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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

If hypertension in patients with diabetes mellitus type II is not adequately controlled by angiotensin-converting enzyme inhibitors (ACE-i), a beta-blocker is frequently added as second-line therapy. Recently, large randomized trials demonstrated the beneficial effect of second-generation dihydropyridine calcium-channel blockers in these patients. These compounds are increasingly being used to replace beta-blockers. Withdrawal of beta-blockers may influence diabetic control and may cause rebound hypertension. Any rebound hypertension from beta-blocker withdrawal may not occur if the beta-blocker is replaced with a calcium-channel blocker. A calcium-channel blocker will influence vascular resistance (VR) and blood pressure differently than a beta-blocker. Thirty-four patients with diabetes mellitus type II and a resting diastolic blood pressure above 90 mm Hg despite enalapril 10 mg daily (or equipotent dosages of other ACE-i) for at least 3 months were treated in an open label sequential comparison with the same ACE-i in combination with the beta-blocker metoprolol 100 mg for 3 months, and, subsequently for 3 more months with the same ACE-i in combination with the dihydropyridine calcium-channel blocker lercanidipine 10 mg once daily. After 6 weeks, patients with a diastolic blood pressure above 90 mm Hg were titrated up to 200 mg metoprolol or 20 mg lercanidipine once daily. Patients were examined every 6 weeks during the trial, and after 2 weeks while receiving lercanidipine. In addition to blood pressure measurements, VR was measured by iridium strain gauge plethysmography and expressed in units (1 unit = 1 mm Hg/mL blood/100 mL tissue per minute). Two of 34 patients did not complete the protocol because of non-compliance with the lercanidipine treatment in the first 2 weeks of treatment. Their data are included in the analysis. No rebound hypertension 14 days after the change-over of therapies was observed. (Mean arterial pressures [MAPs] were not significantly different from the point of withdrawal of the beta-blockers.) However, heart rate rose from 69+/-7 to 94+/-10 beats/min (p < 0.001). After 3 months on lercanidipine, MAP fell by 6+/-10 mm Hg (p = 0.002) compared to the point of withdrawal of the beta-blocker. Vascular resistance fell by 6.28+/-11.91 units (p<0.01), while glucosylated hemoglobin (HbA1c) rose by 0.4+/-0.5% (p<0.001) and body weight rose by 0.6+/-0.6 kg (p < 0.01). Multiple regression analysis revealed significant associations between decrease in VR, increase in HbAlc, and decrease in MAP, and partial dependence of these variables on one another. In hypertensive patients with diabetes type II, replacement of ACE-i and metoprolol with ACE-i and lercanidipine does not appreciably influence metabolic control and does not cause rebound hypertension. Lercanidipine was more effective than metoprolol as a second-line antihypertensive drug in these patients. At least two mechanisms may be involved: withdrawal of a pressor effect from the beta-blocker, and calcium-channel-mediated vasodilation.
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PMID:Diabetics with hypertension not controlled with ACE inhibitors: alternate therapies. 1151 86

Insulin induces a broad spectrum of effects over a wide time interval. It also stimulates the phosphorylation of some cellular proteins, while decreasing the state of phosphorylation of others. These observations indicate the presence of different, but not necessarily mutually exclusive, pathways of insulin action. One well-known pathway represents a phosphorylation cascade initiated by the tyrosine kinase activity of the insulin receptor followed by involvement of different MAP-kinases. Another pathway suggests the existence of low molecular weight insulin mediators whose synthesis and/or release is initiated by insulin. Comparable analysis of two kinds of insulin mediators, namely inositolphosphoglycans and prostaglandylinositol cyclic phosphate (cPIP), has been carried out. It has been shown that the expression of a number of enzymes, such as phospholipase A(2), phospholipase C, cyclo-oxygenase and IRS-1-like enzyme, could regulate the biosynthesis of cPIP in both normal and diabetes-related conditions. Data on the activity of a key enzyme of cPIP biosynthesis termed cPIP synthase (IRS-1-like enzyme) in various monkey tissues before and twice during an euglycemic hyperinsulinemic clamp have been presented. It has been concluded that in vivo insulin increases cPIP synthase activity in both liver and subcutaneous adipose tissue of lean normal monkeys. It has been also suggested that abnormal production of cPIP could be related to several pathologies including glucocorticoid-induced insulin resistance and diabetic embryopathy. Further studies on cPIP and other types of insulin mediators are necessary to aid our understanding of insulin action.
Diabetes Metab Res Rev
PMID:Prostaglandylinositol cyclic phosphate (cPIP): a novel second messenger of insulin action. Comparative analysis of two kinds of "insulin mediators". 1154 11

RAGE (receptor for advanced glycation end products) is a multiligand cell surface molecule of the immunoglobulin superfamily. It was originally described as a receptor for protein adducts formed by glycoxidation (AGEs) that accumulate in diseases such as diabetes and renal failure. Performing RT-PCR and Western blot analysis we intended to determine RAGE expression in the human colon adenocarcinoma cell line Caco-2. Moreover, Caco-2 cells were incubated in the presence of AGEs. Since RAGE ligation triggers the p21(ras) signal transduction pathway the activation state of p44/42 (ERK1/2) MAP kinases was determined. Here we demonstrate for the first time that Caco-2 cells express RAGE and that administration of the food-derived casein-linked AGE N(epsilon)-(carboxymethyl)lysine (Cas-CML) results in Caco-2 p44/42 (ERK1/2) MAP kinase activation.
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PMID:RAGE expression and AGE-induced MAP kinase activation in Caco-2 cells. 1170 25

Hyperinsulinemia has been shown to be associated with diabetic angiopathy. Migration and proliferation of vascular smooth muscle cells (VSMC) are the processes required for the development of atherosclerosis. In this study, we attempted to determine whether insulin affects mitogenic signaling induced by platelet-derived growth factor (PDGF) in a rat VSMC cell line (A10 cells). PDGF stimulated DNA synthesis which was totally dependent on Ras, because transfection of dominant negative Ras resulted in complete loss of PDGF-stimulated DNA synthesis. Initiation of DNA synthesis was preceded by activation of Raf-1, MEK and MAP kinases (Erk 1 and Erk2). Treatment of the cells with PD98059, an inhibitor of MAPK kinase (MEK) attenuated but did not abolish PDGF-stimulated DNA synthesis, suggesting that MAPK is required but not essential for DNA synthesis. PDGF also stimulated phosphorylation of protein kinase B (Akt/PKB) and p70 S6Kinase (p70S6K) in a wortmannin-sensitive manner. Rapamycin, an inhibitor of p70S6K, markedly suppressed DNA synthesis. Low concentrations of insulin (1-10 nmol/l) alone showed little mitogenic activity and no significant effect on MAPK activity. However, the presence of insulin enhanced both DNA synthesis and MAPK activation by PDGF. The enhancing effect of insulin was not seen in cells treated with PD98059. Insulin was without effect on PDGF-stimulated activations of protein kinase B (Akt/PKB) and p70S6K. We conclude that insulin, at pathophysiologically relevant concentrations, potentiates the PDGF-stimulated DNA synthesis, at least in part, by potentiating activation of the MAPK cascade. These results are consistent with the notion that hyperinsulinemia is a risk factor for the development of atherosclerosis.
Int J Exp Diabetes Res
PMID:Potentiation of mitogenic activity of platelet-derived growth factor by physiological concentrations of insulin via the MAP kinase cascade in rat A10 vascular smooth muscle cells. 1199 Nov 99

The aim of our in vitro experiments was to study the effects of EGF on rabbit ovarian cells, as well as the possible mechanisms of these effects. The influence of EGF on steroidogenesis, proliferation, cyclic nucleotides and MAP-kinase in rabbit granulosa cells were studied. Results of RIA showed, that EGF stimulated the release of progesterone (1-100 ng/ml), cAMP (at 100 ng/ml), cGMP (1-100 ng/ml). EGF effect on estradiol output was biphasic: at dose 1 ng/ml it inhibited, whilst at 100 ng/ml it strongly increased estradiol secretion. Immunocytochemical study demonstrated an EGF-induced (10 ng/ml) increase in the proportion of cells revealing proliferating cell nuclear antigen (41% vs 24.7% in control, p < 0.01). EGF (10 ng/ml) increased the proportion of cells with immunoreactivity to ERK-1 (more than two-fold) and ERK-3 (three-fold) members of the MAP-kinase family. Moreover, EGF induced the translocation of ERK-1 to the nucleus, whilst preferentially cytoplasmic localization of ERK-3 was not changed after EGF addition. This can indicate regulation of ERK-1 and -3 by EGF, as well as differential patterns of ERK-1 and ERK-3 expression in response to EGF in cultured granulosa cells. - These results indicate that EGF can be a stimulator of proliferation, steroidogenesis and cyclic nucleotide release by rabbit granulosa cells. Stimulation of cAMP and cGMP release, and activation of ERK-related MAP kinase in granulosa cells after EGF addition indicates the involvement of these intracellular messengers in mediating the EGF action on the ovary.
Exp Clin Endocrinol Diabetes 2002 May
PMID:Effect of epidermal growth factor (EGF) on steroid and cyclic nucleotide secretion, proliferation and ERK-related MAP-kinase in cultured rabbit granulosa cells. 1201 72

Couples in the Philippines are free to choose the family planning method that best satisfies their health needs and religious beliefs. All service delivery outlets of the Philippines Department of Health and participating agencies should have all approved, safe, effective, and legal family planning methods available. Oral contraceptives (OCs), IUDs, tubal ligation, and vasectomy are at least 92% effective. OCs protect against pelvic infection and reduce the risk of ovarian and uterine cancer. Older OC users who smoke face an increased risk of blood clotting, stroke, and heart attack. The progestogen-only pill is the best OC for lactating women. The IUD can be effective for 6 years assuming no pain or other side effects. Breast feeding mothers can use the IUD safely. IUD contraindications are anemia, active cervical or pelvic infection, abnormal vaginal bleeding, and genital cancer. Condoms protect against pregnancy as well as sexually transmitted diseases, including HIV/AIDS. When practiced correctly, natural family planning methods are 70-90% effective. They are the cervical mucus method, basal body temperature method, sympto-thermal method, and breast feeding. Norplant contraceptive implants are available to Philippine women on a trial basis. They release a progestin slowly into the blood stream, suppressing ovulation and thickening cervical mucus. The long-acting contraceptive injectables are DMPA, Cycloprovera, and HRP 102. Women must receive an injection every 3 months to protect against pregnancy. The first injection should occur within the first 5 days of the menstrual cycle. Women choosing tubal ligation and men choosing vasectomy should be sure in their decision because they are permanent methods and sterilization reversal procedures are rare in the Philippines. Men with diabetes, an infection at the incision site, clotting disorders, enlarged or painful testicles, and an inguinal hernia should not have a vasectomy.
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PMID:The family planning methods. 1217 21

The use of depo-medroxyprogesterone acetate (DMPA), or Depo Provera, has been debated for the 20 years since it became available in 1967. The US Food and Drug Administration (FDA) refused to approve Depo Provera on the basis that it caused breast tumors in a controlled study of Beagle dogs and Rhesus monkeys conducted by Upjohn, the manufacturer. Depo Provera has been approved in over 60 other countries and is in use in 30 or 40 others with an estimated total of almost 5 million users. A natural hormone, progesterone, DMPA is injected intramuscularly and absorbed slowly. Common dosage is 150 mg every 3 months and usually is administered during the 1st week of the menstrual cycle. The pregnancy rate with Depo Provera is .44 pregnancies/100 women years for women receiving 100 mg every 3 months. No pregnancies were recorded in recent studies for women receiving 150 mg. Possible side effects include amenorrhea, weight gain, dizziness and headaches. The median time for contraception after the presumed duration of one's last injection is 5-1/2 months. Some countries only permit women who already have 1 child to use Depo Provera. The FDA in the US approves the use of Depo Provera for treatment of endometrial and renal cancer but accuses it of causing cancer in Beagles and Rhesus monkeys. The studies were conducted over 7 and 10-year periods, respectively, with extremely negative results including the death of 3 dogs due to "drug-induced diabetes," atrophication of adrenal glands, and malignant tumors. There were similar results for the monkey study. In the UK, the Committee for Safety in Medicine supports Upjohn's view that Beagles are unsuitable for comparison testing because "all dogs are acutely sensitive to progesterone." Groups such as the National Women's Health Network, the institute for Food and Development Policy, and "Mother Jones" have used the media to generate opposition to Depo Provera, citing a double standard for rich and poor women, developed and less developed countries. The proponents of Depo Provera criticize health activists for imposing their own standards on women in developing countries. Regarding concerns about greater risk of Acquired Immune Deficiency Syndrome (AIDS), Depo Provera can be injected with disposable needles. In response to the controversy, Upjohn withdrew its application to the FDA in September 1986 but intends to resubmit with new information from a World Health Organization report, which showed no evidence of an increased risk of cancers of the endometrium, liver, or breast.
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PMID:Depo Provera: still controversial. 1217 73

This article consists of 5 case reports of women who developed abnormal glucose tolerance, glycosemia and/or glucosuria while taking oral contraceptives, and a review of the literature on diabetogenic effects of 3 estrogen and 7 progestagens commonly used as contraceptives, as well as predisposing factors for this disorder. The 5 women all improved after stopping pills. There are reports that diethylstilbestrol decreases glucose tolerance, that ethinyl estradiol augments insulinemia and decreases iv glucose uptake. 2 studies reported that mestranol decreased glucose tolerance in 50 and 57% of women. Mestranol has been said to have no diabetogenic effects when given as a combined pill, and to ameliorate maturity-onset diabetes. Progesterone, the 19-nor-testosterone derivatives norethisterone and norethisterone enanthate, and ethynodiol diacetate have no effect. 17-alpha-hydroxy-progesterone caproate, medroxyprogesterone acetate and chlormadinone have received contradictory reports. Megestrol acetate has been been known to normalize diabetic symptoms. Family history of diabetes or glycosuria of pregnancy, large infants or stillbirths predispose to diabetes during oral contraception, but age, weight parity and duration of oral contraception have received contradictory reports. Diabetes developing during oral contraception is usually reversible.
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PMID:[Diabetogenic effect of contraceptives]. 1225 61

Effects of oral contraception (OC) on glucose tolerance is well known; it is unclear, however, whether there can be increased risks of diabetes during and after treatment. Progesterone and, especially, testosterone, seems to be responsible for most glucose metabolic effects, which are usually reversible. Action of OC on lipid metabolism causes hyperlipemia and sensible variations in plasma cholesterol. Modifications of coagulation factors, also caused by OC, can lead to thrombotic accidents; these modifications, however, are all reversible with proper treatment. Other side effects from OC are hepatic dysfunctions, although rare, and increased teratogenic risk in predisposed people.
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PMID:[Metabolic side effects and contraindications of oral contraceptives]. 1226 68

The author describes a range of contraceptive methods, and their side effects, which may be acceptable for new parents. The methods are the oral contraceptive pill, Norplant, Depo-Provera, and intrauterine devices (IUD). Natural methods and permanent contraception are options described in insets. The author notes that differences in the effectiveness rates among available types of oral contraceptive pills are small enough not to merit consideration when deciding which kind of pill may be appropriate. Combination birth control pills are taken daily at the same time for 21 out of 28 days. Combination pills are not recommended for women with a history of hypertension or other cardiovascular diseases, thrombophlebitis, migraine headaches, diabetes, active gallbladder disease, or mononucleosis. Any hormonal method may be particularly risky for smokers over age 35. The mini-pill, containing a smaller amount of progesterone and no estrogen, is taken every day and is also on a 28-day cycle. Containing no estrogen, the mini-pill is often recommended for women who are nursing, who are over age 35, or who suffer from hypertension or migraines. Both adverse and positive side effects may be experienced from use. Norplant is the brand name of a contraceptive system which releases progesterone from under the skin of a woman's upper arm over the course of a five-year period. The system has a theoretical effectiveness rate of more than 99%, although the duration of effectiveness may be less than five years in overweight women. The most common side effect is irregular bleeding, and removal is often a longer and more difficult procedure than insertion. The most commonly used injectable hormonal contraceptive is Depo-Provera, a progesterone solution which works for up to three months. The majority of users experience some side effects. Finally, IUDs are highly effective and need to be replaced only every 1-10 years depending upon how they are made. Women typically experience discomfort during IUD insertion, and they should not be used by women under age 20 years, who have never had children, or who have ever had a pelvic infection.
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PMID:Birth control for new parents. 1229 Aug 91


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