Sodium-Glucose Cotransporter-2 Inhibitors and the Risk for Dialysis and Cardiovascular Disease in Patients With Stage 5 Chronic Kidney Disease.

BACKGROUND: No studies have reported the long-term outcomes of initiating sodium-glucose cotransporter-2 inhibitors (SGLT2is) in patients with estimated glomerular filtration rates less than 20 mL/min/1.73 m2 to predialysis. OBJECTIVE: To compare the risk for dialysis, cardiovascular events, and death between SGLT2i users and nonusers in patients with type 2 diabetes (T2D) and stage 5 chronic kidney disease (CKD). DESIGN: Target trial emulation study. SETTING: Taiwan's National Health Insurance Research Database (NHIRD). PARTICIPANTS: By applying sequential target trial emulation principle, 23 854 SGLT2i users and 23 892 SGLT2i nonusers were selected from the NHIRD for patients with T2D and stage 5 CKD from 1 May 2016 to 31 October 2021. MEASUREMENTS: Conditional Cox proportional hazards models were used to compare the risks for dialysis, hospitalization for heart failure, acute myocardial infarction (AMI), diabetic ketoacidosis (DKA), acute kidney injury (AKI), and all-cause mortality between SGLT2i users and nonusers. RESULTS: In the intention-to-treat model, compared with no SGLT2i use, SGLT2i use was associated with lower risks for dialysis (hazard ratio [HR], 0.34 [95% CI, 0.27 to 0.43]), hospitalization for heart failure (HR, 0.80 [CI, 0.73 to 0.86]), AMI (HR, 0.61 [CI, 0.52 to 0.73]), DKA (HR, 0.78 [CI, 0.71 to 0.85]), and AKI (HR, 0.80 [CI, 0.70 to 0.90]), but there was no difference in the risk for all-cause mortality (HR, 1.11 [CI, 0.99 to 1.24]). The Kaplan-Meier curves and subgroup analyses also showed that initiation of an SGLT2i in stage 5 CKD was associated with a lower risk for long-term dialysis than no SGLT2i use. LIMITATION: This result may not apply to patients without T2D. CONCLUSION: This emulated target trial showed that SGLT2i use was associated with a lower risk for dialysis, cardiovascular events, DKA, and AKI than no SGLT2i use in patients with T2D and stage 5 CKD. PRIMARY FUNDING SOURCE: National Health Research Institutes, Taiwan.

Recent advances in the treatment of type 2 diabetes mellitus using new drug therapies.

Several recent advances provide multiple health benefits to individuals with type 2 diabetes mellitus (T2DM). Pharmacological therapy is governed by person-centered factors, including comorbidities and treatment goals. Adults with T2DM who have an established/high risk of atherosclerotic cardiovascular disease, heart failure, and/or chronic kidney disease, require a treatment regimen that includes agents that are proven to reduce cardiorenal risk. Weight management plays a key role in reducing glucose for patients with T2DM. A glucose-reduction treatment regimen must consider weight management. Sodium glucose co-transporter 2 (SGLT2) inhibitors reduce the risk of heart failure, cardiovascular and renal events. Glucagon-like peptide-1 (GLP-1) receptor agonists allow better control of glycemia, promote weight loss and reduce the risk of cardiovascular events. Newer Glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 dual agonist, which activate GIP and GLP-1 receptors improve glycemic control and promote greater weight loss than GLP-1 receptor agonists. Several novel drugs are in the clinical development phase. This review pertains to recent advances in pharmacological management of type 2 diabetes.

Roux-en-Y and One-Anastomosis Gastric Bypass Surgery Are Superior to Sleeve Gastrectomy in Lowering Glucose and Cholesterol Levels Independent of Weight Loss: a Propensity-Score Weighting Analysis.

BACKGROUND: The superior effects of gastric bypass surgery in preventing cardiovascular diseases compared with sleeve gastrectomy are well-established. However, whether these effects are independent of weight loss is not known. METHODS: In this retrospective cohort study, we compared the change in cardiometabolic risks of 1073 diabetic patients undergoing Roux-en-Y gastric bypass (RYGB) (n = 265), one-anastomosis gastric bypass (OAGB) (n = 619), and sleeve gastrectomy (SG) (n = 189) with equivalent weight loss from the Min-Shen General Hospital. Propensity score-weighting, multivariate regression, and matching were performed to adjust for baseline differences. RESULTS: After 12 months, OAGB and, to a lesser extent, RYGB exhibited superior effects on glycemic control compared with SG in patients with equivalent weight loss. The effect was significant in patients with mild-to-modest BMI reduction but diminished in patients with severe BMI reduction. RYGB and OAGB had significantly greater effects in lowering total and low-density lipoprotein cholesterol than SG, regardless of weight loss. The results of matching patients with equivalent weight loss yielded similar results. The longer length of bypassed biliopancreatic (BP) limbs was correlated with a greater decrease in glycemic levels, insulin resistance index, lipids, C-reactive protein (CRP) levels, and creatinine levels in patients receiving RYBG. It was correlated with greater decreases in BMI, fasting insulin, insulin resistance index, and C-reactive protein levels in patients receiving OAGB. CONCLUSION: Diabetic patients receiving OAGB and RYGB had lower glucose and cholesterol levels compared with SG independent of weight loss. Our results suggest diabetic patients with cardiovascular risk factors such as hypercholesterolemia to receive bypass surgery.

The Potential Influence of Uremic Toxins on the Homeostasis of Bones and Muscles in Chronic Kidney Disease.

Patients with chronic kidney disease (CKD) often experience a high accumulation of protein-bound uremic toxins (PBUTs), specifically indoxyl sulfate (IS) and p-cresyl sulfate (pCS). In the early stages of CKD, the buildup of PBUTs inhibits bone and muscle function. As CKD progresses, elevated PBUT levels further hinder bone turnover and exacerbate muscle wasting. In the late stage of CKD, hyperparathyroidism worsens PBUT-induced muscle damage but can improve low bone turnover. PBUTs play a significant role in reducing both the quantity and quality of bone by affecting osteoblast and osteoclast lineage. IS, in particular, interferes with osteoblastogenesis by activating aryl hydrocarbon receptor (AhR) signaling, which reduces the expression of Runx2 and impedes osteoblast differentiation. High PBUT levels can also reduce calcitriol production, increase the expression of Wnt antagonists (SOST, DKK1), and decrease klotho expression, all of which contribute to low bone turnover disorders. Furthermore, PBUT accumulation leads to continuous muscle protein breakdown through the excessive production of reactive oxygen species (ROS) and inflammatory cytokines. Interactions between muscles and bones, mediated by various factors released from individual tissues, play a crucial role in the mutual modulation of bone and muscle in CKD. Exercise and nutritional therapy have the potential to yield favorable outcomes. Understanding the underlying mechanisms of bone and muscle loss in CKD can aid in developing new therapies for musculoskeletal diseases, particularly those related to bone loss and muscle wasting.

The Effects of Bariatric Surgery on Renal, Neurological, and Ophthalmic Complications in Patients with Type 2 Diabetes: the Taiwan Diabesity Study.

BACKGROUND: Bariatric surgery has been shown to improve glycemic control in patients with type 2 diabetes. However, less is known whether it can also reduce diabetic renal, neurological, and ophthalmic complications. METHODS: This prospective multicenter cohort study compared renal, ophthalmic, and neurological complications between 49 patients with obesity/overweight receiving bariatric surgery and 338 patients receiving standard medical treatment after follow-up for 2 years. Patients received neurological examinations including toe tuning fork vibration test, ankle tendon reflex test, 10-g monofilament test, and ophthalmic examinations including visual acuity measurement and fundus examinations. Multiple regressions, propensity score weighting, and matching were employed to adjust for baseline differences. RESULTS: After 2 years of follow-up, patients with type 2 diabetes receiving bariatric surgery had greater reduction in BMI, HbA1c, and urine albumin-creatinine ratio, greater improvement in estimated glomerular filtration rate, and greater increase in tuning fork test score of right and left toes compared with the medical group. However, there is no improvement in 10 g-monofilament test, visual acuity, diabetic non-proliferative retinopathy, and proliferative retinopathy. Similar results were obtained using multiple regression adjustment, propensity-score weighting, or comparing age-, sex-, and BMI-matched subjects. CONCLUSIONS: After 2-year follow-up, patients with obesity/overweight and type 2 diabetes receiving bariatric surgery have increased glomerular filtration rate, reduced albuminuria, and improved tuning folk vibration sensation.

Cardiovascular Benefits of Acarbose vs Sulfonylureas in Patients With Type 2 Diabetes Treated With Metformin.

Context: Although α-glucosidase inhibitors (AGIs) have been shown to reduce the risk of myocardial infarction in patients with impaired glucose tolerance, the cardiovascular benefits of AGIs in those with type 2 diabetes (T2D) remains unclear. Objective: We compared the clinical outcomes of adding acarbose vs sulfonylureas to metformin therapy in patients with T2D. Design, Setting, and Participants: The study population was drawn from the database of the Diabetes Pay-for-Performance program in Taiwan. Sulfonylureas and acarbose were prescribed to 196,143 and 14,306 patients with T2D, respectively, from 2004 to 2015, who had been treated with metformin. A propensity score-matched cohort study was conducted. The patients were followed up for clinical adverse events of all-cause mortality and hospitalizations of major atherosclerotic events (i.e., myocardial infarction and ischemic stroke), heart failure, or hypoglycemia. Results: A total of 14,306 propensity score-matched pairs (age, 55.8 ± 13.1 years; 47.8% men) were enrolled in the present analysis. Compared with sulfonylureas as the add-on therapy to metformin, the use of acarbose was associated with significantly lower risks of hospitalizations for major atherosclerotic events [hazard ratio (HR), 0.69; 95% CI, 0.52 to 0.91], ischemic stroke (HR, 0.68; 95% CI, 0.49 to 0.94), and hypoglycemia (HR, 0.23; 95% CI, 0.08 to 0.71), after accounting for major confounding factors. Conclusions: In T2D treatment, the use of acarbose as an add-on remedy to metformin was associated with lower risks of major atherosclerotic events, ischemic stroke, and hypoglycemia compared with the use of sulfonylurea as an add-on remedy.

Laparoscopic gastric bypass for the treatment of type 2 diabetes: a comparison of Roux-en-Y versus single anastomosis gastric bypass.

BACKGROUND: In recent years, gastric bypass surgery has been found to have therapeutic potential for the treatment of type 2 diabetes (T2D). However, the difference between 2 bypass procedures, Roux-en-Y gastric bypass (RYGB) and another single anastomosis gastric bypass (SAGB), is not clear. OBJECTIVE: To evaluate the differences between SAGB and RYGB in the efficacy of T2D remission in obese patients. SETTING: Tertiary teaching hospital. METHODS: Outcomes of 406 (259 women and 147 male) patients who had undergone RYGB (157) or SAGB (249) for the treatment of T2D with 1-year follow-up were assessed. The remission of T2D after surgery was evaluated in matched groups, including body mass index (BMI) and the ABCD scoring system, which comprises patient age, BMI, C-peptide levels, and duration of T2D (yr). RESULTS: The weight loss of the SAGB patients at 1 year after surgery was better than the RYGB patients (24.1% [8.4%] versus 30.7% [8.7%]; P<.001). The mean BMI decreased from 39.9 (8.0) to 27.4 (4.6) kg/m2 in SAGB patients at 1 year after surgery and decreased from 34.5 (6.6) to 26.2 (4.2) kg/m2 in the RYGB patients. The mean glycated hemoglobin A1C (HbA1C) decreased from 8.6% to 6.2% of the RYGB group and from 8.6% to 5.5% of the SAGB group. Eighty-seven (55.4%) patients of the RYGB group and 204 (81.9%) of the SAGB group achieved complete remission of T2D (HbA1C<6.0%) at 1 year after surgery (P<.001). SAGB exhibited significantly better glycemic control than RYGB surgery in selected groups stratified by different BMI and ABCD score. At 5 years after surgery, SAGB still had a better remission of T2D than RYGB (70.5% versus 39.4%; P = .002). Multivariate analysis confirms that both SAGB and ABCD score are independent predictors of T2D remission after bypass surgery. CONCLUSIONS: Both RYGB and SAGB are effective metabolic surgery. SAGB carries a higher power on T2D remission than RYGB in a small group of patients. ABCD score is useful in T2D patient classification and selection for different procedures.

Lifestyle Intervention and Medical Management With vs Without Roux-en-Y Gastric Bypass and Control of Hemoglobin A1c, LDL Cholesterol, and Systolic Blood Pressure at 5 Years in the Diabetes Surgery Study.

Importance: The Roux-en-Y gastric bypass is effective in achieving established diabetes treatment targets, but durability is unknown. Objective: To compare durability of Roux-en-Y gastric bypass added to intensive lifestyle and medical management in achieving diabetes control targets. Design, Setting, and Participants: Observational follow-up of a randomized clinical trial at 4 sites in the United States and Taiwan, involving 120 participants who had a hemoglobin A1c (HbA1c) level of 8.0% or higher and a body mass index between 30.0 and 39.9 (enrolled between April 2008 and December 2011) were followed up for 5 years, ending in November 2016. Interventions: Lifestyle-intensive medical management intervention based on the Diabetes Prevention Program and LookAHEAD trials for 2 years, with and without (60 participants each) Roux-en-Y gastric bypass surgery followed by observation to year 5. Main Outcomes and Measures: The American Diabetes Association composite triple end point of hemoglobin A1c less than 7.0%, low-density lipoprotein cholesterol less than 100 mg/dL, and systolic blood pressure less than 130 mm Hg at 5 years. Results: Of 120 participants who were initially randomized (mean age, 49 years [SD, 8 years], 72 women [60%]), 98 (82%) completed 5 years of follow-up. Baseline characteristics were similar between groups: mean (SD) body mass index 34.4 (3.2) for the lifestyle-medical management group and 34.9 (3.0) for the gastric bypass group and had hemoglobin A1c levels of 9.6% (1.2) and 9.6% (1.0), respectively. At 5 years, 13 participants (23%) in the gastric bypass group and 2 (4%) in the lifestyle-intensive medical management group had achieved the composite triple end point (difference, 19%; 95% CI, 4%-34%; P = .01). In the fifth year, 31 patients (55%) in the gastric bypass group vs 8 (14%) in the lifestyle-medical management group achieved an HbA1c level of less than 7.0% (difference, 41%; 95% CI, 19%-63%; P = .002). Gastric bypass had more serious adverse events than did the lifestyle-medical management intervention, 66 events vs 38 events, most frequently gastrointestinal events and surgical complications such as strictures, small bowel obstructions, and leaks. Gastric bypass had more parathyroid hormone elevation but no difference in B12 deficiency. Conclusions and Relevance: In extended follow-up of obese adults with type 2 diabetes randomized to adding gastric bypass compared with lifestyle and intensive medical management alone, there remained a significantly better composite triple end point in the surgical group at 5 years. However, because the effect size diminished over 5 years, further follow-up is needed to understand the durability of the improvement. Trial Registration: clinicaltrials.gov Identifier: NCT00641251.

High Incidence of Secondary Hyperparathyroidism in Bariatric Patients: Comparing Different Procedures.

BACKGROUND: Bariatric surgery is an effective therapy for morbid obesity but may reduce calcium absorption and significantly decrease the bone mineral density. This study examined the prevalence of secondary hyperparathyroidism (SHPT) in obese subjects during follow-up after different bariatric surgeries. We investigated predictors of SHPT. METHODS: We enrolled 1470 obese subjects undergoing bariatric/metabolic surgery with at least 1-year follow-up, including 322 patients undergoing Roux-en-Y gastric bypass (RYGB), 695 undergoing single anastomosis (mini-) gastric bypass (SAGB), 93 undergoing laparoscopic adjustable gastric banding (LAGB), and 360 undergoing sleeve gastrectomy (SG). Five years of data were available for 215 patients. Patients were instructed to supplement their diet according to the guideline. Calcium, parathyroid hormone (PTH), and vitamin D levels were measured before surgery and at 1 and 5 years after surgery. SHPT was defined as PTH > 69 pg/mL. RESULTS: The overall prevalence of SHPT was high, 21.0% before surgery and was not different between patients with different bariatric procedures. Pre-operative PTH correlated with age, BMI, and vitamin D levels. Multi-variate analysis confirmed that vitamin D level was the only independent predictor of SHPT before surgery. The prevalence of SHPT increased to 35.4% at 1 year after surgery and 63.3% at 5 years after surgery. SAGB had the highest prevalence of SHPT (50.6%) followed by RYGB (33.2%), LAGB (25.8%), and SG (17.8%) at 1 year after surgery. At 5 years after surgery, SAGB still had the highest prevalence of SHPT (73.6%), followed by RYGB (56.6%), LAGB (38.5%), and SG (41.7%). Serum PTH at 1 year after surgery correlated with decreased BMI and weight loss. Multi-variate analysis confirmed that age, sex, calcium level, and bypass procedure were independent predictor of SHPT after surgery. CONCLUSIONS: The prevalence of SHPT is high in morbidly obese patients before bariatric surgery which is related to vitamin D deficiency. The prevalence of SHPT increased continually along with the time after bariatric surgery, especially in patients receiving SAGB, followed by RYGB. The supplementation of vitamin D and calcium have to be higher in bypass procedure, especially in malabsorptive procedure.

National Differences in Remission of Type 2 Diabetes Mellitus After Roux-en-Y Gastric Bypass Surgery-Subgroup Analysis of 2-Year Results of the Diabetes Surgery Study Comparing Taiwanese with Americans with Mild Obesity (BMI 30-35 kg/m2).

BACKGROUND: The purpose of this study is to compare effects of different nations on Roux-en-Y gastric bypass (RYGB) vs. intensive medical management (IMM) in achieving remission of type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: Between April 2008 and December 2011, this randomized, controlled clinical trial was conducted at four teaching hospitals in the United States and Taiwan involving 71 participants with mild obesity (BMI 30-35 kg/m2). Thirty-six of 71 participants were randomly assigned to the RYGB group, and the others were in IMM group. Partial or complete remission of T2DM was defined as blood HbA1c < 6.5 % (48 mmol/mol) or <6 % (42 mmol/mol) without any antihyperglycemic medication for at least 1-year duration, respectively. RESULTS: At baseline, Taiwanese participants had a lower BMI, younger age, and shorter duration of T2DM than American participants. At 24 months, weight loss was greater in the RYGB group in both populations than in the IMM group. No IMM participant of either population had partial or complete remission of T2DM. In the RYGB group, a substantial proportion of the subjects achieved complete or partial remission (57 % in Taiwanese and 27 % in American participants, P = 0.08). Logistic regression revealed stimulated C-peptide (Odds ratio 2.22, P = 0.02) but not nationality as a significant predictor of diabetes remission. CONCLUSION: Adding RYGB to lifestyle and medical management was associated with a greater likelihood of remission of T2DM in both Taiwanese and American subjects with mild obesity with type 2 diabetes. Residual beta-cell function at baseline appears to be the major factor predicting remission of T2DM. Trial registry number: clinicaltrials.gov Identifier: NCT00641251.

Metabolic Surgery for Diabetes Treatment: Sleeve Gastrectomy or Gastric Bypass?

BACKGROUND: Bariatric surgery has gained reputation for its metabolic effect and is increasingly being performed to treat type 2 diabetes mellitus (T2DM). However, there is still a gray area regarding the choice of surgical procedure according to patient characteristics due to inadequate evidences, so far. We aim to compare the efficacy of two most commonly performed bariatric/metabolic surgeries, sleeve gastrectomy (SG) and gastric bypass (GB) with regard to remission of T2DM after surgery. METHODS: Outcomes of 579 (349 female and 230 male) patients who had undergone SG (109) or GB (470) for the treatment of T2DM with 1-year follow-up were assessed. The remission of T2DM after SG or GB surgery was evaluated in matched groups using the ABCD scoring system. The ABCD score is composed of the age, BMI, C-peptide levels and duration of T2DM (years). RESULTS: The weight loss of the SG patient at 1 year after surgery was similar to the GB patients [26.3 (1.1) vs. 32.6 (1.2) %; p = 0.258]. The mean BMI decreased from 35.7 (7.2) to 28.3 (3.7) Kg/m2 in SG patients at 1 year after surgery and decreased from 36.9 (7.2) to 26.7 (4.5) Kg/m2 in the GB patients. The mean HbA1c decreased from 8.8 to 6.1 % of the SG group and from 8.6 to 5.9 % of the GB group. Sixty-one (56.0 %) patients of the SG group and 300 (63.8 %) of the GB group achieved complete remission of T2DM (HbA1c < 6.0 %) at 1 year after surgery without statistical difference. However, GB exhibited significantly better glycemic control than the SG surgery in groups stratified by different ABCD score. At 5 year after surgery, GB had a better remission of T2DM than SG (53.1 vs. 35.3 %; p = 0.055). CONCLUSIONS: In conclusion, although both SG and GB are effective metabolic surgery, GB carries a higher power on T2DM remission than SG. ABCD score is useful in T2DM patient classification and selection for different procedures.

Bariatric Surgery for Patients With Early-Onset vs Late-Onset Type 2 Diabetes.

IMPORTANCE: The prevalence of early-onset type 2 diabetes mellitus (T2DM), which responds poorly to medical treatment, is increasing. Bariatric surgery has been well recognized for its effectiveness in the remission of T2DM, but its effectiveness and durability in the remission of early-onset T2DM has not yet been explored. OBJECTIVE: To compare the short- and long-term outcomes of bariatric surgery with a specific focus on the rate of remission of T2DM in patients with early-onset (age <40 years) and late-onset (age ≥40 years) T2DM. DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, 558 Taiwanese patients (339 with early-onset T2DM and 219 with late-onset T2DM) with a body mass index (calculated as weight in kilograms divided by height in meters squared) above 25 underwent bariatric surgery to ameliorate T2DM between January 1, 2007, and December 31, 2013. Patients were followed up for at least 1 year. Preoperative, perioperative, and postoperative clinical and laboratory data were prospectively collected and compared between the 2 groups. MAIN OUTCOMES AND MEASURES: Rate of remission of T2DM (hemoglobin A1C <6.0% without antiglycemic medication) was the primary outcome measure. RESULTS: Of the 558 patients (345 women) in the study, mean (SD) ages were 33.5 (7.5) for those with early-onset T2DM and 50.6 (6.5) with late onset T2DM. Those with early-onset T2DM had higher mean (SD) preoperative BMI and hemoglobin A1C values (39.4 [8.5] and 8.7% [3.8%] of total hemoglobin [to convert hemoglobin to a proportion of total hemoglobin, multiply by 0.01], respectively) than did patients with late-onset T2DM (36.7 [7.5] and 8.2% [1.6%], respectively). Distribution of surgical procedures and major complications were similar between the 2 groups. At 1 year, patients with early-onset T2DM achieved greater weight loss than those with late-onset T2DM, although the difference was not statistically significant. A higher rate of complete remission of T2DM was observed in patients with early-onset T2DM than in those with late-onset disease (193 [56.9%] vs 110 [50.2%]; P = .02). At 5 years, patients with early-onset T2DM still maintained a higher rate of weight loss (mean [SD], 30.4% [11.8%] vs 21.6% [11.7%]; P = .002) and higher rate of remission (47 of 72 [65.3%] vs 26 of 48 [54.2%]; P = .04) than did those with late-onset disease. Age at bariatric surgery, duration of T2DM, and preoperative C-peptide level were independent predictors of remission. The remission rate was directly related to extent of weight loss. Multivariate analysis confirmed the higher rate of remission in the group with early-onset T2DM. CONCLUSIONS AND RELEVANCE: This article describes the largest long-term study examining bariatric surgery for patients with early-onset T2DM. Bariatric surgery may achieve better and more long-lasting glycemic control in select patients with early-onset T2DM than in those with late-onset T2DM.

Durability of Addition of Roux-en-Y Gastric Bypass to Lifestyle Intervention and Medical Management in Achieving Primary Treatment Goals for Uncontrolled Type 2 Diabetes in Mild to Moderate Obesity: A Randomized Control Trial.

OBJECTIVE: We compared 3-year achievement of an American Diabetes Association composite treatment goal (HbA1c <7.0%, LDL cholesterol <100 mg/dL, and systolic blood pressure <130 mmHg) after 2 years of intensive lifestyle-medical management intervention, with and without Roux-en-Y gastric bypass, with one additional year of usual care. RESEARCH DESIGN AND METHODS: A total of 120 adult participants, with BMI 30.0-39.9 kg/m(2) and HbA1c ≥8.0%, were randomized 1:1 to two treatment arms at three clinical sites in the U.S. and one in Taiwan. All patients received the lifestyle-medical management intervention for 24 months; half were randomized to also receive gastric bypass. RESULTS: At 36 months, the triple end point goal was met in 9% of lifestyle-medical management patients and 28% of gastric bypass patients (P = 0.01): 10% and 19% lower than at 12 months. Mean (SD) HbA1c values at 3 years were 8.6% (3.5) and 6.7% (2.0) (P < 0.001). No lifestyle-medical management patient had remission of diabetes at 36 months, whereas 17% of gastric bypass patients had full remission and 19% had partial remission. Lifestyle-medical management patients used more medications than gastric bypass patients: mean (SD) 3.8 (3.3) vs. 1.8 (2.4). Percent weight loss was mean (SD) 6.3% (16.1) in lifestyle-medical management vs. 21.0% (14.5) in gastric bypass (P < 0.001). Over 3 years, 24 serious or clinically significant adverse events were observed in lifestyle-medical management vs. 51 with gastric bypass. CONCLUSIONS: Gastric bypass is more effective than lifestyle-medical management intervention in achieving diabetes treatment goals, mainly by improved glycemic control. However, the effect of surgery diminishes with time and is associated with more adverse events.

Preoperative Prediction of Type 2 Diabetes Remission After Gastric Bypass Surgery: a Comparison of DiaRem Scores and ABCD Scores.

BACKGROUND: Gastric bypass surgery has been well accepted as a novel treatment modality for type 2 diabetes mellitus (T2DM) in obese patients. Some scoring systems have been proposed for the selection of T2DM patients who are eligible for gastric bypass surgery. This study compares two scoring systems with regard to remission of T2DM after gastric bypass surgery. METHODS: This retrospective cohort study included 245 patients (150 females and 95 males) who had undergone gastric bypass surgery for the treatment of T2DM with 1 year follow-up. We examined the predictive power of complete remission of two scoring systems, the DiaRem score, and the ABCD score. The DiaRem score includes the factors of age, HbA1c, medication, and insulin usage. The ABCD score includes the factors of age, BMI, C-peptide level, and duration of T2DM. The rate of remission of T2DM after gastric bypass surgery was evaluated using both scoring systems. RESULTS: At 1 year after surgery, the percent weight loss was 26.5 % and the mean BMI decreased from 35.7 to 26.2 kg/m(2). The mean HbA1c decreased from 8.8 to 6.2 %. A significant number of patients showed improvement in glycemic control, including 130 (53.1 %) patients with complete remission (HbA1c < 6.0 %), 36 (14.7 %) patients with partial remission (HbA1c < 6.5 %), and 26 (10.6 %) patients with improvement (HbA1c < 7 %). Both the DiaRem score and the ABCD score predicted the success of the gastric bypass surgery, but the ABCD score was better at differentiating patients with poorer score (27.9 vs. 9.1 %, p < 0.001). CONCLUSIONS: Gastric bypass surgery is a treatment option for obese T2DM patients. The ABCD score is better at predicting T2DM remission at 1 year after gastric bypass surgery than the DiaRem score.

Bariatric versus diabetes surgery after five years of follow up.

BACKGROUND: Bariatric surgery (BS) is totally different from diabetes surgery (DS) in the patient characters, goals of surgery, and management although similar in surgical procedure. Comparison of BS and DS with long-term data is lacking. MATERIALS AND METHODS: A retrospective review of patients who received BS and patients who received DS at Min-Sheng General Hospital from 2007 to 2013 was designed. All inpatient and outpatient follow-up data were analyzed. Patients undergoing BS for the treatment of morbid obesity were compared with patients undergoing metabolic surgery for the treatment of type 2 diabetes mellitus (T2DM). Patients who received revision surgeries were excluded. The main outcome measures were: (1) operation risk; (2) weight loss; and (3) diabetes remission. RESULTS: Between 2007 and 2013, 2073 patients who received BS and 741 patients who received DS were recruited from both centers. DS patients were older (41.1 ± 10.9 years vs. 33.1 ± 9.3 years, p < 0.05) and were more likely to be male (40.2% vs. 28.2%, p < 0.05) and to have diabetes (100% vs. 6.0%, p < 0.05), however, they had similar body mass index (BMI) (37.9 ± 8.0 vs. 38.5 ± 9.7, p = 0.78) compared to the BS patients. Surgical procedures are significantly different between the two groups (73.3% of the DS surgeries were gastric bypass procedure, whereas this procedure made up only 47.1% of BS surgeries). Although the major complication rates were similar (2.0% vs. 2.4%), the DS program had a significant higher mortality rate than the BS program (0.54% vs. 0.1%; p < 0.05). At the 5-year follow-up time point, 58.0% of the BS patients had achieved successful results (weight loss > 30%) and 80% of the DS patients had complete remission of their diabetes [hemoglobin A1c (HbA1c) < 6.0%]. Both the DS and the BS group had good results in up to 85% of the patients at the 5-year follow-up time point. CONCLUSION: The clinical profiles were very different between the BS and the DS programs. Both programs achieved the desired outcomes equally well, however, the DS program had a higher risk than the BS program.

Roux-en-Y gastric bypass for diabetes (the Diabetes Surgery Study): 2-year outcomes of a 5-year, randomised, controlled trial.

BACKGROUND: Conventional treatments for patients with type 2 diabetes are often inadequate. We aimed to assess outcomes of diabetes control and treatment risks 2 years after adding Roux-en-Y gastric bypass to intensive lifestyle and medical management. METHODS: We report 2-year outcomes of a 5-year randomised trial (the Diabetes Surgery Study) at four teaching hospitals (three in the USA and one in Taiwan). At baseline, eligible participants had to have HbA1c of at least 8·0% (64 mmol/mol), BMI between 30·0 and 39·9 kg/m(2), and type 2 diabetes for at least 6 months, and be aged 30-67 years. We randomly assigned participants to receive either intensive lifestyle and medical management alone (lifestyle and medical management), or lifestyle and medical management plus standard Roux-en-Y gastric bypass surgery (gastric bypass). Staff from the clinical centres had access to data from individual patients, but were masked to other patients' data and aggregated data until the 2-year follow-up. Drugs for hyperglycaemia, hypertension, and dyslipidaemia were prescribed by protocol. The primary endpoint was achievement of the composite treatment goal of HbA1c less than 7·0% (53 mmol/mol), LDL cholesterol less than 2·59 mmol/L, and systolic blood pressure less than 130 mm Hg at 12 months; here we report the composite outcome and other pre-planned secondary outcomes at 24 months. Analyses were done on an intention-to-treat basis, with multiple imputations for missing data. This study is registered with ClinicalTrials.gov, number NCT00641251, and is still ongoing. FINDINGS: Between April 21, 2008, and Nov 21, 2011, we randomly assigned 120 eligible patients to either lifestyle and medical management alone (n=60) or with the addition of gastric bypass (n=60). One patient in the lifestyle and medical management group died (from pancreatic cancer), thus 119 were included in the primary analysis. Significantly more participants in the gastric bypass group achieved the composite triple endpoint at 24 months than in the lifestyle and medical management group (26 [43%] vs eight [14%]; odds ratio 5·1 [95% CI 2·0-12·6], p=0·0004), mainly through improved glycaemic control (HbA1c <7·0% [53 mmol/mol] in 45 [75%] vs 14 [24%]; treatment difference -1·9% (-2·5 to -1·4); p=0·0001). 46 clinically important adverse events occurred in the gastric bypass group and 25 in the lifestyle and medical management group (mainly infections in both groups [four in the lifestyle and medical management group, eight in the gastric bypass group]). With a negative binomial model adjusted for site, the event rate for the gastric bypass group was non-significantly higher than the lifestyle and medical management group by a factor of 1·67 (95% CI 0·98-2·87, p=0·06). Across both years of the study, the gastric bypass group had seven serious falls with five fractures, compared with three serious falls and one fracture in the lifestyle and medical management group. All fractures happened in women. Many more nutritional deficiencies occurred in the gastric bypass group (mainly deficiencies in iron, albumin, calcium, and vitamin D), despite protocol use of nutritional supplements. INTERPRETATION: The addition of gastric bypass to lifestyle and medical management in patients with type 2 diabetes improved diabetes control, but adverse events and nutritional deficiencies were more frequent. Larger and longer studies are needed to investigate whether the benefits and risk of gastric bypass for type 2 diabetes can be balanced. FUNDING: Covidien, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases Nutrition Obesity Research Centers, and the National Center for Advancing Translational Sciences.

Predictors of long-term diabetes remission after metabolic surgery.

BACKGROUND DATA: Bariatric/metabolic surgery has been proposed for the treatment of inadequately controlled type 2 diabetes mellitus (T2DM) in obese patients. However, prediction on successful long-term remission of T2DM after metabolic surgery has not been clearly studied. Our objectives were to evaluate rates of long-term remission of T2DM after metabolic surgery and determine the independent predictors of remission. METHODS: Outcomes of 157 patients who underwent metabolic surgery between 2006 and 2009 and who had complete 5-year follow-up data were assessed. Prolonged complete remission was defined as glycated hemoglobin (HbA1c) less than 6 % without diabetes medication up to 5 years. Predictors of prolonged remission studies included patient characteristics such as glucose level, HbA1c, body weight, waist circumference, blood pressure, total cholesterol, LDL, triglyceride, uric acid, AST, alanine transaminase (ALT), albumin, insulin, C-peptide, iron, calcium, complete blood cell count, the ABCD score (a multidimensional grading system composed of age, body mass index (BMI), C-peptide levels, and duration of T2DM), and postoperative weight loss. RESULTS: At 5 years after surgery, the weight loss was 27.1 % and the mean BMI decreased from 39.8 to 28.8 kg/m(2). The mean HbA1c decreased from 8.3 to 6.0 %. A significant number of patients had improvement in their glycemic control, including 97 (71.3 %) patients who had complete remission (HbA1c < 6.0 %), 27 (19.9 %) partial remission (HbA1c < 6.5 %), and 12 (8.8 %) improved condition (HbA1c < 7 %). In univariate analysis, patients with prolonged T2DM remission after surgery were younger and heavier; had a wider waist, higher C-peptide, shorter duration of T2DM, higher liver enzyme, higher insulin resistance, higher C-peptide level, and higher white blood cell count; were taking smaller insulin dosage; had higher ABCD score; and had greater weight loss than those without remission. Multivariate logistical regression analyses showed that the ABCD score and weight loss were the only predictors of remission after metabolic surgery. CONCLUSIONS: Metabolic surgery is a treatment option for patients with obesity and T2DM. Baseline ABCD score and weight loss have a major influence on outcome.

Gastro-intestinal Quality of Life After Metabolic Surgery for the Treatment of Type 2 Diabetes Mellitus.

BACKGROUND: Emerging evidence has shown that bariatric/metabolic surgery ameliorates type 2 diabetes (T2DM) in mildly obese patients (BMI < 35 kg/m(2)) but long-term data is inadequate. We investigated the change of the quality of life after metabolic surgery in not well-controlled T2DM patients with BMI < 35 kg/m(2). METHODS: The quality of life was measured by the gastrointestinal quality of life index (GIQLI), a 36-item questionnaire divided into three domains of general health and one domain of specific gastro-intestinal symptoms, administered before operation, at 3, 6, and 12 months after surgery. A control group matched in age, gender, and BMI was recruited for comparison. RESULTS: A total of 86 patients were enrolled, and the preoperative BMI and HbA1C (mean ± SD) were 30.7 ± 2.8 kg/m(2) and 9.3 ± 2.1 %, respectively. At 1 year after surgery, the BMI and HbA1C were 24.3 ± 2.3 kg/m(2) and 6.2 ± 1.1 %, respectively. There was a significantly improvement in all of the measures of glucose metabolism. Complete remission (HbA1C < 6.0 %) was achieved in 56 subjects (65 %) at 12 months. The GIQLI score was significantly impaired in T2DM patients before surgery compared with the control group. The GIQLI score significantly increased from 109.2 ± 20.0 to 116.1 ± 14.2 points 1 year after surgery. The patients had improvement in the three domains of general health (social, physical, and emotional function) without a difference with the normal control but deteriorated in the domain of specific symptoms. Most of the patients experienced symptoms including abdominal pain, bloating, flatulence, belching, abdominal noise, regurgitation, dysphagia, slow eating speed, nausea, bowel urgency, and incontinence after metabolic syndrome. CONCLUSIONS: Health-related QOL improved dramatically after metabolic surgery for not well-controlled T2DM patients with BMI < 35 kg/m(2), but patients might develop specific gastro-intestinal symptoms after surgery.

The Effect and Predictive Score of Gastric Bypass and Sleeve Gastrectomy on Type 2 Diabetes Mellitus Patients with BMI < 30 kg/m(2).

BACKGROUND: Metabolic surgery is a novel therapy for mild obesity (BMI 30-35 Kg/m(2)) in type 2 diabetes mellitus (T2DM) patients. The ABCD score, which comprise age, BMI, C-peptide level, and duration of T2DM (years), was reported as useful in predicting the success of T2DM treatment using metabolic surgery. This study examines gastric bypass and sleeve gastrectomy as a salvage treatment for non-obese (BMI < 30 kg/m(2)) T2DM patients and evaluates the role of ABCD scores. METHODS: From January 2007 to July 2013, 512 (71.2%) of 711 T2DM patients enrolled in a metabolic surgical program had at least 1-year follow-up were recruited. Clinical data and outcomes of 80 (15.6%) patients with BMI < 30 Kg/m(2) were compared with those of the other 432 (84.4%) patients with BMI ≥ 30 Kg/m(2). Complete remission was defined as HbA1c ≤ 6%, and partial remission was defined as HbA1c < 6.5%. A binary logistic regression was used to identify predictors of T2DM remission. RESULTS: Mean age of the 80 non-obese T2DM patients was 47.7 ± 9.1 years, and mean HbA1c and disease duration were 9.1 ± 1.8% and 6.5 ± 5.1 years, respectively. Mean total body weight loss was 17.1 ± 7.4% at 1 year, and mean BMI decreased from 26.9 ± 2.2 to 22.7 ± 2.5 kg/m(2) at 1 year. Complete remission of T2DM was achieved in 25.0% of patients, and partial remission was achieved in 23.8%. The complete remission rate was significantly lower than the 49.5% found in patients with BMI 30-35 and 79.0% of patients with BMI > 35 Kg/m(2). In univariate analysis, non-obese patients who had T2DM remission after surgery were heavier and had a wider waist, higher C-peptide levels, shorter disease duration, more weight loss, and higher ABCD score than those without remission. The ABCD score remained the only independent predictor of success after multivariate logistical regression analyses (P = 0.003). CONCLUSIONS: Metabolic surgery may be useful in achieving glycemic control of selected non-obese T2DM patients. The ABCD score is a simple multidimensional grading system that can predict the success of T2DM treatment.