Context: In primary hyperparathyroidism (PHPT) bone mineral density (BMD) is typically decreased in cortical bone and relatively preserved in trabecular bone. An increased fracture rate is observed... Show moreContext: In primary hyperparathyroidism (PHPT) bone mineral density (BMD) is typically decreased in cortical bone and relatively preserved in trabecular bone. An increased fracture rate is observed however not only at peripheral sites but also at the spine, and fractures occur at higher BMD values than expected. We hypothesized that components of bone quality other than BMD are affected in PHPT as well.Objective: To evaluate bone material properties using impact microindentation (IMI) in PHPT patients.Methods: In this cross-sectional study, the Bone Material Strength index (BMSi) was measured by IMI at the midshaft of the tibia in 37 patients with PHPT (28 women), 11 of whom had prevalent fragility fractures, and 37 euparathyroid controls (28 women) matched for age, gender, and fragility fracture status.Results: Mean age of PHPT patients and controls was 61.813.3 and 61.0 +/- 11.8 years, respectively, P = .77. Calcium and PTH levels were significantly higher in PHPT patients but BMD at the lumbar spine (0.92 +/- 0.15 vs 0.89 +/- 0.11, P = .37) and the femoral neck (0.70 +/- 0.11 vs 0.67 +/- 0.07, P = .15) were comparable between groups. BMSi however was significantly lower in PHPT patients than in controls (78.2 +/- 5.7 vs 82.8 +/- 4.5, P < .001). In addition, BMSi was significantly lower in 11 PHPT patients with fragility fractures than in the 26 PHPT patients without fragility fractures (74.7 +/- 6.0 vs 79.6 +/- 5.0, P = .015).Conclusion: Our data indicate that bone material properties are altered in PHPT patients and most affected in those with prevalent fractures. IMI might be a valuable additional tool in the evaluation of bone fragility in patients with PHPT. Show less
Conclusions/interpretation This study shows that type 2 diabetes is characterised by increased fasting and postprandial plasma alpha-dicarbonyl stress, which can be reduced by improving glucose... Show moreConclusions/interpretation This study shows that type 2 diabetes is characterised by increased fasting and postprandial plasma alpha-dicarbonyl stress, which can be reduced by improving glucose metabolism through a VLCD or RYGB. These data highlight the potential to reduce reactive alpha-dicarbonyls in obese individuals with type 2 diabetes. Trial registration: ClinicalTrials.gov NCT01167959 Show less
Heemskerk, M.M.; Giera, M.; Bouazzaoui, F. el; Lips, M.A.; Pijl, H.; Dijk, K.W. van; Harmelen, V. van 2015
OBJECTIVE\nObesity and type 2 diabetes mellitus (T2DM) have been associated with increased levels of circulating branched-chain amino acids (BCAAs) that may be involved in the pathogenesis of... Show moreOBJECTIVE\nObesity and type 2 diabetes mellitus (T2DM) have been associated with increased levels of circulating branched-chain amino acids (BCAAs) that may be involved in the pathogenesis of insulin resistance. However, weight loss has not been consistently associated with the reduction of BCAA levels.\nRESEARCH DESIGN AND METHODS\nWe included 30 obese normal glucose-tolerant (NGT) subjects, 32 obese subjects with T2DM, and 12 lean female subjects. Obese subjects underwent either a restrictive procedure (gastric banding [GB], a very low-calorie diet [VLCD]), or a restrictive/bypass procedure (Roux-en-Y gastric bypass [RYGB] surgery). Fasting blood samples were taken for the determination of amine group containing metabolites 4 weeks before, as well as 3 weeks and 3 months after the intervention.\nRESULTS\nBCAA levels were higher in T2DM subjects, but not in NGT subjects, compared with lean subjects. Principal component (PC) analysis revealed a concise PC consisting of all BCAAs, which showed a correlation with measures of insulin sensitivity and glucose tolerance. Only after the RYGB procedure, and at both 3 weeks and 3 months, were circulating BCAA levels reduced.\nCONCLUSIONS\nOur data confirm an association between deregulation of BCAA metabolism in plasma and insulin resistance and glucose intolerance. Three weeks after undergoing RYGB surgery, a significant decrease in BCAAs in both NGT as well as T2DM subjects was observed. After 3 months, despite inducing significant weight loss, neither GB nor VLCD induced a reduction in BCAA levels. Our results indicate that the bypass procedure of RYGB surgery, independent of weight loss or the presence of T2DM, reduces BCAA levels in obese subjects. Show less
In this thesis, we evaluated the acute and more long-term effects of different weight loss strategies; pure calorie restriction by very low calorie diet and gastric banding, versus the drastic... Show moreIn this thesis, we evaluated the acute and more long-term effects of different weight loss strategies; pure calorie restriction by very low calorie diet and gastric banding, versus the drastic surgical procedure Roux-en-Y gastric bypass. Moreover, we found differences between NGT and T2DM subjects at baseline, which enable us to better be able to dissect the subsequent effects of the procedures. To our surprise, and in contrast to previous studies, we observed no additional effect of the RYGB as compared to calorie restriction, on our main outcome parameters: postprandial glucose, insulin and the gut peptide levels three weeks after surgery. Furthermore, both restrictive and RYGB induced weight loss resulted in comparable effects on the lipidome, circulating thyroid hormone levels and the autonomic nervous system. For these outcome parameters, it seems that calorie restriction is the common denominator of the effect of the different weight loss strategies on the short term. Clearly distinct effects of RYGB, however, were seen on bile salt, FGF21 and glucagon levels in response to food intake. Although neither the exact mechanisms, nor the eventual metabolic effect are as yet clear, the gut-liver-pancreas axis may be an important mediator of the effect of the RYGB Show less
Lips, M.A.; Wijngaarden, M.A.; Grond, J. van der; Buchem, M.A. van; Groot, G.H. de; Rombouts, S.A.R.B.; ... ; Veer, I.M. 2014
