimmet P, Shaw J, Alberti KG. Preventing type 2 diabetes and the metabolic syndrome in the real world: a realistic view. Diabetic Med 2003;20:693–702. [26] Gu K, Cowie CC, Harris MI. Mortality in adults with and without diabetes in a national cohort of the U.S. population: 1971–1993. Diabetes Care 1998;21:1138 – 45. [27] Daousi C, Pinkney JH. The impact of obesity on the prevalence of cardiovascular disease and diabetic complications in a hospital diabetic population. Diabetes Med 2003;20:102. [28] Leibbrand R, Fichter MM. Maintenance of weight loss after obesity treatment: is continuous support necessary? Behav Res Ther 2002; 40:1275– 89. [29] Buchwald H, Avidor Y, Braunwald E, et al. Bariatric surgery: a systematic review and meta-analysis. JAMA 2004;292:1724 –37. [30] Buchwald H, Estok R, Fahrbach K, et al. Weight and type 2 diabetes after bariatric surgery: systematic review and meta-analysis. Am J Med 2009;122:248 –56. [31] The International Expert Committee. International Expert Committee Report on the role of the A1C assay in the diagnosis of diabetes. Diabetes Care 2009;32:1327–34. [32] Polyzogopoulou EV, Kalfarentzos F, Vagenakis AG. Restoration of euglycemia and normal acute insulin response to glucose in obese subjects with type 2 diabetes following bariatric surgery. Diabetes 2003;52:1098 –103. [33] Roberts KE, Duffy AJ, Bell RL. Laparoscopic transgastric repair of gastrogastric fistula after gastric bypass: a novel technique. Surg Innov 2007;14:18 –23. [34] Cucchi SGD, Pories WJ, MacDonald KG. Gastrogastric fistula: a complication of divided gastric bypass surgery. Ann Surg 1995;221: 387–91. [35] Rubino F, Forgione A, Cummings D, et al. 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;244:741–9. [36] Cummings DE, Overduin J, Foster-Schubert, KE. Gastric bypass for obesity: mechanisms of weight loss and diabetes resolution. J Clin Endocrinol Metab 2009;86:4753– 8. [37] Ferchak V, Meneghini LF. Obesity, bariatric surgery and type 2 diabetes—a systematic review. Diabetes Metab Res Rev 2004;20: 438 – 45.