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. Author manuscript; available in PMC: 2025 Oct 1.
Published in final edited form as: Clin Obes. 2024 Dec 17;15(2):e12726. doi: 10.1111/cob.12726

Changes in insulin sensitivity and gut peptides 8 and 52 weeks after bariatric surgery or low-calorie diet

Adam C Lowe 1, Dorien Reijnders 1, Charmaine S Tam 1,2, Leanne M Redman 1, Robbie Beyl 1, Karl A LeBlanc 3, Mark G Hausmann 3, Vance L Albaugh 1, Frank L Greenway 1, Eric Ravussin 1
PMCID: PMC12199209  NIHMSID: NIHMS2071231  PMID: 39688305

Summary

The endocrine consequences of weight loss by bariatric surgery (BS) and caloric restriction are not fully understood but contribute to variable improvements in insulin sensitivity and cardiometabolic health. This study compared changes in insulin sensitivity and plasma concentrations of gut peptides 8 weeks and 1 year after BS and a low-calorie diet (LCD). Nineteen female patients with obesity self-selected BS (gastric bypass [n = 5] or sleeve gastrectomy [n = 7]) or LCD (n = 7) in this parallel-arm, prospective observational study. We assessed insulin sensitivity via a two-step hyperinsulinemic–euglycemic clamp (20 and 80 mU/min/m2 insulin). Plasma glucose, insulin, and gut peptides were measured around a mixed meal tolerance test (400 kcal). Visual analogue scales (VAS) were used to rate subjective appetite sensations. All assessments were conducted at baseline and after 8 weeks and 1 year of intervention. Whole-body insulin sensitivity was unchanged 8 weeks after the intervention. One year after surgery, insulin sensitivity at both 20 and 80 mU/m2/min insulin infusion doses increased with BS weight loss (−33.8% ± 1.4% body weight) but was unchanged in LCD with small weight loss (−3.7% ± 2.0% body weight). Postprandial total PYY increased more following BS while total and acylated ghrelin decreased more following BS compared to LCD. Hunger decreased and fullness increased with BS compared to LCD (p = .037; p = .010, respectively). Insulin sensitivity was improved only 1 year after BS, despite significant weight loss after 8 weeks. Changes in gut peptides after BS paralleled reduced hunger and increased fullness. Most improvements in cardiometabolic health were related to weight loss.

1. INTRODUCTION

Adiposity is one of the main metabolic risk factors for insulin resistance and metabolic diseases including type 2 diabetes mellitus (T2DM).1 Bariatric surgery (BS) is recognized as the most effective approach for weight loss2, 3 with Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) being the most predominant procedures worldwide.2

RYGB and SG also contribute to remission of T2DM via improvements of glucose metabolism that often occur within days after surgery.4, 5 These short-term postoperative improvements are greater than expected for the concomitant body weight loss but have been explained by calorie restriction, enhanced incretin responses, and a higher rate of ingested glucose absorption into systemic circulation.6, 7 Conversely, changes in peripheral insulin sensitivity seem to occur in a delayed fashion and, following a substantial amount of weight loss.8–11 Whether the anatomical manipulation of the upper gastrointestinal tract or the permanent intake of fewer calories is the reason for late changes in insulin sensitivity is debated.4, 9, 12 Studies have assessed insulin sensitivity by means of the hyperinsulinemic–euglycemic clamp only up to several weeks following BS while longer-term outcomes are primarily reported after RYGB compared to SG.8, 9, 12, 13 From the limited available literature, improvements in insulin sensitivity appear to be similar following RYGB and SG among individuals with and without T2DM.10 A recent elegant study has shown that the metabolic benefits of gastric bypass surgery and diet were similar and were apparently related to weight loss itself.14

BS is typically accompanied by reduced appetite. However, the mechanisms driving this post-surgery reduction in appetite have not been fully elucidated.15 The level of gut peptides that contribute to appetite regulation change following BS and likely provide additive appetite-suppressing effects. Conversely, diet-induced weight loss increases subjective appetite and is also associated with changes in gut peptides known to increase hunger.16, 17 The duration of these alterations in gut peptides and subjective appetite following RYGB and SG as well as diet-induced weight loss are inconsistently identified among the limited studies that report longer-term outcomes.18

The primary aim of this study was to investigate whether RYGB and SG (BS) or a LCD differentially affects insulin sensitivity 8 weeks and 1 year after the intervention. Our secondary aim was to evaluate the relation between weight loss, changes in insulin sensitivity, the postprandial plasma gut peptide responses to a mixed meal tolerance test, and subjective ratings of appetite on the short (8 weeks) and longer term (1-year post-intervention).

2. METHODS

2.1. Study participants

The present study is a secondary analysis designed to investigate the short- (8 weeks) and longer-term (1 year) effects of BS procedures versus a LCD on changes in insulin sensitivity (two-step hyperinsulinemic–euglycemic clamp) as well as changes in plasma glucose, insulin, and gut peptides following a 400-kcal mixed meal tolerance test. Details of the screening process and study population are described in the primary outcomes paper.19

In brief, 30 participants with obesity (age 18–65 years old; BMI > 40 kg/m2 or BMI > 35 kg/m2 with at least one obesity-associated comorbidity such as diabetes, hypertension, dyslipidemia, or sleep apnoea) consented to participate in this study. Individuals were excluded for diabetes diagnosed more than 5 years ago, previous malabsorptive or restrictive surgery, a history of inflammatory intestinal disease, psychiatric conditions, or the use of medications that affect weight or energy metabolism. Participants were recruited through offices of bariatric surgeons in Southeastern Louisiana. The LCD group was recruited from the same offices and consisted of individuals with the same inclusion/exclusion criteria and were medically qualified for obesity surgery or met the NIH criteria for BS but elected to not undergo BS. Recruitment and data collection occurred between 2010 and 2014. The study was conducted at Pennington Biomedical Research Center (PBRC) under oversight by the Pennington Biomedical and Western Institutional Review Boards and was registered at Clinicaltrials.gov (NCT00936130). A flowchart summarising the throughput of the individuals in the present study is provided in Figure S1.

2.2. Study design

This was a parallel-arm, prospective observational study. Data were collected at baseline before surgery or initiation of LCD (baseline), as well as 8 weeks and 1 year after the surgery or the start of the LCD. Subjects who elected to undergo BS self-selected their preferred procedure [RYGB, SG or laparoscopic adjustable gastric banding (LAGB)] following a preoperative evaluation conducted by the surgeons. All surgical procedures were performed laparoscopically according to each surgeon’s routine practice. Participants in the LCD group were instructed to consume an 800 kcal/day liquid diet (6% fat, 56% carbohydrate, and 38% protein) for 8 weeks (Health One, Health and Nutrition Technology, Carmel-By-The-Sea, CA, USA). Energy required for the maintenance of body weight was determined after 8 weeks from the average of two energy expenditure calculations20, 21 and 24-h metabolic chamber energy expenditure,22 and participants were prescribed a balanced diet containing 500 kcal/day less than the calculated value. Body composition was assessed at baseline, 8 weeks, and 1 year by DXA scans (Lunar iDXA: GE Healthcare). All clinical study measurements [hyperinsulinemic clamp, mixed meal tolerance test, DXA scans, and visual analogue scales (VAS)-scores] were conducted following a 10-h overnight fast. Surgery subjects attended monthly clinic visits, whereas the LCD group had weekly visits with a dietician for the first 8 weeks and monthly visits thereafter.

2.3. Assessment of insulin sensitivity

A two-step hyperinsulinemic–euglycemic clamp combined with a [6,6-2H2]-glucose tracer (Cambridge Isotope Laboratories, Andover, MA, USA) was performed to measure endogenous glucose production (EGP),23 hepatic insulin sensitivity (%suppression of EGP) and peripheral insulin sensitivity [insulin-stimulated glucose disposal rate (GDR)].24 The ~24 h prior to the clamp, participants stayed in a metabolic chamber. At 6:00 AM, a primed, continuous infusion of [6,6-2H2] glucose was started (2 mg/min/kg) which was continued throughout the clamp procedure. After 3.5 h of basal state measurements, insulin was infused for 180 min at 20 mU/min/m2 (low dose), followed by 120 min at 80 mU/min/m2 (high dose). Plasma glucose concentrations were driven to and maintained at 120 mg/dL by variable co-infusion of a 20%-dextrose solution.

To account for the improved clearance of plasma insulin after weight loss, the insulin infusion doses of the post-surgery clamps were increased to 22 and 88 mU/min/m2 (step 1 and step 2, respectively) at week 8 and to 25 and 100 mU/min/m2 for the surgery groups only at 1 year. For the LCD group at 1 year, the insulin infusion dose was individualised according to the degree of weight loss achieved since baseline using the following criteria: (a) <3% weight loss = 22 and 88 mU/min/m2; (b) 3%–7% weight loss = 22.5 and 90 mU/min/m2; and (c) >7% weight loss = 25 and 100 mU/min/m2.

During the last 30 min of baseline, low-dose, and high-dose insulin infusions, resting metabolic rate and respiratory exchange ratio (RER) were measured (Max II Metabolic Cart, AEI Technologies, Bastrop, TX, USA) and three arterialised blood samples (using a heat-box at ~41°C) were collected from a superficial dorsal hand vein to measure plasma glucose and insulin concentrations. Steady-state insulin sensitivity was assessed as the glucose disposal rate (GDR) during the last 30 min of each step of the clamp [20 mU/min/m2 insulin (GDRlow) and 80 mU/min/m2 insulin (GDRhigh)].24, 25 Urine was collected to determine urinary nitrogen excretion rate and calculate substrate oxidation.26 The non-oxidative glucose disposal (NOGD or glucose storage) was calculated as the difference between the total GDR and the oxidative component of the GDR.27

2.4. Metabolic response to a mixed meal

After an overnight fast, participants ingested a 400-kcal test mixed meal consisting of a soft egg dish prepared by the metabolic kitchen (21 E% protein, 39 E% carbohydrate, and 40 E% fat) over 15 min. Blood samples were collected in the fasting (−15 and −5 min) and postprandial state (15, 30, 45, 60, 75, 90, 120, and 180 min) to measure glucose, insulin, total ghrelin (pooled acylated and deacylated versions of ghrelin), acylated ghrelin, and total peptide YY (PYY). Glucagon-like peptide-1 was also measured but is not reported due to problems with the assays. The average of the −15- and −5-min samples were considered the baseline fasting values. The postprandial response was computed as the area under the curve (AUC; total ghrelin, acylated ghrelin), and incremental area under the curve (iAUC; glucose, insulin, PYY) for all 180 min after initiating meal consumption, by the trapezoidal method.

VAS were used to retrospectively rate subjective appetite sensations during the week preceding the clinical visit. VAS scales (0–100 mm) measured ‘hunger’, ‘fullness’, ‘satisfaction’, ‘desire to eat’ and ‘prospective eating’. VAS were scored by measuring the distance from the left end (0 mm) of the line to the participant’s mark.28

2.5. Clinical chemistry

Plasma insulin concentrations were determined by immunoassay with chemiluminescent detection (Siemens, Washington, DC, USA). Glucose was analysed using an oxidase electrode method (DXC600; Beckman Coulter, Indianapolis, IN, USA). Plasma concentrations of total ghrelin, acylated ghrelin, and PYY were measured by radioimmunoassay according to manufacturer’s instructions (Millipore-Sigma, Burlington, MA, USA).

Ghrelin is primarily synthesised in the gastric fundus but is also produced in the proximal small intestines and other areas of the body.29 The gastric fundus tissue is removed during SG while it is bypassed in RYGB, typically resulting in a stronger reduction in fasting and postprandial levels following SG compared to RYGB.30–33

2.6. Sample size calculations

The change in GDR was used as the primary endpoint to calculate sample size. A mean and standard deviation GDR change of 2.51 ± 2.17 mg/min/kg of fat free mass was previously reported following 10% weight loss during a 1-year lifestyle intervention.34 Sample size in the present study was calculated to target an increase in GDR after 8 weeks and 1 year of weight loss by BS or a LCD. The required sample size to detect a 30% increase in GDR from baseline with 80% power and 0.05 significance was 11 subjects per group.

2.7. Statistical analyses

Only 12 female participants who elected to undergo RYGB or SG were analyzed in this study. This decision was made based on the very small numbers of male participants (n = 3) and of LAGB procedures (n = 7), which has fallen out of favour due to poor weight loss response overall. In contrast, merging RYGB and SG was due to the similarity of outcomes of these surgical procedures, which are posited to act through similar neurohormonal mechanisms (e.g., increased GLP-1 secretion). Among the five participants in BS who underwent RYGB, only two participants had a complete dataset for the mixed meal tolerance test (two participants required >60 min to consume the meal and one was unable to finish the meal).

Statistical analyses were performed using SPSS version 29 (IBM Corp.). Data are presented as mean ± standard error of the mean (SEM). Independent samples t-tests were used to assess baseline differences between groups. Linear mixed models were used to examine the effect of group (BS vs. LCD), time (8 weeks or 1 year), and group × time interactions on dependent variables. The absolute changes from baseline to each time-point (8 weeks or 1 year) were used as dependent variables; pairwise comparisons were used to evaluate differences between the change in dependant variables from baseline to 8 weeks and from baseline to 1 year when a significant interaction effect was identified. Pearson correlation coefficients were used to evaluate the relationship of dependant variables with body weight and body fat across all participants. Statistical significance was set at p < .05.

3. RESULTS

3.1. Study participants

Of the 19 female participants (BS: n = 12; LCD: n = 7), 12 participants (63%) were Caucasian, 6 (32%) African American/Black, and 1 (5%) Pacific Islander. At baseline, study groups did not significantly differ in mean age (45.5 ± 2.8 years), body weight (128.9 ± 5.4 kg), body mass index (47.6 ± 2.0 kg/m2), fat-free mass (54.6 ± 1.7 kg), or cardiometabolic health indicators (Table 1). Four of the 19 study participants (3 BS and 1 LCD) were diagnosed with diabetes within 5 years of the study start.

TABLE 1.

Baseline descriptive statistics for the bariatric surgery (BS) and low-calorie diet (LCD) groups.

BS group (n = 12)
Mean ± SEM		 LCD group (n = 7)
Mean ± SEM		 p
Age (years) 45.4 ± 3.2 45.7 ± 5.9 .96
Weight (kg) 133.2 ± 7.2 121.4 ± 7.6 .30
BMI 49.1 ± 2.7 45.1 ± 2.7 .35
SBP (mmHg) 122.5 ± 3.1 127.9 ± 5.9 .39
DBP (mmHg) 82.7 ± 2.2 80.4 ± 3.0 .55
GLU (mg/dL) 106.2 ± 3.6 101.4 ± 3.6 .40
INS (mU/mL) 18.8 ± 4.3 18.5 ± 4.8 .96
BF (%) 54.4 ± 1.6 52.7 ± 1.6 .50
Fat mass (kg) 69.0 ± 4.1 57.5 ± 4.0 .11
Lean mass (kg) 56.2 ± 2.3 51.2 ± 1.4 .19
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Note: Data are presented as mean ± SEM. The p-values indicate differences between BS and LCD group values at baseline.

Abbreviations: BF, body fat; BMI, body mass index; DBP, diastolic blood pressure; GLU, fasting plasma glucose; INS, fasting plasma insulin; SBP, systolic blood pressure.

3.2. Weight loss trajectories

Greater weight loss occurred following BS compared to LCD (pgroup < .001). Weight loss was also greater after 1 year compared to after 8 weeks (ptime < .001). A significant interaction effect was also noted for change in body weight (pinteraction <.001). Body weight decreased similarly between groups after 8 weeks [BS: −15.7 ± 2.6 kg (−11.9% ± 1.4%), LCD: −9.3 ± 3.4 kg (−7.7% ± 1.9%); p = .144], while a greater decrease in weight within BS compared to LCD was found after 1 year [BS: −45.5 ± 2.6 kg (−33.8% ± 1.4%), LCD: −4.9 ± 3.6 kg (−3.7% ± 2.0%); p < .001] (Figure 1).

FIGURE 1.

FIGURE 1

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Change in total weight and fat mass from baseline to 8 weeks and 1 year in BS and LCD. 1Y, 1 year; BL, baseline; BS, bariatric surgery; LCD, low calorie diet; W8, week 8.

Body fat mass decreased more in BS (pgroup < .001), after 1 year (ptime < .001), and demonstrated a significant interaction (pinteraction < .001). Fat mass tended to decrease more in BS than LCD after 8 weeks (p = .075), while a much greater decrease in body fat mass was exhibited within BS at 1 year compared to LCD participants (p < .001) (Figure 1).

3.3. EGP and hepatic insulin sensitivity

Changes in fasting EGP were similar between groups (pgroup = .505) but increased more after 1 year compared to 8 weeks (ptime = 0.014) (data not shown). An interaction effect was identified (pinteraction = .003), and fasting EGP tended to increase more in BS compared to LCD at 1 year (p = .064).

A marginally greater increase in hepatic insulin sensitivity was found in LCD (pgroup = 0.070) and increased more after 8 weeks (ptime = .013). An interaction was noted (pinteraction = 0.036), indicating similar increases between groups from baseline to 8 weeks (p = .222), but a sustained increase in LCD at 1 year that was greater than the decrease apparent in BS (p = .024).

The changes in fasting EGP correlated with both the changes in body weight (r = −0.39, p = .019) and fat mass (r = −0.67, p < .001). Similarly, the changes in hepatic insulin sensitivity correlated with changes in body weight (r = 0.43, p = .013) and fat mass (r = 0.41, p = .028).

3.4. Glucose disposal rate

GDR data are reported in Table 2 and Figure 2. GDR (mg/kg/min) at 20 mU/kg/m2 insulin (GDRLow) increased marginally more in BS but was similar between groups at 80 mU/kg/m2 insulin (GDRHigh). GDRLow and GDRHigh increased more at 1 year compared to 8 weeks but differently (interaction) in the two groups; both GDRLow, and GDRHigh increased more in BS than in LCD after 1 year (p = .001; p = .002, respectively) (Figure 2). Changes in GDR Low and GDRHigh were inversely related with changes in body weight (r = −0.69, p < .001; r = −0.61, p < .001, respectively) and fat mass (r = −0.76, p < .001; r = −0.66, p < .001, respectively).

TABLE 2.

Insulin sensitivity as determined by a two-step hyperinsulinemic–euglycemic clamp at 8 weeks and 1 year after bariatric surgery or a low-calorie diet.

Bariatric surgery
group (n = 12) Low-calorie diet group (n = 7) p
BL ΔW8 Δ1Y BL ΔW8 Δ1Y Group Time Interaction
GDRLow (mg/kg/min) 2.63 ± 0.24 −0.12 ± 0.30 2.19 ± 0.29 3.11 ± 0.29 −0.14 ± 0.22 0.41 ± 0.55 0.053 .<.001 <.001
GDRHigh (mg/kg/min) 7.26 ± 0.76 −0.44 ± 0.78 5.62 ± 0.74 7.67 ± 0.93 1.03 ± 0.73 1.24 ± 1.10 0.227 .<.001 <.001
NOGDLow (mg/kg/min) 2.34 ± 0.20 −0.39 ± 0.23 1.65 ± 0.28 2.43 ± 0.28 −0.64 ± 0.39 0.51 ± 0.31 0.071 <.001 0.125
NOGDHigh (mg/kg/min) 6.27 ± 0.67 −0.14 ± 0.73 4.95 ± 0.59 6.93 ± 0.89 0.66 ± 0.68 1.04 ± 0.91 0.098 <.001 <.001
ΔRERLow 0.04 ± 0.02 0.00 ± 0.02 0.06 ± 0.01 0.07 ± 0.01 0.00 ± 0.02 −0.04 ± 0.02 .022 0.376 0.006
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Note: Data are presented as mean ± SEM. Linear mixed models were used to analyze group, time, and interaction effects.

Abbreviations: ΔRERLow, change in respiratory exchange ratio (RER) at 20 mU/min/m2 insulin; ΔW8, change from baseline to week 8 (week 8 - baseline); Δ1Y, change from baseline to 1 year (1 year - baseline); BL, baseline; GDRLow, glucose disposal rate at 20 mU/min/m2 insulin; GDRHigh, glucose disposal rate at 80 mU/min/m2 insulin; NOGDLow, non-oxidative glucose disposal (NOGD) at 20 mU/min/m2 insulin; NOGDHigh, non-oxidative glucose disposal at 80 mU/min/m2 insulin.

FIGURE 2.

FIGURE 2

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Glucose disposal rate during low (20 mU/min/m2) and high (80 mU/min/m2) insulin dose infusion across timepoints in bariatric surgery (BS) group and low-calorie diet group (LCD) participants. GDR, glucose disposal rate.

As shown in Table 2, NOGD increased marginally more in BS during the steady state of low insulin infusion (NOGDLow) but even lesser so during high insulin infusion (NOGDHigh). Both NOGDLow and NOGDHigh showed greater increases after 1 year. An interaction effect was noted only for NOGDHigh, indicating a greater increase in NOGDHigh 1 year following BS compared to LCD (p < .001).

Metabolic flexibility measured by delta RER during low insulin infusion (ΔRERLow)35 increased more in BS. An interaction effect on changes in ΔRERLow was found, with a greater increase in ΔRERLow only after 1 year in BS compared to LCD (p < .001). Like the changes in GDR, the changes in metabolic flexibility were inversely related with changes in body weight (r = −0.43, p = .009) and fat mass (r = −0.55, p = .001).

3.5. Mixed meal tolerance test

Glycaemic parameters in response to the mixed meal tolerance test are reported in Table 3. Changes in fasting glucose were similar between groups and timepoints; however, a larger decrease only after 1 year following BS compared LCD (p = .041) was noted after a marginal interaction. Postprandial plasma glucose changes were similar between groups but tended to increase more after 8 weeks compared to 1 year. Fasting insulin was decreased more in BS and a greater decrease among BS after 1 year compared to LCD (p = .002) was noted. While the change in postprandial plasma insulin (iAUC insulin) indicated no effect of group or time, an interaction was observed showing a greater increase in iAUC insulin among BS compared to LCD only up to 8 weeks (p = .002).

TABLE 3.

Fasting and meal-stimulated glycaemic and GI peptide response at 8 weeks and 1 year after bariatric surgery or a low-calorie diet.

Bariatric surgery group (n = 7) Low-calorie diet group (n = 7) p
BL ΔW8 Δ1Y BL ΔW8 Δ1Y Group Time Interaction
Fasting
Fasting GLU (mg/dL) 103 ± 5 −9 ± 7 −18 ± 5 97 ± 4 −6 ± 2 −3 ± 2 0.187 0.322 0.051
Fasting INS (μU/mL) 13.9 ± 3.3 − 7.7 ± 2.6 −10.4 ± 3.0 12.0 ± 3.4 −5.1 ± 2.4 2.1 ± 1.4 0.025 0.215 0.012
Fasting PYY (pg/mL) 88 ± 9 − 13 ± 15 6 ± 6 89 ± 15 −14 ± 9 − 5 ± 4 0.567 0.178 0.663
Fasting total ghrelin (pg/mL) 510 ± 39 − 205 ± 31 −161 ± 35 477 ± 47 29 ± 31 48 ± 30 <.001 0.289 0.669
Fasting acylated ghrelin (pg/mL) 131 ± 31 − 74 ± 31 −50 ± 31 104 ± 20 9 ± 29 − 6 ± 14 0.126 0.672 0.105
Meal-stimulated
iAUC GLU (mg/dL) 1946 ± 402 1787 ± 866 455 ± 430 1714 ± 329 15 ± 476 −102 ± 316 0.126 0.076 0.149
iAUC INS (μU/mL) 4586 ± 1136 2128 ± 688 −596 ± 597 5230 ± 1465 − 1951 ± 1068 − 127 ± 944 0.101 0.431 <.001
iAUC PYY (pg/mL) 2303 ± 679 7709 ± 1911 6290 ± 1682 997 ± 417 1043 ± 767 1045 ± 791 <.001 0.654 0.653
AUC total ghrelin (pg/mL) 88 488 ± 5677 − 38 297 ± 5533 − 28 391 ± 4908 80 839 ± 6211 1115 ± 3181 2936 ± 2196 <.001 0.151 0.311
AUC acylated ghrelin (pg/mL) 18 298 ± 707 −8271 ± 1288 −6674 ± 1017 15 571 ± 3281 1217 ± 2817 71 ± 1949 0.006 0.816 0.175
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Note: Data are presented as mean ± SEM. Linear mixed models were used to analyse group, time, and interaction effects.

Abbreviations: ΔW8, change from baseline to week 8 (week 8 baseline); Δ1Y, change from baseline to 1 year (1 year baseline); AUC, area under the curve; BL, baseline; GLU, glucose; iAUC, incremental area under the curve; INS, insulin; PYY, peptide YY.

Change in fasting glucose was correlated with changes in body weight (r = 0.58, p = .002) and fat mass (r = 0.57, p = .004). Similarly, the change in fasting insulin was correlated changes in body weight (r = 0.52, p = .007) and fat mass (r = 0.47, p = .020).

Gut peptide responses are reported in Table 3. Fasting PYY changes were unaffected by group, time, or their interaction. Postprandial plasma PYY concentration (iAUC PYY) increased significantly more in BS compared to LCD, but was similarly changed at 8 weeks and 1 year irrespective of group. No interaction effect of group by time was found for iAUC PYY (Figure 3). Fasting and postprandial (AUC) total ghrelin decreased in BS compared to an increase in LCD, with no other effects on total ghrelin. Fasting acylated ghrelin showed no main effects or interaction. Postprandial plasma acylated ghrelin concentration (AUC acylated ghrelin) decreased more in BS compared to an increase in LCD (Figure 3).

FIGURE 3.

FIGURE 3

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Plasma PYY and plasma acylated ghrelin levels in bariatric surgery (BS) group and low-calorie diet (LCD) group participants during the mixed meal test. Data are presented as mean ± SEM.

Only fasting total and acylated ghrelin were correlated with change in body mass (r = 0.40, p = .040; r = 0.36, p = .073, respectively). The change in postprandial total ghrelin was correlated with the change in body mass (r = 0.43, p = .024) and marginally correlated with the change in fat mass (r = 0.391, p = .059).

3.6. Appetite sensations (VAS) scores

Appetite sensation scores of the individual components for appetite sensations as measured by VAS are displayed in Figure S2. Following BS, hunger was decreased and fullness was increased compared to LCD (pgroup = 0.037; pgroup = 0.010, respectively). Desire to eat tended to decrease more in BS than LCD (pgroup = 0.055). No other significant effects were found for appetite sensations.

Changes in fullness (r = −0.40, p = .023), satisfaction (r = −0.45, p = .010), and desire to eat (r = 0.38, p = .034) were correlated with changes in body mass. Changes in hunger (r = 0.40, p = .035), satisfaction (r = −0.48, p = .010) and desire to eat (r = 0.39, p = .041) were correlated with changes in fat mass.

4. DISCUSSION

The effects of BS on insulin sensitivity have been insufficiently studied despite its wide use. In the present study, changes in body composition, insulin sensitivity, the postprandial gut hormone response and subjective ratings of appetite were assessed 8 weeks and 1 year after either bariatric surgery (BS; n = 12) or initiating a low-calorie diet (LCD; n = 7). Eight weeks after surgery or initiating the diet, both groups lowered body weight, but insulin sensitivity was unchanged. In contrast, after 1 year, peripheral insulin sensitivity was significantly improved in the subjects that underwent BS but not in those on a calorie-restricted diet. As commonly observed, subjects in the LCD group did not exhibit significant weight loss after 1 year, while subjects who underwent BS continued a weight loss trajectory even at 1 year. Importantly, BS increased postprandial PYY and decreased postprandial total and acylated ghrelin compared to a LCD. As expected, fullness was increased and hunger was decreased more following BS compared to initiation of a LCD.

4.1. Clamp insulin sensitivity

After 8 weeks, both groups had lower body weights but maintained rather high basal EGP. Fasting plasma glucose and insulin concentrations were reduced 8 weeks after BS, reflecting some improvement in insulin sensitivity.19 Surprisingly, we did not observe changes in peripheral insulin sensitivity as determined by the gold-standard hyperinsulinemic–euglycemic clamp technique in either group 8 weeks after surgery or starting a LCD. Such a lack of early post-surgery improvements in hepatic13 and peripheral insulin sensitivity was reported following RYGB and duodenal bypass liner despite weight loss similar to that seen in our participants.8, 13, 36 The degree of pre-operative glucose tolerance may play a role in hepatic and peripheral insulin sensitivity changes shortly after BS. Bojsen-Møller et al. showed marked effects of BS on insulin concentration in subjects with T2DM compared to those with normal glucose tolerance,11 and Mittendorfer et al. reported a negative correlation between baseline peripheral sensitivity and improvements in this outcome following 20% weight loss.37 Study participants who underwent BS were mostly (except for three BS and one LCD) non-diabetic and exhibited only marginal impaired fasting glucose (BS: 103 ± 5; LCD: 97 ± 4 mg/dL),38 which might have reduced the effect size of outcomes related to carbohydrate metabolism after 8 weeks.

After 1 year, and a substantial amount of weight loss (>30%), peripheral insulin sensitivity was drastically improved in BS participants. Conversely, no effect on insulin sensitivity was found in LCD after 1 year likely due to a near return to baseline body weight. Our data are in line with other studies demonstrating that changes in peripheral insulin sensitivity by BS only occur following substantial weight loss.8–12 Bradley et al. showed no differences in the improvement of insulin sensitivity following RYGB or SG when weight loss following surgery was similar.10 In a recent study, insulin sensitivity improved equivalently with approximately 18% weight loss after undergoing RYGB or maintaining an LCD.14 Taken together, the data indicate that the improvement in insulin sensitivity is mostly related to the magnitude of weight loss.

4.2. Postprandial insulin sensitivity

Fasting plasma glucose and insulin concentrations were improved to a greater degree in BS compared to LCD only after 1 year. These findings bring our results further in line with those of de Weijer et al. and Lima et al., who showed improvements in fasting glucose and insulin with 6%–11% weight loss independent of peripheral and hepatic insulin sensitivity within weeks of surgery.13, 36 Interestingly, the postprandial insulin response was similar between groups and was only increased more in BS compared to LCD after 8 weeks, when both groups were on a similar weight loss trajectory. While insulin kinetics following RYGB and SG are not well understood, our results add to previous findings that plasma insulin concentration is increased following an oral glucose tolerance test 3 months and 1 year following RYGB.11

4.3. Gut peptides

SG maintains nutrient exposure in the upper gut but largely removes the part of the stomach that accounts for the majority of plasma ghrelin concentration; this altered gastrointestinal anatomy likely decreases ghrelin and increases glucagon-like peptide 1 (GLP-1) and PYY.39 We combined postprandial data from participants who had RYGB with those who had SG and found a greater increase in postprandial plasma PYY concentration in our combined BS patients compared to LCD. Peterli et al. reported postprandial PYY concentration increased similarly 3 months after RYGB and SG, which was maintained in RGYB but returned to baseline after 1 year in SG.18 Diet-induced weight loss may reduce or maintain fasting and postprandial PYY levels compared to BS.40 Fasting PYY has been shown to return to pre-weight loss levels during weight loss maintenance.41

Studies comparing post-bariatric surgery patients to weight loss-matched subjects who achieved diet-induced weight loss have shown different ghrelin responses, suggesting that changes in gastrointestinal anatomy rather than weight loss per se are driving some of the metabolic improvements.7, 42 Fasting plasma total ghrelin decrease by 40% at 8 weeks and 30% at 1 year in BS, similar to values previously reported 3 months after SG (34%–46%) but exceeding the decreases reported following RYGB (4%–10%).5, 43 Participants in our BS group underwent predominantly SG, and the decrease in fasting plasma total ghrelin in BS corresponds with our sample makeup. We also found that postprandial total and acylated ghrelin decreased in BS compared to LCD irrespective of timepoint. These results align with the predominant conclusion that BS decreases postprandial plasma ghrelin compared to diet-induced weight loss in the short and long term, with SG likely providing the stronger influence in the present study.31

4.4. Subjective appetite sensations

Compared to LCD, we found greater reductions in subjective appetite sensations 8 weeks and 1 year after BS which were correlated to losses in total body weight and body fat. Greater decreases in hunger and increases in fullness after BS compared to LCD were the only effects that we found for appetite sensation. Such findings are understandable in view of the larger decrease in fasting plasma total ghrelin, an orexigenic peptide, and increase in postprandial plasma PYY, an anorexigenic peptide, after BS compared to LCD. Changes in gut peptides following BS are consistently shown to occur in unison with changes in subjective appetite, while the association between gut peptides and subjective appetite sensation after diet-induced weight loss is not well supported.44 Decreased appetite 1 month after RYGB has been reported to rebound progressively 3, 6, and 12 months post-surgery,43 and a tendency for hunger to increase and fullness to decrease from 8 weeks to 1 year following BS is visible in Figure S2. These results following BS were noted with a concomitant increase in postprandial PYY, an appetite suppressing hormone.42

The 1–2-month postoperative period of RYGB and SG is characterised by energy deficit, prompt weight loss, and mobilisation of free-fatty acids that can lead to mild ketosis.45, 46 Very-low-calorie diets (<800 kcal per day) may also induce ketosis due to the limited provision of carbohydrates. Appetite suppression has been reported following BS and during very-low-calorie diets when ketosis is present, an effect hypothesised to derive in part from changes in gut peptides.47, 48 Induction of ketosis in the short-term postoperative period as well as following diet-induced weight loss is associated with decreased fasting acylated ghrelin and increased PYY and GLP-1.48, 49 While BS typically prompts these gut peptides changes and reduced subjective appetite, the effects of ketosis on gut peptides and appetite are contrary to what normally occurs during diet-induced weight loss. BS elicited a greater anorexigenic effect compared to LCD based on subjective appetite and gut peptide changes in the present study, suggesting minimal occurrence of ketosis in LCD participants, particularly during the first 8 weeks of the study when they were provided a diet of 800 kcal/day.

4.5. Study limitations

Some of the limitations are: the small sample size in each group presented in this prospective observational study of individuals self-selecting BS; three participants in BS who underwent RYGB were excluded from the mixed meal tolerance test analysis thus leaving only two RYGB participants for these analyses; combining RYBG and SG into the BS group may have limited the usefulness for gut peptide comparison with LCD due to the alternative gut profile effects that these two different surgery types have; the relative stimulus presented by the meal tolerance test differed at each timepoint because an absolute caloric content was used irrespective of weight loss; finally, the role of the intestinal microbiome and its related metabolites such as bile acid metabolites and short-chain fatty acids were not considered in our study.50

In conclusion, substantial weight loss after 1 year and improved insulin sensitivity was only observed following BS. Surprisingly, insulin sensitivity did not improve 8 weeks after the BS despite significant weight loss. Changes in gut peptides after BS paralleled reduced hunger and increased fullness. Most of the improvements in cardiometabolic health were related to weight loss. Additional research is needed to further elucidate the time course and driving factors of insulin sensitivity improvement and gut peptide changes following BS.

Supplementary Material

supplemental

ACKNOWLEDGEMENTS

The authors thank the participants in this study and the dedicated staff of the PBRC inpatient and outpatient units.

FUNDING INFORMATION

This work was supported by Ethicon-Endo Surgery Inc. and partially supported by the infrastructure of National Institute of Diabetes & Digestive & Kidney Diseases Grant P30DK072476 (to Eric Ravussin). Clinicaltrials.gov registration number: NCT00936130.

CONFLICT OF INTEREST STATEMENT

Adam C. Lowe, Dorien Reijnders, Charmaine S. Tam, Leanne M. Redman, Robbie Beyl, Karl A. LeBlanc, Mark G. Hausmann, Vance L. Albaugh, and Frank L. Greenway have nothing to declare. Eric Ravussin was the recipient of a research grant from Ethicon-Endo Surgery Inc. to conduct this study. Other than that, he has nothing to declare.

DATA AVAILABILITY STATEMENT

Some or all datasets generated during and/or analyzed during the current study are not publicly available but are available from the corresponding author or reasonable request.

REFERENCES

  • 1.Chadt A, Scherneck S, Joost HG, Al-Hasani H. Molecular links between obesity and diabetes: “Diabesity”. In: Feingold KR, Anawalt B, Blackman MR, et al. , eds. Endotext. MDText.com, Inc.; 2000:2000–2023. [Google Scholar]
  • 2.Ramos A, Kow L, Brown W, et al. The International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO). 5th IFSO Global Registry Report. Dendrite Clinical Systems; 2019. [Google Scholar]
  • 3.American Diabetes Association. Obesity management for the treatment of type 2 diabetes: standards of medical care in diabetes—2018. Diabetes Care. 2017;41(suppl 1):S65–S72. doi: 10.2337/dc18-S007 [DOI] [PubMed] [Google Scholar]
  • 4.Gastaldelli A, Iaconelli A, Gaggini M, et al. Short-term effects of laparoscopic adjustable gastric banding versus Roux-en-Y gastric bypass. Diabetes Care. 2016;39(11):1925–1931. doi: 10.2337/dc15-2823 [DOI] [PubMed] [Google Scholar]
  • 5.Peterli R, Wölnerhanssen B, Peters T, et al. Improvement in glucose metabolism after bariatric surgery: comparison of laparoscopic Rouxen-Y gastric bypass and laparoscopic sleeve gastrectomy: a prospective randomized trial. Ann Surg. 2009;250(2):234–241. doi: 10.1097/SLA.0b013e3181ae32e3 [DOI] [PubMed] [Google Scholar]
  • 6.Jacobsen SH, Bojsen-Møller KN, Dirksen C, et al. Effects of gastric bypass surgery on glucose absorption and metabolism during a mixed meal in glucose-tolerant individuals. Diabetologia. 2013;56(10):2250–2254. doi: 10.1007/s00125-013-3003-0 [DOI] [PubMed] [Google Scholar]
  • 7.Laferrère B, Teixeira J, McGinty J, et al. Effect of weight loss by gastric bypass surgery versus hypocaloric diet on glucose and incretin levels in patients with type 2 diabetes. J Clin Endocrinol Metab. 2008;93(7):2479–2485. doi: 10.1210/jc.2007-2851 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Campos GM, Rabl C, Peeva S, et al. Improvement in peripheral glucose uptake after gastric bypass surgery is observed only after substantial weight loss has occurred and correlates with the magnitude of weight lost. J Gastrointest Surg. 2010;14(1):15–23. doi: 10.1007/s11605-009-1060-y [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Camastra S, Gastaldelli A, Mari A, et al. Early and longer term effects of gastric bypass surgery on tissue-specific insulin sensitivity and beta cell function in morbidly obese patients with and without type 2 diabetes. Diabetologia. 2011;54(8):2093–2102. doi: 10.1007/s00125-011-2193-6 [DOI] [PubMed] [Google Scholar]
  • 10.Bradley D, Magkos F, Eagon JC, et al. Matched weight loss induced by sleeve gastrectomy or gastric bypass similarly improves metabolic function in obese subjects. Obesity (Silver Spring). 2014;22(9):2026–2031. doi: 10.1002/oby.20803 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Bojsen-Møller KN, Dirksen C, Jørgensen NB, et al. Early enhancements of hepatic and later of peripheral insulin sensitivity combined with increased postprandial insulin secretion contribute to improved glycemic control after Roux-en-Y gastric bypass. Diabetes. 2014;63(5):1725–1737. doi: 10.2337/db13-1307 [DOI] [PubMed] [Google Scholar]
  • 12.Dunn JP, Abumrad NN, Breitman I, et al. Hepatic and peripheral insulin sensitivity and diabetes remission at 1 month after Roux-en-Y gastric bypass surgery in patients randomized to omentectomy. Diabetes Care. 2012;35(1):137–142. doi: 10.2337/dc11-1383 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.de Weijer BA, Aarts E, Janssen IM, et al. Hepatic and peripheral insulin sensitivity do not improve 2 weeks after bariatric surgery. Obesity (Silver Spring). 2013;21(6):1143–1147. doi: 10.1002/oby.20220 [DOI] [PubMed] [Google Scholar]
  • 14.Yoshino M, Kayser BD, Yoshino J, et al. Effects of diet versus gastric bypass on metabolic function in diabetes. N Engl J Med. 2020;383(8):721–732. doi: 10.1056/NEJMoa2003697 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Münzberg H, Laque A, Yu S, Rezai-Zadeh K, Berthoud HR. Appetite and body weight regulation after bariatric surgery. Obes Rev. 2015;16 (suppl 1):77–90. doi: 10.1111/obr.12258 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Cummings DE, Weigle DS, Frayo RS, et al. Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. N Engl J Med.2002;346(21):1623–1630. doi: 10.1056/NEJMoa012908 [DOI] [PubMed] [Google Scholar]
  • 17.Keim NL, Stern JS, Havel PJ. Relation between circulating leptin concentrations and appetite during a prolonged, moderate energy deficit in women. Am J Clin Nutr. 1998;68(4):794–801. doi: 10.1093/ajcn/68.4.794 [DOI] [PubMed] [Google Scholar]
  • 18.Peterli R, Steinert RE, Woelnerhanssen B, et al. Metabolic and hormonal changes after laparoscopic Roux-en-Y gastric bypass and sleeve gastrectomy: a randomized, prospective trial. Obes Surg. 2012;22(5):740–748. doi: 10.1007/s11695-012-0622-3 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Tam CS, Redman LM, Greenway F, LeBlanc KA, Haussmann MG, Ravussin E. Energy metabolic adaptation and cardiometabolic improvements one year after gastric bypass, sleeve gastrectomy, and gastric band. J Clin Endocrinol Metab. 2016;101(10):3755–3764. doi: 10.1210/jc.2016-1814 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Gerrior S, Juan W, Basiotis P. An easy approach to calculating estimated energy requirements. Prev Chronic Dis. 2006;3(4):A129. [PMC free article] [PubMed] [Google Scholar]
  • 21.National Research Council (US) Subcommittee on the Tenth Edition of the Recommended Dietary Allowances. Recommended Dietary Allowances: 10th Edition. The National Academies Collection: Reports funded by National Institutes of Health. National Academies Press (US); 1989. [PubMed] [Google Scholar]
  • 22.Lam YY, Redman LM, Smith SR, et al. Determinants of sedentary 24-h energy expenditure: equations for energy prescription and adjustment in a respiratory chamber. Am J Clin Nutr. 2014;99(4):834–842. doi: 10.3945/ajcn.113.079566 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Hulzebos CV, Renfurm L, Bandsma RH, et al. Measurement of parameters of cholic acid kinetics in plasma using a microscale stable isotope dilution technique: application to rodents and humans. J Lipid Res. 2001;42(11):1923–1929. doi: 10.1016/S0022-2275(20)31519-4 [DOI] [PubMed] [Google Scholar]
  • 24.DeFronzo RA, Tobin JD, Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol. 1979;237(3):E214–E223. doi: 10.1152/ajpendo.1979.237.3.E214 [DOI] [PubMed] [Google Scholar]
  • 25.Lillioja S, Bogardus C. Obesity and insulin resistance: lessons learned from the Pima Indians. Diabetes Metab Rev. 1988;4(5):517–540. doi: 10.1002/dmr.5610040508 [DOI] [PubMed] [Google Scholar]
  • 26.Jéquier E, Acheson K, Schutz Y. Assessment of energy expenditure and fuel utilization in man. Annu Rev Nutr. 1987;7:187–208. doi: 10.1146/annurev.nu.07.070187.001155 [DOI] [PubMed] [Google Scholar]
  • 27.Ravussin E, Bogardus C, Schwartz RS, et al. Thermic effect of infused glucose and insulin in man. Decreased response with increased insulin resistance in obesity and noninsulin-dependent diabetes mellitus. J Clin Invest. 1983;72(3):893–902. doi: 10.1172/jci111060 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.Flint A, Raben A, Blundell JE, Astrup A. Reproducibility, power and validity of visual analogue scales in assessment of appetite sensations in single test meal studies. Int J Obes Relat Metab Disord.2000;24(1): 38–48. doi: 10.1038/sj.ijo.0801083 [DOI] [PubMed] [Google Scholar]
  • 29.Akalu Y, Molla MD, Dessie G, Ayelign B. Physiological effect of ghrelin on body systems. Int J Endocrinol. 2020;2020(1):1385138. doi: 10.1155/2020/1385138 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Kalinowski P, Paluszkiewicz R, Wróblewski T, et al. Ghrelin, leptin, and glycemic control after sleeve gastrectomy versus Roux-en-Y gastric bypass-results of a randomized clinical trial. Surg Obes Relat Dis. 2017;13(2):181–188. doi: 10.1016/j.soard.2016.08.025 [DOI] [PubMed] [Google Scholar]
  • 31.Malin SK, Samat A, Wolski K, et al. Improved acylated ghrelin suppression at 2 years in obese patients with type 2 diabetes: effects of bariatric surgery vs standard medical therapy. Int J Obes (Lond). 2014; 38(3):364–370. doi: 10.1038/ijo.2013.196 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32.Alamuddin N, Vetter ML, Ahima RS, et al. Changes in fasting and prandial gut and adiposity hormones following vertical sleeve gastrectomy or Roux-en-Y-gastric bypass: an 18-month prospective study. Obes Surg. 2017;27(6):1563–1572. doi: 10.1007/s11695-016-2505-5 [DOI] [PubMed] [Google Scholar]
  • 33.Arakawa R, Febres G, Cheng B, Krikhely A, Bessler M, Korner J. Prospective study of gut hormone and metabolic changes after laparoscopic sleeve gastrectomy and Roux-en-Y gastric bypass. PLoS One. 2020;15(7):e0236133. doi: 10.1371/journal.pone.0236133 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34.Azuma K, Heilbronn LK, Albu JB, Smith SR, Ravussin E, Kelley DE. Adipose tissue distribution in relation to insulin resistance in type 2 diabetes mellitus. Am J Physiol Endocrinol Metab. 2007;293(1):E435–E442. doi: 10.1152/ajpendo.00394.2006 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35.Kelley DE, Mandarino LJ. Hyperglycemia normalizes insulin stimulated skeletal muscle glucose oxidation and storage in noninsulin-dependent diabetes mellitus. J Clin Invest. 1990;86(6):1999–2007. doi: 10.1172/jci114935 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36.Lima MM, Pareja JC, Alegre SM, et al. Acute effect of Roux-en-Y gastric bypass on whole-body insulin sensitivity: a study with the euglycemic-hyperinsulinemic clamp. J Clin Endocrinol Metab. 2010;95(8):3871–3875. doi: 10.1210/jc.2010-0085 [DOI] [PubMed] [Google Scholar]
  • 37.Mittendorfer B, Kayser BD, Yoshino M, et al. Heterogeneity in the effect of marked weight loss on metabolic function in women with obesity. JCI Insight. 2023;8(12):E169541.doi: 10.1172/jci.insight.169541 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38.Rao SS, Disraeli P, McGregor T. Impaired glucose tolerance and impaired fasting glucose. Am Fam Physician. 2004;69(8):1961–1968. [PubMed] [Google Scholar]
  • 39.Scott WR, Batterham RL. Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy: understanding weight loss and improvements in type 2 diabetes after bariatric surgery. Am J Physiol Regul Integr Comp Physiol. 2011;301(1):R15–R27. doi: 10.1152/ajpregu.00038.2011 [DOI] [PubMed] [Google Scholar]
  • 40.Oliván B, Teixeira J, Bose M, et al. Effect of weight loss by diet or gastric bypass surgery on peptide YY3–36 levels. Ann Surg. 2009;249(6):948–953. doi: 10.1097/SLA.0b013e3181a6cdb0 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 41.Näätänen M, Kolehmainen M, Laaksonen DE, Herzig K-H, Poutanen K, Karhunen L. Post-weight loss changes in fasting appetite- and energy balance-related hormone concentrations and the effect of the macronutrient content of a weight maintenance diet:a randomised controlled trial. Eur J Nutr. 2021;60(5):2603–2616. doi: 10.1007/s00394-020-02438-3 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 42.Morínigo R, Moizé V, Musri M, et al. Glucagon-like peptide-1, peptide YY, hunger, and satiety after gastric bypass surgery in morbidly obese subjects. J Clin Endocrinol Metab. 2006;91(5):1735–1740. doi: 10.1210/jc.2005-0904 [DOI] [PubMed] [Google Scholar]
  • 43.Karamanakos SN, Vagenas K, Kalfarentzos F, Alexandrides TK. Weight loss, appetite suppression, and changes in fasting and postprandial ghrelin and peptide-YY levels after Roux-en-Y gastric bypass and sleeve gastrectomy: a prospective, double blind study. Ann Surg. 2008;247(3):401–407. doi: 10.1097/SLA.0b013e318156f012 [DOI] [PubMed] [Google Scholar]
  • 44.Lim JJ, Liu Y, Lu LW, Sequeira IR, Poppitt SD. No evidence that circulating GLP-1 or PYY are associated with increased satiety during low energy diet-induced weight loss: modelling biomarkers of appetite. Nutrients. 2023;15(10):2399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 45.Crujeiras AB, Gomez-Arbelaez D, Zulet MA, et al. Plasma FGF21 levels in obese patients undergoing energy-restricted diets or bariatric surgery: a marker of metabolic stress? Int J Obes (Lond). 2017;41(10):1570–1578. doi: 10.1038/ijo.2017.138 [DOI] [PubMed] [Google Scholar]
  • 46.Pindozzi F, Socci C, Bissolati M, et al. Role of nutritional ketosis in the improvement of metabolic parameters following bariatric surgery. World J Diabetes. 2022;13(1):54–64. doi: 10.4239/wjd.v13.i1.54 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 47.Gibson AA, Seimon RV, Lee CMY, et al. Do ketogenic diets really suppress appetite? A systematic review and meta-analysis. Obes Rev.2015;16(1):64–76. doi: 10.1111/obr.12230 [DOI] [PubMed] [Google Scholar]
  • 48.Aukan MI, Skårvold S, Brandsaeter I, et al. Gastrointestinal hormones and appetite ratings after weight loss induced by diet or bariatric surgery. Obesity (Silver Spring). 2023;31(2):399–411.doi: 10.1002/oby.23655 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 49.Martins C, Nymo S, Truby H, Rehfeld JF, Hunter GR, Gower BA. Association between ketosis and changes in appetite markers with weight loss following a very low-energy diet. Obesity. 2020;28(12):2331–2338. doi: 10.1002/oby.23011 [DOI] [PubMed] [Google Scholar]
  • 50.Ochner CN, Kwok Y, Conceição E, et al. Selective reduction in neural responses to high calorie foods following gastric bypass surgery. Ann Surg. 2011;253(3):502–507. doi: 10.1097/SLA.0b013e318203a289 [DOI] [PMC free article] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

supplemental
NIHMS2071231-supplement-supplemental.pdf (121.6KB, pdf)

Data Availability Statement

Some or all datasets generated during and/or analyzed during the current study are not publicly available but are available from the corresponding author or reasonable request.

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