A 39-year-old Chinese man with hypertension being evaluated for elevated serum alkaline phosphatase (SAP) levels was found to have an incidental right adrenal mass. The radiological features were characteristic of a large adrenal myelolipoma. This mass was resected and the diagnosis confirmed pathologically. His blood pressure normalised after removal of the myelolipoma, suggesting that the frequently observed association between myelolipomas and hypertension may not be entirely coincidental. Persistent elevation of the SAP levels and the discovery of hypercalcaemia after surgery led to further investigations which confirmed primary hyperparathyroidism due to a parathyroid adenoma. The patient's serum biochemistry normalised after removal of the adenoma. The association of adrenal myelolipoma with primary hyperparathyroidism has been reported in the literature only once previously. Although unconfirmed by genetic studies this association may possibly represent an unusual variation of the multiple endocrine neoplasia type 1 syndrome.
Fu-Sheng Fang, Yan-Ping Gong, Chun-Lin Li, Jian Li, Hui Tian, Wei Huang, Liang-Chen Wang and Lin Li
We aimed to compare the effect of repaglinide and metformin monotherapy as an initial therapy in Chinese patients with newly diagnosed type 2 diabetes mellitus (T2DM).
Patients and methods
In this 15-week, open-labelled, parallel-controlled, randomised study, 60 Chinese drug-naive patients with newly diagnosed T2DM were randomised (2:1) to receive repaglinide or metformin monotherapy. Primary endpoint was change in HbA1c from baseline to the end of the trial. Secondary endpoints included changes in glycaemic variability, insulin sensitivity and β-cell function.
Patients in both repaglinide and metformin groups achieved significant reductions in HbA1c (−1.8±1.5 vs −1.6±1.5%), FPG (fasting blood glucose) (−1.7±1.7 vs −2.1±1.7 mmol/l) and 2-h PPG (post-prandial glucose) (−3.8±3.1 vs −3.8±3.6 mmol/l), with no statistical differences between the groups. Glycaemic variability, glucose infusion rate and β-cell function were all significantly improved from baseline in the two groups (all P<0.05), without any statistical differences in the improvement between the groups.
Repaglinide and metformin achieved comparable efficacy in improving glycaemic control, reducing glycaemic variability, enhancing insulin sensitivity and ameliorating β-cell function. Therefore, repaglinide is an optional agent for initial therapy in Chinese patients with newly diagnosed T2DM.
Jameel Iqbal, Li Sun and Mone Zaidi
Bone loss due to menopause, natural or artificial, has been attributed solely to low estrogen. However, in a woman's life, the most precipitous bone loss begins 2 years prior to the last menstrual period, during which time estrogen levels are unperturbed whereas FSH is elevated. Our cell-based and mouse genetic studies have shown that FSH stimulates bone resorption by osteoclasts directly in a pituitary–bone axis, independently of the estrogen effect. On the basis of this and evolving clinical and scientific evidence, we propose that elevated FSH contributes to bone loss across the menopausal transition, particularly during late perimenopause. In the current issue of the European Journal of Endocrinology, Rendina et al. strengthen the view for a primary role of FSH signaling in the regulation of bone mass and bone remodeling in humans by demonstrating that an ‘activating’ polymorphism AA rs6166 causes low bone mass and high bone turnover.
GN Shah, J Li and AD Mooradian
The technique of reverse transcriptase-polymerase chain reaction differential display was used to identify thyroid hormone (TH) responsive mRNAs in the adult rat cerebral tissue. A partial cDNA (0.76 kb) was cloned and sequenced. Comparison of the sequence to the GenBank data base showed almost 100% homology to mouse translational repressor (NAT-1) mRNA 3'-end. In a northern blot analysis this cDNA hybridized with a mRNA whose expression in hyperthyroid rat cerebral tissue was approximately 6-fold higher than in euthyroid rats. The time course studies showed a rapid induction of this mRNA within 3 h following thyroxine administration. This mRNA is widely expressed in various tissues, and in hepatic tissue it is also TH responsive. To determine if TH responsiveness of this mRNA persists during aging, 25-month-old aged rats were studied and the results were compared with those of 4-month-old rats. Unlike young mature rats, the TH responsiveness of NAT-1 mRNA in both the cerebral and hepatic tissue of aged rats was blunted. It is concluded that cerebral tissue in aging rats beyond the developmental stages, like the hepatic tissue, is associated with altered TH responsiveness.
SN De Biasi, LI Apfelbaum and ME Apfelbaum
OBJECTIVE: The purpose of this work was to study the direct effect of leptin on LH release by anterior pituitary glands from female rats at the time of spontaneous and steroid-induced LH surge. METHODS: LH responsiveness to leptin by pituitaries from rats killed in the afternoon (1500 h) at different stages of the 4-day estrous cycle (diestrus-1: D1; diestrus-2: D2; proestrus; estrus), ovariectomized (OVX; 15 days post-castration) and ovariectomized steroid-primed (OVX-E(2)/Pg; pretreated with 5 microg estradiol and 1 mg progesterone), was evaluated in vitro. Hemi-adenohypophyses were incubated in the presence of synthetic murine leptin for 3 h. RESULTS: Addition of increasing concentrations of leptin (0.1-100 nmol/l) to the incubation medium of proestrus pituitaries produced a dose-related stimulation of LH release; the maximal increase to 315% of control was obtained with 10 nmol/l leptin. Leptin (10 nmol/l) enhanced LH release at all days of the estrous cycle, the greatest response occurring in proestrus (318%) and the lowest at D1 (123%). In order to evaluate the role of nitric oxide (NO) in the action of leptin on LH release, glands from proestrus rats were incubated in the presence of 10 nmol/l leptin with or without 0.3 mmol/l N(G)-monomethyl-l-arginine (NMMA), a competitive inhibitor of NO synthase (NOS). NMMA completely suppressed the stimulation of LH release induced by leptin. Leptin also stimulated LH release by pituitaries from OVX rats, and treatment with steroid hormones led to a marked increase in the response (OVX: 162% compared with OVX-E(2)/Pg: 263%; P<0.05). For comparative analysis, a similar experimental procedure was carried out using GnRH (10 nmol/l). Leptin acts at the pituitary level in a similar manner as GnRH, although with significantly lower potency. CONCLUSIONS: These results confirm and extend previous reports regarding a direct action of leptin at the pituitary level, stimulating LH release by anterior pituitaries from female rats at the time of spontaneous and steroid-induced LH surge. In the female rat pituitary this leptin action is controlled by gonadal steroids and mediated by NO.
Ke Li, Ling Li, Mengliu Yang, Hua Liu, Dongfang Liu, Hao Yang, Guenther Boden and Gangyi Yang
To investigate the effects of short-term continuous subcutaneous insulin infusion (CSII) on plasma vaspin levels in patients with newly diagnosed type 2 diabetes mellitus (T2DM).
Thirty patients with severe newly diagnosed T2DM, 37 subjects with impaired glucose tolerance (IGT) and 38 gender-, age- and body mass index (BMI)-matched normal GT (NGT) controls participated in the study. The T2DM group was treated with CSII for 2 weeks. Euglycemic–hyperinsulinemic clamps were performed in 16 subjects of the T2DM group. Plasma vaspin concentrations were measured with a commercial ELISA kit. The relationship between plasma vaspin levels and metabolic parameters was also analyzed.
Fasting plasma vaspin levels were higher in the T2DM group than in IGT and NGT groups (1.83±0.55 vs 0.51±0.21 vs 0.53±0.24 μg/l, P<0.05), but there was no difference between IGT and NGT groups. In T2DM patients, fasting plasma vaspin concentrations were significantly decreased after CSII treatment for 2 weeks (1.83±0.55 vs 1.19±0.57 μg/l, P<0.05), accompanied by significant amelioration of insulin sensitivity and glucose control. The changes in plasma vaspin levels were positively associated with the amelioration of insulin resistance (IR) shown by the changes in homeostasis model assessment of IR.
Plasma vaspin level is associated with IR and is significantly reduced following short-term CSII treatment.
Huibin Huang, Xisheng Li, Ling Lin, Yaxiong Shi, Xiahong Lin, Liangyi Li and Dongming Xu
An increase in the expression of autoantigens and their presenting molecules human leukocyte antigen (HLA) class I has been demonstrated to be responsible for autoimmune diseases. Thyroid transcription factor-1 (TTF-1 or NKX2-1) synchronously upregulates both HLA class I and thyroid-specific autoantigen, which may be involved in the pathological process of autoimmune thyroiditis. In this study, the expressions and potential role of TTF-1 and HLA class I in Hashimoto's disease (HT) were examined.
In this study, 22 resection specimens clinically and histopathologically confirmed to have Hashimoto's disease and 30 normal thyroid specimens from adjacent tissues of thyroid adenoma were used.
Western blot, real-time PCR, and immunohistochemistry were performed to assay TTF-1 and HLA class I in the thyrocytes of Hashimoto's disease as well as in the normal thyroid from adjacent tissues of thyroid adenoma.
The TTF-1 and HLA class I in Hashimoto's disease were significantly higher than those in the controls.
Upregulation of TTF-1 and HLA class I in Hashimoto's disease provide a clinical evidence for possible triggering of autoimmune reaction.
Ke Li, Ling Li, Mengliu Yang, Haihong Zong, Hua Liu and Gangyi Yang
Fibroblast growth factor-21 (FGF-21) has recently been characterized as a potent metabolic regulator, but its pathophysiologic roles in humans remain unknown. This study aimed to investigate the effects of rosiglitazone on plasma FGF-21 levels in patients with type 2 diabetes mellitus (T2DM).
Design and methods
Thirty patients with new-onset T2DM (nT2DM), 34 type 2 diabetic patients with poor glycemic control (pT2DM) after the treatment with single hypoglycemic agent metformin, and 30 sex- and age-matched normal glycaemic controls (NGT) participated in the study. The pT2DM group was treated with rosiglitazone for 12 weeks. Plasma FGF-21 levels were measured with a RIA. The relationship between plasma FGF-21 levels and metabolic parameters was also analyzed.
Fasting plasma FGF-21 levels were higher in nT2DM and pT2DM groups than in the control (1.81±0.64 vs 1.87±0.63 vs 1.52±0.61 μg/l, P<0.05), but there was no difference between nT2DM and pT2DM groups. Fasting plasma FGF-21 levels were decreased significantly in pT2DM group after the treatment with rosiglitazone compared with pre-treatment (1.59±0.63 vs 1.87±0.64 μ/l, P<0.05). In all diabetic patients, multiple regression analysis showed that HbA1c, fasting insulin, and homeostasis model assessment-insulin resistance index were independently associated with plasma FGF-21 levels.
In pT2DM patients, plasma FGF-21 levels are increased, but significantly decreased after the treatment with rosiglitazone on top of ongoing metformin therapy. These data suggest that rosiglitazone may play a role in lowering FGF-21 levels in T2DM patients.
Weibin Zhou, Yanyun Gu, Hong Li and Min Luo
Objective: To assess the cutoff values at different time points for impaired glucose regulation (IGR) and diabetes, the glucose curve and isolated 1-h hyperglycemia were monitored during an oral glucose tolerance test (OGTT).
Methods: Two thousand eight hundred and eighty-six subjects (1300 men and 1586 women) were recruited to have an OGTT. Plasma was collected at 0, 30, 60, 120, and 180 min to analyze glucose and insulin. The diagnosis of impaired fasting glucose, impaired glucose tolerance, and diabetes was based on World Health Organization and American Diabetes Association’s criteria. Those with fasting plasma glucose (FPG)<5.6 and 2-h plasma glucose (PG)<7.8, but 1-h PG≥7.8 and <11.1 mmol/l were defined as 1h-High7.8, and those with FPG<7.0 and 2-h PG<11.1, but 1-h PG≥11.1 mmol/l as 1h-High11.1. The cutoff values were calculated by receiver operating characteristic (ROC) curve. The correlation between β-cell function and the area under the curve of glucose (AUCg) and the shape index was analyzed with linear regression.
Results: The cutoff values for IGR were 5.6, 9.7, 10.1, 7.8 and 6.1 mmol/l for blood glucose at 0, 30, 60, 120 and 180 min, 24 for AUCg and 1.3 mmol/l for the shape index. The cutoff values for diabetes were 6.8, 11.2, 13, 11.1 and 7 mmol/l for 0, 30, 60, 120 and 180 min, 30.9 for AUCg and 2 mmol/l for the shape index. Both AUCg and the shape index were inversely related to β-cell function. The profiles of glucose and insulin in the subgroup with isolated 1-h hyperglycemia were very different from those seen in subjects with normal glucose tolerance or IGR.
Conclusions: The present study provides new information on measures other than the fasting and 2-h PG to evaluate glucose metabolism in vivo and stimulates further research aimed at assessing the value of the OGTT 1-h PG concentration prospectively.
Dandong Wu, Ling Li, Mengliu Yang, Hua Liu and Gangyi Yang
Secreted protein acidic and rich in cysteine (SPARC) also known as BM-40 which has been studied in various pathological conditions, has recently been suggested as a key player in the pathology of obesity and type 2 diabetes mellitus (T2DM). However, there are few studies on putative pathophysiologic roles of SPARC in glucose metabolism. The aim of this study was to determine whether plasma SPARC concentrations were altered in subjects with different glucose metabolic conditions and to investigate the affecting factors.
Design and methods
In this study, 54 newly diagnosed T2DM subjects, 53 subjects with impaired glucose regulation (IGR), and 53 normal subjects (body mass index (BMI): 24.98±3.75 vs 24.70±2.78 and 24.53±3.66 kg/m2, P>0.05) were enrolled. Plasma SPARC levels were measured with an ELISA under overnight fasting conditions. The relationships between plasma SPARC and several metabolic factors, such as BMI, blood lipids, blood glucose, plasma insulin levels, and other factors were also assessed.
SPARC levels were higher in subjects with T2DM compared with IGR and control subjects (16.74±6.99 vs 14.04±8.03 μg/l, P<0.05 and 16.74±6.99 vs 11.72±4.47 μg/l, P<0.01). However, there was no difference in plasma SPARC levels between IGR subjects and the controls. Plasma SPARC levels correlated positively with BMI, the percentage of fat, triglyceride, fasting plasma insulin, 2 h plasma insulin after a glucose load, and the homeostasis model assessment of insulin resistance in simple regression analysis.
The present work indicates a potential link between SPARC and the pathogenesis of T2DM.