Best Home Treatment to Cure Diabetes

Reverse Diabetes Now

Reverse Diabetes Now by Matt Traverso is a program that encourages people to follow healthy lifestyle by eating well and performing exercises frequently to get in shape and manage the blood sugar levels well. This remedy will teach users how to eat right with healthy foods and the best time to eat for preventing the increase of blood sugar levels. The easy to implement concepts and techniques taught in the Reverse Your Diabetes Today system use simple, but highly effective diet and lifestyle changes to cleanse your body from harmful acids and heal your pancreas, allowing it to produce and regulate insulin naturally again. The diet advocated by the Reverse Diabetes book is not well known, but I have heard of it for at least 10 years. However, this diet, like all others, can only be good if you follow it. Funny how that works! Wouldnt it be great if we could just read about a diet and get its advantages? Continue reading...

Reverse Diabetes Now Overview

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The author presents a well detailed summery of the major headings. As a professional in this field, I must say that the points shared in this manual are precise.

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Brandstrup and H Okkels Pregnancy complicated with diabetes Acta Obstet Gynecol Scand 1938 18 1366332

The immediate post-insulin period was marked by some euphoria by both patients and their doctors, but it took a long time for the very considerable fear of pregnancy to diminish, and to some extent that fear remains to the present day. A careful retrospective assessment of those early years of insulin at the Rikshospital in Copenhagen from 1926 to 1938 showed that although there had been no maternal deaths in 22 pregnancies in 19 diabetic women mostly treated with insulin (probably the more severe and often referred cases), the perinatal mortality was still 57 .32 The 13 perinatal deaths included six stillbirths, two intrapartum deaths and five early neonatal deaths of the 10 living children three were asphyxiated at birth, one weighed only 1500 g and one was 5250 g. Histological examination of the pancreas in two full-weight fetuses showed a pronounced increase in the size and number of the islets of Langerhans. Dr Brandstrup, who was in charge of these mothers' care during that...

HG Bennewitz Diabetes mellitus a symptom of pregnancy MD Thesis University of Berlin 1824 [Translated from Latin28

This is the first reference to diabetes in pregnancy. Although the patient was young the clearly described onset of her symptoms during the pregnancy would now classify this as gesta-tional diabetes. Is it possible that she only survived because she was a milder case who responded to diet, while all the more severe Type 1 diabetic patients died Henry Gottleib Bennewitz publicly defended his thesis for the degree of Doctor of Medicine at the University of Berlin on 24 June 1824 (Figure 1.1). It is a simple case report and review of the literature on the causes and treatments of diabetes known at that time. His Greek derivation of the word diabetes and his one-line definition of the symptoms are unchanged today DIABETES MELLITUS A SYMPTOM OF PREGNANCY

Diabetes and pregnancy 1980present

In 1976 the Copenhagen Centre started to perform consecutively an ultrasound examination in the first trimester in all diabetic pregnancies to confirm the gestational age. Quite unexpectedly, it was observed that some fetuses in early diabetic pregnancy were smaller by ultrasound measurements than expected from the menstrual history and the term early growth delay was used to describe this phenomenon.19 When assessing gestational age from a crown-rump length (CRL) measurement, the 95 confidence interval (CI) is +4-5 days. Therefore, significant early growth delay defines an ultrasound age that is at least 6 days less than the menstrual age.20 There is a significant association between early growth delay and the quality of the diabetes regulation as assessed from the HbAlc concentration.21 Correspondingly, there has been a significant decrease in the average early growth delay over the past 20 years, from 5.5 to 2.0 days, which is ascribed to the efforts made to improve diabetes...

Mechanisms of pregnancyinduced insulin resistance

The mechanisms involved in pregnancy-induced insulin resistance, although not fully understood, seem to be related to different factors. Firstly, in pregnant rats there is increased degradation of insulin by the placenta,26 therefore insulin removal is accelerated. A similar phenomenon may occur in human pregnancies. Secondly, and probably most important, during the second half of gestation, there are several hormonal and metabolic alterations that facilitate the development of insulin resistance. Among them, there is the hypertriglyceridemia and the high plasma levels of non-esterified fatty acids, secondary to increased plasma levels of placental lactogen and increased lipolysis,14,15 which lead to an increased cell metabolism of fatty acids, causing in turn, to an intracel-lular increase in the levels of NADH and ATP. This intracellu-lar condition lowers the glucokinase activity and the cell ability to phosphorylate glucose, decreasing the cell uptake of this substance. Increased...

Mechanisms leading to the development of gestational diabetes

The mechanisms leading to the development of gestational diabetes mellitus (GDM) have not been fully defined but are probably related to both an exacerbation of the beta-cell dysfunction in subjects genetically predisposed to beta-cell alterations, which favors the development of GDM. In that sense, GDM will act like a Type 2 DM. In the present chapter we do not take into account situations where diabetes, although diagnosed during pregnancy, is secondary to auto-inmune processes or to the diagnosis of mature onset diabetes of the young (MODY) during pregnancy. Regarding the beta-cell dysfunction, several mechanisms could be involved in this process. High progesterone levels may play a relevant role.30,31 Recently, in models of knock-out mice,31 it has been shown that the lack of progesterone receptors is associated with a higher insulin secretion by beta-cells. Therefore the high levels of progesterone that develop during pregnancy may damage these cells. The hyperlipidemia observed...

Lipid alterations in gestational diabetes mellitus

In gestational diabetes, as occurs in other conditions of insulin resistance and beta-cell dysfunction, there is an increase in plasma levels of triglycerides and cholesterol. This effect should be added to the physiological hyperlypidemia induced by pregnancy (Figure 6.1C).10,11 Therefore, women with GDM have higher plasma levels of triglycerides and cholesterol than found in normal pregnancies (Figure 6.2).44,45 The hyper-triglyceridemia found in gestational diabetes may also play a role in the fetal macrosomia observed in these pregnancies, as several authors have shown a positive correlation between the plasma levels of triglycerides and birthweight.20,21 To sum up, in gestational diabetes, there is a combination of factors that may affect the nutrient supply to the fetus. Under certain conditions, increased supply of glucose and triglycerides towards the fetus may lead to increased fetal growth and macrosomia (Figure 6.3). Nevertheless, under certain conditions, the dyslipedemia...

Amino acid alterations in pregnancies complicated by gestational diabetes

Studies in vitro show that among the different amino acid transporters, the expression of system A, which mediates the transfer of neutral amino acids such as alanine, serine, and glutamine, is increased in diabetic pregnancies.62,63 This, in turn, could increase the uptake and delivery of neutral amino acids into the fetus. However, it does not seem to be the primary cause of accelerated fetal growth. Other transporters such as the specific system for leucine (system L), have also been shown to be increased in microvillous plasma membranes isolated from GDM pregnancies with large babies for their gestational age.62,63 Nevertheless, other authors did not find an increased activity of these transporters.64 It is remarkable that leucine has been proven to be an effective stimulus for fetal insulin secretion in human pancreas studied in vitro.65 In vivo studies applying stable isotope techniques have provided evidence to suggest that leucine, taken up across the microvillous plasma...

Pathophysiology of placenta alterations in diabetes

Maternal diabetes mellitus complicates pregnancy with combinations of growth-promoting and growth-restricting forces which may alter the normal growth trajectories of both the fetus and placenta. Diabetes may affect the maternal intrauterine environment by altering uteroplacental vascular function via the mediators of oxidative stress and inflammation. In an environment of abnormal metabolism, the placenta, which is the sole source of oxygen and nutrients for the fetus, affects the development of fetus. receptivity,4 and insulin has been shown to modulate ovarian steroidogenesis.5 Human pregnancy is associated with hyper-insulinemia and a progressive decline in insulin sensitivity.6 Women with gestational diabetes mellitus appear to have abnormalities both in insulin secretion7 and pronounced insulin resistance,8 compared to women with normal glucose tolerance during pregnancy. Endothelial dysfunctions of decidual capillary network associated with insulin resistance include decreased...

Northwestern Universitys Diabetes in Pregnancy Center Vehicle of the legacy

After making major, pioneering contributions to the understanding of thyroid hormone metabolism2-4 and to other areas of endocrinology early in his career, in the mid 1960s Norbert Freinkel turned his interests and talents to the study of intermediary metabolism in normal and diabetic pregnancy.4-7 By the early 1907s, he had established a Diabetes in Pregnancy Center (DPC) at Northwestern University and had attracted research collaborations globally. Over the next two decades, a virtual 'who's who' of the world's leading established and future investigators of intermediary metabolism in normal and diabetic pregnancy (basic and clinical) could be compiled from those that spent time as visiting scientists at the Northwestern University DPC. Several sources of objective support for this contention are cited below. Following Norbie's sudden, untimely death,8 the American Diabetes Association established the Norbert Freinkel Lecture through the support and encouragement of many colleagues,...

Fetal insulin secretion

Glucose-stimulated fetal insulin secretion (measured as an acute increase in fetal plasma insulin concentration) increases more than five-fold during the second half of gestation in fetal sheep.40 Similar results appear to occur in human fetuses, derived from studies of human fetal islets in vitro and insulin secretion in preterm infants.41 Fetal insulin secretion also can be modified by the degree, duration, and pattern of changes in the fetal plasma glucose concentration. Experiments in fetal sheep,42 for example, have shown that sustained, marked, relatively constant hyperglycemia actually decreases both basal and glucose stimulated fetal insulin secretion (GSIS) responsiveness to amino acids such as arginine also is diminished. In contrast, glucose-stimulated insulin secretion is augmented in most gestational diabetic women in these cases, there is a strong tendency to develop increasingly exaggerated, meal-associated hyperglycemia in late gestation.43 Similar results have been...

Insulin IGF and other growth factors

Plasma insulin also independently promotes IGF-I synthesis.57,58 These observations indicate that the intracellular supply and or concentration of glucose can regulate fetal IGF-I production. In turn, increased plasma IGF-I concentrations can inhibit protein breakdown,58 as does insulin,59 although this effect of IGF-I occurs primarily at higher glucose concentrations. Thus, both insulin and IGF-I indirectly enhance the capacity for glucose to promote fetal nitrogen balance and growth. In fetal sheep, an acute increase in the fetal insulin concentration activates proteins in the mitogen activated protein (MAP) kinase cascade but glucose does not, indicating that insulin might have independent and direct effects on stimulating protein synthesis, cell growth, and cell replication.60 Similarly, acutely increased insulin concentrations in fetal sheep promote amino acid utilization and net nitrogen balance.61 Such effects are probably short-lived, in that chronic infusions of insulin do...

Insulin sensitivity and resistance in pregnancy

The majority of women with GDM appear to have beta-cell dysfunction that occurs on a background of chronic insulin resistance. As noted above, pregnancy normally induces quite marked insulin resistance. This physiological insulin resistance also occurs in women with GDM. However, it occurs on a background of chronic insulin resistance to which the insulin resistance of pregnancy is partially additive. As a result, pregnant women with GDM tend to have even greater insulin resistance than normal pregnant women. The cellular mechanisms underlying insulin resistance in normal and diabetic pregnancy are still unknown. The measurement of fasting insulin concentrations and the calculation of fasting insulin glucose ratios can provide a qualitative but not a quantitative estimation of insulin sensitivity. In non-pregnant patients, hyperinsulinemic-euglycemic clamps5 and minimal-model analysis of intravenous glucose tolerance tests (IVGTT)6,7 have been used to obtain quantitative data about...

JM Duncan On puerperal diabetes Trans Obstet Soc London 1882 24 2568529

Matthews Duncan 1882

From his own experience first identified the serious problem of diabetes to the obstetrical world. He recorded at least 22 pregnancies in 15 mothers between the ages of 21 and 38 (the data are confused in places) the mother survived the pregnancy for long enough to become pregnant again in nine instances, in five she died at the delivery and in six within a few months. The cause of maternal death was usually diabetic coma, although it is not possible to exclude eclampsia, and some must also have developed puerperal sepsis and one died from exacerbation of tuberculosis. Twelve of the 22 babies died, usually in utero, and they were usually of a large size at least 10 survived and only three miscarriages are recorded another 20 pregnancies seem to have occurred before the recorded cases, so some of these mothers must represent late-onset Type 2 or gestational diabetes, and these seemed to have a better prognosis for both mother and child. Diabetes may come on during the pregnancy....

Insulin signaling system in normal pregnancy and in gestational diabetes mellitus

The action of insulin is triggered when it binds to the insulin receptor (IR). The IR belongs to the IGF receptor (IGFR) family, which possesses an intrinsic tyrosine kinase (TK) activity. The receptor is composed of two alfa subunits, each linked to a beta subunit and to each other by disulfide bonds only the beta subunit has enzymatic TK activity. When insulin binds to the receptor, the conformational change activates the beta-subunit and autophosphorylation begins. Thus, activation of the TK enzyme leads to increased tyrosine phosphorylation of cellular substrates. IRS-1, a cytosolic protein, binds to the phosphorylated intracellular substrates, thereby transmitting the insulin signal downstream. The distribution of the IRS proteins tends to be tissue specific IRS-2 is more copious in the liver and pancreas, whereas both IRS-1 and IRS-2 are widely expressed in skeletal muscle. Insulin stimulates the activation and binding of the lipid kinase enzyme, phos-phatidylinositol...

533 Preeclampsia and Gestational Diabetes

While the normal pregnancy is characterized by maternal hemodynamic changes and an insulin resistant state, obesity in pregnancy appears to complicate these expected physiological adaptations to pregnancy. Accordingly, the risk for hypertensive disorders and gestational diabetes (GDM) is reportedly higher in obese and morbidly obese women compared to women who are not obese. In a prospective, multicenter study of more than 16,000 women, Weiss et al. 31 observed a 2.5-fold greater risk of gestational hypertension, and a 2.6-fold greater risk of GDM among obese versus nonobese women. Risk for these conditions was even greater in a morbidly obese subset, e.g., 3.2- and 4-fold respectively. Similarly, these researchers found the risk for developing preeclampsia was 1.6 and 3.3 times more likely to develop in obese and morbidly obese women, respectively. Results from this study have been confirmed by others 32, 33 and found to be independent of other related factors including age, parity,...

Infants of women with gestational diabetes

There is an increased risk of fetal overgrowth or macrosomia in the infant of the women with gestational diabetes (GDM). The percentage of infants of women with GDM who fall within the normal birthweight centiles is often used as a positive outcome measure of glucose control and obstetrical management. We have recently published a series of studies comparing the body composition analysis of infants of women with normal glucose tolerance (NGT) and GDM within 48 hours of birth Table 11.1.33 Although there was no significant difference in birthweight or fat-free mass between Table 11.2 Neonatal body composition and anthropometrics in average for gestational age (AGA) infants of women with gestational diabetes (GDM) and normal glucose tolerance (NGT)* Table 11.2 Neonatal body composition and anthropometrics in average for gestational age (AGA) infants of women with gestational diabetes (GDM) and normal glucose tolerance (NGT)* Infants of women with gestational diabetes 83 Table 11.3...

Glucose and glycogen metabolism in STZinduced diabetes

The decreased glucose uptake by muscles, the reduction in glucose transporter activity and concentration, and the increased hepatic glucose production in diabetes are well documented and discernible early. The hyperglycemia of diabetes is also a concentration-dependent factor causing increased deposition of glycogen in both rodent and human placentas (Figure 12.1).20,21 It is remarkable that glycogen accumulation in the placenta occurs despite the maternal insulin deficiency, while the glycogen content in the typical insulin-sensitive maternal tissues (e.g. adipose tissue, muscle and liver) becomes reduced. Fetal liver glycogen content is increased most probably in response to the fetal hyperglycemia and consequent hyperinsulinemia. The responses Figure 12.1 Glycogen content in the placenta and in maternal and fetal liver of control and streptozotocin (STZ)-induced diabetic rats on day 20 of gestation. Values are means of determinations in 20-26 rats at the mean level of plasma...

Pregnant animals with genetically determined Type 2like diabetes

As mentioned before, animals with Type 2-like diabetic syndromes are generally infertile. This appears to be related to insulin resistance impairing the mediobasal hypothalamus-pituitary system, resulting in decreased gonadotropin release.90,91 Table 12.5 Macrosomia in the offspring of young, mildly diabetic NOD mice prior to the onset of insulin dependency Table 12.5 Macrosomia in the offspring of young, mildly diabetic NOD mice prior to the onset of insulin dependency Pancreas insulin (mg g)

Nutritioninduced diabetes

When animals are fed a high carbohydrate diet, consisting mainly of fructose, they display features of Type 2 diabetes within a short time. Fasting hyperglycemia, hyperinsulinemia and hyper-lipidemia as well as insulin resistance develop.101-103 Some of these features can be ameliorated by supplementing the diet with fish oil104 or by troglitazone as a food admixture.105 Although this has been known for a long time surprisingly little use has been made of this model in pregnancy. One additional effect of the diet is the development of hypertension. This was also found in pregnancy106 suggesting that the fructose-induced diabetes may result in the development of sustained hypertension during pregnancy via the insulin-resistance-hyperinsulinemia link. A similar model was developed on a high sucrose diet107 but the effect of pregnancy on its metabolism is pending.

Autoimmune gestational diabetes as a clinical entity

In diabetic pregnancy, immunological abnormalities occurring in diabetes are superimposed on immunological changes of pregnancy, eventually influencing maternal and fetal outcomes. Gestational diabetes mellitus (GDM) is defined as an impairment of glucose tolerance first recognised at the index pregnancy.11 For this category of women, an increased risk of progression to Type 2 diabetes mellitus (DM-2) has been repeatedly reported.12-15 Nevertheless, a subset of women with GDM depicts one or several autoantibodies (AA) against various pancreatic islet cell autoantigens, typically detected in Type 1 diabetes (DM-1),16 as well as in high risk subjects for the development of the disease, in particular, first degree relatives of patients with DM-1 (FDRs-DM1).17 In Type 1A diabetes, a selective destruction of the insulin-producing cells occurred, mediated by T cells. Autoimmune destruction of the beta cells is determined by multiple genetic susceptibility and modulated by undefined...

Insulin autoantibodies in GDM

The presence of IAA in the sera of DM-1 subjects before initiating insulin therapy was first reported by Palmer et al.66 Later, IAA have been detected in 18-50 of newly diagnosed Type 1 diabetic patients.67,68 Overall, 4-6 of FDRs are positive for IAA, a prevalence that is higher in young ICA Table 13.1 Diabetes-related antibodies in women with gestational diabetes mellitus Table 13.1 Diabetes-related antibodies in women with gestational diabetes mellitus ICA, islet cell antibodies IAA, insulin autoantibodies GADA, glutamic-acid decarboxylase autoantibodies IA2A, antibodies against IA2 protein (thyrosin-phosphatase). *Measurements were performed at different times after delivery +NS versus the control population P< 0.05 versus the control population 0 women had both GDM and a positive family history for diabetes mellitus. (Adapted from de Leiva et al.83) positive individuals. There are only a few reports on the prevalence of IAA in GDM, depicting rates of 0-6 .44> 48> 52>...

Diabetes and pregnancy 19401980

In 1946 it was decided, with Professor Brandstrup at the Rigshospital, University of Copenhagen, to centralize the management and study of diabetes and pregnancy to the Obstetrical Department of Professor Brandstrup, who previously had interest in the problems involved.1,2 The first study from the Copenhagen Centre was designed to find possible characteristics of the course of diabetes during pregnancy, to contribute to a quantitative elucidation of the incidence of alterations occurring and to set up rules for the supervision of pregnant diabetics.3 Two typical periods in diabetic alterations took place, reaching a peak at about the second to third month and at about the seventh month. During the former period, an improvement in tolerance, lasting for an average of 2-3 months, was commonly observed. The manifestation of this improvement was insulin coma, or other insulin reactions, or an improvement in the degree of compensation. During the latter period there is often a decreased...

Racial distribution of gestational diabetes mellitus

The prevalence of GDM varies in direct proportion to the prevalence of Type 2 DM in a given population or ethnic group.1 The reported prevalence of GDM in the United States (US) ranges from 1 to 14 , with 2-5 being the most common rate.3 In a study of the prevalence of diabetes and IGT in diverse populations in women between the ages of 20 and 39, the World Health Organization (WHO) Ad Hoc Diabetes Reporting Group4 noted lower rates of diabetes (< 1 ) in Bantu (Tanzania), Chinese, rural Indian, Sri Lankan and some Pacific populations followed (1-3 ) by Italian women, and white, black and Hispanic women in the US. Rural Fijian Indian and Aboriginal Australian women had a 7 prevalence the highest rate was found in Pima Papago and Nauruan Indians (14-22 ). The prevalence of IGT was low (< 3 ) in Chinese and Malays, and was > 10 in black and Hispanic women in the US, urban Indian women in Tanzania, Pima and Nauruan Indians, and some other Pacific communities. The combined...

Polycystic ovary syndrome and gestational diabetes mellitus

PCOS is a heterogeneous disorder affecting 5-10 of women of reproductive age. It is characterized by chronic anovulation with oligo- amenorrhea, infertility, typical sonographic appearance of the ovaries, and clinical or biochemical hyper-androgenism. Insulin resistance is present in 40-50 of patients, especially in obese women.23 Holte et al.24 reported a higher rate of ultrasonographic, clinical, and endocrine signs of PCOS in 34 women who had had GDM 3-5 years before, compared to 36 matched controls with uncomplicated pregnancies. Five of the women (15 ) with previous GDM had developed manifest diabetes. The authors concluded that women with previous GDM and PCOS may form a distinct subgroup from women with normal ovaries and previous GDM, who may be more prone to develop features of insulin-resistance syndrome.

Fetal hyperinsulinemia as a cause of macrosomia in pregnancy

Diabetes produces major changes in the hormonal and metabolic homeostasis in pregnancy that has divergent effects on maternal and feto-placental tissues. The hyperglycemia in cytotoxin-induced diabetes was considered to cause maternal tissue malfunction on the one hand and to induce the precocious commencement of fetal insulin secretion on the other. The profuse insulin secretion was assumed to promote fetal overgrowth by the excess of glucose, amino acids and other fuels.67 The fetuses of STZ-induced diabetic rats were shown to have lower tissue DNA contents and DNA polymerase activities than those of normal or mildly diabetic mothers,68 suggesting that the fetal tissue growth recedes as the severity of maternal diabetes increases. However, numerous observations underscore that the fetal macrosomia is insulin induced. In mild diabetes it comprises obesity as an important element, in addition to the selective organ overgrowth. Fetal fat accretion may result from excessive de novo...

Recurrence of gestational diabetes mellitus

Higher recurrence rates (69 of 78 patients) were reported by Major et al.46 Recurrence was more common when the following variables were present in the index pregnancy parity > 1 (OR 3.0), BMI > 30 (OR 3.6), GDM diagnosis < 24 weeks gestation (OR 20.4) and insulin requirement (OR 2.3). A weight gain of 7 kg (c. 15 pounds) (OR 2.9) and an interval between pregnancies of < 24 months (OR 1.6) were also associated with a recurrence of GDM. Spong et al.47 found a similarly high recurrence rate of 68 in 164 women with GDM. Risk factors for recurrence in this study were earlier diagnosis of GDM, insulin requirement and hospital admissions in the index pregnancy. Nohira et al.48 evaluated the recurrence rate and risk factors of recurrent GDM. In 32 patients with GDM and 37 with one abnormal OGTT value (OAV) in their index pregnancies. The recurrence rate from index GDM and OAV were 65.6 and 40.5 . Age, BMI before pregnancy, an increased weight gain between pregnancies and a short...

Streptozotocininduced diabetes

Streptozotocin (STZ)-induced diabetes results from either intravenous or intraperitoneal (i.p.) injection of the toxin. Alloxan is also an effective diabetogenic agent but is now rarely used in pregnant animals. The mode of action of STZ and typical observations on the resulting diabetic derangements in various animal species have been extensively described in several reviews.1-5 A wide range of animals may be used to elicit diabetes in pregnancy by STZ, including rabbits, pigs, sheep, and subhuman primates.6-9 There is a marked difference in the effect of diabetes on the maternal, fetal and placental histopathology and metabolism depending on STZ dosage and time of injection. Rodents rendered diabetic before conception manifest hyperglycemia and hypoinsulinemia during organogenesis. As a result, they experience a high degree of fetal resorption and a high percentage of malformed fetuses.12-16 Injection of STZ into rats in midgestation between days 5 and 14 of gestation, produces...

Early gestational diabetes mellitus diagnosis as a risk factor

Early onset of GDM is a high-risk factor. Bartha et al.64 found that among 3986 pregnant women, those with early-onset GDM (n 65) were more likely to be hypertensive (18.46 vs. 5.88 , P 0.006), have higher glycemic values and greater needs for insulin therapy (33.85 vs. 7.06 , P < 0.001) than those in whom diabetes developed later (n 170). All cases of neonatal hypoglycemia (n 4) and all perinatal deaths (n 3) were in this group. The women with early GDM also had an increased risk of postpartum diabetes mellitus, whereas those with late-onset GDM had a minimal risk.65 The percentages of overt diabetes and abnormal glucose tolerance were significantly higher in the early pregnancy group (n 30) than in the late-pregnancy group (n 72) (26.7 vs. 1.4 and 40 vs. 5.56 , respectively).

Risk of Type 2 diabetes

Women with GDM have a 17-63 risk of Type 2 DM within 5-16 years.77 However, the risk varies according to different parameters. For example, Greenberg et al.,78 in a study of 94 patients with GDM, reported that the most significant predictor of 6-weeks postpartum diabetes was insulin requirement, with RR 17.28 (95 CI 2.46-134.42), followed by poor glycemic control, IGT and a GCT 200mg dL. All of these factors probably represent the magnitude of the insulin resistance, which is the hallmark of future diabetes and of other vascular complications. Similarly, Bian et al.79 reported a diagnosis of diabetes 5-10 years postpartum in 33.3 of patients with previous GDM (n 45), but only 9.7 (n 31) of these with IGT and 2.6 (n 39) of normal controls. Two or more abnormal OGTT values during pregnancy, a blood glucose level exceeding the maximal values at 1 and 2 h after oral glucose loading, and high pregnancy BMI were all useful predictors of diabetes in later life. In a recent study of 227...

Frequency of diabetes mellitus in the region

The prevalence of gestational diabetes in Latin American and the Caribbean Region may range from 1 to 14 of pregnancies, depending on the population studied. Gestational diabetes mellitus (GDM) represents nearly 90 of all pregnancies complicated by diabetes.10 In a recent communication of the World Health Organization in 2005,11 it was reported that the global frequency of diabetes in pregnancy in the region was 0.77 while in Cuba it was 1.75 , the highest rate in Latin America, followed by Argentina with 1.39 (Table 16.1). According to the Argentine Ministry of Health,12 over a total number of pregnant women (100,556 patients) the prevalence of diabetes in pregnancy in 2005 was 0.8 (n 789 patients) (Table 16.2).

Pancreatic betacell function in normal pregnancy and gestational diabetes mellitus

Insulin is the main hormone controlling blood glucose concentration. Most commonly, assessment of beta-cell function is made by measuring the fasting insulin concentration or the response to glucose infusion. Fasting plasma insulin increases gradually during pregnancy - by the third trimester levels are 2-fold higher than before pregnancy. Patients with GDM have fasting insulin levels equal to or higher than those of women with non-diabetic pregnancies, with the highest levels occurring in obese women with GDM. During normal pregnancy, oral and intravenous glucose tolerance deteriorates only slightly, despite the reduction in insulin sensitivity.13 The main mechanism responsible for that phenomenon is a gradual increase in insulin secretion by the beta cells. Kual12 reported a hyperbolic relationship between insulin sensitivity and beta-cell responsiveness to glucose in both pregnant and non-pregnant women, pointing to a role for the beta cells in pathological states such as GDM and...

EP Joslin Pregnancy and diabetes mellitus Boston Med Surg J 1915 173 841931

Joslin was the first internist to specialize in diabetes and wrote the first textbook on the subject. In 1915, 6 years before the discovery of insulin, he was able to describe seven personal cases of moderate or severe diabetes associated with pregnancy. He wished to take a more hopeful view, but admitted that little progress had been made. Of his seven cases, four were dead - one by suicide, one with uremic manifestations ( eclampsia), one of diabetic coma while under the care of a clairvoyant, and the fourth having survived one pregnancy with a healthy child died of pulmonary tuberculosis 2 months after losing her second child. But he was pleased that of the three remaining cases, one was in exceptionally good health, free from sugar and had a normal child, another in a tolerable condition having been pregnant three times but with only one child now living, and the remaining patient alive although severely ill with diabetes 6 years after confinement. He closed his paper with an...

Early history of diabetes

Diabetes was well recognized as a medical disorder more than 2000 years ago, and some well-known references are worth quoting. The ancient Egyptian Ebers papyrus, dating to 1500 bc, records abnormal polyuria the Greek father of medicine, Hippocrates (466-377 bc), mentioned 'making water too often' and Aristotle also referred to 'wasting of the body.' Aretaeus of Cappodocia (ad 30-90) in Asia Minor (now Turkey) is credited with first using the name diabetes, which is Greek for a siphon, meaning water passing through the body 'diabetes is a wasting of the flesh and limbs into urine - the nature of the disease is chronic, but the patient is short lived thirst unquenchable, the mouth parched and the body dry '. The famous Arabian physician Avicenna (ad 980-1027) recorded further important observations that maintained and extended the previous Greek knowledge through what became known in Europe as the Dark Ages he described the irregular appetite, mental exhaustion, loss of sexual...

Multiple pregnancy and gestational diabetes mellitus

Similar results were reported by Schwartz et al.31 in a study of 29,644 deliveries. They found that GDM was significantly more frequent in the 429 twin deliveries (7.7 vs. 4.1 , P < 0.05). However, insulin requirements were not different, suggesting a minor clinical impact. Wein et al.32 compared the prevalence of GDM between 61,914 singleton and 798 twin deliveries performed between 1971 and 1991. The difference was significant only for the earlier decade (5.6 vs. 7.4 , P 0.025). However, in a follow-up program there was a trend toward a higher prevalence of overt diabetes in the women who had had a diabetic twin pregnancy (18.5 ) compared to those who had had a diabetic singleton pregnancy (7.4 ). Whether this represents a true increased risk for diabetes is unknown. By contrast, using data derived from the Medical Birth Registry of Norway, Egeland and Irgens,33 controlling for other risk factors such as advanced age, parity, maternal history of diabetes and the woman's own...

Risk factors for gestational diabetes mellitus

The traditional and most often reported risk factors for GDM are high maternal age, weight and parity, previous delivery of a macrosomic infant and a family history of diabetes. These and other reported risk factors are summarized in Table 15.2. It is of great importance that the clinician understand and use these characteristics, along with others, such as the racial and geographic attributed risk (discussed above), to improve screening programs and diagnostic accuracy, and perhaps to design better and more cost-effective selective screening and diagnostic tests. Jang et al.8 examined 3581 consecutive Korean women and found a 2.2 prevalence of GDM. The affected women were older, had higher prepregnancy weights, higher BMI, higher parities and higher frequencies of known diabetes in the family. The risk of diabetes was closely associated with previous obstetric outcome, such as congenital malformation, stillbirth, and macrosomia. The number of risk factors present in each individual...

Criteria for GDM in New Zealand and epidemiology of diabetes in pregnancy

New Zealand currently diagnoses GDM using a 75-g 2-h oral glucose tolerance test. Criteria for GDM are a fasting glucose of > 5.5 mmol L and or 2-h glucose of > 9.0 mmol L. This is undertaken if there is a high risk of GDM early in pregnancy or after a 50 g glucose challenge test > 7.8 mmol L at 24-28 weeks gestation. These criteria are known as the Australasian Diabetes in Pregnancy Society (ADIPS) New Zealand criteria14 or New Zealand Society for the Study of Diabetes (NZSSD) criteria.15 They are more restrictive than the ADIPS Australia criteria (which uses a 2-h post-load level of > 8.0 mmol L) in a United Arab Emirates study,16 approximately 26-46 fewer cases were diagnosed depending on gestation. While these diagnostic criteria are used throughout New Zealand,17 there have been differences in perspectives on whether to screen all women for GDM or only those with risk factors. Although ADIPS recommends that all women be offered screening for GDM,14 until 2006, the New...

Genetics immunology and gestational diabetes mellitus

Some GDM patients manifest evidence for autoimmunity towards beta cells (insulin autoantibodies and anti-islet cell antibodies) however, the prevalence of such autoimmunity has been reported to be extremely low (< 10 ).62,63 Mutations in the glucokinase gene occur in no more than 5 of GDM patients.64 The inheritance of GDM was studied in a group Insulin signaling system in normal pregnancy and in gestational diabetes mellitus 75 of 100 women with previous GDM.65 The women were reinvestigated 11 years postpartum and 60 were found to have either IGT or Type 2 diabetes. An investigation of their parents showed that a substantial proportion had neither parent affected with IGT or Type 2 diabetes, which suggests a polygenic inheritance or environmental influence rather autosomal dominance inheritance with high penetration rates. In addition, animal studies have shown that prenatal exposure to a diabetic intrauterine milieu increases the risk of GDM. Harder et al.66 reported that the...

Management and outcomes of diabetes in pregnancy

Management guidelines now generally follow those published by ADIPS for either GDM14 or pre-gestational diabetes.25 The importance of pre-conceptual care was audited in the early 1990s from the long-standing Canterbury (New Zealand) insulin-treated register.26 This cohort includes predominantly European participants with Type 1 diabetes. With an 86 response, all women recognized the importance of good blood glucose control during pregnancy and 69 were using some form of contraception (combined oral contraceptive pill (35 ), the progesterone-only pill (12 ), condoms (24 ), vasectomy (12 ), and tubal ligation (12 )). Outcomes at National Womens Hospital were particularly poor in women with Type 2 diabetes in pregnancy between Figure 18.2 Prevalence of known diabetes among women of child-bearing age. 1985 and 1997. The cohort had high rates of perinatal mortality in Type 2 diabetes in pregnancy (46.1 1000), when compared with general rates (12.5 1000), Type 1 diabetes (12.5 1000) and GDM...

Pregnancy and diabetes before the discovery of insulin

A full historical review of fertility and of the outcome of pregnancy in different parts of the world is beyond the scope of this chapter, but there are a number of aspects that are of particular relevance to the story of diabetes. Medical history, in particular, is constrained by publication bias, and there is much more available data regarding Europe and North America than in other parts of the world. The geographical and ethnic differences in the distribution, development and management of diabetes in different places at different times would be of great interest to review, but as the data are patchy and both diabetic and obstetric treatments often poorly defined, it may be that 'History followed different courses for different peoples, because of differences among peoples' environments, not because of biological differences among peoples themselves.'7 There are certainly both environmental and genetic reasons for the differing prevalence and incidence of diabetes in different...

Insulin and hypoglycemic compounds

The passage of plasma proteins across the human placental barrier in humans is a highly selective process. It cannot be predicted on a simple way based on physical properties, i.e. protein binding, lipid solubility or molecular weight. In diabetic pregnancy, the safe use of insulin, insulin analogs and oral hypoglycemic agents relies on the absence of transfer from maternal to fetal circulation. It has been known for years that free maternal insulin does not cross the materno-fetal barrier either in early or late pregnancy.97-99 In addition, the absence of significant transfer of insulin lispro100 makes insulins the primary therapeutic choices for treatment of pregnant women with diabetes. However, insulin-binding antibodies have been detected in newborn infants whose diabetic mothers received insulin therapy. This is due to increased titer of antibodies in insulin-treated mothers and, the higher the antibody titer of the mother the greater is the total insulin in the fetal...

Young Japanese diabetics are mainly Type

As I have reported from time to time, Japanese diabetes is predominantly Type 2. This also applies to juvenile onset diabetes. Figure 20.1 shows the chronological change of pregnant diabetics treated by myself from the first delivery of diabetic pregnant women in Tokyo Women's Medical University from 1964 until my retirement in 1997. This figure demonstrates two characteristics of pregnant diabetics. Firstly, there is a drastic increase of the number of diabetic pregnant women since the 1960s. Secondly, it indicates that the number of Type 2 diabetic pregnant women is greater than Type 1. In the Diabetes Center of Tokyo Women's Medical University (TWMU), Type 1 diabetic pregnant women constituted 32.3 of the total. This was made possible by the rigid supervision of the diabetologists for children of the hospital. However, generally, there is 95 Type 2 diabetic women and only 5 Type 1 throughout Japan. Figure 20.2 shows the type of diabetes diagnosed before the age of 30 at the...

Incidence and prevalence of diabetes in the region

Diabetes continues to be a major concern for public health in the Americas and, unfortunately, its prevalence is likely to increase in Latin America and the Caribbean countries due to the demographic changes these countries are experiencing. According to King et al.,7 the number of diabetic people in the Americas is expected to rise from 35 million in 2000 to 64 million in 2025, and the incidence of diabetes in Latin America will increase from 52 to about 62 (around 40 million people),7 as a result of the aging process of the population and of increased sedentary habits and hypercaloric diets, both of which lead to obesity. King et al. also found that the incidence of diabetes is higher in women than in men in both developed and developing countries in the latter it usually affects middle-aged women rather than the elderly, as is the case in developed countries. The male female ratio shows how risk factors such as diet, low physical activity and obesity are distributed differently...

Glucose alterations in gestational diabetes mellitus

Independent of the mechanisms involved, in GDM, there is a relative lack of insulin during a period of time with high insulin needs to compensate the insulin resistance that develops in the third trimester of pregnancy. When gestational diabetes develops, in the maternal tissues, where glucose uptake is insulin-dependent, this is further decreased and hyperglycemia develops. Because the materno-placenta-fetal transfer of glucose is concentration-dependent9 under conditions of maternal hyperglycemia and placental normal function, there is increased placental transfer of glucose (Figure 6.1C), fetal hyperglycemia develops and secondary to this alteration, hyperinsulinism. As insulin is one of the main growth factors during fetal life,40 this hyperinsulinemia leads to macrosomia and to the complications secondary to the delivery of a large baby, mainly both maternal perineal damage and birth trauma, including shoulder dystocia, Erbs palsy, etc. The hyperinsulinism remains in the newborn...

Possible mechanisms of action of diabetes on the early embryo

Several mechanisms were shown to play a role in diabetes-induced early embryopathy in animals. Elucidation of these mechanisms of action may help to understand the human situation. We will, therefore, discuss these mechanisms mainly based on experimental animal models. Of the different glucose transporters existing in the early embryo, GLUT8 was recently found to be one of the most important.20 This transporter is regulated by insulin. During early differentiation of the mouse blastocyst there is a significant increase in glucose demand, and insulin causes GLUT8 to Possible mechanisms of action of diabetes on the early embryo 169 It can be concluded that the significant loss of progenitor cells from the ICM makes the embryos more sensitive to later developmental deficiencies. Furthermore, it was reported that normal embryogenesis can occur only if sufficient number of functional ICM cells are available.21 Increased apoptosis at this early stage of development may lead to spontaneous...

73 Type 1 Diabetes Mellitus

Type 1 diabetes mellitus (T1DM) accounts for 15-20 of all diabetes mellitus. Since it usually presents in childhood or early adulthood, it accounts for the majority of cases of pregestational diabetes. It is caused by autoimmune destruction of the insulin-producing P-cells of the pancreatic islets leading to insulin dependency, and there is a genetic pre-disposition to the condition.

Diabetes and pregnancy

Global fetal and infant loss, perinatal mortality, neonatal mortality, and malformations rates are significantly greater if the mother is affected by diabetes than in the nondiabetic population.1 Studies conducted by Casson et al.2 confirm that among unselected populations of women with insulin dependent diabetes mellitus (IDDM), pregnancy loss remains significantly higher than in the normal population. The diagnosis of congenital anomalies is also more accurate in infants of diabetic mothers since they are more carefully looked for in respect to control infants and because of the more frequent autoptic evaluation due to the higher mortality rate.3 Consolidated experiences clearly correlate fetal and maternal complications to the degree of metabolic control during pregnancy indicating without a doubt the need for an effective metabolic and obstetric management of women with different degrees of alteration of the glucose homeostasis during pregnancy.

Gestational diabetes mellitus

Risk factors for GDM are well known and their presence allows the identification of three risk categories (1) high risk, which is characterized by marked obesity, diabetes in first-degree relatives, history of glucose intolerance, previous infants with macrosomia, current glycosuria (2) average risk, which includes women that fit neither in the low- nor high-risk categories and (3) low risk, which includes women of the age < 25 years, normal weight before pregnancy, member of an ethnic group with a low prevalence of GDM, with no known diabetes in first-degree relatives, and no history of abnormal glucose tolerance, nor of poor obstetric outcome.5 with a high risk of GDM should undergo glucose testing as soon as feasible. A fasting plasma glucose level > 126 mg dL (7.0 mmol L) or a casual plasma glucose > 200 mg dL (11.1 mmol L) meets the threshold for the diagnosis of diabetes and if confirmed on a subsequent day rules out the need for any glucose challenge. In the absence of...

Pregestational diabetes

Pre-conceptional care of women with diabetes Despite progress in diabetes treatment pregnancies in women with either Type 1 or Type 2 diabetes are still associated with poorer outcomes with respect to healthy nondiabetic women. Another study conducted in the Netherlands in the period 199-2000 showed higher rate of perinatal mortality (2.8 ), preterm delivery (32.2 ), Cesarean section (44.1 ) and congenital malformation (8.8 ) in pregnant women with Type 1 diabetes related to the referring general population they also showed an higher incidence of poor outcomes in unplanned pregnancies.72 The model for diabetes preconception and early pregnancy health care includes four main elements (1) education of the patient about the interaction between diabetes, pregnancy, and family planning (2) education in diabetes self-management skills (3) physician-directed medical care and laboratory testing and (4) counselling by a mental health professional, when indicated, to reduce stress and improve...

103classification of diabetes

The American Diabetes Association defines diabetes mellitus as a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action or both 12 . The main classification of diabetes mellitus is type 1, type 2, and GDM. Type 1 diabetes, formerly known as insulin-dependent or juvenile-onset diabetes, is characterized by autoimmune destruction of the pancreatic beta-cells and accounts for 5-10 of all diabetes cases. Type 1 diabetes requires exogenous insulin for survival and is diagnosed primarily in persons less than 30 years of age. Type 2 diabetes, which accounts for almost 90 of diabetes cases, was previously known as adult-onset or non-insulin dependent diabetes. Insulin resistance rather than insulin deficiency and obesity are associated with type 2 diabetes. GDM is defined as any degree of glucose intolerance with onset or first recognition during pregnancy. The definition applies if medication or MNT is used in treatment or the...

1042 Complications Associated with Preexisting Diabetes

Complications associated with diabetes can adversely affect both the woman and fetus. The incidence of fetal complications is correlated with maternal glycemic control and the trimester of pregnancy. Macrosomia is the most common complication associated with diabetes and pregnancy, estimated at 20-45 , depending on the population 24, 25 . The definition of macrosomia varies and ranges from 4,000 to 4,500 g 26 . Macrosomia is thought to occur if maternal glycemic levels are elevated in the third trimester. Pedersen hypothesized that maternal hyperglycemia leads to fetal hyperglycemia, which stimulates the fetal pancreas to produce excessive insulin and results in excess growth 27 . Macrosomic infants have disproportional large fetal trunks in relation to their head size, thereby increasing the risk of difficult delivery, shoulder dystocia, brachial plexus palsy, or facial nerve injury. Advances in diabetes research and management have led to decreased risks of stillbirth in infants...

Concern about antiinsulin antibody formation during pregnancy

Anti-insulin antibodies that cross the placenta may contribute to hyperinsulinemia in utero and thus potentiate the metabolic aberrations in the fetus. Although insulin does not cross the placenta, antibodies to insulin do cross it and may bind fetal insulin this necessitates the increased production of free insulin to re-establish normoglycemia. Thus, the anti-insulin antibodies may potentiate the effect of maternal hyperglycemia to produce fetal hyperinsulinemia. Human and highly purified insulins are significantly less immunogenic than mixed beef-pork insulins.16 Human insulin treatment has been reported to achieve improved pregnancy and infant outcome compared to using highly purified animal insulins.14 Insulin lispro (which has the amino acid sequence in the beta chain reversed at positions B28 and B29) has been reported to be more efficacious than human regular insulin to normalize the blood glucose levels in GDM women. This insulin rapidly lowered the postprandial glucose...

Insulin algorithms for continuous insulin infusion pump therapy in pregnancy

The basal need is usually 50 of the total daily insulin dose (0.5I) and may be delivered using a constant infusion pump (Table 27.2) or by multiple doses of intermediate-acting insulin (Table 27.1). When using a constant infusion pump the basal need is calculated as an hourly rate (Table 27.2) and is delivered such that the calculated rate (0.5I or total dose over 24 h divided by 24) is given between 10 am and midnight. The rate is cut in half (i.e. 0.5I divided by 24 times 0.5) from midnight to 4 am, and increased by another 50 (i.e. 0.5I divided by 24 times 1.5) to counteract the morning rise of cortisol levels that are potentiated during pregnancy. Also, low-dose NPH before bedtime has been used by some clinicians to prevent the possible occurrence of diabetic ketoacidosis if the needle slips out of position during the overnight period. This dose of NPH insulin needs to be sufficient to provide protection from ketosis, or 0.1 unit of NPH times the weight of the women in kilograms....

Oral antidiabetic agents Classification and characteristics

In contrast to systematic studies that led to the isolation of insulin, sulfonylureas were discovered accidentally. Additional clinical trials led to the discovery of tolbutamide in the 1950s and since that time many agents in this class of drugs have been developed, e.g. chlorpropamide. Second-generation sulfonylureas were subsequently developed that include glyburide and glipizide. In 1997, the first drug in a new class of oral insulin secretagogues called meglitinides (benzoic acid derivatives) was approved for clinical use. The agent repaglin-ide has gained acceptance as a fast-acting, pre-meal therapy to limit postprandial hyperglycemia.21 The oral anti-diabetic agents act, depending upon the specific group, directly upon the beta cells to increase insulin secretion and or to decrease hepatic glucose production and to increase peripheral insulin sensitivity. The advantage of using these agents rather than administering exogenous insulin is their ability to have an impact by...

CSII decreases variability in insulin absorption

Variability in the action of insulin can cause fluctuations in glucose levels leading to the unpredictability of glucose levels. The cause is multifactorial among those described23 are different injections sites, physical activity, insulin preparations, insulin dose, insulin handling and mixing. Continuous subcutaneous insulin infusion offers a precise and a reproducible way of insulin administration resulting in less variability in absorption rates (< 3 ) in comparison to MDI.24,25 Contributing factors to the stability of insulin absorption is the single site of a continuous low rate flow of insulin (preferably a short-acting analogue) that prevents inter-regional variation in absorption, prevention of a subcutaneous reservoir formation and thus preventing third-space dynamics. The use of the distended abdominal region during pregnancy is not associated with clinically significant changes in insulin absorption. CSII decreases glycemic variability by stabilizing day-to-day insulin...

CSII and pregnancyrelated adjustments in insulin requirements

Insulin requirements during pregnancy change significantly in comparison to the nonpregnant state. These changes are caused by the physiological increase in insulin resistance that accompanies pregnancy and the weight gain. The adjustment of insulin treatment dose is complex because the increase is not linear and there are in-between periods of reduction in the insulin requirements. It is important to follow patients meticulously and to change the insulin doses appropriately. During gestation, the periods of decrease in insulin requirements are around week 12 and during periods when food intake is reduced. Notably, when patients suffer from hyperemesis gravi-darum, particularly in the first trimester, and when the pregnancy induces reflux disorders later on in gestation, patients suffer nausea and vomiting and thus decrease their food intake and insulin requirements. These constant changes and the need for sudden dose adjustments is best met by CSII which is currently the most...

Insulin pumps Hardware and disposables

Insulin pumps that are currently available carry the following components Insulin reservoir placed in the housing containing the pump The insulin pump weighs between 75 and 107 g. It holds the insulin reservoir, the volume of which differs between the models and varies between 2 and 3 mL (200 and 300 U). As the reservoir is changed every 2-3 days, the choice of model is dependent upon the daily insulin dosage. As the daily use of insulin at close to delivery averages 1.2 U kg it is recommended to choose pumps with 3-mL reservoirs. The different models shown in Figure 30.1 have much in common. Differences can be noted regarding reservoir volume and water compatibility. insulin pumps Bolus calculators and software 235

10113Risk Factors for Gestational Diabetes Mellitus

There is considerable controversy over the screening and diagnosis of GDM. The American Diabetes Association recommends assessing all pregnant women for risk of GDM at their first prenatal visit. Risk factors for diabetes are categorized as low, average, and high 3 . Women in the low risk category must meet all of the following criteria and require. No further screening No first-degree family history of diabetes Not a member of a group with a high prevalence of diabetes, which includes those of African, Hispanic, Asian, Pacific Islander, or Native American descent Strong family history of diabetes Member of an ethnic group with a high prevalence of diabetes (see above)

Insulin pumps Software

An important component of up-to-date insulin pump therapy is the computer-based information management system. These systems include both the software and the hardware for uploading and downloading data. Incorporation of these systems in the clinical setting enables the integration of the ever-growing data accumulated during the daily use of insulin pumps, and provides a unified platform useful Health team-generated information - basal rates, carbohydrate to insulin ratios, correction factors Information on patient's pattern of insulin use - total daily insulin use, basal bolus ratios, bolus patterns, pump disconnection periods An illustration of such an information management system is shown in Figure 30.2. In this system (e.g. CareLink Medtronic Minimed) the patient can download the data collected on the pump and on the glucose meter either at home or at the clinic. Data is then sent over the Internet to a server that can be accessed by an authorized physician. The integrated data...

10115Management of Gestational Diabetes

There are no universal guidelines in the management of GDM. A recent Australian randomized, controlled trial of 1,000 women with gestational diabetes showed that treating women with GDM reduced the risk of perinatal complications 60 . In this study by Crowther et al., the intervention group received MNT, self-monitored their blood glucose levels, and if indicated received insulin therapy. Perinatal complications were 1 in the intervention group and 4 in the group receiving routine care. MNT is the cornerstone of treatment in the management of GDM. The American Diabetes Association and the American College of Obstetricians and Gynecologists recommend nutritional counseling by a registered dietitian and an individualized meal plan 3, 58 . The American Dietetic Association's evidence-based Nutrition Practice Guidelines have identified the following MNT goals for GDM (1) to achieve and main- Diagnostic Criteria for Gestational Diabetes Mellitus tain normoglycemia, (2) to provide...

Insulin requirements during pregnancy

Although women with diabetes need to manage their blood glucose at all times, it is even more important prior to and during pregnancy, as blood glucose extremes can have an enormous effect on the health of the fetus. Preconceptional counseling and care are of extreme importance when a woman with Type 1 diabetes is planning a family. Preconception counseling and glucose control is essential because once pregnancy is diagnosed organogenesis is nearly completed. Poor blood glucose control during organogenesis can lead to both spontaneous abortions and congenital malformations.1 Frequently, women do not know that they are pregnant prior to the end of organogenesis. Without preconception glucose control, up to 25 of pregnancies may be affected.2 Near the end of the first trimester of pregnancy, maternal insulin needs decrease. This decrease in insulin requirement was first noted by Jorgen Pedersen,1 who warned other physicians to be aware of hypoglycemic events in women with diabetes, as...

Table 311 Insulin dosage regimen for diabetic pregnancy

Insulin dosage regimen for diabetic pregnancy 1. Pregnancy NPH plus rapid-acting insulin schedule Patient weight in kg Date & Time Big I total daily units of insulin Calculate desired units of insulin from above line. Big I Basal insulin requirement + Bolus (meal-related) insulin requirement Bolus Divide so that 1 6 of Big I is rapid-acting insulin given before breakfast, 1 6 of Big I is rapid-acting insulin given before lunch, and 1 6 of Big I is rapid-acting insulin given before dinner. The rapid-acting insulin is then titrated based on the blood glucose. A review article by Shalitin and Phillip8 gives an excellent history of attempts at and improvements upon the development of an artificial pancreas. The first major attempt at the artificial pancreas was made in the early 1970s with the Biostator , a glucose-controlled insulin infusion system which relied on glucose-sensing equipment and an algorithm dependent on the rate of change of the glucose readings to determine the amount...

Should a pregnant woman with diabetes use an artificial pancreas

The benefits of an artificial pancreas are ever increasing and potentially vast. Current deficiencies with fully functioning models render them imperfect, though improvements are quick to come and it is possible that there could be a fully functioning and accurate model of the entire device within the next few years. Benefits of wearing an artificial pancreas include peace of mind, such as not having to worry about not having enough insulin or having too much insulin, not having to remember to take blood glucose readings multiple times every day, and not having to remember to inject oneself with insulin before every meal and before going to bed. In addition, with an artificial pancreas there would be fewer finger sticks, less counting of calories and carbohydrates, and, if the patient's insulin delivery device and continuous glucose sensor are internal, no devices to clip to one's hip or carry in one's purse. The risk of diabetic ketoacidosis (DKA) during pregnancy would be lower with...

Gestational Diabetes Mellitus GDM

Diabetes can happen in pregnancy when the body does not produce adequate amounts of the hormone insulin to deal with sugar control during pregnancy. As a result, the sugar levels may climb. In most cases, the condition disappears after the delivery. In others, the condition may persist and long term follow-up and treatment of the diabetes is required. A repeat oral glucose test (OGTT) for diabetes will be performed six weeks after delivery. Once diagnosed, it is essential to control your blood sugar levels during the course of your pregnancy. The various measures include self-monitoring of blood glucose levels, diet and exercise management, insulin injections in more severe cases, and the close monitoring of you and your baby's well being by an experienced team of caregivers. This minimizes the risks to you and your baby. Good control means pre-meal level of 4.4-5.5 mmoL and post-meal level of 5.5-6.6 mmoL.

Clinical consequences of insulin resistance

Insulin resistance impairs glucose tolerance while promoting dyslipidemia, obesity, hypertension, and atherosclerosis. Its effects on salt handling by the kidneys predisposes the individual to renal dysfunction. Obesity, glucose intolerance, hyperinsu-linemia, hypertension, and dyslipidemia represent cumulative risk factors that generate an escalating cycle of vascular compromise and collapse. Patients with three or more of these risk factors have an increased incidence of stroke, nephropathy, ischemic heart disease, and peripheral vascular disease.82 Long-term diabetic complications are the most common cause of blindness, renal failure, and limb amputation in the United States today. Meticulous glycemic control has been shown to decrease the incidence of eye disease among diabetic patients. Antihypertensive therapy, specifically with angiotensin converting enzyme inhibitors (ACE-I), is effective in reducing the rate of progression of diabetic kidney disease. To prevent the peripheral...

Pregestational diabetes and hypertensive complications

In most cases, pregestational diabetes refers to Type 1 DM. The incidence of Type 1 DM in pregnancy ranges from 0.2 to 0.5 .119,120 Affected women contribute a heterogenous group in terms of duration of diabetes, White's classification, presence of hypertension, and end-organ damage, especially to the eye (retinopathy) and kidney (nephropathy). Pregnancy in women with Type 1 DM is associated with increased risks of pre-eclampsia, IUGR, neonatal morbidity, and perinatal mortality.110-127 The diagnosis of pre-eclampsia is difficult in women with preexisting hypertension and proteinuria,120 and women with chronic hypertension are at increased risk of superimposed pre-eclampsia independent of the presence of diabetes.128 The rate of hypertensive disorders (PIH and pre-eclampsia) in the various studies ranged from 9 to 66 . The lowest rate occurred in women with milder forms of DM (class B), and the highest in women with diabetic nephropa-thy. Table 41.1 summarizes the reported rates of...

Pathophysiology and treatment of diabetic nephropathy

Diabetic nephropathy is a progressive disease that affects approximately 30 of patients with diabetes and it is the most common cause of end stage renal disease in USA. The first clinical sign is increased excretion of albumin in the urine, so called microalbuminuria in the range 30-300 mg 24 h, corresponding to a spot urine albumine to creatinine ratio of 30 mg g. Untreated microalbuminuria progresses to overt diabetic nephropathy characterised by persistent proteinuria, hypertension and a relentless decline in glomerular filtration rate.4 Histological changes in the glomeruli with increased basal membrane thickness and glomerulosclerosis are characteristics, but universal leakage of albumin over the endothelium in the whole body is also present. Progression to end stage renal disease occurs with a median duration of 7 years after onset of diabetic nephropathy, if let untreated. The introduction of inhibition of the renin-angiotensin system in combination with other antihypertensive...

Effects of pregnancy on diabetic nephropathy

Few studies have examined the long-term effect of pregnancy on renal function in women with diabetic nephropathy after strict antihypertensive treatment has been widely used and improved the survivial. The most recent is a case-control study including 26 pregnant women with diabetic nephropa-thy and normal serum creatinine followed for up to 13 years and the decline in kidney function was compared to women with diabetic nephropathy who did not became pregnant in the study period.8 The women were offered strict antihypertensive treatment as routine treatment.during the whole study period. They found that in women with serum creatinine within the normal range, pregnancy did not accelerate the decline in kidney function or impair the long-term survival of the mother.8 However, in women with a reduced creatinine clearance reports suggest that there is an increased risk of deterioration of kidney function during pregnancy.9,10 The long-term survival of a mother with diabetic nephropathy...

Effect of diabetic nephropathy on pregnancy outcome

The presence of diabetic nephropathy significantly affects the outcome of pregnancy, primarily due to three reasons (1) the increased risk of maternal hypertensive complications (2) the increased risk of preterm delivery due to deteriorating maternal blood pressure and pre-eclampsia and (3) the increased risk of intrauterine fetal growth restriction and fetal distress caused by placental dysfunction. Severe malformations have been described with a slightly higher prevalence in women with diabetic nephropathy compared to diabetic women with normal kidney function. However, this is most likely due to the poorer metabolic control early in pregnancy often found in these women. The risk of perinatal mortality in pregnancies complicated by diabetic nephropathy is now close to that of women with Type 1 diabetes without diabetic nephropathy.1-3 The rate of pre-eclampsia in women with diabetic nephropathy is high 53-64 1,2,3,11 especially when reduced kidney function,12 hypertension at onset...

Treatment of women with diabetic nephropathy during pregnancy

Strict metabolic control during pregnancy is of utmost importance but may be difficult because women with Type 1 diabetes and diabetic nephropathy often have an increased risk of severe hypoglycaemia. Close surveillance of blood pressure and urinary albumin excretion is central while 24 h ambulatory blood pressure recording has not been shown to be of benefit in the care of these women.15 Early onset and strict antihypertensive treatment as in the nonpregnant state might improve the outcome. In patients with microalbuminuria introduction of early onset antihypertensive treatment with methyldopa in normotensive pregnant women with Type 1 diabetes and microalbuminuria resulted in a significant reduction in preterm delivery before gestational week 34.16 Furthermore, early onset and strict antihypertensive treatment in women with diabetic nephropathy most likely also reduce the severity of pre-eclampsia end preterm delivery. Our center recommends initiating antihypertensive treatment in...

Counseling women with diabetic nephropathy

Careful counseling of the woman and her partner of the risk for herself and the newborn is important before the couple can take a well-considered decision regarding pregnancy. An updated diabetes status including hemoglobin A1c, risk of hypoglycemia, degree of retinopathy, serum creatinine, blood pressure, and proteinuria is necessary to estimate the risk for complications during pregnancy. The number of antihypertensive drugs to control the blood pressure sufficiently prior to pregnancy is also of importance, since there has to be room for further intensification of antihypertensive treatment in late pregnancy, if necessary.

Breastfeeding and maternal diabetes

Fifteen observational studies have been written about the role of breastfeeding in IDM and IGDM.54 There is no contraindication to breastfeeding in these infants, and diabetic women should have the same opportunity to breastfeed as women without diabetes. Higher rates of pregnancy and neonatal complications among diabetic women can pose significant challenges to breastfeeding. Thus, women with diabetes should be strongly encouraged to breastfeed because of maternal and childhood benefits specific to diabetes that are above and beyond other known benefits of breastfeeding.54 Although maternal hypoglycemia does not cause a reduction in breast milk lactose level, it does lead to increased secretion of epinephrine, which inhibits milk production and the ejection reflex. In addition, elevated acetone levels can be expressed in breast milk, placing stress on the newborn liver.55 As a result, the diabetic mother should be well instructed in order to achieve the right adjustment of diabetes...

The effects of diabetes on postnatal intellectual and neurological development

The development of children born to diabetic mothers was studied for almost 40 years. Churchill et al.44 were apparently the first to describe the finding of lower IQ scores in children born to diabetic mothers with acetonuria while children born to diabetic mothers without acetonuria, functioned normally. No effect of insulin treatment on the IQ of the offspring was noted, and there was no correlation of the IQ with the duration of maternal diabetes. Schulte et al.,45 in their study on the neurological development of newborn infants born to diabetic mothers found longer rapid eye movement (REM) sleep time, seemingly as a sign of reduced brain maturation, in these newborns in comparison to controls. Stehbens et al.46 examined children born to diabetic mothers at 1, 3 and 5 years of age. The SGA children born to diabetic mothers had lower cognitive scores in comparison to controls. Similarly, Petersen et al.47 found that SGA children of diabetic mothers had lower verbal performance at...

Diabetes mellitus and impaired glucose tolerance in women with previous GDM

Although glucose tolerance returns to normal in the majority of women with GDM shortly after delivery, there is substantial evidence that these women have an increased risk of developing overt diabetes later in life.1 In the classical studies by O'Sullivan, diabetes was diagnosed in 36 of women 22-28 years after a pregnancy with GDM.2 A significantly increased risk for diabetes has later been confirmed in other populations, some of which are presented in Table 50.1. However, large variations exist among the different published studies. The trend has been that the reported risk for diabetes is higher in studies from the US compared to European studies. This has been ascribed to many factors where differences in ethnicity, degrees of obesity and diagnostic and screening criteria are the most important.

Predictive factors for development of overt diabetes in women with previous GDM

Having confirmed that women with GDM are at risk for subsequent development of overt diabetes it could be relevant, at least in populations with a low prevalence of diabetes, to be able to predict which women among the women with previous GDM who have the highest risk. Yet, the high proportion with diabetes among women with a history of GDM, even in populations previously considered as low risk populations, insinuate that these women comprise a group of potential diabetics decades after delivery. Many potential predictive factors like, e.g. plasma glucose, plasma insulin, relative weight and age are closely related and hence it is necessary to control for covariance and confounding factors in the analysis of predictive factors for diabetes development, a fact not always taken into consideration. Table 50.2 summarizes the pregnancy related predictive factors for future diabetes, both Type 1 and Type 2 diabetes, identified by multivariate analysis. Other obvious factors predictive for...

Insulin resistance and the metabolic syndrome

Type 2 diabetes is characterized by insulin resistance decreased insulin sensitivity primarily in skeletal muscle and decreased insulin secretion,37 but the primary defect in the pathogenesis of Type 2 diabetes is still unknown. In normoglycemic individuals insulin secretory dysfunction as well as decreased insulin sensitivity have been found to be precursors of diabetes.33 Several studies have documented decreased insulin sensitivity in lean as well as obese glucose tolerant women with previous GDM.38,39 The decreased insulin sensitivity is mainly caused by a reduced non-oxidative glucose metabolism in skeletal muscle tissue.38 The cellular background for this is not known. A relatively decreased insulin secretion in lean and obese glucose tolerant women with previous GDM has also been found.9,38,39 Thus women with previous GDM exhibit the metabolic profile of Type 2 diabetes several years after the GDM pregnancy despite a normal glucose tolerance. The presence of insulin resistance...

Diagnosis of gestational diabetes mellitus

Proving that a diagnostic test is reproducible and accurate is only the beginning, and not the end, of its evaluation. Introduction of an effective new screening policy, or a diagnostic test, into clinical practice should be expected to have a major impact on the outcome of diabetic pregnancies. One expects that a test with a better performance (sensitivity, specificity) would restrict interventions, such as blood glucose monitoring and treatment (diet, insulin), to those women who are likely to benefit from such interventions. However,

Costeffectiveness of preconception care for women with pregestational diabetes

Preconception care for women with established diabetes reduces the incidence of fetal malformations and spontaneous abortions.21 Three groups have assessed the costs of preconception care relative to the savings resulting from adverse maternal and neonatal outcomes averted. All demonstrated that preconception care for women with established diabetes is cost saving (Table 52.1).22-24 A case-control study of women with Type 1 diabetes mel-litus was conducted by Scheffler et al to assess the cost-benefit of preconception care.22 The study estimated the costs of a preconception care program using a time-motion methodology, and analyzed actual hospital charges and length of stay for women enrolled in the California Diabetes and Pregnancy Program (CDAPP). These included 102 women with Type 1 diabetes who participated in the preconception care program and subsequently received standard prenatal care a group of 218 women with Type 1 diabetes who did not participate in the program but who...

Table 522 Cost per case of gestational diabetes mellitus GDM diagnosed using various screening protocols

Risk factors birth of a baby weighing > 4000 g (c.) (> 9lb) a history of two or more pregnancies of fetal death, neonatal death, congenital anomaly, prematurity, excessive weight gain, hypertension or proteinuria family history of diabetes mellitus. (Adapted from Reed.29) The Fourth International Workshop-Conference on Gestational Diabetes Mellitus31 suggested that two techniques -the two-tiered protocol with Carpenter-Coustan modifications and the one-tiered protocol (2-h 75-g OGTT) - are both acceptable methods to screen for GDM. Lavin et al.32 compared the costs and the patient time associated with the two-tiered protocol and the one-tiered modification employing the 2-h OGTT. The two-tiered protocol had lower costs than the one-tiered protocol low-range and high-range costs for the two-tiered protocol were 3 and 8 per woman low-range and high-range costs for the one-tiered protocol were 6 and 11 per woman. Test times were 1.4-1.5 h for the two-tiered protocol and 2 h for the...

Quality assessment and improvement in diabetes care

Patients' organizations from all European countries met diabetes experts to discuss a set of recommendations - the St Vincent Declaration,1 a joint initiative of the World Health Organization-Europe and the International Diabetes Federation-Europe (WHO IDF) - with the intention of creating conditions allowing major reductions in deaths and the burden caused by diabetes mellitus. The declaration meant an important step forward in the general improvement in the quality of delivery of diabetes health care. One of the main targets of the declaration was to establish monitoring and control systems using state-of-the-art information technology (IT) for quality assurance of diabetes health care provision. A European group of experts was established to design and implement mechanisms for the continuous improvement of the quality of diabetes care in Europe. The term 'continuous quality improvement' was accepted to emphasize the progressive nature of the never-ending process after reaching a...

Screening for diabetes in pregnancy

In 1994, a court in Alberta tried a 1988 case5 in which a macro-somic baby suffered Erb's palsy after shoulder dystocia. During pregnancy the family doctor had failed to implement the universal screening policy for gestational diabetes that had been recommended by the Alberta Medical Association and the Society of Obstetricians of Canada. He also overlooked maternal glycosuria and significant maternal weight gain. He then failed to recognize fetal macrosomia on manual palpation and failed to request an ultrasound scan. The court found that his care was negligent in that he failed to follow guideline recommendations and that he failed to recognize clinical signs. This Canadian case contrasts with a similar English case decided shortly afterwards. In 1998 the English Court of Appeal decided a 1990 case6 relating to the screening for diabetes in pregnancy. At 30 weeks gestation a woman exhibited glycosuria ++. Her family doctor carried out a random blood glucose test, which was normal at...

Insulin and glucose treatment during labor

The artificial beta cell may be used to maintain normoglycemia during labor and delivery, but normoglycemia can be maintained easily by subcutaneous injections. Before active labor, insulin is required, and glucose infusion is not necessary to maintain a blood glucose level of 70-90 mg dL. With the onset of active labor, insulin requirements decrease to zero and glucose requirements are relatively constant at 2.5 mg kg min. From these data, a protocol for supplying the glucose needs of labor has been developed.67 The goal is to maintain the maternal plasma glucose between 70 and 90 mg dL. In cases of the onset of active spontaneous labor, insulin is withheld and an intravenous (i.v.) dextrose infusion is begun at a rate of 2.55 mg kg min. If labor is latent, normal saline is usually sufficient to maintain normo-glycemia until active labor begins, at which time dextrose is infused at 2.55 mg kg min. Blood glucose is then monitored hourly and if it is < 60 mg dL then the infusion rate...

Diabetes before pregnancy

If you have a history of diabetes, talk to your doctor about it before you get pregnant. If you have your blood sugar level under good control before you conceive, your pregnancy is more likely to proceed smoothly. Women with pregestational diabetes stand a higher-than-average risk of having a fetus with certain birth defects, but you can reduce this risk down to the normal range if you achieve excellent glucose control. Some doctors suggest that you have a blood test called a hemoglobin A1C to check how well your sugar has been controlled over the past few months. Your doctor may also suggest that you have a special sonogram, called a fetal echocardiogram (see Chapter 8), to make sure that the baby's heart is okay. If you take an oral medication to control your blood sugar, your practitioner may suggest you switch to insulin injections for better control. Some women with diabetes suffer kidney complications, but this kind of problem isn't likely to worsen during pregnancy. If you...

4119 Insulin and oral antidiabetics

Insulin as a proteohormone does not reach the mother's milk, and is not absorbed intestinally. Any effect on the infant can therefore be ruled out. There are no data on the other oral antidiabetics, acarbose, gli-bornuride, gliclazide, glimepiride, gliquidone, glisoxepide, miglitol, pioglitazone, repaglinide, and rosiglitazone. Recommendation. Insulin and metformin are not problems during breastfeeding. Glibenclamide may also be taken however, the infant should be observed for symptoms of hypoglycemia after the start of therapy. Other oral antidiabetic should not be taken, but single doses do not require any limitation of breastfeeding.

Effects of diabetes mellitus on postmenopausal women

Women with Type 1 diabetes frequently go through menopause at an earlier age, in average age of 41.6 years than nondiabetic women with an average age of 49.9 years.33 Diabetes mellitus (DM) was found to be associated with an increase in uterine size in postmenopausal women.34 In addition, the relative risk of endometrial cancer in diabetic women is 4-fold higher than in nondiabetic women.27,35 The risk of endometrial cancer also increases with the use of unopposed estrogen in non-hysterectomized women36 and is reduced with the use of cyclical or continuous progestins.37-39 Women become more prone to urinary and vaginal infections during and after menopause, this problem is greater in women with diabetes.40 Over the course of 2 years, women with diabetes were 1.5 times as likely to have a urinary tract infection with symptoms and twice as likely to have one without symptoms as women without diabetes were. Both risks were higher in women who took insulin and women who had had diabetes...

Genes in the etiology of maternal diabetes

Genetic predisposition plays an important role in determining whether a mother has diabetes before she is pregnant or whether she develops diabetes during pregnancy. In most cases in addition to this genetic susceptibility, there is also a considerable environmental component in both Type 1 diabetes or Type 2 diabetes. It is only in monogenic diabetes that the diabetes or hyperglycemia occurs almost exclusively as a result of genes. There are very different issues in the polygenic, complex forms of diabetic pregnancy and the rarer mono-genic forms. These are therefore dealt with separately.

Prepregnancy Type 1 diabetes

In most European, Caucasian diabetic pregnancy clinics Type 1 diabetes is the commonest cause of diabetes diagnosed before pregnancy. This is not the case in patients from high prevalence Type 2 populations from the Asian and African continents, where Type 2 diabetes is often as common, or more common, than Type 1. Genetic factors are very important in Type 1 diabetes, even though it is rarely familial. The risk of diabetes before the age of 18 is approximately 6 in siblings of Type 1 diabetic patients, 2 in the offspring of diabetic mothers and 4 in the offspring of diabetic fathers. Although these familial risks are low, the relative risk is greatly increased compared to a population risk of Type 1 diabetes of 0.4 . The critical role of non-genetic factors is made clear in observations in identical twins if one twin has Type 1 diabetes the risks of the second twin developing diabetes is in the region of 40 . The nature of the environmental component is uncertain and might possibly...

Prepregnancy Type 2 diabetes

Pre-pregnancy Type 2 diabetes is increasingly common. To have Type 2 diabetes prior to becoming pregnant, onset would have to be early compared to the typical late middle or old age. A key component of subjects diagnosed when young is that they are very likely to have a considerable genetic predisposition, coupled with increased environmental factors such as increased obesity and reduced physical exercise. Table 61.1 includes a comparison of the likely characteristics of early-onset and compares it with late-onset Type 2 diabetes and gestational diabetes. Evidence for the genetic susceptibility includes the increased prevalence of Type 2 diabetes among Table 61.1 Comparison of the relative role of genetic factors and obesity in young-onset Type 2 diabetes, gestational diabetes and late-onset Type 2 diabetes Table 61.1 Comparison of the relative role of genetic factors and obesity in young-onset Type 2 diabetes, gestational diabetes and late-onset Type 2 diabetes Early-onset Type 2...

Gestational diabetes and the relationship to Type 1 diabetes

Type 1 diabetes may be diagnosed for the first time in pregnancy but this is relatively rare. There is an increase in the presence of islet antibodies in gestational diabetes especially in Scandinavian populations suggesting a proportion of patients with gestational diabetes have a slow autoimmune destruction of the beta cell.13,14 It might be expected that the molecular genetics are similar to latent-autoimmune diabetes in adults (LADA). In keeping with this here is some evidence that HLA associations are present, in patients with gestational diabetes and pancreatic autoantibodies.13

Gestational diabetes and the relationship to Type 2 diabetes

Patients who are diagnosed with diabetes or glucose intolerance in pregnancy, and who then return to normal glucose tolerance after pregnancy are known to be at high risk of developing Type 2 diabetes. Estimates of the risk vary between 10 and 50 within 5 years of the pregnancy, depending on the racial group and diagnostic criteria used for gestational diabetes. This would suggest that there is likely to be a similar etiology in gestational diabetes and Type 2 diabetes, with the pregnancy associated insulin resistance precipitating hyperglycemia during pregnancy. It also suggests that the molecular genetics for gestational diabetes will considerably overlap with Type 2 diabetes in the same population. To date, studies into defining the genetic predisposition to gestational diabetes have had limited success, with no genes showing reproducible association across studies. The main problem has been achieving sufficiently large cohorts for these studies. This has proved considerably more...

Other monogenic forms of diabetes

Patients with many other monogenic forms of diabetes may occur in pregnant women (Table 61.3). In some patients the likelihood of pregnancy is reduced patients with severe insulin resistance may have reduced fertility as a result of the associated polycystic ovarian syndrome and some of the multi-system syndromes that include diabetes suffer from severe neurological defects. The commonest form of mono-genic diabetes in the diabetic pregnancy clinic outside the MODY genes is maternally inherited diabetes and deafness due to the mitochondrial 3243tRNA leucine mutation. Permanent neonatal diabetes has recently been shown to frequently result from mutations in the Kir6.2 gene. These are dealt with in more detail below. Mitochondrial tRNA leucine 3243 mutation. The 3243mtDNA was common is a large Japanese study of the patients attending a diabetic pregnancy clinic. The mutation was present in 6-8 of pre-gestational Type 2 diabetes and gestational diabetes but it was not found in Type 1...

Diabetes genes in fetal growth

The idea that diabetes genes were important in the predisposition of mothers to hyperglycemia in pregnancy is not unexpected, given their role in the predisposition to Type 2 diabetes. A novel concept which has been developed since 1998 is that the genes that cause monogenic diabetes or predisposed to Type 2 diabetes may result in reduced fetal growth.40,41 This is an interesting area where further study is required and may help to explain at least part of the association between low birthweight babies and the predisposition to Type 2 diabetes as adults. The initial observations were made in monogenic diabetes, but there is increasing evidence that these same observations apply to Type 2 diabetes and the general population. Fetal genetic effects in glucokinase pregnancy Glucokinase mutation effects on glycemia are present from birth. This means therefore, that any mutation carrier, whenever diagnosed, will have had relative fasting hyperglycemia during pregnancy. Therefore their...

Fetal insulin hypothesis

The most important impact of these results in glucokinase mutations is that it establishes that a gene involved in glucose metabolism can also have a considerable impact on birth-weight. This led to the fetal insulin hypothesis which proposes that the association of low birthweight, with subsequent Type 2 diabetes and insulin resistance could have a genetic explana-tion.41 On the basis of the glucokinase observations it was proposed that altered insulin sensing, insulin secretion or insulin action could result in reduced fetal growth by reducing insulin mediated growth in utero as well as predisposing to Type 2 diabetes by altering glucose metabolism. This hypothesis has been tested in a wide variety of situations. There is increasing evidence to support that at least part of the explanation of the association between low birthweight and later diabetes may be due to a genetic mechanism.

Support for the fetal insulin hypothesis from monogenic diabetes studies

There has been strong evidence for the principle that genes resulting in monogenic diabetes have a large impact on fetal growth. In addition to the observation of glucokinase, which acts on glucose sensing (see above), there is also greatly reduced birthweight in mutations that reduce insulin secretion or action. The impact n fetal growth on monogenic diabetes mutations are outlined in Table 61.3. When hyperglycemia is detectable soon after birth due to reduced insulin secretion (e.g. Kir6.2 neonatal diabetes) it is not surprising that there is also reduced insulin secretion in utero and hence low birth-weight.42 More striking is that mutations in HNF-1P are associated with a 800g reduction in birthweight despite diabetes not usually developing until early adult life (Edghill and Hattersley, personal communication). This observation is compatible with the role of HNF-1P in pancreatic stem cells43 which is supported by loss of function mutations resulting in reduced pancreatic size and...

Insulin resistance and polycystic ovary syndrome

Insulin resistance is present in 40-50 of patients, especially in obese women,31 making PCOS a prediabetic state. The prevalence of impaired glucose tolerance (IGT) in PCOS is 31-35 , and the prevalence of Type 2 diabetes mellitus is 7.5-10 .32 The conversion rate from IGT to overt Type 2 diabetes is increased 5- to 10-fold in women with PCOS.33 Women with PCOS are at increased risk of pregnancy and neonatal complications a recent meta-analysis34 demonstrated that these women are at higher risk of developing gestational diabetes odds ratio (OR) 2.94 95 confidence interval (CI) 1.70-5.08 , pregnancy-induced hypertension (OR 3.67 95 CI 1.98-6.81), pre-eclampsia (OR 3.47 95 CI 1.95-6.17) and preterm birth (OR 1.75 95 CI 1.16-2.62). Their babies had a significantly higher risk of admission to a neonatal intensive care unit (OR 2.31 95 CI 1.25-4.26) and a higher perinatal mortality (OR 3.07 95 CI 1.03-9.21), unrelated to multiple births.

Hyperinsulinemic insulin resistance

Insulin resistance is defined as the decreased ability of insulin to stimulate glucose disposal into target tissues, or a reduced glucose response to a given amount of insulin. Chronic hyper-insulinemia is a compensatory response to this target tissue resistance. Several mechanisms have been suggested to explain insulin resistance, including peripheral target tissue resistance, decreased hepatic clearance, or increased pancreatic sensitivity. Studies with the euglycemic clamp technique indicate that hyperandrogenic woman with hyperinsulinemia have peripheral insulin resistance and a reduced insulin clearance rate due to decreased hepatic insulin extraction.35,36 The peripheral insulin resistance in PCOS is uniquely due to a defect beyond the activation of the receptor kinase, namely, reduced tyrosine autophosphorylation of the insulin receptor.37,38 The reduced signal transmission caused by excessive phosphorylation of serine residues on the insulin receptor also explains the...

Hyperinsulinemia and impaired ovulation

Dale et al.59 examined the correlation between insulin metabolism and outcome of gonadotropin stimulation in 42 infertile, CC-resistant women with PCOS. Using continuous infusion of glucose with the model assessment test, they identified 17 patients with insulin resistance who required higher doses of gonadotropins and a longer duration of treatment to achieve follicular maturation. In this group, 35 of the cycles were cancelled due to a multifollicular response compared to 2.5 in the noninsulin-resistant PCOS group. Moreover, although the ovulation rate in completed cycles was similar between the groups, the conception rate was significantly better in the women with noninsulin-resistant PCOS. Hyperinsulinemia and obesity correlate directly with the failure to ovulate in response to CC, or with the need for multiple repeated courses and increasing doses of CC.60,61 Thus, women with PCOS and severe insulin resistance are more likely to fail to respond to CC.62 BMI is a major...

Successful Pregnancy in Women with Type 1 Diabetes From Preconception Through Postpartum Care

AKeck School of Medicine, University of Southern California at Los Angeles, Los Angeles, CA, USA b University of California at Santa Barbara, Santa Barbara, CA, USA cSansum Diabetes Research Institute, Santa Barbara, CA, USA dDepartment of Medicine, University of California Davis Health Systems, Sacramento, CA, USA Using 2002 birth data 1 , it is estimated that diabetes affects an estimated 8 of the more than 4 million pregnancies that come to term annually in the United States. Identifying women who require aggressive monitoring and treatment of their diabetes to minimize both maternal and fetal complications during and after pregnancy is a significant challenge for physicians and the health system because almost 75 of pregnancy-related diabetes occurs in women with gestational diabetes or undiagnosed type 2 diabetes. Conversely, although type 1 diabetes is estimated to account for only 1 to 2 of the pregnancies complicated by diabetes ( 6000 births in the United States annually),...

What can be done to reduce the rate of perinatal mortality in pregnancies complicated by diabetes

The St Vincent declaration given in 1989 set a goal to equalize pregnancy outcomes of women with diabetes mellitus to those of nondiabetic women within 5 years. Although there has been considerable advancement in the ability to detect fetal anomalies, establish fetal well-being and maturity, this goal, which was perceived as feasible at the time (especially in light of the conceivable improvement in pregnancy outcomes of insulin-dependant diabetic women), has not been met. The presence of diabetes is thought to increase the risk for congenital malformation by as much as 10-fold, stillbirth (up to 5-fold), and neonatal death (3- to 4-fold).3 There are very few randomized control trials (RCTs) regarding the relationship between glycemic control and pregnancy outcome.69 The DCCT (Diabetes Control and Complications Trial) suggested that early and tight glycemic control might reduce pregnancy-loss rates and congenital anomalies rates equal to those of general population.70 This finding was...

Insulin and glucose requirements postpartum

Maternal insulin requirements usually drop precipitously postpartum, possibly for 48-96 h. Insulin requirements should be recalculated at 0.6 unit kg based on the postpartum weight and should be started when the 1 h postprandial plasma glucose value is > 150 mg dL or the fasting glucose level is > 100 mg dL. The postpartum caloric requirements are 25 kcal kg day, based on the postpartum weight. For women who wish to breast feed, the calculation is 27 kcal kg day and insulin requirements are 0.6 unit kg day. The insulin requirement during the night drops dramatically during lactation, owing to the glucose siphoning into the breast milk. Thus, the majority of the insulin requirement is needed during the daytime to cover the increased caloric needs of breast feeding. Normoglycemia should especially be prescribed for nursing diabetic women, because hyperglycemia elevates milk glucose levels.68

Rationale for the use of human insulin during pregnancy

Maternal glucose.1-5 Perhaps the debate remains because some reports claim that neonatal complications occur in spite of excellent metabolic control, although there fail to measure postprandial glucose levels.11,12 Postprandial glucose control has been suggested as key to neonatal outcome for the pregnant woman with either Type 1 diabetes or GDM.6-8 Alternatively, some have suggested that neonatal morbidity is secondary to the variability of maternal serum glucose and the presence of antibodies to insulin.13 Placental transfer of insulin complexed with immunoglobulin (IgG) has also been associated with fetal macrosomia in mothers with near-normal glycemic control during gestation. Menon et al.13 reported that antibody-bound insulin transferred to the fetus was proportional to the concentration of antibody-bound insulin measured in the mother. Also, the amount of antibody-bound insulin transferred to the fetus correlated directly with macrosomia in the infant and was independent of...

Delicious Diabetic Recipes

Delicious Diabetic Recipes

This brilliant guide will teach you how to cook all those delicious recipes for people who have diabetes.

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