Nonischemic Cardiomyopathy Associated with Autoimmune Polyglandular Syndrome Type II

ObjectiveTo report a case of nonischemic cardiomyopathy associated with autoimmune polyglandular syndrome type II (APS-II).MethodsWe describe our patient’s clinical features, evaluation, and outcome. In addition, a literature review of cardiomyopathy associated with polyendocrinopathy syndromes is presented.ResultsThe component disorders of APS-II are Addison’s disease in combination with either autoimmune thyroid disease or type 1 (insulin-dependent) diabetes. Although numerous other autoimmune conditions have been reported in conjunction with APS-II, cardiomyopathy has not been previously described as part of this syndrome. The current patient was a 32-year-old man who, during a 5-year period, was diagnosed as having type 1 diabetes mellitus, Crohn’s disease, and Addison’s disease. In 2001, he presented with severe heart failure that progressed rapidly and eventually necessitated cardiac transplantation.ConclusionAlthough autoimmune cardiomyopathy has been associated with other autoimmune disorders, to our knowledge this is the first reported case of cardiomyopathy in association with an autoimmune polyglandular syndrome. Patients with this syndrome should undergo clinical evaluation for heart failure. (Endocr Pract. 2007;13:59-62)     

Mauriac syndrome still exists

Background/objectiveMauriac syndrome (MS) is a rare complication of type 1 diabetes mellitus (DM1). It is related to low insulin concentrations and is less common since longer-acting insulins became available. It is characterized by hepatomegaly, growth and puberty delay, and the presence of elevated transaminases and serum lipids. The aim of this study was to describe the patients from a pediatric diabetic population that fulfill the criteria of MS.Materials and methodsA retrospective analysis of the pediatric diabetic population with diagnostic criteria of MS currently followed at Hospital de Braga, was performed.ResultsFrom a population of 91 patients with DM1 18 years, 6 patients with the criteria for MS were identified: 5 girls, and 1 boy. The age at presentation was 13–17 years, with a minimum interval between DM1 diagnosis and MS criteria of 4 years. All the patients were prescribed intensive insulin therapy (median daily insulin dose: 0.88 U/kg). All had a previous history of poor glycemic control before the diagnosis of MS with glycated hemoglobin (HbA1c) between 8.8 and 12.9%. Increase of hepatic enzymes was present in all the patients; 4 of them had associated hepatomegaly. All the girls presented puberty delay and cushingoid features. None of the patients presented short stature and 5 of them presented mixed dyslipidemia.ConclusionsAlthough MS is an ancient entity described in DM1, it still exists, particularly in adolescent females. Being aware of MS is of extreme importance since most of the clinical features are reversible with better glycemic control.     

Mody-3: Novel HNF1A Mutation and the Utility of Glucagon-Like Peptide (GLP)-1 Receptor Agonist Therapy

ObjectiveAn estimated 1 to 2% of cases of diabetes mellitus have a monogenic basis; however, delayed diagnosis and misdiagnosis as type 1 and 2 diabetes are common. Correctly identifying the molecular basis of an individual’s diabetes may significantly alter the management approach to both the patient and his or her relatives. We describe a case of mature onset diabetes of the young (MODY) with sufficient evidence to support the classification of a novel HNF1A (hepatocyte nuclear factor-1-α) mutation as a cause of MODY-3.MethodsA 21-year-old Caucasian female presented to our office with a diagnosis of noninsulin-dependent diabetes mellitus (NIDDM) at age 10; glycemia was initially managed with oral antidiabetic (OAD) agents and insulin detemir. The patient reported a strong family history of early-onset NIDDM in both her mother and maternal grandmother, both of whom eventually required insulin therapy to control glycemia. The patient’s medical and family history were highly suggestive of maturity-onset diabetes of the young (MODY), and genetic testing was performed.ResultsGenetic screening detected a mutation p.Arg200Trp in the HNF1A gene in the patient, her mother, and maternal grandmother, suggesting a diagnosis of MODY-3. This finding resulted in a change of antidiabetic therapy in all 3 patients, including the addition of once-daily liraglutide therapy, which helped improve their glycemic control.ConclusionOur case report supports the classification of the p.Arg200Trp mutation as a cause of MODY-3. The findings also suggest that glucagon-like peptide-1 (GLP-1) receptor agonist therapy may be of value in managing glycemia in patients with MODY-3. (Endocr Pract. 2014;20:107-111)     

Failure of Multiple Therapies in the Treatment of a Type 1 Diabetic Patient with Insulin Allergy: A Case Report

ObjectiveTo describe the clinical manifestations of insulin allergy and explain a systematic management approach.MethodsWe present the clinical, laboratory, and pathologic findings of a type 1 diabetic patient with allergy to subcutaneous insulin and briefly review the related literature.ResultsAn 18-year old woman with type 1 diabetes mellitus had an insulin allergy and developed subcutaneous nodules after insulin administration. Human and analogue insulins were used, but painful nodule formation persisted. Treatment with antihistamines, steroids, and omalizumab and insulin desensitization were ineffective. The patient required pancreatic transplant because glycemic control could not be achieved due to the insulin allergy.ConclusionsInsulin allergy is not a common condition and can be challenging in patients with type 1 diabetes. Therefore, identifying patients with true insulin allergy and applying a stepwise approach to their treatment is important. (Endocr Pract. 2011;17:91-94)     

Diabetes Mellitus after Hematopoietic Stem Cell Transplantation

ObjectiveTo review the current literature on posttransplant diabetes mellitus after hematopoietic stem cell transplantation, including its epidemiologic features, transplant-related risk factors, and treatment.MethodsA literature search was conducted in PubMed for articles on diabetes mellitus after hematopoietic stem cell transplantation and effects of immunosuppressants on glucose metabolism.ResultsWithin 2 years after hematopoietic stem cell transplantation, up to 30% of patients may have diabetes. Although some of these cases resolve, the rates of diabetes and metabolic syndrome remain elevated in comparison with those in the nontransplant patient population during long-term follow-up. Traditional risk factors for diabetes as well as features related to the transplantation process, including immunosuppressive medications, are associated with posttransplant diabetes. Cardiovascular risk also appears to be increased in this population. Limited data are available on hypoglycemic agents for posttransplant diabetes; thus, treatment decisions must be based on safety, efficacy, and tolerability, with consideration of each patient’s transplant-related medications and comorbidities.ConclusionTreatment of diabetes mellitus in patients who have undergone hematopoietic stem cell transplantation necessitates attention to the posttransplant medication regimen and clinical course. Although no guidelines specific to treatment of posttransplant diabetes in this patient population currently exist, treatment to goals similar to those for nontransplant patients with diabetes should be considered in an attempt to help reduce long-term morbidity and mortality. (Endocr Pract. 2010;16:699-706)     

Markedly Low Hemoglobin A1c in a Patient with an Unusual Presentation of ß-Thalassemia Minor

ObjectiveTo describe very low hemoglobin A_1c levels in a patient with type 2 diabetes mellitus and an unusual presentation of β-thalassemia minor.MethodsWe present the clinical and laboratory findings of the study patient.ResultsA 64-year-old African American man with type 2 diabetes mellitus was referred to the endocrinology clinic with a hemoglobin A_1c level of 1.6% despite elevated blood glucose concentrations. A red blood cell survival study with chromium-51 revealed that he had a reduced erythrocyte life span less than 25% of normal. He also had a markedly elevated reticulocyte count ranging from 236 to 534 x 10³/μL (reference range, 25-75 x 103/μL). The laboratory findings, which are not characteristic of ß-thalassemia minor, could be the cause of the markedly low hemoglobin A_1c in this patient.ConclusionsAlthough rare, when associated with marked erythrocyte turnover, β-thalassemia minor can lead to a severe reduction in HbA_1c levels. In this scenario, glycemic control is best assessed by measuring fructosamine. (Endocr Pract. 2010;16:89-92)     

Postmortem Diagnosis of Diabetic Ketoacidosis Presenting as the "Dead-in-Bed Syndrome"

Objective:To report a case of a young male with type 1 diabetes mellitus found dead in his bed, initially assumed to have died from hypoglycemia (i.e., the “dead in bed” syndrome). However, his autopsy findings revealed that diabetic ketoacidosis (DKA) was the cause of death.MethodsWe present the laboratory and autopsy findings of the patient, highlighting the importance of laboratory analyses of the vitreous humor and microscopy of kidney tissue when investigating the cause of sudden death in patients with type 1 diabetes.ResultsA 25-year-old healthy male with type 1 diabetes on continuous subcutaneous insulin infusion therapy was found dead in his undisturbed bed. An autopsy included vitreous humor analyses. His results were as follows: glucose of 755 mg/dL (reference range 70-105 mg/dL), anion gap > 36 mEq (reference range 4-12 mEq/L), elevated acetone at 66 mg/dL (reference range negative), which were consistent with DKA. Renal microscopy demonstrated subnuclear vacuoles in the proximal tubules, 1 of 2 lesions were described as an Armanni-Ebstein lesion, which is a postmortem finding in patients who die from diabetic coma.ConclusionThe most likely cause of death at home in young patients with type 1 diabetes is severe hypoglycemia. However, an autopsy of the present case confirmed DKA based on vitreous humor biochemistry and microscopic examination of the kidneys, which demonstrated the Armanni-Ebstein phenomenon. Analysis of the vitreous fluid and microscopic examination of the kidneys for the presence of Armanni-Ebstein lesion can be used to help determine the cause of death in patients with type 1 diabetes mellitus. (Endocr Pract. 2014;20:e123-e125)     

Imatinib and Type 2 Diabetes

ObjectiveTo characterize the effect, if any, of imatinib mesylate, an inhibitor of abl tyrosine kinase used in the treatment of chronic myeloid leukemia, on type 2 diabetes.MethodsThe centralized pharmacy database was used to identify all patients who had received imatinib at the Mayo Clinic in Rochester, Minnesota, during a 5-year period. The electronic medical records were subsequently reviewed to identify which of these patients had type 2 diabetes. In addition, relevant biochemical data, prior to, during, and after imatinib treatment, were abstracted from the electronic laboratory database and medical records.ResultsAt the Mayo Clinic in Rochester, Minnesota, a total of 164 patients received imatinib during the period of study (1999 to 2004). Of these 164 patients, 7 had preexisting type 2 diabetes, and diabetes developed in 2 patients during treatment with imatinib. Despite 2 previous reports of improvement in glycemic control with use of imatinib in patients with type 2 diabetes, no net effect on glycemic control or diabetes therapy was noted in our study cohort.ConclusionOn the basis of our current study, it seems unlikely that imatinib substantially affects glycemic control in patients with type 2 diabetes. (Endocr Pract. 2007;13:126-130)     

Atypical Diabetes Mellitus Associated with Bone Marrow Transplantation

ObjectiveTo describe 3 cases of atypical diabetes mellitus following bone marrow transplantation.MethodsWe describe the clinical presentation and relevant laboratory findings of 3 patients who presented with new-onset diabetes mellitus after bone marrow transplantation and discuss the possible mechanisms.ResultsA 52-year-old white man with chronic myelogenous leukemia, a 51-year-old white woman with acute myelogenous leukemia, and a 38-year-old Hispanic woman with acute myelogenous leukemia presented with acute onset of diabetes mellitus after bone marrow transplantation. Although blood glucose levels were initially very high, the patients required only small insulin dosages for glycemic control. Both the acute onset and requirement of relatively small insulin dosages were characteristic of type 1 diabetes mellitus. Onset of diabetes appeared to be unrelated to immunosuppressive drug therapy because it happened several months after starting these drugs. C-peptide was detectable, and glutamic acid decarboxylase antibodies were absent. Diabetes mellitus remitted spontaneously after a few months while the immunosuppressive drugs were continued.ConclusionAlthough the underlying mechanisms are unknown, cytokine changes after bone marrow transplantation may have led to temporary b-cell dysfunction in these patients. (Endocr Pract. 2010;16:93-96)     

Glycemia and Cardiova Scular Disease in Type 1 Diabetes Mellitus

ObjectiveTo evaluate the role of glycemic control in the development of cardiovascular disease (CVD) in type 1 diabetes mellitus (DM).MethodsWe review the literature regarding coronary atherosclerosis, coronary artery calcification, and the epidemiologic studies related to the role of glycemia and the classic risk factors for coronary artery disease (CAD) in type 1 DM.ResultsFour prospective studies (Wisconsin Epidemiologic Study of Diabetic Retinopathy, EURODIAB, Steno Diabetes Center Study of Adults With Type 1 DM, and Pittsburgh Epidemiology of Diabetes Complications study) do not show that glycemic control predicts CAD occurrence. Findings from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications study show that compared with conventional insulin therapy, intensive insulin therapy reduces CVD among patients with type 1 DM and is associated with lower prevalence of coronary artery calcification. The discrepancies between the findings from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications study and the Pittsburgh Epidemiology of Diabetes Complication study are likely due to differences between the study populations and the lower prevalence of renal disease in the former study. Besides duration of DM and albuminuria/overt nephropathy, insulin resistance is a major determinant of CAD associated with type 1 DM.ConclusionsDiscrepant study results regarding the relationship between glycemia and CAD/coronary artery calcification may be related to the prevalence of renal disease and the presence of the metabolic syndrome. Published data suggest that addressing traditional risk factors including albuminuria, the metabolic syndrome, and inflammatory markers is better for preventing and treating CAD than focusing exclusively on glycemic control, which is still necessary for preventing microvascular complications. Furthermore, there is a synergistic effect of glycemic control and albuminuria on the development of CVD. (Endocr Pract. 2008;14:912-923)     

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)     

Severe Hyponatre mia Due to Rosiglita zone Use in an Elderly Woman With Diabetes Mellitus: A Rare Cause of Syndrome of Inappropriate Antidiuretic Hormone Secretion

ObjectiveTo describe the first case of syndrome of inappropriate antidiuretic hormone secretion with lifethreatening hyponatremia due to rosiglitazone therapy.MethodsWe describe the clinical, laboratory, and imaging findings of the study patient.ResultsAn 89-year-old woman with a 5-year history of type 2 diabetes mellitus was admitted to the emergency department because of unconsciousness. She had reported generalized weakness for 15 days and nausea and vomiting for 3 days. Findings from laboratory analysis showed severe hyponatremia (sodium, 110 mEq/L). She had normal renal, cardiac, and adrenal function, and she did not have edema or volume depletion. The cause of hyponatremia was syndrome of inappropriate antidiuretic hormone secretion. We did not find any cause for her condition other than rosiglitazone, an antihyperglycemic drug that is increasingly being used in patients with type 2 diabetes mellitus. According to her medical history, rosiglitazone was prescribed 1 month previously after withdrawal of gliclazide. We stopped the rosiglitazone and administered hypertonic saline infusion to treat the hyponatremia. Saline infusion was stopped and blood sodium levels were stabilized in the normal range after 2 days. The patient’s plasma sodium concentration has remained in the reference range at follow-up visits.ConclusionsThis is the first reported case of syndrome of inappropriate antidiuretic hormone secretion as an adverse effect of rosiglitazone, and this drug should possibly be considered for addition to the list of drugs that cause this condition. (Endocr Pract. 2008;14:1017-1019)     

Recurrent Macular Edema and Stroke Syndrome in Type 1 Diabetes Mellitus with Potent Endothelial Cell Inhibitory Autoantibodies

ObjectiveTo describe a case of type 1 diabetes mellitus with recurrent macular edema and stroke in association with potent endothelial cell inhibitory autoantibodies.MethodsThe clinical, radiologic, and biochemical data from the study patient are presented, as is the bioactivity in endothelial cells from the immunoglobulin G fraction of the patient’s serum.ResultsA 52-year-old man with a 15-year history of poorly controlled type 1 diabetes mellitus had diabetic autonomic neuropathy, gastroparesis, depression, macular edema, proliferative retinopathy, diabetic nephropathy, refractory hypertension, and transient ischemic attacks that progressed to recurrent strokes despite aspirin therapy. Magnetic resonance imaging of the brain showed multifocal, bilateral ischemic infarcts consistent with recurrent stroke affecting small vessels. The patient’s serum contained endothelial cell inhibitory autoantibodies; the titer doubled during a 2-year period when the patient required repeated focal laser to treat macular edema and experienced transient ischemic attacks. The IgG autoantibodies induced stress fiber formation and apoptosis in endothelial cells and inhibited neurite outgrowth in rat pheochromocytoma PC12 cells.ConclusionsLow concentrations of purified autoantibodies (1-2 μg/mL) induce endothelial cell contraction in vitro, suggesting a role for autoantibodies in modulating endothelial cell permeability, which may affect multiple target organs. Potent IgG autoantibodies may be a useful marker (with a possible pathophysiologic role) in an unusual syndrome characterized by poorly controlled diabetes, hypertension, dementia, and recurrent small-vessel stroke. (Endocr Pract. 2010;16:842-850)     

Advanced Insulin Management program reduces A1C levels and regimen-related distress without weight gain in patients with type 1 diabetes mellitus

Background: Despite the availability of effective treatments, many patients with diabetes have suboptimal glycemic control.Objective: This study was designed to determine whether the Advanced Insulin Management (AIM) program could help patients with type 1 diabetes mellitus (DM) reduce their A1C levels to ≤7.5% without weight gain, increased incidence of hypoglycemia, or increased diabetes-related distress.Methods: The AIM program, developed to intensify glycemic control in patients with type 1 DM, consisted of a screening visit and 3 to 6 interactive group sessions, depending on whether the patient elects multiple daily injections (MDIs) or an insulin pump. Patients who wanted to learn additional diabetes management skills were referred by their endocrinologist, and those with competent carbohydrate-counting skills and record-keeping practices were eligible to enroll. A nurse, dietitian, psychologist, and physician provided group instruction and supported individual goal setting. The program included depression screening, regimen adjustments, and problem-solving activities. Outcome measures, including blood glucose, A1C, weight, and diabetes-related distress, were tracked for 12 months.Results: The study included 113 adult patients with type 1 DM (59% female; mean age, 39 years). Twenty patients already had insulin pumps, 46 patients initiated pump therapy during the study, and 47 patients elected MDIs. Mean A1C declined by 0.5% (to 7.3%) after 12 months, without weight gain or increased hypoglycemia. A significant decrease in diabetes-related distress was observed.Conclusion: The AIM program was associated with important improvements in glycemic control in patients with type 1 DM, without weight gain or increased hypoglycemic episodes.     

Development of Type 2 Diabetes Mellitus in the Obese Adolescent:A Growing Challenge

ObjectiveTo describe the metabolic phenotype of type 2 diabetes mellitus in youth and possible metabolic defects leading to its development with particular emphasis on fatty liver.MethodsWe present data gathered from studies performed in obese adolescents across the spectrum of glucose tolerance to assess both alterations in insulin sensitivity and secretion. Discussion regarding treatment options is presented using the data from the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study.ResultsAs the number of children with obesity continues to grow, the health implications of the condition are becoming increasingly evident. An unprecedented phenomenon rarely seen before has emerged: type 2 diabetes mellitus. At the time of diabetes diagnosis, cardiovascular disease may already be present, even in young adults. The progression from normal glucose tolerance to type 2 diabetes in adults occurs through an intermediate phase of altered glucose metabolism known as impaired glucose tolerance or prediabetes. Previous studies from our group and others reported a high prevalence of impaired glucose tolerance among children and adolescents with marked obesity. Cross-sectional studies demonstrate that impaired glucose tolerance in obese youth is associated with severe insulin resistance, β-cell dysfunction, and altered abdominal and muscle fat partitioning. We end briefly by discussing the current data available on treatment of this condition from the TODAY study, the largest clinical trial ever performed in youth with type 2 diabetes.ConclusionThe observed rapid progression of the glucose homeostasis alterations in adolescents underlines the importance of focusing attention on the earliest stages of the disease before the onset of any alterations in glucose tolerance. (Endocr Pract. 2012;18:791-795)     

Impact of Switching Youth With Diabetes to Insulin Degludec in Clinical Practice

Objective: Many youth with diabetes struggle to meet glycemic targets. The new ultralong duration of action of insulin degludec (iDeg) holds potential to ameliorate missed doses of basal insulin and improve glycemic control in youth with diabetes.Methods: A retrospective chart review was undertaken of youth age 13 to <24 years in our practice with type 1 diabetes (T1D) or type 2 diabetes (T2D) who had been switched from glargine or detemir to iDeg to evaluate the impact of this transition on glycemic control.Results: Glycated hemoglobin A1c (HbA1c) in youth with T1D (n = 82) remained stable during 6 months of treatment with iDeg (10.1 ± 2.11% &lsqb;87 ± 23 mmol/mol] at start of iDeg compared to 10.1 ± 2.12% &lsqb;87 ± 23 mmol/mol] at 6 months of treatment), whereas in youth with T2D (n = 16), HbA1c significantly declined from 10.6 ± 2.3% (92 ± 25 mmol/mol) to 8.3 ± 2.2% (67 ± 24 mmol/mol) (P = .0024).Conclusion: In youth switched to iDeg, which in our practice is commonly due to ineffectiveness of the patient's current regimen, the outcome differences we saw may be due to preserved beta-cell function in youth with T2D. It remains to be seen whether there are benefits of transition to iDeg in youth with T1D beyond glycemic outcomes, such as reduction in ketosis and episodes of diabetic ketoacidosis.Abbreviations: DKA = diabetic ketoacidosis; DPV = Diabetes-Patienten-Verlaufsdokumentation (German/Austrian Prospective Diabetes Follow-Up Registry); HbA1c = glycated hemoglobin A1c; iDeg = insulin degludec; T1D = type 1 diabetes; T2D = type 2 diabetes     

Sitagliptin in Glutamic Acid Decarboxylase Antibody-Positive Diabetes Mellitus

ObjectiveTo describe a case illustrating the use of sitagliptin, an inhibitor of dipeptidyl-peptidase-4 (DPP-4), in anti-glutamic acid decarboxylase antibody-positive diabetes mellitus in association with a rare ataxic variant of stiff person syndrome.MethodsWe present our experience with use of the DPP-4 inhibitor sitagliptin for management of autoimmune diabetes in a elderly woman and highlight the association of diabetes with other autoimmune conditions.ResultsA 68-year-old Japanese woman presented with poorly controlled “type 2” diabetes mellitus, cerebral palsy, cerebellar ataxia, and hypothyroidism. She complained of stiffness and spasms, which had resulted in multiple falls and immobility. Antidiabetic medications included gliclazide, rosiglitazone, and acarbose; various insulins had been tried but discontinued because they worsened her stiffness and spasms. Her hemoglobin A_1c values remained above 9% despite maximal doses of the aforementioned orally administered hypoglycemic agents. After sitagliptin therapy was initiated, her hemoglobin A_1c level decreased from 9.3% (78 mmol/mol) to 7.3% (56 mmol/mol) in 5 months. Investigations confirmed the presence of an ataxic variant of stiff person syndrome. On repeated testing 18 months later, her anti-glutamic acid decarboxylase antibody levels had declined by more than 85%.ConclusionApart from the well-known mechanism of an increase in glucagonlike peptide-1, sitagliptin may exert its glucose-lowering effect by other mechanisms in patients with autoimmune diabetes. Further studies should be undertaken to address the effectiveness of DPP-4 inhibitors in non-type 2 diabetes. (Endocr Pract. 2012;18: e65-e68)     

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)     

Insulin Glargine or Neutral Protamine Hagedorn in Patients with Severe Insulin Resistance: is There A Benefit?

ObjectiveTo determine the benefit of neutral protamine Hagedorn (NPH) insulin compared with insulin glargine in a patient with type 2 diabetes mellitus and severe insulin resistance.MethodsWe describe the patient’s clinical findings and treatment course.ResultsA 52-year-old man with a 3-year history of type 2 diabetes mellitus did not achieve adequate glucose control despite escalation of his treatment regimen to insulin glargine, 80 units twice daily; insulin lispro, 60 units before each meal; and metformin. Dietary and lifestyle changes were emphasized and implemented while medication adherence with appropriate insulin technique was reviewed at each visit. Insulin glargine was replaced with the same dosage of NPH insulin. After 3 months, a significant drop in hemoglobin A_1c was noted, from 9.5% to 6.1%, consistent with the improved capillary glucose measurements. The effect was maintained over the following year, without any major hypoglycemic events.ConclusionNPH insulin might be superior to the long-acting analogue insulin glargine in cases of severe insulin resistance, but randomized studies are needed to confirm our finding and clarify the involved mechanisms. (Endocr Pract. 2012;18:e49-e51)     

Patients Achieving Good Glycemic Control (HBA1c <7%) Experience A Lower Rate of Hypoglycemia With Insulin Degludec Than with Insulin Glargine: A Meta-Analysis of Phase 3A Trials

Objective: Meta-analysis to compare hypoglycemia rates of basal insulin degludec (IDeg) with insulin glargine (IGlar) in patients with diabetes achieving good glycemic control (hemoglobin A_1c [HbA_1c] <7% at end of trial).Methods: In a preplanned meta-analysis, patient data from 7 randomized, treat-to-target, 26- or 52-week trials in patients with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) who administered IDeg (n = 2,899) or IGlar (n = 1,431) once daily were analyzed. Using a negative binomial regression model, this meta-analysis compared hypoglycemia rates in patients achieving HbA_1c <7% at end of trial with IDeg (n = 1,347) and IGlar (n = 697).Results: In all trials, IDeg was noninferior to IGlar in HbA_1c reduction from baseline. At end of trial, 2,044 patients (T2DM, n = 1,661; T1DM, n = 383) achieved HbA_1c <7%. The overall confirmed hypoglycemia rate, defined as plasma glucose <56 mg/dL or severe hypoglycemia if requiring assistance, was significantly lower with IDeg versus IGlar (estimated rate ratio [ERR] IDeg:IGlar, 0.86; 95% confidence interval [CI], 0.76 to 0.98). The nocturnal confirmed hypoglycemia rate, defined as occurring between midnight and 6:00 am, was significantly lower with IDeg (ERR, 0.63; 95% CI, 0.52 to 0.77). In the maintenance period (16 weeks onward when average insulin dose and glycemic levels stabilized), the overall confirmed hypoglycemia rate was significantly lower (ERR, 0.79; 95% CI, 0.68 to 0.92) and the nocturnal confirmed hypoglycemia rate was significantly lower (ERR, 0.57; 95% CI, 0.45 to 0.72) with IDeg versus IGlar.Conclusion: Patients with T1DM and T2DM achieved HbA_1c <7% with significantly lower rates of overall and nocturnal confirmed hypoglycemia with IDeg versus IGlar. The lower hypoglycemia rate with IDeg was more pronounced in the maintenance period.Abbreviations: ERR = estimated rate ratio; HbA_1c = hemoglobin A_1c; IDeg = insulin degludec; IGlar = insulin glargine; NPH = Neutral Protamine Hagedorn; PG = plasma glucose; T1DM = type 1 diabetes mellitus; T2DM = type 2 diabetes mellitus