Age Of Menopause

There are some data to suggest that women with both type 1 diabetes (DM1) (15,16) and DM2 (17) may enter menopause a few years earlier than those without. Another study suggested no difference in age of menopause in women with DM2 (18). DM1 can also occur as part of the autoimmune polyglandular type 2 syndrome. The polyglandular type 2 syndrome is the most common of the immunoendocrinopathy syndromes and is inherited in an autosomal dominant pattern with variable penetrance (19). Premature...

Defective Insulin Secretion

Decreased insulin secretion in offspring of mothers with diabetes has been reported in both animal studies involving the GK rat (48, 69), as well as human studies (29, 43, 70). It is thought that exposure to excess maternal fuels during critical periods in fetal development may lead to permanent changes in physiology, referred to as programming. In the course of fetal development, the endocrine pancreas begins developing at around 7-8 weeks of gestation, with evidence of insulin, glucagon and...

Lipid Changes in Normal Pregnancy

Pregnancy is marked by hyperlipidemia (64, 65). There is a hypertriglyceridemia with very low density lipoprotein (VLDL) triglyceride concentrations increasing threefold from 14 weeks, gestation (66) to term. Postheparin hepatic lipase and lipoprotein lipase activities are decreased from the first and third trimesters, respectively (64). The increase in plasma triglyceride concentration results in the appearance of small dense low density lipoprotein (LDL) particles in late pregnancy (67)....

Cardiovascular Risk in PCOS Women

PCOS is considered a pathological condition at high risk for CVDs. This is not only due to the presence of androgen excess, insulin resistance, obesity, DM2, and dyslipidemia, but also because of many other risk factors (120) (Table 2). These cardiovascular risk factors are often evident at an early age, suggesting that women with PCOS represent a large population at increased risk for developing Prevalence of Impaired Glucose Tolerance (IGT) and Type 2 Diabetes Mellitus (DM2) in Women with...

Celiac disease

Celiac disease (CD) is an immune-mediated enteropathy that results from the exposure to gluten found in wheat, barley, and rye. The gluten causes an immune response that causes an inflammatory reaction in the upper small intestine leading to villous atrophy. CD occurs in about 1 of the population in the USA, and it is estimated that 97 of those people are not diagnosed (34). Approximately 6-10 of individuals with type 1 diabetes have CD (35). Clinical symptoms vary dramatically according to the...

Depression And Diabetes

The term depression refers both to a mood state and, when severe, persistent, and associated with a number of other symptoms, to a clinical syndrome or disorder. Depressive disorders include major depressive disorder, bipolar disorder and dysthymic disorder, a more chronic, less severe form of depression. The term minor depression or subthreshold depression refers to depressive symptoms of at least 2 weeks duration that fall short of full diagnostic criteria for a major depressive episode or...

Diabetes And CardiovASCuLar Risk Factors In Women

There is emerging evidence that DM2 is an important risk factor for the development of CvD, with some difference between women and men. As discussed in more detail in Chap. 3, death rates for coronary heart disease (CHD) are 3-7 times greater among diabetic than nondiabetic women, whereas rates are twice or three times greater in diabetic vs. nondiabetic men (45). Furthermore, evidence suggests that the positive association between adiposity and risk for DM2 is stronger for women com pared with...

Diabetic Retinopathy in Pregnancy

Pregnancy per se is a risk factor for progression of diabetic retinopathy (DR). Achieving good glucose control prior to pregnancy can decrease the risk of development and or progression of DR (14). The classification of retinopathy during pregnancy is the same as the classification in nonpreg-nant diabetic patients. DR progresses from mild nonproliferative abnormalities with increased vascular permeability, to moderate and severe nonproliferative diabetic retinopathy (NPDR), characterized by...

Eating Disorders And Depression An Introduction

Eating disorders are a group of psychosomatic conditions characterized by disturbed eating behavior and a constellation of psychological traits and symptoms. Disturbed eating behavior refers to dieting and fasting, binge eating episodes and compensatory behavior for weight control. The latter includes excessive exercise for weight loss, and purging behavior, such as self-induced vomiting and the abuse of laxatives, diuretics and diet pills. Individuals with diabetes have an additional purging...

Eating Disorders And Depression Screening And Treatment

In view of the high rates of both depression and eating disorders and their medical consequences in girls and women with diabetes, regular screening for these problems should be incorporated into their primary medical care, beginning in the preteen years. Questions about persistent mood alterations, loss of interest in activities, lowering of motivation or energy level, or sleep problems, can reveal the presence of a mood disturbance. Enquiry about satisfaction with weight and shape, dieting,...

Evidence For The Developmental Origins Of Pcos

Two sources of evidence in human beings and animals suggest that PCOS may originate in intrauterine life. The first is evidence from clinical observations and experimental animal research suggesting that fetal exposure to androgen excess may program in utero, the development of PCOS traits that are expressed in adulthood (24). Further evidence comes from longitudinal observations of girls with LBW that follow a path through postnatal catch-up weight gain, amplified adrenarche, and ovarian...

Final Postpartum Visit

The final postpartum visit, which is usually done 6 weeks after delivery, is comprehensive and covers a wide range of systems from general well-being, coping with changes since delivery, and breastfeeding support. The visit focuses on questions pertaining to diabetes care, insulin requirements, blood pressure control (especially if preeclampsia occurred), eye health, maternal weight loss, a thorough physical exam, and contraception. Please see Chap. 9 for a more comprehensive review of...

First Trimester Weeks

The first prenatal visit may be the first time a patient with diabetes is seen. Ideally baseline evaluation and education take place before preconception as outlined in Chap. 15, but in many cases, pregnancies are unplanned. In the case of the unplanned pregnancy, this evaluation and education should take place as soon as the pregnancy is diagnosed. For patients who have had the benefit of preconception care, the first prenatal visit is usually scheduled between 6 and 8 weeks of gestation. This...

Gonadotropin Releasing Hormone

Both GnRH agonists and antagonists are being investigated for their roles in ovulation induction in patients with PCOS. While GnRH agonists in conjunction with gonadotropins may increase pregnancy rates, reduce the risk of miscarriage, and may be of use in patients with high LH levels who have either failed gonadotropin therapy alone or who have had recurrent miscarriages, the concern for multiple follicle development has hampered their use in these patients (6, 107, 108). Only small studies...

How The Definition Of The Metabolic Syndrome Oyerlaps That Of Insulin Resistance

As reported above, the NCEP ATP III report designated a cluster of related CvD risk factors as a definition of the metabolic syndrome, and stated that this syndrome is closely linked to insulin resistance (25). Insulin resistance and or compensatory hyperinsulinemia are undoubtedly CVD risk factors (10). On the other hand, although insulin resistance is believed to be the basic pathophysiological alteration leading to the metabolic syndrome, neither assessment of insulin resistance nor...

Hyperglycemia and Adverse Pregnancy Outcome HAPO Study

A primary aim of the HAPO Trial was to establish uniform GDM screening criteria based on maternal and fetal outcomes (38). A total of 25,505 pregnant women at 15 centers in 9 countries underwent 2-h 75-g OGTTs between 24 and 32 weeks of gestation. Primary outcomes included mac-rosomia, Cesarean delivery and neonatal hypoglycemia. Secondary outcomes included delivery before 37 weeks, shoulder dystocia or other birth injury, hyperbilirubinemia and preeclampsia. While the risk of adverse pregnancy...

In Vitro Fertilization

IVF represents a last resort for PCOS patients with infertility. A meta-analysis examining IVF outcomes in patients with PCOS compared with normal controls found an increased cycle cancellation rate and lower fertilization rates among patients with PCOS (111). However, they were also found to have more oocytes per retrieval and comparable pregnancy and live birth rates when compared with the control group. In vitro maturation of oocytes in which immature oocytes are retrieved without...

Infertility Treatment In Pcos

Inducing ovulation in patients with PCOS can be accomplished through several approaches reducing insulin concentrations, follicle stimulating hormone (FSH) stimulation or reducing LH concentrations (6). Reducing insulin concentrations can be accomplished by either weight loss or insulin-sensitizing agents, like metformin. Clomiphene citrate or gonadotrophin therapies have traditionally been used to stimulate FSH more recently, aromatase inhibitors have been investigated for this purpose....

Insulin Resistance in PCOS

Insulin resistance in women with PCOS appears even more common than in the general population (79, 83). It should, however, be emphasized that the majority of the studies have simply demonstrated that, in comparison to adequate control groups, insulin resistance, as measured by various techniques or methods, was more common in subjects with PCOS. There are no epidemiological studies focusing on the prevalence of insulin resistance in PCOS. In one study examining the characteristics of more than...

Kelsey ES Salley and John E Nestler

Polycystic ovary syndrome (PCOS) affects 5-10 of women of reproductive age. One of the hallmarks of the syndrome is chronic oligo- or anovulation, making it one of the most common causes of infertility. While infertile PCOS patients have traditionally undergone conventional fertility treatments, insulin-sensitizing agents are also being explored because of the hyperinsulinemic insulin resistance intrinsic to the syndrome. Once women with PCOS become pregnant they are at increased risk for...

Lipid changes during pregnancy and preexisting diabetes

Cholesterol levels and LDL-C levels increased up to 50 during normal pregnancy (107). Triglycerides may increase threefold during normal pregnancy (115, 116). Especially among women with DM2 who have increased triglycerides prepregnancy, the risk of progressive elevation in triglycerides to > 2,000 mg dL increases the risk for pancreatitis during pregnancy (117, 118). The goals of managing dyslipidemia during pregnancy are similar to those of nondiabetic patients with cardiometabolic risk,...

Lipid Changes in Obesity

Obese women demonstrated similar increases in fat oxidation, in the absence of changes to carbohydrate metabolism, to those observed in lean individuals (11). In obese NGT and GDM women there was an inverse correlation between endogenous glucose production and fat oxidation from prepregnancy to early gestation (11). Triglyceride oxidation, as assessed by recovery of exogenous 13C Hiolein (a biosynthetic triglyceride) as exhaled 13CO2 (19), was significantly lower in GDM independent of obesity....

Lipid Metabolism In Pregnancy

There is no change in either basal carbohydrate oxidation or nonoxidizable carbohydrate metabolism but there is a significant 50-80 increase in fat oxidation during pregnancy both in the basal state and also during an euglycemic hyperinsulinemic clamp (11). These data underline the importance of the switch from carbohydrate to fat metabolism in pregnancy that is potentially regulated by placenta-produced leptin. During fasting, pregnancy is a state of accelerated starvation with increased...

Maternal Diabetes and Cardiovascular Disease Risk

GDM confers a sixfold risk for future maternal diabetes, independent of other significant risk factors such as weight, visceral adiposity and physical activity (58, 59). Up to a third of women with diabetes may have been affected by prior GDM (60). Additionally, GDM is associated with vascular dysfunction and future cardiovascular disease. Heitritter et al. found that women with a GDM history had greater vascular resistance, lower stroke volume and lower cardiac output than women without a GDM...

Meal Plan RecoMmendatioNs

It is important to establish a meal plan to help meet calorie and macronutrient recommendations for pregnancy. A macronutrient balance of 45-55 of carbohydrate, 20-25 protein, and 30-40 fat is essential in meeting the nutrient needs of both mom and baby (6). The timing of meals and snacks is important to optimize blood glucose control and to provide the fetus with glucose needs for growth. Planning a daily food intake of three meals and two to four snacks, including a bedtime snack, will help...

Nutrition and meal planning in gestational diabetes

MNT is the cornerstone of treatment for gestational diabetes (GDM). Within 48 h of diagnosis, a woman should see a diabetes educator, preferably a registered dietitian for meal planning to assist with blood glucose control (31). Education can be conducted in a class or an individual counseling session. The ideal amount of carbohydrate is unknown but is generally limited to 40-45 of the total calories needed for the day (32). For obese women one can reduce the amount of carbohydrate to 35-40...

Plausible Genetic Contribution to Prenatal Androgenization

Evidence is accumulating that genetic modifiers of placental barrier to androgens, such as polymorphisms of the SHBG and P450 aromatase (CYP19) genes, or genetic variants associated with increased androgen receptor (AR) sensitivity may also contribute to fetal programming of PCOS by androgen excess. Genetic Contribution to Placental Barrier Function Human SHBG is a homodimeric glycoprotein produced in the liver as well as the placenta and gonadal tissues, and is encoded by a 4-kb gene spanning...

Population lessons from the pcos paradigm

The androgen balance is profoundly affected in the presence of metabolic disorders, particularly obesity and the metabolic syndrome (2). Androgens have an important impact on both glucose and lipid metabolism, and on fat homeostasis, therefore it is not unlikely that androgen imbalance may play a role in the pathophysiology of the metabolic syndrome. Although the few large prospective studies have not confirmed a significant association, cross-sectional studies have nonetheless provided some...

Protein

The Recommended Dietary Allowance (RDA) for protein in the first trimester is 0.88 g kg daily, and in the second half of pregnancy it increases to 1.1 gm kg of desirable body weight or 20-25 total daily calories for a singleton pregnancy (Table 2). Twin pregnancies require an additional 50 g of protein a day beginning in the second trimester. Protein is needed for growth, maintenance, and repair of tissues and during pregnancy to meet the high rate of protein turnover in the second and third...

Seafood recommendations during pregnancy

During rapid fetal growth, postpartum and breastfeeding, long chain omega 3s cannot be made fast enough to meet maternal and fetal needs and must be consumed in the maternal diet (17). A controversy has existed in regard to the risk-benefit of eating fish during pregnancy because of the possible harmful effects of methyl mercury present in ocean fish. Present recommendations for pregnancy, however, are to eat 12 oz of fish per week, which can include shrimp, canned light tuna, salmon, pollock,...

Steroid Hormones And Body Fat Distribution Patterns

We still know little about the etiological factors leading to preferential deposition of intra-abdominal fat in the presence of excess energy intake. It is widely believed that sex hormones and more generally steroid hormones play a key role in the regulation of body fat distribution (106). However, their specific influence on fat cells has remained elusive, especially in humans. The following section will address the role of steroid hormones, namely cortisol, androgens, and estrogens in the...

The Genetics of Polycystic Ovarian Syndrome

PCOS, like diabetes, is a multigenic disorder with clear evidence for familial aggregation (317). There is a 5-10 prevalence of this disorder in women of reproductive age (318). As insulin resistance and hyperinsulinemia are a cause of PCOS, it has been expected that there is some overlap between the genes implicated in PCOS and those for diabetes. However, to date, no DM2-associated genetic variation has been validated for PCOS association. This may not be surprising, as most of the known DM2...

The Biology Of Sex Difference In Health And Disease

There is increasing evidence that there are many differences between the sexes in the susceptibility and development of chronic metabolic diseases and cardiovascular diseases (CvDs). This implies that mechanisms may partly differ in males and females, involving both endogenous and environmental factors. The fundamental differences between males and females are primarily attributed to hormones, which define the differentiation of secondary sex characteristics at puberty, regulate fertility,...

The Impact of Maternal Obesity on the Energy Cost of Pregnancy

The total energy cost of pregnancy is positively associated with prepregnancy fat mass, body fat, and pregnancy weight gain (6), but maintenance costs are only associated with prepregnancy fatness. This might be explained by the fact that prepregnancy fatness is a marker of overall nutritional status or that prepregnancy fatness may indicate a positive energy balance before conception, and this energy balance might be maintained throughout pregnancy. Either mechanism would explain the wide...

The Metabolic Syndrome CardiovASCuLar Risk Factors And Cardiovascular Events In Women

In 1988, Reaven proposed that individuals who displayed the cluster of abnormalities associated with insulin resistance and compensatory hyperinsulinemia were at significant risk for CvDs (10). Over the last 15 years, the concept underlying the common aggregation of major abnormalities associated with an insulin-resistant state has emerged as a unique entity, the so-called metabolic syndrome. Although there is a concept that insulin resistance is ontologically different from the metabolic...

The Placental Barrier to Excess Androgens

The experimental animal research and the clinical observations cited above suggest a common prenatal etiology for the postnatal endocrine metabolic manifestations of PCOS. The potential sources of excess androgens during intrauterine life to account for fetal programming of PCOS in humans, however, are not clearly known and remain an issue for further research. Normally, the female fetus is protected from the effect of maternal or fetal adrenal androgens by a combination of high SHBG that binds...

Weight Gain in Pregnancy

Very similar mean increases in body weight of around 12 kg have been observed by a number of groups (9, 23, 28). Prentice and Goldberg (5) observed that women from poorer countries have a lower percentage weight gain and have a wide variation in absolute weight gain (0-23 kg in women of moderate nutritional status). Women who gain weight prior to 20 weeks gestation were more likely to retain this weight postpartum than women who gained weight after 20 weeks when fetal growth rate is higher...

Introduction

Human males and females differ greatly in terms of body composition and body fat distribution. In fact, such substantial gross anatomical differences attributable to regional adipose tissue partitioning are practically unique to this species (1). Vague (2, 3) first documented this sex difference in relation to disease risk, stating that men are usually characterized by a body fat distribution pattern that he termed android, with adipose accumulation in the abdominal region, whereas women often...

Angelina L Trujillo Lorena Wright and Lois Jovanovic

Medical Management of Complications During Diabetic Pregnancy Lipid Changes During Pregnancy and Preexisting Diabetes Thyroid Disease in Preexisting Diabetic Pregnancy Management of Diabetic Ketoacidosis During Pregnancy Summary References Approximately 1.3 of pregnancies in the USA occur in women with preexisting diabetes mellitus. Women with pregestational diabetes mellitus who are in poor glycemic control during the first 7 weeks of pregnancy when fetal organogenesis is occurring have an...

Androgens

In men, abdominal obesity has usually been associated with low plasma testosterone levels in cross-sectional (123) as well as in longitudinal studies (124, 125). Waist circumference and waist-to-hip ratio are also inversely associated with plasma sex hormone-binding globulin (SHBG) levels (123-125). Many studies that have measured abdominal fat areas using imaging techniques such as computed tomography or magnetic resonance have confirmed that low plasma testosterone concentrations are often...

Decreased Production of NO and Prostacyclin

Prostacyclin (PGI2) and NO attenuate platelet adhesion to the endothelium as well as platelet aggregation. Upon binding of PGI2 to its G-protein-coupled cell surface receptor, an increment in the intraplatelet concentration of cyclic adenosine monophosphate (cAMP) is seen. Contemporaneously, as NO diffuses across the platelet membrane it activates guanylate cyclase and increases cyclic guanosine monophosphate (cGMP) concentrations. These inhibitory pathways culminate in the phosphorylation of...

Menopausal Status and the Androgen Milieu

The correlation between menopausal status and sexual health among diabetic women has been poorly investigated. Data seem to suggest, however, that the postmenopausal condition does not cause a significantly negative impact on women's sexuality particularly because of the diabetes mellitus itself (9, 23, 37, 38, 40). Similarly, the potential associations among the circulating androgen milieu total and free testosterone, dehydroepiandrosterone (DHEA), DHEA sulphate (DHEAS), and A4-androstenedione...

Weight Loss

Excess body fat accentuates insulin resistance in patients with PCOS, and obese women with PCOS are more likely than lean women to manifest menstrual irregularities (12). Furthermore, increased body mass index (BMI) is associated with impaired response to standard doses of clomi-phene citrate (18,19). Obesity, independent from hyperinsulinemia, is related to lower oocyte retrieval in IVF and increased total FSH requirements for ovarian stimulation (20, 21). Weight loss has been found to enhance...

Medical Aspects

GDM substantially increases the risk of future DM2. Risk estimates of type 2 diabetes after GDM vary from 17 to 63 within 5-16 years after pregnancy, depending upon the ethnic background of the study population and the detection method for GDM and glucose intolerance 78 . Coustan et al. studied former gestational diabetic women and found diabetes or IGT in 6 of those tested at 0-2 years, 13 at 3-4 years, 15 at 5-6 years, and 30 at 7-10 years postpartum 79 . Kim et al. analyzed 28 studies and...

References

Holemans K, Aerts L, Van Assche F Lifetime consequences of abnormal fetal pancreatic development. J Physiol 547 11-20, 2003 2. Plagemann A, harder T, Rake A, Janert U, Melchior K, Rohde W, Dorner G Malformation of hypothalamic nuclei in hyperinsulinaemic offspring of gestational diabetic mother rats. Int J Dev Neurosci 17 37-44, 1999 3. Barker D, Hales C, Fall C, Osmond C, Phipps K, Clark P Type 2 diabetes mellitus, hypertension and hyperlipidaemia syndrome X relation to reduced fetal...

THE pREvALENcE of Diabetes IN WoMen In Third WoRLD couNTRIEs

The prevalence of diabetes, especially type 2 diabetes mellitus DM2 is increasing by leaps and bounds, and presently it is thought to be in the vicinity of 5.9 of the adult population 20-79 age group or approximately 246 million people globally with the vast majority of diabetes affecting subjects living in developing countries Table 1 . T2DM is the most common form of diabetes and accounts for 85-95 of all diabetes in developed countries and an even higher proportion in developing countries 2...

Counseling and Preconception Care Recommendations to Reduce Maternal and Fetal Risks of Preexisting Diabetes What Are

Women with diabetes and their families need a clear understanding of the risks of diabetes in pregnancy, as the women themselves must play the key role in preventing many of these complications. Diabetes education, both general and specific to pregnancy, is essential, as is a clear, straightforward discussion of risks and strategies to prevent complications. Table 2 provides a checklist for some of the specific components of preconception counseling and care. Structuring preconception...

Pregnancy Induced Hypertension

During normal pregnancy, blood pressure usually falls in the late first to early second trimester and rises again to prepregnancy levels in the third trimester 115 . PIH complicates 5-10 of pregnancies in the USA, including 3-5 of pregnancies in previously normotensive women 115 . Gestational hypertension is defined as elevated blood pressure on two occasions that develops after the twentieth week of pregnancy, without systemic symptoms, in previously normotensive women 171 . Preeclampsia is...

Clomiphene Citrate

Clomiphene citrate, an indirect stimulator of FSH secretion, has been the traditional approach to ovulation induction in infertile patients with PCOS. It is typically given at a dose of 50 mg per day for 5 days starting from day 2 to day 5 of spontaneous or induced menses. The dose of clomiphene can be increased in increments of 50 mg per day each cycle if ovulation is not achieved up to a maximum dose of 250 mg, although doses in excess of 150 mg are not typically prescribed 6 . Ovulation...

Gestational Hyperandrogenism of Maternal Origin

The possible role of PCOS itself as a cause for gestational hyperandrogenism was evaluated in a recent study by Sir-Petermann et al. 60 . Pregnant PCOS women were found to have higher concentrations of androgens than normal pregnant women, thus potentially exposing their unborn daughters to elevated androgen levels in utero. The origin of the androgen excess during pregnancy in women with PCOS women is uncertain but it could be due to increase in androgen production by the maternal theca...

Carbohydrate counting

Either basic or advanced carbohydrate counting can be used, depending on the needs of the patient. Basic carbohydrate counting makes use of a carbohydrate allowance for meals and snacks and provides education on portion sizes. Skills are taught that help identify carbohydrate foods, quantify the amount of carbohydrate in a food serving, and determine the actual portion size eaten. Patients are taught how food, insulin, and physical activity affect blood glucoses. A portion size of each serving...

Thiazolidenediones

Thiazolidenediones TZDs have also been examined for their possible role in the treatment of infertility in PCOS. The main mechanism of action is through activation of the nuclear peroxisome proliferator-activated receptor gamma PPAR-g , which decreases peripheral insulin resistance 73, 74 . Troglitazone was the first drug of this class that was shown to improve ovulation rates, hyperandrogenemia and insulin resistance compared with placebo 75 . It has been shown in vitro to impede LH and...

The Clinical And Molecular Phenotype Of Pcos

PCOS is a common endocrine-metabolic disorder affecting 6-8 of women during their reproductive age. The endocrine abnormalities include hyperandrogenism of ovarian and or adrenal origin, with variable clinical expression, and arrested follicular development leading to oligo- or anovulation and manifesting with oligo- or amenorrhea. Often women with PCOS have augmented luteinizing hormone LH secretion that contributes to hyperandrogenemia 11, 12 . The metabolic trait of PCOS is characterized by...

Effects of HRT on Risk of Developing Diabetes

Given the suggestions of beneficial effects of hormone replacement on glucose homeostasis, the question has been asked as to whether HRT can impact the risk for the development of diabetes. Several observational studies have shown a decreased risk for diabetes in women on HRT 58, 59 although this reduction was not seen in all studies 60 . In a post hoc analysis of the Heart and Estrogen Progestin Replacement Study HERS , a large randomized, double-blind placebo-controlled study, the use of CEE...

Thyroid disease in preexisting diabetic pregnancy

During pregnancy, thyroid levels are altered by several mechanisms hCG stimulation of the TSH receptor increases the free T4 during early pregnancy, and increased thyroid-binding globulin related to estrogen stimulation later in pregnancy results in lowering of free T4. Currently, there is not a consensus regarding routine screening of TSH during pregnancy. However, 10-12 of women of reproductive age have thyroid antibodies 123 . Prepregnancy screening of women with DM1 or DM2 seems warranted...

Cortisol

Increased exposure of fat tissue to cortisol may influence its mass and distribution 107 . This is clearly evident in Cushing's syndrome, in which alterations of the hypothalamic-pituitary-adrenal axis leading to cortisol hypersecretion create a phenotype of abdominal obesity, dyslipidemia, insulin resistance, and hypertension 108 . Common abdominal obesity obviously shares the latter features, although more subtle alterations of cortisol activity have been documented. Specifically, plasma...

Mechanisms Underlying Endothelial Dysfunction in Diabetes

Endothelial dysfunction in diabetes stems from three main sources chronic hyperglycemia, oxidative stress, and the increased production of cytokines and growth factors. Hyperglycemia and Its Immediate Biochemical Sequelae High concentrations of glucose have been shown to be associated with endothelial dysfunction both in vivo 75 and in vitro 76 . Underlying mechanisms contributing to this process include decreased activity and or expression of eNOS, decreased activity and or expression of the...

Mechanisms Adipoinsular Axis

The mechanisms behind the metabolic effects of a diabetic intrauterine environment on exposed offspring are not entirely understood. In 1980, Freinkel's Banting Lecture focused on the hypothesis of fuel-mediated teratogenesis 7 , which suggests that permanent changes in fetal development occur as a result of exposure to altered maternal fuels in the mother with diabetes. Fetal growth is deranged in pregnancies complicated by diabetes 57 , and the excess growth appears to be mainly driven by...

Janet K Snell Bergeon and Dana Dabelea

Diabetes in Pregnancy Epidemiological Studies Mechanisms Public Health and Clinical Implications References Diabetes during pregnancy is thought to contribute to metabolic changes in the fetus, which predispose the offspring of diabetic mothers to obesity, insulin resistance, diabetes and cardiovascular disease. Altered maternal fuels, including but not limited to glucose, may affect the development of the endocrine pancreas in the fetus, resulting in increased adiposity and decreased beta cell...

Effects of HRT on Glycemic Control in Women with Diabetes

Women with diabetes were found to use HRT less commonly than women without diabetes 49 . Yet studies have suggested neutral or beneficial effects of HRT on glycemic control among postmenopausal women with diabetes. Large observational studies have shown that glycemic control is improved in postmenopausal women with diabetes who use HRT compared with those who do not use HRT. One large study of women with diabetes aged gt 50 years included in the Northern California Kaiser Permanente Diabetes...

Other Monogenic Forms of Diabetes

A number of other monogenic forms of early onset diabetes have been reported. These diabetes syndromes can be classified into three main types, that is, congenital pancreatic islet cell dysfunction, congenital insulin resistance, and early autoimmune destruction of pancreatic islet see Table 4 . Monogenic Forms of Congenital Diabetes 1. Transient neonatal diabetes mellitus TNDM is a rare type of diabetes incidence of 1 in 1 million neonates that presents soon after birth, resolves by 18 months,...

The Energy Cost of Pregnancy in Gestational Diabetes Mellitus

In common with others, Okereke et al. 11 observed an increase in BMR from the prepregnant state to late pregnancy in obese women with normal glucose tolerance NGT and obese women with gestational diabetes mellitus GDM . There were no significant differences in basal energy expenditure between NGT and GDM obese women 11 . Obese GDM women had total energy expenditure similar to that of obese NGT women 11 . Similar observations were made for lean GDM and NGT women 18 . GDM women had oxygen...

Sexual Disorders Among Women with Type Diabetes Mellitus

The study by Doruk et al. 38 showed a SD prevalence of 42 within the DM2 women. Low sexual desire was reported in 82 of the DM2 women, whereas 68 complained of low arousal, 38 of reduced lubrication, 38 of orgasm difficulties, 46 of coital pain, and 50 of sexual dissatisfaction. Troubles in sexual arousal, lubrication, and orgasmic function were significantly more prevalent among DM2 subjects than among the healthy controls 23, 38 . Erol et al. 40 assessed the SF profile in 72 premenopausal DM2...

Complications Of Preeclampsia

Preeclampsia may cause both acute complications to the mother and neonate, as well as long-term complications for the mother. Usually maternal and perinatal outcomes are more favorable in women with mild preeclampsia that develops after 36 weeks of gestation 116-118 . Women who develop preeclampsia prior to 33 weeks who have preexisting medical conditions or who live in developing countries have increased maternal and neonatal morbidity and mortality. Immediate complications for the mother...

Short and Long Term Consequences of Fetal Complications

Fetal complications associated with the presence of gestational diabetes in the mother include macrosomia, neonatal hypoglycemia, perinatal mortality, congenital malformations in the case of undiagnosed preexisting DM , hyperbilirubinemia, polycythemia, hypocalcemia, and respiratory distress syndrome, and associated complications of labor and delivery are the most frequent and serious types of morbidity. Macrosomia, defined as birth weight gt 4,000 g, occurs in 20-30 of infants whose mothers...

Diabetic Nephropathy and Superimposed Preeclampsia

Women with diabetes and microalbuminuria or nephropathy are at an increased risk for preeclampsia compared to women with diabetes and no renal disease. In a Danish study 110 of 203 women with type 1 diabetes, 85 had normal albumin excretion, 11 had microalbuminuria, and 5 had diabetic nephropathy. Of those with normal albumin excretion 6 developed preeclampsia, and there was pre-term delivery in 35 . In those with microalbuminuria, 42 developed preeclampsia and 62 with preterm delivery, and in...

Management of GDM Based on Maternal Glucose Control Combined with Fetal Growth

The group of Buchanan and Kjos from Los Angeles picked up Weiss' concept of a fetal-based GDM management and investigated if the fetal AC in the third trimester could serve as a noninvasive method to target GDM pregnancies that need intensive treatment. This fetal-growth based strategy uses the diabetes-specific growth pattern of accelerated growth of the abdomen. This is mainly due to increased subcutaneous fat, which determines 63 of the variation of the fetal AC 24 . While the measurement of...

Summary and conclusions

There are many differences between the sexes in the susceptibility and development of chronic metabolic diseases and CvDs. Fundamental differences between males and females primarily involve hormones, which define the secondary sex characteristics at puberty, regulate fertility, metabolism, and behavior, and play an important role in regulating many functions of different nonreproductive tissues. Changes in the androgen balance have been found to be associated with a series of chronic metabolic...

Circulating Angiogenic Factors

Vegf Diabetic Nephropathy

Soluble fms-like Tyrosine Kinase-1 sFlt-1 Fig. 1 The search for circulating factors that mediate the generalized maternal endothelial function has been the focus of much research, and recent studies have demonstrated an increase in placental expression and secretion of soluble fms-like tyrosine kinase 1 sFLT-1 or sVEGFR-1 , which is a naturally occurring circulating vascular endothelial growth factor VEGF antagonist. VEGF has several receptors, including Flt1 VEGFR1 and Flk1 VEGFR2 , and sFlt1...

Optimal Timing and Frequency

For most patients with DM1 SMBG before and after meals and exercise will provide useful information for adjusting insulin and carbohydrate intake. The ADA suggests that there are no data to support that postmeal glucose monitoring has a specific role in preconception diabetes care beyond what is needed to achieve the target for A1C 30 . However, there is increasing evidence that elevated PPG levels exert a more deleterious effect than elevation of fasting plasma glucose 49 . Many studies...

Risk Factors for Maternal Postpartum Diabetes Among Women with GDM

Glucose intolerance during the index GDM pregnancy, reflected by the glucose values on the 50-g glucose challenge screening test as well as the diagnostic prenatal OGTT, is associated with postpartum hyperglycemia and diabetes 88-93 . Because of variation in diagnostic testing procedures for GDM, as well as the continuous relationship between glucose values and future risk, no single glucose value consistently identifies women at risk for future diabetes 88 . As discussed earlier in the...

Preconception counseling

All women of reproductive age with diabetes should receive preconception counseling, as reviewed in Chap. 15. Both preconception counseling and prenatal care entail a team approach including an obstetrician, endocrinologist, nurse educator, dietitian, and social worker. Education should focus on the rationale for good blood glucose control, blood glucose goals for preconception and pregnancy, MNT, exercise, insulin, and effects of diabetes on pregnancy and of pregnancy on diabetes with an...

Diabetes And Eating Disorders Epidemiology And Clinical Features

There has been controversy in the literature about the association of eating disorders and DM1 50 . However, the evidence from methodologically rigorous studies and from a meta-analytic review 51 supports the view that there is an increased risk for both subthreshold and full-syndrome eating disorders in girls and women with DM1. In studies using a diagnostic interview, the prevalence of full-syndrome eating disorders in girls and women with DM1 ranged from 0 to 11 , and the prevalence of...

Laparoscopic Ovarian Drilling

Surgical ovarian wedge resection was the first surgical treatment for anovulatory PCOS but fell out of favor due to the risk of postsurgical adhesion formation 95-97 . Alternatively, LOD involves cautery of the ovarian surface using electrocoagulation or laser, which can be done on an outpatient basis, results in fewer postoperative adhesions, and requires no ongoing monitoring 98-100 . It has been used as an alternate therapy in patients who do not conceive with clomiphene or gonadotropin...

Agathocles Tsatsoulis

The Clinical and Molecular Phenotype of PCOS Evidence for the Developmental Origins of PCOS Potential Origin of Prenatal Androgen Excess in Humans Plausible Biological Mechanisms Conclusions and Future Implications References Polycystic ovary syndrome PCOS is a common endocrine metabolic disorder in women, characterized by hyperandrogenism, chronic anovulation, and or polycystic ovaries in association with android fat distribution and insulin resistance hyperinsulinism. The etiology of PCOS...

Early Pregnancy Loss

Early pregnancy loss EPL is defined as miscarriage of a clinically recognized pregnancy during the first trimester 39 . While EPL occurs in 10-15 of normal women 116 , rates in women with PCOS are as high as 30-50 117 . Because of the prevalence of infertility in patients with PCOS, many women require fertility treatments which in themselves increase the prevalence of miscarriage 118 . However, several studies in women undergoing fertility treatment with IVF have demonstrated that women with...

Renato Pasquali and Alessandra Gambineri

The Biology of Sex Difference in Health and Disease Insulin Resistance in The General Female Population The Metabolic Syndrome, Cardiovascular Risk Factors and Cardiovascular Events in Women How the Definition of the Metabolic Syndrome Overlaps that of Insulin Resistance Diabetes and Cardiovascular Risk Factors in Women The Paradigm of PCOS Androgens and Risk for CvD and Diabetes in the Female Population Lessons From the PCOS Paradigm Summary and Conclusions References There are many...

Coc

COCs contain a wide variety of progestin formulations and doses. Most progestins are testosterone derivatives and have varying degrees of androgenic effects, e.g., decreasing sex-binding globulin, increasing insulin resistance, and adverse changes in serum lipids 3 . Newer formulations of oral progestins desogestrel, gestodene or older lower dose potency norethindrone formulations minimize androgenic side effects and, therefore, generally are preferable. Their net effect is estrogen-dominant...

Diagnosis of Preeclampsia

Although preeclampsia is usually diagnosed clinically based on clinical criteria as outlined by ACOG, the diagnosis can be a challenge in some patients in differentiating preeclampsia from progestational diabetes, gestational hypertension, and or chronic hypertension. In this regard, it has been recently reported in a small pilot study 99 that both sFltl and sEng may be useful in differentiating preeclampsia from other hypertensive disorders in pregnancy. This study found that the sensitivity...

Gonadotropin Therapy

A second-line option for infertility treatment is direct gonadotropin therapy with either FSH or human menopausal gonadotropin hMG . Because of the increased number of FSH-responsive follicles in polycystic ovaries, patients with PCOS are more at risk for OHSS and multiple gestations 82-84 . A low-dose, step-up protocol has been developed, which yields an increased pregnancy rate while reducing the incidence of OHSS and multiple gestations 83, 85, 86 . Treatment consists of employing a low...

Clinical Health Care Concerns

The hypothesis of fuel-mediated teratogenesis suggests that excess fetal growth caused by maternal fuel abnormalities results in adult disease in the offspring, and so interventions to reduce the transmission of obesity, cardiovascular disease and type 2 diabetes would logically focus on normalizing maternal metabolism and fuel delivery to the infant. There is evidence that hyperglycemia increases fetal growth and also may induce other metabolic changes that are associated with adult chronic...

Coagulation Abnormalities in Diabetes Mellitus

Eighty percent of the premature deaths in DM2 patients are secondary to thrombotic events, with 75 of these cases occurring in the cardiovascular system 38 . Diabetic patients are prone to enhanced thrombosis and platelet aggregation adhesion, endothelial dysfunction, altered fibrinolysis, and lipid disorders 2 . Hemostasis is the process of blood clot formation at the site of vessel injury. The coagulation system involves a complex cascade of proteins, which, after activation, lead to thrombin...

The paradigm of pcos

PCOS is one of the most common causes of ovulatory infertility, affecting 4-7 of women. After the original description by Stein and Leventhal 76 , this syndrome has been defined in different ways over the last 15 years. In 1990 the National Institutes of Health NIH established very simple new diagnostic criteria, which were based on the presence of hyperandrogenism either clinical, such as hirsutism, etc., or biochemical and chronic oligo-anovulation, with the exclusion of other causes of blood...

Allison L Cohen and S Ananth Karumanchi

Epidemiology of Preeclampsia Pathophysiology of Preeclampsia Prediction and Diagnosis of Preeclampsia Complications of Preeclampsia Summary References Preeclampsia is a syndrome of new-onset hypertension and proteinuria after 20-weeks gestation in a previously normotensive woman. Preeclampsia is a leading cause of maternal, fetal, and neonatal morbidity and mortality throughout the world. There are multiple risk factors for preeclampsia, including pregestational diabetes and obesity. Women with...

Teleological Significance

The sex difference in body composition, with females having greater body fat accumulation than men, seems to transcend culture and time 101 . Moreover, such a marked sex dimorphism in body fat distribution is rather unique to the human species 1 . The evolutionary mechanisms underlying these dimorphisms and their teleological significance will be briefly discussed in this section. Hoyenga put forward a theory stating that through sexually dimorphic natural selection, females were placed under...

Gestational Diabetes

GDM is defined as diabetes or impaired glucose tolerance that develops during pregnancy 39 . It affects 4-7 of pregnant women 151, 152 and carries considerable perinatal risk including mac-rosomia, hypoglycemia, stillbirth, jaundice and respiratory distress syndrome 153 . A randomized controlled trial has shown that rates of serious perinatal complications were reduced, birth weight was lower, and macrosomia was less frequent in patients who were treated intensively for impaired glucose...

Maternal Endothelial Dysfunction

Endothelial Dysfunction Preeclampsia

All of the clinical features of preeclampsia can be explained as a maternal response to generalized endothelial dysfunction 29, 30 , and women with underlying vascular disease may be at higher risk of developing preeclampsia due to preexisting endothelial dysfunction 31 . Increased vascular permeability results in proteinuria and edema disturbed endothelial control of vascular tone leads to hypertension, and abnormal endothelial expression of procoagulants leads to coagulopathy. In the kidney,...

Screening And Diagnosis Of

No specific guidelines are available for screening of CVD or CAD in women with diabetes. If patients are symptomatic further testing is likely to be undertaken without delay. However, guidelines on screening asymptomatic individuals are not clearly defined. Recently the American Diabetes Association released a new expert panel recommendation regarding screening for CAD in diabetic patients based on recent evidence that did not support their previous recommendation of screening asymptomatic...

Screening for gestational diabetes in third world countries do we need ethnic and national specific criteria

Defining the performance characteristics of screening strategies for GDM is complicated by the lack of a universally accepted gold standard for the diagnosis of GDM. As can be seen from Table 4, studies that have been carried out in developing countries have used differing screening and diagnostic criteria, mirroring the same lack of consensus in the developed world. More work needs to be done to address a cost-effective diagnostic strategy for GDM that takes into account fetal outcomes rather...

Fibrinolytic System in Diabetes Mellitus Plasminogen Activator Inhibitor

PAI-1, one of the inhibitors of the fibrinolytic system, is synthesized by hepatocytes, fibroblasts, adipocytes, and ECs and is stored within the platelet granules. Elevated PAI-1 levels have been noted in patients with CAD and are strongly correlated with components of cardiometabolic syndrome CMS such as BMI, blood pressure, and triglycerides 2, 27 . Festa et al. examined the relationship between new-onset diabetes and dynamic changes of PAI-1 and fibrinogen 39, 40 . In nondiabetic, healthy...

Hormonal Contraception

Hormonal contraception contains either a progestin compound alone or in conjunction with estrogen. They can be administered orally, intramuscularly, transdermally, and transvaginally. Some IUDs also contain progestin. Estrogen does not affect glucose tolerance 5 , but progestins do increase insulin resistance and decrease glucose tolerance in a dose and potency fashion 6-8 . Estrogen slightly increases blood pressure 9 by increasing angiotensin production while progestins have no effect....

Risk Factors for Preeclampsia

There are multiple risk factors for preeclampsia Table 5 12 . First pregnancy is associated with an increase risk in preeclampsia, though it is not clear why this is such an important factor RR 2.91, 95 CI 1.28-6.61 13 . There are some data suggesting that the risk increases in women who have had limited sperm exposure with the same partner prior to conception 14-16 , though this theory has been challenged. A past history of preeclampsia is a very strong risk factor for preeclampsia in a future...

Prenatal Androgenization and PCOS

The developmental origins hypothesis of PCOS emerged following astute clinical observations in women with congenital virilizing disorders and was further substantiated by experimental animal research. Examples of prenatally androgenized humans are women with classical congenital adrenal hyperplasia from 21-hydroxylase deficiency and rare cases of women with congenital adrenal virilizing tumors 25, 26 . These women are exposed to excess adrenal androgens during intrauterine life and, despite the...

The Metabolic Syndrome in PCOS

Due to the high prevalence of insulin resistance in PCOS, some recent studies used the NCEP ATP III criteria to assess the prevalence of the metabolic syndrome in PCOS women. Glueck et al. 95 studied 138 PCOS patients and found a prevalence rate of 46 , whereas, more recently, Apridonidze et al. 82 found a prevalence of 43 by retrospectively reviewing the medical charts of 106 PCOS women attending the Endocrine Clinic of Richmond, Virginia. Both these studies, therefore, described a prevalence...

Obesity and the Abdominal Phenotype in PCOS

This could be due to a depot-specific inhibition of the expression of hormone-sensitive lipase HSL by testosterone and or to a decrease in the amount of b2 adrenergic receptors. This could also be an important pathophysiological factor behind the insulin-resistant phenotype of the upper-body obesity in men and of the hyperandrogenic PCOS 104 . In humans, it is demonstrated that testosterone increases visceral fat in women. Female-to-male transsexuals treated...

Basal Metabolic Rate in Pregnancy

The large differences in calculated energy costs of pregnancy between studies can be attributed to a high level of intrapopulation variability 9 and also to the level of affluence of the country from which the population was selected 6 . Women from affluent, developed countries showed a rapid early increase in BMR in response to pregnancy 1 . In contrast, women from less affluent countries either show a delayed increase in BMR, or in some there is an initial rapid fall in BMR during the first...

Continuous Glucose Monitoring

SMBG is, without question, one of the most important advances in the field of diabetes and pregnancy, since the discovery of insulin in 1921. To achieve glucose control, it is important to know the target blood glucose levels, and frequent glucose measurements allow a more precise understanding of daily glucose fluctuations. A recent study by Kerssen, which included 43 women with DM1, demonstrated that the detection rate of hyperand hypoglycemic episodes was significantly higher in patients...

Efficacy of PRECoNCEPTIoN Care At ReduCing Pregnancy Complications Why Do I Need Preconception Care

Hemoglobin A1c Congenital Malformations

PCC reduces the risk of congenital malformations and perinatal mortality. In 1949, Dr. Priscilla White published a landmark case series on 439 pregnancies in patients with preexisting diabetes, which highlighted the association of congenital malformations, preeclampsia and prematurity with excess perinatal mortality in infants of mothers with diabetes 11 . Since that time, numerous studies have demonstrated an association between glycemic control and the occurrence of congenital malformations...

With Fetal Growth

In women with preexisting diabetes, ultrasound is considered essential for the detection of congenital malformations. In early pregnancy, maternal hyperglycemia is associated with a high frequency of congenital anomalies. This is a major concern in pregnancies with preexisting diabetes, while in GDM maternal hyperglycemia normally occurs after organogenesis is complete. However, in women with fasting glucose values at diagnosis above 120 mg dl there is obviously an increased risk of congenital...

Metformin Clomiphene Citrate or Both for Ovulation Induction in PCOS

Given the demonstrated efficacy of metformin as monotherapy in increasing ovulation, the question arises whether it might constitute first-line therapy in the treatment of the anovulatory infertility of PCOS. The literature on this issue is conflicting and controversial. Palombo et al. performed a prospective, randomized, double-blind trial of metformin compared with clomiphene 150 mg in 100 nonobese PCOS patients 40 . While there was no difference in ovulation rates, the pregnancy rate was...