Evaluation,Medical Therapy,and Course of Adult Persistent Hyperinsulinemic Hypoglycemia After Roux-En-Y Gastric Bypass Surgery: A Case Series

ObjectiveTo describe the evaluation and treatment of hyperinsulinemic hypoglycemia in adults who had undergone gastric bypass surgery. A small number of patients who undergo Roux-en-Y bypass surgery develop postprandial hypoglycemia in the absence of dumping. In some cases, such patients have been treated with pancreatectomy.MethodsWe report the demographics, diagnostic results, response to medical therapy, and subsequent course of 6 referral patients with post–Roux-en-Y gastric bypass hypoglycemia.ResultsCharacteristic clinical and metabolic parameters consistent with hyperinsulinemic hypoglycemia were identified. Parameters were similar for both spontaneous and glucose-challenge-induced hypoglycemia. In the context of exclusively postprandial symptoms, simultaneous glucose ≤ 55 mg/dL, insulin ≥ 17 μU/mL, C peptide ≥ 3.0 ng/mL, and insulin to glucose ratio > 0.3 were associated with Roux-en-Y gastric bypass hyperinsulinemic hypoglycemia. Five of 6 patients improved on therapy consisting of dietary modification plus either calcium channel blockade, acarbose, or both. Two patients have remained on therapy for 12 to 15 months. The nonresponder was atypical and had had hypoglycemic events for several decades. Three treated patients were subsequently observed to have undergone partial or complete remission from hypoglycemic episodes after 2 to 37 months of therapy. None of the 6 have undergone pancreatectomy, and none have evidence of insulinoma. Invasive diagnostic procedures were of limited utility.ConclusionIn a subset of patients with post–Roux-en-Y gastric bypass hyperinsulinemic hypoglycemia, medical management can be efficacious and an alternative to partial pancreatectomy. In some cases, the disorder remits spontaneously. (Endocr Pract. 2015;21:237-246)     

Successful Treatment of Persistent Hyperinsulinemic Hypoglycemia with Nifedipine in an Adult Patient

ObjectiveTo describe the successful treatment of severe noninsulinoma hyperinsulinemic hypoglycemia with use of a calcium channel blocking agent in an adult patient who had previously undergone a gastric bypass surgical procedure.MethodsA 65-year-old woman who had undergone a gastric bypass surgical procedure 26 years earlier was hospitalized because of severe postprandial hypoglycemia. During and after hospitalization, the patient underwent assessment with conventional measurements of glucose, insulin, proinsulin, and C-peptide; toxicologic studies; magnetic resonance imaging studies of the pancreas; and determination of hepatic vein insulin concentrations after selective splanchnic artery calcium infusion.ResultsMetabolic variables were consistent with the diagnosis of hyperinsulinemic hypoglycemia. Magnetic resonance imaging revealed the presence of a side branch intraductal papillary mucinous tumor that had been stable for more than 1 year. The results of the calcium-stimulated insulin release study were consistent with nonlocalized hypersecretion of insulin. A trial of frequent small feedings failed to prevent hypoglycemia. On the basis of reports of successful treatment of childhood nesidioblastosis, the patient was then prescribed nifedipine, 30 mg daily. She has subsequently remained free of symptomatic hypoglycemia for 20 months.ConclusionA calcium channel blocking agent may be efficacious and a potential alternative to partial pancreatectomy in cases of noninsulinoma hyperinsulinemic hypoglycemia in adults. (Endocr Pract. 2010;16:107-111)     

Octreotide Therapy for Recurrent Refractory Hypoglycemia Due to Sulfonylurea In Diabetes-Related Kidney Failure

ObjectiveTo describe a patient with kidney insufficiency from diabetes treated with glyburide, who presented with prolonged and recurrent hypoglycemia unresponsive to large intravenous doses of glucose, which was treated successfully with intravenously administered octreotide, and to review the therapeutic options for hypoglycemia.MethodsWe present a case report of a 66-year-old man with diabetes causing chronic kidney disease, who was treated with orally administered glyburide, 7.5 mg twice a day. He initially presented to another hospital because of hypoglycemia and was treated with intravenously administered glucose and discharged. The next day, his family brought him to our emergency department because of recurring low blood glucose levels and symptoms of sweating, fever, and nightmares. Laboratory tests revealed a blood glucose level of 33 mg/dL and a creatinine concentration of 6.2 mg/dL.ResultsThe patient was treated with a 5% dextrose and, subsequently, a 10% dextrose infusion without any sustained improvement. The blood glucose level remained low despite the additional administration of 3 ampules of 50% dextrose in water. The patient was given a bolus of octreotide (50 μg subcutaneously) 14 hours after his second presentation. He received another 50-μg dose of octreotide 6 hours later. After this bolus, the hypoglycemia resolved, and he no longer required intravenous administration of glucose to maintain euglycemia.ConclusionPatients with diabetes and kidney disease frequently have persistent and difficult-to-treat hypoglycemia, unresponsive to conventional therapy. Octreotide is an effective and safe treatment for patients with refractory hypoglycemia attributable to sulfonylureas. (Endocr Pract. 2007;13:417-423)     

Is Liraglutide A Useful Addition to Diabetes Therapy?

ObjectiveTo evaluate liraglutide as an antidiabetic agent.MethodsThe pertinent English-language medical literature was reviewed for the period from 1985 to April 2010 with use of data from MEDLINE.ResultsLiraglutide is a glucagonlike peptide-1 receptor analogue that stimulates insulin secretion, reduces postprandial glucagon release, causes a mild delay in gastric emptying, and may slightly decrease appetite. Mean reductions in hemoglobin A1c levels with liraglutide therapy range from 1.0% to 1.5% in comparison with baseline and are 1.0% and 1.3% in comparison with placebo. Head-to-head trials suggest that liraglutide may be more effective than glimepiride, rosiglitazone, insulin glargine, and exenatide. Some of the previous trials, however, are limited by use of submaximal doses of comparator drugs and an open-label design. The use of liraglutide is associated with a mean weight loss of 0.2 to 3.2 kg relative to baseline and 0.1 to 2.6 kg relative to placebo. Liraglutiderelated hypoglycemia is generally mild, but its incidence and severity substantially increase in conjunction with sulfonylureas. Gastrointestinal adverse effects such as nausea, diarrhea, or vomiting occurred in 44% to 56% of patients who received liraglutide versus 17% to 19% with placebo. Premature withdrawal from trials occurred in 4% to 15% of liraglutide-treated patients (mainly attributable to gastrointestinal adverse effects), in comparison with 3% to 5% of those receiving placebo.ConclusionThe 2 main advantages of liraglutide are mild degrees of weight loss and hypoglycemia. Important limitations, however, are the frequent occurrence of gastrointestinal adverse effects, the requirement of subcutaneous injection once daily, and the lack of long-term efficacy and safety data. Liraglutide may be a useful add-on therapy in patients with type 2 diabetes uncontrolled with metformin, when hypoglycemia, weight gain, or both are major concerns. (Endocr Pract. 2010;16:1028-1037)     

The Use of Premixed Insulin Analogues in the Treatment of Patients with Type 2 Diabetes Mellitus: Advantages and Limitations

Background:Intensive, target-oriented therapy is the standard of care in the management of patients with type 2 diabetesmellitus (DM). Early and aggressive use of insulin that is as close as possible to the physiologic pattern of insulin secretion from healthy pancreatic β-cells is advocated to achieve glycemic goals and reduce complications of DM.Objective:The objective of this article was to review the characteristics, advantages, and drawbacks of premixedinsulin analogues and to evaluate their role in the treatment of patients with type 2 DM.Methods:A PubMed search of articles from 1990 to 2006 was undertaken using the search terms type 2 diabetes, basalbolus therapy, premixed insulins, biphasic insulins, and insulin analogues. Pertinent content from relevant articles was extracted and combined with the authors' knowledge, experience, and clinical expertise.Results:The advent of insulin analogues has streamlined the treatment of patients with DM. When to initiate insulin during the course of treatment is the subject of much debate. Insulin therapy targeting both fasting and postprandial hyperglycemia is important in achieving optimal blood glucose (BG) control in patients with type 2 DM. A practical and feasible option is the use of >1 injection of premixed insulin analogues. Premixed insulin preparations provide both basal and prandial coverage because of their biphasic pharmacokinetic properties. Clinical trials have shown that these agents improve glycemic control, are associated with an acceptably low rate of severe hypoglycemia, and have a high degree of patient acceptance. Limitations include the inability to adjust the long- and short-acting components separately, to use a flexible regimen of self-titration and premeal bolus-insulin calculations, and to adequately treat postlunch and earlymorning BG elevations.Conclusion:Clinicians should be aware of premixed insulin analogues' advantages and limitations so that these agentscan be used appropriately in the treatment of patients with type 2 DM.     

Free Fatty Acids,Insulin Resistance,and Corrected QT Intervals in Morbid Obesity: Effect of Weight Loss During 6 Months With Differing Dietary Interventions

ObjectiveTo assess whether shortening of the corrected QT (QTc) interval is most closely associated with changes in weight, insulin resistance, or free fatty acids (FFAs) (or some combination of these factors).MethodsWe randomized 75 severely obese subjects without diabetes to either a low-carbohydrate or a conventional low-fat weight-loss diet for 6 months. We measured QTc, insulin sensitivity, body mass index, and FFAs at baseline and at 6 months. Analysis was performed to determine whether improvement in weight, in insulin resistance, or in FFAs has the greatest effect on reducing the QTc interval.Results“Completers” of both the low-carbohydrate diet (N = 25) and the low-fat diet (N = 22) had a decrease in weight, but the weight loss was greater in the low-carbohydrate group. A statistically significant decrease in QTc from baseline was observed only in the low-carbohydrate group. QTc in the low-carbohydrate group correlated with improvement in insulin resistance, but this finding was not significant after correction for the greater weight loss. FFAs or weight loss was not correlated with QTc in either dietary group.ConclusionLow-carbohydrate dieting is associated with a greater decrease in the QTc interval in comparison with low-fat dieting. Improvements in insulin resistance seem to have a relatively weak mechanistic role, and a decrease in FFAs has no apparent role in the reduction of the QTc interval. (Endocr Pract. 2005;11:234-239)     

Hypoglycemia: Still The Limiting Factor in the Glycemic Management of Diabetes

ObjectiveTo review the prevalence of, risk factors for, and prevention of hypoglycemia from the perspective of the pathophysiologic aspects of glucose counterregulation in diabetes.MethodsThis review is based on personal experience and research and the relevant literature.ResultsAlthough it can result from insulin excess alone, iatrogenic hypoglycemia is generally the result of the interplay of therapeutic insulin excess and compromised defenses against declining plasma glucose concentrations. Failure of β-cells of the pancreas—early in patients with type 1 diabetes mellitus but later in those with type 2 diabetes mellitus (T2DM)—causes loss of the first 2 physiologic defenses: a decrease in insulin and an increase in glucagon. Such patients are critically dependent on epinephrine, the third physiologic defense, and neurogenic symptoms that prompt the behavioral defense (carbohydrate ingestion). An attenuated sympathoadrenal response to declining glucose levels—caused by recent antecedent hypoglycemia, prior exercise, or sleep—causes hypoglycemia-associated autonomic failure (HAAF) and thus a vicious cycle of recurrent hypoglycemia. Accordingly, hypoglycemia is infrequent early in T2DM but becomes increasingly more frequent in advanced (absolutely endogenous insulin-deficient) T2DM, and risk factors for HAAF include absolute endogenous insulin deficiency; a history of severe hypoglycemia, hypoglycemia unawareness, or both; and aggressive glycemic therapy per se.ConclusionBy practicing hypoglycemia risk reduction— addressing the issue, applying the principles of aggressive glycemic therapy, and considering both the conventional risk factors and those indicative of HAAF— it is possible both to improve glycemic control and to minimize the risk of hypoglycemia in many patients. (Endocr Pract. 2008;14:750-756)     

Management of Type 2 Diabetes Mellitus with Basal-Prandial Insulin Therapy: A Case-Based Review

Background: Diabetes mellitus (DM) is a growing epidemic in the United States—20.8 million people are affected and 90% to 95% of all diagnosed cases are type 2 DM. Nevertheless, implementation of insulin therapy is often delayed in patients with type 2 DM. This delay can increase the risk of DM-related complications, including microvascular neuropathy, nephropathy, retinopathy, and cardiovascular disease.Objective: This article provides a case-based review outlining a novel strategy for advancing therapy with a modified basal and prandial insulin regimen to achieve recommended glycemic targets in type 2 DM as quickly as possible. Evidence-based treatment strategies are also discussed.Methods: Materials used for this article were identified through an English-language literature search of MEDLINE (1967-2007) using the following terms: insulin, postprandial glucose control, and type 2 diabetes.Results: As shown with this male 46-year-old case study patient, type 2 DM is treated initially with diet and exercise, followed by oral antidiabetic drugs (OADs). However, oral therapy typically reduces glycosylated hemoglobin values only by -1.5% to 2.0%. Intensive therapy with once-daily basal insulin in combination with a previously prescribed OAD regimen can achieve normoglycemia and reduce the long-term complications of DM. In patients with postprandial glucose excursions, prandial insulin can be added using a rapid-acting insulin analogue (aspart, lispro, or glulisine).Conclusions: A key factor in this case patient's ability to reach glycemic targets within I year of diagnosis of type 2 DM was the accelerated implementation of insulin therapy. Such a therapeutic approach obviates the risk for uncontrolled hyperglycemia, which is associated with the standard practice of beginning treatment with diet and exercise alone and slowly advancing by i OAD at a time, ending with insulin therapy as a last resort. (Insulin. 2007;2:118-126)     

Temporal Occurrences and Recurrence Patterns of Hypoglycemia During Hospitalization

Objective: To describe the temporal distribution of hypoglycemia and its rate of recurrence during hospitalization to aid in the development of strategies to prevent hypoglycemia in hospitalized patients.Methods: Retrospective review of hypoglycemia (blood glucose <50 mg/dL) audit data in adult hospitalized patients at 2 academic hospitals. Demographics, timing, and blood glucose values were recorded. Antihyperglycemic medications, number of recurrent events, and change in basal insulin dose following the hypoglycemic event were also extracted.Results: A total of 274 index occurrences of hypoglycemia were analyzed. The mean age of the patients was 53.8 years, with roughly equal gender distributions. Twenty-eight percent of the events occurred in the absence of antihyperglycemic therapy. The incidence of hypoglycemia peaked between midnight and 6 AM. There were 36 instances of recurrent hypoglycemia associated with antihyperglycemic therapy, with 78% (n = 28) cases involving basal insulin. Patients on basal insulin who developed hypoglycemia did not have their dose changed prior to the time of the next administration in 75% of the cases.Conclusion: Hypoglycemia in hospitalized patients may occur with greater frequency overnight. Although cumbersome, routine nocturnal glycemic testing should be considered. Education regarding insulin management in the hospital and improved communication between night and day staff may aid in decreasing subsequent hypoglycemic events.Abbreviations: BG = blood glucose EHR = electronic health record ICU = intensive care unit IV = intravenous     

Pseudohypoglycemia: a Cause for Unreliable Finger-Stick Glucose Measurements

ObjectiveTo identify patients with an inaccurate diagnosis of hypoglycemia and discuss predisposing factors.MethodsWe describe our patient’s clinical presentation, laboratory work-up, hospital course, and follow-up and review similar cases from the literature.ResultsA 27-year-old woman with Raynaud phenomenon was admitted because of symptomatic hypoglycemia. Physical examination showed tremulousness, sweating, and the classic Raynaud color changes of the hands during episodic symptoms. A 72-hour fast revealed finger-stick capillary glucose values ranging from 32 to 45 mg/dL on multiple occasions, while concurrent plasma glucose values were consistently 1.5 to 2 times higher. Capillary measurements of glucose performed in the arms and legs at room temperature and after warming of each extremity disclosed an increase in glucose levels from a range of 35 to 52 mg/dL at room temperature to a range of 82 to 100 mg/dL after warming, confirming a discordance between capillary and venous blood results. The diagnosis of pseudohypoglycemia was made. Pseudohypoglycemia has been reported in patients with Raynaud phenomenon, peripheral vascular disease, and shock and may result from increased glucose extraction by the tissues because of low capillary flow and increased glucose transit time.ConclusionPseudohypoglycemia should be suspected in the setting of impaired microcirculation and can be confirmed by readily available means. (Endocr Pract. 2008;14:337-339)     

Hot Flashes and Fatigue Relieved by Metformin

ObjectiveTo describe 3 patients with long-standing hot flashes, excessive sweating, and fatigue whose symptoms were ameliorated with metformin.MethodsIn this case series, we report the findings of laboratory evaluations, including assessments for thyroid, gonadal, adrenal, and pancreatic disorders, in 3 patients referred for endocrine evaluation. A 75-g oral glucose tolerance test with measurement of fasting and postprandial glucose and insulin concentrations was conducted. A trial of metformin, 500 mg twice daily, was initiated in all patients.ResultsEvaluation of factors that are associated with hot flashes and increased sweating did not establish the cause of the patients’ symptoms. The 3 patients had normal glucose tolerance test results and hyperinsulinemia. Metformin therapy markedly relieved the symptoms in all patients.ConclusionsHyperinsulinemia without hypoglycemia may produce a sympathoexcitatory response that manifests as hot flashes and increased sweating. Metformin may have sympathoinhibitory actions that alleviate these symptoms. (Endocr Pract. 2009;15:30-34)     

The role of rapid-acting insulin analogues and inhaled insulin in type 2 diabetes mellitus

sBackground:The availability of rapid-acting insulin analogues and inhaled insulin gives clinicians additional treatmentoptions in the management of patients with diabetes mellitus (DM). Combining rapid-acting insulin analogues with basal insulin can more closely mimic physiologic insulin release to maximize glycemic control.Objective:The objective of this article was to discuss the role of rapid-acting insulin analogues and inhaled insulin inthe treatment of patients with type 2 DM.Methods:Materials for this article were obtained through an online search of MEDLINE/PubMed and Google(1996-2006) using the search terms bolus insulin, postprandial, rapid-acting insulin analogues, titration, hypoglycemia, glycemic control, inhaled insulin, and insulins lispro, aspart, and glulisine.Results:Glycosylated hemoglobin (A1C) levels and number of all hypoglycemic episodes were similar in patients withtype 2 DM taking either mealtime rapid-acting insulin analogues or regular human insulin (RHI). Rapid-acting insulins have been successfully used in basal-bolus regimens with a variety of long- and intermediate-acting insulins, as well as with oral hypoglycemic agents. Injectable rapid-acting insulin analogues markedly decreased postprandial glucose (PPG) levels compared with RHI. Better reduction in PPG levels may be key to achieving target A1C levels in some patients, but long-term outcome studies are needed to assess whether lowering PPG levels decreases cardiovascular risk in patients with type 2 DM. Inhaled insulin may be an option for patients who cannot inject insulin, but route of administration and dosing issues limit its use in many patients. The effect of inhaled insulin on PPG is unclear at this time.Conclusions:Although rapid-acting insulin analogues are effective in the management of patients with type 2 DM, the limited numbers of studies have yet to demonstrate that these agents have any significant long-term advantage compared with RHI. In addition, they cost more than RHI. Further studies are needed to compare the efficacy of the rapid-acting insulin analogues, to compare the different dosing regimens used with mealtime insulin administration, and to ascertain if the decrease in PPG levels seen with the use of rapid-acting insulin analogues translates into improved glycemic control and perhaps even a reduction in cardiovascular risk in patients with type 2 DM. (Insulin. 2007;2:61-67) Copyright 2007 Excerpta Medica, Inc.     

Residual dysphasia after severe hypoglycemia in a patient with immune-mediated primary Adrenal insufficiency and type 1 diabetes mellitus: Case report and systematic review of the literature

ObjectiveTo describe a 24-year-old patient with immune-mediated primary adrenal insufficiency and type 1 diabetes mellitus (T1DM) receiving intensive diabetes management who was comatose at presentation attributable to severe hypoglycemia and had residual dysphasia after recovery and to summarize the related literature.MethodsWe present a case report and the findings on systematic review of the pertinent literature to identify the cumulative incidence of severe hypoglycemia with use of intensive insulin therapy in patients with primary adrenal insufficiency and T1DM and to determine the incidence of dysphasia after severe hypoglycemia.ResultsAfter 5 days of mechanical ventilation, our patient was revived. He had severe dysphasia after recovery of consciousness. Magnetic resonance imaging of the brain revealed encephalomalacia in the left temporal, frontal, and parietal lobes. After 6 years of follow-up, he continues to have residual deficits of expressive dysphasia and difficult-to-control seizures but no other neurologic disorders. Systematic review of the literature revealed that studies from the 1950s reported mortality due to hypoglycemia in such a cohort, but no recent studies have described the cumulative incidence of severe hypoglycemia in a cohort of patients with primary adrenal insufficiency and T1DM. To the best of our knowledge, we report the first findings on magnetic resonance imaging of the head in such a patient.ConclusionFortunately, residual dysphasia is an infrequent outcome after severe hypoglycemia. (Endocr Pract. 2007;13:384-388)     

Fasting Versus Postprandial Hyperglycemia as a Treatment Target to Lower Elevated Hemoglobin A1C

Objective: Postprandial hyperglycemia (PPHG) may need addressing when glycemic control cannot be maintained in patients with type 2 diabetes mellitus. We investigated whether glycated hemoglobin A_1c (A_1c) levels ≥7.0% can indicate postprandial defects warranting prandial therapy after optimized basal insulin therapy.Methods: From 6 clinical trials of insulin glargine treatment, data were pooled from 496 patients with A_1c ≥7.0% after 24 weeks. Patient characteristics and clinical outcomes were summarized according to fasting plasma glucose (FPG) target achievement (<130 mg/dL), postprandial blood glucose (PPBG) levels, and PPBG increments (ΔPPBG). Basal and postprandial contributions to hyperglycemia were determined.Results: After 24 weeks of insulin glargine titration, A_1c change from baseline was greater in patients with FPG <130 mg/dL versus ≥130 mg/dL (-1.35% versus -1.11%, respectively; P = .0275), but with increased confirmed hypoglycemia rates (blood glucose <70 mg/dL; 4.06 events/patient-year versus 3.31 events/patient-year; P = .0170). However, increased severe hypoglycemia rates were observed in patients with FPG ≥130 mg/dL. At week 24, postprandial contributions to hyperglycemia increased (>60% regardless of PPBG). Patients with high FPG had lower, but substantial, relative postprandial contributions versus patients achieving FPG target. A similar pattern was observed according to whether patients had a ΔPPBG ≥50 mg/dL after any meal.Conclusion: After optimized basal insulin therapy, elevated A_1c is the most effective indicator of residual PPHG, regardless of existent FPG or PPBG. When confronted with an uncontrolled A_1c after reasonable titration of basal insulin, clinicians should be aware of probable postprandial contributions to hyperglycemia and consider prandial therapy.Abbreviations:A_1c = glycated hemoglobin A_1cAUC = area under the curveAUC_B = area under the curve (basal hyperglycemia)AUC_G = total area under the curve (total glucose)AUC_N = area under the curve (normal glycemic exposure)AUC_P = area under the curve (postprandial hyperglycemia)BHG = basal hyperglycemiaFBG = fasting blood glucoseFPG = fasting plasma glucoseGLP-1 = glucagon-like peptide 1HE = hyperglycemic exposureOADs = oral antidiabetes drugsPPBG = postprandial blood glucoseΔPPBG = change in postprandial blood glucosePPHG = postprandial hyperglycemiaSMBG = self-monitored blood glucoseT2DM = type 2 diabetes mellitus     

Hypoglycemia: Minimizing Its Impact in Type 2 Diabetes

ObjectiveTo review and discuss the risks and impact of hypoglycemia and provide guidance for the prevention of hypoglycemia in type 2 diabetes (T2DM).MethodsWe review and discuss the risks and impact of hypoglycemia, providing specific guidance regarding the prevention of hypoglycemia and judicial selection of glucose-lowering agents in individuals with T2DM.ResultsHypoglycemia in T2DM is underrecognized and underreported. Emerging evidence from large clinical trials suggest that hypoglycemia may be an important risk factor for morbidity and mortality in T2DM. In addition, hypoglycemia is associated with reduced quality of life, greater healthcare utilization costs, and poor adherence to medical regiments.ConclusionThese findings have led professional organizations to emphasize the prevention of hypoglycemia as an important consideration when initiating or intensifying treatment regimens. In clinical settings, particular attention should be paid to a patient’s risk for hypoglycemia when initiating or intensifying the pharmacological treatment regimen. The endocrinologist can play an important role in educating not only the patient, but also other members of the diabetes-management team regarding the need for individualized therapy. (Endocr Pract. 2013;19:526-535)     

Efficacy and Safety of Iglarlixi in Hispanics and Non-Hispanic Whites with Type 2 Diabetes

Objective: Type 2 diabetes (T2D) is more common in Hispanic than non-Hispanic white (NHW) populations worldwide, and ethnicity, among other factors, may affect response to therapy. The efficacy and safety of insulin glargine 100 units/mL (iGlar) and the fixed-ratio combination of iGlar and the glucagon-like peptide 1 receptor agonist lixisenatide (iGlarLixi) was assessed in Hispanic and NHW patients with T2D from 25 countries.Methods: In this post hoc analysis, data from two 30-week randomized controlled trials comparing iGlar and iGlarLixi in patients with T2D uncontrolled on basal insulin ± oral antidiabetes drugs (OADs; LixiLan-L: NCT02058160) or uncontrolled on metformin ± OADs (LixiLan-O: NCT02058147) were evaluated.Results: Of the 1,512 patients included across trials, 301 were Hispanic and 1,211 NHW. Compared with iGlar, iGlarLixi resulted in greater reductions in glycated hemoglobin (A1C) and 2-hour postprandial glucose and a higher proportion of patients at target A1C <7.0% (<53 mmol/mol), regardless of ethnicity. Among NHWs from the LixiLan-L trial, documented symptomatic hypoglycemia (plasma glucose ≤70 mg/dL) rates were higher with iGlar compared with iGlarLixi (P = .06), whereas this trend was reversed among Hispanics (P = .07). Nevertheless, in both trials, a greater proportion of patients taking iGlarLixi than iGlar reached the composite efficacy endpoints of target A1C without hypoglycemia and target A1C without weight gain, regardless of ethnicity.Conclusion: These results indicate that iGlarLixi is a viable therapeutic option for both Hispanic and NHW patients with T2D, as it is efficacious without a significant increase in hypoglycemia, irrespective of ethnicity.Abbreviations: A1C = glycated hemoglobin; BMI = body mass index; FPG = fasting plasma glucose; FRC = fixed-ratio combination; GLP-1 RA = glucagon-like peptide 1 receptor agonist; HDL-C = high-density-lipoprotein cholesterol; iGlar = insulin glargine; iGlarLixi = insulin glargine + lixisenatide; LDL-C = low-density-lipoprotein cholesterol; NHW = non-Hispanic white; OAD = oral antidiabetes drug; PPG = postprandial glucose; T2D = type 2 diabetes     

Danger of Hypoglycemia Due to Acute Tramadol Poisoning

ObjectiveTo report a case of prolonged hypoglycemia after acute tramadol poisoning.MethodsWe describe a patient’s clinical presentation and outcome with prolonged hypoglycemia attributable to acute tramadol poisoning. In addition, the possible mechanism for the hypoglycemia is discussed, and a brief review of the pertinent literature is presented.ResultsA 54-year-old woman had previously under- gone a partial hepatectomy because of involvement of her liver by a gastrointestinal stromal tumor. After ingestion of 3,000 mg of tramadol with suicidal intent, she developed prolonged hypoglycemia that necessitated treatment with continuous intravenous glucose infusion for 24 hours. Reports in the literature have described central nervous system depression, nausea, vomiting, tachycardia, seizures, and even death from tramadol overdoses.ConclusionThis report alerts clinicians to the potential danger of severe hypoglycemia in tramadol poisoning. (Endocr Pract. 2012;18:e151-e152)     

Insulinoma in a Young Female Patient With Systemic Lupus Erythematosus: A Case Report

ObjectiveFasting hypoglycemia may occur in subjects with systemic lupus erythematosus (SLE) when accompanied with insulin-binding antibodies or insulin-receptor antibodies. However, insulinoma has not been reported in SLE subjects with hypoglycemia.MethodsWe present a case report and review the relevant literature.ResultsA 26-year-old female with underlying SLE experienced several episodes of neuropsychiatric symptoms in a fasting state. The steroid dosage was titrated up, but in vain. Timely imaging studies showed a pancreatic tumor, and insulinoma was proven by pathology. Hypoglycemia did not recur after surgery.ConclusionPhysicians should distinguish insulinoma from autoimmunity-mediated hypoglycemia in SLE patients with fasting hypoglycemia. (Endocr Pract. 2014; 20:e256-e259)     

The Role of Recombinant Human Thyrotropin for Diagnostic Monitoring of Patients with Differentiated Thyroid Cancer

ObjectiveTo describe the evolving role of recombinant human thyrotropin in the diagnostic evaluation of patients treated for differentiated thyroid carcinoma.MethodsA systematic review was performed of published English language articles appearing in PubMed using terms “recombinant thyrotropin” and “thyroid cancer”. The author selected articles for inclusion based upon potential for clinical impact of the reported findings.ResultsThe addition of recombinant human thyrotropin to diagnostic testing replaced the requirement for thyroid hormone withdrawal and symptomatic hypothyroidism that had been necessary to generate sufficient endogenous thyrotropin for radioiodine scanning and thyroglobulin testing. The high negative predictive value of stimulated thyroglobulin testing removed the need for serial radioiodine scanning for many patients, but repeated stimulated testing rarely appeared to add significantly. The development of highly sensitive second generation thyroglobulin assays may replace the need for stimulated testing in a subset of patients.ConclusionRecombinant human thyrotropin-stimulated testing continues to be a valuable component of follow-up testing in the first year after initial treatment of differentiated thyroid cancer. (Endocr Pract. 2013;19: 157-161)