Hypertriglyceridemia is associated with insulin levels in adult cystic fibrosis patients

BackgroundRecent studies have identified hypertriglyceridemic cystic fibrosis patients (CF-TG). However, whether hypertriglyceridemia is associated with an altered metabolic profile remains unknown.ObjectiveTo characterize CF-TG and determine whether triglycerides (TG) levels are associated with metabolic alterations.Methods210 adult CF subjects from the Montreal Cystic Fibrosis Cohort without known diabetes were included in the analysis. All subjects underwent an OGTT to assess glucose tolerance, insulin secretion (insulin AUC) and insulin sensitivity (Stumvoll index). Fasting lipid profiles, pulmonary function (%FEV₁) and BMI were determined. Hypertriglyceridemia (TG > 1.7 mmol/L) was observed in 20 CF patients. These subjects were matched for age, sex and glucose tolerance category with 20 CF patients (CF-normal-TG) and 20 healthy controls that had TG levels below 1.7 mmol/L. Pearson correlations were performed in the complete study sample (n = 210) to examine the associations between TG levels and other parameters.ResultsThe prevalence of hypertriglyceridemia was 9.5%. Compared to CF-normal-TG, CF-TG subjects displayed significantly higher %FEV_1, insulin AUC (AUC_0–120, AUC_0–30, AUC_30–120), cholesterol levels and a higher ratio of total cholesterol to HDL-cholesterol. Pearson analysis demonstrated that TG levels were associated with BMI, %FEV₁, fasting insulin, insulin AUC_0–120 and AUC_30–120, Stumvoll index, cholesterol levels and the ratio of total cholesterol to HDL-cholesterol. All these correlations remained significant after correction for BMI except %FEV₁.ConclusionTG levels are associated with a mild alteration of the metabolic profile. Whether these changes will increase the long-term risk of CF patients in developing cardiometabolic complications remains to be investigated.     

Patients with cystic fibrosis and normoglycemia exhibit diabetic glucose tolerance during pulmonary exacerbation

BackgroundPatients with cystic fibrosis and normoglycemia (CF-NGT) have higher but still “normal” glucose levels in the Oral Glucose Tolerance Test (OGTT). Respiratory exacerbation is associated with metabolic stress. The objective of this study was to assess the glucose metabolism and its relation to the steady state pulmonary function (FEV1) in patients with CF-NGT, specifically during pulmonary exacerbations (PE).MethodsCF-NGT patients who were not on steroids, underwent OGTT and intravenous glucose tolerance tests (IVGTT) during PE and 4 weeks after complete recovery.ResultsOf the ten recruited patients two had diabetic OGTT and were excluded. The remaining normoglycemic patients displayed during PE a diabetic glucose tolerance with mean glucose levels of 233 ± 8 and 262 ± 11 mg/dl at 90 and 120 min respectively, compared with normal levels of 154 ± 21and 126 ± 20 mg/dl (p < 0.002) during the steady state. IVGTT showed a tendency to higher first phase insulin release during PE compared with the steady state.(min 3; 305 ± 80 vs. 216 ± 40 pmol\l p = 0.075). Finally, when relating the diabetic status to the general respiratory function we found a negative correlation between baseline FEV1 and glucose levels at 2 h after OGTT during PE (r = − 0.88, p = 0.002).ConclusionIn this pilot study we show that during PE patients with CF and normal glucose tolerance exhibited early latent diabetic glucose intolerance. As this hyperglycemia presents in the later parts of the OGTT it probably results from insufficient second phase insulin secretion during PE. The negative correlation observed here between the diabetic glucose tolerance and FEV1 indicate the need of interventional studies using insulin during PE in non-diabetic patients to determine its potential benefit on the outcome from recurrent PEs.     

Análisis de la pérdida ponderal a medio plazo después del bypass gastroyeyunal en Y de Roux y de la gastrectomía vertical: propuesta de gráficos de percentiles del porcentaje de peso total perdido para su uso en la práctica clínica diaria

IntroductionThe aim of this study is to analyze weight evolution after the main bariatric surgical techniques (Roux-en-Y gastric bypass [RYGB] and sleeve gastrectomy [SG]) performed at a representative sample of Spanish hospitals in order to develop percentile charts for the percentage of total weight loss during the first 3 years after surgery.MethodsA retrospective longitudinal cohort study was conducted based on the data provided by 9 Spanish hospitals. Weight data were analyzed both in % total weight loss and % excess weight lost corresponding to the RYGB (n = 1,887) and SG (n = 1,210).ResultsRYGB continues to be the most frequently performed technique in our sample. In both surgical techniques, maximum weight loss occurred 18 months after surgery. Both techniques followed the same weight evolution, although the % total weight loss values were lower in the case of the SG after 36 months (29.3 ± 10 vs. 33.6 ± 10). Age and gender are decisive in the weight results (better in younger patients for both techniques and better in women for RYGB).ConclusionsPercentile charts of % total weight loss after bariatric surgery represent a very useful tool and an important advance in the quality of patient management.     

Relationship between biochemical and symptomatic hypoglycemia after RYGB. Responses to a mixed meal test: a case-control study

BackgroundPostprandial hypoglycemia is a relatively common complication after Roux-en-Y gastric bypass (RYGB). The cause remains incompletely understood, and the association between biochemical hypoglycemia and hypoglycemic symptoms is unclear.ObjectivesTo evaluate the association between postprandial hormonal responses and biochemical and symptomatic hypoglycemia after RYGB.SettingUniversity Hospital, Denmark.MethodsA case-control study with 3 groups: (1) RYGB group with postprandial hypoglycemic symptoms (HS), n = 13; (2) RYGB-group with no symptoms of hypoglycemia (NHS), n = 13; and (3) nonoperated body mass index–matched controls (CON), n = 7. Plasma glucose (PG) and hormonal responses (insulin, glucagon-like peptide-1, gastric inhibitory polypeptide, glucagon) were measured after a mixed meal test (MMT), and hypoglycemic symptoms were determined by a questionnaire. The primary outcomes were differences in subjective and biochemical responses related to hypoglycemia among the 3 groups.ResultsNadir PG was lower (3.1 versus 4.0 mmol/L (56 versus 72 mg/dL); P = .0002) and peak insulin higher in HS than NHS patients (1073 versus 734 pmol/L; P = .0499). Of the 13 patients with a peak insulin >850 pmol/L, 8 patients developed symptoms whereas only 2 out of the 13 patients with peak insulin ≤850 pmol/L developed symptoms, corresponding to an odds ratio of 12 (1.8; 81.7). Post hoc analyses comparing all RYGB patients with biochemical hypoglycemia after the MMT (nadir glucose ≤3.0 mmol/L [54 mg/dL]) with those with glucose >3 mmol/L (54 mg/dL) revealed a difference in both peak insulin (1138 versus 760 pmol/L; P = .042) and peak glucagon-like peptide-1 (182 versus 86 pmol/L; P = .016) concentrations.ConclusionsPatients with HS had lower nadir PG and higher insulin responses than NHS patients after MMT. Regarding PG, PG ≤3.0 mmol/L (54 mg/dL) was the best discriminator of having hypoglycemic symptoms after the MMT. However, high insulin level seems the most important predictor for having both biochemical and symptomatic hypoglycemia.     

Dexamethasone and perioperative blood glucose in patients undergoing total joint arthroplasty: A retrospective study

Study objectivePerioperative dexamethasone is commonly used to prevent nausea. It can also increase blood glucose levels, and recent concern about its blood glucose-elevating effect in humans has been raised. This study aimed to demonstrate relationships between dexamethasone administration and elevated perioperative blood glucose in patients undergoing total joint arthroplasty.DesignRetrospective study.SettingAcademic, orthopedic hospital.PatientsA total of 625 patients (18–99 years) who underwent total hip or total knee arthroplasty with an ASA ≤ 3 were included in the study.InterventionsPatients who received dexamethasone perioperatively were compared to those who did not receive dexamethasone.MeasurementsThe primary outcome, which was any postoperative glucose > 200 mg/dl, was compared between groups using multiple logistic regression. Demographic information, intraoperative information, incidence of postoperative nausea and vomiting, white blood cell count, medication use, and length of stay were also collected.Main resultsPerioperative dexamethasone (median [1st quartile, 3rd quartile] dose = 4 [4, 8] mg) was administered to 76% of patients. Only 5.6% (95% CI: 3.8–7.5) of patients had postoperative glucose levels > 200 mg/dl. After covariate adjustment, there was no evidence of a difference in odds of experiencing postoperative glucose levels > 200 mg/dl (odds ratio [95% CI]: 0.76 [0.28–2.07]; P = 0.594) and maximum glucose levels (P = 0.518) between groups. Dexamethasone-treated patients had greater changes in white blood cell count between baseline and postoperative days 0–1. There was no evidence of a difference in wound healing and length of stay between groups.ConclusionsThere was no evidence of an association between perioperative dexamethasone administration and the odds of having postoperative glucose levels > 200 mg/dl or higher maximum glucose levels. However, these findings may not be generalizable to patients having different baseline characteristics or procedures.     

The effect of selective gut stimulation on glucose metabolism after gastric bypass in the Zucker diabetic fatty rat model

BackgroundPotential mechanisms underlying the antidiabetic effects of Roux-en-Y gastric bypass (RYGB) include altered nutrient exposure in the gut. The aim of this study was to evaluate the effects of selective gut stimulation on glucose metabolism in an obese diabetic rat model.MethodsSixteen male Zucker diabetic fatty rats were randomly assigned to 1 of 2 groups: RYGB with gastrostomy tube (GT) insertion into the excluded stomach or a control group with GT insertion into the stomach. An insulin tolerance test (ITT), oral glucose tolerance test (OGTT), and mixed meal tolerance test (MMTT) were performed before and 14–28 days after surgery. A glucose tolerance test via GT (GTT-GT) and MMTT via GT were performed postoperatively.ResultsPostoperatively, the RYGB group had significant decreases in weight and food intake. Both the ITT and OGTT tests revealed significantly improved glucose tolerance after RYGB. The GTT-GT showed a reversal of the improved glucose tolerance in the RYGB group. In response to meal stimulation, postoperatively, the RYGB group increased glucagon-like peptide 1 (GLP-1) secretion via the oral route and peptide YY secretion by both oral and GT routes.ConclusionWhen foregut exposure to nutrients was reversed after RYGB, the improvement in glucose metabolism was abrogated. This model can be extended to identify the role of gut in glucose homeostasis in type 2 diabetes.     

Novel homozygous inactivating mutation of the calcium-sensing receptor gene (CASR) in neonatal severe hyperparathyroidism—lack of effect of cinacalcet

BackgroundNSHPT is a life-threatening disorder caused by homozygous inactivating calcium-sensing receptor (CASR) mutations. In some cases, the CaSR allosteric activator, cinacalcet, may reduce serum PTH and calcium levels, but surgery is the treatment of choice.ObjectiveTo describe a case of NSHPT unresponsive to cinacalcet.Patient and ResultsA 23-day-old girl was admitted with hypercalcemia, hypotonia, bell-shaped chest and respiratory distress. The parents were first-degree cousins once removed. Serum Ca was 4.75 mmol/l (N: 2.10–2.62), P: 0.83 mmol/l (1.55–2.64), PTH: 1096 pg/ml (9–52) and urinary Ca/Cr ratio: 0.5 mg/mg. First, calcitonin was given (10 IU/kg × 4/day), and then 2 days later, pamidronate (0.5 mg/kg) for 2 days. Doses of cinacalcet were given daily from day 28 of life starting at 30 mg/m² and increasing to 90 mg/m² on day 43. On day 33, 6 days after pamidronate, serum Ca levels had fallen to 2.5 mmol/l but, thereafter, rose to 5 mmol/l despite the cinacalcet. Total parathyroidectomy was performed at day 45. Hungry bone disease after surgery required daily Ca replacement and calcitriol for 18 days. At 3 months, the girl was mildly hypercalcemic, with no supplementation, and at 6 months, she developed hypocalcemia and has since been maintained on Ca and calcitriol. By CASR mutation analysis, the infant was homozygous and both parents heterozygous for a deletion–frameshift mutation.ConclusionThe predicted nonfunctional CaSR is consistent with lack of response to cinacalcet, but total parathyroidectomy was successful. An empiric trial of the drug and/or prompt mutation testing should help minimize the period of unnecessary pharmacotherapy.     

Exaggerated glucagon-like peptide-1 and blunted glucose-dependent insulinotropic peptide secretion are associated with Roux-en-Y gastric bypass but not adjustable gastric banding

BACKGROUND: The aim of this study was to measure the circulating levels of glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and glucagon in patients who had undergone adjustable gastric banding (BND) or Roux-en-Y gastric bypass (RYGB) to understand the differences in glucose and insulin regulation after these procedures. METHODS: This was a cross-sectional study of 3 groups of women matched for age and body mass index: group 1, overweight controls (n = 13); group 2, BND (n = 10); and group 3, RYGB (n = 13). Venous blood was drawn with the patient in the fasted state and throughout a 3-hour period after a liquid meal. RESULTS: The fasting glucose level was similar between the 2 surgery groups; however, the fasting insulin concentrations were greater in the BND (10.0 microU/mL) than in the RYGB (6.2 microU/mL; P <0.05) group. The glucose level at 60 minutes was significantly lower in the RYGB group (70 mg/dL, range 38-82) than in the BND group (83 mg/dL, range 63-98). The GLP-1 levels at 30 minutes were more than threefold greater in the RYGB group (96 pmol/L) compared with the BND and overweight control (28 pmol/L) groups. The GLP-1 and insulin concentrations correlated at 30 minutes only in the RYGB group (r = .66; P = .013). The glucose-dependent insulinotropic peptide levels at 30 minutes were lower in the RYGB group (20 pmol/L) than in the BND group (31 pmol/L) or overweight control group (33 pmol/L). The peak glucagon levels were similar among the 3 groups. CONCLUSION: Exaggerated postprandial GLP-1 and blunted glucose-dependent insulinotropic peptide secretion after RYGB might contribute to the greater weight loss and improved glucose homeostasis compared with BND.     

GLP-1 and Adiponectin: Effect of Weight Loss After Dietary Restriction and Gastric Bypass in Morbidly Obese Patients with Normal and Abnormal Glucose Metabolism

Background  It has been proposed that there is improvement in glucose and insulin metabolism after weight loss in patients who underwent diet restriction and bariatric surgery. Methods  Eleven normal glucose tolerant (NGT) morbidly obese patients [body mass index (BMI), 46.1 ± 2.27 g/m²] and eight abnormal glucose metabolism (AGM) obese patients (BMI, 51.20 kg/m²) were submitted to diet-restriction and bariatric surgery. Prospective study on weight loss changes, over the glucose, insulin metabolism, glucagon-like peptide-1 (GLP-1), and adiponectin levels were evaluated by oral glucose tolerance test during three periods: T1 (first evaluation), T2 (pre-surgery), and T3 (9 months after surgery). Results  Insulin levels improved after surgery. T1 was 131.1 ± 17.60 pmol/l in the NGT group and 197.57 ± 57.94 pmol/l in the AGM group, and T3 was 72.48 ± 3.67 pmol/l in the NGT group and 61.2 ± 9.33 pmol/l in the AGM group. The major reduction was at the first hour of the glucose load as well as fasting levels. At 9 months after surgery (T3), GLP-1 levels at 30 and 60 min had significantly increased in both groups. It was observed that the AGM group had higher levels of GLP-1 at 30 min (34.06 ± 6.18 pmol/l) when compared to the NGT group (22.69 ± 4.04 pmol/l). Homeostasis model assessment of insulin resistance from the NGT and AGM groups had a significant reduction at periods T3 in relation to T1 and T2. Adiponectin levels had increased concentration in both groups before and after surgical weight loss. However, it did not have any statistical difference between periods T1 vs. T2. Conclusions  Weight loss by surgery leads to improvement in the metabolism of carbohydrates in relation to sensitivity to the insulin, contributing to the reduction of type 2 diabetes incidence. This improvement also was expressed by the improvement of the levels of adiponectin and GLP-1.     

Early assessment of glucose abnormalities during continuous glucose monitoring associated with lung function impairment in cystic fibrosis patients

BackgroundCystic fibrosis-related diabetes (CFRD) is correlated with a decline in lung function. Under certain circumstances, oral glucose tolerance test (OGTT) screening, used to diagnose CFRD, fails to reveal early glucose tolerance abnormalities. In this situation, continuous glucose monitoring (CGM) could be a useful tool for evaluating early abnormalities of glucose tolerance in CF patients. We aimed to study the CGM glucose profile in CF patients with normal OGTT screening results and to evaluate lung function and nutritional status according to the CGM glucose profile.MethodsWe assessed glycemic control, the CGM glucose profile, nutritional status, lung function antibiotic courses and colonization (P. aeruginosa and S. aureus) in CF patients, aged 10 years and over, with normal screening OGTT results (blood glucose at T120 min < 7.8 mmol/l). Two groups were identified according to the max CGM glucose value: Group 1 < 11 mmol/l and Group 2 ≥ 11 mmol/l.ResultsAmong the 38 patients with normal OGTT, 12 (31.6%) were in Group 2. Compared to Group 1, Group 2 patients exhibited a significant impairment in lung function: FEV₁, 68.2 ± 25.6% vs. 87.3 ± 17%, p = 0.01 and FVC, 86.1% ± 19.4% vs. 99.3% ± 13.4%, p = 0.021, as well as a higher rate of colonization by P. aeruginosa: 83.3% vs. 44%, p = 0.024. Nevertheless, there were no differences in nutritional status (BMI standard deviation score: p = 0.079; prealbumin: p = 0.364).ConclusionsCGM reveals early abnormalities of glucose tolerance that remain undiagnosed by OGTT screening and are associated with worse lung function and a higher prevalence of P. aeruginosa colonization in patients with CF.Clinical trial registration number: NCT00476281.     

Predictors for future cystic fibrosis-related diabetes by oral glucose tolerance test

BackgroundAn annual oral glucose tolerance test (OGTT) has become part of standard care in cystic fibrosis (CF) to screen for CF-related diabetes (CFRD). The objective of this study was to determine predictors for future CFRD derived from an OGTT.MethodsData were collected from 2001 to 2009 during a longitudinal prospective study on “Early Diagnosis of Diabetes Mellitus in CF Patients, trial number NCT00662714”. The 1093 patients included in the analysis had at least two valid OGTTs each and no CFRD at the first glucose challenge. Normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and CFRD were defined using WHO criteria. In a subsample of 521 patients, the NGT group was further divided into patients with a 1-hour glucose level > 11.1 mmol/l (indeterminate glucose tolerance — INDET) and those with a lower level (no-INDET). Logistic regression analysis was used to identify predictors from the first OGTT for future diabetes.ResultsCompared with NGT (n = 838), IFG (n = 70; odds ratio [OR], 95% confidence interval: 2.92, 1.60–5.33) and IGT without IFG (n = 155, OR 2.37, 1.48–3.79) were both significant and independent risk factors for future CFRD. Patients with IGT and IFG (n = 30) had the highest risk (OR 5.30, 2.32–12.10). In the subsample analysis, INDET (n = 116) was associated with a significantly increased risk for future CFRD compared with no-INDET (n = 269; OR 2.81, 1.43–5.51).ConclusionsIn this large study, IFT, IGT, and INDET were all predictors of future CFRD. The OGTT in patients with CF should include a 1-hour post-challenge value.     

Sugammadex efficacy for reversal of rocuronium- and vecuronium-induced neuromuscular blockade: A pooled analysis of 26 studies

Study objectiveTo summarize and compare efficacy of sugammadex with neostigmine or placebo for reversal of rocuronium- or vecuronium-induced neuromuscular blockade (NMB), and to demonstrate consistency of sugammadex results across various patient populations.DesignPooled analysis on data from 26 multicenter, randomized, Phase II and III studies.SettingOperating room.Patients1855 adults undergoing surgery under general anesthesia and receiving rocuronium or vecuronium for NMB.InterventionsSugammadex (2.0 mg/kg at second twitch reappearance [T₂; moderate NMB], 4.0 mg/kg at 1–2 post-tetanic counts [PTC; deep NMB] or 16.0 mg/kg at 3 min after rocuronium 1.2 mg/kg), neostigmine or placebo.MeasurementsTime to recovery of the train-of-four (TOF) ratio to 0.9.Main resultsGeometric mean (95% CI) times to recovery to TOF ratio of 0.9 were 1.9 (1.8–2.0) min following sugammadex 2.0 mg/kg and 10.6 (9.8–11.6) min following neostigmine administration at T₂ after rocuronium, and 2.9 (2.5–3.4) min and 17.4 (13.4–22.6) min, respectively, after vecuronium. Recovery times were 2.2 (2.1–2.3) min following sugammadex 4.0 mg/kg and 19.0 (14.8–24.6) min following neostigmine administered at a target of 1–2 PTC after rocuronium, and 3.8 (3.0–5.0) min and 67.6 (56.3–81.2) min after vecuronium. Sugammadex administered 3 min after rocuronium 1.2 mg/kg resulted in rapid recovery (1.7 [1.5–2.0] min). Modest increases in mean recovery time were associated with vecuronium use (+ 1.6 min [78%; (61%–98%)] versus rocuronium), mild-to-moderate renal impairment (+ 0.4 min [20%; (9%–32%)] versus normal renal function) and geographic location (+ 1.0 min [38%; (25%–52%)] in subjects in USA/Canada versus Europe/Japan).ConclusionsSugammadex administered at recommended doses provides rapid and predictable reversal of rocuronium and vecuronium-induced moderate and deep NMB, and effective reversal 3 min after rocuronium 1.2 mg/kg. Robust recovery was seen across various patient factors, providing further confirmation of labeled dose recommendations.     

Evaluation of salt supplementation in CF infants

BackgroundCF infants may be at increased risk of sodium depletion which may lead to impaired growth. The objective of this study was to evaluate their sodium supplementation requirements.MethodsTen CF infants had serial measurements of weight and plasma/urine sodium and creatinine. Sodium supplementation was adjusted with the aim of maintaining fractional excretion (FENa) between 0.5% and 1.5% and urinary sodium > 10 mmol/L.ResultsUrine sodium:creatinine (UNa:Cr) ratio strongly correlated with FENa [UNa:Cr (mmol/mmol) = 35.0 × FENa (r = 0.99)]. The FENa target range corresponded to UNa:Cr 17–52 mmol/mmol. All infants required sodium supplementation to achieve UNa:Cr >17 mmol/mmol. Sodium supplement requirements (mean ± SD) at ages 0–3, 3–6, 6–9 and 9–12 months were 1.9 ± 0.5, 1.8 ± 0.8, 1.9 ± 0.9 and 0.8 ± 0.4 mmol/kg/d. No infant required calorie supplementation to achieve expected weight gain.ConclusionsUsing current UK guidelines, many cases of sodium depletion may be overlooked. Some infants require more than the recommended 1–2 mmol/kg/d. UNa:Cr ratio is a useful non-invasive measure to monitor sodium supplementation.     

The relation between postprandial glucagon-like peptide-1 release and insulin sensitivity before and after bariatric surgery in humans with class II/III obesity

BackgroundGlucagon-like peptide-1 (GLP-1) receptor agonist treatment is beneficial for the human glucose metabolism, and GLP-1 secretion is greatly enhanced following Roux-en-Y gastric bypass (RYGB).ObjectivesTo elucidate the relationship between GLP-1 concentrations and insulin sensitivity in subjects with class II/III obesity without diabetes and to assess the relation between GLP-1 and the improvements in glucose metabolism following RYGB.SettingClinical research facility in a university hospital.MethodsWe recruited 35 patients scheduled for RYGB and assessed their plasma GLP-1, insulin, and glucose responses to a high-fat mixed meal. Basal and insulin-mediated glucose fluxes were determined during a 2-step hyperinsulinemic-euglycemic clamp with stable isotope-labeled tracers. Out of 35 subjects, 10 were studied both before surgery and at 1 year of follow-up.ResultsPlasma GLP-1 increased following the high-fat mixed meal. Postprandial GLP-1 excursions correlated positively with hepatic and peripheral insulin sensitivity, but not with body mass index. At 1 year after RYGB, participants had lost 24% ± 6% of their body weight. Plasma GLP-1, insulin, and glucose levels peaked earlier and higher after the mixed meal. The positive association between the postprandial GLP-1 response and peripheral insulin sensitivity persisted.ConclusionsPostprandial GLP-1 concentrations correlate with insulin sensitivity in subjects with class II/III obesity without diabetes before and 1 year after RYGB. Increased GLP-1 signaling in postbariatric patients may, directly or indirectly, contribute to the observed improvements in insulin sensitivity and metabolic health.     

Water-clear cell adenoma: A rare form of hyperparathyroidism

INTRODUCTIONPrimary hyperparathyroidism is a common endocrine disorder, with an incidence of 21.6 per 100,000 person-years. Asymptomatic elevated serum calcium levels on routine biochemical investigations accounts for 80% of newly diagnosed primary hyperparathyroidism. Solitary adenoma is the commonest cause of primary hyperparathyroidism and can be treated by excision of a single gland.PRESENTATION OF CASEWe present a case of primary hyperparathyroidism in a 74-year-old female was referred to our surgery endocrine outpatients for assessment of a persistently elevated calcium level, lower abdominal pain and constipation. Biochemical analysis revealed corrected serum calcium of 3.13 mmol/L (reference range 2.17–2.51 mmol/L) and an intact parathyroid hormone level (iPTH) of 488.9 ng/L (reference range 15–65 ng/L). Sestamibi scan localised a persistent increased area of activity inferior to the lower pole of the left lobe of thyroid gland.DISCUSSIONThe patient underwent a minimally invasive parathyroidectomy using a 3 cm incision with intra-op radionucliotide localisation. At surgery a single large parathyroid gland measuring 5.5 cm was excised without complication. Grossly the parathyroid gland was an encapsulated tan mass measuring 5.5 cm × 2.5 cm × 2 cm and weight 13 g and histological assessment revealed a water-clear cell (WCC) adenoma. She made an uneventful post op recovery with normalisation of her serum calcium.CONCLUSIONWCC adenomas have a “low endocrinological activity” in which serum calcium levels do not elevate until the adenoma has reached considerable size. Our case supports this hypothesis and aids to the understanding of these rare tumours.     

Serum tobramycin levels following delivery of tobramycin (Tobi®) via eFlow® advanced nebuliser in children with cystic fibrosis

BackgroundSafety and toxicity data for nebulised tobramycin are mainly derived from use of the Pari LC® Plus nebuliser, yet many centres are now using advanced nebulisers, such as the eFlow®.MethodsTen children (ages 2–16 years) receiving 300 mg TOBI® via eFlow® for clinical reasons participated. Serum tobramycin levels were obtained 1 h post nebulisation. Nine provided samples for urinary NAG, and 10 underwent audiology.ResultsTobramycin levels were > 1 mg/L in 3 children (maximum 3.8, 2 children aged 2 years). Urine NAG/creatinine levels were raised (> 0.94 μmol/min/mmol) in 5 children, 1 of these had a tobramycin level of > 1 mg/L. One patient had high frequency hearing loss.ConclusionSerum tobramycin levels over 1 mg/L can occur 1 h post 300 mg TOBI® delivered by eFlow®. Raised urinary NAG levels suggest that some children may have some associated early renal toxicity.     

Different osteocalcin forms,markers of metabolic syndrome and anthropometric measures in children within the IDEFICS cohort

ObjectiveOsteocalcin (OC), an aboundant non-collagenous bone protein, is inversely associated with parameters of glucose metabolism. Interactions between bone tissue and energy metabolism have not been thoroughly investigated during childhood. This study investigated OC, metabolic parameters and anthropometric characteristics in normal weight and overweight/obese children.MethodsThis study comprised 108 (46 normal weight/62 overweight/obese) Swedish 2–9 year old children. Anthropometric data, insulin, glucose, glycosylated haemoglobin (HbA1c), HOMA index, vitamin D, adiponectin, total OC, carboxylated OC (cOC) and undercarboxylated OC (ucOC) were analysed.ResultsNo difference was found for total OC between the normal and overweight/obese groups, with a mean (± SD) value of 82.6 (± 2.8) ng/mL and 77.0 (± 2.4) ng/mL, (P = 0.11), respectively. Overweight children had lower cOC levels, mean 69.1 (± 2.2) ng/mL, vs. normal weight children, mean 75.6 (± 2.5) ng/mL (P = 0.03). The mean ucOC levels of 7.9 (± 0.4) ng/mL in overweight children did not differ vs. normal weight children, mean level 7.0 (± 0.4) ng/mL, (P = 0.067). None of the three OC forms correlated with any of the measured parameters.ConclusionsThe cOC levels were lower in overweight children. There was no correlation between the three OC forms and any of the measured anthropometric or metabolic parameters. OC has been suggested to have a possible metabolic role, but in general the current study in prepubertal children does not support the hypothesis of an association between OC and a positive metabolic profile.     

Association between bone stiffness and nutritional biomarkers combined with weight-bearing exercise,physical activity,and sedentary time in preadolescent children. A case–control study

Physical activity (PA) and micronutrients such as calcium (Ca), vitamin D (25OHD), and phosphate (PO) are important determinants of skeletal development. This case–control study examined the association of these nutritional biomarkers and different PA behaviours, such as habitual PA, weight-bearing exercise (WBE) and sedentary time (SED) with bone stiffness (SI) in 1819 2–9-year-old children from the IDEFICS study (2007–2008). SI was measured on the calcaneus using quantitative ultrasound. Serum and urine Ca and PO and serum 25OHD were determined. Children's sports activities were reported by parents using a standardised questionnaire. A subsample of 1089 children had accelerometer-based PA data (counts per minute, cpm). Moderate-to-vigorous PA (MVPA) and SED were estimated. Children with poor SI (below the 15th age-/sex-/height-specific percentile) were defined as cases (N = 603). Randomly selected controls (N = 1216) were matched by age, sex, and country. Odds ratios (OR) for poor SI were calculated by conditional logistic regression for all biomarkers and PA behaviour variables separately and combined (expressed as tertiles and dichotomised variables, respectively). ORs were adjusted for fat-free mass, dairy product consumption, and daylight duration. We observed increased ORs for no sports (OR = 1.39, p < 0.05), PA levels below 524 cpm (OR = 1.85, p < 0.05) and MVPA below 4.2% a day (OR = 1.69, p < 0.05) compared to WBE, high PA levels (< 688 cpm) and high MVPA (6.7%), respectively. SED was not associated with SI. ORs were moderately elevated for low serum Ca and 25OHD. However, biomarkers were not statistically significantly associated with SI and did not modify the association between PA behaviours and SI. Although nutritional biomarkers appear to play a minor role compared to the osteogenic effect of PA and WBE, it is noteworthy that the highest risk for poor SI was observed for no sports or low MVPA combined with lower serum Ca (< 2.5 mmol/l) or lower 25OHD (< 43.0 nmol/l).     

An observational study of plasma vascular endothelial growth factors (VEGF) A and D expression in non-localized prostate cancer

BackgroundThe aim of the study was to measure plasma levels of the vascular endothelial growth factors (VEGF) A and D in serially collected blood specimens from non-localized prostate cancer (PCa) subjects.MethodsPlasma VEGF A and D levels were measured in two serial specimens 3–6 months apart in two groups of non-localized stage PCa patients. Group 1 was comprised of patients with biochemical relapse after localized PCa treatments and/or patients with clinically metastatic hormone-sensitive stage PCa prior to receiving hormonal therapy. Group 2 included patients failing hormonal therapy for non-localized hormone-sensitive stage PCa. VEGF A and D levels were compared within each cancer group between the two time-points using the Wilcoxon Rank Sum test.ResultsAt the first time-point in Group 1 (n = 46), median VEGF-A and D levels were measured at 5.2 (pg/ml) (range = 0–97) and 319 (range = 172–780) (pg/ml). For Group 2 (n = 34) VEGF-A level was 9.6 pg/ml (range = 0–78) and VEGF-D level was 377 pg/ml (range = 243–989) for the first measurement. Median time-period for the serial second specimen was 189 days in Group 1 and 84 days in Group 2. At the second time-point, in Group 1, VEGF-A levels were 0.0 pg/ml (P = 0.0002) while VEGF-D increased to 349 pg/ml (P = 0.002). For Group 2 patients at the second time-point, median VEGF-A was 0.0 pg/ml (P = 1.0) and VEGF-D was measured at 442 pg/ml (P = 0.008).ConclusionsHigher plasma VEGF-D than VEGF-A expression in advanced PCa stages suggests a greater role for VEGF-D dependent lymph angiogenesis in advanced stage PCa, which needs further evaluation.     

Circulating magnesium status is associated with type 2 diabetes remission after Roux-en-Y gastric bypass surgery: a long-term cohort study

BackgroundLow serum magnesium levels predict cardiovascular and all-cause mortality in patients with typ 2 diabetes.SettingOutpatient clinic of obesity and central hospital.ObjectivesTo assess long-term alterations in circulating magnesium status after Roux-en-Y gastric bypass (RYGB) surgery and associations with remission of type 2 diabetes (T2D).MethodsRetrospective analysis of 5-year outcomes of plasma magnesium (p-Mg) and glucometabolic statuses in patients who underwent primary RYGB and who completed the annual follow-up program. Data were investigated from 84 patients without diabetes and 62 with T2D before RYGB, who showed either prolonged remission (n = 30), temporary remission (n = 16), or no remission (n = 16) after surgery.ResultsBody mass indexes before RYGB were similar in patients with and without T2D, irrespective of remission. The patients not achieving remission showed longer diabetes durations; higher circulating glucose levels; more intensive antidiabetic drug treatment, including insulin; and significantly lower p-Mg concentrations (.73 [±.08] mmol/L compared with .80–.82 [±.07] mmol/L, respectively; P < .01) than the groups showing remission or without diabetes before surgery. After RYGB, the p-Mg increased similarly, by 10–12% in the groups with T2D before surgery, irrespective of remission; however, the nonremission group did not reach the p-Mg levels registered in the other groups after follow-up. The nonremission group reached .82 (.09) mmol/L, compared with .87 (.06) and .88 (.08) mmol/L (P < .05), respectively, in patients with remission or without a history of diabetes.ConclusionThe p-Mg concentrations increased after RYGB, with similar increments irrespective of T2D remission; however, the nonremission group started from an inferior level and did not reach the p-Mg concentrations seen in the groups achieving remission or without a history of diabetes before surgery.