Risk of fractures following bariatric surgery with Roux-en-Y gastric bypass or sleeve gastrectomy: a Danish population-based cohort study.

OBJECTIVE: We examined the association between Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) and fracture risk, including major osteoporotic fractures (MOF), and the use of anti-osteoporosis medication (AOM). While RYGB is associated with impaired bone health and increased fracture risk, it remains uncertain whether SG has a similar impact and whether this risk is primarily due to MOF or any fracture. DESIGN: We conducted a nationwide cohort study covering patients treated with RYGB (n = 16 121, 10.2-year follow-up) or SG (n = 1509, 3.7-year follow-up), from 2006 to 2018, comparing them with an age- and sex-matched cohort (n = 407 580). METHODS: We computed incidence rates and adjusted hazard ratios (HRs) with 95% CIs, using Cox regression for any fracture, MOF, and use of AOM with adjustment for comorbidities. RESULTS: Compared with the general population cohort, RYGB was associated with an increased risk of any fracture (HR 1.56 [95% CI, 1.48-1.64]) and MOF (HR 1.49 [1.35-1.64]). Sleeve gastrectomy was associated with an increased risk of any fracture (HR 1.38 [1.13-1.68]), while the HR of MOF was 1.43 (0.97-2.12). The use of AOM was low but similar in all cohorts (approximately 1%). CONCLUSIONS: Bariatric surgery increased the risk of any fracture and MOF to similar extend. Risks were similar for RYGB and SG. However, SG had a shorter follow-up than RYGB, and the cohort size was rather small. More research is needed for long-term SG fracture risk assessment. The use of AOM was low in all cohorts.

Changes in Symptoms and General Well-being After Reversal of Roux-en-Y Gastric Bypass: A Questionnaire Survey.

PURPOSE: After Roux-en-Y gastric bypass (RYGB), few patients develop severe complications, which ultimately may require reversal of RYGB. We aimed to examine the effect of reversal of RYGB on symptoms and well-being. MATERIALS AND METHODS: Via contact to medical and surgical departments treating patients with RYGB, we identified 18 patients, who had undergone reversal, 2009-2019. We conducted a Danish, nationwide questionnaire survey concerning symptoms before and after reversal of the RYGB including the patients' own perceptions of their well-being. RESULTS: Fourteen patients responded to the questionnaire (86% female; median age at RYGB, 36.2 years [IQR, 30.9-38.6 years]). The median time from RYGB to reversal was 5.8 years (IQR, 5.1-7.5 years). After RYGB, 13 patients (93%) reported abdominal pain, while 12 patients still had abdominal pain after reversal. Six out of 11 patients (45%) reported complete remission of dumping/post-bariatric hypoglycemia (PBH) after reversal. Malabsorption disappeared in 10 out of 11 patients (90%). Reversal had minor effect on neuropathy. The median weight loss from RYGB was 61 kg (IQR, 56-75 kg), while the median weight regain after reversal was 30 kg (IQR, 13-46 kg). Regarding the well-being, 72 of the patients felt better or much better after reversal. CONCLUSION: In total, 72% of the patients felt better or much better after reversal of RYGB, though some still had RYGB-related symptoms. The reversal relieved dumping/PBH and malabsorption, but not abdominal pain and neuropathy. Finally, half of the weight loss was regained after reversal. Reversal of RYGB may be an option in highly selected cases.

Roux-en-Y Gastric Bypass Increases Glycemic Excursions During Pregnancy and Postpartum: A Prospective Cohort Study.

OBJECTIVE: Roux-en-Y gastric bypass (RYGB) and pregnancy markedly alter glucose metabolism, but evidence on glucose metabolism in pregnancy after RYGB is limited. Thus, the aims of the Bariatric Surgery and Consequences for Mother and Baby in Pregnancy study were to investigate interstitial glucose (IG) profiles during pregnancy, risk factors associated with hypoglycemia, and the association between fetal growth and hypoglycemia in pregnant women previously treated with RYGB, compared with control participants. RESEARCH DESIGN AND METHODS: Twenty-three pregnant women with RYGB and 23 BMI- and parity-matched pregnant women (control group) were prospectively studied with continuous glucose monitoring in their first, second, and third trimesters, and 4 weeks postpartum. Time in range (TIR) was defined as time with an IG level of 3.5-7.8 mmol/L. RESULTS: Women with RYGB were 4 years (interquartile range [IQR] 0-7) older than control participants. Pregnancies occurred 30 months (IQR 15-98) after RYGB, which induced a reduction in BMI from 45 kg/m2 (IQR 42-54) presurgery to 32 kg/m2 (IQR 27-39) prepregnancy. Women with RYGB spent decreased TIR (87.3-89.5% vs. 93.3-96.1%; P < 0.01) owing to an approximately twofold increased time above range and increased time below range (TBR) throughout pregnancy and postpartum compared with control participants. Women with increased TBR had a longer surgery-to-conception interval, lower nadir weight, and greater weight loss after RYGB. Finally, women giving birth to small-for-gestational age neonates experienced slightly increased TBR. CONCLUSIONS: Women with RYGB were more exposed to hypoglycemia and hyperglycemia during pregnancy compared with control participants. Further research should investigate whether hypoglycemia during pregnancy in women with RYGB is associated with decreased fetal growth.

Influence of food matrix delivery system on the bioavailability of vitamin D3: A randomized crossover trial in postmenopausal women.

OBJECTIVES: Vitamin D insufficiency (blood 25-hydroxyvitamin D <50 nmol/L) is a global health problem. Vitamin D food fortification might be a solution, but knowledge is sparse on which food matrices yield the highest bioavailability. The aim of this study was to investigate the influence of different food matrices including complex formations with whey proteins on the human bioavailability of vitamin D. METHODS: In this randomized, multiple crossover trial, we enrolled 30 postmenopausal women 60 to 80 y of age with vitamin D insufficiency. We measured changes in serum concentrations of vitamin D3 (D3) postprandially for 24 h in response to the intake of 500 mL of different food matrices with 200 µg D3 added compared with a control (500 mL of water). Foods included apple juice with whey protein isolate (WPI), apple juice, semi-skim milk, and water (with D3). The food matrices were provided in a randomized order with ≥10-d washout period between them. On each intervention day, blood samples were collected at 0, 2, 4, 6, 8, 10, 12 and 24 h. RESULTS: D3 with WPI in juice did not enhance area under the curve (AUC) of serum D3 compared with juice without WPI (370 nmol ×  24 h/L; 95% confidence interval [CI], 321-419 versus 357 nmol ×  24 h/L; 95% CI, 308-406 nmol ×  24 h/L; P = 0.65). However, compared with juice, the AUC was significantly higher in response to the intake of D3 in milk (452 nmol ×  24 h/L; 95% CI, 402-502 nmol ×  24 h/L) and water with D3 (479 nmol ×  24 h/L; 95% CI, 430-527 nmol ×  24 h/L; P < 0.05). No difference was observed between milk and water (P = 0.34). CONCLUSIONS: The bioavailability of D3 was superior in milk and water compared with juice, regardless of whether WPI was added.

Hypoglycemia in Pregnancies Following Gastric Bypass-a Systematic Review and Meta-analysis.

The aims of this systematic review were to identify the prevalence of hypoglycemia among pregnant women treated with gastric bypass, and risk factors of hypoglycemic events in pregnancy. We searched MEDLINE, EMBASE, Cochrane, and Scopus databases from inception to April 6, 2021. Six studies investigating glucose metabolism in pregnancy following gastric bypass were included (n = 330). As assessed by the oral glucose tolerance test and continuous glucose monitoring, 57.6% (95% CI [40.1, 75.1]) of women with gastric bypass were exposed to hypoglycemia during pregnancy. No studies performed the mixed meal test, and no studies reported on risk factors associated with hypoglycemia. Further studies are required to determine the magnitude of hypoglycemia in these women's everyday-life using continuous glucose monitoring and mixed meal test.

Do variations in insulin sensitivity and insulin secretion in pregnancy predict differences in obstetric and neonatal outcomes?

AIMS/HYPOTHESIS: Gestational diabetes mellitus (GDM) is generally defined based on glycaemia during an OGTT, but aetiologically includes women with defects in insulin secretion, insulin sensitivity or a combination of both. In this observational study, we aimed to determine if underlying pathophysiological defects evaluated as continuous variables predict the risk of important obstetric and neonatal outcomes better than the previously used dichotomised or categorical approaches. METHODS: Using data from blinded OGTTs at mean gestational week 28 from five Hyperglycemia and Adverse Pregnancy Outcome study centres, we estimated insulin secretion (Stumvoll first phase) and sensitivity (Matsuda index) and their product (oral disposition index [DI]) in 6337 untreated women (1090 [17.2%] with GDM as defined by the International Association of Diabetes and Pregnancy Study Groups). Rather than dichotomising these variables (i.e. GDM yes/no) or subtyping by insulin impairment, we related insulin secretion and sensitivity as continuous variables, along with other maternal characteristics, to obstetric and neonatal outcomes using multiple regression and receiver operating characteristic curve analysis. RESULTS: Stratifying by GDM subtype offered superior prediction to GDM yes/no only for neonatal hyperinsulinaemia and pregnancy-related hypertension. Including the DI and the Matsuda score significantly increased the area under the receiver operating characteristic curve (AUROC) and improved prediction for multiple outcomes (large for gestational age [AUROC 0.632], neonatal adiposity [AUROC 0.630], pregnancy-related hypertension [AUROC 0.669] and neonatal hyperinsulinaemia [AUROC 0.688]). Neonatal hypoglycaemia was poorly predicted by all models. Combining the DI and the Matsuda score with maternal characteristics substantially improved the predictive power of the model for large for gestational age, neonatal adiposity and pregnancy-related hypertension. CONCLUSION/INTERPRETATION: Continuous measurement of insulin secretion and insulin sensitivity combined with basic clinical variables appeared to be superior to GDM (yes/no) or subtyping by insulin secretion and/or sensitivity impairment in predicting obstetric and neonatal outcomes in a multi-ethnic cohort. Graphical abstract.

Testing for gestational diabetes during the COVID-19 pandemic. An evaluation of proposed protocols for the United Kingdom, Canada and Australia.

AIMS: We assessed how altered diagnostic processes and criteria for gestational diabetes mellitus (GDM) recommended by the United Kingdom (UK), Canada and Australia for use during the COVID-19 pandemic would affect both GDM frequency and related adverse outcomes. METHODS: Secondary analysis of 5974 HAPO study women with singleton pregnancies who underwent 75 g OGTTs and HbA1c assays between 24 and 32 weeks' gestation and who received no treatment for GDM. RESULTS: All post COVID-19 modified pathways reduced GDM frequency - UK (81%), Canada (82%) and Australia (25%). Canadian women whose GDM would remain undetected post COVID-19 (missed GDMs) displayed similar rates of pregnancy complications to those with post COVID-19 GDM. Using UK modifications, the missed GDM group were at slightly lower risk whilst the women missed using the Australian modifications were at substantially lower risk. CONCLUSIONS: The modifications in GDM diagnosis proposed for the UK, Canada and Australia result in differing reductions of GDM frequency. Each has both potential benefits in terms of reduction in potential exposure to COVID-19 and costs in terms of missed opportunities to influence pregnancy and postpartum outcomes. These factors should be considered when deciding which protocol is most appropriate for a particular context.

Effect of Roux-en-Y gastric bypass surgery on diabetes remission and complications in individuals with type 2 diabetes: a Danish population-based matched cohort study.

AIMS/HYPOTHESIS: The aim of this study was to examine the effect of Roux-en-Y gastric bypass (RYGB) surgery on diabetes remission, subsequent diabetes relapse and micro- and macrovascular complications in individuals with type 2 diabetes and obesity (BMI >35 kg/m2) in a real-world setting. METHODS: This was a population-based cohort study of 1111 individuals with type 2 diabetes treated by RYGB at hospitals in Northern Denmark (2006-2015), and 1074 matched non-operated individuals with type 2 diabetes. Diabetes remission was defined as no glucose-lowering drug use with HbA1c <48 mmol/mol (<6.5%), or metformin monotherapy with HbA1c <42 mmol/mol (<6.0%). Data on complications were ascertained from medical registries with complete follow-up. RESULTS: At 1 year of follow-up, 74% of the cohort treated by RYGB experienced diabetes remission, while 27% had relapsed after 5 years. Predictors of non-remission were age >50 years, diabetes duration >5 years, use of glucose-lowering drugs other than metformin, and baseline HbA1c >53 mmol/mol (>7.0%). Compared with the non-operated cohort using adjusted Cox regression (5.3 years follow-up), the cohort treated by RYGB had 47% lower risk of microvascular complications (HR 0.53 [95% CI 0.38, 0.73]) and a statistically non-significant 24% lower risk of macrovascular complications (HR 0.76 [95% CI 0.49, 1.18]). Diabetes remission vs non-remission at 1 year was associated with reduced HR of 0.43 (95% CI 0.25, 0.72) for microvascular complications and with HR of 0.76 (95% CI 0.40, 1.45) for macrovascular complications. CONCLUSIONS/INTERPRETATION: In routine clinical care, three out of four individuals with type 2 diabetes and obesity treated by RYGB experienced diabetes remission after 1 year, whereas 27% of these individuals had relapsed at 5 years follow-up. RYGB was associated with substantially decreased risk of microvascular complications and non-significantly fewer macrovascular complications, with early diabetes remission as a clear predictor of reduced microvascular complications.