Frequency of COVID-19 Infection as a Function of Vitamin D Levels.

BACKGROUND: It has been speculated that higher concentrations of 25-hydroxy-vitamin D (25OHD) provide some protection against COVID-19. We assessed whether there is any relationship between 25OHD concentrations and the subsequent development of COVID-19 infection. MATERIALS AND METHODS: Concentrations of 25OHD were measured in March-April 2020 in 134 healthy subjects (57 males), age range 6-50, from a single urban general practice in central Poland. Data on COVID-19 infection during the subsequent 12 months (prior to the vaccination program) were obtained from the national database of COVID-19 cases. None of the subjects received any 25OHD supplements. RESULTS: The average 25OHD concentrations were 18.1 ± 7.39 ng/mL (37.3% had 25OHD above 20 ng/mL). Thirty-one (23.1%) patients developed COVID-19 infection, but an increased risk was only observed in individuals with 25OHD concentrations below 12 ng/mL (COVID-19 infection in 11 out of 25 patients (44%) with 25OHD < 12 ng/mL versus 20 out of 109 (18.3%) for those with 25OHD above 12 ng/mL, p = 0.0063). Such a relationship was no longer observed for subjects with 25OHD concentrations above 20 ng/mL (p = 0.2787). CONCLUSIONS: Although only a minority of healthy subjects had 25OHD concentrations above 20 ng/mL in spring, an increased risk of subsequent COVID-19 infection was only observed in those with severe 25OHD deficiency (<12 ng/mL).

The effects of season (spring versus autumn) on diagnosis of normocalcemic primary hyperparathyroidism.

Background: Raised parathormone (PTH) and normal calcium concentrations can be observed both in normocalcemic primary hyperparathyroidism (nPHPT) and in secondary hyperparathyroidism, e.g. due to vitamin D deficiency. We assessed the impact of season on the validity of diagnosis of nPHPT in terms of screening investigations to be performed in the primary care settings. Material and methods: On two occasions (March/April & September/October) we measured vitamin D (25OHD), PTH and total calcium in 125 healthy subjects, age range 6-50, not taking any vitamin D supplements. Results: In autumn there was an increase in 25OHD concentrations (from 18.1 ± 7.37ng/ml to 24.58 ± 7.72ng/ml, p<0.0001), a decline in PTH from 44.40 ± 17.76pg/ml to 36.63 ± 14.84pg/ml, p<0.001), without change in calcium levels. Only 45 subjects (36%) were vitamin D sufficient (25OHD>20/ml) in spring versus 83 (66.4%) in autumn, p<0.001. Elevated PTH concentrations were noted in 10 subjects in spring (8%) and in six subjects (4.8%) (p<0.05) in autumn. In spring, however, eight out of ten of these subjects (80%) had 25OHD<20 ng/ml, versus one in six (16.7%) in autumn (p<0.01). Normalization of PTH was observed in seven out ten subjects (70%), and all of them had 25-OHD<20 ng/ml in spring. Conclusions: In spring elevated PTH concentrations in the setting of normocalcemia are more likely to be caused by 25OHD deficiency rather by nPHPT. In contrast, in autumn, increased PTH concentrations are more likely to reflect nPHPT. We postulate that screening for nPHPT should be done in 25OHD replete subjects, i.e. in autumn rather than in spring.

Effect of Summer Sunshine Exposure on Vitamin D Status in Young and Middle Age Poles: Is 30 ng/mL Vitamin D Cut-Off Really Suitable for the Polish Population?

BACKGROUND: There is no consensus regarding vitamin sufficiency status with either 20 ng/mL or 30 ng/mL sufficiency cut-off. We assessed the effects of summer sunshine exposure on vitamin D status. PARTICIPANTS: We measured vitamin D concentrations, PTH, creatinine, and total calcium in 132 healthy subjects, age 29.36 ± 13.57 years, in spring and autumn. RESULTS: There was an overall increase in vitamin D concentrations from spring to autumn from 18.1 ± 7.39 ng/mL to 24.58 ± 7.72 ng/mL, (p < 0.001), accompanied by a decrease in PTH from 44.4 ± 17.76 pg/mL to 36.6 ± 14.84 pg/mL, (p < 0.001). In spring, only 5.3% of individuals were vitamin D sufficient for a 30 ng/mL cut-off, increasing to 23.2% in autumn (p < 0.001). In contrast, when a 20 ng/mL cut-off was employed, vitamin D sufficiency was found in 34.1% in spring and 66.4% individuals in autumn, respectively, (p < 0.001). In multiple regression analysis, holiday leave was the only significant determinant of vitamin D increase (p < 0.001). CONCLUSIONS: Holiday leave is the strongest determinant of an increase in vitamin D. The majority of healthy individuals fail to reach a 30 ng/mL vitamin D cut-off after summer sunshine exposure. This raises the question, whether such a cut-off is indeed suitable for the Polish population.

Adequate timing and constant supervision are the keys for successful implementation of levothyroxine or levothyroxine/paracetamol absorption test.

BACKGROUND: Levothyroxine (LT4) pseudomalabsorption due to medication non-adherence results in significant costs for Health Service. High dose LT4 or LT4/paracetamol absorption test is used in such cases. Hence, establishment of an optimal test protocol and timing of sample collection is of utmost importance. CASE PRESENTATION: A 34-year old woman was admitted to our Department because of severe hypothyroidism [on admission thyrotropin (TSH) > 100 µIU/ml, free thyroxine (FT4) 0.13 ng/dl (ref. range 0.93-1.7)] despite apparently taking 1000 µg of LT4 a day. Autoimmune hypothyroidism had been diagnosed 4 years before during post-partum thyroiditis. Subsequently, it was not possible to control her hypothyroidism despite several admissions to two University Hospitals and despite vehement denial of compliance problems. There was no evidence of coeliac disease or other malabsorption problems, though gluten-free and lactose-free diet was empirically instigated without success. A combined paracetamol (1000 mg)/LT4 (1000 µg) absorption test was performed in one of these Hospitals. This showed good paracetamol absorption (from < 2 µg/ml to 14.11 µg/ml at 120 min), with inadequate LT4 absorption (FT4 increase from 5.95 pmol/l to 9.92 pmol/l at 0 and 120 min respectively). About 2 years prior to admission to our Department the patient was treated with escalating doses of levothyroxine [up to 3000 µg of T4 and 40 µg of triiodothyronine (T3) daily] without significant impact on TSH (still > 75 µIU/ml, and FT4 still below reference range).After admission to our Department we performed a 2500 µg LT4 absorption test with controlled ingestion of crushed tablets, strict patient monitoring and sampling at 30 min intervals. We observed a quick and striking increase in FT4 from 0.13 to 0.46, 1.78, 3.05 and 3.81 ng/dl, at 0, 30, 60, 90 and 120 min, respectively. Her TSH concentration decreased to 13.77 µIU/ml within 4 days. When informed, that we had managed to "overcome" her absorption problems, she discharged herself against medical advice and declined psychiatric consultation. CONCLUSIONS: Adequate patient supervision and frequent sampling (e.g. every 30 min for 210 min) is the key for successful implementation of LT4 absorption test. Paracetamol coadministration appears superfluous in such cases.

Retinol-binding protein 4 (RBP-4) levels do not change after oral glucose tolerance test and after dexamethasone, but correlate with some indices of insulin resistance in humans.

INTRODUCTION: Secretory products from adipocytes may contribute to deterioration in glycaemic control and increased insulin resistance (IR). Retinol-binding protein 4 (RBP-4) may increase IR in mice, with elevated levels in insulin-resistant mice and humans with obesity and type 2 diabetes. However, the mechanisms regulating RBP-4 synthesis remain not fully understood. It is not clear whether short-term glucose-induced hyperglycaemia and hyperinsulinaemia as well as glucocorticosteroid-induced increase in IR might be reflected in alterations in serum RBP-4 levels in humans. In order to investigate this, we measured serum RBP-4, glucose and insulin concentrations during 75.0 gram oral glucose tolerance test (OGTT) - Study 1, as well as before and after oral administration of dexamethasone - Study 2. MATERIAL AND METHODS: Both studies included 35 subjects (8 males), age (mean +/- SD) 39.1 +/- 15.6 years, BMI 35.8 +/- 8.7 kg/m(2). Twenty-four of those subjects (5 males), age 38.7 +/- 15.1 years, BMI 34.4 +/- 8.3 kg/m(2), had 75 gram oral glucose tolerance test (OGTT) - Study 1. Blood samples were taken before (0 minutes), and at 60 and 120 minutes of OGTT. 17 subjects (3 males, 4 subjects with type 2 diabetes), age 43.1 +/- 18.1 years, BMI 36.7 +/- 9.0 kg/m(2) underwent screening for Cushing's disease/syndrome (Study 2). Dexamethasone was administered in a dose of 0.5 mg every 6 hours for 48 hours. Fasting serum concentrations of RBP-4, glucose and insulin were assessed before (D0) and after 48 hours of dexamethasone administration (D2). IR was assessed by HOMA in all non-diabetic subjects and in subjects participating in study 1 also by Insulin Resistance Index (IRI), which takes into account glucose and insulin levels during OGTT. RESULTS: Glucose administration resulted in significant increases in insulin and glucose (p < 0.0001). There was, however, no change in RBP-4 concentrations (124.1 +/- 32 mg/ml at 0 minutes, 123 +/- 35 mg/ml at 60 minutes and 126.5 +/- 37.5 mg/ml at 120 minutes of OGTT, p = ns). All subjects in Study 2 achieved suppression of cortisol below 50 nmo/l. Dexamethasone administration resulted in an increase in fasting insulin (from 11.6 +/- 6.8 to 17.1 +/- 7.2 muU/ml; p = 0.003), and an increase in HOMA (from 2.73 +/- 1.74 to 4.02 +/- 2.27; p = 0.015), although without a significant change in RBP-4 levels (119 +/- 26.8 vs. 117.5 +/- 24.8 mg/ml, p = ns). RBP-4 correlated with fasting insulin (r = 0.40, p = 0.025), fasting glucose (r = 0.41, p = 0.02) and HOMA (r = 0.43, p = 0.015), but not with IRI (r = 0.19, p = 0.31). There was, however, only a moderate correlation between HOMA and IRI (r = 0.49 [r(2) = 0.24]; p = 0.006, Spearman rank correlation), while the best correlation was obtained between the product of glucose and insulin levels at 60 min of OGTT and IRI in a non-linear model (r = 0.94 [r(2) = 0.88]; p<0.00001). In subjects who received dexamethasone, a positive correlation between RBP-4 and HOMA (p = 0.01) was lost after two days of dexamethasone administration (p = 0.61). CONCLUSIONS: RBP-4 levels do not change during oral glucose tolerance test or after a dexamethasone-induced increase in insulin resistance. This implies that it is highly unlikely that RBP-4 is involved in short-term regulation of glucose homeostasis in humans and that it responds to short-term changes in insulin resistance. A moderate correlation between RBP-4 and some insulin resistance indices (HOMA) does not exclude the fact that RBP-4 might be one of many factors that can influence insulin sensitivity in humans.

Visfatin levels do not change after the oral glucose tolerance test and after a dexamethasone-induced increase in insulin resistance in humans.

UNLABELLED: INTRODUCTION, MATERIAL AND METHODS: Visfatin is a cytokine, mainly expressed in visceral fat, that exerts insulin-mimicking effects in rodents through activation of an insulin receptor, although the binding-site is distinct from that of insulin. However, the mechanisms that regulate visfatin synthesis are still not fully understood. In particular, it is not clear whether short-term glucose-induced hyperglycaemia and hyperinsulinaemia as well as a glucocorticoid-induced increase in insulin resistance are reflected in appreciable alterations in serum visfatin levels in humans. In order to investigate this we measured serum visfatin, glucose and insulin concentrations during a 75.0 gram oral glucose tolerance test (OGTT) [Study 1], as well as before and after oral administration of dexamethasone [Study 2]. Study 1 included 17 subjects (2 males), aged 35.7 +/- 15.6 (mean +/- SD) years of BMI 35.2 +/- 9.3 kg/m(2). Blood samples were taken before (0 minutes) and at 60 and 120 minutes after glucose administration. Study 2 included 20 subjects (4 males, 5 subjects with type 2 diabetes), aged 42.1 +/- 17.2 years of BMI 36.7 +/- 8.38 kg/m(2) who underwent screening for Cushing's disease/syndrome. Dexamethasone was administered at a dose of 0.5 mg every 6 hours for 48 hours. Fasting serum concentrations of visfatin, glucose and insulin were assessed before (D0) and after 48 hours of dexamethasone administration (D2). Insulin resistance was assessed according to the HOMA method in non-diabetic individuals (n = 15). RESULTS: In Study 1 two subjects were found to have impaired glucose tolerance and one subject was found to have diabetes mellitus. Glucose administration resulted in a highly significant increase in insulin (from 11.4 +/- 7.2 microU/mL at 0 min to 98.9 +/- 68.6 microU/mL at 60 min and 72.6 +/- 45.1 microU/mL at 120 minute of OGTT, p < 0.001 for 60 and 120 minutes in comparison to baseline). However, there was no change in serum visfatin concentrations (84.6 +/- 11.6 ng/mL at 0 minutes, 82.6 +/- 12.7 ng/mL at 60 minutes and 81.1 +/- 14.5 ng/mL at 120 minutes of OGTT, p = ns). All subjects in Study 2 achieved suppression of cortisol concentrations below 50 nmo/l. Dexamethasone administration resulted in an increase in fasting insulin (from 11.5 +/- 6.9 to 16.9 +/- 7.6 microU/mL; p = 0.011) and an increase in HOMA (from 2.73 +/- 1.74 to 4.02 +/- 2.27; p = 0.015), albeit without a significant change in serum visfatin concentrations (61.1 +/- 19.8 vs. 68.3 +/- 19.4 ng/mL, p = ns). In neither Study 1 nor Study 2 was there any significant correlation between serum visfatin and age, BMI or HOMA. CONCLUSIONS: There is a striking difference between the marked rise in insulin concentrations and the lack of change in visfatin concentrations during the oral glucose tolerance test. This implies that it is highly unlikely that visfatin is involved in the short-term regulation of glucose homeostasis in human subjects. Dexamethasone administration (4 mg/48 hours) induces an increase in insulin resistance, although without significant change in serum visfatin concentrations. Therefore in contrast to the in vitro data, short term glucocorticoid administration does not result in appreciable changes in serum levels of this adipocytokine. Furthermore, the results of our study do not support the notion that glucocorticoid-induced insulin resistance is likely to be related to changes in serum concentrations of visfatin.