Original article
Factors associated with complete and partial remission,
improvement, or unchanged diabetes status of obese adults 1 year after sleeve gastrectomy
Isra Elgenaied, M.B.B.Ch.a,
Walid El Ansari, M.B.B.Ch., D.C.H., D.T.M.&H., M.P.H., Ph.D., Ph.D.b,c,d,*, Mohamed Aly Elsherif, M.B.B.Ch., M.Sc., Ph.D.a, Sama Abdulrazzaq, M.B.B.Ch.a,
Amjad Salah Qabbani, M.B.B.Ch.b, Wahiba Elhag, M.B.B.Ch.a
aDepartment of Bariatric Surgery/Bariatric Medicine, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar
bDepartment of Surgery, Hamad General Hospital, Doha, Qatar
cCollege of Medicine, Qatar University, Doha, Qatar
dSchool of Health and Education, University of Skovde, Skovde, Sweden Received 23 February 2020; accepted 19 May 2020
Abstract Background: Laparoscopic sleeve gastrectomy (SG) achieves type 2 diabetes (T2D) remission to various extents, and reasons for such variations are unknown.
Objectives: We assessed patients’ characteristics associated with T2D remission 1 year post SG.
Setting: University hospital.
Methods: Retrospective study of 230 T2D patients (18–64 yr) who underwent SG at our institution.
We examined pre- and postoperative demographic, anthropometric, biochemical, and clinical char- acteristics associated with T2D complete remission, partial remission, improvement, or unchanged status. Independent predictors of T2D complete remission were assessed by binary logistic regression and then included in 7 predictive models. Logistic regression assessed the pre- and postoperative pre- dictors of T2D complete remission and their predictive performance was measured with the area un- der the curve of the receiver operating characteristic curve.
Results: A total of 230 patients were included in the study, females comprised 69%, and mean age was 45.666 8.84 years. Mean preoperative weight and body mass index were 115.69 6 20.76 kg and 43.536 6.98 kg/m2, respectively. Approximately two thirds (64.4%) of the sample had diabetes for .5 years. Insulin therapy users comprised 36.9% of the sample and 29.6% of patients were on 2 oral hypoglycemic agents (OHA). At 1 year, mean body mass index was 32.776 6.09 kg/m2, percent excess weight loss (%EWL) was 62.296 23.60% and glycosylated hemoglobin (HbA1C) improved from 8.1% to 6.18%. Approximately 42.2% of the sample achieved T2D complete remission.
Compared with those with no remission, patients with complete remission were significantly younger, had shorter duration of diabetes, were not on insulin therapy, took fewer OHA, had higher C-peptide, lower preoperative HbA1C, were less likely to have had hypertension or dyslipidemia, and more likely to have achieved higher %EWL. Seven proposed models for prediction of complete remission showed the most useful model comprised diabetes duration1 pre-HbA1C 1 %EWL 1 insulin therapy1 age 1 OHA (area under the curve 5 .81). Independent predictors of complete remission were preoperative HbA1C, %EWL, insulin therapy, age, and OHA (but not diabetes duration).
* Correspondence: Prof. Walid El Ansari, Department of Surgery, Hamad General Hospital, Doha 3050, Qatar.
E-mail address:welansari9@gmail.com(W. El Ansari).
https://doi.org/10.1016/j.soard.2020.05.013
1550-7289/Ó 2020 American Society for Bariatric Surgery. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://
creativecommons.org/licenses/by-nc-nd/4.0/).
Conclusion:SG results in significant weight reduction and various extents of T2D remission.
HbA1C, %EWL, insulin therapy, age, and OHA were independent predictors of complete remission.
Assessing these factors before bariatric surgery is important to identify any modifiable characteristics that can be altered to increase the likelihood of remission. (Surg Obes Relat Dis 2020;16:1521–
1530.)Ó 2020 American Society for Bariatric Surgery. Published by Elsevier Inc. This is an open ac- cess article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Key words: Laparoscopic sleeve gastrectomy; Type 2 diabetes; Complete remission; Partial remission; Improvement
The increase in type 2 diabetes (T2D) has prompted the need for more effective prevention and treatment strategies.
Bariatric surgery is effective in providing significant and du- rable weight loss proven to be superior to medical therapy in achieving glycemic control and improving cardiovascular risks among obese T2D patients [1,2]. Sleeve gastrectomy (SG) has become the most common bariatric surgery because it is technically simple, has lower complications than bypass surgery, and carries lower risk of nutritional de- ficiencies, and most importantly, it has metabolic effect in terms of improvement of T2D [3–5].
However, while most SG patients achieve weight loss and marked T2D improvement, the magnitude of such improve- ment is not evenly distributed among all patients [1]. For some diabetics, substantial improvement is not observed, and complete remission is not achieved [1]. Such variations in patient’s responses, even within the same bariatric pro- cedure, suggest other factors may be associated with T2D remission [6,7]. Others have identified preoperative (e.g., age, body mass index [BMI], glycosylated hemoglobin [HbA1C], C-peptide level, diabetes duration, number of oral hypoglycemic agents [OHA] used, insulin therapy) and postoperative (e.g., achieved weight loss) features that are associated with T2D remission [6,8–11]. Ascertaining such associations can assist in identifying patients most likely to benefit from SG in terms of extent of the T2D remission.
The literature reveals several gaps. Most studies that examined T2D remission rate after bariatric surgery did not asses the characteristics associated with such remissions [12], and were mostly after gastric bypass surgery [6,10,13,14]. The few studies that assessed features associ- ated with T2D remission after SG examined only a few clin- ical predictors [9,11,15], among small samples [11,16,17], and focused only on complete remission.
The present study bridged these gaps. We evaluated a range of characteristics associated with 4 types of T2D sta- tus (complete remission, partial remission, improvement, unchanged status) among 230 obese adults 1 year after SG. The preoperative characteristics were demographic and anthropometric (age, sex, weight, and body mass index [BMI]), biochemical (fasting blood glucose [FBG], HbA1C, C-peptide, and insulin level), and clinical (insulin therapy, T2D duration, hypertension, and dyslipidemia). The
postoperative characteristics comprised anthropometric (weight, BMI, weight loss [WL], and percentage of excess weight loss [%EWL]). The specific objectives assessed the characteristics associated with T2D remission after SG, and explored the independent predictors of T2D complete remission and their predictive performance.
Methods
Study design, ethics, and participants
This retrospective study was approved by the ethics com- mittee at the Medical Research Center at our institution (Protocol No. 16169/16). The study comprised patients who underwent SG between January 2012 and June 2016 at the Bariatric and Metabolic Surgery Centre at Hamad Medical Corporation, Doha, Qatar. Inclusion criteria were patients with T2D, aged 18 to 65 years, with BMI 35 and co-morbidities. Exclusion criteria were patients who had revisional LSG and patients with type 1 diabetes. A total of 243 patients were eligible based on the inclusion criteria;
however, preoperative HbA1C was not available for 13 pa- tients who therefore were excluded. There was no loss of follow-up for the remaining 230 patients at the 1-year visit.
Data collection
Patients’ medical charts and electronic records were reviewed at baseline and 1 year post SG. Data retrieved were demographic and anthropometric (age, sex, weight), biochemical (FBG, HbA1C, C-peptide, insulin level), and clinical (insulin therapy, diabetes duration, presence of hy- pertension, dyslipidemia) features. Percent EWL, WL, and BMI change were calculated using the methods described previously [18]. Insulin resistance was assessed by the ho- meostasis model assessment of insulin resistance (HOMA- IR) [19].
Definition T2D remission
This study used the standardized American Society of Bariatric and Metabolic Surgery definitions of evolution of T2D postbariatric surgery [20] (Table1). This is in line with previous studies [6,10,21,22].
Surgical technique
The procedure started with division of gastrosplenic liga- ment along the greater curvature 4 cm from the pylorus up to the left diaphragmatic crus with ultrasonic shears. The stom- ach was then mobilized and divided along the lesser curva- ture from antrum (4 cm from pylorus) up to the angle of His using buttressed (SeamGuard, Gore, Inc., Flagstaff, Ari- zona, USA) linear 60-mm stapler (Covidien Tristapler, Medtronic, Minneapolis, Minnesota, USA) or Echelon Flex (Johnson and Johnson, New Brunswick, New Jersey, USA) over the calibration tube (Midsleeve 38 Fr) introduced into the stomach. Specimen was removed through the um- bilical port. The procedure was concluded with methylene blue leak test.
Statistical analysis
Categorical variables were expressed as frequencies and percentages and were compared byc2test. Continuous vari- ables were presented as means and standard deviations and compared employing Student’s t test. Independent predic- tors of diabetes remission were identified by binary logistic regression and then included in several predictive models.
Models that presented a P. .05 on the Hosmer and Leme- show test were considered a good fit, and then their predic- tive performance was measured with the area under the curve of the receiver operating characteristic curve. Re- ported P values are 2-tailed, and P,.05 was considered sig- nificant. Analyses were performed using the statistical package SPSS 21 (IBM Corp, Armonk, NY, USA).
Results
Pre- and postoperative characteristics
Table 2shows pre- and 1-year postoperative characteristics of the sample. A total of 230 patients were included in this analysis. The mean age was 45.666 8.84 years, and 69.1%
were females. The mean preoperative BMI was 43.53 6 6.98 kg/m2 and 64.4% were diabetic for .5 years, with approximately 37% of patients on insulin. For patients on OHA, 27.8% were on sulphonylurea, 89.1% on insulin sensi- tizers (e.g., metformin), and 24.7% on incretin mimics (e.g., glucagon-like protein-1 agonist; data not presented). One year postoperatively, the mean BMI achieved was 32.77 6 6.09 kg/m2, with a BMI change of 210.83 6 4.22 kg/m2 and %EWL of 62.29 6 23.60%. HbA1C improved from 8.1% to 6.18%, FBG was reduced from 9.356 4.17 to 5.80 6 1.57 mmol/L. Complete diabetes remission was observed
Table 1
Definitions of status of type 2 diabetes [18]
Status Description and criteria
Complete remission Normal readings of glucose metabolism (HbA1C,6% and FBG ,100 mg/dL [, 5.5 mmol]) in absence of antidiabetic medication
No complete remission*
Partial remission Defined as HbA1C 6%–6.4% and FBG 100–
125 mg/dL (5.5–6.9 mmol/L) in absence of antidiabetic medication
Improvement Reduction in HbA1C and FBG not meeting criteria for remission, or decrease in antidiabetic medication requirement Unchanged Absence of remission or improvement
HbA1C5 glycosylated hemoglobin; FBG 5 fasting blood glucose.
* Includes partial remission, improvement, and unchanged status together.
Table 2
Pre- and 1-year postoperative characteristics of whole sample (n5 230)
Characteristic Value
Preoperative
Age, yr, mean6 SD 45.666 8.84
Sex, n (%)
Male 71 (30.9)
Female 159 (69.1)
Weight, kg, mean6 SD 115.696 20.76
BMI, kg/m2, mean6 SD 43.536 6.98
Diabetes duration, yr, n (%)
5 78 (35.6)
.5 141 (64.4)
Insulin therapy, n (%)
Yes 82 (36.9)
No 140 (63.1)
OHA*, n (%)
1 162 (70.4)
2 68 (29.6)
C-peptide, ng/dL, mean6 SD 3.066 2.13
Insulin level,m/dL, mean 6 SD 19.196 20.07
HOMA-IR, mean6 SD 7.546 10.54
FBG, mmol/L, mean6 SD 9.356 4.17
HbA1C, %, mean6 SD 8.136 1.75
Hypertension, n (%)
Yes 121 (53.5)
No 105 (46.5)
Dyslipidemia, n (%)
Yes 111 (49.6)
No 113 (50.4)
1 yr postoperative
Weight, kg, mean6 SD 86.996 16.35
BMI, kg/m2, mean6 SD 32.776 6.09
BMI change, kg/m2, mean6 SD 10.836 4.22
%EWL,mean6 SD 62.296 23.60
WL, kg, mean6 SD 29.046 12.17
Failed weight loss (,50%), n (%) 69 (30)
FBG, mmol/L, mean6 SD 5.806 1.57
HbA1C, %, mean6 SD 6.186 1.02
Diabetes status, n (%)
Complete remission 97 (42.2)
No complete remission 133 (57.8)
Partial remission 25 (18.8)
Improved 102 (76.7)
Unchanged 6 (4.5)
SD5 standard deviation; BMI 5 body mass index; OHA 5 oral hypo- glycemic agents; FBG5 fasting blood glucose; HbA1C 5 glycosylated he- moglobin; HOMA-IR 5 homeostatic model assessment for insulin resistance; %EWL5 percentage of excess weight loss; WL 5 weight loss.
* Includes sulphonylureas, insulin sensitizers, and incretin mimics.
in 42.2% of patients. Of those with no complete remission (57.8%), 18.8% achieved partial remission, 76.7% showed improvement, and 4.5% of had unchanged diabetes status.
Pre- and postoperative characteristics of complete remission
Table 3shows the comparison of means (6standard de- viation) of pre- and postoperative patient characteristics by remission status (complete remission versus no com- plete remission). In terms of preoperative features, pa- tients with complete remission were significantly younger, had shorter diabetes duration, and better glyce- mic control (reflected by lower FBG and HbA1C). As for the postoperative features, those with complete remis- sion had significantly greater BMI change, higher % EWL, and more absolute weight loss compared with pa- tients with no complete remission. The remaining charac- teristics (weight, BMI, preoperative insulin level) were not significantly different between complete versus not complete remission.
Table 4 shows the association of pre- and 1-year postoperative characteristics with remission status. In terms of preoperative features, compared with those with no remission, patients achieving complete remis- sion were significantly more likely to be younger, had shorter duration of diabetes, were not on insulin
therapy, were on fewer OHA, had higher C-peptide level, and had lower HbA1C. In addition, patients achieving complete remission were significantly less likely to have had preoperative hypertension or dyslipi- demia. As for postoperative features, patients achieving complete remission were significantly more likely to have achieved higher %EWL compared with those with no remission.
Pre- and postoperative predictors of complete remission Table 5shows the comparison of 7 proposed models for prediction of T2D complete remission after SG. Model V was judged the most useful model (diabetes duration 1 pre-HBA1C1 %EWL 1 insulin 1 age 1 OHA), with an area under the curve (AUC) amounting to .81 (P, 0.0001). Employing an additional 3 variables (Model VII, which additionally included hypertension1 dyslipide- mia1 C-peptide) only marginally improved the AUC to .82.
Table 6depicts the predictors of T2D complete remission employing multivariate logistic regression that further de- tails the independent effects of the individual variables.
When controlling was undertaken for the effects of all the variables in the model (Model V), diabetes duration emerged as an insignificant predictor of T2D complete remission. All the other 5 variables were significant
Table 3
Comparison (mean6 SD) of pre- and 1-year postoperative characteristics by remission status* (n5 230)
Characteristic Complete remission mean6 SD
No complete remission mean6 SD
P value
Total, n (%) 97 (42.2) 133 (57.8)
Preoperativey
Age, yr 43.536 8.17 47.216 9.01 .002
Weight, kg 118.116 20.82 113.926 20.60 .130
BMI, kg/m2 43.746 6.61 43.376 7.25 .691
Diabetes duration, yr 6.546 4.60 10.746 6.45 ,.0001
C-peptide, ng/dL 3.376 1.76 2.836 2.33 .135
Insulin level, u/dLz 15.786 12.88 20.946 22.90 .314
HOMA-IRx 3.96 3.92 9.306 12.23 .038
FBG, mmol/L 7.886 3.35 10.216 4.36 ,.0001
HbA1C, % 7.456 1.60 8.636 1.69 ,.0001
1 yr postoperativez
Weight, kg 86.476 18.47 87.336 14.89 .709
BMI, kg/m2 31.806 6.38 33.406 5.84 .059
BMI change, kg/m2 12.106 4.31 10.016 3.98 ,.0001
%EWL 69.136 24.33 57.886 22.11 .001
WL, kg 32.906 12.17 26.566 11.54 ,.0001
SD5 standard deviation; BMI 5 body mass index; HOMA-IR 5 homeostatic model assessment for insulin resistance; FBG5 fasting blood glucose; HbA1C 5 glycosylated hemoglobin; %EWL 5 percentage of excess weight loss; WL 5 weight loss.
Italics indicate statistical significance.
* Complete remission defined as normal readings of glucose metabolism (HbA1C,6% and FBG,100 mg/dL (5.5 mmol/L) in absence of diabetic medications. No complete remission in- cludes partial remission, improvement and unchanged status.
yFor all variables in the table, number of patients included in the analysis was 61–133 patients.
z17–33 patients included in this analysis.
x14–29 patients included in this analysis.
independent predictors T2D complete remission, with ef- fects ranging from (2.31–4.93).
Pre- and postoperative characteristics of partial remission and improvement
In terms patients who achieved partial T2D remission or improvement, Table 7 compares the pre- and 1-year postoperative characteristics of patients with complete remission versus partial remission and versus improve- ment. Patients with partial remission had significantly higher preoperative FBG, HbA1C, and HOMA, and at postoperative follow up, significantly lower BMI change and absolute weight loss compared with those with com- plete remission. The remaining characteristics were not significantly different between complete versus partial
remission. Table 7also depicts a comparison of the char- acteristics of patients with complete remission versus those with improvement. Patients who showed improve- ment were significantly older, had higher preoperative FBG, and HbA1C, and at postoperative follow up, signif- icantly smaller BMI change and lower %EWL compared with those with complete remission. The remaining char- acteristics were not significantly different between com- plete remission versus partial improvement.
Discussion
The literature on the association of a range of character- istics with T2D remission after SG is limited [6,7] and re- veals several gaps. Most studies that examined the T2D
Table 4
Association of pre- and 1-year postoperative characteristics with remission status*(n5 230)
Characteristic Category Complete
remission n (%)
No complete remission n (%)
Unadjusted OR (95%CI)
P value
Total n (%) 97 (42.2) 133 (57.8)
Preoperative
Age, yr ,.0001
45 58 (55.2) 47 (44.8) 2.72 (1.59–4.67)
.45 39 (31.2) 86 (68.8) 1
Sex .144
Male 35 (49.3) 36 (50.7) 1.52 (.86–2.67)
Female 62 (39) 97 (61) 1
BMI, kg/m2 .759
.50 16 (40) 24 (60) .90 (.45–1.80)
50 81 (42.6) 109 (57.4) 1
Diabetes duration, yr ,.0001
5 46 (59) 32 (41) 3.51 (1.96–6.26)
.5 41 (29.1) 100 (70.9) 1
Insulin therapy ,.0001
No 78 (55.7) 62 (44.3) 4.17 (2.62–7.70)
Yes 19 (23.2) 63 (76.8) 1
OHA ,.0001
1 81 (50) 81 (50) 3.25 (1.71–6.16)
.1 16 (23.5) 52 (76.5) 1
C-peptide, ng/dL .024
.2.8 36 (50.7) 35 (49.3) 2.14 (1.10–4.17)
2.8 25 (32.5) 52 (67.5) 1
HbA1C ,.0001
7 % 52 (70.3) 22 (29.7) 5.83 (3.18–10.70)
.7 % 45 (28.8) 111 (71.2) 1
Hypertension ,.0001
Yes 37 (30.6) 84 (69.4) .34 (.20–.59)
No 59 (56.2) 46 (43.8) 1
Dyslipidemia .010
Yes 38 (34.2) 73 (65.8) .49 (.29–.85)
No 58 (51.3) 55 (48.7) 1
1 yr postoperative
%EWL .007
.50 66 (45.5) 79 (54.5) 2.33 (1.26–4.32)
50 19 (26.4) 53 (73.6) 1
OR5 odds ratio; CI 5 confidence interval; BMI 5 body mass index; OHA 5 oral hypoglycemic agents; HbA1C 5 glycosylated hemoglo- bin; %EWL5 percentage of excess weight loss.
Italics indicate statistical significance.
* Complete remission defined as normal readings of glucose metabolism (HbA1C,6% and FBG ,100 mg/dL (5.5 mmol/L) in absence of diabetic medications. No complete remission includes partial remission, improvement and unchanged status.
remission after bariatric surgery but did not assess the fea- tures associated with such remissions [12]. In addition, research assessed such characteristics in gastric bypass sur- gery more than in SG [6,10,13,14], despite the widespread use of SG. The sparse research that examined features associated with T2D remission after SG scrutinized few clinical predictors while omitting others (e.g., age, HbA1C, C-peptide, OHA, insulin therapy, and %EWL) [9,11,15], employed modest sample sizes [11,16,17], did not undertake multivariate analyses necessary to identify in- dependent predictors [23], and focused on complete remis- sion but not partial remission, improvement, or unchanged status. The present study found that, compared with those
with no remission, patients with complete remission were significantly younger, had shorter duration of diabetes, were not on insulin therapy, took fewer OHA, had higher C-peptide and lower preoperative HbA1C, were less likely to have had hypertension or dyslipidemia, and were more likely to have achieved higher %EWL. Independent predic- tors of complete remission were HbA1C, insulin therapy, age, OHA, and postoperative %EWL.
In terms of T2D remission at 1 year, the present study observed 42.2% complete remission and 18.8% partial remission rates. Both these levels were lower than those re- ported by other authors (66.2%–79.1% complete remission, 11.9% partial remission) [24–26]. Such variations in remission rates are probably because of the heterogeneity of definitions of T2D remission employed by various studies [6,8,16]. For instance, others observed a decrease in complete remission from 92.7% to 43.6% when using a more stringent definition [27]. Hence, we support the use of agreed upon standard criteria for T2D complete remission enables more precise comparisons between studies [28].
Certain characteristics of the patients in our study are indic- ative of greater disease severity, and therefore may explain the lower remission rate we observed compared with other studies. These factors include an older patient population (45 versus 36.1 yr) [25], and a higher percentage of patients with longer diabetes duration (61% versus 31%) [26]. We also noted a higher percentage of patients on insulin therapy (36% versus 5.3%) [26] and using multiple OHA (29.6%
versus 7.1%) [29].
Table 5
Comparison of 7 proposed models for prediction of T2D complete remission after SG*
Model Logistic regression ROC analysis
P valuey AUC 95%CI P value
1 Diabetes duration1 pre-HbA1C .985 .74 .67–.81 ,.0001
II Diabetes duration1 pre-HbA1C 1 %EWLz .980 .75 .68–.82 ,.0001
III Diabetes duration1 pre-HbA1C 1 %EWLz 1 insulinx
.999 .77 .71–.84 ,.0001
IV Diabetes duration1 pre-HbA1C 1 %EWLz
1 insulinx1 age .604 .79 .72–.85 ,.0001
V Diabetes duration1 pre-HbA1C 1 %EWLz
1 insulinx1 age 1 OHA .162 .81 .74–.87 ,.0001
VI Diabetes duration1 pre-HbA1C 1 %EWLz 1 insulinx1 age 1 hypertension 1 dyslipidemia
.354 .78 .71–.84 ,.0001
VII Diabetes duration1 pre-HbA1C 1 %EWLz 1 insulinx1 age 1 hypertension 1 dyslipidemia1 OHA 1 C-peptide
.346 .82 .75–.89 ,.0001
T2D5 type 2 diabetes; SG 5 sleeve gastrectomy; ROC 5 receiver operating characteristics; AUC 5 area under the curve; CI5 confidence interval; pre-HbA1C 5 preoperative glycosylated hemoglobin; %EWL 5 percent excess weight loss; OHA5 oral hypoglycemic agents.
Italics indicate statistical significance.
* Logistic regression was employed. Only models that represented a good-fit (Hosmer and Lemeshow test P. .05) were then assessed for their discrimination power using ROC analysis.
yP value for Hosmer and Lemeshow test.
z%EWL percentage of excess weight loss at 1 yr.
xPreoperative insulin therapy.
Table 6
Independent predictors of T2D complete remission*
Variable Category Adjusted OR (95%CI) P
Diabetes duration 5 1.90 (.92–3.89) .081
Pre-HbA1C 7 4.93 (2.32–10.45) ,.0001
%EWLy .50 2.39 (1.12–5.12) .025
Insulinz No 2.34 (1.10–4.97) .027
Age 45 2.31 (1.17–4.58) .016
Oral hypoglycemic agent 1 2.75 (1.29–5.88) .009 T2D5 type 2 diabetes; OR 5 odds ratio; CI 5 confidence interval; pre- HbA1C5 preoperative glycosylated hemoglobin; %EWL 5 percentage of excess weight loss.
Italics indicate statistical significance.
* Based on multivariate logistic regression for the variables comprising Model V.
y%EWL at 1 yr.
zPreoperative insulin therapy.
Likewise, our 76.6% T2D improvement rate was compa- rable to the 86% reported elsewhere [30]; while our 4.5%
unchanged diabetes status was higher than others who re- ported no patients with unchanged diabetes status, probably due to their small sample size (44 patients) [31]. T2D remis- sion after SG could be because of the dramatic reductions in caloric intake leading to decreased insulin requirement, together with an increase in glucagon-like protein-1 hor- mone level critical for glucose homeostasis, as well as im- provements in insulin resistance associated with weight loss [32,33].
In terms of patient characteristics, our patients who achieved complete remission were likely to be younger (odds ratio [OR] 2.72, 95% confidence interval [CI] 1.59–
4.67) (Table 4), consistent with others [6,7,26], and with research where patients who achieved complete remission were approximately 6.48 years younger compared with those who did not [8]. Aging is associated with greater dete- rioration of pancreatic reserve and disease progression, both resulting in lower remission rates [34]. As for the duration of diabetes, shorter T2D duration was associated with com- plete remission (OR 3.51, 95%CI 1.96–6.26), consistent with research where patients in remission had a shorter mean T2D duration compared with those with no remission (4.7 versus 10.3 yr) [6]. Longer T2D duration reflects dis- ease severity because of reduced beta-cell function and secretory capacity, which significantly reduces the chances
of complete remission [23,26,35]. In addition, absence of in- sulin therapy was 4.17 more likely to be associated with complete remission. This supports research where patients not requiring insulin exhibited higher remission rates than those on insulin [6,16]. Insulin therapy reflects significantly reduced beta cells function that may not fully respond to the weight loss and increase in incretin after bariatric surgery [6,26].
In the present study, using fewer OHA medications was associated with a higher chance of remission (OR 3.25, 95%CI 1.71–6.16), in agreement with others [8,35]; and higher C-peptide was associated with greater chance of remission (OR 2.14; 95%CI 1.10–4.17), supporting other studies [7,8,17,23]. C-peptide reflects pancreatic beta cell function, therefor higher level is associated with greater dia- betes remission [36]. High C-peptide may also implicate in- sulin resistance, known to improve with weight loss after surgery [17,37].
Across the current sample, lower preoperative HbA1C was associated with remission (OR 5.83 95%CI 3.18–
10.70), supporting other research [6,8–11]. Higher HbA1C may indicate poorer glycemic control and greater disease severity, known to reduce the chance of T2D remission.
However, T2D patients with higher HbA1C should not be denied bariatric surgery, as they are at high risk of T2D complications [38], and hence more likely to benefit from surgery.
Table 7
Comparison (mean6 SD) of pre- and 1-year postoperative characteristics: complete remission versus partial remission and versus improvement (n 5 230)
Variable Complete remission,
n mean6 SD
Partial remission, n mean6 SD
P value* Improvement, n mean6 SD
P valuey
Total n (%) 97(42.2) 25 (18.8) 102 (76.7)
Preoperativez
Age, yr 43.536 8.17 456 7.80 .422 48.026 9.34 ,.0001
Weight, kg 118.116 20.82 112.846 21.72 .265 113.436 19.48 .103
BMI, kg/m2 43.746 6.61 41.066 5.72 .067 43.756 7.48 .990
Diabetes duration, yr 6.546 4.60 8.146 6.60 .266 11.456 6.37 ,.0001
Insulin level,m/dLx 15.786 12.88 26.016 16.73 .136 206 24.63 .468
C-peptide, ng/dL 3.376 1.76 3.036 1.46 .466 2.776 2.53 .130
HOMA-IR{ 3.906 3.92 8.906 6.05 .049 9.536 13.53 .072
FBG, mmol/L 7.876 3.35 9.996 3.84 .014 10.256 4.48 ,.0001
HbA1C, % 7.456 1.60 8.576 2 .004 8.706 1.63 ,.0001
1 yr postoperativez
Weight, kg 86.476 18.47 86.026 13.17 .911 87.216 14.36 .761
BMI, kg/m2 31.806 6.38 31.686 4.37 .926 33.726 5.93 .035
BMI change, kg/m2 12.106 4.31 9.556 3.99 .011 10.036 3.99 .001
%EWL 69.136 24.33 61.266 20.34 .151 57.026 22.47 .001
WL, kg 32.906 12.17 26.606 12.96 .029 26.226 10.99 .761
SD5 standard deviation; BMI 5 body mass index; HOMA-IR 5 homeostatic model assessment for insulin resistance; FBG 5 fasting blood glucose;
HbA1C5 glycosylated hemoglobin; %EWL 5 percentage of excess weight loss; WL 5 weight loss.
Italics indicate statistical significance.
* Complete remission versus partial remission.
yComplete remission versus improvement.
zFor all variables in the table, number of patients included in the analysis was 201–230 patients.
x50 patients included in this analysis.
{43 patients included in this analysis.
As for postoperative features, achieving higher %EWL (.50%) was associated with complete remission (OR 2.33, 95%CI 1.26–4.32), consistent with others [6]. Weight loss ameliorates insulin resistance and improves insulin sensitivity, leading to T2D remission [39].
In terms of prediction models of complete remission, we proposed 7 models (Table 5), and found the most useful model (Model V, AUC .81) comprised diabetes duration 1 pre-HbA1C 1 %EWL 1 insulin therapy 1 age 1 OHA (P , 0.0001). Although our Model VII had greater AUC (.82), it nevertheless comprised 3 more factors (i.e., all factors of Model V1 hypertension 1 dyslipidemia 1 C-peptide). One study proposed 8 models to predict T2D remission and concluded the most useful model was the model that included age 1 HbA1C 1 C-peptide (AUC .76, P, .001) [8]. Compared with Souteiro et al. [8], our Model V displayed a slightly greater AUC, and did not include C-peptide as a predictor.
As for independent predictors of complete remission, younger age, lower HbA1C, insulin therapy, and higher % EWL independently predicted remission (Table 6), consis- tent with other research [8,15,35]. We also observed that fewer OHA independently predicted remission, in contrast with others [8]; and T2D duration was not an independent predictor of remission, in contrast to other studies [7,15,35].
We compared the characteristics of patients with com- plete remission versus partial remission; and also, those of complete remission versus improvement (Table 7).
Compared with complete remission, both partial remission and improvement patients had higher FBG and HbA1C, and lower BMI change. We are unable to compare these findings with others because of the lack of studies on the factors associated with partial remission or improvement af- ter SG. However, we observed that older age, longer T2D duration, and lower %EWL were associated with improve- ment, in support of research among Roux-en-Y gastric bypass patients [40].
This study has limitations. It is a single-center study and some patients with missing follow-up data were excluded from the analysis. We used HbA1C cut off level of,6% in line with others [6,21,22], but the use of lower ,5.7 [8] could have resulted in a different remission rates.
Assessment of outcomes at several time points could have contributed suggestions about the exact time point when remission occurred. We did not undertake analysis at a time point before 12 months, hence it is difficult to deter- mine if some patients remitted earlier. Using a single time point may have confounded the results. On the other hand, most studies assessed diabetes remission at 1 year [6,15,16,35], with the exception of 1 study [9] that assessed early diabetes metabolic nonresponse at 3 months [9]. This study found, across 82 diabetic patients, that there was no correlation between insufficient weight loss and metabolic failure/response [9]. Longer-term follow- up would have been beneficial in identifying the durability
of remission. However, our observations at 12 months agree with that the stabilization of weight loss occurs mostly within 1 year after bariatric surgery [41]. Applying existing scoring systems (e.g., DiaRem) [42] in the pre- sent study would have provided useful information on the effectiveness of each factor in predicting diabetes remission after SG [22]. However the score is based on preoperative variables with no consideration of postopera- tive weight loss, which is the main mechanism of remis- sion of T2D after SG.
Despite this, the study has strengths. It evaluated a range of demographic, anthropometric, biochemical, and clinical factors associated with remission among a larger sample size than most other studies [6,11], and included only SG patients, contrary to others [9,7]. Understanding the modifi- able factors that influence T2D remission after SG could lead to better strategies to enhance durable remission.
Employing the American Society of Bariatric and Metabolic Surgery definitions, we categorized 4 remission levels (com- plete remission, partial remission, improvement, unchanged status), unlike others [6,11,15]. Such ‘fine grained’ catego- rization allowed the additional detailed classification of pa- tients into partial remission or improvement (collectively amounting to.50% of incomplete remissions) for more ac- curate results. The use of logistic regression allowed the assessment of factors that independently predicted T2D remission.
Conclusion
SG results in significant weight reduction and various ex- tents of T2D remission. Partial remission was associated with higher FBG, HbA1C, and HOMA, and lower BMI change. Improvement was associated with older age, higher FBG and HbA1C, and lower BMI change and %EWL.
Several factors independently predicted T2D complete remission, including younger age, fewer OHA, absence of insulin therapy, lower HbA1C, and greater %EWL. These findings can assist in identifying patients that are most likely to benefit from SG in terms of the extent of T2D remission.
Identifying such patients with modifiable characteristics that can be altered to increase their likelihood of remission after SG is important.
Disclosures
The authors have no commercial associations that might be a conflict of interest in relation to this article.
Acknowledgments
The authors thank Mr. Arnel Briones Alviz and Dr. P.
Chandra for their assistance with data processing and data analysis, respectively. The authors also thank the patients included in this study and acknowledge the surgeons and perioperative staff involved in the procedures.
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