Edith ter Braak

Injection Site Effects on the Pharmacokinetics and Glucodynamics of Insulin Lispro and Regular Insulin

OBJECTIVE The pharmacokinetics and glucodynamics of a new insulin analog, insulin lispro, and regular human insulin were compared and contrasted after subcutaneous administrations in femoral, deltoid, and abdominal injection sites. RESEARCH DESIGN AND METHODS Single 0.2 U/kg doses of insulin lispro and regular insulin were administered to 12 healthy subjects in a six-way randomized crossover fashion. Each dose was given after an overnight fast in one of three injection sites: abdominal, deltoid, or femoral. Study drugs were given during a manual euglycemic glucose clamp. Blood samples were collected over the 12-h clamp for measurement of insulin-reactive components, with pharmacokinetic and glucodynamic measurements derived from these serum insulin and clamp measurements. RESULTS Glucodynamic comparisons between insulin lispro and regular insulin showed a greater maximum infusion rate (Rmax) at an earlier time (TRmax), regardless of injection site. The total glucose infused (Gtot) showed nearly identical values between sites for insulin lispro. Regular insulin showed greater Gtot values from deltoid and femoral injections. When comparisons were made between drugs, regular insulin produced significantly greater Gtot, primarily driven by the increased Gtot from deltoid and femoral injections. Greater maximum serum insulin concentrations (Cmax) were experienced with insulin lispro at earlier times (tmax), regardless of the injection site (P < 0.001). Abdominal administrations produced the greatest Cmax values at the earliest tmax for both regular insulin and insulin lispro. Deltoid and femoral injections had lower Cmax values for both compounds. Shifts also occurred with tmax, although these shifts were much greater with regular insulin than with insulin lispro. Equivalent area under the curve (AUC) values were found when compared between compounds. CONCLUSIONS Slower absorption from deltoid and femoral administrations resulted in an increased duration of action for both regular insulin and insulin lispro when compared to abdominal administration. However, notable increases in the onset of action were only apparent with regular insulin. The consistency with insulin lispro response from abdominal and extremity injection sites allows more potential sites for subcutaneous injection with an assured rapid response.

Maternal hypoglycemia during pregnancy in type 1 diabetes: maternal and fetal consequences.

There is strong evidence that the avoidance of hyperglycemia is essential inoptimizing pregnancy outcome in type 1 diabetes. The price to pay is a striking increase in severe hypoglycemia (SH), defined as episodes requiring help from another person. During type 1 diabetic pregnancy, occurrence rates of SH up to 15 times higher as in the intensively treated group of the Diabetes Control and Complications Trial (DCCT) are reported. Blood glucose (BG) treatment targets differ considerably between clinics; some authors advocate lower limits as low as 3.3 mmol/l. Improved glycemic control and/or recurrent hypoglycemia (i.e. BG <3.9 mmol/l) may result in impairment of glucose counterregulatory responses. Also, glucose counterregulation may be altered by pregnancy itself. Short‐acting insulin analogs may help reduce hypoglycemia with preservation of good glycemic control, but their use during pregnancy has yet to be proven safe.

Mentoring portfolio use in undergraduate and postgraduate medical education

Aim: Mentoring is widely acknowledged as being crucial for portfolio learning. The aim of this study is to examine how mentoring portfolio use has been implemented in undergraduate and postgraduate settings. Method: The results of interviews with six key persons involved in setting up portfolio use in medical education programmes were used to develop a questionnaire, which was administered to 30 coordinators of undergraduate and postgraduate portfolio programmes in the Netherlands and Flanders. Results: The interviews yielded four main aspects of the portfolio mentoring process – educational aims, individual meetings, small group sessions and mentor characteristics. Based on the questionnaire data, 16 undergraduate and 14 postgraduate programmes were described. Providing feedback and stimulating reflection were the main objectives of the mentoring process. Individual meetings were the favourite method for mentoring (26 programmes). Small group sessions to support the use of portfolios were held in 16 programmes, mostly in the undergraduate setting. In general, portfolio mentors were clinically qualified academic staff trained for their mentoring tasks. Conclusion: This study provides a variety of practical insights into implementing mentoring processes in portfolio programmes.

Cognitive function in patients with type 2 diabetes mellitus

Patients with type 2 (non-insulin dependent) diabetes mellitus may express moderate degrees of cognitive impairment. The aim of this study was to further characterise these cognitive deficits. Cognitive functions were assessed in 13 patients and 16 controls, matched for age, sex, education and occupational level. In addition, a neurological examination was performed. The performance of diabetic patients was impaired on the neuropsychological examination, in particular in tasks assessing learning and memory. Attention, motor planning and reaction time appeared to be unaffected. Symptoms and/or signs of distal symmetric polyneuropathy were detected in 31% and 56% of the diabetic patients, respectively. The observed deficits are in line with previous neuropsychological studies in type 2 diabetic patients, showing deficits in learning and memory and complex information processing. The fact that these cognitive impairments are reported consistently stresses the need to obtain further insights into pathogenic mechanisms, in order to be able to take adequate preventive measures.

Educational interventions to improve the meaningful use of Electronic Health Records: A review of the literature: BEME Guide No. 29

Background: Electronic health records (EHRs) are increasingly available and this was expected to reduce healthcare costs and medical errors. This promise has not been realized because healthcare professionals are unable to use EHRs in a manner that contributes to significant improvements in care, i.e. meaningful. Policymakers now acknowledge that training healthcare professionals in meaningful use is essential for successful EHR implementation. To help educators and policymakers design evidence based educational interventions (i.e. interventions that involve educational activities but no practical lessons) and training (i.e. interventions that involve practical components), we summarized all evidence regarding the efficacy of different educational interventions to improve meaningful use of EHRs. Methods: We used a predefined search filter to search eight databases for studies that considered an educational intervention to promote meaningful use of EHRs by healthcare professionals. Results: Seven of the 4507 reviewed articles met the in- and exclusion criteria. Conclusions: These studies suggest that a combination of classroom training, computer-based training and feedback is most effective to improve meaningful use. In addition, the training should be tailored to the needs of the trainees and they should be able to practice in their own time. However, the evidence is very limited and we recommend that governments, hospitals and other policymakers invest more in the development of evidence based educational interventions to improve meaningful use of EHRs.

The importance of the osmolality gap in ethylene glycol intoxication.

In patients with very high lactate levels, calculate the osmolality gap, as ethylene glycol poisoning may falsely elevate lactate levels

Type 1 Diabetes

Type 1 diabetes is a life long metabolic disorder that is characterized by absolute insulin deficiency resulting in hyperglycemia and lipolysis. Type 1 diabetes accounts for 5–10% of the total diabetes population, the majority of the other patients has type 2 diabetes. Insulin deficiency originates with autoimmune mediated β-cell destruction. Without insulin treatment, type 1 diabetes leads to dehydration and ketoacidosis and can ultimately be fatal. Prolonged exposure to hyperglycemia is responsible for microvascular damage in the eye, kidneys and nervous system and contributes to macrovascular disease of the coronary, cerebral and peripheral arteries. Limited joint mobility and the diabetic foot are other complications related to chronic hyperglycemia. Currently, the corner stone of the treatment of type 1 diabetes is exogenous insulin substitution aiming to restore near-normal glycemia in order to prevent or delay long-term complications. Recurrent hypoglycemia is a frequent complication and a serious burden for both patients and their significant others. Additional therapeutic interventions consist of lifestyle modifications, particularly aiming to reduce cardiovascular risk factors. In the future,the necessity for substitution with exogenous insulin may be replaced by β-cell transplantation or even preventive β-cell preservation. Patients must receive proper education and support, since they have to manage their chronic disease on a daily basis.