- Email: [email protected]
The long-term impact of biliopancreatic diversion on glycemic control in the severely obese with type 2 diabetes mellitus in relation to preoperative duration of diabetes
Surgery for Obesity and Related Diseases ] (2015) 00–00
Original article
The long-term impact of biliopancreatic diversion on glycemic control in the severely obese with type 2 diabetes mellitus in relation to preoperative duration of diabetes Giovanni B. Camerini, M.D., Francesco S. Papadia, M.D., Flavia Carlini, M.D., Mariafrancesca Catalano, Ph.D., Gian Franco Adami, M.D.*, Nicola Scopinaro, M.D., F.A.C.S. hon Department of Surgery, University of Genova, Azienda Ospedale-Università San Martino, Genova, Italy Received February 24, 2015; accepted May 22, 2015
Abstract
Background: Bariatric surgery has been shown to be effective in severely obese patients with type 2 diabetes mellitus (T2DM). Objective: Evaluate the long-term efficacy of biliopancreatic diversion (BPD) for the treatment of T2DM depending on the preoperative duration of T2DM. Setting: University Hospital. Methods: Retrospective analysis investigating 2 subsets of severely obese patients who had undergone BPD from 1984 to 1995. The first included 52 patients with a preoperative T2DM duration of 1 year (SD group – 49 on oral agents and 3 on insulin), and the second included 68 patients who had been diabetic for 4 5 years before BPD (LD group – 52 on oral agents and 16 on insulin). Postoperatively, T2DM was regarded as in remission when fasting serum glucose (FSG) was lower than 100 mg/dL on regular diet and without antidiabetic therapy. Results: In the SD patients, the number of individuals without T2DM remission were lower both at 5–10 (0/31, 0% of patients, versus 8/54, 15% of patients, p o .04) and at 4 15 years (1/28, 3% of patients, versus 10/41, 24% of patients, p o .0012). Furthermore, after BPD, the number of patients with dyslipidemia strongly reduced (p o .001) in both groups, values at 5–10 years remaining very similar to those observed at 4 15 years. Conclusion: These results indicate that severely obese patients with longer T2DM duration have a worse metabolic outcome maintained at long and very long term following BPD. (Surg Obes Relat Dis 2015;]:00–00.) r 2015 Published by Elsevier Inc. on behalf of American Society for Metabolic and Bariatric Surgery.
Keywords:
Type 2 diabetes; Bariatric surgery; Biliopancreatic diversion; Diabetes resolution; Retrospective study; Very long term results
Introduction In recent years, strong evidence of remission or sharp improvement of diabetic status in obese type 2 diabetics *
Correspondence: Gian Franco Adami, Department of Surgery at the University of Genova, Largo Benzi 8, Genova 16132, Italy. E-mail: [email protected]
after all types of bariatric surgery has emerged [1–3]. The metabolic outcome seems to be substantially related to the extent of weight reduction, the best results being observed following the surgeries that induce consistent loss of body mass: after adjustable gastric banding, only a 20–30% of type 2 diabetes patients succeed in normalizing or reducing fasting serum glucose level; after laparoscopic Roux-en-Y gastric bypass (LRYGBP) or biliopancreatic diversion
http://dx.doi.org/10.1016/j.soard.2015.05.012 1550-7289/r 2015 Published by Elsevier Inc. on behalf of American Society for Metabolic and Bariatric Surgery.
G. B. Camerini et al. / Surgery for Obesity and Related Diseases ] (2015) 00–00
2
(BPD), a successful metabolic outcome after the surgery is observed in 60–70% and 85–95% of the operated patients, respectively, most likely from postoperative changes in enterohormonal pattern [4–8]. Nevertheless, few data are available to evaluate the metabolic results’ stability over a very long term [9]. The purpose of this retrospective analysis is to ascertain the maintenance of a normal metabolic state at very long term in severely obese patients and the role of preoperative diabetes duration in the long term diabetes remission following BPD. Material and methods The analysis was carried out in the vast cohort of severely obese patients with type 2 diabetes having consecutively undergone BPD at the Surgical Department of Genoa University, Italy, from May 1984 to May 1999 [10]. Patients were considered to have type 2 diabetes when fasting serum glucose concentration (FSG) was higher than 125 mg/dL either before or during their preoperative evaluation and/or if they were on chronic use of antidiabetic therapy. Among this cohort, 2 groups of patients were selected; the first included 52 obese patients (30 female, aging 31–61 years) with a preoperative diabetes duration of 1 year (mean 13.2 ⫾ 1.1 months, SD group) and the second was composed of 68 individuals (46 female, aging 28–59 years) with a preoperative T2DM duration of 45 years (mean 6.3 ⫾ 2.8 years, LD group). The duration of diabetes was determined at the time of the preoperative assessment. Within the SD group, 3 patients were on insulin and 49 on oral agents presurgery; within the LD group, 16 patients were on insulin and 52 on oral agents presurgery. The demographic, preoperative anthropometric, and clinical data of the patients are referred to in Table 1. The patients underwent the ad hoc stomach type of BPD, where the gastric volume, which is the main determinant of the initial weight loss, is adapted to the preoperative excess
weight and to other individual characteristics, such as sex, age, eating habits, socioeconomic status, and expected degree of compliance [10]. Patients were evaluated before the surgery and after 1, 2, and 3 years with routine followup visits. The majority of the patients came to an additional visit at 5–10 years following the surgery mean (8.5 ⫾ 1.3 years). The analysis was carried out on the individual chart of any surgical patient. The data at 415 years (mean 16.4 ⫾ 5 years) was obtained by requesting a further follow-up visit and/or blood exams. For this analysis, the preoperative data recorded at 5–10 years and at 415 years following BPD were considered. At the 5–10 year and at the 415-year evaluation, serum glucose value was available in 65% and 57% of cases, respectively, and serum triglyceride and high density lipoprotein (HDL) cholesterol (total and HDL) levels in 56% and 36% of cases. After BPD, type 2 diabetes was regarded as resolved when serum glucose level was lower than 100 mg/dL on regular diet and without the use of any antidiabetic medications. Patients were considered as having dyslipidemia when triglycerides and/or total cholesterol serum concentration were higher than 150 mg/dL and 200 mg/dL, respectively, and/or HDL cholesterol lower than 40 mg/dL [11]. For this type of study, formal consent is not required. Considering all patients, the follow-up rate was 70% at 5–10 years and 66% at 415 years (Table 1). Data is given as means ⫾ SDs. The differences between continuous data were analyzed with the Student’s t-test for paired and unpaired comparisons when appropriate, and the differences between categorical variables were analyzed with the Fisher’s exact test. For calculation, StatView release 5.0.1, SAS Inc., Carey, NC, was used. Results In both the SD and LD group, at 5–10 years following the surgery, a sharp and significant reduction of both body weight (BW) and body mass index (BMI) were found.
Table 1 Severely obese patients with type 2 diabetes: anthropometric and clinical data in patients with short-term (ST) and long-term (LT) diabetes duration. (ST) Diabetes duration 1 year
diabetes duration (yrs) Observed patients (#) Insulin therapy (#, %) Weight (kg) BMI (kg/m2) Percent weight loss (%) Fasting serum glucose (mg/dL) Serum triglycerides (mg/dL) Total cholesterol (mg/dL) Serum HDL cholesterol (mg/dL)
(LT) Diabetes duration 45 yrs
prior BPD
at 5–10 yrs
at 415 yrs
1 year 52 3 (6%) 133 ⫾ 21 49.0 ⫾ 7.7
31
28
86.7 ⫾ 14.7* 31.3 ⫾ 8.2* 66 ⫾ 12 84 ⫾ 11* 77 ⫾ 38* 117 ⫾ 68* 45.4 ⫾ 12.4*
87 ⫾ 18* 33.1 ⫾ 6.9* 67 ⫾ 12 85 ⫾ 20* 91 ⫾ 37* 129 ⫾ 28* 45.3 ⫾ 14.1*
182 ⫾ 52 287 ⫾ 229 215 ⫾ 47 36.8 ⫾ 13.1
BMI, Body mass index; HDL, high density lipoprotein; BPD, biliopancreatic diversion. * ¼ p o .01 versus before BPD. § ¼ p o .01 versus ST.
prior BPD 7.1 ⫾ 3.3 68 16 (24%) 127 ⫾ 23 48.2 ⫾ 8.4 206 ⫾ 77 236 ⫾ 255 249 ⫾ 32 36.7 ⫾ 9.3
at 5–10 yrs
at 415 yrs
54
51
83.1 ⫾ 17.3* 32.1 ⫾ 6.1* 67 ⫾ 12 93 ⫾ 27*§ 99 ⫾ 37* 132 ⫾ 33* 45.3 ⫾ 17.2
84 ⫾ 20* 32.4 ⫾ 7.5* 67 ⫾ 11 99 ⫾ 39*§ 100 ⫾ 53* 139 ⫾ 42* 41.7 ⫾ 9.9*
BPD and T2 Long Term Remission / Surgery for Obesity and Related Diseases ] (2015) 00–00
3
Fig 1. Severely obese patients with type 2 diabetes with short-term (ST) and long-term (LT) diabetes duration: frequency of diabetes and dyslipidemia before biliopancreatic diversion (BPD), at 5–10 years, and at 415 years postoperatively. Dyslipidemia: * ¼ p o .001 versus before BPD. Type 2 diabetes: § ¼ p o .04 versus ST group. ‡ ¼ p o .0012 versus ST group.
These values remained substantially unchanged at 415 years; the percent of weight loss at 5–10 years was substantially similar to that observed at 415 years (Table 1). Likewise, the values of FSG, total cholesterol, and triglyceride levels decreased at 5–10 years in both groups, which strictly maintained at 4 15 years, and an increase of serum HDL cholesterol level was also observed at very long term. Though still in the normal range, the FSG mean values were higher in the LD group than in the SD group both at 5–10 years and at 415 years following the surgery (Table 1). In the SD groups, all patients showed FSG level in the normal range at 5–10 years, and at 415 years, only 1 of 28 individuals in the FSG level was higher than 100 mg/dL. In the LD groups, while the mean values were in the normal range throughout all the post-BPD period, the FSG level was higher than 100 mg/dL in 8 of 54 patients at 5–10 years and in 10 of 41 patients 415 years following BPD (Fig. 1). Within the SD subset, nearly all of the T2DM patients showed normal FSG throughout the period following BPD regardless of the type of preoperative antidiabetic therapy. On the contrary, within the group of patients treated with insulin prior to the surgery in the LD subset, the number of
hyperglycemic individuals at 5–10 years and at 415 years following BPD was greater (p o .02 and p o .01, respectively) than that observed in their counterparts preoperatively treated only with oral antidiabetics (Table 2). The number of patients showing dyslipidemia before the surgery was substantially similar in the 2 groups (42 of 51 in the SD and 47 of 67 in the LD). Following BPD, a decrease (p o .01) of the frequency of dyslipidemia at 5– 10 years (7 of 27 in the SD and 12 of 40 in the LD) and at 415 years (3 of 14 in the SD and 12 of 31 in the LD) was observed (Fig. 1). Discussion There is ample evidence in the literature that all types of bariatric surgeries lead to an improvement in the diabetic status in obese individuals, with BPD and Roux-en-Y gastric bypass leading to better metabolic outcome compared with a purely restrictive procedure like gastric banding [1,2,12–14]. However, few results at very long term are available, and very little work has been done to study and establish the preoperative factors that can reliably predict postoperative diabetes remission in the long run [9].
Table 2 Severely obese patients with type 2 diabetes with short-term (ST) and long-term (LT) diabetes duration; patients with postoperative hyperglycemia in relation to the preoperative antidiabetic therapy (ST) diabetes duration 1 year
Preoperative use of insulin Preoperative use of oral antidiabetics
(LT) diabetes duration 45 yrs
at 5–10 yrs
at 415 yrs
at 5–10 yrs
at 415 yrs
0/2 0/29
0/2 1/26
5/14 3/40
6/15 4/39
4
G. B. Camerini et al. / Surgery for Obesity and Related Diseases ] (2015) 00–00
In this retrospective analysis, the results at 415 years following BPD are reported. Previous studies following BPD have included both obese patients with wellestablished diabetes and patients with diabetic conditions unknown before the surgery, or with a disease of very recent onset and/or treated with diet only. This baseline heterogeneity could considerably influence the overall results [15]. For this reason, all patients with a diabetic status lasting o 1 year before BPD and not taking chronically antidiabetic drug were excluded from the analysis. Furthermore, to increase the visibility of the effects of diabetes duration on the postoperative metabolic outcome, obese patients with a diabetes duration of 1 year are compared with patients with T2DM of at least 5 years. Given that the analysis encompasses a very long period time, the preoperative data of glycosylated hemoglobin are lacking in many patients. Therefore, this data was not considered, and diabetes was regarded as remitted only according to FSG level data, with cut off values being conservatively settled at 100 mg/dL. This analysis fully confirms that for severely obese patients with type 2 diabetes, BPD is followed by a diabetes remission maintained at very long term in the great majority of patients [15]. In the SD group, the complete normalization of FSG at 5–10 years occurred in all patients, and at 415 years, only one patient’s FSG was in the diabetic range. Conversely, among the LD patients, the number of individuals with type 2 diabetes both at 5–10 and at 415 years after BPD was nearly 14% and 25%, respectively. Since the weight is maintained, the long-term increase of recurrence rate is most likely explained by the progressive beta cell exhaustion that characterize the natural history of type 2 diabetes [16]. The predicting role of diabetic duration and of type of antidiabetic therapy on the metabolic outcome after bariatric surgery observed in the first postoperative years [13,17–20] is fully confirmed at very long term in a consistent sample of patients. Both in the SD and in the LD group, a reduction of mean values of serum triglycerides and total cholesterol within the normal range was observed at 5–10 years following BPD, while of the mean values of HDL cholesterol increased up to physiologic limits; both values remained within normal ranges at 15 or more years postoperatively. Consequently, within the 2 groups, the rate of individuals with dyslipidemia sharply decreased at 5–10 years after BPD, without any further noticeable change at longer term. Therefore, this analysis showed that in severely obese diabetic individuals, the results on lipid profiles obtained in the first year post– bariatric surgery [21–25] are maintained at long and very long term following BPD. Conclusion In obese patients with overt type 2 diabetes undergoing BPD, the diabetes duration and the type of therapy are
factors that predict the very long term postoperative metabolic outcome. In the population under study, the rate of diabetes remission is significantly lower in patients with long-duration diabetes before surgery compared with those patients who had a recent diagnosis of diabetes. In the latter group, whose diagnosis of diabetes was 1 year before surgery, diabetes remission was observed after BPD in nearly every case. It is, therefore, important to quantify the preoperative duration of diabetes in studies assessing the impact of bariatric procedures on T2DM to better understand the effect of the intervention. Dyslipidemia, which is a very common condition among severely obese diabetic patients and represents a true risk for cardiovascular events, disappears in more than two thirds of patients after BPD, regardless of the diabetes duration. In severely obese T2DM patients, the recovery rate from dyslipidemia after BPD is very similar to that observed in obese patients regardless of the diabetic condition; moreover, this analysis shows that this improvement is maintained at very long term. Besides the retrospective design, the main limitation of this analysis is that at 415 years after BPD, the metabolic outcome of only 60% of the baseline patients was available. However, though definitive conclusions cannot be drawn, this investigation suggests that in severely obese patients with type 2 diabetes, the metabolic outcome after BPD is maintained throughout the years. Furthermore, it has to be pointed out that in the obese individuals with overt type 2 diabetes, the post–bariatric surgery outcome is also dependent on each individual subject.
References [1] Sjöström L, Peltonen M, Jacobson P, et al. Association of bariatric surgery with long-term remission of type 2 diabetes and with microvascular and macrovascular complications. JAMA 2014;311 (22):2297–304. [2] 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(3):248–56. [3] Maggard-Gibbons M, Maglione M, Livhits M, et al. Bariatric surgery for weight loss and glycemic control in nonmorbidly obese adults with diabetes: a systematic review. JAMA 2013;309(21):2250–61. [4] Dixon JB, O'Brien PE, Playfair J, et al. Adjustable gastric banding and conventional therapy for type 2 diabetes: a randomized controlled trial. JAMA 2008;299(3):316–23. [5] Nguyen NT, Slone JA, Nguyen XM, Hartman JS, Hoyt DB. A prospective randomized trial of laparoscopic gastric bypass versus laparoscopic adjustable gastric banding for the treatment of morbid obesity: outcomes, quality of life, and costs. Ann Surg 2009;250 (4):631–41. [6] van Dielen FM, Soeters PB, de Brauw LM, Greve JW. Laparoscopic adjustable gastric banding versus open vertical banded gastroplasty: a prospective randomized trial. Obes Surg 2005;15(9):1292–8. [7] Bhasker AG, Remedios C, Batra P, Sood A, Shaikh S, Lakdawala M. Predictors of remission of T2DM and metabolic effects after laparoscopic Roux-en-Y gastric bypass in obese Indian diabetics a 5-year study. Obes Surg. Epub 2014 Nov 16.
BPD and T2 Long Term Remission / Surgery for Obesity and Related Diseases ] (2015) 00–00 [8] Ferrannini E, Mingrone G. Impact of different bariatric surgical procedures on insulin action and beta-cell function in type 2 diabetes. Diabetes Care 2009;32(3):514–20. [9] Puzziferri N, Roshek TB 3rd, Mayo HG, Gallagher R, Belle SH, Livingston EH. Long-term follow-up after bariatric surgery: a systematic review. JAMA 2014;312(9):934–42. [10] Scopinaro N, Adami GF, Marinari GM, et al. Biliopancreatic diversion. World J Surg 1998;22(9):936–46. [11] Reiner Z, Catapano AL, De Backer G, et al. European Association for Cardiovascular Prevention & Rehabilitation, ESC Committee for Practice Guidelines (CPG)2008-2010 and 2010-2012 Committees. ESC/EAS Guidelines for the management of dyslipidaemias: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur Heart J 2011; 32(14):1769–818. [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 mellitus. Ann Surg 1995;222(3):339–50. [13] 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(4):467–84. [14] 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;235(5):640–5. [15] Scopinaro N, Marinari GM, Camerini GB, Papadia FS, Adami GF. Specific effects of biliopancreatic diversion on the major components of metabolic syndrome: a long-term follow-up study. Diabetes Care 2005;28(10):2406–11. [16] Butler AE, Janson J, Bonner-Weir S, Ritzel R, Rizza RA, Butler PC. Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes 2003;52(1):102–10.
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[17] Lee WJ, Hur KY, Lakadawala M, et al. Predicting success of metabolic surgery: age, body mass index, C-peptide, and duration score. Surg Obes Relat Dis 2013;9(3):379–84. [18] Robert M, Ferrand-Gaillard C, Disse E, et al. Predictive factors of type 2 diabetes remission 1 year after bariatric surgery: impact of surgical techniques. Obes Surg 2013;23(6):770–5. [19] Ramos-Levi AM, Matia P, Cabrerizo L, et al. Statistical models to predict type 2 diabetes remission after bariatric surgery. J Diabetes 2014;6(5):472–7. [20] Steven S, Carey PE, Small PK, Taylor R. Reversal of Type 2 diabetes after bariatric surgery is determined by the degree of achieved weight loss in both short- and long-duration diabetes. Diabet Med 2015; 32(1):47–53. [21] Dhabuwala A, Cannan RJ, Stubbs RS. Improvement in co-morbidities following weight loss from gastric bypass surgery. Obes Surg 2000;10(5):428–35. [22] Benaiges D, Flores-Le-Roux JA, Pedro-Botet J, et al. Impact of restrictive (sleeve gastrectomy) vs hybrid bariatric surgery (Roux-enY gastric bypass) on lipid profile. Obes Surg 2012;22(8):1268–75. [23] Courcoulas AP, Christian NJ, Belle SH, et al. Longitudinal Assessment of Bariatric Surgery (LABS) Consortium. Weight change and health outcomes at 3 years after bariatric surgery among individuals with severe obesity. JAMA 2013;310(22):2416–25. [24] Søvik TT, Aasheim ET, Taha O, et al. Weight loss, cardiovascular risk factors, and quality of life after gastric bypass and duodenal switch: a randomized trial. Ann Intern Med 2011; 155(5):281–91. [25] Adams TD, Pendleton RC, Strong MB, et al. Health outcomes of gastric bypass patients compared to nonsurgical, nonintervened severely obese. Obesity (Silver Spring) 2010;18(1):121–30.
Original article
The long-term impact of biliopancreatic diversion on glycemic control in the severely obese with type 2 diabetes mellitus in relation to preoperative duration of diabetes Giovanni B. Camerini, M.D., Francesco S. Papadia, M.D., Flavia Carlini, M.D., Mariafrancesca Catalano, Ph.D., Gian Franco Adami, M.D.*, Nicola Scopinaro, M.D., F.A.C.S. hon Department of Surgery, University of Genova, Azienda Ospedale-Università San Martino, Genova, Italy Received February 24, 2015; accepted May 22, 2015
Abstract
Background: Bariatric surgery has been shown to be effective in severely obese patients with type 2 diabetes mellitus (T2DM). Objective: Evaluate the long-term efficacy of biliopancreatic diversion (BPD) for the treatment of T2DM depending on the preoperative duration of T2DM. Setting: University Hospital. Methods: Retrospective analysis investigating 2 subsets of severely obese patients who had undergone BPD from 1984 to 1995. The first included 52 patients with a preoperative T2DM duration of 1 year (SD group – 49 on oral agents and 3 on insulin), and the second included 68 patients who had been diabetic for 4 5 years before BPD (LD group – 52 on oral agents and 16 on insulin). Postoperatively, T2DM was regarded as in remission when fasting serum glucose (FSG) was lower than 100 mg/dL on regular diet and without antidiabetic therapy. Results: In the SD patients, the number of individuals without T2DM remission were lower both at 5–10 (0/31, 0% of patients, versus 8/54, 15% of patients, p o .04) and at 4 15 years (1/28, 3% of patients, versus 10/41, 24% of patients, p o .0012). Furthermore, after BPD, the number of patients with dyslipidemia strongly reduced (p o .001) in both groups, values at 5–10 years remaining very similar to those observed at 4 15 years. Conclusion: These results indicate that severely obese patients with longer T2DM duration have a worse metabolic outcome maintained at long and very long term following BPD. (Surg Obes Relat Dis 2015;]:00–00.) r 2015 Published by Elsevier Inc. on behalf of American Society for Metabolic and Bariatric Surgery.
Keywords:
Type 2 diabetes; Bariatric surgery; Biliopancreatic diversion; Diabetes resolution; Retrospective study; Very long term results
Introduction In recent years, strong evidence of remission or sharp improvement of diabetic status in obese type 2 diabetics *
Correspondence: Gian Franco Adami, Department of Surgery at the University of Genova, Largo Benzi 8, Genova 16132, Italy. E-mail: [email protected]
after all types of bariatric surgery has emerged [1–3]. The metabolic outcome seems to be substantially related to the extent of weight reduction, the best results being observed following the surgeries that induce consistent loss of body mass: after adjustable gastric banding, only a 20–30% of type 2 diabetes patients succeed in normalizing or reducing fasting serum glucose level; after laparoscopic Roux-en-Y gastric bypass (LRYGBP) or biliopancreatic diversion
http://dx.doi.org/10.1016/j.soard.2015.05.012 1550-7289/r 2015 Published by Elsevier Inc. on behalf of American Society for Metabolic and Bariatric Surgery.
G. B. Camerini et al. / Surgery for Obesity and Related Diseases ] (2015) 00–00
2
(BPD), a successful metabolic outcome after the surgery is observed in 60–70% and 85–95% of the operated patients, respectively, most likely from postoperative changes in enterohormonal pattern [4–8]. Nevertheless, few data are available to evaluate the metabolic results’ stability over a very long term [9]. The purpose of this retrospective analysis is to ascertain the maintenance of a normal metabolic state at very long term in severely obese patients and the role of preoperative diabetes duration in the long term diabetes remission following BPD. Material and methods The analysis was carried out in the vast cohort of severely obese patients with type 2 diabetes having consecutively undergone BPD at the Surgical Department of Genoa University, Italy, from May 1984 to May 1999 [10]. Patients were considered to have type 2 diabetes when fasting serum glucose concentration (FSG) was higher than 125 mg/dL either before or during their preoperative evaluation and/or if they were on chronic use of antidiabetic therapy. Among this cohort, 2 groups of patients were selected; the first included 52 obese patients (30 female, aging 31–61 years) with a preoperative diabetes duration of 1 year (mean 13.2 ⫾ 1.1 months, SD group) and the second was composed of 68 individuals (46 female, aging 28–59 years) with a preoperative T2DM duration of 45 years (mean 6.3 ⫾ 2.8 years, LD group). The duration of diabetes was determined at the time of the preoperative assessment. Within the SD group, 3 patients were on insulin and 49 on oral agents presurgery; within the LD group, 16 patients were on insulin and 52 on oral agents presurgery. The demographic, preoperative anthropometric, and clinical data of the patients are referred to in Table 1. The patients underwent the ad hoc stomach type of BPD, where the gastric volume, which is the main determinant of the initial weight loss, is adapted to the preoperative excess
weight and to other individual characteristics, such as sex, age, eating habits, socioeconomic status, and expected degree of compliance [10]. Patients were evaluated before the surgery and after 1, 2, and 3 years with routine followup visits. The majority of the patients came to an additional visit at 5–10 years following the surgery mean (8.5 ⫾ 1.3 years). The analysis was carried out on the individual chart of any surgical patient. The data at 415 years (mean 16.4 ⫾ 5 years) was obtained by requesting a further follow-up visit and/or blood exams. For this analysis, the preoperative data recorded at 5–10 years and at 415 years following BPD were considered. At the 5–10 year and at the 415-year evaluation, serum glucose value was available in 65% and 57% of cases, respectively, and serum triglyceride and high density lipoprotein (HDL) cholesterol (total and HDL) levels in 56% and 36% of cases. After BPD, type 2 diabetes was regarded as resolved when serum glucose level was lower than 100 mg/dL on regular diet and without the use of any antidiabetic medications. Patients were considered as having dyslipidemia when triglycerides and/or total cholesterol serum concentration were higher than 150 mg/dL and 200 mg/dL, respectively, and/or HDL cholesterol lower than 40 mg/dL [11]. For this type of study, formal consent is not required. Considering all patients, the follow-up rate was 70% at 5–10 years and 66% at 415 years (Table 1). Data is given as means ⫾ SDs. The differences between continuous data were analyzed with the Student’s t-test for paired and unpaired comparisons when appropriate, and the differences between categorical variables were analyzed with the Fisher’s exact test. For calculation, StatView release 5.0.1, SAS Inc., Carey, NC, was used. Results In both the SD and LD group, at 5–10 years following the surgery, a sharp and significant reduction of both body weight (BW) and body mass index (BMI) were found.
Table 1 Severely obese patients with type 2 diabetes: anthropometric and clinical data in patients with short-term (ST) and long-term (LT) diabetes duration. (ST) Diabetes duration 1 year
diabetes duration (yrs) Observed patients (#) Insulin therapy (#, %) Weight (kg) BMI (kg/m2) Percent weight loss (%) Fasting serum glucose (mg/dL) Serum triglycerides (mg/dL) Total cholesterol (mg/dL) Serum HDL cholesterol (mg/dL)
(LT) Diabetes duration 45 yrs
prior BPD
at 5–10 yrs
at 415 yrs
1 year 52 3 (6%) 133 ⫾ 21 49.0 ⫾ 7.7
31
28
86.7 ⫾ 14.7* 31.3 ⫾ 8.2* 66 ⫾ 12 84 ⫾ 11* 77 ⫾ 38* 117 ⫾ 68* 45.4 ⫾ 12.4*
87 ⫾ 18* 33.1 ⫾ 6.9* 67 ⫾ 12 85 ⫾ 20* 91 ⫾ 37* 129 ⫾ 28* 45.3 ⫾ 14.1*
182 ⫾ 52 287 ⫾ 229 215 ⫾ 47 36.8 ⫾ 13.1
BMI, Body mass index; HDL, high density lipoprotein; BPD, biliopancreatic diversion. * ¼ p o .01 versus before BPD. § ¼ p o .01 versus ST.
prior BPD 7.1 ⫾ 3.3 68 16 (24%) 127 ⫾ 23 48.2 ⫾ 8.4 206 ⫾ 77 236 ⫾ 255 249 ⫾ 32 36.7 ⫾ 9.3
at 5–10 yrs
at 415 yrs
54
51
83.1 ⫾ 17.3* 32.1 ⫾ 6.1* 67 ⫾ 12 93 ⫾ 27*§ 99 ⫾ 37* 132 ⫾ 33* 45.3 ⫾ 17.2
84 ⫾ 20* 32.4 ⫾ 7.5* 67 ⫾ 11 99 ⫾ 39*§ 100 ⫾ 53* 139 ⫾ 42* 41.7 ⫾ 9.9*
BPD and T2 Long Term Remission / Surgery for Obesity and Related Diseases ] (2015) 00–00
3
Fig 1. Severely obese patients with type 2 diabetes with short-term (ST) and long-term (LT) diabetes duration: frequency of diabetes and dyslipidemia before biliopancreatic diversion (BPD), at 5–10 years, and at 415 years postoperatively. Dyslipidemia: * ¼ p o .001 versus before BPD. Type 2 diabetes: § ¼ p o .04 versus ST group. ‡ ¼ p o .0012 versus ST group.
These values remained substantially unchanged at 415 years; the percent of weight loss at 5–10 years was substantially similar to that observed at 415 years (Table 1). Likewise, the values of FSG, total cholesterol, and triglyceride levels decreased at 5–10 years in both groups, which strictly maintained at 4 15 years, and an increase of serum HDL cholesterol level was also observed at very long term. Though still in the normal range, the FSG mean values were higher in the LD group than in the SD group both at 5–10 years and at 415 years following the surgery (Table 1). In the SD groups, all patients showed FSG level in the normal range at 5–10 years, and at 415 years, only 1 of 28 individuals in the FSG level was higher than 100 mg/dL. In the LD groups, while the mean values were in the normal range throughout all the post-BPD period, the FSG level was higher than 100 mg/dL in 8 of 54 patients at 5–10 years and in 10 of 41 patients 415 years following BPD (Fig. 1). Within the SD subset, nearly all of the T2DM patients showed normal FSG throughout the period following BPD regardless of the type of preoperative antidiabetic therapy. On the contrary, within the group of patients treated with insulin prior to the surgery in the LD subset, the number of
hyperglycemic individuals at 5–10 years and at 415 years following BPD was greater (p o .02 and p o .01, respectively) than that observed in their counterparts preoperatively treated only with oral antidiabetics (Table 2). The number of patients showing dyslipidemia before the surgery was substantially similar in the 2 groups (42 of 51 in the SD and 47 of 67 in the LD). Following BPD, a decrease (p o .01) of the frequency of dyslipidemia at 5– 10 years (7 of 27 in the SD and 12 of 40 in the LD) and at 415 years (3 of 14 in the SD and 12 of 31 in the LD) was observed (Fig. 1). Discussion There is ample evidence in the literature that all types of bariatric surgeries lead to an improvement in the diabetic status in obese individuals, with BPD and Roux-en-Y gastric bypass leading to better metabolic outcome compared with a purely restrictive procedure like gastric banding [1,2,12–14]. However, few results at very long term are available, and very little work has been done to study and establish the preoperative factors that can reliably predict postoperative diabetes remission in the long run [9].
Table 2 Severely obese patients with type 2 diabetes with short-term (ST) and long-term (LT) diabetes duration; patients with postoperative hyperglycemia in relation to the preoperative antidiabetic therapy (ST) diabetes duration 1 year
Preoperative use of insulin Preoperative use of oral antidiabetics
(LT) diabetes duration 45 yrs
at 5–10 yrs
at 415 yrs
at 5–10 yrs
at 415 yrs
0/2 0/29
0/2 1/26
5/14 3/40
6/15 4/39
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G. B. Camerini et al. / Surgery for Obesity and Related Diseases ] (2015) 00–00
In this retrospective analysis, the results at 415 years following BPD are reported. Previous studies following BPD have included both obese patients with wellestablished diabetes and patients with diabetic conditions unknown before the surgery, or with a disease of very recent onset and/or treated with diet only. This baseline heterogeneity could considerably influence the overall results [15]. For this reason, all patients with a diabetic status lasting o 1 year before BPD and not taking chronically antidiabetic drug were excluded from the analysis. Furthermore, to increase the visibility of the effects of diabetes duration on the postoperative metabolic outcome, obese patients with a diabetes duration of 1 year are compared with patients with T2DM of at least 5 years. Given that the analysis encompasses a very long period time, the preoperative data of glycosylated hemoglobin are lacking in many patients. Therefore, this data was not considered, and diabetes was regarded as remitted only according to FSG level data, with cut off values being conservatively settled at 100 mg/dL. This analysis fully confirms that for severely obese patients with type 2 diabetes, BPD is followed by a diabetes remission maintained at very long term in the great majority of patients [15]. In the SD group, the complete normalization of FSG at 5–10 years occurred in all patients, and at 415 years, only one patient’s FSG was in the diabetic range. Conversely, among the LD patients, the number of individuals with type 2 diabetes both at 5–10 and at 415 years after BPD was nearly 14% and 25%, respectively. Since the weight is maintained, the long-term increase of recurrence rate is most likely explained by the progressive beta cell exhaustion that characterize the natural history of type 2 diabetes [16]. The predicting role of diabetic duration and of type of antidiabetic therapy on the metabolic outcome after bariatric surgery observed in the first postoperative years [13,17–20] is fully confirmed at very long term in a consistent sample of patients. Both in the SD and in the LD group, a reduction of mean values of serum triglycerides and total cholesterol within the normal range was observed at 5–10 years following BPD, while of the mean values of HDL cholesterol increased up to physiologic limits; both values remained within normal ranges at 15 or more years postoperatively. Consequently, within the 2 groups, the rate of individuals with dyslipidemia sharply decreased at 5–10 years after BPD, without any further noticeable change at longer term. Therefore, this analysis showed that in severely obese diabetic individuals, the results on lipid profiles obtained in the first year post– bariatric surgery [21–25] are maintained at long and very long term following BPD. Conclusion In obese patients with overt type 2 diabetes undergoing BPD, the diabetes duration and the type of therapy are
factors that predict the very long term postoperative metabolic outcome. In the population under study, the rate of diabetes remission is significantly lower in patients with long-duration diabetes before surgery compared with those patients who had a recent diagnosis of diabetes. In the latter group, whose diagnosis of diabetes was 1 year before surgery, diabetes remission was observed after BPD in nearly every case. It is, therefore, important to quantify the preoperative duration of diabetes in studies assessing the impact of bariatric procedures on T2DM to better understand the effect of the intervention. Dyslipidemia, which is a very common condition among severely obese diabetic patients and represents a true risk for cardiovascular events, disappears in more than two thirds of patients after BPD, regardless of the diabetes duration. In severely obese T2DM patients, the recovery rate from dyslipidemia after BPD is very similar to that observed in obese patients regardless of the diabetic condition; moreover, this analysis shows that this improvement is maintained at very long term. Besides the retrospective design, the main limitation of this analysis is that at 415 years after BPD, the metabolic outcome of only 60% of the baseline patients was available. However, though definitive conclusions cannot be drawn, this investigation suggests that in severely obese patients with type 2 diabetes, the metabolic outcome after BPD is maintained throughout the years. Furthermore, it has to be pointed out that in the obese individuals with overt type 2 diabetes, the post–bariatric surgery outcome is also dependent on each individual subject.
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