Xanthogranuloma as an Unsuspected Cause of Idiopathic Central Diabetes Insipidus

ObjectiveTo demonstrate that xanthogranuloma is a rare cause of idiopathic central diabetes insipidus in the early phase of the disease and that it presents as a suprasellar mass at a later stage. In addition, we emphasize the importance of identifying the cause of idiopathic central diabetes insipidus and review the literature concerning endocrine disturbance in central xanthogranuloma.MethodsReview of recently published case reports of central xanthogranuloma with endocrine disorders. The case of a 35-year-old man who presented with a very large suprasellar mass is also reported. The patient was diagnosed with idiopathic central diabetes insipidus 20 years ago with normal brain magnetic resonance imaging.ResultMost cases of this disease present as supra-or parasellar masses with endocrine involvement, the most common of which (in approximately 75% of patients) is sex hormone deficiency. Diabetes insipidus was found in 65% of patients.ConclusionXanthogranuloma should be in the differential diagnosis of idiopathic central diabetes insipidus and sellar and parasellar masses. A detailed skin examination is very important in making the diagnosis of central diabetes insipidus. (Endocr Pract. 2014;20:e42-e46)     

Vasopressin Analogue DDAVP in Diabetes Insipidus: Clinical and Laboratory Studies

In seven patients with cranial diabetes insipidus an analogue of vasopressin, DDAVP, produced an antidiuresis lasting up to 20 hours after a single intranasal dose. Lysine vasopressin (LVP) in the same dose produced a less potent antidiuresis which lasted for only three to four hours. The plasma half life of DDAVP was 7·8 and 75·5 min for the fast and slow phases, compared with 2·5 and 14·5 min for LVP. Radioiodine-labelled DDAVP was not destroyed by incubation with late pregnancy plasma, which contains an enzyme that inactivates vasopressin. The slow metabolic clearance of DDAVP, its absorption through the nasal mucosa, and its lack of side effects make this the ideal drug for the treatment of vasopressin-sensitive diabetes insipidus. Patients usually require 10 to 20 μg DDAVP given intranasally twice daily for good clinical control of their diabetes insipidus.     

A Combined Outpatient and Inpatient Overnight Water Deprivation Test is Effective and Safe in Diagnosing Patients with Polyuria-Polydipsia Syndrome

Objective: The water deprivation test (WDT) is widely used for the differential diagnosis of the polyuria-polydipsia syndrome (PPS). However, it is inconvenient and may not always be precise in differentiating partial forms of diabetes insipidus (DI) from primary polydipsia (PP). The aim of this study was to evaluate the results of a combined outpatient and inpatient overnight WDT protocol that included an overnight unsupervised period concerning its feasibility and safety.Methods: We performed a retrospective analysis of clinical data and laboratory results of 52 patients with PPS undergoing WDT at a single center.Results: PP was the most frequent diagnosis, followed by complete central DI (cCDI), partial central DI (pCDI), and nephrogenic DI (NDI). Over 90% of the patients showed an expected increase in serum osmolality at the end of the dehydration period. There were no reports of complications during the overnight deprivation period. Post-dehydration urine osmolality and urine-to-serum osmolality ratio significantly differentiated all the groups (P<.05), except for cCDI and NDI, which could be differentiated by basal and post-dehydration vasopressin (AVP) levels (P<.05 for both). Although these measurements were useful for differentiating patients according to their allocation groups, results from WDT and direct AVP levels may often require a comprehensive diagnostic approach, particularly in the challenging groups of PP and pCDI.Conclusion: A combined outpatient and inpatient overnight WDT protocol is safe and feasible when the test is performed with special care at experienced centers. Newer diagnostic tools are expected to improve the accuracy of PPS diagnosis.Abbreviations: AQP2 = aquaporin-2; AVP = vasopressin; CDI = central diabetes insipidus; cCDI = complete central diabetes insipidus; DDAVP = desmopressin; DI = diabetes insipidus; IQR = interquartile range; MRI = magnetic resonance imaging; Na⁺ = sodium; NDI = nephrogenic diabetes insipidus; pCDI = partial central diabetes insipidus; PP = primary polydipsia; PPS = polyuria-polydipsia syndrome; S_osm = serum osmolality; U_osm = urine osmolality; WDT = water deprivation test     

DDAVP in Treatment of Vasopressin-Sensitive Diabetes Insipidus

In 11 patients with vasopressin-sensitive diabetes insipidus the effectiveness of the vasopressin analogue 1-desamino-8-D-arginine vasopressin (DDAVP) for controlling diabetes insipidus has been compared with that of lysine vasopressin. DDAVP in equivalent intravenous dosage has been found to be at least as potent and to have a more prolonged action, lasting 13-22 hours instead of 1-2 hours. Twice-daily intranasal DDAVP effected satisfactory control in all these patients, without side effects, and all the patients preferred this to their previous treatment. Single daily intramuscular injections of DDAVP were found to offer excellent control for any subject unable to manage intranasal administration.     

Sheehan Syndrome Presenting as Central Diabetes Insipidus: A Rare Presentation of an Uncommon Disorder

ObjectiveTo add to the current scant literature on rare clinical presentations of Sheehan syndrome.MethodsWe describe the study patient’s clinical, laboratory, and imaging findings and review the literature for publications regarding varied clinical presentations of Sheehan syndrome.ResultsA 36-year-old multigravida woman developed severe postpartum hemorrhage and disseminated intravascular coagulation followed by Sheehan syndrome, with central diabetes insipidus as the primary presenting feature. This was diagnosed when, postoperatively, she developed polyuria with a urine output of 11 L in 24 hours with an accompanying rise in creatinine. She had laboratory evidence of diabetes insipidus, with serum osmolality greater than urine osmolality. Her clinical status improved significantly with intranasal desmopressin supplementation, thus confirming the diagnosis of Sheehan syndrome. Although Sheehan syndrome is a known complication of postpartum hemorrhage, central diabetes insipidus is seldom considered or suspected. Hypovolemia is usually presumed to be secondary to blood loss and polyuria resulting from a diuretic phase of acute renal failure.ConclusionsIt is important to consider posterior pituitary ischemia resulting from Sheehan syndrome presenting as central diabetes insipidus as a cause of polyuria because appropriate hormonal replacement initiated early can possibly improve clinical status and patient outcomes. (Endocr Pract. 2011;17:108-114)     

Diabetes Insipidus Associated with Hehmophagocytic Lymphohistiocytosis: First Case Report

ObjectiveTo report the first case of central diabetes insipidus associated with hemophagocytic lymphohistiocytosis.MethodsWe describe the clinical course of a 75-yearold woman who developed febrile illness 1 month after receiving the H1N1 influenza vaccination. Shortly thereafter, she developed central diabetes insipidus, which responded to treatment with intranasal desmopressin acetate. She was then hospitalized with another febrile illness and diagnosed with hemophagocytic lymphohistiocytosis.ResultsMagnetic resonance imaging of the pituitary gland was significant for plaquelike meningeal enhancement and thickening surrounding the infundibulum, which has been previously reported as a manifestation of histiocytosis.ConclusionWe believe this is the first case of central diabetes insipidus associated with hemophagocytic lymphohistiocytosis. (Endocr Pract. 2011;17:e118-e122)     

Pituitary Stalk Thickening in a Large Cohort: Toward More Accurate Predictors of Pituitary Dysfunction and Etiology

Objective: To summarize the characteristics of patients with pituitary stalk thickening, analyze the association between pituitary stalk width and hypopituitarism, and develop a diagnostic model to differentiate neoplastic and inflammatory origins.Methods: A total of 325 patients with pituitary stalk thickening in a tertiary teaching hospital between January 2012 and February 2018 were enrolled. Basic characteristics and hormonal status were evaluated. Indicators to predict etiology in patients with histologic diagnoses were analyzed.Results: Of the 325 patients, 62.5% were female. Deficiency in gonadotropin was most common, followed by corticotropin, growth hormone, and thyrotropin. The increase in pituitary stalk width was associated with a risk of central diabetes insipidus (odds ratio &lsqb;OR], 3.57; P<.001) and with a combination of central diabetes insipidus and anterior pituitary deficiency (OR, 2.28; P = .029). The cut-off pituitary stalk width of 4.75 mm had a sensitivity of 69.2% and a specificity of 71.4% for the presence of central diabetes insipidus together with anterior pituitary deficiency. Six indicators (central diabetes insipidus, pattern of pituitary stalk thickening, pituitary stalk width, neutrophilic granulocyte percentage, serum sodium level, and gender) were used to develop a model having an accuracy of 95.7% to differentiate neoplastic from inflammatory causes.Conclusion: Pituitary stalk width could indicate the presence of anterior pituitary dysfunction, especially in central diabetes insipidus patients. With the use of a diagnostic model, the neoplastic and inflammatory causes of pituitary stalk thickening could be preliminarily differentiated.Abbreviations: APD = anterior pituitary dysfunction; AUC = area under the curve; CDI = central diabetes insipidus; GH = growth hormone; MRI = magnetic resonance imaging; OR = odd ratio; PHBS = posterior hypophyseal bright spots; PST = pituitary stalk thickening; PSW = pituitary stalk width     

Using Meal-Based Self-Monitoring of Blood Glucose as a Tool to Improve Outcomes in Pregnancy Complicated By Diabetes

ObjectiveTo review the importance of controlling blood glucose levels and the role of self-monitoring of blood glucose (SMBG) in the management of pregnancy complicated by diabetes.MethodsThis report describes the relationship between hyperglycemia and maternal and neonatal complications, reviews the utility of meal-based SMBG in modifying food choices and adjusting insulin doses, and proposes an algorithm to achieve normoglycemia in pregnancies complicated by diabetes.ResultsThe risk of diabetes-related complications in pregnancy is more strongly associated with 1-hour post-prandial plasma glucose concentrations than with fasting plasma glucose levels. SMBG strategies that incorporate postprandial glucose testing provide better glycemic control and greater reductions in risk of complications than does preprandial glucose testing alone. Although the optimal timing and frequency of SMBG remain controversial, available clinical evidence supports testing 4 times per day (before breakfast and 1 hour after each meal) in women with gestational diabetes managed by medical nutrition therapy only and 6 times per day (before and 1 hour after each meal) in pregnant women treated with insulin.ConclusionMeal-based SMBG is a valuable tool for improving outcomes in pregnancy complicated by diabetes. The lessons learned in this setting should have relevance to the general population of patients with diabetes, in whom microvascular and macrovascular complications are the outcomes of importance. (Endocr Pract. 2008; 14:239-247)     

Multiple Endocrinopathies Associated with Lithium Therapy

ObjectiveTo illustrate a case of lithium-associated primary hyperparathyroidism, thyrotoxicosis, and nephrogenic diabetes insipidus and to discuss the potential mechanisms for these complications.MethodsWe describe the clinical and laboratory findings in our current patient and review the related medical literature.ResultsA 65-year-old Chinese woman with bipolar affective disorder, who had received maintenance lithium therapy for 10 years, was seen in an acute care hospital because of fever and confusion. Investigations showed that she had primary hyperparathyroidism and hyperthyroidism. She underwent a parathyroidectomy, which revealed a parathyroid adenoma. Her initial subclinical hyperthyroidism evolved into overt hyperthyroidism after use of lithium was discontinued. Therapy was initiated with carbimazole, which was up-titrated briefly; the patient was subsequently weaned off this medication. Her postoperative course was complicated by persistent polyuria in conjunction with a negative fluid balance, consistent with nephrogenic diabetes insipidus. Thus, amiloride therapy was instituted. The results of an objective causality assessment suggested that the primary hyperparathyroidism, hyperthyroidism, and nephrogenic diabetes insipidus were possibly or probably related to the lithium therapy.ConclusionLithium remains an intriguing drug with numerous potential endocrinologic complications. It is important that clinicians prescribing lithium are aware of its side effects and have a strategy for their detection and management. (Endocr Pract. 2007;13:758-763)     

Diabetes insipidus

Diabetes insipidus is a heterogeneous condition characterized by polyuria and polydipsia caused by a lack of secretion of vasopressin, its physiological suppression following excessive water intake, or kidney resistance to its action. In many patients, it is caused by the destruction or degeneration of the neurons that originate in the supraoptic and paraventricular nuclei of the hypothalamus. Known causes of these lesions include: germinoma or craniopharyngioma; Langerhans cell histiocytosis and sarcoidosis of the central nervous system; local inflammatory, autoimmune or vascular diseases; trauma following surgery or accident; and, rarely, genetic defects in vasopressin biosynthesis inherited as autosomal dominant or X-linked recessive traits. Thirty to fifty percent of cases are considered idiopathic. Magnetic resonance imaging (MRI) allows identification of the posterior pituitary hyperintensity and of hypothalamic-pituitary abnormalities. Thickening of the pituitary stalk is the second most common finding on MRI scans in several local inflammatory pathologies and autoimmune diseases or germinoma, but it is not specific to any single subtype. A progressive increase in the size of the anterior pituitary gland should alert physicians to the possibility that a germinoma is present, whereas a decrease can suggest the presence of an inflammatory or autoimmune process. Most children with acquired central diabetes insipidus and a thickened pituitary stalk have anterior pituitary hormone deficiencies during follow-up. Biopsy of enlarged pituitary stalk should be reserved for patients with a hypothalamic-pituitary mass and progressive thickening of the pituitary stalk, since spontaneous recovery may occur.     

Clinical Aspects of Hyperthyroidism,Hypothyroidism, and Thyroid Screening in Pregnancy

ObjectiveTo evaluate the peer-reviewed literature on hypothyroidism, hyperthyroidism, and thyroid autoimmunity in pregnancy.MethodsWe review published studies on thyroid autoimmunity and dysfunction in pregnancy, the impact of thyroid disease on pregnancy, and discuss implications for screening.ResultsOvert hyperthyroidism and hypothyroidism are responsible for adverse obstetric and neonatal events. Several studies of association suggest that either subclinical hypothyroidism or thyroid autoimmunity increase the risk of complications. One randomized controlled trial showed that pregnant women with subclinical hypothyroidism benefit from treatment in terms of obstetric and neonatal complications, whereas another study demonstrated no benefit in the intelligence quotient of babies born to women with subclinical hypothyroidism. Thyroid autoimmunity has been associated with increased rate of pregnancy loss, recurrent miscarriage, and preterm delivery.ConclusionCurrent guidelines agree that overt hyperthyroidism and hypothyroidism need to be promptly treated and that as potential benefits outweigh potential harm, subclinical hypothyroidism also requires substitutive treatment. The chance that women with thyroid autoimmunity may benefit from levothyroxine treatment to improve obstetric outcome is intriguing, but adequately powered randomized controlled trials are needed. The issue of universal thyroid screening at the beginning of pregnancy is still a matter of debate, and aggressive case-finding is supported. (Endocr Pract. 2014;20:597-607)     

Glycemia Management and Cardiovascular Risk in Type 2 Diabetes: An Evolving Perspective

ObjectiveTo review recent glycemia trials focused on reducing cardiovascular disease (CVD) risk in patients with type 2 diabetes and to describe how the results of these studies have altered our approach to the management of glycemia in patients with diabetes.MethodsResults of some of the previous as well as recent trials, including the Action to Control Cardiovascular Risk in Diabetes (ACCORD), Action in Diabetes and Vascular Disease (ADVANCE), and Veterans Affairs Diabetes Trial (VADT), are reviewed.ResultsThe results demonstrate that the establishment of glycemia (hemoglobin A1c) goals in patients with type 2 diabetes aimed at reducing CVD events is complex, should be highly individualized, and should probably be varied depending on the duration of diabetes as well as the presence or absence of CVD and microvascular complications.ConclusionResults of the ACCORD, ADVANCE, and VADT studies have considerably increased our knowledge and refined our approach to establishing glycemia goals in patients with type 2 diabetes. In patients with recently recognized diabetes with no prior CVD events, glycemic control to normal or near-normal levels appears to be effective in preventing CVD events and mortality. In patients with established diabetes (8 to 10 or more years) and recognized CVD, however, glycemic control to normal or near-normal levels does not reduce the risk of further CVD events or mortality. Importantly, strict control of all known risk factors for CVD and microvascular complications by aggressive management of hypertension, dyslipidemia, and glycemia, use of aspirin, and cessation of smoking in patients with type 2 diabetes has proved to be highly beneficial. (Endocr Pract. 2008;14:639-643)     

ADHD symptoms in a young patient with central diabetes insipidus

Diabetes insipidus is known to be associated with neurodevelopmental disorders. In this case report, we present a child suffering from a central diabetes insipidus (DI) and an attention-deficit/hyperactivity disorder (ADHD). The DI was due to a mutation on the vasopressin gene, impairing its secretion. We discuss the effects of this impairment on the central nervous system and how it might be linked to ADHD symptoms.     

Effect of the Diagnostic Criteria of the International Association of Diabetes and Pregnancy Study Groups on the Prevalence of Gestational Diabetes Mellitus In Urban Mexican Women: A Cross-Sectional Study

ObjectiveTo explore the prevalence of gestational diabetes mellitus (GDM), defined by the previous criteria of the American Diabetes Association (ADA), as well as the criteria suggested by the International Association of Diabetes and Pregnancy Study Groups (IADPSG), in an unselected group of urban Mexican pregnant women and to analyze the frequency of large for gestational age (LGA) newborns in this same group of women with use of both diagnostic criteria.MethodsA cross-sectional study included 803 consecutive Mexican urban women with a singleton pregnancy, without concomitant diseases and no prior history of GDM, who underwent a 2-step screening protocol for diagnosis of GDM at admission to prenatal care.ResultsThe ADA criteria identified 83 women (10.3%) whereas the IADPSG criteria diagnosed 242 women (30.1%) having GDM (P = .0001). Fasting glucose concentrations during the 100-g 3-hour oral glucose tolerance test were abnormal in 116 women (14.4%) and in 160 women (19.9%) on the basis of ADA and IADPSG criteria, respectively (P = .004). The frequency of LGA newborns was 7.4% based on IADPSG criteria and 6.0% based on ADA criteria—no significant difference (P = .64).ConclusionWith use of the IADPSG criteria, the prevalence of GDM increased almost 3-fold in comparison with that for the ADA criteria. Nevertheless, no significant difference was found in the prevalence of LGA newborns. (Endocr Pract. 2012;18:146-151)     

Prolonged antidiuresis by 1-desamino-8-D-arginine vasopressin (DDAVP): correlation to its plasma levels and nephrogenous cyclic AMP production

In an attempt to clarify the mechanism responsible for the prolonged effect of DDAVP (1-desamino-8-D-arginine vasopressin), plasma levels of DDAVP and nephrogenous cyclic AMP were determined in patients with diabetes insipidus after a single intranasal administration of 10 micrograms of DDAVP. Plasma DDAVP levels were uniformly elevated within 30 min, and showed a peak ranging from 5.6 to 25.0 pg/ml between 30 and 120 min. The subsequent time-course of plasma DDAVP differed however, from patient to patient, and was irregular in most of them. In all of the patients whose plasma DDAVP dropped below 1.0 pg/ml, antidiuresis was still observed. Although the mean basal level of nephrogenous cyclic AMP in patients with diabetes insipidus was not significantly different from that in control subjects, the administration of DDAVP resulted in a 2-fold increase. A negative correlation between nephrogenous cyclic AMP and free water clearance was obtained. These results suggest that the long-acting nature of DDAVP may be attributed, in addition to its gradual absorption from nasal mucosa and slow metabolic clearance, to a higher or persistent biological activity at the receptor site in the kidney and that a nearly physiological level of antidiuretic hormone may cause de novo synthesis of cyclic AMP in the kidney and exert its biological action.     

Graves Hyperthyroidism and Pregnancy: A Clinical Update

ObjectiveTo provide a clinical update on Graves’ hyperthyroidism and pregnancy with a focus on treatment with antithyroid drugs.MethodsWe searched the English-language literature for studies published between 1929 and 2009 related to management of hyperthyroidism in pregnancy. In this review, we discuss differential diagnosis of hyperthyroidism, management, importance of early diagnosis, and importance of achieving proper control to avoid maternal and fetal complications.ResultsDiagnosing hyperthyroidism during pregnancy can be challenging because many of the signs and symptoms are similar to normal physiologic changes that occur in pregnancy. Patients with Graves disease require prompt treatment with antithyroid drugs and should undergo frequent monitoring for signs of fetal and maternal hyperthyroidism and hypothyroidism. Rates of maternal and perinatal complications are directly related to control of hyperthyroidism in the mother. Thyroid receptor antibodies should be assessed in all women with hyperthyroidism to help predict and reduce the risk of fetal or neonatal hyperthyroidism or hypothyroidism. The maternal thyroxine level should be kept in the upper third of the reference range or just above normal, using the lowest possible antithyroid drug dosage. Hyperthyroidism may recurin the postpartum period as Graves disease or postpartum thyroiditis; thus, it is prudent to evaluate thyroid function 6 weeks after delivery. Preconception counseling, a multidisciplinary approach to care, and patient education regarding potential maternal and fetal complications that can occur with different types of treatment are important.ConclusionPreconception counseling and a multifaceted approach to care by the endocrinologist and the obstetric team are imperative for a successful pregnancy in women with Graves hyperthyroidism. (Endocr Pract. 2010;16:118-129)     

Metastatic Burkitt's Lymphoma Presenting as Diabetes Insipidus

ObjectiveTo present the first reported case of metastatic Burkitt's lymphoma with a single central nervous system (CNS) metastasis to the pituitary stalk.MethodsWe provided details of the case presentation and review the literature.ResultsAlthough other malignancies are known to metastasize to the pituitary, and diabetes insipidus is often the presenting symptom, there has not been a previously reported case of Burkitt's lymphoma with a single CNS metastasis to the pituitary.ConclusionA careful history and an endocrine review of systems may aid early identification of pituitary or central nervous system metastases. (Endocr. Pract. 2013; 19:e102-e104)     

Goals for Medical Treatment in Obesity and Prediabetes: Improving Outcomes for Both

Objective: The purpose of this review is to expose the surprising prevalence of diabetes-related complications in people with persistent prediabetes, and hence, to expand the paradigm of diabetes prevention to include the prevention of complications related to both hyperglycemia and obesity.Methods: Published literature was reviewed.Results: Approximately 84 million Americans have prediabetes, 85% of whom are overweight or obese. Although the incidence of diabetes-related complications is lower in people with prediabetes versus those with type 2 diabetes, the overall prevalence is virtually identical. Furthermore, many people with prediabetes not only suffer from the complications related to hyperglycemia, they also experience complications of obesity. Treating obesity as a disease has the potential to prevent complications of both hyperglycemia and obesity. Emerging data reveal the untapped potential for clinicians to enhance the effectiveness of anti-obesity medications through a mindful health care delivery style. This involves an understanding and ethical utilization of the placebo effect in conjunction with active medical therapy. This approach is not intended to mislead patients but rather to activate neurocircuitry that synergizes with the central action of the approved anti-obesity medications to potentiate weight loss.Conclusion: Mindful administration of anti-obesity medications has the potential for widespread health benefits in people with obesity and prediabetes.Abbreviations: ADA = American Diabetes Association; DPP = Diabetes Prevention Program; CVD = cardiovascular disease     

Adipsic Diabetes Insipidus: A Review

Objective: Adipsic diabetes insipidus (ADI) is a rare disorder consisting of central diabetes insipidus (CDI) and a deficient or absent thirst response to hyperosmolality. Patients with ADI experience marked morbidity and mortality. Diagnosis and management of these patients is quite challenging, even in expert hands. In this review, we aim to provide an updated overview of this difficult clinical scenario.Methods: We conducted a PubMed search for articles related to ADI. The search terms “adipsia,” “adipsic,” “thirst,” and “diabetes insipidus” were used to identify relevant literature.Results: ADI has been described in only approximately 100 patients. This rarity has limited the quality and quantity of literature to case reports, case series, and expert opinion. Diagnosis focuses on confirmation of CDI followed by documenting subnormal or completely absent thirst in response to a hypertonic stimulus. Among the described patients with ADI, the majority experience morbidity (e.g., severe hypernatremia, sleep apnea, venous thromboembolism [VTE], and obesity) and an increased mortality risk. Management focuses on frequent reassessment of daily prescribed water intake with fixed antidiuretic therapy (desmopressin) and comorbidity screening.Conclusion: The complexity of patients with ADI provides a difficult challenge for clinicians. Prompt recognition of thirst disorders in patients with CDI should lead to appropriately regimented management strategies and can result in safe outpatient care for these unique patients.Abbreviations:ACoA = anterior communicating arteryADI = adipsic diabetes insipidusAVP = arginine vasopressinCDI = central diabetes insipidusDDAVP = desmopressinDI = diabetes insipidusSDB = sleep-disordered breathingVTE = venous thromboembolism     

Pregnancy loss and neonatal death in women with type 1 or type 2 diabetes mellitus

Background: Diabetes mellitus (DM) is known to be a significant risk factor for pregnancy loss, either through still-birth or late intrauterine death or as the result of severe congenital malformation. Improved glycemic control and other advances in care substantially reduced the incidence of pregnancy loss in women with type 1 DM in most countries by the 1970s. However, because of a greater prevalence of obesity since the 1980s, the emergence of type 2 DM in pregnancy has become a significant problem. Although more pregnancies now occur in women with type 2 DM than in those with type 1 DM in many locations, relatively little information has been published about pregnancy loss in type 2 DM.Objectives: This article examines the prevalence and causes of pregnancy loss in type 1 and type 2 DM and identifies factors in addition to glycemic control that may influence pregnancy outcome.Methods: A MEDLINE search was conducted for recent literature on pregnancy loss in DM. Series reporting >200 pregnancies in type 1 DM and/or >100 pregnancies in type 2 DM were included.Results: Thirty-four studies were identified (15 in type 1 DM [1997-2007], 19 in type 2 DM [1986-2007]). In type 1 DM, major congenital anomalies now account for ~50% of pregnancy losses, and all-cause perinatal mortality remains higher than in the general population. Several studies have suggested that the perinatal mortality rate is higher in type 2 DM than in type 1 DM. Factors other than glycemic control probably explain this phenomenon: women with type 2 DM typically are older and more obese, and they come from disadvantaged communities—all risk factors for pregnancy loss, particularly late intrauterine death and chorioamnionitis. In some women, type 2 DM may be recognized for the first time during pregnancy; pregnancies in these women carry the same risks of pregnancy loss as those in women with established DM.Conclusions: Demographic changes in the prevalence of obesity suggest that the prevalence of type 2 DM in pregnancy will almost certainly increase. Although meticulous glycemic control is undoubtedly important in achieving good pregnancy outcomes, clinicians should be aware of the multiple risk factors faced by women with DM.