Intravenous calcitriol normalizes insulin sensitivity in uremic patients

Kautzky‐Willer, Alexandra; Pacini, Giovanni; Barnas, Ursula; Ludvik, Bernhard; Streli, C; Graf, Helmut; Prager, Rudolf

doi:10.1038/ki.1995.24

Cited by 86 publications

(75 citation statements)

References 36 publications

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“…Insulin resistance is a common feature of ESRD, and an independent predictor of cardiovascular death in hemodialysis patients [32]. However, treatment with 1,25 dihydroxyvitamin D significantly improves insulin sensitivity in severely insulin resistant hemodialysis patients [33] and has been shown to be independently associated with reduced risks for cardiovascular [34] and all-cause death [35] in the hemodialysis population. Taken together, these studies suggest that vitamin D may have multiple effects in skeletal muscle, regulating processes that contribute to muscle anabolism, metabolism, and function, with far reaching effects on survival.…”

Section: Discussionmentioning

confidence: 99%

Relationship Between Vitamin D and Muscle Size and Strength in Patients on Hemodialysis

Gordon

Sakkas

Doyle

et al. 2007

Journal of Renal Nutrition

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OBJECTIVE-Vitamin D has various actions in skeletal muscle. The purpose of this study was to compare lower limb muscle size and strength in hemodialysis (HD) patients being treated with 1,25-dihydroxyvitamin D (calcitriol) or a 1,25-dihydroxyvitamin D analog (paricalcitol) to HD patients who were receiving none.DESIGN-This was a retrospective cross-sectional study. SETTING-Outpatient hemodialysis centers.PATIENTS-HD patients receiving calcitriol or paricalcitol (active vitamin D) for control of secondary hyperparathyroidism (VitD, n = 49) were compared to HD patients who were not (n = 30).MAIN OUTCOME MEASURES-Cross-sectional areas (CSA) of thigh and tibialis anterior muscles by magnetic resonance imaging (MRI), and three measures of strength; three-repetition maximum (3RM) for knee extension (isotonic), peak torque of knee extensors (isokinetic), and maximal voluntary contraction (MVC) of the ankle dorsiflexor muscles (isometric).RESULTS-There were no differences in age, weight, dialysis vintage, or intact parathyroid hormone levels between the groups, although serum albumin was higher in the VitD group (p <0.05). Patients in the VitD group had larger thigh muscle CSA (p < 0.05) and were stronger across all strength measures (p< 0.05) after controlling for age and gender (ANCOVA). When all analyses were subsequently adjusted for serum albumin concentration, only the difference in 3RM knee extension strength lost significance. There were no significant differences in any measurements between patients who received calcitriol or paricalcitol.CONCLUSION-Treatment with active vitamin D was associated with greater muscle size and strength in this cohort of HD patients.

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Section: Discussionmentioning

confidence: 99%

Relationship Between Vitamin D and Muscle Size and Strength in Patients on Hemodialysis

Gordon

Sakkas

Doyle

et al. 2007

Journal of Renal Nutrition

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“…16 Intravenous 12-week vitamin D treatment of HD patients led to a significant reduction of PTH levels and to a complete normalization of insulin sensitivity. 6 Since there was a signi¢cant reduction of PTH levels upon treatment, the authors could not di¡erentiate between the actions of calcitriol per se and those of PTH reduction. The effect of four-week intravenous calcitriol therapy on insulin metabolism was therefore examined, during which time the PTH concentration did not change, so that the direct actions of calcitriol could be assessed independently.…”

Section: Discussionmentioning

confidence: 99%

“…7 Intravenous vitamin D treatment leads to a signi¢cant reduction of PTH concentrations and to a complete normalization of insulin sensitivity in HD patients. 6 Thus, intravenous 1,25 dihydroxycholecalciferol improves insulin resistance in uraemic patients, acting per se or by reducing secondary hyperparathyroidism. In our study, treatment with pulse oral 1-a-D3 only had an e¡ect on PC-1 of Con A-transformed lymphocytes of haemodialysed patients.…”

Section: Discussionmentioning

confidence: 99%

“…The mechanisms of the action of calcitriol on glucose intolerance, insulin resistance and insulin secretion in HD patients are not yet resolved. 6,7 The possible implication of alkaline phosphodiesterase I (EC 3.1.3.1) --plasma cell di¡erentiation antigen 1 (PC-1) in the origin of tissue resistance to insulin action was recently suggested. In insulin-resistant tissues, an increase of PC-1content was found, and a negative correlation between PC-1 content and some parameters of tissue insulin sensitivity were demonstrated.…”

Section: Introductionmentioning

confidence: 99%

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Lymphocyte PC-1 activity in patients on maintenance haemodialysis treated with human erythropoietin and 1-α-D3

Stefanović

Djordjević²,

Ivic³

et al. 2005

Ann Clin Biochem

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Background: Plasma cell differentiation antigen 1 (PC-1) is an inhibitor of insulinreceptor tyrosine-kinase. PC-1 content is elevated in muscle and adipose tissue from insulin-resistant subjects and its elevation correlates with in vivo insulin resistance. It is known that insulin resistance in uraemia may be improved with erythropoietin (EPO) and vitamin D therapy. Therefore, in this study the effects of human recombinant EPO and 1-alpha-D3 treatments on lymphocyte PC-1 expression in patients with end-stage renal failure on haemodialysis (HD) were investigated. Methods: Lymphocyte basal, concanavalin A (Con A), and phorbol-12-myristate13-acetate (PMA)-stimulated PC-1 activity were investigated in HD patients before and after a two-month treatment with subcutaneous EPO (15 patients, 2000-3000 U thrice weekly) or oral 1-α-D3 (14 patients, 2 μg thrice weekly). Twenty-nine patients (16 men and 13 women), aged 22-68 years (49 ± 7 years), on HD from 13 to 112 months, and 30 healthy controls participated in the study. None was obese and all had normal fasting plasma glucose. Results: A two-month EPO treatment produced a 41% haematocrit increase, with a rise in haemoglobin from 6.51 ± 0.18 g/dL to 9.69 ± 0.14 g/dL. Basal lymphocyte PC-1 activity in HD patients was found to be significantly increased ( P < 0.005) over the level in healthy controls. Treatment of patients with EPO decreased unstimulated lymphocyte PC-1 activity to values significantly lower than before the treatment ( P < 0.001). Lymphocyte Con A and PMA-stimulated PC-1 activity in patients on HD was found to be slightly increased over the level in healthy controls, but significantly reduced ( P < 0.005 and 0.05, respectively) after the EPO treatment. A two-month pulse oral 1-α-D3 treatment increased haematocrit by 21% and raised haemoglobin from 7.11 ± 0.32 g/dL to 8.80 ± 0.39 g/dL. This treatment normalized serum alkaline phosphatase activity and slightly reduced serum parathyroid hormone concentration. PC-1 in unstimulated and PMA-stimulated lymphocytes was unchanged, but significantly decreased ( P < 0.05) in Con A-stimulated lymphocytes after 1-α-D3 treatment. Fasting plasma glucose was not changed by the treatment. Conclusion: An increased lymphocyte PC-1 activity over control was found in HD patients. A two-month EPO therapy significantly decreased PC-1 activity to the control values, suggesting that an effect on PC-1 expression could be implicated in the amelioration of insulin resistance in uraemic patients treated with EPO. Treatment with pulse oral 1-α-D3 had an effect only on PC-1 of Con A-transformed lymphocytes of haemodialysed patients and requires further investigation.

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“…Moreover, an increased insulin release causing hypoglycemia following parathyroidectomy was observed in a hemodialysis patient (24). The majority of authors, however, observed hyperinsulinemia or insulin resistance in PHPT (15)(16)(17), in secondary hyperparathyroidism (15,25,26) or in hyperparathyroidism associated with multiple endocrine neoplasia syndrome type 1 (18). It is believed that hyperinsulinism and insulin resistance play a role in the pathogenesis of arterial hypertension.…”

Section: Discussionmentioning

confidence: 99%

The effect of surgical treatment on secondary hyperaldosteronism and relative hyperinsulinemia in primary hyperparathyroidism

Kovács¹,

Góth²,

Szabolcs³

et al. 1998

European Journal of Endocrinology

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Objective: To evaluate the renin-aldosterone system and insulin secretion in hyperparathyroidism and their effects on blood pressure regulation. Design: Studies were carried out on patients with primary hyperparathyroidism (PHPT) prior to and following removal of the parathyroid tumor. Methods: Sixteen normotensive and euglycemic patients with PHPT were studied. The following parameters were measured: basal and stimulated plasma renin activity (PRA) and aldosterone (ALD) secretion; parathormone (PTH) and serum electrolytes. Insulin and glucose levels were measured during an oral glucose tolerance test. Results: Systolic but not diastolic blood pressure showed a decrease following surgery, from 123.3 Ϯ 13.0/80 Ϯ 8.6 to 116.7 Ϯ 13.5/77.3 Ϯ 8.8 mmHg. The decrease in the systolic pressure was not clinically significant. After surgery, both the basal and stimulated PRA and ALD values decreased, and the preoperative pathological values returned to normal: PRA basal: 1.79 → 0.70 ng/ml/h, P ¼ 0.0049; PRA stimulated: 7.76 → 1.90 ng/ml/h, P ¼ 0.0031; ALD basal: 111.5 → 73.0 pg/ml, P ¼ 0.0258; ALD stimulated: 392.5 → 236.0 pg/ml, P ¼ 0.0157. The postoperative decrease in the PRA correlated with the changes in PTH levels (r ¼ 0.5442, P < 0.05, n ¼ 16) but did not correlate with the changes in serum calcium concentrations. Both the fasting and stimulated insulin levels decreased after surgery but remained within the normal range: insulin fasting: 10.2 → 5.0 mIU/l, P ¼ 0.0218; insulin area under the curve: 5555 → 3296 mIU/l*min, P ¼ 0.0218. There was no correlation between the changes in insulin levels and PTH or ion levels. Sodium, potassium and blood glucose levels remained unaffected by parathyroid surgery. Conclusions: In a population of normotensive hyperparathyroid patients an increased activity of the renin-aldosterone system related to PTH was found and surgery resulted in a small and insignificant decrease in blood pressure. This change was accompanied by a significant decrease in the activity of the renin-aldosterone system indicating the role of the renin-aldosterone system in the regulation of blood pressure in PHPT. Both fasting and stimulated insulin values decreased following removal of the parathyroid tumor, but with no individual correlation with PTH and calcium levels.

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Intravenous calcitriol normalizes insulin sensitivity in uremic patients

Cited by 86 publications

References 36 publications

Relationship Between Vitamin D and Muscle Size and Strength in Patients on Hemodialysis

Relationship Between Vitamin D and Muscle Size and Strength in Patients on Hemodialysis

Lymphocyte PC-1 activity in patients on maintenance haemodialysis treated with human erythropoietin and 1-α-D3

The effect of surgical treatment on secondary hyperaldosteronism and relative hyperinsulinemia in primary hyperparathyroidism

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