Malignant Somatostatinoma Presenting with Diabetic Ketoacidosis and Inhibitory Syndrome: Pathophysiologic Considerations

ObjectiveTo describe a patient with diabetic ketoacidosis secondary to a malignant somatostatinoma.MethodsWe present the clinical, laboratory, radiologic, and pathologic findings of a patient with diabetic ketoacidosis secondary to a malignant somatostatinoma. We also review the potential effects of somatostatin on glucose homeostasis and discuss the underlying pathophysiologic mechanisms.ResultsA 30-year-old woman presented with diabetic ketoacidosis and had a malignant somatostatinoma with hepatic, bone, and lymph node metastasis. She exhibited features of somatostatinoma “inhibitory syndrome” characterized by mild nonketotic hyperglycemia, hypochlorhydria, cholelithiasis, steatorrhea, anemia, and weight loss. In these tumors, the absence of ketoacidosis is thought to arise from the somatostatin-induced simultaneous suppression of the secretion of insulin and glucagon. The patient’s primary tumor could not be located.ConclusionsDiabetic ketoacidosis may occur in somatostatinomas. The secretion of larger molecular weight forms of somatostatin from the tumor may contribute to the ketogenesis. (Endocr Pract. 2010;16:835-837)     

Destructive Thyroiditis Followed by Hypothyroidism Associated with Infliximab Therapy

ObjectiveTo present the rare case of a patient who developed destructive thyroiditis accompanied by transient thyrotoxicosis resulting from infliximab therapy for the treatment of psoriasis.MethodsThe clinical presentation and management of a case with infliximab-associated thyroiditis is described with a brief review of the literature.ResultsA 57-year-old male who suffered from psoriasis was treated with infliximab therapy for 4 years. Thyroid function tests were normal before infliximab therapy. When the patient presented in our clinic, he had thyrotoxicosis and was using propylthiouracil. A 99m Technetiumpertechnetate thyroid scintigraphy scan showed no visualization of either thyroid lobe or decreased thyroid iodine uptake. Thyroid-stimulating hormone (TSH) receptor antibody, thyroid peroxidase antibody (anti-TPO Ab) and thyroglobulin antibody (anti-Tg Ab) were negative. Thyroid ultrasonography revealed a heterogeneous thyroid gland without nodules. After stopping propylthiouracil therapy, we advised monitoring of his thyroid function tests in the following weeks, and infliximab therapy for psoriasis was continued. Four weeks later, his thyroid function tests showed an elevated TSH level with normal levels of free triiodothyronine and thyroxine (FT3 and FT4, respectively), and levothyroxine treatment was administered to the patient. Thyroid function tests normalized after levothyroxine treatment. One year later, infliximab therapy was stopped because of clinical remission. Simultaneously, levothyroxine treatment was also stopped. His thyroid function tests were normal 6 weeks after the cessation of levothyroxine treatment.ConclusionTo our knowledge, the present report is the third infliximab-associated thyroid disorder case. Periodic follow-up of thyroid function tests is necessary during infliximab therapy. (Endocr Pract. 2014;20:e207-e210)     

Role of Ultrasonography in the Differential Diagnosis of Thyrotoxicosis: A Non Invasive,Cost-Effective,and Widely Available But Underutilized Diagnostic Tool

ObjectiveTo explore the use of ultrasonography as a diagnostic alternative to the traditional “gold standard” imaging study of nuclear scintigraphy in the evaluation of thyrotoxicosis.MethodsWe review the relevant literature and share our own experience to highlight the promising role of ultrasonography in thyrotoxicosis. In addition, we present a diagnostic algorithm suggesting liberal use of ultrasonography in the evaluation of thyrotoxicosis.ResultsUltrasonography has proved effective not only in the differentiation of Graves disease from other types and causes of thyrotoxicosis but also in the detection of subtle thyroid nodules. The latter role is emphasized in light of the recent observation of an increased risk of occurrence of papillary thyroid carcinoma in patients with Graves disease.ConclusionUltrasonography is a cost-effective, noninvasive, portable, and safe imaging modality in the evaluation of thyrotoxicosis, both for physiologic assessment and for detection of nonpalpable thyroid cancers that may elude identification on physical examination and nuclear imaging studies. Although thyroid scintigraphy remains a standard radiologic study, thyroid ultrasonography can be a practical alternative in many cases and the primary imaging modality in some situations such as during pregnancy and lactation and for evaluation and management of amiodarone-induced thyrotoxicosis. (Endocr Pract. 2012;18: 567-578)     

Case Finding for Hypothyroidism Should Include Type 2 Diabetes and Metabolic Syndrome Patients: A Latin American Thyroid Society (LATS) Position Statement

Objective: Latin American Thyroid Society (LATS) Hypothyroidism Clinical Practice Guidelines recommend case finding of hypothyroid patients in multiple and different situations that agree with other Society guidelines. However, the detection of hypothyroidism in type 2 diabetes mellitus (T2DM) or metabolic syndrome (MetS) patients is not mentioned in particular. In the recent years, several basic and epidemiologic studies have appeared showing that a lower thyroid function and MetS/T2DM are associated. Hence, the aim of this review is to manifest the LATS position on the diagnosis of hypothyroidism in both MetS and T2DM patients.Methods: A search was made in PubMed using the following terms: “hypothyroidism” AND “diabetes” OR “metabolic syndrome.” The most relevant studies describing the prevalence and complications due to hypothyroidism in both MetS and T2DM patients were selected.Results: The current document reviews new information from studies that have shown that the prevalence of hypothyroidism is higher in T2DM patients (odds ratio [OR], 3.45; 95% confidence interval [CI], 2.5 to 4.7) and that diabetic complications are more prevalent in subclinical hypothyroidism (ScH). The incidence of T2DM is 1.09-fold higher with each doubling of thyroid-stimulating hormone (TSH) mIU/L (95% CI, 1.06 to 1.12), and the incidence of prediabetes increases 15% (hazard ratio, 1.15; 95% CI, 1.04 to 1.26) in patients with TSH >5 mIU/L. Similarly, MetS is more prevalent in ScH compared to euthyroid individuals (OR, 1.31; 95% CI, 1.08 to 1.60).Conclusion: Thyroid function is affected in MetS and T2DM, and hypothyroidism is more common in these patients. Diabetic complications are more frequent in ScH patients. Therefore, LATS now recommends aggressive case finding of hypothyroidism in both MetS and T2DM patients.Abbreviations: CI = confidence interval; GLUT4 = glucose transporter 4; HOMA-IR = homeostatic model assessment for insulin resistance; HR = hazard ratio; LATS = Latin American Thyroid Society; MetS = metabolic syndrome; OR = odds ratio; ScH = subclinical hypothyroidism; T2DM = type 2 diabetes mellitus; T3 = triiodothyronine; T4 = thyroxine; TSH = thyroid-stimulating hormone     

Hürthle cell carcinoma of the thyroid presenting as thyrotoxicosis

ObjectiveTo report a case of hyperthyroidism associated with Hülllnnvl-ürthle cellcarcinoma and to review the literature regarding this relationship.MethodsWe describe the clinical, biochemical, radiologic, and pathologic data of a patient with Hürthle cellcarcinoma associated with thyrotoxicosis and reversible heart failure. We discuss the mechanistic aspects and review previously reported cases of functionalHürthle cellcarcinomas.ResultsA 43-year-old womanpresented with thyrotoxicosis and nonischemic cardiomyopathy. She had a “hot” nodule inthe left lobe of the thyroid onsodium pertechnetate scan. She underwent a left hemithyroidec-tomy and isthmusectomy. Pathologic findings revealed a minimally invasive Hürthle cellcarcinoma. Onfollow-up, the dilated cardiomyopathy had resolved. The associationof thyroid carcinoma with thyrotoxicosis is rare.ConclusionsSome Hürthle cellcarcinomas canbe functionaland lead to thyrotoxicosis. To our knowledge, we present the first case of reversible dilated cardiomyopathy due to thyrotoxicosis originating from Hülll-ürthle cellcarcinoma. (Endocr Pract. 2012;18:e5-e9)     

Development of Thyroid Storm After Surgical Resection of A Thyrotropin-Secreting Pituitary Adenoma

ObjectiveTo describe a patient with a thyrotropinsecreting pituitary adenoma in whom postoperative thyroid storm developed.MethodsWe present a case report with details of the initial presentation, laboratory evaluation, surgical and pathologic findings, and subsequent course in a patient with a thyrotropin (thyroid-stimulating hormone or TSH)- secreting adenoma and postoperative thyroid storm.ResultsAn 18-year-old male patient presented with severe headaches and was found to have a large suprasellar tumor and a mildly elevated level of TSH. Thyroid storm developed immediately after surgical resection of the pituitary mass. Results of laboratory evaluation undertaken preoperatively became available after the patient had undergone the surgical procedure and revealed thyroid hormone levels 2 to 3 times the upper limit of normal. Propylthiouracil and β-adrenergic blocking agents controlled the postoperative thyrotoxicosis and were subsequently discontinued as his TSH and thyroid hormone levels normalized.ConclusionThis case demonstrates the rare case of a TSH-secreting adenoma in a young patient, which was complicated by the development of postoperative thyroid storm. In addition, this case emphasizes the importance of preoperative pituitary hormonal evaluation and treatment of hormonal abnormalities in all patients presenting with sellar or suprasellar tumors. (Endocr Pract. 2008;14:732- 737)     

Clinical Characteristics and Outcome of Thyroid Storm: A Case Series and Review of Neuropsychiatric Derangements in Thyrotoxicosis

ObjectiveThe objectives of this study were (1) to describe the presentation, demographics, and clinical course of patients admitted for thyroid storm, and (2) to identify factors associated with mortality.MethodsA retrospective review of subjects admitted to a single academic hospital from 2006 through 2011 was conducted. Medical records for all patients who were admitted with a diagnosis of thyrotoxicosis were systematically reviewed for clinical features of thyroid storm.ResultsA total of 28 cases were identified. Thyroid storm was the first clinical presentation of thyrotoxicosis in 13 patients (46.4%). Noncompliance with treatment was a major trigger in previously diagnosed patients, followed by infection. The mortality rate was 25% in this series. Cardiac manifestations were predominant, with > 60% of patients having severe tachycardia (heart rate > 140 beats per minunte) and/or atrial fibrillation. Although central nervous system (CNS) involvement was less frequent (n = 8, 28.6%), CNS derangement of worse than mild severity was statistically associated with mortality (P = .021). There was good agreement between the Burch-Wartofsky Point Scale and Japanese Thyroid Association criteria in the diagnosis of thyroid storm in this study cohort.ConclusionThyroid storm was the first presentation of thyrotoxicosis in a significant proportion of patients, highlighting the importance of a high index of suspicion in an appropriate clinical context. The presence of neuropsychiatric manifestations appeared to portend greater risk of mortality. Prevailing evidence suggests that there are complex interactions between thyroid hormones and neurotransmitter circuits in the pathogenesis of CNS symptomology in thyrotoxicosis. (Endocr Pract. 2015;21:182-189)     

Role of Thyroid Doppler in Differential Diagnosis of Thyrotoxicosis

ObjectiveTo evaluate the role of thyroid blood flow assessment by color-flow Doppler ultrasonography in the differential diagnosis of thyrotoxicosis.MethodsConsecutive patients with thyrotoxicosis presenting to our center between June 2007 and March 2008 were included in the study. Clinical data were collected, and thyroid function tests including measurements of thyrotropin, total thyroxine, and total triiodothyronine were performed. Thyroid glands of all patients were evaluated with color-flow Doppler ultrasonography for size, vascularity, and peak systolic velocity of the inferior thyroid artery. Technetium Tc 99m pertechnetate scan was done when the diagnosis was not clear on the basis of clinical findings. Patients were divided into 2 groups for analysis: patients with destructive thyrotoxicosis and patients with Graves disease. Paired t tests and Fisher exact tests were used for statistical analysis.ResultsA total of 65 patients participated in the study; 31 had destructive thyrotoxicosis and 34 had Graves disease. Thyroid blood flow, as assessed by peak systolic velocity of the inferior thyroid artery, was significantly higher in patients with Graves disease than in patients with destructive thyroiditis (57.6 ± 13.1 cm/s vs 22.4 ± 5.4 cm/s; P < .05). All patients with destructive thyroiditis had low peak systolic velocity of the inferior thyroid artery, and 32 of 34 patients with Graves disease had high peak systolic velocity. Color-flow Doppler ultrasonography parameters correlated significantly with pertechnetate scan results, demonstrating a comparable sensitivity of 96% and specificity of 95%.ConclusionsDifferentiating Graves thyrotoxicosis from destructive thyrotoxicosis is essential for proper selection of therapy. Assessment of thyroid blood flow by color-flow Doppler ultrasonography is useful in this differentiation. (Endocr Pract. 2009;15:6-9)     

Unusual Case of Amiodarone-Induced Thyrotoxicosis “Illicit” use of a Technetium Scan to Diagnose a Transiently Toxic Thyroid Nodule

ObjectiveTo present an unusual case of amiodarone-induced thyrotoxicosis (AIT) associated with an autonomously functioning thyroid nodule, which was detected by means of a technetium scan; review the existing literature regarding the association of AIT with autonomous thyroid nodules; and explore the use of radioisotope imaging studies in patients with AIT.MethodsWe describe a 62-year-old man with paroxysmal atrial fibrillation, receiving long-term amiodarone therapy, who was referred by his cardiologist for evaluation of abnormal thyroid function tests. He was found to have an unusual case of AIT, associated with an autonomously functioning thyroid nodule.ResultsThyroid function studies obtained by the patient’s cardiologist had shown a completely suppressed thyrotropin level and a free thyroxine level of 3.5 ng/dL. A 24-hour thyroid iodine 123 uptake and technetium Tc 99m pertechnetate scan revealed a “single, strong focus in the right thyroid lobe, with the rest of the thyroid gland...not well visualized.” Thyroid ultrasonography disclosed a single, well-defined 1.5-cm solid nodule. Repeated thyroid function studies revealed a normal thyrotropin level of 2.87 μIU/mL and a normal free thyroxine level of 2.4 ng/dL. The patient was managed conservatively with follow-up surveillance.ConclusionProspective studies should be performed to better ascertain the value of Tc 99m thyroid scanning in determining the cause of AIT. Until such studies have been completed, we suggest that nuclear studies are unlikely to be cost-effective for assessing all patients with AIT. One logical strategy would be to gain experience with scans in only those patients with known thyroid nodules, which have been detected during physical examination or by ultrasonography. The potential clinical utility of such an approach would be of considerable interest. (Endocr Pract. 2007;13:413-416)     

Management of Thyrotoxicosis Among General Practitioners in Trinidad Compared with 2016 American Thyroid Association Guidelines for Hyperthyroidism

Objective: A previous Trinidadian survey highlighted the investigative and therapeutic approaches selected by general practitioners (GPs) in managing thyrotoxicosis. The main objective of this study was to compare practice with existing guidelines.Methods: In this cross-sectional study a pretested de novo questionnaire was self-administered to GPs throughout Trinidad. The survey evaluated GPs' choices in management of thyrotoxicosis cases and compared their responses to the 2016 American Thyroid Association guidelines as well as with those previously reported locally.Results: A total of 159 completed questionnaires were analyzed (59% response rate). Thyroid stimulating hormone was the preferred (94%) biochemical test to confirm thyrotoxicosis etiology. A combination of ultra-sound and thyroid scintigraphy, thyroid ultrasound alone, and scintigraphy only were the testing options selected by 41%, 38%, and 12%, respectively. Generally medical therapy with antithyroid drugs was the preferred treatment option with 86% of respondents selecting this option for the index case of newly diagnosed female Graves disease. The greatest proportion of respondents that selected radioactive iodine (RAI) was 35% for both the index case as well as the male equivalent. Surgery was the most popular option at 25% for patients with a toxic multinodular goiter. Having access to RAI and scintigraphy was reported by 32% and 28%, respectively.Conclusion: GPs appear to be constrained to making rational choices based upon availability rather than what the guidelines recommend. In the absence of formal continuing medical education for GPs on thyrotoxicosis, dissemination of guidelines at the primary care level may reduce this gap.Abbreviations: ATA = American Thyroid Association; ATD = antithyroid drugs; CME = continued medical education; GP = general practitioner; RAI = radioactive iodine; SURG = surgery; T4 = thyroxine; TSH = thyroid-stimulating hormone     

Individualization Through Standardization: Electronic Orders for Subcutaneous Insulin in the Hospital

ObjectiveThe objective was to design electronic order sets that would promote safe, effective, and individualized order entry for subcutaneous insulin in the hospital, based on a review of best practices.MethodsSaint Francis Hospital in Evanston, Illinois, a community teaching hospital, was selected as the pilot site for 6 hospitals in the Health Care System to introduce an electronic medical record. Articles dealing with man agement of hospital hyperglycemia, medical order entry systems, and patient safety were reviewed selectively.ResultsIn the published literature on institutional glycemic management programs and insulin order sets, features were identified that improve safety and effectiveness of subcutaneous insulin therapy. Subcutaneous electronic insulin order sets were created, designated in short: “patients eating”, “patients not eating”, and “patients receiving overnight enteral feedings.” Together with an option for free text entry, menus of administra tion instructions were designed within each order set that were applicable to specific insulin orders and expressed in standardized language, such as “hold if tube feeds stop” or “do not withhold.”ConclusionTwo design features are advocated for electronic order sets for subcutaneous insulin that will both standardize care and protect individualization. First, within the order sets, the glycemic management plan should be matched to the carbohydrate exposure of the patients, with juxtaposition of appropriate orders for both glucose monitoring and insulin. Second, in order to convey precautions of insulin use to pharmacy and nursing staff, the prescriber must be able to attach administration instructions to specific insulin orders. (Endocr Pract. 2012;18:976-987)     

Parathyroidectomy-Induced Thyroiditis

ObjectiveTo highlight the possibility of development of thyroiditis after parathyroidectomy.MethodsClinical and laboratory findings in 2 cases are presented, and the relevant literature is reviewed.ResultsIn 2 women (84 years old and 55 years old) with no history of thyroid disease in one of them and a remote history of excision of a follicular adenoma in the other, thyrotoxicosis developed a few days to a week after parathyroidectomy for primary hyperparathyroidism. The first patient underwent bilateral cervical exploration with removal of a right inferior parathyroid adenoma, whereas the second patient had excision of 3¹/₂ parathyroid glands for 4-gland hyperplasia and 2 benign nodules from the left thyroid lobe. Both surgical procedures were uncomplicated. Neither patient had received any iodinated contrast agents or medications such as lithium or amiodarone before presentation. Laboratory results showed elevated levels of free thyroxine, suppressed thyroid-stimulating hormone levels, very low radioiodine uptake (in the second patient), and an elevated thyroglobulin level (in the first patient). Both patients were treated symptomatically with β-adrenergic antagonists. Thyroid function normalized and symptoms diminished after 1 to 2 months.ConclusionParathyroidectomy-induced thyroiditis is underrecognized. The majority of patients are asymptomatic, although clinically significant thyrotoxicosis can also occur. Candidates for parathyroidectomy should be informed of this potential complication, and thyroid function should be assessed if clinically indicated. (Endocr Pract. 2010;16:656-659)     

Efficacy of High-Fiber Diets in the Management of Type 2 Diabetes Mellitus

ObjectiveTo review outcomes of randomized controlled clinical trials exploring the efficacy of different types of diets containing various amounts of fiber in the management of type 2 diabetes mellitus.MethodsWe searched PubMed, Medline, and Google Scholar for published data from the past decade (through December 2009) on dietary patterns and risk of type 2 diabetes mellitus. Only randomized controlled trials investigating the effect of whole grains, fiber, or vegetarian diets on type 2 diabetes were included. Search criteria included whole grain, fruit, vegetable, fiber, and meat intake regarding insulin sensitivity and glycemic responses in healthy, prediabetic, and diabetic persons.ResultsA total of 14 randomized clinical trials were included. Addition of insoluble or soluble fiber to meals, increased consumption of diets rich in whole grains and vegetables, and vegan diets improve glucose metabolism and increase insulin sensitivity. The greatest improvement in blood lipids, body weight, and hemoglobin A_1c level occurred in participants following low-fat, plant-based diets.ConclusionsIncreased consumption of vegetables, whole grains, and soluble and insoluble fiber is associated with improved glucose metabolism in both diabetic and nondiabetic individuals. Improvements in insulin sensitivity and glucose homeostasis were more evident in participants following a plant-based diet compared with other commonly used diets. (Endocr Pract. 2011;17:132-142)     

Effects of Amiodarone,Thyroid Hormones and CYP2C9 and VKORC1 Polymorphisms on Warfarin Metabolism: A Review of the Literature

ObjectiveTo review the literature regarding the interaction among amiodarone therapy, thyroid hormone levels, and warfarin metabolism.Methods73-year-old male with type 2 after describing an unusual case of amiodarone-induced thyrotoxicosis (AIT) who experienced a severe rise in international normalized ratio (INR) values after initiating warfarin therapy due to an unusual combination of excessive thyroid hormones, amiodarone therapy, and a genetic abnormality affecting warfarin metabolism.ResultsGenetic analysis revealed that the patient was CYP2C9*2 wild-type, CYP2C9*3/*3 homozygous mutant, and VKORC1*3/*3 homozygous mutant. A review of the literature revealed that both mutations can independently affect warfarin metabolism. In addition, amiodarone therapy and the presence of thyrotoxicosis per se can affect warfarin metabolism and reduce the dose needed to maintain INR in the therapeutic range. The association of the 2 genetic polymorphisms in a patient with AIT is extremely rare and strongly impairs warfarin metabolism, exposing the patient to a high risk of overtreatment.ConclusionsIn patients with AIT, warfarin therapy should be gradually introduced, starting with a very low dose, because of the significant risk of warfarin overtreatment. Whether the genetic analysis of CYP2C9 and VKORC1 polymorphisms should be routinely performed in AIT patients remains conjectural. (Endocr Pract. 2013; 19:1043-1049)     

Tyrosine Kinase Inhibitors and the Thyroid as Both an Unintended and an Intended Target

ObjectiveTo review the association of the tyrosine kinase inhibitor sunitinib with hypothyroidism as well as the mean time to onset, possible mechanisms, reversibility, and mean duration.MethodsWe performed a MEDLINE search of the English-language literature using a combination of words (“sunitinib,” “tyrosine kinase inhibitors,” “thyroid,” and “hypothyroidism”) to identify original studies and reviews on sunitinib and thyroid function.ResultsHypothyroidism was reported in 36% to 46% of patients who took sunitinib in prospective studies. A higher incidence (53% to 85%) was reported in studies containing both retrospective and prospective data. The mean time to onset of hypothyroidism after initiation of sunitinib therapy ranged from 12 to 50 weeks. The risk of development of hypothyroidism appears to increase with the increasing duration of sunitinib therapy, and the condition is likely reversible once therapy has been discontinued.ConclusionBaseline thyroid function tests should be performed before the initiation of sunitinib treatment. Because hypothyroidism can develop early in the course of therapy, thyroid function tests should be monitored frequently throughout the duration of treatment. Possible mechanisms for thyroid dysfunction include impaired thyroid hormone synthesis, a destructive thyroiditis preceding the development of hypothyroidism, and increased thyroid hormone clearance. If hypothyroidism is identified, levothyroxine therapy should be promptly initiated. (Endocr Pract. 2008;14:618-624)     

Vitamin D and Prebiotics may benefit The Intestinal Microbacteria and improve Glucose Homeostasis in Prediabetes and Type 2 Diabetes

ObjectiveTo review the role of human large bowel microbacteria (microbiota) in the glucose homeostasis, to address vitamin D (VD) and prebiotics interactions with microbiota, and to summarize recent randomized clinical trials (RCTs) of VD and prebiotics supplementation in prediabetes (PreDM) and type 2 diabetes mellitus (T2DM).MethodsPrimary literature was reviewed in the following areas: composition and activity of human microbiota associated with PreDM and T2DM, interactions between microbiota and glucose homeostasis, the interaction of microbiota with VD/prebiotics, and RCTs of VD/prebiotics in subjects with PreDM or T2DM.ResultsThe human microbiota is comprised of 100 trillion bacteria with an aggregate genome that is 150-fold larger than the human genome. Data from the animal models and human studies reveal that an “obesogenic” diet results into the initial event of microbiota transformation from symbiosis to dysbiosis. The microbial antigens, such as Gram(-) bacteria and lipopolysaccharide (LPS), translocate to the host interior and trigger increased energy harvesting and Toll-like receptor (TLR) activation with subsequent inflammatory pathways signaling. The “double hit” of steatosis (ectopic fat accumulation) and “—itis” (inflammation) and contribution of “corisks” (e.g., vitamin D deficiency [VDD]) are required to activate molecular signaling, including impaired insulin signaling and secretion, that ends with T2DM and associated diseases. Dietary changes (e.g., prebiotics, VD supplementation) may ameliorate this process if initiated prior to the process becoming irreversible.ConclusionEmerging evidence suggests an important role of microbiota in glucose homeostasis. VD supplementation and prebiotics may be useful in managing PreDM and T2DM. (Endocr Pract. 2013;19:497-510)     

Ketosis-Prone Type 2 Diabetes: Effect of Hyperglycemia on β-Cell Function and Skeletal Muscle Insulin Signaling

ObjectiveTo determine the underlying mechanism for the severe and transient β-cell dysfunction and impaired insulin action in obese African American patients with ketosis-prone diabetes.MethodsThe effect of sustained hyperglycemia (glucotoxicity) and increased free fatty acids (lipotoxicity) on β-cell function was assessed by changes in insulin secretion during a 20-hour glucose (200 mg/m² per minute) and a 48-hour Intralipid (40 mL/h) infusion, respectively. Insulin-activated signaling pathways and pattern of Akt-1 and Akt-2 expression and insulin-stimulated phosphorylation were analyzed in skeletal muscle biopsy specimens. Studies were performed in an obese African American woman within 48 hours after resolution of diabetic ketoacidosis and 1 week after discontinuation of insulin treatment.ResultsDextrose infusion rapidly increased C-pep-tide levels from a baseline of 3.2 ng/mL to a mean of 7.1 ± 0.5 ng/mL during the first 8 hours of infusion; thereafter, C-peptide levels progressively declined. Lipid infusion was not associated with any deleterious effect on insulin and C-peptide secretion. Initial in vitro stimulation of muscle tissue with insulin resulted in a substantial and selectively decreased Akt-2 expression and insulin-stimulated phosphorylation on the serine residue. Improved metabolic control resulted in 70% greater Akt expression at near-normoglycemic remission in comparison with the period of hyperglycemia.ConclusionHyperglycemia, but not increased free fatty acid levels, led to progressive β-cell dysfunction and impaired insulin secretion. Hyperglycemia was also associated with diminished skeletal muscle Akt expression and phosphorylation in an African American woman with ketosis-prone diabetes, and this defect improved notably with aggressive insulin therapy. These results indicate the importance of glucose toxicity in the pathogenesis of keto-sis-prone diabetes in obese African American patients. (Endocr Pract. 2007;13:283-290)     

Profound Hypokalemia in Diabetic Ketoacidosis: A Therapeutic Challenge

ObjectiveTo describe profound hypokalemia in a comatose patient with diabetic ketoacidosis.MethodsWe present a case report, review the mechanisms for the occurrence of hypokalemia in diabetic ketoacidosis, and discuss its management in the setting of hyperglycemia and hyperosmolality.ResultsA 22-year-old woman with a history of type 1 diabetes mellitus was admitted in a comatose state. Laboratory tests revealed a blood glucose level of 747 mg/dL, serum potassium of 1.9 mEq/L, pH of 6.8, and calculated effective serum osmolality of 320 mOsm/kg. She was intubated and resuscitated with intravenously administered fluids. Intravenous administration of vasopressors was necessary for stabilization of the blood pressure. Intravenous infusion of insulin was initiated to control the hyperglycemia, and repletion of total body potassium stores was undertaken. A total of 660 mEq of potassium was administered intravenously during the first 12.5 hours. Despite such aggressive initial repletion of potassium, the patient required 40 to 80 mEq of potassium daily for the next 8 days to increase the serum potassium concentration to normal.ConclusionProfound hypokalemia, an uncommon initial manifestation in patients with diabetic ketoacidosis, is indicative of severe total body potassium deficiency. Under such circumstances, aggressive potassium repletion in a comatose patient must be undertaken during correction of other metabolic abnormalities, including hyperglycemia and hyperosmolality. Intravenously administered insulin should be withheld until the serum potassium concentration is ≥ 3.3 mEq/L. (Endocr Pract. 2005;11:331-334)     

Role of Insulin Signaling in Maintaining Energy Homeostasis

ObjectiveTo examine the role that insulin signaling plays in modulating metabolic functions involving both peripheral and hypothalamic systems.MethodsWe review the literature regarding insulin signaling as it relates to energy homeostasis.ResultsInsulin signaling in the periphery is known to affect hepatic glucose production and glucose uptake in muscle and adipose tissue. In the brain, insulin is involved in a variety of signaling pathways that control positive and negative aspects of food intake and energy metabolism. Disruption of insulin signaling can affect key cellular pathways that serve to maintain energy balance and glucose homeostasis, which can then lead to insulin resistance and progression toward various metabolic disorders, including cardiovascular disease, obesity, and type 2 diabetes. The use of exogenous insulin as therapy for patients with type 2 diabetes is traditionally associated with increases in weight.ConclusionAn enhanced understanding of how these insulin signaling pathways function may provide answers about how to control weight gain associated with exogenous insulin use. Pharmacologic agents, such as the long-acting insulin analogues and particularly insulin detemir, that may reduce these weight effects hold considerable advantage. (Endocr Pract. 2008;14:373-380)     

Inpatient insulin therapy

Background: Many diabetic, as well as nondiabetic, hospitalized patients develop hyperglycemia. Numerous studies have demonstrated that critically ill, as well as noncritically ill, hospitalized patients who develop hyperglycemia are at increased risk for morbidity and mortality.Objective: The objective of this article was to review the risks associated with hyperglycemia in hospitalized patients, the biologic rationale for using insulin to prevent increases in glucose levels, and strategies for managing hyperglycemia in the hospital setting.Methods: We conducted a computerized search of biomedical journal literature from MEDLINE, PubMed, and Ovid published from 1994 to March 2008. We reviewed English-language original and review articles found under the subject headings “hospitalization and insulin therapy,” “inpatient diabetes and complications,” and “insulin and inflammation.”Results: More than 200 references were found during the literature search. According to the literature, the adverse outcomes that are associated with hyperglycemia may be attributed to the inflammatory and pro-oxidant effects of elevated glucose levels. The use of insulin, which has anti-inflammatory, vasodilatory, and antioxidant properties as well as the ability to inhibit lipolysis and platelet aggregation, can prevent many of these adverse outcomes.Conclusions: Hospitals should have protocols in place for using insulin to treat and prevent hyperglycemia. Subcutaneous insulin may be used for both purposes in most noncritically ill patients, whereas intravenous infusion of insulin is preferred in critically ill patients.