The Rapid Changes in Bodyweight and Glycemic Control Are Determined by Pre-status After Bariatric Surgery in Both Genders in Young Chinese Individuals

Purposes: The primary aim of this clinical study is to identify the factors associated with rapid glycemic, bodyweight, and lipid profile remission in young obese patients following bariatric surgery. Materials and methods: In a total of 131 Chinese in-patients at Shanghai Pudong Hospital, China, we retrospectively analyzed in-patient data of metabolic parameters, including BMI, waist circumference, blood pressure (BP), and blood laboratory tests, such as plasma lipids and lipoprotein, hemoglobulin A1c (HbA1c), and oral glucose tolerance tests (OGTT) before bariatric surgery. We followed up these indices at the first month, third months, half-year, and one year later. Results: The results showed that bodyweight, BP, fasting plasma glucose (FPG), HbA1c, and triglyceride (TG) levels decreased significantly in one to three months following surgery in both male and female patients (p<0.05). We demonstrated that age (male: β=-0.181; female: β=-0.292) and the pre-operation HbA1c levels (male: β=0.935; female: β=0.919) were independent predictors of HbA1c reduction in both young obese male and female patients in three months after surgery. For body weight loss, age (β=-0.229) and pre-operation bodyweight (β=0.735) are the predictors in females, but only pre-operation body weight (β=0.798) is the independent predictor in obese young male patients. Conclusion: This study discovered that changes in bodyweight were determined by age, pre-operation status of bodyweight, and HbA1C in obese young Chinese.


Introduction
Obesity or overweight is the leading cause of type 2 diabetes mellitus (T2D) today [1].Obesity (defined as a BMI of 30 kg/m 2 ) was 10.8% and 15.0% in men and women, respectively, in 2014.Overweight (defined as a BMI of 25-30 kg/m 2 ) was 24.4% and 27.9% in men and women, respectively.By 2025, it is expected that the global prevalence of obesity will climb to 18% in men and 21% in women [2].Obesity is a spectrum of disorders characterized by the BMI criteria (a BMI of 30 kg/m 2 is considered obese by the WHO in Caucasians; however, 28 kg/m 2 is considered obese in Chinese) [3].Despite the fact that bariatric surgery was the approach to treating morbid obesity, recent research and clinical settings have repeatedly shown that it can result in glucose metabolism remission [4,5].Multiple studies show that bariatric surgical therapies, such as Roux-en-Y gastric bypass (RYGB), vertical sleeve gastrectomy (VSG), and biliopancreatic diversion (BPD), could improve diabetes in the majority of patients, with results that are independent of bodyweight loss [6].The underlying mechanisms may include caloric restrictions or malabsorption, changes in gut hormones (especially glucagon-like peptide 1 (GLP-1)), gut microbiota, and others [7].Moreover, few studies in the literature compare the metabolic consequences of bariatric surgery on male and female patients.As a result, the impacts of gender variation in glucose metabolism, bodyweight, blood pressure, lipids, and lipoprotein, as well as the predictor of rapid change of previous clinical parameters in different genders, were studied retrospectively in this study.The purpose of this study is to figure out how to tailor treatment for different genders and predict surgery outcomes.

Ethics Statements
The study, including surveys, sampling, examinations, and raw data access or utilization, has obtained ethics approvals and permissions from the Ethics Committee of Shanghai Pudong Hospital (No. WZ-010).The informed consent was received from study participants before the whole study.The guidelines outlined and procedures were under the Declaration of Helsinki.All the data used in this study were anonymized before its use.

Source of In-patient Data
Patients' information was collected from the in-patient information system at Shanghai Pudong Hospital.Based on the Chinese diagnosis standard for obesity (BMI≥28 kg/m 2 ), we included 131 adult, obese patients from the year 2016-2019 who underwent bariatric surgery (including 119 sleeve gastrectomy (SG), and one biliopancreatic diversion with duodenal switch (BPD-DS), three stomach-intestinal pylorus sparing (SIPS), six RYGB, and two adjustable gastric band (AGB)) in the Department of Gastrointestinal Surgery.These individuals had their pancreatic function evaluated in the Department of Endocrinology prior to surgery, including OGTT and insulin release assays.Secondary obesity, such as Cushing syndrome, is among the exclusion criteria.

Statistical analyses
Statistics analyses were performed in Statistical Product and Service Solutions (SPSS) (version 26.0;IBM SPSS Statistics for Windows, Armonk, NY) and Prism (GraphPad, version 9.0).Two-way ANOVA was used to compare changes in the levels of bodyweight, HbA1c, FPG, and plasma lipids.Multilinear regression analyses were performed to establish the models of the proper predictors of bodyweight and HbA1c changes in three months, respectively.Statistical significance was set at p<0.05 level for all analyses.

Analyses of the glycemic state and pancreatic function prior to bariatric surgery
We first observed that male and female patients had comparable venous glucose plots evaluated by OGTT.Then, we evaluated the insulin and C-peptide release tests and found that there were no significant differences between the genders.Furthermore, our findings indicated that HbA1c, HOMA-β, and HOMA-IR were equivalent in both male and female patients (Fig. 1, Table 2).

Analyses of the bodyweight change, HbA1c, FPG, BP, plasma lipids, and lipoprotein after bariatric surgery
The findings revealed that the extent of bodyweight loss from the baseline was significant in both genders when compared to the first month with three months, six months, and one year.Similarly, blood pressure including systolic (SBP) and diastolic pressure (DBP) declined dramatically in the first month after surgery (Table 3).Note: pre-op: pre-operation; SBP: systolic blood pressure; DBP: diastolic blood pressure; 1 m: first month after operation; 3 m: 3 months after operation; 6 m: 6 months after operation; 1 y: 1 year after operation.

Males
When comparing the amplitude of HbA1c and FPG value drop from the baseline, we found a significant decrease in both male and female patients after three months compared to those of six months and one year (Table 4).Note: HbA1c: glycated hemoglobin A1c; FPG: fasting plasma glucose; pre-op: pre-operation; 3 m: 3 months after operation; 6 m: 6 months after operation; 1 y: 1 year after operation.

Males
The TG levels, similar to HbA1c, also decreased significantly in three months.However, when compared to BMI and blood glucose, alterations in HDL and LDL were less obvious in the first one to three months after surgery.The HDL level in female patients considerably increased after six months, while male patients' HDL levels dramatically increased after a year.We only found that a significant decrease in the level of LDL occurred in females one year post-operation (Fig. 2, Table 5).Significant BMI changes occur one month after surgery, while HbA1c, FPG, and TG changes occur three months after surgery, according to the data.However, in both male and female patients, a tendency of change in HDL and LDL has lately occurred after six months.

Effects of independent factors on bodyweight loss and HbA1c reduction three months following bariatric surgery studied using multilinear regression
Furthermore, we established a multilinear regression model to investigate the factors that contributed to the significant change in post-operation bodyweight and HbA1c three months following bariatric surgery (Table 6).Surprisingly, the findings revealed that the bodyweight loss differentiates by gender.We discovered that, in males, pre-operation bodyweight was the only independent determinant of significant bodyweight loss in three months (β=0.798,p<0.001), whereas, in females, pre-operation bodyweight and ages were the independent determinants (pre-operation bodyweight: β=0.735, p<0.001; age: β=-0.229,p=0.004) of postoperation bodyweight.For HbA1c reduction at three months, the regression model showed that both in males and females, pre-operation HbA1c (male: β=0.935; female: β=0.919) and age (male: β=-0.181;female: β=-0.292) were the independent predictors.

Discussion
Bariatric surgery was first developed to treat morbid obesity by changing the gastrointestinal tract (GI) in a variety of ways, resulting in a change in physiological digestion and absorption function, a reduction in energy intake, and rapid weight loss [8].Bariatric surgery, on the other hand, has been demonstrated to be effective in treating hyperglycemia, dyslipidemia, hyperuricemia, hypertension, and other metabolic syndrome disorders [9][10][11].Numerous clinical studies have suggested that a significant portion of the incidence of improvement in hyperglycemia or diabetes remission may be independent of bodyweight loss [12][13][14].Bodyweight, FPG, HbA1c, and blood pressure all decreased rapidly in the first one to three months after surgery, according to this study.Patients' baseline conditions, such as pre-operation BMI and HbA1c, as well as their age, were the underlying clinical causes for this rapid decrease.Other factors that may have an impact after surgery include nutrition [15,16], physical activity [17], and medicines [18], which were not examined in this study.As reported in earlier research, baseline metabolic variables and age could account for 63%-88% of the causes for dramatic improvements in bodyweight and HbA1c in the first three months after surgery.
Before surgery, we compared the glycemic state and pancreatic function of the two genders.We discovered that the OGTT profile was generally similar in males and females, with a peak appearing 30 minutes to one hour after oral glucose intake and declining to fasting three hours later.In insulin and c-peptide release assays, female patients had lower insulin and c-peptide release than male patients.The difference, however, was not statistically significant.In both genders, the mean insulin and c-peptide release was less than five times that of fasting insulin and c-peptide release, indicating that pancreatic function was slightly impaired.Additionally, we noticed that HbA1c was slightly lower in female groups, indicating that female patients had better glycemic control in the three months previous to surgery than male patients.Furthermore, we utilized the HOMA model to assess pancreatic function and insulin resistance in male and female patients.While pancreatic functions were equivalent, male patients' insulin resistance was higher than female patients, which could be attributed to male patients' higher bodyweight.
Then, in both men and women, we evaluated the rate of bodyweight reduction and metabolic indicators, which were mostly consistent with previous findings [19][20][21].The substantial decrease in bodyweight, HbA1c, FPG, BP, and TG levels changed in the first one to three months; however, the level of HDL and LDL changed approximately six months or one year later.We hypothesize that caloric restriction [22], relief of hyperglycemia, lipid toxicity, and insulin resistance are clinically responsible for this effect [23].Unfortunately, we were unable to perform OGTT or insulin and c-peptide assays following surgery.Hence, we could not determine the dynamic changes in pancreatic function and insulin resistance.Nonetheless, we ultimately concluded that, in the first one to three months, a decrease in HbA1c was related to a lower mean level of FPG, indicating normalization of glucose tolerance and pancreatic function.The significantly delayed reduction in HDL and LDL may be due to the following change in bodyweight and reduced adipose tissue [24][25][26].
In the present study, we further explored the assessable indices in relation to the rapid loss of bodyweight and improvement of HbA1C.We discovered that pre-operation bodyweight and age were the strongest predictors of the bodyweight reduction, accounting for 63%-67% of the causes.Although it remains to be confirmed whether there is a relationship between age and bodyweight, our hypothesis regarding preoperative bodyweight is consistent with previous evidence [27].Because the patients were young, we believe that the gender variations in this study are due to sex hormones.Sex hormone disturbance due to metabolic syndrome before the surgery may account.The normal effect of estrogen has been associated with weight loss, adipose tissue inflammation, and insulin resistance in obese people [28].The fact that some unpregnant female patients (n=7) were able to become pregnant following an SG in this study supports this theory.
Finally, we discovered that pre-operation HbA1c levels and age accurately predicted HbA1c change in the one to three months following surgery [29], indicating that aging is associated with a loss of pancreatic function and increased insulin resistance.The greater the HbA1c and the younger the patient, the better glycemic control or diabetes remission.The changes in gastrointestinal hormonal response [30] and gut microbiota with aging may be the additional causes for the effects we identified in this investigation.

Limitations
The conclusion was supported by research conducted at one research center.In addition, further data on alteration of the serum GLP-1, SNS activity, and adipose mass data should be included.Therefore, further research should be conducted to corroborate the recent results.

Conclusions
Altogether, we demonstrated that, regardless of gender, bariatric surgery could effectively reduce bodyweight and contribute to the improvement of hyperglycemia, hypertension, and dyslipidemia.Age is an independent indicator that predicts the rapid change in bodyweight in females, but predicts the HbA1c changes in both genders after surgery.The different profiles of metabolic indices after bariatric surgery could be traced to the variation between genders in these young patients, according to this study.

FIGURE 1 :
FIGURE 1: The indices related to glycemic state and pancreatic function before bariatric surgery.The figure showed the results of the analyses on OGTT (A), insulin (B), and c-peptide release tests (C), HbA1c (D), HOMA-IR (E), and HOMA-β (F).All the indices were not significantly different between the male and female patients (p>0.05).Note: OGTT: oral glucose tolerance tests; OP: bariatric surgery; HOMA-IR: homeostasis model assessment of insulin resistance; HOMA-β homeostasis model assessment of β-cell function