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Pregnancy-induced hypertension (PIH), which includes both gestational hypertension and preeclampsia, is a common and morbid pregnancy complication for which the pathogenesis remains unclear. Emerging evidence suggests that insulin resistance, which has been linked to essential hypertension, may play a role in PIH. Conditions associated with increased insulin resistance, including gestational diabetes, polycystic ovary syndrome, and obesity, may predispose to hypertensive pregnancy. Furthermore, metabolic abnormalities linked to the insulin resistance syndrome are also observed in women with PIH to a greater degree than in normotensive pregnant women: These include glucose intolerance, hyperinsulinemia, hyperlipidemia, and high levels of plasminogen activator inhibitor-1, leptin, and tumor necrosis factor-alpha. These observations suggest the possibility that insulin resistance may be involved in the pathogenesis of PIH and that approaches that improve insulin sensitivity might have benefit in the prevention or treatment of this syndrome, although this requires further study.
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PMID:Brief review: hypertension in pregnancy : a manifestation of the insulin resistance syndrome? 1123 Feb 77

Epidemiological studies clearly indicate that combined oral contraceptives (OCs) increase risks of vascular thromboses. The risk of myocardial infarct is increased by 3 for combined OC users aged 30-39 and by 5 for those aged 40-44. Risks of deep phlebitis and cerebral thromboses are also 5 times greater in OC users. The effects of OCs on serum lipid levels depend on the dose and type of estrogens and progestin. Ethinyl estradiol causes an increase in triglycerides and HDL cholesterol, while progestins tend to increase total cholesterol and decrease HDL cholesterol. Low-dose combined OCs have slight or no effect on cholesterol, HDL cholesterol or triglycerides. Moderately dosed combined OCs elevate triglycerides but their effects on total cholesterol and HDL are moderate. High dose combined OCs increase triglyceride and cholesterol levels. The combined effects of the estrogen and progestin in high dose pills usually increase HDL cholesterol, but there is some doubt as to whether the increase is beneficial. Although all combined OCs have deleterious effects on serum lipids, only persons predisposed to hyperlipidemia are truly at risk. Young women using OCs require systematic control, of serum lipid and lipoprotein levels. Low-dose formulations are generally preferable. Standard or high dosed OCs can cause disturbances of glucose metabolism in predisposed women, but risks of patent diabetes are small. Glucose intolerance developed during pill use is not always reversible. The risk appears more serious with pills containing estranes or norgestrel than with those containing pregnanes. Low-dose pills entail less deterioration than higher dosed pills. Low-dose progestin-only pills also have deleterious effects. OCs interfere with glucose metabolism in part by creating an effect of peripheral insulin resistance and in part by diminishing the insulin-secreting capacities of the islets of Langerhans. All OCs are contraindicated in women with histories of gestational diabetes or glucose intolerance. Insulin-dependent diabetes in adolescents is a relative contraindication. Regular surveillance is required of weight and blood sugar for normal women using OCs. Estrogens have been the major factor identified in variations of coagulation factors and fibrinolysis in OC users. Platelet aggregation has been less well studied. OCs should be avoided in case of hypercoagulative states of platelet hyperaggregation.
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PMID:[Metabolic risks of oral contraception]. 1228 76

Effects of oral contraceptives (OCs) on glucose metabolism can be considered on 2 levels: production of diabetes or impaired glucose tolerance, and production or aggravation of vascular complications caused by chronic hyperglycemia. Combined OCs can promote development of diabetes in predisposed women. The frequency of impaired glucose tolerance increases and the reversibility of the condition decreases with duration of use. Subjects with impaired glucose tolerance are known to have much higher eventual rates of diabetes than normal subjects. It can be concluded that OC usage in the long run can indirectly increase the incidence of diabetes. It is now accepted that diabetic microangiopathy is related to the degree and duration of hyperglycemia, although a genetic component appears to determine its severity. The possibility that OCs thicken the basal membranes of capillaries, an index of diabetic microangiopathy, cannot be formally ruled out. On the macroangiopathic level, OCs considerably increase the incidence of cardiovascular maladies. The relative risk of death for all cardiovascular diseases taken together is tripled in OC users. The excess mortality is related primarily to increased incidence of myocardial infarcts, cerebral vascular accidents, and pulmonary emboli. 2 kinds of vascular accidents are related to pill use: early venous or arterial accidents of poorly elucidated physiopathology, and arterial accidents after longer use which recall the classic atherosclerotic factors related to chronic hyperglycemia. A study by Whitehall of 18,403 subjects indicated that even slight deterioration of glucose tolerance caused by pills might aggravate vascular risks. All pills produce a state of chronic hyperinsulinemia. Chronic hyperinsulinemia has been incriminated as an atherosclerotic risk factor because of its effects on the arterial walls, including proliferation of smooth muscle fibers and development of fat-filled lesions similar to those of early atherosclerosis. Atherosclerosis is multifactorial, and OCs aggravate most of the factors. Pill-induced hypertension is associated with more serious deterioration of glucose tolerance and more severe hyperlipidemia. Few epidemiologic studies have examined the vascular risks of OCs in a population of diabetic women, but 1 study of 120 insulin-dependent diabetic women using OCs and 136 insulin dependent nonusers found 4 vascular accidents in users under 30 years old and none in nonusers. Deterioration of glucose tolerance in normal women using OCs should be regarded as a sign of increased vascular risk. Glucose tolerance should be determined for all women prior to OC prescription. OCs in any form are contraindicated in cases of a history of gestational diabetes or of diabetes or impaired glucose tolerance appearing with pill use and disappearing on termination of use; in cases of impaired glucose tolerance with a familial or obstetric history of diabetes; and of diabetes or impaired glucose tolerance complicated with angiopathy. Relative contraindications to OC use include diabetes and impaired glucose tolerance in cases where angiopathy is absent. Low-dose pregestin pills may be used in such cases. Effective contraception is necessary for diabetic women. The IUD may be used in well controlled diabetics with careful surveillance for infection.
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PMID:[Oral contraception and carbohydrate metabolism: III--practical implications]. 1234 Dec 42

A 33-year-old secundipara with a history of gestational diabetes and familial hypertriglyceridemia exacerbated during her previous pregnancy was admitted in the 36th week of gestation with diffuse abdominal pain, vomiting, low-grade fever, and general malaise. A blood sample had a lipemic, milky-pink appearance and plasma concentrations were as follows: triglycerides 2173 mg/dL, cholesterol 320 mg/dL, amylase 801 U/L, lactate dehydrogenase 650 U/L, creatinine 1.5 mg/dL, glucose 380 mg/dL, and left-shifted white cells. Acute pancreatitis was diagnosed and owing to signs of fetal distress, a cesarean was performed under light general anesthesia with propofol, succinylcholine, and sevoflurane. After the umbilical cord was cut, rocoronium and fentanyl were administered. The neonate was healthy and the patient's condition evolved favorably with conservative treatment. The incidence of pancreatitis during pregnancy is low but related morbidity and mortality are high. The usual cause is biliary tract disease, although rare metabolic alterations such as hyperlipidemia may occasionally act as the trigger. Early diagnosis and treatment are the keys to successful surgery and postoperative recovery.
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PMID:[Hypertriglyceridemic pancreatitis and pregnancy]. 1475 42

We set out to reevaluate the hypothesis that high normal (negative) results of 50 g oral glucose challenge test or high normal glucose level on 100 g oral glucose tolerance test are associated with complications of pregnancy and delivery. This was a prospective study involving 735 nondiabetic women. The first group (n=352) was made up of pregnant women with normal 50 g oral glucose challenge test without previous history of diabetes mellitus or gestational diabetes. The second group (n=383) was made up of pregnant women without previous history of diabetes mellitus or gestational diabetes with an abnormal 50 g oral glucose challenge test and with normal 100 g oral glucose tolerance test and not more than one previous delivery. In nondiabetic women, we demonstrated a positive correlation between high normal 50 g glucose challenge test values and the incidence of preeclampsia, caesarean section rate, macrosomia, neonatal hyperlipidaemia and minor congenital abnormalities. We failed to confirm any relationship to any pregnancy complication in pregnant women with 2-hour glucose levels in the range 6.7-9.1 mmol/l on the 100 g oral glucose tolerance test. We have demonstrated a positive relationship between the incidence of premature rupture of membranes and 1-hour glucose level, caesarean section rate and maternal 1-hour glucose level or 1-hour glucose level minus fasting glucose level of 4.2 mmol/l, instrumental delivery rate and maternal 3-hour glucose level, incidence of neonatal macrosomia and 1-hour glucose level, and incidence of neonatal hyperlipidaemia and at least one high but normal glucose level on the 100 g oral glucose tolerance test. With regard to pregnancy and delivery complications there were no significant difference if the high normal value is on the 50 g glucose challenge test or on the 100 g oral glucose tolerance test. It is concluded that one high normal 100 g oral glucose tolerance test or high normal 50 g glucose challenge test are associated with adverse pregnancy and delivery outcome. Nondiabetic women with 50 g glucose challenge test value of 6.1 mmol/l and/or 100 g oral glucose tolerance test values of 5 mmol/l have a favourable pregnancy and delivery outcome.
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PMID:Low values on 50 gram glucose challenge test or oral 100 gram glucose tolerance test are associated with good perinatal outcome. 1551 42

Type 2 diabetes is a serious, costly, and increasingly common disease. Several conditions commonly seen in family medicine settings confer increased risk of developing diabetes. Among these conditions are impaired glucose tolerance, impaired fasting glucose, obesity, gestational diabetes, hypertension, hyperlipidemia, and menopause. We here present the results of a systematic review of the literature examining the evidence for different strategies aimed at preventing type 2 diabetes in patients with these conditions. The strongest evidence supports an intensive lifestyle intervention designed to induce modest weight loss. The greatest degree of prevention, based on lesser quality evidence, may be imparted by bariatric surgery. Metformin and troglitazone have appreciable evidence in specific populations, and orlistat and acarbose have slightly less evidence among obese patients, for preventing diabetes. Ramipril, captopril, losartan, pravastatin, and estrogens show some very preliminary promise for preventing diabetes in patients treated for hypertension, hyperlipidemia, and menopause, but each needs a more rigorous evaluation. Although more questions remain to be answered, family physicians now have tools available to help our patients lead lives free of diabetes.
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PMID:Preventing type 2 diabetes mellitus. 1570 62

About one third of all pregnant women in the United States are obese. Maternal obesity at conception alters gestational metabolic adjustments and affects placental, embryonic, and fetal growth and development. Neural tube defects and other developmental anomalies are more common in infants born to obese women; these defects have been linked to poor glycemic control. Preeclampsia, a gestational disorder occurring more frequently in obese women, appears to be due to a subclinical inflammatory state that impairs early placentation and development of its blood supply. Fetal growth and development during the last half of pregnancy depends on maternal metabolic adjustments dictated by placental hormones and the subsequent oxygen and nutrient supply. Maternal obesity affects these metabolic adjustments as well. Basal metabolic rates are significantly higher in obese women, and maternal fat gain is lower, possibly in response to altered leptin function. The usual increase in insulin resistance seen in late pregnancy is enhanced in obese mothers, causing marked postprandial increases in glucose, lipids, and amino acids and excessive fetal exposure to fuel sources, which in turn increases fetal size, fat stores, and risk for disease postnatally. Impaired glucose tolerance, gestational diabetes, and hyperlipidemia are more common among obese mothers. To date, little attention has been given to the role of diet among obese women in preventing these problems. However, studies of women with impaired glucose tolerance show that replacing refined carbohydrates and saturated fat with complex, low-glycemic carbohydrates and polyunsaturated fatty acids improves metabolic homeostasis and pregnancy outcomes. Thus, current dietary guidelines regarding the amount and type of carbohydrates and fat for nonpregnant women seem appropriate for pregnant women as well.
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PMID:Maternal obesity, metabolism, and pregnancy outcomes. 1670 47

Diabetes is a growing health problem worldwide. It is recognized as a particular threat to public health of the third world communities, particularly those living in rapidly developing countries. Therefore, the present study was conducted aiming at: assessment of the quality of primary health care (PHC) services provided for the control of diabetes mellitus (DM) in Alexandria; and opportunistic screening of high risk individuals attending PHC facilities for DM. Accordingly, the availability of human and nonhuman resources for DM control in two rural and two urban PHC centers in Alexandria (one of them was serving a desert area) was assessed by a pre-designed checklist 920 adult PHC attendants were screened for risk factors of DM. Individuals having more than one of the following risk factors: age above 50 years, overweight (body mass index > or =27 kg/m2), family history of DM in first degree relatives, history of hypertension, hypertension (systolic blood pressure > or =140 mm Hg and /or diastolic blood pressure > or =90 mm Hg), history of hyperlipidemia and history of gestational diabetes or birth of a large sized baby in females- were subjected to random capillary blood glucose (RCBG) testing. Cases were considered likely diabetic if RCBG was >200 mg/dl The performance of all PHC physicians examining and managing 560 diabetic patients was observed over a period of two months. One fourth of the diabetic cases were checked for the level of glycaemic control by fasting capillary blood glucose testing. The results revealed that 61.7% of the studied PHC attendants were at risk of developing DM and 14% were likely diabetic, with an urban: desert ratio of 2:1 The following factors were found to be independently associated with an increasing risk of DM occurrence among males: overweight (about 14 folds), family history of DM (9 folds), age above 50 years and history of hypertension (4 folds each). Whereas, among females the following risk factors were found: family history of DM (8 folds), history of gestational diabetes (6 folds) and overweight (4 folds). The majority of diabetic patients were poorly examined, investigated and managed; and an optimal level of glycaemic control was achieved in only 12.9% of the cases, as the PHC physicians didn't follow a model treatment plan for DM and due to unavailability of some equipment, laboratory facilities and essential drugs.
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PMID:Quality assessment of primary health care services provided for diabetes mellitus control in Alexandria. 1721 42

The lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (OLR1) is a newly described receptor for oxidatively modified LDL. The human pregnancy is associated with hyperlipidemia and oxidative stress. It has been reported that modification in maternal lipid profile can induce disturbance during pregnancy. In this study, we have evaluated the expression protein level of OLR1 in human term placenta of women having plasma cholesterol level lower to 7 mM or higher to 8 mM and women of gestational diabetes mellitus (GDM) by western blot analysis. The present study demonstrates that the maternal lipid profile is associated with placental protein expression of OLR1. A significant increase in the protein expression of OLR1 was observed in placenta of women with elevated plasmatic total cholesterol level (>8 mM). In addition, the placental protein expression of OLR1 is increased in mothers having the highest pre-pregnancy body mass index (BMI) and low (<7 mM) plasmatic total cholesterol level at term. Interestingly, the placental protein expression of OLR1 is increased in the presence of GDM pregnancies compared with normal lipids level pregnancies, without the modification of mRNA expression. In conclusion, placental OLR1 protein expression is associated with maternal lipid profile, pre-pregnancy BMI, and pathology of GDM.
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PMID:Modulation of placental protein expression of OLR1: implication in pregnancy-related disorders or pathologies. 1859 43

It is currently unknown whether gestational diabetes mellitus (GDM), a prevalent obstetrical complication, compounds the changes in drug disposition that occur naturally in pregnancy. Hyperlipidemia occurs in GDM. Using a rat model of GDM, we determined whether excess lipids compete with drugs for plasma protein binding. Because lipids activate nuclear receptors that regulate drug transporters and metabolic enzymes, we used proteome analysis to determine whether hyperlipidemia indirectly leads to the dysregulation of these proteins in the liver. GDM was induced on gestational day 6 (GD6) via streptozotocin injection. Controls received either vehicle alone or streptozotocin with subsequent insulin treatment. Liver and plasma were collected on GD20. Glyburide and saquinavir protein binding was determined by ultrafiltration, and an established solvent method was used for plasma delipidation. Proteomics analysis was performed by using isobaric tags for relative and absolute quantitation methodology with membrane-enriched hepatic protein samples. Relative to controls, GDM rat plasma contained more cholesterol and triglycerides. Plasma protein binding of glyburide and saquinavir was decreased in GDM. Delipidation normalized protein binding in GDM plasma. Proteins linked to lipid metabolism were strongly affected in the GDM proteomics data set, with prohyperlipidemic and antihyperlipidemic changes observed, and formed networks that implicated several nuclear receptors. Up-regulation of drug transporters and metabolic enzymes was observed (e.g., multidrug resistance 1/2, CYP2A1, CYP2B9, and CYP2D3). In this study, GDM-induced hyperlipidemia decreased protein binding and was associated with drug transporter and metabolic enzyme up-regulation in the liver. Both of these findings could change drug disposition in affected pregnancies, compounding changes associated with pregnancy itself.
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PMID:Impact of hyperlipidemia on plasma protein binding and hepatic drug transporter and metabolic enzyme regulation in a rat model of gestational diabetes. 2034 5


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