Intrauterine devices

The legacy of the Dalkon Shield intrauterine device (IUD) was to associate IUD use with pelvic inflammatory disease (PID), a complication that in diabetic women could precipitate life-threatening ketoacidosis. Physicians caring for diabetic women have since been reluctant to prescribe the IUD. This misconception is being slowly reversed. Studies have shown that the development of pelvic inflammatory disease and subsequent tubal infertility were not related to the use of the IUD, per se, but the...

Data that may support higher GDM rate in multiples

GDM is one of the most frequent pregnancy complications and is related to co-morbidities such as premature delivery, fetal macrosomia, birth trauma, unexplained antepartum fetal demise, pregnancy-induced hypertension, and placental abruption. Specifically, a retrospective population-based study of twins conceived by in vitro fertilization (IVF) found that patients who developed severe pre-eclampsia were more likely to have GDM.7 Hyperplacentosis presumably increases hormonal levels in multiple...

Diab Card as an instrument for quality assurance

The DiabCard project (EU-AIM 2051) developed the specifications for a chip-card-based medical information system and the requirements for Europewide collection of data about diabetes for clinical and managerial purposes. A common diabetes Figure 53.5 Basic Information Sheet for Diabetes and Pregnancy (DiabCare). Figure 53.5 Basic Information Sheet for Diabetes and Pregnancy (DiabCare). data set based on EuroDiabeta was produced and validated in ambulatory and hospital care. An open architecture...

Prevalence Of Diabetes And Fertility

The reported prevalence of neonatal hypoglycemia in diabetic pregnancy varies because of variations in the definition of the disorder this is in addition to differences in methods of glucose examination, maternal control of diabetes during pregnancy and labor, and neonatal treatment, particularly feeding. It is not surprising in the light of these great variations that the previous figures for neonatal hypoglycemia in infants of diabetic mothers (IDM) have only historical significance. During...

Microalbuminuria diabetes and hypertension in pregnancy

The role of microalbuminuria in DM has been established over the last 20 years. At the early stage of DM, when glucose metabolism is not controlled, the increase in glomerular plasma flow and intraglomerular pressure is probably responsible for the increased protein excretion.144 Some authors believe these hemodynamic alterations are major determinants of both the initiation and progression of diabetic nephropathy.145 Several studies have reported that patients with Type 1146 or Type 2 DM147...

Insulin resistance and hypertension in pregnancy

In normal pregnancy, insulin resistance results in a metabolic advantage for the fetus. The mother enters a state of accelerated starvation in which she increases her reliance on lipolysis and protein catabolism as a source of energy. Thus, glucose is reserved for the fetus, which uses it as its primary fuel.89 A steady supply of glucose is essential for the growing fetomater-nal unit normally, pregnant women are able to increase their insulin secretion to three times that of nonpregnant...

Metabolic syndrome When hypertension and diabetes meet

The striking increase in the prevalence of obesity, diabetes mellitus (DM), hypertension, and cardiovascular disease in the last two decades1 has led to the concept of the metabolic syndrome.2 Also termed syndrome X,3 insulin resistance syndrome,4 and the deadly quartet,5 metabolic syndrome is characterized by a constellation of well-documented risk factors for cardiovascular disease, namely, glucose intolerance, insulin resistance, central obesity, dyslipidemia, and hypertension, that co-occur...

Doppler velocimetry of fetal cardiac and venous areas

Newborns of diabetic mothers are at risk for hypertrophic miocardiopathy. This condition is characterized by thickening of the interventricular septum,42 of ventricular walls and by alterations of systolic and diastolic function that can lead to congestive cardiac failure.43 Doppler evaluation of fetal heart in diabetic pregnant women has mainly the aim of finding flow abnormalities at the atrioventricular and ventriculoarterial valves, to identify the signs of a potential chronic hypoxemia and...

The Diabetes in Pregnancy Center at Northwestern University in Chicago

This is the other longitudinal study that has reported excessive growth in the offspring of women with diabetes during pregnancy.11,12 In this study, amniotic fluid insulin was Figure 48.3 Mean relative weight for height in offspring by age and mothers diabetes in normal birthweight offspring (birthweight 90-109 of the median weight for gestational age). (Reprinted with permission from Pettitt et al.6) Figure 48.3 Mean relative weight for height in offspring by age and mothers diabetes in...

Lipids and fatty acids

At birth about 12-15 of the fetal body mass is fat, and about half of that fat is derived from maternal sources passing across the placenta over the whole period of gestation. The remainder may be due to the lipogenic activity of the fetal liver and other tissues. For most fatty acids a maternal-fetal concentration gradient exists and, hence, free fatty acids may traverse the placenta by simple diffusion, but the major proportion will bind to fatty acid transfer proteins on the microvillous...

Diabetogenic forces of normal pregnancy increase insulin requirements10

The fetal demise associated with pregnancy complicated by Type 1 diabetes seems to arise from glucose extremes. Elevated maternal plasma glucose levels should always be avoided, because of the association of maternal hyperglycemia with subsequent congenital malformation and spontaneous abortions.2,5 To achieve normoglycemia, a clear understanding of 'normal' carbohydrate metabolism in pregnancy is paramount. Thus, the amount of insulin required to treat Type 1 diabetic women throughout...

Intrauterine factors in metabolic syndrome The fetal origin of adult disease

Barker6 pioneered the idea that the epidemic of coronary heart disease in Western countries in the twentieth century, which paradoxically coincided with improved standards of living and nutrition, originated in fetal life. He postulated that the low birthweight and impaired fetal growth which were characteristic of deprived regions in the 1900s may have predisposed the survivors to heart disease in later life. Support was provided by studies conducted in Hertfordshire, England, showing a higher...

Diabetologic education

The objective of medical care for diabetic patients is to normalize glycemia levels and to minimize the complications of the disease. Achieving near normal glycemia levels delays the onset of chronic complications, reduces the number of medical visits and hospital stays, and lowers health costs. During pregnancy, the goal of metabolic management (glycemic monitoring, dietary regulation and insulin therapy) is to prevent or minimize the postnatal sequelae of diabetes -macrosomia, shoulder...

Management of diabetic retinopathy during pregnancy

As discussed earlier, diabetic retinopathy can worsen during pregnancy. Thus, patients with diabetic retinopathy should undergo preconception counseling and follow-up during pregnancy by a multidisciplinary team that includes a perinatologist, endocrinologist, and ophthalmologist that are experienced in the management of diabetic retinopathy. Patients with diabetes who are planning to become pregnant should be given a thorough explanation on the risk of development or progression of diabetic...

Mechanisms underlying metabolic syndrome

Metabolic syndrome is characterized by a cluster of clinically recognizable physiological abnormalities glucose intolerance, high BP, and unfavorable lipid profile - all alterations induced by the compensatory hyperinsulinemia. It also involves biochemical abnormalities.45 Up-regulation of the inflammatory cascade has recently been recognized as an additional risk factor for the impaired cardiovascular component of the syndrome.46 Insulin resistance now appears to be the epidemiological link...

Fetal effects of diabetic ketoacidosis

The greatest hazard facing the pregnant diabetic patient with DKA is fetal loss. The exact fetal loss rate is difficult to assess because of the small reported series in the literature. Historically, the reported fetal mortality ranged between 30 and 90 7 but remarkable progress has been made both in fetal assessment techniques and in the treatment of DKA, and mortality rates in more recent reviews are 10 .20 Needless to say, fetal loss is primarily related to the severity of the maternal...

Problems with and solutions for the artificial pancreas

Over the many years that researchers have been attempting to create an artificial pancreas, many obstacles have crept in. Early insulin pumps did not have a means of adjusting basal levels throughout the day. Additionally, many glucose sensors were unable to perform their job accurately because of interference or inability to take measurements on a continuous basis. Currently, pumps have adjustable basal rates and glucose sensors, are becoming accurate, but one important component of the...

Gestational diabetes and hypertensive disorders

The study of both GDM and PIH has suffered from the lack of international consensus about classification, definitions, and nomenclature, leading to difficulties in comparing studies that used different diagnostic criteria. Nevertheless, epidemiologi-cal and physiological evidence suggests that GDM and PIH are etiologically distinct entities and that GDM is strongly associated with insulin resistance and glucose intolerance, whereas pre-eclampsia is probably not. Diabetic pregnancy is associated...

Optimizing insulin therapy during pregnancy

Following the initial set up of the basal rate CF, CIR, and the glucose goals, the patient returns for the fine tuning of the pump. In order to optimize the basal rate one can observe the pattern of the preprandial glucose either from SMBG or from continuous glucose monitoring. The latter is especially useful for determining and fine tuning the overnight basal rate. Additional technique is meal skipping that is, a meal is postponed and the glucose trend is followed either by SMBG every 30 min...

European Diab Care quality network

A subgroup of the St Vincent Declaration Steering Committee was established to develop instruments and mechanisms for quality assurance in diabetes care. The first initiative of the DiabCare Program was the development of the St Vincent Diabetes Dataset from three main sources (1) EuroDiabeta, a research project on modeling health care and the implementation of IT in diabetes 2 (2) the specific recommendations provided by the different working groups of the St Vincent Declaration Steering...

Use of rapidacting insulin analogs in pregnancies complicated by diabetes

Postprandial glucose control in the patient with GDM is important to neonatal outcome.6-8 The Diabetes in Early Pregnancy (DIEP) Study identified 28.5 of infants from diabetic mothers who were > 90th percentile in infant birth-weights.8 The birthweight in this 28.5 correlated positively with fasting blood glucose and A1C. When adjusted for fasting blood glucose and A1C, the nonfasting blood glucose concentration in the third trimester was an even stronger predictor of infant birthweight and...

Longterm outcomes

No prospective follow up study of women with past GDM has yet been published. A median 6-year follow-up of 14 women with diabetic nephropathy after pregnancy showed significant morbidity particularly progression to renal replacement therapy in 36 .32 Inter-generational effects of diabetes in pregnancy have been researched in a number of ways. Possible ethnic differences in predisposition to Type 2 diabetes have been shown from studies of umbilical cord blood and neonatal anthropometry. The...

Conclusion

Gestational diabetes is a period of glucose intolerance that manifests at the beginning of the third trimester. Metabolic changes in the normal pregnant women also have a degree of insulin resistance that shunts glucose preferentially to the fetus. To maintain blood glucose levels within a tight range, the normal pregnant woman must increase her insulin secretion up to 4-fold. When the pancreas is not able to compensate for the increased insulin needs of pregnancy, GDM occurs resulting in...

Neurological and psychological development

Reports of long-term neurological deficits in the offspring of diabetic mothers include impaired visual motor function, Erb's palsy, seizure disorders, cerebral palsy, mental retardation, speech disturbances, reading difficulties, behavior disturbances and deafness.57-63 Mechanisms potentially involved in the occurrence of such problems are (1) birth trauma, especially trauma to the head and neck because of large infant size and shoulder dystocia 64 (2) prolonged, severe neonatal hypoglycemia,...

Insulin infusion pumps

Insulin infusion pumps have been used for treatment for over two decades.57 However, the data on the safety and efficacy of Table 27.2 Basal insulin pump program (using human regular, insulin lispro or insulin aspart) Table 27.2 Basal insulin pump program (using human regular, insulin lispro or insulin aspart) Basal requirement (B*) (hourly infusion rate) *B 0.5I (the total daily insulin) or an hourly rate of B 24. To refine basal settings, have the patient perform self-blood glucose monitoring...

Diab Care BIS for diabetes and pregnancy

One of the main recommendations of the St Vincent Declaration was the following 'Achieve pregnancy outcome in diabetic women that approximates to that of nondiabetic women'. In consequence, WHO IDF guidelines for care and management of pregnant diabetic women have been proposed by an invited group of international experts in the field.14 The document brought attention to the important differences in the provision of diabetes and obstetrical care in different European countries. Specifically,...

In vitro studies performed by us

Culture in 'diabetic' culture medium We cultured pre-implantation mouse blastocysts for 72 h in RPMI medium with the addition of 10 fetal bovine serum, and found 20-24 of embryonic developmental arrest.12 Addition of high concentrations of glucose, acetoacetate, P-hydroxybutyrate, glucagon and insulin were all embry-otoxic, inducing a high percentage of embryonic death. However, while the concentrations of most substances were much higher than possibly found in diabetes, the embryotoxic glucose...

The incidence of GDM in China

Descriptions of DM can be seen in ancient literatures from China, India, Egypt, Greece, and Rome, although it is not necessarily the same as the 'DM' we are talking about today. In the last two decades, the Chinese economy has developed rapidly, and the disease profile of Chinese people has changed greatly because of the new way of life. Diseases due to malnutrition and infection have been greatly reduced, while cancer and chronic diseases such as cardiovascular diseases and DM are now major...

Disadvantages of CSII

The major disadvantage of CSII is ketoacidosis resulting from disturbance in insulin delivery. Though pump malfunction is rarely the cause for ketoacidosis, occlusions of the infusion sets and or cannula by a mechanical kink or deposits can cause nondelivery of insulin. In these cases occlusion detectors provide alarms triggered by increasing pressure in the system. More problematic, are low pressures the more common cause is dislodgement of the catheter, empty reservoir, air bubbles, and...

Summary

The 1997 WHO estimates of the prevalence of diabetes in adults showed an expected total rise of > 120 from 135 million in 1995 to 300 million in 2025.2 These numbers also include GDM, and should alert physicians to the need to direct special attention to this population, especially in developing countries. The data presented in this chapter indicate that the epidemiology of GDM is characterized by several features. Differences in screening programs and diagnostic criteria make it difficult to...

Does treatment of GDM make a difference in pregnancy outcome

In June 2005, Crowther and colleagues24 published the results of a 10-year multi-center randomized clinical trial in Australia and the United Kingdom called the Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS) (Table 26.1). The purpose of the ACHOIS was to determine whether medical nutritional therapy, glucose monitoring, and insulin therapy was superior to routine prenatal care with regard to reducing the risk of perinatal complications and postpartum maternal health...

Clinical studies

The use of oral anti-diabetic agents was historically contraindi-cated in the US. This dogma, supported by scant data, was predicated on the assumption that the drugs could cause fetal damage and or demise. The results of numerous studies during the current decade have systematically revealed the error in the above assumptions. Yet, there persists a group of nay-sayers who are tenacious in their disregard of new research findings thus denying the mother and fetus alternative, more convenient...

C57 BIKS leprdb heterozygotes

These mice are highly attractive for the study of GDM. Only a few experimental protocols have been carried out with these animals,92 but the information gained suggests that they may represent an excellent experimental approach. Heterozygous leprdb+ mice have a significant glucose intolerance and elevated glycohemoglobin levels during pregnancy, compared with pregnant homozygous non-diabetic siblings. There was no difference in litter size, whereas the mean weight of pups of heterozygous mice...

Single nodule of the thyroid gland

Nodular thyroid disease is clinically detectable in 10 of pregnant women. In most cases, it is discovered during the first routine clinical examination or detected by the patient herself. The chances for a single or solitary thyroid nodule to be malignant are between 5 and 10 , depending on risk factors such as previous radiation therapy to the upper body, rapid growth of a painless nodule, patient age, and family history of thyroid cancer. Papillary carcinoma accounts for almost 75-80 of...

Lack of awareness of hypoglycemia

The inability of patients to recognize impending hypoglycemia is a major clinical problem in the management of insulin treated diabetes and it represents an important barrier to tight metabolic control especially in patients that have been encouraged to treat their diabetes intensively. Lack of awareness of hypoglycemia is a common long-term complication of diabetes. Epidemiological surveys in unselected population have reported that around 25 of subjects with Type 1 diabetes experience...

Glycated serum proteins

Mostly albumin, and other serum proteins, undergo the process of glycation. The turnover of serum albumin depicts a half-life of 25 days it provides an index of a mean glycemic level of a shorter interval than HbAlc. The fructosamine assay is the most widely method being used for estimating glycated serum proteins. Nevertheless, although fructosamine levels correlate with HbAlc levels within a population, transference cannot apply for individual values.41 Also, changes in serum proteins affect...

In diabetes

Hypoglycemia is the most frequent acute complication of Type 1 diabetes mellitus therapy. It has been reported that diabetic people live about 10 of their life with glycemic values lower than 60 mg dL (3.3 mmol L) and that, on average, once a week they present an episode of symptomatic hypoglycemia. About every 4-5 years a case of these can lead to coma with the need of assistance and admission to hospital.1 In 2-4 of the cases hypoglycemia causes death for people with Type 1 diabetes...

References

Diabetes care and research in Europe The Saint Vincent declaration. Diabet Med 1990 19 360. 2. Platt MJ, Stanisstreet M, Casson IF, Howard CV, Walkinshaw S, Pennycook S, McKendrick O. St Vincent's Declaration 10 years on outcomes of diabetic pregnancies. Diabet Med. 2002 19 216-20. 3. Evers IM, de Valk HW, Visser GHA. Risk of complications of pregnancy in women with type 1 diabetes nationwide prospective study in the Netherlands. BMJ 2004 328 915-8. 4. Kauffman RP. The Diabetes...

Omnipod And Pregnant Patients

Figure 30.1 (A) Various types of insulin pump. From left to right Animas IR-1250 Deltec Cozmo ACCU-CHEK Spirit Medtronic MiniMed Paradigm 522 722 and OmniPod.(B) Various infusion sets. Infusion sets have various lengths and the choice will depend on the patient's height and pump positioning preference. Typical lengths of the infusions sets are 23,24, 31,42, and 43 inches. Most cannulas used today are made of Teflon, introduced subcutaneously with a removable metal inserter. Cannulas of older...

Treatment

Prompt and vigorous treatment in an obstetric intensive care unit is generally needed to decrease the high maternal and fetal mortalities accompanying DKA. All treatment protocols are based on correcting volume depletion, supplying insulin, correcting acidosis and electrolyte imbalance, and, most importantly, identifying and correcting any possible precipitating factor. Continuous fetal heart rate monitoring and biophysical assessment are essential to assess fetal well-being during the third...

Diabetes characteristics in pregnant STZinduced diabetic rats

STZ-induced diabetes should serve mainly as a model for pregestational diabetes since the hyperglycemia and metabolic derangements are the result of beta-cell destruction, whereas GDM is characterized by insulin resistance and compensatory hyperinsulinemia with possible secondary lesion to beta cells as a result of the strain of oversecretion. Even moderate doses of STZ, which result in mild hyperglycemia, do not represent GDM, since the result is a limited insulin deficiency due to a reduced...

Hormone replacement therapy in the diabetic patient

Traditionally, the prevention of severe renal disease and retinopathy has been the primary target in the long-term management of diabetes. It seems that HRT carries neutral effect toward these goals. In a 10-year follow-up of women with late-onset diabetes, HRT use was found to be unrelated to the severity of retinopathy or the incidence of macular edema.61 In another study, 6 months of CEE MPA treatment failed to reverse micro-albuminuria in postmenopausal diabetic patients.62

Rationale for the use of human insulin during pregnancy

Although controversial, the rate of complications in pregnancies of diabetic women has been tied to the metabolic control of 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...

Box 353 Guidelines from the RCOG94 on the antenatal use of glucocorticosteroids

Guidelines of Royal College of Obstetricians and Gynecologists Antenatal corticosteroids to prevent Respiratory Distress Syndrome Effectiveness Antenatal corticosteroids are associated with a significant reduction in rates of RDS, neonatal death and intraventricular hemorrhage. Evidence level Ia The cost and duration of neonatal intensive care is reduced following corticosteroid therapy. Evidence level III The optimal treatment-delivery interval for administration of antenatal corticosteroids...

Principle of beneficence

The principle of beneficence requires each of us to act in a way that is expected reliably to produce the greater balance of goods over harms in the lives of others.5,8,12 To put this principle into clinical practice requires a reliable account of the goods and harms pertinent to the care of the patient, and of how those goods and harms should be reasonably balanced against each other when not all of them can be achieved in a particular situation. In medical ethics, the principle of beneficence...

Timing of delivery

There is no convincing data as to the optimal timing of delivery of the macrosomic fetus of the woman with diabetes. Gestational age, estimated fetal weight and the degree of glucose control all play a role.In one randomized controlled trial in 200 low-risk women with insulin dependent pre gesta-tional diabetes, a lower incidence of Cesarean sections, large-for-gestional age infants and shoulder dystocia was found in case of induction of labor at 38 weeks as compared to expectant management.32...

Impaired semen production

In adult rats, long-term diabetes with sustained hyperglycemia leads to significant testicular dysfunction associated with decreased fertility potential,132 and this may also be true for humans. Garcia-Diez et al.,133 in a study of 80 patients with Type 1 diabetes, found significant alterations in semen parameters and levels of prolactin and testosterone. In all patients, seminal insulin concentrations were higher than serum concentrations. The authors speculated that the hormone freely crosses...

Pulse oximetry

Pulse oximetry is focused on recording the actual level of fetal hypoxemia and relates the level of oxygenation of organ function as indicated by FHR.9 A US multicenter randomized trial of 1010 women in labor with a non-reassuring FHR tracing showed a reduction in emergency Cesarean sections from 10 to 5 . However, unexpectedly, the study also showed an increase in the Cesarean section rate for failure to progressin the test group, 19 vs. 9 , and the overall Cesarean section rates were not...

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 gt 150 mg dL or the fasting glucose level is gt 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...

Screening strategies

There is no debate about the longstanding observation that when overt diabetes mellitus DM occurs during pregnancy it is associated with adverse maternal and fetal outcomes. Since early diabetes, especially Type 2 DM, is usually asymptomatic, virtually all care-givers are alert to the need to detect and treat overt diabetes. Therefore, they all engage in some form of a screening process. Indeed, it has been acknowledged that systematically taking a personal and family medical history represents...

Congenital anomalies

An association between maternal diabetes mellitus and congenital malformations has been suspected since the nineteenth century.21,22 Despite the considerable advances in the management of the pregnancy complicated by diabetes, the rate of congenital malformations has not changed dramatically. Congenital malformations and their sequelae have replaced intrauterine fetal death and respiratory distress syndrome as the major causes of morbidity and mortality in infants of diabetic mothers.21 Their...

Insulin and glucose treatment during labor

With improvement in antenatal care, intra-partum events play an increasingly crucial role in the outcome of pregnancy. 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...

Types of malformations

The congenital malformations of IDM and IGDM constitute a spectrum known as diabetic embryopathy DE .21,24 This spectrum implies errors of morphogenesis which appear between the third and the seventh week of embryonic development end of blastogenesis and organogenesis .25 Within this spectrum of DE, cardiac, skeletal, central nervous system CNS , uro-genital, gastro-intestinal, facial and multiple malformations were repeatedly described Table 23.1 . Congenital malformations in IGDM and...

Estrogen and progesterone

In early pregnancy, both progesterone and estrogen rise but their effects on insulin activity are counterbalanced. Progesterone causes insulin resistance whereas estrogen is protective.20 An IVGTT test given to estrogen-treated rats showed a significant decrease in glucose concentrations and a 2-fold increase in insulin concentration 21 the addition of progesterone was associated with a 70 increase in the insulin response to a glucose challenge test, but there were no alterations in glucose...

Pump use during labor and delivery

Maintaining euglycemia during the peripartum is essential for the prevention of neonatal hypoglycemia. When the pregnant diabetic woman enters active labor the insulin requirements fall drastically while the glucose infusion rate necessary to maintain a blood glucose level of 70-90 mg dL was found to be constant at 2.55 mg kg min.39 Protocols for maintaining euglycemia during labor are usually based on i.v. infusion of glucose, to maintain glucose consumption, and low rate of insulin 1-4 U h...

Box 22 Priscilla Whites last classification

Gestational diabetes Abnormal glucose tolerance test, euglycemia maintained by diet alone. Diet alone insufficient, insulin required Class A Diet alone sufficient, any duration or onset age Class B Onset at the age of 20 or older, duration lt 10 years Class C Onset between the ages of 10 and 19, or duration 10-19 years Class D Onset before the age of 10, duration gt 20 years, background retinopathy or hypertension not Class R Proliferative retinopathy or vitreous hemorrhage Class F Nephropathy...

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...

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...

C57BL6J mice

The non-obese, non-diabetic BL 6J mice, the genomic host of the ob ob mutation, when placed on an affluent fat and sucrose-rich diet become hypertensive and insulin resistant with first-phase insulin release disappearing at 6 months of age.95-97 Abnormalities, characterized by increased outflow from the sympathetic nervous system, deranged beta-cell function and adipocyte metabolism were found to be responsible for the resultant IGT and insulin-resistance syndrome. No hyper-phagia or elevation...

Cord and fetal membranes

The length of the cord at term is between 40 and 70 cm and the diameter is usually between 1 and 3 cm. A short or excessively long cord is related to an increased risk for fetal damage. Marginal cord insertion or velamentous cord insertion, which probably are due to disturbed implantation, may be also associated with fetal or neonatal damage. Histopathologic features such as thrombosis of vessels or the observation of a single artery should be already suspected by a macroscopic analysis of cord...

Rationale for universal screening

Selective screening based on risk factors scored poorly in predicting GDM.22 If selective screening is employed, it is likely that 16 of GDM women will go undetected.23 Further selective screening recommended by ADA may be applicable for women belonging to the ethnic group with low prevalence of GDM. Whereas, among ethnic groups in South Asian countries, Indian women have the highest frequency of GDM necessitating universal screening.24 The recognition of glucose intolerance during pregnancy is...

Prolactin

During pregnancy, maternal prolactin levels increase 7- to 10-fold. Gustafson et al.27 reported that the basal insulin concentration and post-challenge glucose and insulin responses were greater in women with hyperprolactinemia than in healthy controls. These findings were supported by studies showing that the culture of pancreatic islet cells with prolactin induces an increase in insulin secretion.28 Skouby et al.29 investigated the relationship between the deterioration in glucose tolerance...

Introduction

A diseased foetus without his placenta is an imperfect specimen, and a description of a foetal malady, unless accompanied by a notice of the placental condition, is incomplete. Deductions drawn from such a case cannot be considered as conclusive, for in the missing placenta or cord may have existed the cause of the disease and death. During intrauterine life the foetus, the membranes, the cord and the placenta form an organic whole, and disease of any part must react upon and affect the...

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...

Concluding remarks

Autoimmune GDM appears to be the result of the variable expression of autoimmunity against the beta cell, challenged by the higher functional demand associated with the insulin-resistant state of pregnancy. In this respect, autoimmune gestational diabetes can be considered a distinct clinical entity. There are different time-course patterns in the progression of autoimmune GDM from the restoration of normal glucose tolerance when pregnancy is over even with eventual disappearance of autoimmune...

ItHMl rnibFnici TA nr MI I

Figure 1.1 The title page of Dr Bennewitz's thesis De diabete mellito, graviditatis symptomate,28 with translation into English. The disease appeared along with pregnancy, and at the very same time when pregnancy appeared, it appeared while pregnancy lasted, it lasted it terminated soon after the pregnancy. He showed a degree of humility when he remarked that his patient must be something of a rare bird. The case history commences on 13 November 1823, when Frederica Pape, aged 22, was admitted...

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...

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 lt 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...

Changes in intermediary metabolism during pregnancy

As has been shown in previous chapters, throughout pregnancy there are major changes in intermediary metabolism, changes that will facilitate the fetal needs of energy and precursors for fetal and placental growth, as well as for placental hormone synthesis. From a metabolic point of view, during gestation there are two different periods. In the first half of pregnancy, during the embryo development period, there are maternal changes that lead to storage of energy and nutri-ents.1-3 The stored...

Monitoring glycemic control

The continuous glucose monitoring has demonstrated that the time interval from meal to peak postprandial glucose level was approximately 90 min and was similar in all the evaluated types of diabetic pregnancies insulin treated or diet only and is not affected by the level of glycemic control. Moreover, no difference was obtained in postprandial glycemic profile between breakfast, lunch or dinner.43 Hence the present policy in India, from August 2006, is to maintain FPG lt 90 mg dL and 1.5 h...

Conclusions

From this group's personal experience, it can be concluded that, despite late first prenatal visits, when pregnant women receive prenatal care before birth, perinatal results are acceptable. However, the question remains as to how many diabetic patients never reach prenatal care, are never detected, or approach the hospital to deliver a dead or macrosomic fetus without a final diagnosis of the pathology that has led to this end. These are the deficiencies of a developing country which lacks a...

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...

Multiple pregnancy and gestational diabetes mellitus

The number of fetuses in multifetal pregnancies is expected to influence the incidence of GDM owing to the increased placental mass and, thereby, the increase in diabetogenic hormones. However, the reports are somewhat conflicting, probably because of the heterogeneous populations studied. In an interesting study of the prevalence of GDM in dizygotic DZ twin pregnancies with two placentae compared to monozygotic MZ twin pregnancies with one placenta, Hoskins29 evaluated 3458 recorded twin...

Autoimmune GDM and the risk of developing postpartum DM1

A main issue regarding autoimmune GDM is that of the potential increased risk for the development of DM-1 either at short term after partum or at longer follow-up. We can accept the proposal that the majority of women developing DM after GDM will evolve to DM-2 12,14 nevertheless, a small but meaningful fraction will evolve to DM-1. After delivery, the autoimmune process directed against beta cells may follow different pathways 1 the restoration of normal glucose tolerance when pregnancy is...

Placental lipid metabolism and fetal lipid supply

The amount and type of fatty acid or complex lipid transported by the placenta varies among species. Lipid transport varies according to the transport capacity of the placenta it is greatest in the hemochorial placenta of the human, guinea pig and rabbit, and least in the epitheliochorial placenta of the ruminant and the endotheliochorial placenta of the carni-vores.71 There are many lipid substances in the plasma that are transported across the placenta that are essential for pla-cental and...

Genetic markers in autoimmune GDM

Although genetic markers hold a most relevant promise for the future, they are of only limited clinical value in the evaluation and management of diabetic patients. To screen for the genetic susceptibility for autoimmune-mediated Type 1A diabetes, HLA typing is most useful. The HLA complex on chromosome 6p21.3 is a major susceptibility locus, IDDM1. The HLA complex contains class I and II genes that code for several polypeptide chains. The class I genes are HLA-A, -B, and -C. The loci of class...

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...

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,...

Embryopathy in STZinduced diabetic animals

One of the numerous problems confronted in overt diabetic pregnancy is fetal wastage together with a large percentage of congenital malformations, mainly in neural tissues and skeleton development. Cytotoxin-induced diabetic rodents are therefore preferred models for the study of fetal malformations. As mentioned before, a correlation exists between hyperglycemia in the organogenesis phase and the extent of malformations in the offspring of diabetic rodents.16,37 Since hyperglycemia is the main...

Is there an associated increased adverse outcome in GDM

The infants of GDM women are at an increased risk for stillbirth and aberrant fetal growth macrosomia and growth restriction as well as metabolic e.g. hypoglycemia and hypocal-cemia , hematological e.g. bilirubinemia and polycythemia and respiratory complications that increase neonatal intensive care unit admission rates and birth trauma e.g. shoulder dystocia 19,20 Table 14.1 . Congenital anomalies and spontaneous abortions are not as serious complications in GDM as they are in pre-gestational...

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...

Diabetogenecity Of Pregnancy Due To

Action of toxic drugs on islet cells. In Cooperstein SJ, Watkins D, eds. The Islets of Langerhans. New York Academic Press 1981, pp. 387-425. 2. Shafrir E. Diabetes in animals. In Porte Jr. D, Sherwin R, Baron A, eds. Diabetes Mellitus, 6th edn. New York McGraw-Hill 2003. 3. Okamoto H. The molecular basis of experimental diabetes. In Okamoto H, ed. Molecular Biology of the Islets of Langerhans. Cambridge Cambridge University Press 1990, pp. 209-31. 4. Boquist L....

Human placental lactogen

Human placental lactogen hPL levels rise at the beginning of the second trimester, causing a decrease in phosphorylation of insulin receptor substrate IRS -1 and profound insulin resistance.20 Beck and Daughday30 demonstrated that overnight infusion of hPL results in abnormal glucose tolerance, and increased insulin and glucose concentration in response to an oral glucose challenge. Accordingly, Brelje et al.31 found that in islet cell culture, hPL directly stimulates insulin secretion. This...

Cognitive development in children of diabetic mothers

Several studies evaluated the association between cognitive development and metabolic fuels in pre-existing and gt LGA infants of GDM mothers had a higher BMI, greater waist circumference and abdominal skinfold compared to AGA-GDM. gt No difference between non-GDM LGA and AGA. Modified from Vohr et al, Diabetes care, 1999 Figure 14.3 Long-term complications of the infant of the diabetic mother. Infant's age 4-7 years. Modified from Vohr B et al. Diabetes Care 1999 22 8 128-91. AGA-NON-GDM...

Neonatally STZadministered rats nSTZ

Among the syndromes resembling mild Type 2 diabetes as a consequence of reduced beta-cell mass are rats which received neonatal STZ injection nSTZ , either at the time of birth45,46 or 2 days after birth.46,47 It should be stressed, however, that these animals, although non-obese, do not represent a true Type 2 diabetes, but rather a model of limited insulin deficiency with little, if any, peripheral or hepatic insulin resistance. The i.p. or intravenous injection of 90-100 mg kg STZ into...

Metabolic change as teratogens

In the late 1970s and early 1980s, Freinkel and his group extended their focus beyond the factors that mediate insulin secretion in the fetus, insulin-dependent fetal growth and other manifestations of third trimester fetal hyperinsulinism to consider the consequences of an altered intrauterine metabolic environment throughout gestation. Describing pregnancy as 'a tissue culture experience'17 put this concept into sharp relief and Norbert Freinkel's 1980 Banting Lecture18 was a masterful blend...

Placental structure and morphology

The placenta is a complex organ made up of a variety of tissues that theoretically can contribute to transplacental transfer. All materials destined for transfer to the fetus must first be taken up by the microvillous membrane of the syncy-tiotrophoblast, the tissue which is in direct contact with maternal blood in the intervillous space. Once within the syncytium the molecules are either sequestered for modification lipids or metabolized for placental purposes glucose , or they leave the...

Goto Kakizaki rats

Apart from animals with spontaneous alterations leading to inappropriate hyperglycemia, a diabetic line was isolated by repeated breeding of normal animals. The selection was of individuals with minimal deviation from the mean response to a glucose load. This emphasizes the polygenic basis of diabetes within a 'normal' genetic mosaic. A GK diabetic line was obtained by breeding Wistar rats for gt 35 generations in Japan, using a relative intolerance to a 2 g kg glucose load as a selection...

Hyperlipidemia

Hyperlipidemia normally develops during the last third of gestation and mainly corresponds to increases in triacylglycerols, with smaller rises in phospholipids and cholesterol.17,19 Besides an increase in VLDL levels as a result of their enhanced liver production and decreased removal from circulation as a consequence of reduced adipose tissue LPL activity, the increase in plasma triacylglycerols corresponds to their proportional enrichment in both LDL and HDL,19 lipopro-teins that are...

Hlg During Pregnancy

Knopp RH, Montes A, Childs M, Li JR, Mabuchi H. Metabolic adjustments in normal and diabetic pregnancy. Clin Obstet Gynecol 1981 24 21-49. 2. Knopp RH, Bonet B, Zhu XD. Lipid Metabolism in pregnancy. In Cowett RM, ed. Principles of Perinatal-Neonatal Metabolism. New York Springer 1998, pp. 221-58. 3. Catalana PM, Tyzbir ED, Wolfe RR, et al. Longitudinal changes in basal hepatic glucose production and suppression during insulin infusion in normal pregnant woman. Am J Obstet Gynecol 1992 167...

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...

Fetal glucose carbon contribution to glycogen formation

Fetal Glycogen Accumulation

Many fetal tissues, including the placenta, as well as the brain, liver, lung, heart, and skeletal muscle, produce glycogen over the second half of gestation.63 Liver glycogen content increases with gestational age Figure 9.2 and is the most important store of glycogen for systemic glucose needs, because only the liver contains sufficient glucose-6-phosphatase for release of glucose into the circulation. Skeletal muscle glycogen content increases during late gestation, whereas lung glycogen...

The GDM controversy

Diabetes mellitus is one of the most common medical complications of pregnancy. Of all types of diabetes, gestational diabetes GDM accounts for approximately 90-95 of all cases of diabetes in pregnancy. GDM is defined as carbohydrate intolerance of variable severity with onset or first recognition during pregnancy. The definition is applicable regardless of whether insulin is used for treatment or the condition persists after pregnancy. It does not exclude the possibility that unrecognized...

Bennewitz Hg Diabete Mellito

A historical review of diabetes and pregnancy. Obstet Gynaecol Br Commun 1972 79 385-95. 2. Reece EA. The history of diabetes mellitus. In Reece EA, Coustan DR, eds. Diabetes Mellitus in Pregnancy, 2nd edn. New York Churchill Livingstone 1995, pp. 1-10. 3. Banting FG, Best CH. The internal secretion of the pancreas. J Lab Clin Med 1 922 7 256-71. 4. Bliss M. The Discovery of Insulin. Edinburgh Paul Harris Publishing 1983, pp. 20-58. 5. Joslin EP. Pregnancy and diabetes mellitus....

Gross examination

The presence of chronic placental anomalies indicative of chronic insult small or large placenta size, infarcts or hemorrhages, anomalies of insertion and defects of the cord, variations of placental shape, loss of transparency or increases of thickening of membranes, etc. may already be diagnosed or suspected by gross macroscopic evaluation. Generally, human placentas are round or oval, but other shapes are not uncommon. Anomalies of the placenta shape or multilobated placenta may develop from...

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...

Maternal and paternal factors associated with fetal growth

The problem of maternal diabetes and the increased population risk of obesity is becoming a greater problem not only in the developed areas of the world but also in developing countries with large populations and high birth rates. Because the increased risk of diabetes and obesity is now becoming manifest in adolescents and even children as young as 2-5 years,1 the concept of in utero fetal programming assumes even more importance. Fetal programming is the effect of the in utero environment on...

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...

Gestational diabetes

The concept of gestational diabetes, actually meaning hyper-glycemia due to the pregnancy itself but in practice defined as 'carbohydrate intolerance of varying severity with onset or first recognition during pregnancy,' is also recent.15 In the very first recorded case Bennewitz, in 1823, considered that the diabetes was actually a symptom of the pregnancy, and as the symptoms and the glycosuria disappeared after at least two successive pregnancies he had some evidence to support his views.16...

Vorden Fetametsd

The Disease and Deformities of the Foetus, Vol. I. Edinburgh Oliver and Boyd 1892. 2. Benirschke K, Kaufman P, Baergen RN. The Pathology of the Human Placenta. Heidelberg Springer-Verlag 2006. 3. Roberts DJ, Oliva E. Clinical significance of placental examination in perinatal medicine. J Matern Fetal Neonat Med 2006 19 255-64. 4. Dominguez F, Avila S, Cervero A, et al. A combined approach for gene discovery identifies insulin-like growth factor-binding protein-related protein...