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

Prescribing contraceptives to diabetic women requires cognizance of metabolic effects and the risks of type I or type II and gestational diabetes mellitus (GDM) in prediabetic women. Studies have show that poor maternal glycemic control in the 1st trimester in diabetic women has resulted in a twofold to threefold increased risk for congenital malformations. A reduction from 6.6% to 1.1% in malformations could be realized by euglycemic control before conception and during the first 8 weeks of gestation. A low-estrogen preparation should be selected and blood pressure should be monitored regularly. Progestins adversely affect carbohydrate and lipid metabolism, as they decrease glucose tolerance by increased insulin resistance, thus the selection of proper progestin dose/potency is important in prescribing OCs. The lowest-dose OCs may be prescribed under close medical supervision to women with insulin-dependent diabetes mellitus (IDDM) without serious vascular complications. Patients should be evaluated after the 1st cycle of OC use and every 3-4 months thereafter with monitoring of weight, blood pressure, postprandial glucose, and glycosylated hemoglobin levels. Women with prior GDM should be evaluated annually utilizing a 2-hour, 75-g glucose tolerance test (OGTT) at the postpartum visit. For OCs, a low-dose estrogen ( 0.05 mg ethinyl estradiol) and a low-dose/potency progestin (or = 0.50 mg of norethindrone or or= 0.100 mg of levonorgestrel) should be selected. The safety of prescription of OCs to women with type II diabetes is unclear, but a supervised program similar to that of IDDM patients is recommended. Currently neither of the long-term contraceptives, depo-medroxy-progesterone acetate (Depo-Provera) injection or the levonorgestrel-containing implant, Norplant, are recommended as first-time methods for women with diabetes. On the other hand, the IUD is an effective, reversible method, particularly for older women with hypertension, provided antibiotic prophylaxis is undertaken at the time of insertion.
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PMID:Contraception in the diabetic woman. 822 75

Increased routing of glucose through the hexosamine-biosynthetic pathway has been implicated in the development of glucose-induced insulin resistance of glucose transport in cultured adipocytes. Because both glucosamine and glucose enter this pathway as glucosamine-6-phosphate, we examined the effects of preincubation with glucosamine in isolated rat diaphragms and in fibroblasts overexpressing the human insulin receptor (HIR-cells). In muscles, pre-exposure to glucosamine inhibited subsequent basal and, to a greater extent, insulin-stimulated glucose transport in a time- and dose-dependent manner and abolished the stimulation by insulin of glycogen synthesis. Insulin receptor number, activation of the insulin receptor tyrosine kinase in situ and after solubilization, and the total pool of glucose transporters (GLUT4) were unaffected, and glycogen synthase was activated by glucosamine pretreatment. In HIR-cells, which express GLUT1 and not GLUT4, basal and insulin-stimulated glucose transport were unaffected by glucosamine, but glycogen synthesis was markedly inhibited. Insulin-stimulated activation of protein kinases (MAP and S6) was unaffected, and the fractional velocity and apparent total activity of glycogen synthase was increased in glucosamine-treated HIR-cells. In pulse-labeling studies, addition of glucosamine during the chase prolonged processing of insulin proreceptors to receptors and altered the electrophoretic mobility of proreceptors and processed alpha-subunits, consistent with altered glycosylation. Glucosamine-induced insulin resistance of glucose transport appears to be restricted to GLUT4-expressing cells, i.e., skeletal muscle and adipocytes; it may reflect impaired translocation of GLUT4 to the plasmalemma. The glucosamine-induced imbalance in UDP sugars, i.e., increased UDP-N-acetylhexosamines and decreased UDP-glucose, may alter glycosylation of critical proteins and limit the flux of glucose into glycogen.
Diabetes 1993 Sep
PMID:Pre-exposure to glucosamine induces insulin resistance of glucose transport and glycogen synthesis in isolated rat skeletal muscles. Study of mechanisms in muscle and in rat-1 fibroblasts overexpressing the human insulin receptor. 834 45

The US Food and Drug Administration finally approved the injectable contraceptive Depo-Provera (DMPA) in October 1992, 25 years after its introduction. Women return to a health facility every 90 days for an intramuscular injection of 150 mg DMPA, which provides them 99% effective contraception. Menstrual changes and spotting are the leading reasons for DMPA discontinuation. Eventually, more than 50% of DMPA users develop amenorrhea. During the first year, women gain about 2 kg and weight increases as time passes. Weight gain is the second leading reason for DMPA discontinuation. DMPA may adversely affect glucose tolerance in women at risk for diabetes, but it does not affect cardiovascular or metabolic functions. It may increase the risk of osteoporosis. A rare side effect is convulsions. 1-10% of DMPA users have other central nervous system effects, such as headaches, dizziness, and depression. Itching and rashes may develop. Fertility returns within 1 year after discontinuation. DMPA is linked to low birth weight. It apparently does not harm breast-fed infants or hinder lactation. A World Health Organization study shows that DMPA users less than 35 years old experience a slight increase in breast cancer but a reduced incidence of endometrial cancer. Nurses are instrumental in guiding women as they choose DMPA and in informing them about its potential side effects, including breast cancer risk. They must screen women for pregnancy and evaluate their risk of breast cancer. They must determine whether women are able to return every 3 months for DMPA injections. Women who select DMPA must use other contraception, e.g., barrier protection, within the first 24 hours after initial injection. Nurses should counsel them about the likely menstrual changes to reduce the likelihood of dissatisfaction. They should recommend a daily dose of 1200 mg of elemental calcium and daily exercise of long bones to minimize the risk of developing osteoporosis.
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PMID:Depo-Provera. 849 47

Although an increased prevalence of hypertension is associated with insulin-dependent diabetes, little is known about the effect of streptozotocin (STZ) diabetes on arterial pressure (AP) regulation in rats. Changes in AP induced by STZ, as well as associated factors in blood pressure regulation such as baroreflex sensitivity, plasma renin activity (PRA), plasma glucose and insulin levels and endothelium participation, were studied in male Wistar rats weighing 287 +/- 10 g. The same seven conscious rats were used for all measurements before and after STZ diabetes. AP pulses were stored on a videotape recorder and processed by a data acquisition system. Baroreflex sensitivity was evaluated by measuring heart rate (HR) changes induced by AP variations produced by phenylephrine and sodium nitroprusside injection. The effect of inhibition of nitric oxide synthesis with NG-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg i.v. bolus plus infusion at 20 mg kg-1 h-1) on AP was evaluated in another set of rats (6 normal and 5 submitted to STZ treatment). STZ induced hyperglycemia (306 +/- 19 mg/dl), a reduction in mean arterial pressure (MAP, from 116 +/- 5 to 101 +/- 4 mmHg) and no changes in HR (320 +/- 10 vs 298 +/- 14 bpm). The tachycardic response to arterial pressure decreases was impaired (-2.29 +/- 0.5 vs -4.5 +/- 0.7 bpm/mmHg, in control) while the bradycardic response to arterial pressure increases was unchanged. Pressure responsiveness to phenylephrine was impaired after STZ (3.78 +/- 0.4 vs 6.73 +/- 0.8 mmHg microU-1 ml-1, in control).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Streptozotocin diabetes modifies arterial pressure and baroreflex sensitivity in rats. 852 May 49

In order to clarify the mechanisms of interaction between endothelin-1 (ET-1) and cyclic AMP (cAMP) or cyclic GMP (cGMP), we examined the effects of cAMP or cGMP on ET-1-induced activation of mitogen-activated protein kinase (MAPK), one of the key enzymes in the signal transduction of ET-1, in cultured rat mesangial cells. ET-1 was able to activate both p42 and p44 MAP kinases in a dose-dependent manner. Cell permeable analogues of cAMP and cGMP, dibutylyl cAMP (BT2-cAMP) and 8 bromo cGMP (8br-GMP), significantly inhibited ET-1-induced activation of MAPK. Atrial natriuretic peptide (ANP), which increased cellular cGMP, was able to inhibit ET-1-induced activation of MAPK in a dose-dependent manner, while c-ANP, an analogue specific to the clearance receptors of ANP, exerted no effect. These results indicate that cAMP and cGMP could modulate the action of ET-1 in mesangial cells at a step of the activation of MAPK.
J Diabetes Complications
PMID:Cyclic nucleotides attenuate endothelin-1-induced activation of mitogen-activated protein kinase in cultured rat mesangial cells. 857 39

In vivo vanadate and vanadyl have been shown to mimic the action of insulin and to be effective treatment for animal models of both Type I and Type II diabetes. The molecular mechanism of action of the vanadium salts on insulin sensitivity remains uncertain, and several potential sites proposed for the insulin-like effects are reviewed. In human trials, insulin sensitivity improved in patients with NIDDM, as well as in some patients with IDDM after two weeks of treatment with sodium metavanadate. This increase in insulin sensitivity was primarily due to an increase in non-oxidative glucose disposal, whereas oxidative glucose disposal and both basal and insulin stimulated suppression of hepatic glucose output (HGP) were unchanged. Clinically, oral vanadate was associated with a small decrease in insulin requirements in IDDM subjects. Of additional benefit, there was a decrease in total cholesterol levels in both IDDM and NIDDM subjects. Furthermore, there was an increase in the basal activities of MAP and S6 kinases to levels similar to the insulin-stimulated levels in controls, but there was little or no further stimulation with insulin was seen. Further understanding of the mechanism of vanadium action may ultimately be useful in the design of drugs that improve glucose tolerance.
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PMID:In vivo and in vitro studies of vanadate in human and rodent diabetes mellitus. 892 42

In order to elucidate the signal transduction pathway from external mechanical stress to nuclear gene expression in mechanical stress-induced cardiac hypertrophy, we examined the time course of activation of Raf-1 kinase (Raf-1), mitogen-activated protein kinase kinase (MAPKK) and MAP kinases (MAPKs) in neonatal rat cardiac myocytes. Mechanical stretch transiently activated Raf-1 and MAPKK with a peak at 2 and 5 min after stretch, respectively. In addition, MAPKs were maximally activated at 8 min after stretch. Next, the relationship between stretch-induced hypertrophy and the cardiac reninangiotensin system was investigated. When the stretch-conditioned culture medium was transferred to non-stretched cardiac myocytes, the medium activated MAPK activity slightly but significantly, and the activation was completely blocked by the type I angiotensin II (AngII) receptor antagonist, CV-11974. Moreover, in in vivo studies using spontaneously hypertensive rats, hypertension-induced cardiac hypertrophy was significantly reduced by treatment with subpressure doses of CV-11974. In addition, CV-11974 reduced the isozymic transition of MHC from VI to V3 and inhibited the accumulation of collagen fibers in the extracellular space of the myocardium. These results suggest that mechanical stress activates the protein kinase cascade of phosphorylation in cardiac myocytes in the order of Raf-1, MAPKK and MAPKs. AngII, which is secreted from stretched myocytes, possibly activates these protein kinases. Moreover, it was shown that CV-11974 causes regression of cardiac hypertrophy and has cardioprotective effects on hypertrophied myocardium in vivo.
Diabetes Res Clin Pract 1996 Feb
PMID:Angiotensin II mediates mechanical stress-induced cardiac hypertrophy. 896 84

We measured erythrocyte Na+/Li+ and Na+/H+ countertransport (CT) activity (millimoles per liter per cell per hour) in 10 healthy control subjects (age, 38 +/- 4 years; body mass index, 25 +/- 1 kg/m2) and in 25 hypertensive patients with non-insulin-dependent diabetes mellitus ([NIDDM] age, 49 +/- 3 years; body mass index, 29 +/- 1 kg/m2; fasting plasma glucose, 157 +/- 12 mg/dL) 4 weeks after discontinuation of previous antihypertensive treatment. Na+/Li+ CT was significantly increased in hypertensive NIDDM patients compared with controls (0.56 +/- 0.04 v 0.30 +/- 0.03, P < .01), whereas Na+/H+ CT was similar to control levels (21 +/- 1 v 20 +/- 2). A positive correlation was found between Na+/Li+ CT and the severity of insulin resistance (r = .69, P < .01), mean arterial pressure ([MAP] r = .64, P < .01), plasma triglyceride concentration (r = .46, P < .05), and plasma total cholesterol (r = .41, P < .05). An inverse correlation was found between Na+/Li+ CT activity and plasma insulin concentration (r = -.47, P < .05). No relationship was observed between Na+/Li+ CT activity and either creatinine clearance or proteinuria. Stepwise multiple regression analysis for all metabolic variables and blood pressure showed that only the severity of insulin resistance was positively correlated with increased Na+/Li+ CT activity. Na+/H+ and Na+/Li+ CT activity were not altered by 3 hours of euglycemic physiologic hyperinsulinemia (84 +/- 3 microU/mL). Hypertensive NIDDM subjects were treated for 3 months with captopril, nifedipine, or doxazosin. After captopril, a reduction of Na+/H+ CT was observed (22 +/- 4 v 13 +/- 2, P < .05); Na+/Li+ CT decreased after doxazosin (0.56 +/- 0.06 v 0.45 +/- 0.05, P < .05) and nifedipine (0.52 +/- 0.06 v 0.42 +/- 0.05, P < .05). In conclusion, in hypertensive NIDDM subjects, (1) Na+/Li+ CT is increased and is correlated with the level of insulin resistance and the MAP; (2) acute physiologic hyperinsulinemia does not affect Na+/Li+ or Na+/H+ CT activity; and (3) Na+/H+ CT activity is reduced by captopril, and Na+/Li+ CT is decreased by doxazosin and nifedipine.
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PMID:Na+/Li+ and Na+/H+ countertransport activity in hypertensive non-insulin-dependent diabetic patients: role of insulin resistance and antihypertensive treatment. 936 92

Menorrhagia--menstrual periods lasting longer than 7 days and totaling blood losses greater than 80mL--affects 9%-14% of otherwise healthy women, and it can signal cancer, an endocrinologic disorder, or gynecologic disease. Blood loss can be high enough to result in anemia, fatigue, and syncope. Most often, abnormal uterine bleeding such as menorrhagia involves a disruption in the hypothalamic-pituitary axis, the ovary, and/or the uterus. Other identified causes include medications (especially psychotropics) that cross the blood-brain barrier; chronic diseases such as cancer, diabetes, and liver and kidney dysfunction; endocrine disorders, perimenopausal anovulation, polycystic ovary disease, pituitary tumors, and abnormal estrogen cycling caused by morbid obesity; and anatomic abnormalities of the uterus. Routine tests include hematocrit or hemoglobin to detect and evaluate anemia, thyroid stimulating hormone (TSH) level to evaluate thyroid function as a possible cause, and a pregnancy test to rule out an incomplete, spontaneous abortion as a cause. A Pap test is recommended to screen for dysplasia that can suggest a gynecologic cancer cause. Additional screening for endocrine disorders that may be causing menorrhagia include tests of thyroid, liver, and kidney function, and tests of follicle stimulating hormone (FSH), prolactin, and cortisol levels. Treatment can be medical or surgical. Medical treatment includes prostaglandin inhibitors, specifically nonsteroidal antiinflammatory drugs (NSAIDs), and hormonal therapy with estrogen, progesterone, gonadotropin-releasing hormone agonists, or oral contraceptives such as medroxyprogesterone (Depo-Provera). Surgical treatment includes hysteroscopic endometrial ablation by physical agents, laser electrodiathermy, and "roller ball," or surgical, resection. Hysterectomy is the treatment of last resort.
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PMID:Treatment Decisions in the Management of Menorrhagia. 974 72

Considerable progress has been made in our understanding of the molecular mechanisms of insulin action. The insulin receptor is a membrane receptor possessing tyrosine kinase activity. The binding of insulin to its receptor induces autophosphorylation of the receptor on tyrosine residues and thereby stimulates its tyrosine kinase activity towards intracellular substrates such as Shc or IRS1. This tyrosine kinase activity, which plays a crucial role in the transmission of the signal, is decreased in several insulin-resistance situations. This decrease was initially attributed to the phosphorylation of the receptor on serine or threonine residues, but this mechanism is now seriously questioned. Tyrosine phosphorylation of IRSs and Shc by the insulin receptor permits the activation of two major signalling pathways, the MAP kinase pathway and the Pl 3-kinase pathway. MAP kinases are involved in proliferation and differentiation processes, in particular by regulating the transcriptional activity of the nucleus. The MAP kinase pathway does not appear to play a significant role in the transmission of the metabolic effects of insulin. In contrast, the Pl 3-kinase pathway is involved in several of the metabolic effects of the hormone, such as glucose transport, glycolysis and glycogen synthesis. The Pl 3-kinase pathway also plays a crucial role in the regulation of protein synthesis by insulin. Moreover, this pathway is involved in cell growth and transmits a strong anti-apoptotic signal.
Diabetes Metab 1998 Dec
PMID:Molecular basis of insulin action. 993 14


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