Cardiovascular autonomic neuropathy as a cause of fatigue in chronic hypoparathyroidism.

PURPOSE: Hypoparathyroidism (hypoPT) results in an impairment of quality of life (QoL), an increase in fatigue and a higher risk of mortality. Cardiovascular autonomic neuropathy (CAN) is an impairment of the cardiovascular autonomic system and is associated with increased mortality and fatigability. Patients with hypoPT show an increased risk of CAN. However, no previous studies have investigated the association between CAN and QoL in hypoPT. To test whether CAN is associated with fatigue and impaired QOL in hypoPT patients. METHODS: We enrolled 48 subjects with postsurgical hypoPT treated with calcium and calcitriol and 38 healthy subjects who underwent thyroidectomy. Subjects completed the RAND 36-Item Short Form (SF-36) Health Survey, evaluating physical (PCS) and mental (MCS) health, and fatigue score. CAN was assessed using cardiovascular autonomic reflex tests (CARTs). Participants were considered to have "early CAN" (EC) if they had one abnormal CART and "definite CAN" (DC) with two or more abnormal CARTs. RESULTS: Compared with controls, hypoPT population had lower fatigue scores (44.5 IQRː9 vs 38.5 IQRː12.3, P = 0.031). In the hypoPT group, only participants with DC had a lower fatigue score than subjects without CAN (DC: ß: -9.55, P = 0.005) after adjusting for age, duration of disease, calcium concentration, TSH, calcitriol and calcium supplementation. No differences were found in the PCS and MCS scores in the hypoPT group. CONCLUSIONS: CAN may explain fatigue, a common complaint of postsurgical hypoPT patients. Further larger and prospective investigations are needed to confirm our findings.

PTH(1-34) for Surgical Hypoparathyroidism: A 2-Year Prospective, Open-Label Investigation of Efficacy and Quality of Life.

Context: Daily parathyroid hormone (PTH) (1-34) administrations can reduce the required total daily dose of calcium and calcitriol and restore normocalcemia in refractory hypoparathyroidism. However, most PTH(1-34) trials have been conducted on small cohorts including subjects with hypoparathyroidism of various etiologies, and quality of life (QOL) was not investigated. Objective: To investigate the effects of 24-month PTH(1-34) treatment in a homogeneous cohort of adult subjects with postoperative hypoparathyroidism and to evaluate QOL changes. Design: Prospective open-label study. Setting: Italian multicenter study. Participants: 42 subjects. Intervention: Twice-daily PTH(1-34) 20 µg subcutaneous injection. Main Outcome Measures: Calcium and vitamin D supplementation requirements, serum calcium, phosphate, and urinary calcium excretion (3, 6, 12, 18, 24 months). At baseline and at 6 and 24 months, QOL was evaluated by the RAND 36-Item Short Form (SF-36) Health Survey, covering eight domains of physical and mental health. Results: Mean serum calcium concentration significantly increased from baseline to 3 months (7.6 ± 0.6 vs 8.9 ± 1.1 mg/dL, P < 0.001) and remained stable until the end of the study, despite reductions in calcium and vitamin D supplementation. Phosphate levels gradually decreased from baseline to 6 months (4.3 ± 1.1 vs 3.9 ± 0.6 mg/dL, P < 0.019), remaining stable until 24 months. Serum alkaline phosphatase and calcium excretion gradually increased from baseline to 24 months. Data from SF-36 showed a significant improvement in the mean scores of all eight domains (P < 0.001). Conclusion: This study demonstrates the efficacy and safety of PTH(1-34) to treat adult patients with postsurgical hypoparathyroidism. PTH(1-34) may improve their mental and physical health.

Vitamin K and osteoporosis: Myth or reality?

Vitamin K is a liposoluble vitamin. The predominant dietary form, phylloquinone or vitamin K1, is found in plants and green vegetables; whereas menaquinone, or vitamin K2, is endogenously synthesized by intestinal bacteria and includes several subtypes that differ in side chain length. Aside from its established role in blood clotting, several studies now support a critical function of vitamin K in improving bone health. Vitamin K is in fact required for osteocalcin carboxylation that in turn regulates bone mineral accretion; it seems to promote the transition of osteoblasts to osteocytes and also limits the process of osteoclastogenesis. Several observational and interventional studies have examined the relationship between vitamin K and bone metabolism, but findings are conflicting and unclear. This systematic review aims to investigate the impact of vitamin K (plasma levels, dietary intake, and oral supplementation) on bone health with a particular interest in bone remodeling, mineral density and fragility fractures.

A pilot study of D-chiro-inositol plus folic acid in overweight patients with type 1 diabetes.

AIMS: To improve insulin sensitivity, insulin-sensitizing drugs such as metformin are commonly used in overweight and obese T1D patients. Similarly to metformin, D-chiro-inositol (DCI), as putative mediator of intracellular insulin action, can act as insulin sensitizer. The aim of this pilot study was to evaluate the hypothesis that DCI plus folic acid may improve glucose control reducing insulin resistance in overweight or obese T1D patients. METHODS: A 24-week randomized control trial was carried out in 26 overweight or obese T1D patients, undergoing intensive insulin therapy. Patients were randomized to 1 g DCI plus 400 mcg folic acid once daily (treated group) or to 400 mcg folic acid only once daily (control group). The primary end point was to evaluate the efficacy of DCI on metabolic control as assessed by HbA1c. As secondary endpoints, BMI and insulin requirement (IR) were evaluated. Paired t test (two tailed) and analysis of variance were used to evaluate differences in HbA1c, BMI and IR at different time points. RESULTS: A significant reduction in HbA1c levels in treated group versus control group (7.5% ± 0.9 vs. 7.9% ± 1.7, respectively, p < 0.05) was observed. However, no significant reduction in BMI and IR was observed [(BMI 25.7 ± 2.8 vs. 26.7 ± 1.0, respectively, p NS); (IR 0.52 ± 0.26 vs. 0.52 ± 0.19, respectively, p NS)]. CONCLUSIONS: This trial demonstrated for the first time that DCI plus folic acid oral supplementation can improve metabolic control in overweight T1D patients. CLINICALTRIAL. GOV ID: NCT02730949.

PTH(1-34) for the Primary Prevention of Postthyroidectomy Hypocalcemia: The THYPOS Trial.

CONTEXT: There are no studies evaluating teriparatide for prevention of post-thyroidectomy hypocalcemia. OBJECTIVE: Our objective was to evaluate whether teriparatide can prevent postsurgical hypocalcemia and shorten the hospitalization in subjects at high risk of hypocalcemia following thyroid surgery. DESIGN: This was a prospective phase II randomized open-label trial. SETTING: This trial was set on a surgical ward. PATIENTS: Twenty-six subjects (six males, 20 females) with intact PTH lower than10 pg/ml 4 hours after thyroidectomy were included. INTERVENTION: Subjects were randomized (1:1) to receive SC administration of 20 mcg of teriparatide every 12 hours until the discharge (treatment group) or to follow standard clinical care (control group). MAIN OUTCOME MEASURE: Adjusted serum calcium, duration of hospitalization, and calcium/calcitriol supplementation were measured. RESULTS: Overall, the incidence of hypocalcemia was 3/13 in treatment group and 11/13 in the control group (P = .006). Treated patients had a lower risk of hypocalcemia than controls (relative risk, 0.26 [95% confidence interval, 0.09-0.723)]). The median duration of hospitalization was 3 days (interquartile range, 1) in control subjects and 2 days (interquartile range, 0) in treated subjects (P = .012). One month after discharge, 10/13 subjects in the treatment group had stopped calcium carbonate supplements, while only 5/13 in the control group had discontinued calcium. The ANOVA for repeated measures showed a significant difference in calcium supplements between groups at 1-month visit (P = .04) as well as a significant difference between discharge and 1-month visit in the treatment group (P for interaction time group = .04) Conclusions: Teriparatide may prevent postsurgical hypocalcemia, shorten the duration of hospitalization, and reduce the need for calcium and vitamin D supplementation after discharge in high risk subjects after thyroid surgery.

Effect of calcitriol on bone turnover and osteocalcin in recent-onset type 1 diabetes.

BACKGROUND: Vitamin D supplementation in childhood improves the achievement of peak bone mass. We investigated the effect of supplementation with calcitriol on bone turnover in recent-onset type 1 diabetes (T1D). Moreover, the association between osteocalcin and parameters of ß-cell function and metabolic control was examined. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a post-hoc analysis of a double-blind, placebo-controlled study of calcitriol supplementation to preserve ß-cell function. 27 recent-onset T1D subjects, mean age 22 years, were randomized to 0.25 µg calcitriol per day or placebo (1:1) and followed up for one year. Changes in bone formation (osteoclacin) and resorption (beta-CrossLaps) markers, and differences between placebo and calcitriol-treated group were evaluated. At baseline, osteocalcin levels were significantly lower in female than in male patients (P<0.01) while no other metabolic parameters as HbA1c and C-peptide differed between gender. No significant correlations were found in relation to HbA1c, insulin requirement and C-peptide. At 1 year follow-up, no significant differences were observed between calcitriol and placebo groups for osteocalcin and ß-CrossLaps. In the placebo group osteocalcin levels were unrelated with parameters of metabolic control, such as C-peptide, insulin requirement or HbA1c. Changes of C-peptide, insulin requirement and HbA1c were not related to osteocalcin levels. CONCLUSIONS: Supplementation with 0.25 µg calcitriol per day to patients with new-onset T1D does not affect circulating markers of bone turnover. OC levels were unrelated to ß-cell function and other metabolic parameters suggesting that OC is ineffective to control pancreatic function in presence of aggressive autoimmune destruction.

No protective effect of calcitriol on beta-cell function in recent-onset type 1 diabetes: the IMDIAB XIII trial.

OBJECTIVE: We investigated whether supplementation of the active form of vitamin D (calcitriol) in recent-onset type 1 diabetes can protect beta-cell function evaluated by C-peptide and improve glycemic control assessed by A1C and insulin requirement. RESEARCH DESIGN AND METHODS: Thirty-four subjects (aged 11-35 years, median 18 years) with recent-onset type 1 diabetes and high basal C-peptide >0.25 nmol/l were randomized in a double-blind trial to 0.25 microg/day calcitriol or placebo and followed-up for 2 years. RESULTS: At 6, 12, and 24 months follow-up, A1C and insulin requirement in the calcitriol group did not differ from the placebo group. C-peptide dropped significantly (P < 0.001) but similarly in both groups, with no significant differences at each time point. CONCLUSIONS: At the doses used, calcitriol is ineffective in protecting beta-cell function in subjects (including children) with recent-onset type 1 diabetes and high C-peptide at diagnosis.