Vitamin D, osteocalcin, and risk for adiposity as comorbidities in middle school children

Nonclassic actions of vitamin D include potential regulation of immune function and glucose homeostasis. The bone-metabolism loop has recently been expanded to include osteocalcin, which appears to play a more direct role in pancreatic beta cell function and energy metabolism. We hypothesized that both vitamin D and osteocalcin would correlate negatively with indices of adiposity-related comorbidity risk in periadolescents, varying by ethnic group. We analyzed anthropometric, metabolic, and inflammatory markers from a multiethnic population of 106 school children 11 to 14 years of age studied as part of the Reduce Obesity and Diabetes (ROAD) consortium. As expected, 25-hydroxyvitamin D (25-OH vitamin D) was inversely correlated with intact parathyroid hormone (iPTH); total osteocalcin (OCN) and uncarboxylated osteocalcin (uOCN) were directly correlated with each other. OCN and uOCN concentrations correlated inversely with age. Vitamin D deficiency was most prevalent among East Asians (EA) and African Americans (AA). The highest lipid risk scores and homeostatic model for assessment of insulin resistance (HOMA-IR) values were seen in the South Asian (SA) group. Overall, adiposity measures were inversely correlated with OCN and iPTH, whereas such relationships were not observed for vitamin D. Acute insulin response to glucose challenge correlated negatively with uOCN in all subjects; however, lipid risk score correlated negatively with uOCN only in whites. The relationships between markers of calcium metabolism and body composition, glucose homeostasis, lipids, and inflammation all showed racial and ethnic differences. No consistent relationship was found between vitamin D and adiposity or vitamin D and glucose metabolism; instead vitamin D levels varied by race and ethnicity in this school-based group. These findings are consistent with the hypothesis that markers of calcium and bone metabolism may reflect risk for adiposity-related comorbidities in children.     

Calcium and its regulating hormones in patients with graves disease: sex differences and relation to postoperative tetany.

OBJECTIVE: To find out why female sex is the most important risk factor for tetany, as calcium and bone metabolism may differ between the sexes. DESIGN: Prospective study. SETTING: Thyroid centre, Japan. PATIENTS AND METHODS: 45 men (mean age 35 years, SD 13) and 178 women (mean age 33 years, SD 12) with Graves disease treated by subtotal thyroidectomy. Interventions: Measurement of serum concentrations of intact parathyroid hormone (iPTH), calcium, electrolytes, 25-hydroxyvitamin D (25 (OH) D), and 1,25-dihydroxyvitamin D (1,25 (OH) 2D). MAIN OUTCOME MEASURES: Mean values of these substances, together with reductions in serum calcium concentration, relative youth, increased alkaline phosphatase activity, large goitre, and increased serum TSH binding inhibitory globulin concentration. RESULTS: Women had significantly lower calcium concentrations than men (mean (SD) 2.37 (0.13) compared with 2.43 (0.07), p = 0.003). Serum calcium concentrations correlated significantly with concentrations of 25 (OH) D (p < 0.001). 121 of the women (68%) compared with 13 (29%) of men had vitamin D deficiency as defined as 25 (OH) D < 25 nmol/l (p < 0.05). 15 patients (8%) developed tetany postoperatively compared with I man (2%, p = 0.2). CONCLUSION: Women with Graves disease are more susceptible to calcium and vitamin D deficiency than men, which may account for the higher incidence of postoperative tetany among women with the disease.     

Longitudinal Evaluation of Vitamin D Status in Healthy Subjects from Southern Italy: Seasonal and Gender Differences

Vitamin D status is currently considered among the relevant determinants of skeletal integrity. Since vitamin D levels present seasonal variations, we longitudinally studied young healthy men and women in order to investigate the related physiologic modifications of both calcium homeostasis and bone remodeling. Thirty-two men (mean age 39.4 ± 7.8 years) and 58 premenopausal women (aged 36.9 ± 6.4 years) from southern Italy were studied. In all subjects the following parameters were measured both in winter and in summer: serum calcium, phosphorus, creatinine, total alkaline phosphatase activity, 25-hydroxyvitamin D (25OHD), parathyroid hormone (PTH), osteocalcin (BGP), together with urinary calcium (Ca/Cr), total pyridinoline (Pyr/Cr) and deoxypyridinoline (d-Pyr/Cr), corrected for creatinine excretion. In both sexes 25OHD levels were significantly higher in summer, while PTH values were lower, than in winter. The prevalence of hypovitaminosis D, defined by concentrations of 25OHD lower than 30 nmol/l, was 17.8% in winter and 2.2% in summer in the whole sample, while it was 27.8% and 3.4%, respectively, among female subjects. Indeed male subjects did not display hypovitaminosis D, having throughout the year significantly higher calcium and 25OHD levels together with lower PTH values, than the women. Moreover, alkaline phosphatase total activity was more elevated in men both in winter and in summer. In women, during winter, bone remodeling markers levels were higher while urinary calcium levels were lower than in summer. In the whole sample serum 25OHD correlated positively with serum calcium and inversely with PTH. The seasonal percentage variations in PTH were inversely correlated with those of Ca/Cr. Our results show a relatively high prevalence of subclinical vitamin D deficiency among young healthy women from southern Italy. Significant gender-specific differences have been demonstrated in both calcium homeostasis and skeletal remodeling indexes; the seasonal fluctuations in the vitamin D–PTH axis are accompanied by cyclical variations of bone turnover rate, which were more pronounced in women. Received: 11 January 2001 / Accepted: 6 July 2001     

Beta-cell function is a major contributor to oral glucose tolerance in high-risk relatives of four ethnic groups in the U.S

First-degree relatives of individuals with type 2 diabetes are at increased risk of developing hyperglycemia. To examine the prevalence and pathogenesis of abnormal glucose homeostasis in these subjects, 531 first-degree relatives with no known history of diabetes (aged 44.1 +/- 0.7 years; BMI 29.0 +/- 0.3 kg/m(2)) underwent an oral glucose tolerance test (OGTT). Newly identified diabetes was found in 19% (n = 100), and impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) was found in 36% (n = 191). Thus, only 45% (n = 240) had normal glucose tolerance (NGT). The homeostasis model assessment of insulin resistance (HOMA-IR) was used to estimate insulin sensitivity; beta-cell function was quantified as the ratio of the incremental insulin to glucose responses over the first 30 min during the OGTT (DeltaI(30)/DeltaG(30)). This latter measure was also adjusted for insulin sensitivity as it modulates beta-cell function ([DeltaI(30)/DeltaG(30)]/HOMA-IR). Decreasing glucose tolerance was associated with increasing insulin resistance (HOMA: NGT 12.01 +/- 0.54 pmol/mmol; IFG/IGT 16.14 +/- 0.84; diabetes 26.99 +/- 2.62; P < 0.001) and decreasing beta-cell function (DeltaI(30)/DeltaG(30): NGT 157.7 +/- 9.7 pmol/mmol; IFG/IGT 100.4 +/- 5.4; diabetes 57.5 +/- 7.3; P < 0.001). Decreasing beta-cell function was also identified when adjusting this measure for insulin sensitivity ([DeltaI(30)/DeltaG(30)]/HOMA-IR). In all four ethnic groups (African-American, n = 55; Asian-American, n = 66; Caucasian, n = 217; Hispanic-American, n = 193), IFG/IGT and diabetic subjects exhibited progressively increasing insulin resistance and decreasing beta-cell function. The relationships of insulin sensitivity and beta-cell function to glucose disposal, as measured by the incremental glucose area under the curve (AUCg), were examined in the whole cohort. Insulin sensitivity and AUCg were linearly related so that insulin resistance was associated with poorer glucose disposal (r(2) = 0.084, P < 0.001). In contrast, there was a strong inverse curvilinear relationship between beta-cell function and AUCg such that poorer insulin release was associated with poorer glucose disposal (log[DeltaI(30)/DeltaG(30)]: r(2) = 0.29, P < 0.001; log[(DeltaI(30)/DeltaG(30))/HOMA-IR]: r(2) = 0.45, P < 0.001). Thus, abnormal glucose metabolism is common in first-degree relatives of subjects with type 2 diabetes. Both insulin resistance and impaired beta-cell function are associated with impaired glucose metabolism in all ethnic groups, with beta-cell function seeming to be more important in determining glucose disposal.     

Determinants of undercarboxylated and carboxylated osteocalcin concentrations in type 1 diabetes

Summary

To determine whether undercarboxylated osteocalcin (UC-OC) or gamma-carboxyglutamic-carboxylated-type osteocalcin (GLA-OC) concentrations deviate from normal in type 1 diabetes (T1D), serum levels were compared between 115 subjects with T1D and 55 age-matched healthy controls. UC-OC and GLA-OC concentrations were similar between groups; however, in T1D, UC-OC correlated positively with markers of insulin exposure, either endogenously produced or exogenously administered.

Introduction

A study was conducted to determine whether dysregulation of circulating concentrations of UC-OC or GLA-OC occurs in patients with type 1 diabetes, a condition of insulin deficiency without insulin resistance.

Methods

We measured serum concentrations of UC-OC and GLA-OC in 115 subjects with T1D, ages 14–40?years, and in 55 age-matched healthy control subjects. Relationships between UC-OC and GLA-OC concentrations and patient characteristics (gender and age), indices of glycemic control (hemoglobin A1c (HbA1c), fasting plasma glucose, C-peptide concentration, 3-day average glucose measured by a continuous glucose sensor, total daily insulin dose) and circulating indices of skeletal homeostasis (total calcium, 25-OH vitamin D, parathyroid hormone, insulin-like growth factor 1 (IGF-1), type 1 collagen degradation fragments (CTX), adiponectin, leptin) were examined. Between group differences in the concentrations of UC-OC and GLA-OC were the main outcome measures.

Results

Although adiponectin levels were higher in the T1D group, between-group comparisons did not reveal statistically significant differences in concentration of UC-OC, GLA-OC, CTX or leptin between the T1D and control populations. Instead, by multivariate regression modeling, UC-OC was correlated with younger age (p?p?p?=?0.013), and higher IGF-1 (p?=?0.086). Moreover, within the T1D subgroup, UC-OC was positively correlated with C-peptide/glucose ratio (reflecting endogenous insulin secretion), with IGF-1 (reflecting intra-portal insulin sufficiency), and with total daily insulin dose.

Conclusions

In T1D, UC-OC appears to correlate positively with markers of insulin exposure, either endogenously produced or exogenously administered.     

Evidence that obesity does not influence the vitamin D-endocrine system in blacks

As compared to nonobese white men and women, age-matched nonobese black subjects and obese white individuals show alterations in the vitamin D-endocrine system that are characterized by increases in mean serum immunoreactive parathyroid hormone (PTH), serum 1,25-dihydroxyvitamin D [1,25-(OH)2D], and urinary cyclic adenosine 3,5-monophosphate (cAMP) and by decreases in mean serum 25-hydroxyvitamin D (25 OHD) and in urinary calcium. Thus, both groups show secondary hyperparathyroidism which is associated with increased renal tubular reabsorption of calcium and increased renal synthesis of 1,25-(OH)2D. In view of these findings, studies were conducted in 10 obese black subjects (3 men and 7 women) and in 12 nonobese black individuals (7 men and 5 women), ranging in age from 20 to 35 yr, to determine whether obesity influences the vitamin D-endocrine system in blacks. Body weight averaged 99 +/- 4 kg in the obese and 73 +/- 3 kg in the nonobese subjects (p less than .001). All of them were hospitalized on a metabolic ward and were given a constant daily diet containing 400 mg of calcium, 900 mg of phosphorus, 110 meq of sodium, 65 meq of potassium, and 18 meq of magnesium.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sevelamer hydrochloride with or without alphacalcidol or higher dialysate calcium vs calcium carbonate in dialysis patients: an open-label, randomized study.

BACKGROUND: Sevelamer hydrochloride was recently proposed as a phosphate binder to prevent hypercalcaemia in place of calcium alkaline salts in dialysis patients. So far, it has been evaluated only in patients receiving calcitriol, without comparison with CaCO(3) alone, although the latter was found to be as effective as the combination of calcitriol and Al(OH)(3) in suppressing parathyroid hormone (PTH) without inducing hypercalcaemia and to have a better lowering effect on serum phosphate. Moreover, this bile salt binder may decrease serum 25-OH vitamin D. Therefore, we compared for 5 months two strategies for controlling moderate hyperparathyroidism: CaCO(3) alone vs sevelamer in conjunction with measures to increase calcium balance. METHODS: Forty-two patients were randomized: 21 continued their treatment with 4.8 g/day CaCO(3) and 21 were switched to sevelamer (initial dose: 2.4 g/day, increased to 4.4 g/day). Each month, when serum-corrected calcium decreased below 2.30 mmol/l, dialysate calcium was increased or alphacalcidol was given at each dialysis session, according to serum PO(4) levels. The following parameters were monitored: serum Ca, PO(4), bicarbonate and protein, weekly; and serum PTH, 25-OH vitamin D and total, LDL and HDL cholesterol monthly. RESULTS: Except for higher serum phosphate at month 1, lower serum bicarbonate at month 2 and lower LDL cholesterol at month 5 in the sevelamer group, no difference was found between the two groups. Compared with baseline levels, PTH increased and 25-OH vitamin D decreased significantly in both groups, these two parameters being inversely correlated. CONCLUSIONS: Given comparable control of plasma calcium, phosphate and 25-OH vitamin D, PTH control is comparable in both strategies. Sevelamer does not induce greater vitamin D depletion than CaCO(3). The transient decrease of serum bicarbonate after discontinuation of CaCO(3) in the sevelamer group suggests a less optimal prevention of acidosis. The sevelamer-induced decrease in LDL cholesterol gives this drug a potential advantage in cardiovascular prevention.     

Influence of nutritional factors on calcium-regulating hormones and bone loss

Summary The relationships between nutritional factors, calcium regulating hormones, and bone density were evaluated in three groups of normal subjects in rural southeast Kansas. Dietary intake of calcium (Ca), phosphorous (P), protein, and vitamin D; and serum 25OHD, Ca, P, parathyroid hormone (iPTH), and bone density (distal 1/3 radius) were measured in 29 elderly women, 35 elderly men, and 50 perimenopausal women. Measurements were repeated 5 years and 4 years later respectively in 16 elderly women and 15 elderly men. The r values for significant regression correlations for each group were as follows: perimenopausal: bone density and dietary Ca:P−r=.29, iPTH and 25OHD−r=−.38; elderly women: 25OHD and dietary Vitamin D(D)−r=.58, change in bone density (ΔBD) and initial bone density (BDI)−r=−.71, ΔBD and serum 25OHD−r=−.60, serum calcium and age−r=−.42; elderly men: Serum 25OHD and D−r=.61, iPTH and 25OHD−r=−.43, iPTH and serum phosphorous−r=.59. Conclusions: (1) The more adequate the state of vitamin D nutriture, the lower the serum iPTH in perimenopausal women and elderly men and the less bone loss in elderly women. (2) The Ca:P ratio in the diet may be important in maintaining bone density in perimenopausal women.     

Primary biliary cirrhosis and osteoporosis: a case-control study

Osteoporosis is a common complication of chronic liver disease, from cholestatic disorders to autoimmune, alcoholic, and posthepatitic cirrhosis. Osteoporosis appears more striking in patients with primary biliary cirrhosis (PBC) because the disease usually affects elderly women, who are naturally prone to osteoporosis. Our aims were (1) to compare the prevalence of osteoporosis (T-score <-2.5 SD) between PBC patients and a group of age-and sex-matched controls consisting of healthy subjects from the general population; and (2) to identify the main risk factors for the development of bone loss. Thirty-three women with PBC (mean age, 47.3 +/- 10.4 years) and 66 healthy subjects were enrolled in the study. Bone mineral density (BMD) was assessed at the lumbar spine by dual-photon X-ray absorptiometry. Bone metabolism was evaluated by measuring serum calcium corrected for serum albumin, 25-hydroxyvitamin D (25-OH vit D), parathyroid hormone, and osteocalcin. Vertebral fractures were analyzed using vertebral fracture assessment (VFA). The mean T-score was lower in the PBC group compared to healthy controls, with a significant statistical difference (-2.39 +/- 0.93 and -1.47 +/- 0.99 in lumbar spine and total hip, respectively, in the PBC group versus -0.99 +/- 0.51 and -0.56 +/- 1.14 in healthy controls (P < 0.001). The prevalence of osteoporosis was 51.5% in the PBC group versus 22.7% in healthy controls with a statistically significant difference (P = 0.004). BMD of the PBC group was significantly correlated positively with body mass index (BMI) and 25-OH vit D, and negatively with menopausal status, duration of disease, and parathyroid hormone (PTH) levels. Vertebral fractures were present in 9% of the patients. We found that osteoporosis is more prevalent in women with PBC than in the general population. BMI, menopausal status, duration of the disease, and vitamin D deficiency are the main risk factors for osteoporosis in this liver disease.     

Thyroid, parathyroid, gonadal, and pancreatic beta-cell function after bone marrow transplantation with chemotherapy-only conditioning

INTRODUCTION: Radiation and cytotoxic chemotherapy can provoke short- and long-term endocrine dysfunction. We studied the prevalence of thyroid, parathyroid, gonadal, and pancreatic beta-cell function in patients undergoing bone marrow transplantation (BMT). MATERIALS AND METHOD: Forty-six patients (12 women, 34 men), aged 1.5 to 49 years (mean, 15.1 years), were evaluated for thyroid, parathyroid, gonadal, and pancreatic beta-cell function before and 3, 6, and 12 months after BMT with a little busulfan-cyclophosphamide conditioning regimen. RESULTS: Thyroid and parathyroid function was unaltered by BMT. Leydig cell function was normal in 11 adult men (G5P5) before and at 3, 6, and 12 months after BMT, but injury to the germinal epithelium (oligo- or azoospermia) was seen before and 12 months after BMT. There was no relationship between serum FSH and germinal epithelial injury. Maturation was normal in six boys (G2P2 or G3P3 at BMT) 12 months post-BMT. Primary hypogonadism was seen in four adult women (B5P5) after BMT. One 14-year-old girl continued to have regular menstrual periods during the 24 months after BMT. Another girl (P1B1 pre-BMT) developed ovarian failure 12 months post-BMT. Pancreatic beta-cell function was normal pre- and post-BMT in 12 thalassemic patients with serum ferritin > 1000 ng/mL. CONCLUSION: BMT with chemotherapy-only conditioning seems primarily to affect gonadal function, without having any significant effect on thyroid, parathyroid, or pancreatic beta-cell function.     

Is vitamin D a determinant of muscle mass and strength?

There remains little consensus on the link between vitamin levels and muscle mass or strength. We therefore investigated the association of serum 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)(2) D), and parathyroid hormone (PTH) levels with skeletal muscle mass and strength. We studied 311 men (mean age, 56 years; range, 23-91 years) and 356 women (mean age, 57 years; range, 21-97 years) representing an age-stratified, random sample of community adults. Multivariate linear regression models were used to examine the association of skeletal muscle mass (by total body dual-energy X-ray absorptiometry) and strength (handgrip force and isometric knee extension moment) with each of 25(OH)D, 1,25(OH)(2) D, and PTH quartiles, adjusted for age, physical activity, fat mass, and season. We found no consistent association between 25(OH)D or PTH and any of our measurements of muscle mass or strength, in either men or women. However, in subjects younger than 65 years, there was a statistically significant association between low 1,25(OH)(2) D levels and low skeletal mass in both men and women and low isometric knee extension moment in women, after adjustment for potential confounders. Modestly low 25(OH)D or high PTH levels may not contribute significantly to sarcopenia or muscle weakness in community adults. The link between low 25(OH)D and increased fall risk reported by others may be due to factors that affect neuromuscular function rather than muscle strength. The association between low 1,25(OH)(2) D and low skeletal mass and low knee extension moment, particularly in younger people, needs further exploration.     

高校大学生循环骨钙素水平及其相关因素分析

目的分析高校大学生循环骨钙素水平及其与选择的钙调节激素、骨及糖脂代谢指标之间的相关性。方法通过问卷调查和血液指标检测,从某大学筛选出103名符合试验要求的非体育专业在校大学生。将受试者按照性别分为男性组和女性组,采用简单和多重线性回归分析两组受试者血清骨钙素水平的相关因素。结果男大学生血清骨钙素水平显著高于女大学生。Pearson相关分析结果表明,男大学生血清骨钙素水平与年龄和体质量指数(body mass index,BMI)呈负相关,而与血清甲状旁腺激素(parathyroid hormone,PTH)和碱性磷酸酶(alkaline phosphatase,ALP)水平呈正相关。经身体形态学指标校正后,与胰岛素水平和稳态模型评估胰岛素抵抗指数呈正相关;女大学生血清骨钙素水平与体重和BMI呈负相关,而与血清PTH、ALP、磷和空腹血糖(fasting blood glucose,FBG)水平呈正相关。经身体形态学指标校正后,与血清25羟维生素D [25-hydroxyvitamine D,25(OH) D]、钙、高密度脂蛋白胆固醇和FBG水平呈正相关。多重线性回归分析进一步表明,男大学生血清骨钙素水平与年龄和BMI独立负相关,而与血清PTH水平独立正相关;女大学生血清骨钙素水平与FBG水平独立正相关。结论高校大学生循环骨钙素水平及其与年龄、BMI、PTH和FBG水平的独立相关性具有性别差异。     

Relationship between serum parathyroid hormone, vitamin D sufficiency, age, and calcium intake

Vitamin D deficiency is extremely common among elderly subjects and it has been associated with poor bone health, and to a number of other conditions. The ideal 25-hydroxy-vitamin D [25(OH)D] concentration, reflecting the size of vitamin D deposits, are generally retained those not associated with any marginal increase in serum parathyroid hormone (PTH). These threshold values vary considerably and this may be due to the interaction of other factors. The aim of the study is to assess whether age and calcium intake interact with the relationship between 25(OH)D and PTH. Data from a survey on the prevalence of hypovitaminosis D in elderly women in Italy were analysed in order to verify whether age and calcium intake were interfering on the 25(OH)D/PTH relationship. A total of 697 women were available for analysis. Serum PTH levels were significantly correlated with age, 25(OH)D and calcium intake (p<0.001) and in a multivariate model they all significantly contributed to explain PTH variance (R(2)=24.4%). In 39 elderly osteoporotic women on a low calcium intake and given vitamin D supplements (2000-3000 IU daily for >8 months) able to increase 25(OH)D levels above 110 nMol/l, PTH levels were maintained below 35 pg/mL. The minimum 25(OH)D levels to be recommended depends largely on the age and the calcium intake. In elderly individuals not taking calcium supplements in order to keep serum PTH levels strictly within the normal range 25(OH)D serum levels should be maintained above ca. 120 nMol/L.     

血清神经肽Y水平与绝经后妇女骨密度相关性研究

目的探讨血清神经肽Y(NPY)水平与绝经后妇女骨密度(BMD)的相关性。方法纳入在我院门诊就诊的绝经后妇女。测量血清钙、磷、白蛋白、甲状旁腺激素(parathyroid hormone,PTH)、促甲状腺激素(thyrotropin,TSH)、25-OH维生素D和NPY浓度。根据骨密度检测结果将受试者分为3组,分别为BMD值:正常(n=66)、骨量减少(n=63)和骨质疏松症(n=63)。根据血清NPY水平,受试者也被分为3组:低NPY(n=30)、正常NPY(n=126)和高NPY(n=36)。结果骨密度正常、骨质疏松、骨质疏松症患者血清NPY、PTH和年龄水平差异有显著统计学意义(P<0.05)。对于不同的NPY水平,各组腰椎、股骨总、股骨颈、转子、股骨转子间和Ward’s三角BMD值有显著差异(P<0.05)。相关性分析显示血清NPY水平与患者年龄、BMI呈现显著正相关(P<0.05),与不同部位的BMD值之间均有显著负相关性(P<0.05)。结论血清NPY水平与患者年龄、体重指数或任何部位测量的BMD值之间有相关性。     

Coordinate changes in plasma glucose and pancreatic beta-cell function in Latino women at high risk for type 2 diabetes

The purpose of this study was to examine longitudinally the relationship among glucose levels, pancreatic beta-cell function, and insulin resistance in women at high risk for type 2 diabetes. Oral glucose tolerance tests (OGTTs) and intravenous glucose tolerance tests (IVGTTs) were performed at 15-month intervals for up to 5 years or until fasting plasma glucose exceeded 140 mg/dl in Hispanic women with recent gestational diabetes. Data were analyzed 1) to compare changes in insulin sensitivity, beta-cell function, and glucose levels between women who had diabetes at one or more visits and women who remained diabetes free and 2) to determine longitudinal patterns of change in glucose levels and acute beta-cell compensation for insulin resistance. Seventy-one women provided data from a total of 280 paired OGTTs and IVGTTs during a median follow-up of 46 months. Compared with the 47 women who remained free of diabetes, the 24 who either had diabetes (n = 9) or developed it during follow-up (n = 15) had higher baseline glucose levels and lower acute beta-cell compensation for insulin resistance. Baseline insulin sensitivity was low in both groups and did not change significantly during follow-up. Fasting and 2-h glucose levels increased more rapidly in the diabetic group despite a decline in acute beta-cell compensation that was significantly slower than the decline in women who did not develop diabetes. This paradox was explained by an accelerated rise in glucose levels for any decline in beta-cell compensation when beta-cell compensation reached approximately 10% of normal, a level that was reached in the women who had or developed diabetes but not in the women who remained diabetes free. These findings define a pathogenesis for type 2 diabetes in one high-risk group that is characterized by a relatively long-term decline in acute beta-cell compensation for chronic insulin resistance that is attended by slowly rising glucose levels. Only relatively late in this process do glucose levels rise rapidly and into the diabetic range.     

Relation between parathyroid hormone and adrenocorticotropic hormone in primary hyperparathyroidism

Parathyroid hormone is concerned with urolithiasis, and regulated by serum ionized calcium concentration. We thought that parathyroid hormone might also be regulated by a hormone. 1 mg of ACTH injection was given intramuscularly to 6 patients with primary hyperparathyroidism, 6 patients with urolithiasis, and 5 control subjects. Serum calcium significantly increased 2 h after ACTH injection in primary hyperparathyroidism. However in the other two groups, an increase of serum calcium was not observed. Parathyroid hormone increased after ACTH injection in most subjects of all three groups. Calcium concentration in a culture medium of parathyroidectomy increased in 4 cases, and the parathyroid hormone concentration in the culture medium increased in 3 cases after ACTH addition. From these data, we believe that ACTH directly influences the parathyroid glands, and that calcium is released from the parathyroid cells. Therefore, the decrease in calcium concentration in the parathyroid cells activates the excretion of parathyroid hormone. The fact that serum parathyroid hormone increases in most subjects in all groups supports our hypothesis, namely that ACTH acts directly on the parathyroid gland.     

Intravenous 1,25 dihydroxycholecalciferol corrects glucose intolerance in hemodialysis patients.

The effects of intravenous 1,25 dihydroxycholecalciferol [(OH)2D3] on glucose tolerance and insulin secretion were studied in eleven uremic patients on regular hemodialysis and compared with eleven healthy controls. Intravenous glucose tolerance tests (IVGTT) were used to assess glucose tolerance, and the hyperglycemic clamp technique was used to quantitate endogenous insulin secretion. Three days after they had discontinued oral 1,25(OH)2D3, the dialysis patients were then studied with (+D) and without (-D) a single intravenous dose of 1,25(OH)2D3 at 2 micrograms/m2, given two hours before the IVGTT or clamp studies. During the -D studies, the uremic patients were glucose intolerant but not hyperinsulinemic. Intravenous 1,25(OH)2D3 in dialysis patients increased glucose uptake (K values) during IVGTT by 38% (P less than 0.02) and increased early component of insulin secretion during hyperglycemic clamps by 48% (P less than 0.01) and the late component by 32% (P less than 0.01). After intravenous 1,25(OH)2D3, the dialysis patients became hyperinsulinemic and regained glucose tolerance. Intravenous 1,25(OH)2D3 did not change the K values during IVGTT nor the insulin secretion during hyperglycemic clamps in the control subjects. During the -D studies, serum concentrations of 1,25(OH)2D3 were significantly lower in uremic patients compared with controls. Serum 1,25(OH)2D3 during the +D studies increased to supraphysiological levels in both uremic patients and controls. Serum concentrations of intact parathyroid hormone, total and ionized calcium, magnesium, potassium, urea nitrogen and creatinine were not different between the +D and -D studies in neither the uremic patients nor the controls. These results suggest that 1,25(OH)2D3 deficiency, independent of parathyroid hormone and calcium, may contribute to the abnormalities in glucose tolerance and insulin secretion in dialysis patients.     

Serum visfatin increases with progressive beta-cell deterioration

Visfatin has shown to be increased in type 2 diabetes but to be unrelated to insulin sensitivity. We hypothesized that visfatin is associated with insulin secretion in humans. To this aim, a cross-sectional study was conducted in 118 nondiabetic men and 64 (35 men and 29 women) type 2 diabetic patients. Type 1 diabetic patients with long-standing disease (n = 58; 31 men and 27 women) were also studied. In nondiabetic subjects, circulating visfatin (enzyme immunoassay) was independently associated with insulin secretion (acute insulin response to glucose [AIRg] from intravenous glucose tolerance tests) but not with insulin sensitivity (Si) or other metabolic or anthropometric parameters, and AIRg alone explained 8% of visfatin variance (beta = -0.29, P = 0.001). Circulating visfatin was increased in type 2 diabetes (mean 18 [95% CI 16-21] vs. 15 ng/ml [13-17] for type 2 diabetic and nondiabetic subjects, respectively; P = 0.017, adjusted for sex, age, and BMI), although this association was largely attenuated after accounting for HbA1c (A1C). Finally, circulating visfatin was found to be increased in patients with long-standing type 1 diabetes, even after adjusting for A1C values (37 ng/ml [34-40]; P < 0.0001, adjusted for sex, age, BMI, and A1C compared with either type 2 diabetic or nondiabetic subjects). In summary, circulating visfatin is increased with progressive beta-cell deterioration. The study of the regulation and role of visfatin in diabetes merits further consideration.     

Biochemical variables associated with bone density in patients with primary hyperparathyroidism.

OBJECTIVE--To clarify the association between primary hyperparathyroidism and cortical osteopenia. DESIGN--Open study. SETTING--Department of Surgery, University of Lund, Sweden. SUBJECTS--38 patients with primary hyperparathyroidism. OUTCOME MEASURES--Correlation between bone density (measured by single photon absorption) and age; sex; serum concentrations of parathyroid hormone and ionised calcium; serum alkaline phosphatase activity; and serum concentration of calcium, phosphate, creatinine, urea, osteocalcin, 25 hydroxycholecalciferol, and 1,25 dihydroxycholecalciferol. RESULTS--There was no difference in bone density between men and women. There was no correlation between bone density and severity of hypercalcaemia or age. No biochemical abnormality was peculiar to the seven patients whose bone density was more than two SD below the population mean. Serum concentrations of 1,25 dihydroxycholecalciferol and osteocalcin both correlated significantly with bone density (p < 0.05) and there was a strong correlation between serum osteocalcin and serum intact parathyroid hormone (p < 0.001). Serum osteocalcin had the strongest correlation with bone density of any of the biochemical variables. CONCLUSION--There is little association between bone density and serum concentration of parathyroid hormone.     

Hypovitaminosis D in a sunny country: relation to lifestyle and bone markers.

Hypovitaminosis D is associated with poor dietary intake and inadequate sunshine exposure. It is common worldwide, particularly in European elderly people. Information about vitamin D status in young adult populations from the Middle East is scarce. Furthermore, the relationship between hypovitaminosis D and some lifestyle factors such as style of clothing and dwelling location is not well defined. We assessed vitamin D intake and measured serum calcium, phosphorus, albumin, alkaline phosphatase, 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), osteocalcin, and urinary-free deoxypyridinoline (DPD) in 316 Lebanese volunteers (99 men and 217 women) aged 30-50 years; 156 were recruited from rural areas and 160 from urban areas. Fifty-one women from each area were veiled. The average daily vitamin D intake was 100.3 +/- 67.9 IU and was found to be higher in men compared with women, in urban subjects compared with rural ones and in nonveiled women compared with veiled ones. The mean level of 25(OH)D was 9.71 +/- 7.07 ng/ml. Hypovitaminosis D [25(OH)D < 12 ng/ml] affected 72.8% of our population. It was more common in women than in men (83.9% vs. 48.5%). Severe hypovitaminosis D [25(OH)D < 5 ng/ml] was observed in 30.7% of our subjects and was more prevalent in women (41.5%), particularly in the veiled ones (61.8%). 25(OH)D levels were the lowest in veiled women, and in women living in rural areas. Rural men had the highest 25(OH)D levels despite their very low vitamin D intake. In a multivariate model, inadequate vitamin D intake, urban dwelling, veil wearing, and high parity in women were independent predictors of hypovitaminosis D. 25(OH)D was related inversely to PTH and free DPD whereas osteocalcin achieved only a weak positive correlation with 25(OH)D. In the absence of information regarding time spent outdoors, our results show that hypovitaminosis D is common among young Lebanese people and is related mostly to low vitamin D intake. This should emphasize the need for more vitamin D in our population.