The prevalence of hypercortisolism in persons with difficult-to-control type 2 diabetes (T2D) may be higher than currently appreciated, particularly in persons who require a greater number of ...antihyperglycemic agents and/or have more comorbidities. To better understand the prevalence and whether treatment of hypercortisolism may result in better control of diabetes and other hypercortisolism-associated comorbidities, we have designed CATALYST, a prospective phase 4 study in adults with difficult-to-control T2D (HbA1c 7.5–11.5%) despite receiving multiple antihyperglycemic agents. CATALYST is being conducted at about 30 sites in the United States. In Part 1, about 1000 persons with difficult-to-control T2D will be screened with a 1-mg dexamethasone suppression test (cutoff: serum cortisol >1.8 µg/dL; dexamethasone ≥140 ng/dL). Patients with ACTH-dependent hypercortisolism will be referred out of the study. The primary study endpoint—the prevalence of ACTH-independent hypercortisolism—will be evaluated in Part 1. Patients with ACTH-independent hypercortisolism may advance to Part 2, a prospective, 2:1 randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of treatment with the competitive glucocorticoid receptor antagonist mifepristone. Patients will be randomized (stratified by the presence/absence of adrenal adenomas on CT) and receive treatment for 24 weeks. The mifepristone dose will be 300 mg QD for 4 weeks, then increased to 600 mg QD for 20 weeks based on glycemic efficacy and tolerability (option to increase to mifepristone 900 mg). Secondary endpoints include changes in HbA1c from baseline to 24 weeks and changes in hypercortisolism-related comorbidities (e.g., blood pressure, weight, waist circumference, quality of life).
Improved glycemic control is associated with a reduced risk of diabetic complications. Optimal management of patients with type 2 diabetes includes nutritional therapy, physical activity, and ...pharmacotherapy for glycemic control. Most patients with type 2 diabetes are initially managed with oral antidiabetic agents, but as β-cell function declines and the disease progresses, insulin therapy is frequently needed to maintain glycemic control. Insulin therapy given with multidose insulin injection regimen or by continuous insulin infusion is needed for patients with type 1 diabetes to achieve control. Obesity and its associated insulin resistance contribute to greater insulin requirements in patients with both type 1 and type 2 diabetes to achieve glycemic control, creating a need for concentrated insulin. Concentrated insulin formulations can be prescribed as an alternative to 100 unit/mL insulin and provide the advantage of low injection volume, leading to less pain and possibly fewer insulin injections. This review includes a stepwise analysis of all currently available concentrated insulin products, analyzes the most up-to-date evidence, and presents this in combination with expert guidance and commentary in an effort to provide clinicians with a thorough overview of the characteristics and benefits of concentrated insulins in patients with type 1 and type 2 diabetes-instilling confidence when recommending, prescribing, and adjusting these medications.
= glycated hemoglobin;
= pancreatic betacell;
= blood glucose;
= confidence interval;
= continuous subcutaneous insulin infusion;
= multiple daily injections;
= National Health and Nutrition Examination Survey;
= pharmacodynamic;
= pharmacokinetic;
= total daily dose;
= 100 units/mL;
= 200 units/mL;
= 300 units/mL;
= 500 units/mL;
= United States dollars.
Type 2 diabetes (T2D), chronic kidney disease (CKD), atherosclerotic cardiovascular disease (ASCVD), and heart failure (HF)—along with their associated risk factors—have overlapping etiologies, and ...two or more of these conditions frequently occur in the same patient. Many recent cardiovascular outcome trials (CVOTs) have demonstrated the benefits of agents originally developed to control T2D, ASCVD, or CKD risk factors, and these agents have transcended their primary indications to confer benefits across a range of conditions. This evolution in CVOT evidence calls for practice recommendations that are not constrained by a single discipline to help clinicians manage patients with complex conditions involving diabetes, cardiorenal, and/or metabolic (DCRM) diseases. The ultimate goal for these recommendations is to be comprehensive yet succinct and easy to follow by the nonexpert—whether a specialist or a primary care clinician. To meet this need, we formed a volunteer task force comprising leading cardiologists, nephrologists, endocrinologists, and primary care physicians to develop the DCRM Practice Recommendations, a multispecialty consensus on the comprehensive management of the patient with complicated metabolic disease. The task force recommendations are based on strong evidence and incorporate practical guidance that is clinically relevant and simple to implement, with the aim of improving outcomes in patients with DCRM. The recommendations are presented as 18 separate graphics covering lifestyle therapy, patient self-management education, technology for DCRM management, prediabetes, cognitive dysfunction, vaccinations, clinical tests, lipids, hypertension, anticoagulation and antiplatelet therapy, antihyperglycemic therapy, hypoglycemia, nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), ASCVD, HF, CKD, and comorbid HF and CKD, as well as a graphical summary of medications used for DCRM.
•Diabetes, cardiorenal, and metabolic disease often occur in the same patient.•Recent outcome trials support use of some agents beyond their primary indications.•Cardiologists, nephrologists, endocrinologists, and PCPs formed a consensus group.•Recommendations address management of patients with complicated metabolic disease.
Context: Polycystic ovary syndrome (PCOS) and the metabolic syndrome have many features in common and may share the same pathogenesis.
Objective: This study was performed to determine the prevalence ...and predictors of the metabolic syndrome in PCOS.
Design: The clinical, hormonal, and oral glucose tolerance test results were analyzed in 394 PCOS women who were screened for participation in a multicenter trial to evaluate the effects of troglitazone on ovulation and hirsutism.
Setting: A multicenter clinical trial is presented.
Patients or Other Participants: The subjects were women with PCOS who had or lacked the metabolic syndrome.
Main Outcome Measures: Waist circumference, fasting glucose, high-density lipoprotein cholesterol and triglyceride concentrations, and blood pressure were the main outcome measures.
Results: Twenty-six (6.6%) subjects had diabetes; among the 368 nondiabetics, the prevalence for individual components comprising the metabolic syndrome were: waist circumference greater than 88 cm in 80%, high-density lipoprotein cholesterol less than 50 mg/dl in 66%, triglycerides greater than or equal to 150 mg/dl in 32%, blood pressure greater than or equal to 130/85 mm Hg in 21%, and fasting glucose concentrations greater than or equal to 110 mg/dl in 5%. Three or more of these individual criteria were present in 123 (33.4%) subjects overall. The prevalence of the metabolic syndrome did not differ significantly between racial/ethnic groups. The prevalence of the metabolic syndrome from lowest to highest quartile of free testosterone concentration was 19.8, 31.3, 46.9, and 35.0%, respectively P = 0.056 adjusted for body mass index (BMI). None of the 52 women with a BMI less than 27.0 kg/m2 had the metabolic syndrome; those in the top BMI quartile were 13.7 times more likely (95% confidence interval, 5.7–33.0) to have the metabolic syndrome compared with those in the lowest quartile. Thirty-eight percent of those with the metabolic syndrome had impaired glucose tolerance compared with 19% without the metabolic syndrome (P < 0.001).
Conclusions: The metabolic syndrome and its individual components are common in PCOS, particularly among women with the highest insulin levels and BMI. Hyperinsulinemia is a likely common pathogenetic factor for both PCOS and the metabolic syndrome.
To assess the prevalence of sleep apnea (SA) in adults with type 2 diabetes mellitus (T2DM) and examine whether demographics and comorbid factors were associated with SA in this population.
This ...study enrolled 330 consecutive adults with T2DM referred to a diabetes clinic, 279 of whom completed the study. Evaluation of the presence of SA was performed with use of a single-channel recording device that measures disordered breathing events from a nasal cannula airflow signal. The device was worn by the study participants in their home, after instruction in appropriate use by clinical staff at the diabetes center. The presence and severity of SA were determined by use of an apnea-hypopnea index (AHI), reflecting periods of diminished and absent breathing. Demographic and medical information data were collected to detect factors associated with SA in this study population. In addition, a time and cost analysis was conducted regarding the screening process for SA by clinical staff at the diabetes center.
The results show a high prevalence of SA in adults with T2DM, ranging from 48% (AHI level of >or=10 events/h) to 29% (AHI level of >or=20 events/h). At an AHI cutoff value of >or=15 events/h, the overall prevalence rate was 36% (49% in male and 21% in female participants). The following variables were associated with SA: age >or=62 years, male sex, body mass index >or=30 kg/m2, snoring, and reports of stopping breathing during sleep. The time and cost analysis showed that the screening device involved minimal setup time, was simple to use, and was a cost-effective method to screen for SA.
SA is a common disorder associated with major morbid conditions, including hypertension, obesity, cardiovascular disease, and insulin resistance. Predisposing factors for SA and T2DM are similar. This study showed that SA has a high prevalence in adults with T2DM and identified factors that may be associated with its presence in this population. Assessment for SA can be easily performed in an outpatient setting with a portable recording device such as the one used in this study. Screening for SA should be considered in the T2DM population.
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