Andjela Drincic

Volumetric Dilution, Rather Than Sequestration Best Explains the Low Vitamin D Status of Obesity

Vitamin D status is known to be poor in obese individuals; there is no consensus as to the reason. Cross‐sectional study of the relation between serum 25‐hydroxyvitamin D (25(OH)D) concentration and body size in the baseline data from unsupplemented adults entering two study cohorts in our research unit, N = 686. Regression analyses of body size variables against serum 25(OH)D concentration, using both linear and hyperbolic models. The fit to a hyperbolic model of 25(OH)D against body weight completely removed the obesity‐related component of inter‐individual variability in serum 25(OH)D concentration. The hyperbolic fit using total body weight was significantly better than any linear model, and specifically better than any using BMI. Dilution of ingested or cutaneously synthesized vitamin D in the large fat mass of obese patients fully explains their typically low vitamin D status. There is no evidence for sequestration of supplemental or endogenous cholecalciferol. Vitamin D replacement therapy needs to be adjusted for body size if desired serum 25(OH)D concentrations are to be achieved.

Trabecular bone histomorphometry in humans with Type 1 Diabetes Mellitus.

Patients with Type 1 Diabetes Mellitus (DM) have markedly increased risk of fracture, but little is known about abnormalities in bone microarchitecture or remodeling properties that might give insight into the pathogenesis of skeletal fragility in these patients. We report here a case-control study comparing bone histomorphometric and micro-CT results from iliac biopsies in 18 otherwise healthy subjects with Type 1 Diabetes Mellitus with those from healthy age- and sex-matched non-diabetic control subjects. Five of the diabetics had histories of low-trauma fracture. Transilial bone biopsies were obtained after tetracycline labeling. The biopsy specimens were fixed, embedded, and scanned using a desktop μCT at 16 μm resolution. They were then sectioned and quantitative histomorphometry was performed as previously described by Recker et al. [1]. Two sections, >250 μm apart, were read from the central part of each biopsy. Overall there were no significant differences between diabetics and controls in histomorphometric or micro-CT measurements. However, fracturing diabetics had structural and dynamic trends different from nonfracturing diabetics by both methods of analysis. In conclusion, Type 1 Diabetes Mellitus does not result in abnormalities in bone histomorphometric or micro-CT variables in the absence of manifest complications from the diabetes. However, diabetics suffering fractures may have defects in their skeletal microarchitecture that may underlie the presence of excess skeletal fragility.

25-Hydroxyvitamin D Response to Graded Vitamin D3 Supplementation Among Obese Adults

CONTEXT Guidelines have suggested that obese adults need 2 to 3 times more vitamin D than lean adults to treat vitamin D deficiency, but few studies have evaluated the vitamin D dose response in obese subjects. OBJECTIVE The purpose of this study was to characterize the pharmacokinetics of 25-hydroxyvitamin D [25(OH)D] response to 3 different doses of vitamin D₃ (cholecalciferol) in a group of obese subjects and to quantify the 25(OH)D dose-response relationship. DESIGN, SETTING, INTERVENTION, PATIENTS: This was a randomized, single-blind study of 3 doses of oral vitamin D₃ (1000, 5000, or 10,000 IU) given daily to 67 obese subjects for 21 weeks during the winter months. MAIN OUTCOME MEASURES Serum 25(OH)D levels were measured at baseline and after vitamin D replacement, and 25(OH)D pharmacokinetic parameters were determined, fitting the 25(OH)D concentrations to an exponential model. RESULTS Mean measured increments in 25(OH)D at week 21 were 12.4 ± 9.7 ng/mL in the 1000 IU/d group, 27.8 ± 10.2 ng/mL in the 5000 IU/d group, and 48.1 ± 19.6 ng/mL in the 10,000 IU/d group. Steady-state increments computed from the model were 20.6 ± 17.1, 35.2 ± 14.6, and 51.3 ± 22.0 ng/mL, respectively. There were no hypercalcuria or hypercalcemia events during the study. CONCLUSION Our data show that in obese people, the 25(OH)D response to vitamin D₃ is directly related to dose and body size with ∼2.5 IU/kg required for every unit increment in 25(OH)D (nanograms per milliliter).

The relationship between physician practice characteristics and physician adoption of electronic health records

BACKGROUND Health information technologies, such as electronic health records (EHRs), can potentially improve patient safety in our health care system. The potential advantages include increased quality and more efficiency in the care of patients. Adoption of EHRs has been slow despite these advantages and a national call for EHR implementation. PURPOSES This article explores factors associated with the adoption of EHR systems using organizational theory to derive hypotheses as to why physicians would adopt EHRs. METHODOLOGY/APPROACH : A survey was administered to all office-based physicians in Nebraska and South Dakota using a modified Dillman technique between July and November 2007. The main outcome variable measured physician EHR adoption status at three levels: not planning to use an EHR, planning to use an EHR, and using an EHR. Factors associated with EHR status were analyzed using a multinomial logistic regression. FINDINGS Approximately 30% of physicians reported using an EHR in his or her practice. Physicians adopting EHRs were younger and had access to internal health information technologies support. In addition, working in an independent practice decreased the likelihood of physicians using and adopting EHRs. PRACTICE IMPLICATIONS This research provides further evidence of the barriers impeding EHR adoption. One such barrier includes the lack of access to internal information technology support staff versus having to outsource for technical support services. From a resource dependency perspective, barriers illustrated by this example may place undue dependencies on physicians if they pursue an EHR system. By addressing these barriers, physicians may be in a better position to adopt EHR system into his or her practice.

Insulin Glargine: a review 8 years after its introduction

Insulin Glargine was the first long-acting insulin analog produced by recombinant DNA technology, approved for use by the US FDA in April 2000 and by the European Agency for the Evaluation of Medicinal Products in June, 2000. It has become the most widely used insulin in the USA owing to its long duration of action without a pronounced peak. The principal advantage of insulin Glargine over neutral protamine Hagedorn (NPH) insulin is in a lower frequency of hypoglycemic reactions, thus affording improved safety. It is used in both type 1 and type 2 diabetes, usually as a single daily dose. In type 2 patients, it is often the first insulin introduced as a single daily dose. Although insulin Glargine is typically administered as a single nighttime dose, it can be given in the morning or at any other time convenient for the patient. In labile type 1 diabetes, it is often most effective given as two daily injections. In obese, insulin-resistant patients, it may be best to administer insulin Glargine in two separate doses, owing to the high volumes of injected insulin required. Insulin Glargine does not treat postprandial hyperglycemia. It is necessary to supplement with short-acting insulin at mealtimes to control glucose surges after meals. Insulin Glargine is effective in hospitalized and postsurgical patients on account of its lack of pronounced insulin peaks and long duration of action. Although there is considerable use of Glargine in pregnant diabetic women, there is no definitive study to confirm its benefits. Insulin Glargine is thought to coprecipitate supplementary short-acting insulins when co-administered in the same syringe. Therefore, more injections are typically needed in the usual treatment regimen for insulin requiring diabetes. In many cases, constant basal insulin levels may be achieved with multiple overlapping doses of NPH insulin given together with short-acting insulin at mealtimes. Such a therapy may be less costly, but the major advantage of insulin Glargine remains the greater safety of a lower frequency of hypoglycemic reactions.

Alogliptin: a new addition to the class of DPP-4 inhibitors

Background Alogliptin is an oral antihyperglycemic agent that is a selective inhibitor of the enzyme dipeptidyl peptidase-4 (DPP-4). Inhibition of DPP-4 elevates levels of the incretin hormones glucagon-like peptide (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) by preventing their degradation. Objective To review the evolution of alogliptin and its pharmacokinetics, pharmacodynamics, clinical efficacy and adverse effects. In addition, we compared alogliptin to other DPP-4 inhibitors. Methods A comprehensive literature search was performed using the term ‘alogliptin’. Original research articles and review articles as well as scientific abstracts were included. Results Alogliptin raises postprandial levels of GLP-1. It has excellent bioavailability exhibiting a median Tmax ranging from 1 to 2 hours and a mean half-life of 12.4 to 21.4 hours across all doses. When given as monotherapy, mean hemoglobin A1c (HbA1c) reductions achieved were 0.5% to 0.6%. Combination therapy yielded similar reductions (−0.5% with metformin, −0.6% with glyburide, −0.8% with pioglitazone and −0.6% with insulin). Administration of alogliptin does not promote weight loss but has not resulted in weight gain. The agent is relatively well tolerated with few adverse effects, the major finding being a marginally higher rate of skin events, primarily pruritus. Conclusions Alogliptin causes significant reductions in HbA1c when used alone or in combination with other oral agents in patients with type 2 diabetes similar to other DPP-4 inhibitors in current clinical use. The side effect profile also does not differ from that of other DPP-4 inhibitors. However, long-term studies are necessary before the place of alogliptin in the management of type 2 diabetes can be established.

Liraglutide-associated acute pancreatitis

PURPOSE A case of acute pancreatitis associated with liraglutide is reported. SUMMARY A 53-year-old African-American man (height, 185.4 cm; weight, 108.6 kg) with type 2 diabetes mellitus arrived at the emergency department (ED) with new-onset intolerable abdominal pain in the right upper quadrant and left upper quadrant that had appeared suddenly and lasted two to three hours. He had nausea but no vomiting, with tenderness in the epigastric region. In the ED, his serum amylase concentration was found to be extremely elevated (3,963 units/L), as was his serum lipase concentration (>15,000 units/L). In addition to type 2 diabetes, his medical history included hyperlipidemia, hypertension, peripheral neuropathy, erectile dysfunction, and obesity. His home medications included aspirin 81 mg orally daily, metformin 1000 mg orally every morning and 1500 mg every evening, simvastatin 80 mg orally daily at bedtime, tadalafil 20 mg orally as needed, glimepiride 4 mg orally twice daily, and liraglutide 1.2 mg subcutaneously daily. Two months before his arrival to the ED, the patients dosage of liraglutide was increased from 0.6 to 1.2 mg subcutaneously daily. Radiographic data were obtained, and acute pancreatitis was diagnosed. Liraglutide was discontinued indefinitely after ruling out elevated triglycerides as the cause of pancreatitis. The patient was initiated on standard therapy for acute pancreatitis and discharged eight days later with complete resolution of symptoms and normal laboratory test values. CONCLUSION A 53-year-old man with type 2 diabetes mellitus developed a probable case of liraglutide-induced acute pancreatitis after receiving the drug for approximately two months.

Medical management of adult transsexual persons

Gender identity disorder (GID), or transsexualism, is an increasingly recognized medical condition with an expanding body of medical literature to support the use of established therapeutic guidelines. Transsexualism can be effectively managed through exogenous cross‐sex hormone administration used to induce development of desired sex characteristics, as well as use of other agents, such as aldosterone antagonists, aimed at decreasing physical characteristics of the undesired sex. Many complications can arise with the use of the available therapies, and these must be considered before determining the appropriate course of action. This review describes methods, including both pharmacotherapy and surgical interventions, for effective medical management of both male and female adults with GID. In addition, specific goals of therapy as well as safety aspects with long‐term use of pharmacotherapeutic agents are discussed. This review also discusses some special considerations for treating patients with significant, yet common, comorbid diseases such as human immunodeficiency virus infection, acquired immunodeficiency syndrome, and viral hepatitis, as these conditions may complicate the clinical course and preclude some patients from using certain therapies. Pharmacist involvement in the management of transsexualism can be extremely beneficial to patients and other health care providers. Pharmacists can help determine the appropriate therapy, optimize dosages, monitor for adverse effects, and educate patients on what to expect during their therapy. Pharmacists should become knowledgeable about guidelines and current literature on transsexualism, understand the monitoring parameters for safe and effective therapy, and establish themselves as partners in the collaborative management of this disorder.

Evidence-based Mobile Medical Applications in Diabetes

This article reviews mobile medical applications that are commercially available in the United States or European Union (EU) and are (1) associated with published data of clinical outcomes in the peer-reviewed literature during the past 5 years, (2) cleared by the US Food and Drug Administration (FDA) in the United States, or (3) a recipient of a CE (Conformité Européenne) mark by the EU. Many of these applications have been shown to positively affect outcomes in the short term, but long-term studies are needed. Until more data are available, consumers and professionals can consider guidance based on FDA/CE status.

Round Table Discussion on Inpatient Use of Continuous Glucose Monitoring at the International Hospital Diabetes Meeting

In May 2015 the Diabetes Technology Society convened a panel of 27 experts in hospital medicine and endocrinology to discuss the current and potential future roles of continuous glucose monitoring (CGM) in delivering optimum health care to hospitalized patients in the United States. The panel focused on 3 potential settings for CGM in the hospital, including (1) the intensive care unit (ICU), (2) non-ICU, and (3) continuation of use of home CGM in the hospital. The group reviewed barriers to use and solutions to overcome the barriers. They concluded that CGM has the potential to improve the quality of patient care and can provide useful information to help health care providers learn more about glucose management. Widespread adoption of CGM by hospitals, however, has been limited by added costs and insufficient outcome data.In May 2015 the Diabetes Technology Society convened a panel of 27 experts in hospital medicine and endocrinology to discuss the current and potential future roles of continuous glucose monitoring (CGM) in delivering optimum health care to hospitalized patients in the United States. The panel focused on 3 potential settings for CGM in the hospital, including (1) the intensive care unit (ICU), (2) non-ICU, and (3) continuation of use of home CGM in the hospital. The group reviewed barriers to use and solutions to overcome the barriers. They concluded that CGM has the potential to improve the quality of patient care and can provide useful information to help health care providers learn more about glucose management. Widespread adoption of CGM by hospitals, however, has been limited by added costs and insufficient outcome data.