Context Bariatric surgery, particularly Roux-en-Y gastric bypass (RYGB), is associated with an increased risk of osteoporotic fractures. It is unknown whether RYGB or sleeve gastrectomy (SG) have different effects on bone health. Objective To compare changes in bone mineral density and markers of bone turnover 1 year after SG and RYGB. Design, Setting, Patients, and Interventions Randomized, triple-blind, single-center trial at a tertiary care center in Norway. The primary outcome was diabetes remission. Patients with severe obesity and type 2 diabetes were randomized and allocated (1:1) to SG or RYGB. Main Outcome Measures Changes in areal bone mineral density (aBMD) and bone turnover markers. Results Femoral neck, total hip, and lumbar spine aBMD, but not total body aBMD, decreased significantly more after RYGB (n = 44) than after SG (n = 48) (mean [95% confidence interval] between group differences -2.8% [-4.7 to -0.8], -3.0% [-5.0 to -0.9], -4.2% [-6.4 to -2.1], and -0.5% [-1.6 to 0.6], respectively). The increase in procollagen type 1 N-terminal propeptide (P1NP) and C-telopeptide of type I collagen (CTX-1) were approximately 100% higher after RYGB than after SG (between group difference at 1 year, both P < 0.001). The changes in femoral neck, total hip, and lumbar spine aBMDs and the changes in P1NP and CTX-1 were independently associated with the surgical procedure (all P < 0.05) and not weight change. Conclusions Roux-en-Y gastric bypass was associated with a greater reduction in aBMD and a greater increase in bone turnover markers compared with SG. This finding could suggest greater skeletal fragility after RYGB.

Nonalcoholic fatty liver disease is characterized by hepatic steatosis that may progress to nonalcoholic steatohepatitis and cirrhosis. Bariatric surgical approaches, such as Roux-en-Y gastric bypa... Visual RYGB Versus SG in T2DM: Effects on Hepatic Steatosis and Fibrosis. Nonalcoholic fatty liver disease is characterized by hepatic steatosis that may progress to nonalcoholic steatohep... Background: Weight loss improves fatty liver disease. No randomized trial has compared the effects of sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) on liver fat content and fibrosis. ...

Aims: To estimate the effect of atorvastatin on muscle symptom intensity in coronary heart disease (CHD) patients with self-perceived statin-associated muscle symptoms (SAMS) and to determine the relationship to blood levels of atorvastatin and/or metabolites. Methods and results: A randomized multi-centre trial consecutively identified 982 patients with previous or ongoing atorvastatin treatment after a CHD event. Of these, 97 (9.9%) reported SAMS and 77 were randomized to 7-week double-blinded treatment with atorvastatin 40 mg/day and placebo in a crossover design. The primary outcome was the individual mean difference in muscle symptom intensity between the treatment periods, measured by visual-analogue scale (VAS) scores. Atorvastatin did not affect the intensity of muscle symptoms among 71 patients who completed the trial. Mean VAS difference (statin-placebo) was 0.31 (95% CI: −0.24 to 0.86). The proportion with more muscle symptoms during placebo than atorvastatin was 17% (n = 12), 55% (n = 39) had the same muscle symptom intensity during both treatment periods whereas 28% (n = 20) had more symptoms during atorvastatin than placebo (confirmed SAMS). There were no differences in clinical or pharmacogenetic characteristics between these groups. The levels of atorvastatin and/or metabolites did not correlate to muscle symptom intensity among patients with confirmed SAMS (Spearman’s rho ≤0.40, for all variables). Conclusion: Re-challenge with high-intensity atorvastatin did not affect the intensity of muscle symptoms in CHD patients with self-perceived SAMS during previous atorvastatin therapy. There was no relationship between muscle symptoms and the systemic exposure to atorvastatin and/or its metabolites. The findings encourage an informed discussion to elucidate other causes of muscle complaints and continued statin use.

Previous studies have demonstrated a high prevalence of biochemical vitamin B12 deficiency in infants in Norway. Increased total homocysteine (tHcy) is the most important marker of B12 deficiency in infants. There is a need to evaluate its clinical relevance. To investigate the prevalence of hyperhomocysteinemia (S-tHcy > 8 μmol/L) suggestive of suboptimal B12 status and the prevalence of clinically relevant hyperhomocysteinemia in presumed healthy infants in Norway. Further, to evaluate risk factors, presence of symptoms and psychomotor development in these children. In a prospective study we clinically examined 252 infants aged 3-7 months using standardized neurological and psychomotor tests prior to analyzing biochemical B12 deficiency markers in 250 infants. Twenty-five of 250 (10%) infants had hyperhomocysteinemia combined with clinically relevant symptoms suggestive of B12 deficiency. Hyperhomocysteinemia was associated with tremor, excessive sleep, and sub-normal scores in the fine motor section of the Ages and Stages Questionnaire. One-hundred and fourteen of 250 (46%) infants had hyperhomocysteinemia. Multiple regression analysis showed months of infant formula use as the strongest negative predictor for hyperhomocysteinemia. We have demonstrated associations between symptoms suggestive of infant B12 deficiency and increased levels of tHcy in presumed healthy infants The combination of hyperhomocysteinemia and associated relevant symptoms suggestive of B12 deficiency was a common finding, albeit most infants with hyperhomocysteinemia did not show symptoms.

Background: The sensitivity of newborn screening (NBS) in detecting infants that later develop symptomatic vitamin B12 deficiency is unknown. We evaluated the predictive value using NBS algorithms in detecting infants that later were clinically diagnosed with symptomatic B12 deficiency. Furthermore, we investigated whether being born in a hospital using nitrous oxide (N₂O) as pain relief in labor may have had an impact on total homocysteine at NBS. Methods: We retrospectively retrieved NBS data and analyzed total homocysteine, methylmalonic acid and methyl citrate on stored NBS dried blood spots (DBS) of 70 infants diagnosed with symptomatic B12 deficiency and compared them to 646 matched and 434 unmatched DBS controls to evaluate the Austrian and Heidelberg B12 NBS algorithms. Results: The sensitivity of NBS in detecting infants later diagnosed with symptomatic B12 deficiency at median age 10.9 weeks was ≤10%. Total homocysteine was higher in DBS for the unmatched controls who were born in hospitals providing N₂O compared to in hospitals not providing N₂O, with median total homocysteine 4.0 µmol/L compared to 3.5 µmol/L (n = 434, 95% CI 0.04–0.87, p = 0.03). Conclusion: NBS algorithms were unable to identify most infants diagnosed with symptomatic B12 deficiency after the neonatal period. Being born in hospitals providing N₂O may impact total homocysteine at NBS.

Metylmalonic acid (MMA) and homocysteine (HCY) are important biomarkers in the assessment of cobalamin and folate metabolism. Correct interpretation of patient results benefit from knowledge of biological variation. The aim of the present study was to determine within-subject (CV_I) and between-subject (CV_G) biological variations of serum MMA and HCY in healthy women. We collected blood samples from 12 healthy volunteers (33–61 years) on the same weekday for 10 consecutive weeks. Samples were stored at −80 °C until analysis in duplicate in a single analytical run in random order. The CV_I and CV_G biological variations were estimated by CV-ANOVA after the data were first subjected to outlier and homogeneity analysis. The CV_I (95% CI) for MMA and HCY were 7.2% (6.1–8.5) and 7.4% (6.5–8.5), respectively. The corresponding CV_G were 21.1% (14.0–32.2) and 24.2% (16.2–36.8). The index of individuality (II) was 0.34 for MMA and 0.31 for HCY and the reference change value (RCV) was −17.7; 21.0 (% decrease; increase) for MMA and −16.2; 19.4 for HCY. We provide within- and between-subject biological variation estimates for MMA and HCY in healthy women using an updated protocol. The results will contribute to a better clinical interpretation of these biomarkers and be of aid when setting analytical performance specifications.