Evidence-Based Medicine,Clinical Practice Guidelines,and Common Sense in the Management of Osteoporosis

ObjectiveTo evaluate the benefits and limitations of randomized controlled trials (RCTs), clinical practice guidelines (CPGs), and clinical judgment in the management of osteoporosis.MethodsA review was conducted of the English-language literature on the origins and applications of RCTs, CPGs, evidence-based medicine, and clinical judgment in the management of osteoporosis.ResultsEvidence-based medicine is use of the currently available best evidence in making clinical decisions for individual patients. CPGs are recommendations for making clinical decisions based on research evidence, sometimes with consideration of expert opinion, health care policy, and costs of care. The highest levels of medical evidence are usually thought to be RCTs and meta-analyses of high-quality RCTs. Although it is desirable and appropriate for clinicians to consider research evidence from RCTs and recommendations presented in CPGs in making clinical decisions, other factors—such as patient preference, comorbidities, affordability, and availability of care—are important for the actual implementation of evidence-based medicine.ConclusionDecisions about who to treat, which drug to use, how best to monitor, and how long to treat require clinical skills in addition to knowledge of medical research. The necessity of integrating common sense and clinical judgment is highlighted by the fact that many patients treated for osteoporosis in clinical practice would not qualify for participation in the pivotal clinical trials that demonstrated efficacy and safety of the drugs used to treat them. (Endocr Pract. 2009;15:573-579)     

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.     

“Metabolic” Surgery For Treatment Of Type 2 Diabetes Mellitus

ObjectiveTo discuss the potential contribution of “metabolic” surgery in providing optimal management of patients with type 2 diabetes mellitus (T2DM).MethodsA literature search was performed with use of PubMed, and the clinical experience of the authors was also considered.ResultsBariatric—or, more appropriately, metabolic—surgical procedures have been shown to provide dramatic improvement in blood glucose levels, blood pressure, and lipid control in obese patients with T2DM. In these patients, metabolic surgery involves a low risk of short-term mortality and a significant long-term survival advantage, whereas the diagnosis of diabetes is associated with significant long-term mortality. Experimental studies in animals and clinical trials suggest that gastrointestinal bypass procedures can control diabetes and associated metabolic alterations by mechanisms independent of weight loss. As a result, the use of bariatric surgery and experimental gastrointestinal manipulations to treat T2DM is increasing, even among less obese patients. Although body mass index (BMI) currently is the most important factor for identifying candidates for bariatric surgery, evidence shows that a specific cutoff BMI value cannot accurately predict successful surgical outcomes. Furthermore, BMI appears limited in defining the risk profile for patients with T2DM.ConclusionCurrent BMI-based criteria for performance of bariatric surgery are not adequate for determining eligibility for operative treatment in patients with diabetes. Large clinical trials, comparing bariatric surgery versus optimal medical care of patients with T2DM, should be given priority in order to define the role of surgery in the management of diabetes. Recognizing the need to work as a multidisciplinary team that includes endocrinologists and surgeons is an initial step in addressing the issues and opportunities that surgery offers to diabetes care and research. (Endocr Pract. 2009;15:624-631)     

Cultural Competence in Diabetes Mellitus Care: An Urgent Need

Background:Multicultural societies exist worldwide. Two important challenges can be appreciated in this scenario. Minority populations, due to a combination of genetic and lifestyle factors, have a particularly high risk for developing type 2 diabetes mellitus (DM). In addition, the quality of health care provided to minority populations, including that for DM, has lagged behind that provided to the white population. Because multiple medical, social, and cultural factors influence the development and progression of type 2 DM, management of patients becomes even more challenging if health care providers cannot identify and address the many contributing factors.Objective:The objective of this article was to raise awareness about the most common social and cultural factors that may influence the development of type 2 DM, progression of the disease, and adherence to treatment plans in patients from culturally diverse populations.Methods:A PubMed search of English-language articles published primarily between 1996 and 2006 was conductedusing the search terms Latino, Hispanic, culture, and diabetes, and a list of social and cultural factors associated with type 2 DM was created based on relevant articles and on the author's expertise and experience in the Latino Diabetes Initiative at the Joslin Diabetes Center.Results:There is increasing evidence that social and cultural factors such as body image, educational level, fears, general family integration and support, health literary, language, myths, and nutritional preferences, among others, may affect the success of the physician patient relationship and influence patients' adherence to treatment. Specific strategies to help clinicians remember to address multiple factors in the day-to-day management of patients with type 2 DM who are from culturally diverse populations include asking questions about patients' personal goals, ascertaining what behaviors they have adopted from mainstream culture, understanding how family ties may affect DM care and prevention, and being aware of patients' educational level when implementing any educational activity.Conclusions:The standards of DM care apply to every individual with this disease and should continue to be the core of every clinicians practice. However, improving health care providers' cultural competence may help improve the quality of care provided to minority groups and may ultimately reduce health care disparities. Increased cultural competence may also improve patient-provider trust and communication, as well as help patients adhere to prevention and treatment plans.     

Can Newer Therapies Delay the Progression of Type 2 Diabetes Mellitus?

ObjectiveTo review the multifactorial and progressive nature of type 2 diabetes mellitus (T2DM), the consequences of its progression, and the potential of traditional and newer therapies to delay the progression of this disease.MethodsThe relevant literature is reviewed, and the mechanisms of action of novel agents for treatment of T2DM are discussed.ResultsThe global prevalence of diabetes has been increasing in recent decades, reaching near-epidemic proportions, and is projected to more than double by 2030. More than 90% of cases of diabetes in most countries consist of T2DM, but many individuals remain undiagnosed or are diagnosed only after their disease has progressed considerably. Inadequate glycemic control in a majority of patients with T2DM is due to the progressive nature of the disease, delay in initiating pharmacotherapy, and failure to intensify treatment more quickly in patients who do not achieve glycemic targets. Traditional oral therapies are usually effective at lowering hyperglycemia initially but do not prevent disease progression; thus, many patients ultimately require insulin. Furthermore, because most antidiabetic therapies are associated with weight gain or risk of hypoglycemia (or both), patients may not adhere to treatment recommendations.ConclusionA new therapeutic approach focuses on the use of the incretin hormone glucagon-like peptide-1. Analogues of this hormone delay the progression of β-cell dysfunction and promote β-cell regeneration in animal models. In clinical trials, they have been shown to improve glycemic control by increasing glucose-stimulated insulin secretion and suppressing glucagon secretion. At high concentrations, they also slow gastric emptying and increase satiety, which often promotes weight loss. Another approach is to inhibit the enzyme dipeptidyl-peptidase 4, which rapidly inactivates glucagon-like peptide- 1 and glucose-dependent insulinotropic polypeptide, thereby increasing endogenous incretin levels. (Endocr Pract. 2008;14:625-638)     

Treatment of Type 2 Diabetes Mellitus With Orally Administered Agents: Advances in Combination Therapy

ObjectiveTo discuss the effects and clinical benefit provided by combining various orally administered antidiabetic drugs (OADs) for the treatment of type 2 diabetes and to examine the advantages of single-tablet combinations with respect to targeting hyperglycemia and adherence.MethodsA review of randomized controlled trials that studied OAD combinations for the treatment of type 2 diabetes was conducted by using search terms in PubMed.ResultsReported data have documented that OAD combination therapies have additional benefits over monotherapy in terms of glycemic efficacy. Results from randomized controlled trials on a range of OAD combinations have demonstrated differences in safety and efficacy. The use of single-tablet OAD combinations has been shown to improve adherence in patients.ConclusionThe development of single-tablet OAD combinations that can address all aspects of glycemia with a favorable tolerability profile has the potential to help patients manage their glycemic control more effectively and to minimize the risk of long-term diabetes-related complications. In addition, single-tablet combinations of agents offer improved convenience for patients as well as potential cost benefits. Thus, they represent an important treatment option for type 2 diabetes. (Endocr Pract. 2009;15:750-762)     

Does Clinical Inertia Vary By Personalized A1C Goal? A Study Of Predictors And Prevalence Of Clinical Inertia In A U.S. Managed Care Setting

Objective: Clinical inertia is defined as failure to initiate or intensify therapy despite an inadequate treatment response. We assessed the prevalence and identified the predictors of clinical inertia among patients with type 2 diabetes (T2DM) based on personalized goals.Methods: Three hemoglobin A_1c (A1C) targets (American Diabetes Association A1C <7.0%; modified Ismail-Beigi et al; and Healthcare Effectiveness Data and Information Set) were used when identifying adult patients with T2DM who experienced above-target A1C values during the index period (July 1, 2008 to June 30, 2012) in a U.S. managed-care claims database (IMPACT™). Clinical inertia was defined as no intensification of treatment during the response period. Demographic and clinical characteristics were analyzed to identify predictors of treatment intensification.Results: Irrespective of A1C target, the majority of patients with T2DM (70.4 to 72.8%) experienced clinical inertia in the 6 months following the index event, with 5.3 to 6.2% of patients intensifying treatment with insulin. Patients with a lower likelihood of intensification were older, used >1 oral antidiabetes drug during the baseline period, and had an above-target A1C more recently. Treatment intensification was associated with patients who had point-of-service insurance, mental illness, an endocrinologist visit in the baseline period, or higher index A1C.Conclusion: The prevalence of clinical inertia among patients with T2DM in a U.S. managed-care setting is high and has increased over more recent years. Factors predicting increased risk of clinical inertia may help identify “at-risk” populations and assist in developing strategies to improve their management.Abbreviations:A1C = hemoglobin A_1cADA = American Diabetes AssociationCCI = Charlson Comorbidity IndexGLP-1 = glucagon-like peptide 1HEDIS = Healthcare Effectiveness Data and Information SetICD-9-CM = International Classification of Diseases, 9th Revision, Clinical ModificationOAD = oral antidiabetes drugPCPs = primary care physiciansT2DM = type 2 diabetes mellitus     

Teriparatide as a Systemic Treatment for Lower Extremity Nonunion Fractures: A Case Series

ObjectiveTo investigate the effect of teriparatide (parathyroid hormone [1-34]) on the healing of long bone nonunion fractures.MethodsWe performed a retrospective chart review of patients with fracture nonunion, aged 10 to 99 years who were treated with teriparatide at the Children’s Hospital of Philadelphia or the Hospital of the University of Pennsylvania between November 2002 and January 2013. The primary endpoints were radiographic evidence of callus formation and fracture union, ability to bear weight without affected limb limp, and normal range of motion and strength.ResultsSix patients aged 19 to 64 years with tibial or femoral fractures that had not healed for 3 to 36 months were treated with teriparatide 20 μg/day. Accelerated healing of fracture nonunion was confirmed in 5 of 6 patients with time to complete union of 3 to 9 months. The shortest time to recovery was observed in younger patients without comorbidities. Treatment was well tolerated.ConclusionTeriparatide is a promising treatment for nonunion fractures, but its response depends on associated comorbidities. The potential benefit of teriparatide as an adjunct to treat nonunion justifies randomized placebo-controlled trials to determine its efficacy and safety in broader populations. (Endocr Pract. 2015;21:136-142)     

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)     

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)     

Clinical Efficacy of Stem Cell Therapy for Diabetes Mellitus: A Meta-Analysis

BackgroundStem cell therapy is a promising therapeutic modality for advanced diabetes mellitus (DM). This study presents a meta-analysis of relevant clinical trials to determine the efficacy of stem cell therapy in DM. We aim to critically evaluate and synthesize clinical evidence on the safety and efficiency of different types of stem cell therapy for both T1DM and T2DM.ConclusionsStem cell transplantation can represent a safe and effective treatment for selected patients with DM. In this cohort of trials, the best therapeutic outcome was achieved with CD34⁺ HSC therapy for T1DM, while the poorest outcome was observed with HUCB for T1DM. Diabetic ketoacidosis impedes therapeutic efficacy.     

Glycemic Control and Diabetic Dyslipidemia in Adolescents with Type 2 Diabetes

ObjectiveThe incidence of type 2 diabetes mellitus (T2DM) is increasing at an alarming rate, especially in ethnic minorities, and T2DM is associated with significant comorbidities. The primary objective of this study was to assess glycemic control and cardiovascular risk outcomes in children with T2DM at 1 year after diagnosis. We also assessed whether insulin treatment at onset of diabetes is beneficial for overall outcome in those with elevated glycated hemoglobin (HbA1C).MethodsA retrospective electronic chart review of non-Hispanic white (NHW) and African American (AA) children with T2DM.ResultsA total of 86 patients (66.3% females, 79.1% AA, mean age, 13.8 ± 2.4 years) with T2DM were included. Analyses of therapeutic outcome measures at the 1-year follow-up showed HbA1C <8% in 27.7% of patients, low-density-lipoprotein cholesterol (LDL-C) >130 mg/dL in 12.5%, non-high-density-lipoprotein cholesterol (non-HDL-C) >160 mg/dL in 15.6%, HDL-C <35 mg/dL in 25%, systolic hypertension (HTN) in 35.6%, and diastolic HTN in 6.8% of subjects. Among those started on insulin at initial diagnosis, there was significant improvement in glycemic outcomes (P<.0001 on insulin vs. P = .02 not on insulin) and dyslipidemia (total cholesterol [TC] [P = .001], LDL-C [P = .02], HDL-C [P = .01], non-HDL-C [P = .0002], and TC/HDL-C [P = .005]) compared with no significant change among those who did not receive insulin at diagnosis.ConclusionSubstantial numbers of children with T2DM do not achieve glycemic and cardiovascular therapeutic goals 1 year after diagnosis. Insulin therapy at diagnosis has significant beneficial effects on diabetic dyslipidemia in those with higher HbA1C. (Endocr Pract. 2013; 19:972-979)     

Potential Place of SGLT2 Inhibitors in Treatment Paradigms for type 2 Diabetes Mellitus

Objective: Following the first Food and Drug Administration (FDA) approval in 2013, sodium glucose cotransporter 2 (SGLT2) inhibitors have generated much interest among physicians treating patients with type 2 diabetes mellitus (T2DM). Here, the role in treatment with this drug class is considered in the context of T2DM treatment paradigms.Methods: The clinical trials for the SGLT2 inhibitors are examined with a focus on canagliflozin, dapagliflozin, and empagliflozin.Results: Evidence from clinical trials in patients with T2DM supports the use of SGLT2 inhibitors either as monotherapy or in addition to other glucose-lowering treatments as adjuncts to diet and exercise, and we have gained significant clinical experience in a relatively short time.Conclusion: The drugs appear to be useful in a variety of T2DM populations, contingent primarily on renal function. Most obviously, SGLT2 inhibitors appear to be well suited for patients with potential for hypoglycemia or weight gain. In clinical trials, patients treated with SGLT2 inhibitors have experienced moderate weight loss and a low risk of hypoglycemic events except when used in combination with an insulin secretagogue. In addition, SGLT2 inhibitors have been shown to reduce blood pressure, so they may be beneficial in patients with T2DM complicated by hypertension. SGLT2 inhibitors were incorporated into the 2015 American Diabetes Association (ADA)/European Association for the Study of Diabetes (EASD) position statement on the management of hyperglycemia and received an even more prominent position in the American Association of Clinical Endocrinologists (AACE)/American College of Endocrinology (ACE) comprehensive diabetes management guidelines and algorithm.Abbreviations: AE = adverse event A1C = glycated hemoglobin CI = confidence interval CKD = chronic kidney disease DKA = diabetic ketoacidosis DPP-4 = dipeptidyl peptidase 4 eGFR = estimated glomerular filtration rate FDA = Food and Drug Administration FPG = fasting plasma glucose GLP-1 = glucagon-like peptide 1 HDL-C = high-density lipoprotein cholesterol HR = hazard ratio LADA = late-onset autoimmune diabetes of adulthood LDL-C = low-density lipoprotein cholesterol MACE = major adverse cardiovascular events SGLT1 = sodium glucose cotransporter 1 SGLT2 = sodium glucose cotransporter 2 T1DM = type 1 diabetes mellitus T2DM = type 2 diabetes mellitus UACR = urine albumin to creatinine ratio     

Metabolic surgery for type 2 diabetes mellitus

Background: Metabolic surgery for morbid obesity induces significant weight loss and resolution of many obesity-related comorbidities, the most notable of which is remission of type 2 diabetes mellitus (DM). Such changes seem to precede significant weight loss in this population shortly after undergoing diversionary procedures.Objective: This article explores the evidence for salutary metabolic benefits of bariatric surgery, with special emphasis on glycemic control and remission of type 2 DM.Methods: We conducted a query of the PubMed database for articles published in English within the past 15 years using the search terms bariatric surgery, obesity, type 2 diabetes, gastric bypass, gastric banding, incretins, enteroinsular axis, GLP-1 (glucagon-like peptide-1), and GIP (glucose-dependent insulinotropic polypeptide). We targeted review articles as well as those discussing the effects of bariatric surgery on the enteroinsular axis and the respective effects on glyce-mic control.Results: Most of the clinical reports indicated a high remission rate (≥85%) for type 2 DM, and relatively higher rates in patients who underwent diversionary procedures. Studies with small cohorts and laboratory data suggested a role for gastrointestinal hormones in the regulation of glucose homeostasis after bariatric surgery.Conclusions: Gastrointestinal surgery for severe obesity, through restrictive and/or neurohormonal effects, is an effective treatment for type 2 DM. Surgically induced weight loss was found to be sustainable, durable, and associated with remission of type 2 DM, a reduction in mortality, and improvement in quality of life.     

Prognostic Impact of Diabetes Mellitus on Overall Survival in a Nationwide Population-Based Cohort of Patients With Pancreatic Cancer

Objective: Diabetes mellitus (DM) is a risk factor for pancreatic cancer but its prognostic impact remains controversial. We aimed to investigate the association between long-standing DM and the risk of mortality.Methods: This population-based cohort study analyzed data from the national healthcare database in Taiwan. We identified all patients diagnosed with pancreatic cancer and excluded those who were diagnosed with DM with-in 2 years of the cancer diagnosis. Eligible patients were grouped into long-standing DM (>2 years) and nondiabetic controls, and were compared for overall survival using a Cox proportional hazard model. Sensitivity tests stratified by cancer stages (as indicated by specific treatment) were performed.Results: Patients with long-standing DM were significantly older (mean age, 71.38 years versus 66.0 years; P<.0001) and had a higher Charlson comorbidity index (9.53 versus 6.78; P<.0001) and diabetes comorbidity severity index (2.38 versus 0.82; P<.0001) compared with the non-DM controls. Although the unadjusted analysis showed a higher risk of mortality in the patients with long-term DM (crude hazard ratio &lsqb;HR], 1.26; 95% confidence interval &lsqb;CI], 1.20 to 1.33; P<.0001), the association became insignificant after adjustment for age, sex, and comorbidity index (adjusted HR, 1.01; 95% CI, 0.95 to 1.06, P = .84). Subgroup analyses also showed no association between long-term DM and mortality in various subgroups stratified by cancer treatment.Conclusion: After adjusting for associated comorbidities and complications, long-standing DM per se was not an independent prognostic factor for overall survival in this nationwide population-based cohort with pancreatic cancer.Abbreviations: CCI = Charlson Comorbidity Index; CI = confidence interval; DCSI = Diabetes Complication Severity Index; DM = diabetes mellitus; HR = hazard ratio; ICD = International Classification of Diseases; NHIRD = National Health Insurance Research Database; RCIPD = Registry for Catastrophic Illness Patient Database     

The Role of Bromocriptine-Qr in the Management of Type 2 Diabetes Expert Panel Recommendations

ObjectiveTo review available data on the efficacy and safety of bromocriptine-QR (BQR) and to consider its role in the management of Type 2 diabetes mellitus (T2DM).MethodsPublished literature reporting the efficacy and safety of BQR in the treatment of T2DM was reviewed, including peer-reviewed abstracts and poster presentations.ResultsBQR is an oral hypoglycemic agent with a novel mechanism of action that appears to involve enhancement of morning central nervous system (CNS) dopaminergic activity, resulting in improved insulin sensitivity and reduced hepatic glucose output. Adjunctive treatment with BQR in the dosing range of 1.6 to 4.8 mg/d may result in a mean (95% confidence interval [CI]) reduction in glycated hemoglobin (A1c) levels of 0.69% (0.97%, 0.41%). Treatment with BQR appears to be associated with minimal intrinsic risk of hypoglycemia, and does not appear to be associated with clinically significant adverse effects on weight, triglycerides, free fatty acids, or blood pressure.ConclusionThe favorable cardiovascular risk profile of BQR suggests that it may be useful in the treatment of patients with T2DM with a history of cardiovascular disease (CVD) or who have significant risk factors for CVD. However, knowledge of the efficacy and safety of BQR is limited by the relatively small clinical trials database. As a result, there is currently insufficient information on the safety and efficacy of adjunctive BQR in T2DM patients being treated with several common diabetes regimens (e.g., thiazolidinediones, insulin). (Endocr Pract. 2013;19:100-106)     

Advances in Lipid Testing and Management in Patients with Diabetes Mellitus

ObjectiveTo review the pathophysiologic basis for the classic phenotype associated with diabetic dyslipidemia, discuss recent advances in lipid and lipoprotein testing for risk assessment and lipid therapy monitoring, and summarize a systematic approach to the clinical management of diabetic dyslipidemia.MethodsWe review the pertinent literature, including treatment guidelines and results of major clinical trials, and discuss the effectiveness of various pharmacologic interventions for management of lipid levels in patients with diabetes.ResultsThe incidence and prevalence of type 2 diabetes mellitus continue to escalate globally at alarming rates. Diabetes predisposes to multiple microvascular and macrovascular complications, including cardiovascular disease, the number 1 cause of mortality in the United States. The third report of the National Cholesterol Education Program Adult Treatment Panel in 2001 identified diabetes as a coronary heart disease (CHD) risk equivalent, in light of the evidence that CHD risk in persons with diabetes is similar to that of nondiabetic persons with established CHD. Diabetic dyslipidemia is characterized by a constellation of lipid derangements—hypertriglyceridemia, a low concentration of high-density lipoprotein cholesterol (HDL-C), and a high concentration of small, dense low-density lipoprotein (LDL) particles—that accelerate the progression of atherosclerotic disease and the development of atherothrombotic events.ConclusionStatin trials have demonstrated significant reductions in morbidity and mortality from cardiovascular diseases, including in patients with diabetes. Nevertheless, many patients who achieve their LDL cholesterol (LDL-C) goal still have residual CHD risk. Diabetic dyslipidemia contributes to this residual risk because of the increased concentration of atherogenic apolipoprotein B-containing lipoproteins that can persist despite normalized LDL-C levels and low HDL-C levels. Recent clinical trials emphasize the importance of intensive lipid lowering to achieve recommended goals for LDL-C, non-HDL-C, and apolipoprotein B. (Endocr Pract. 2009;15:641-652)     

Automated Insulin Delivery Systems as a Treatment for Type 2 Diabetes Mellitus: A Review

ObjectiveApproximately 6.3% of the worldwide population has type 2 diabetes mellitus (T2DM), and the number of people requiring insulin is increasing. Automated insulin delivery (AID) systems integrate continuous subcutaneous insulin infusion and continuous glucose monitoring with a predictive control algorithm to provide more physiologic glycemic control. Personalized glycemic targets are recommended in T2DM owing to the heterogeneity of the disease. Based on the success of hybrid closed-loop systems in improving glycemic control and safety in type 1 diabetes mellitus, there has been further interest in the use of these systems in people with T2DM.MethodsWe performed a review of AID systems with a focus on the T2DM population.ResultsIn 5 randomized controlled trials, AID systems improve time in range and reduce glycemic variability, without increasing insulin requirements or the risk of hypoglycemia.ConclusionAID systems in T2DM are safe and effective in hospitalized and closely monitored settings. Home studies of longer duration are required to assess for long-term benefit and identify target populations of benefit.     

Real-World Insulin Treatment Persistence among Patients with Type 2 Diabetes

ObjectiveTo evaluate real-world treatment persistence among patients with type 2 diabetes mellitus (T2DM) initiating treatment with insulin.MethodsPatient-level data were pooled from 3 previously published observational retrospective studies evaluating patients with T2DM who were previously on oral antidiabetic drugs (OADs) and initiated with a basal analog insulin (insulin glargine or insulin detemir). Treatment persistence was defined as remaining on the study drug during the 1-year follow-up period without discontinuation or switching after study drug initiation. Analyses were conducted to identify baseline factors associated with persistence with insulin therapy and to estimate the association between insulin treatment persistence and patients’ clinical and economic outcomes during the follow-up period.ResultsA total of 4,804 patients with T2DM (insulin glargine: n = 4,172, insulin detemir: n = 632) were included. The average insulin persistence rate over the 1-year follow-up period was 65.0%. A significantly higher persistence rate was associated with older age, initiation with insulin glargine using either disposable pens or vial-and-syringe, and with baseline exenatide or sitagliptin use. Higher insulin treatment persistence was also associated with lower hemoglobin A_1c (A1C) at follow-up, a greater reduction in A1C from baseline, and lower health care utilization.ConclusionIn real-world settings, treatment persistence among patients with T2DM initiating basal insulin is influenced by the type of insulin and patient factors. Greater insulin treatment persistence is linked to improved clinical outcomes and reduced health care utilization. (Endocr Pract. 2014;20:52-61)     

When a unit of insulin is not a unit: Detemir dosing and insulin cost in type 2 diabetes mellitus

Background: Increasing acceptance of basal-bolus insulin therapy for the control of diabetes mellitus (DM) has led to newer formulations of basal insulin analogues. The newest one is detemir.Objectives: Clinical evidence suggests that patients with type 2 DM require higher doses of detemir than other basal insulins to achieve equivalent glycemic control. This study examines evidence for greater dosing requirements and the implications of higher doses on the cost of insulin treatment.Methods: We performed a MEDLINE search for randomized, prospective studies comparing detemir with other basal insulins in patients with type 2 DM that were published in English between January 2000 and November 2008. The mean daily doses of basal and bolus insulin and the mean total daily insulin doses were determined. Overall weighted mean doses of the insulins were used to estimate the mean total daily insulin doses required for a 100-kg patient, and published 2008 US retail prices were used to estimate the retail costs of basal-bolus and basal-only insulin regimens.Results: Seven trials involving 3311 patients were identified in the literature search. The mean total daily insulin dose was 0.80 unit/kg for detemir-based regimens and 0.58 unit/kg for comparison regimens. For basal-bolus regimens, the estimated retail cost of the mean total daily insulin dose was $11.24 for detemir-based regimens compared with $8.99 for glargine-based regimens and $6.41 for neutral protamine Hagedorn (NPH)-based insulins. For basal-only regimens, the estimated retail cost of the mean total daily insulin dose was $8.23 for detemir compared with $5.19 for glargine and $2.35 for NPH.Conclusions: It is important for health care providers and patients to know that patients with type 2 DM may require substantially higher doses of detemir than other basal insulins. This should be considered when titrating the dose as well as in cost-benefit analyses of detemir versus other insulins.