Autocrine/paracrine action of pituitary vasoactive intestinal peptide on lactotroph hyperplasia induced by estrogen.

Vasoactive intestinal polypeptide (VIP) content is increased in the hyperplastic pituitaries of estrogen (E)-treated rats, thus suggesting that this neuropeptide could mediate the E effect on lactotrophs. E also decreases pituitary TGF-beta1 content, an autocrine/paracrine inhibitor of lactotroph proliferation, and induces pituitary angiogenesis. To elucidate the role of VIP in this context, lactotroph hyperplasia was induced in female Fisher 344 rats by implanting sc pellets of diethylstilbestrol (DES). Twenty-five days later, the rats were treated with three different increasing doses of a VIP receptor antagonist or the vehicle for 5 d. DES treatment resulted in a marked increase of serum prolactin (PRL), pituitary PRL content, PRL mRNA expression, pituitary weight, and pituitary proliferating cell nuclear antigen. DES treatment also increased pituitary VIP content and VIP mRNA levels, but not in the hypothalamus and cerebral cortex. Simultaneously, DES treatment decreased the pituitary TGF-beta1 content and increased the pituitary content of vascular endothelial growth factor. VIP receptor antagonist partially reverted the effect of DES on serum PRL and pituitary PRL, proliferating cell nuclear antigen, TGF-beta1, and vascular endothelial growth factor contents, as well as on pituitary weight, in a dose-dependent relation. These data suggest that pituitary VIP mediates the effect of E on lactotroph hyperplasia, pituitary TGF-beta1, and angiogenesis.

Metabolic control and chronic complications during a 3-year follow-up period in a cohort of type 2 diabetic patients attended in primary care in the Community of Madrid (Spain).

BACKGROUND: Our aim was to analyze both metabolic control and chronic complications of type 2 diabetes mellitus (T2D) patients regularly attended in primary care during a 3 years of follow-up in the Community of Madrid (Spain). METHODS: From 2007 to 2010 we prospectively included 3268 patients with T2D attended by 153 primary care physicians from 51 family health centers. An prospective cohort study with annual evaluation over 3 years to the same population was performed. We measured the goals of control in diabetic patients and the incidence of chronic complications of diabetes during the study period. RESULTS: A significant decrease in serum glucose levels (143±42mg/dl vs 137±43mg/dl, p<0.00), HbA1c (7.09±1.2% vs 7.02±1.2%, p<0.00), total cholesterol (191.4±38mg/dl vs 181.5±36mg/dl, p<0.00), LDL cholesterol (114.7±31mg/dl vs 105.5±30mg/dl, p<0.00) and triglyceride levels (144.5±93mg/dl vs 138±84mg/dl, p<0.00) during study period was documented. On the contrary, a significant elevation in HDL cholesterol levels was observed (49.2±14mg/dl vs 49.9±16mg/dl, p<0.00). The incidence of diabetic complications throughout the study period was low, with a incidence of coronary heart disease of 6.2%, peripheral arterial disease 3%, ischemic stroke 2.8%, diabetic foot 11.2%, nephropathy 5.9%, retinopathy 4.5%, and neuropathy 3%. CONCLUSION: Metabolic control in T2D patients attended in primary care in the Community of Madrid throughout 3 years is adequate and is accompanied by low percent of chronic diabetic complications during this period of follow-up.

Phase IV prospective clinical study to evaluate the effect of taurine on liver function in postsurgical adult patients requiring parenteral nutrition.

BACKGROUND: Taurine's role in bile acid metabolism and anti-inflammatory activity could exert a protective effect on hepatobiliary complications associated with parenteral nutrition (PN). In this study, the effects of 2 amino acid solutions, with and without taurine, on liver function administered to nonacutely ill postsurgical patients as part of a short-term PN regimen were prospectively compared. METHODS: Adult patients randomly received (double-blind) Tauramin 10% or a standard PN solution without taurine as the control (1.5 g amino acid/kg body weight [bw]/d; infusion rate of ≤4 mg glucose/kg bw/d) for a period of 5-30 days. γ-Glutamyl transpeptidase (GGT) and other indicators of liver function, glucose metabolism, lipid profile, inflammation markers, and treatment safety data were collected. RESULTS: Thirty-five patients receiving taurine PN and 39 receiving control PN were enrolled (intention-to-treat [ITT] population). Most patients (n = 62) discontinued after day 7 of follow-up (per-protocol [PP] population: n = 24 and n = 27, respectively). ITT patients with high GGT values after 5 days of PN comprised 68.6% and 64.1%, respectively. The mean change in GGT values with respect to the baseline values was 167 ± 192 and 157 ± 185 IU/L, respectively. Low-density lipoprotein (LDL) cholesterol levels after 7 days of PN were significantly decreased in the taurine PN group of PP patients (-2.83 ± 30.9 vs 23.9 ± 27.0 mg/dL for control PN; P < .05). None of the adverse events reported (taurine PN: n = 6; control PN: n = 7) were treatment related. CONCLUSION: PN solutions with and without taurine had similar effects on liver function parameters, except for an LDL reduction in PN with taurine, when administered to nonacutely ill postsurgical patients in the short term (5-7 days).

Estimation of the economic and health impact of complications of type 2 diabetes mellitus in the autonomous community of Madrid (Spain).

OBJECTIVE: To estimate the economic and health impact of chronic complications (macrovascular and microvascular) of type 2 diabetes mellitus (T2DM) in the autonomous community of Madrid (Spain) (ACM). METHODS: The number of expected complications was obtained from a descriptive, cross-sectional study on a cohort of 3,268 patients with T2DM from the ACM. Cost of complications (€, 2012) was assessed both at hospitals and in primary care. The number of medical visits in primary care and drug treatment for complications were collected by a panel of 21 physicians experienced in treatment of T2DM. Population and epidemiological data and healthcare costs were obtained from Spanish sources. Univariate sensitivity analyses were performed. RESULTS: It is estimated that there are 390,944 patients with T2DM in the ACM, and that they experience 172,406 and 212,283 macrovascular and microvascular complications respectively during their lifetimes. Mean cost of T2DM complications per patient is estimated at € 4,121.54 (66% due to macrovascular complications). The economic impact of T2DM complications in the ACM would be € 1,611 million (1,065 and 545 millions from macrovascular and microvascular complications respectively). The economic impact would range from € 1,249 and 2.509 million euro depending on T2DM prevalence. CONCLUSIONS: Complications of T2DM have a great health and economic impact in ACM.

Insulin action in adipose tissue in type 1 diabetes.

BACKGROUND: Insulin action has been reported to be normal in type 1 diabetic patients. However, some studies have reported an insulin resistance state in these patients. The aim of this study was to investigate insulin resistance in a group of type 1 diabetic patients. We studied the insulin action in adipose tissue and analyzed the effects of duration of disease, body mass index (BMI), and glycosylated hemoglobin on insulin action at the receptor and postreceptor levels in adipocytes. METHODS: Nine female type 1 diabetic patients with different durations of disease and eight nondiabetic female patients of comparable age and BMI were studied. (125)I-insulin binding and U-[(14)C]-D-glucose transport was measured in a sample of subcutaneous gluteus adipose tissue obtained by open surgical biopsy from each subject. RESULTS: The duration of disease was negatively correlated with both (125)I-insulin binding capacity (r = -0.70, P < 0.05) and basal and maximum insulin-stimulated glucose transport (r = -0.87, P < 0.01, and r = -0.88, P < 0.01, respectively). Maximum specific (125)I-insulin binding to the receptors in adipocytes was higher in the group of patients with a shorter duration of disease (P < 0.01). Basal and maximum insulin-stimulated glucose transport was significantly higher in the group with less than 5 years of disease (P < 0.01). No correlation was found between BMI and insulin action. CONCLUSION: Female type 1 diabetic patients have normal insulin action. There is a high glucose uptake in the early phase of the disease, although a longer duration of disease appears to be a contributing factor to a decrease in insulin action in these patients, and involving both receptor and postreceptor mechanisms.

Chronic increase of bone turnover markers after biliopancreatic diversion is related to secondary hyperparathyroidism and weight loss. Relation with bone mineral density.

BACKGROUND: Biliopancreatic diversion (BPD) is the most effective bariatric procedure. Around 70% of these patients have secondary hyperparathyroidism (SH) in the long term as a consequence of calcium and vitamin D malabsorption. This work was aimed to study the influence of SH on bone turnover and its relationship with bone mineral density (BMD). METHODS: Bone turnover markers were determined in 63 BPD patients and 34 morbidly obese controls. In the BPD group, we also studied the influence of age, loss of weight, common channel length, PTH, vitamin D, and serum calcium on bone turnover as well as its relation with BMD. RESULTS: BPD patients showed significantly higher PTH, osteocalcin, and beta-CTx levels than controls. In the multivariate regression analysis, only PTH (beta=0.42; P=0.0002), menopausal status (beta=0.31; P=0.007) and the percentage of lost BMI (beta=-0.24; P=0.03) significantly predicted the osteocalcin level (R2=0.33; F=9.56; P<0.0001). Similarly, only PTH (beta=0.39; P=0.0005), menopausal status (beta=0.37; P=0.001) and the percentage of lost BMI (beta=-0.23; P=0.04) significantly predicted the beta-CTx level (R2=0.33; F=9.82; P<0.0001). Osteocalcin and beta-CTx levels correlated negatively with BMD at lumbar spine (r=-0.38, P=0.002 and r=-0.30, P=0.02, respectively). CONCLUSIONS: Chronic SH and the loss of weight determine a high rate of bone turnover that is associated with decreasing BMD in BPD patients.

Implication of pituitary vasoactive intestinal peptide in dopaminergic inhibition of estrogen-induced pituitary hyperplasia and vascular endothelial growth factor expression.

We have shown that pituitary vasoactive intestinal peptide (VIP) mediates the effects of estrogen on lactotrope hyperplasia, angiogenesis and hyperprolactinemia, and reduces the pituitary content of transforming growth factor beta beta1 (TGF-beta1, an inhibitor of lactotrope proliferation). Dopamine agonists reverse lactotrope hyperplasia and hyperprolactinemia and also reduce the pituitary VIP content in hyperestrogenized rats. To elucidate the interaction of bromocriptine (BC) and pituitary VIP, a VIP receptor antagonist (VA), BC, or both drugs were administered for 5 days to F344 rats treated with diethylstilbestrol (DES). Both BC and VA similarly blocked the effects of DES on pituitary weight and pituitary content of prolactin (PRL), proliferating cell nuclear antigen, and vascular endothelial growth factor, without evidence of synergism. The estrogen effect on pituitary TGF-beta1 was completely inhibited by VA, but only partially by BC. On the contrary, serum PRL was close to the normal levels in the BC group 2 h after the first dose, while VA only reduced serum PRL after 5 days. DES increased VIP and VIP mRNA levels specifically at the pituitary, this effect being partially blocked by BC. These data suggest that the dopamine agonists inhibit lactotrope proliferation and angiogenesis by blocking the autocrine/paracrine action of VIP. On the other hand, the dopamine agonists inhibit the estrogen-induced hyperprolactinemia by acting through different pathways than those implicated in the proliferative process.