Listening to patients' voices: linguistic indicators related to diabetes self-management.

A great deal of research in health care has examined a wide range of variables to better understand the degree to which patients follow the advice of medical professionals in managing their health, known as adherence. This paper explains the development of the linguistic systems to describe and evaluate two psychosocial constructs (i.e. control orientation and agency) that have been found to be related to adherence in previous research for subjects with diabetes (Trento et al. 2007; Wangberg 2007; O'Hea et al. 2009). The present data came from 43 semi-structured in-depth interviews of subjects with Type 2 diabetes. One-on-one interviews with open-ended questions elicited subjects' 'stories' about living with diabetes, and the transcribed interviews were analyzed to develop the linguistic systems of control orientation and agency. The resultant systems were applied to the 43 interviews by raters with high inter-rater reliability. The results showed demarcations of clearly identified codings of patient types. The paper presents the linguistic coding systems developed in the study, the results of their application to the patient interview data, and recommendations for improved communication with patients.

Exenatide added to insulin therapy: a retrospective review of clinical practice over two years in an academic endocrinology outpatient setting.

BACKGROUND: Exenatide is an antidiabctic agent currently indicated as adjunctive therapy with oral agents for the treatment of type 2 diabetes mellitus (T2DM). Limited published data exist on the off-label use of exenatide in conjunction with insulin in the treatment of T2DM. OBJECTIVE: The aim of this retrospective study was to examine the effects of exenatide on glycemic control, weight, and insulin dose in patients with T2DM treated with insulin. METHODS: Patients with T2DM receivirg insulin and adjuvant therapy with exenatide at an endocrinology clinic at a university hospital for up to 27 months were eligible for inclusion. Glycosylated hemoglobin (HbA(1c)), weight, insulin doses (total, prandial, and basal), concurrent oral antidiabetic medications, and adverse events were ascertained by retrospective review of medical records and were considered the clinical parameters of interest. The last observation in 4 specified time intervals (0-6, 6-12, 12-18, and 18-27 months) for each clinical parameter was used in the analysis. RESULTS: Of the 3397 patients with a confirmed diagnosis of T2DM who were seen at the clinic during the study period, 268 patients met inclusion criteria and were enrolled in the study. Of the 268 patients enrolled, 38 discontinued therapy within the first 2 months, 30 were lost to follow-up, and 12 did not have evaluable data. These latter patients without sufficient data (n = 42) were not included in the primary analysis but were included in the adverse events analysis. Overall, data from 188 patients (mean [SD] age, 56 (9) years; 85 [45%] men; body mass index, 40.4 [8.4] kg/m(2); 160 [85%] white) were evaluated (mean duration of treatment, 350 [208] days) and included in all analyses. The mean baseline values for HbA(1c), weight, and total daily insulin dose before exenatide therapy were 8.05% (1.47%), 117.8 (24.7) kg, and 99.9 (90.0) U, respectively. For the 4 time intervals, the mean changes in HbA(1c) were: -0.66% (1.54%) at 0 to 6 months (P < 0.001); -0.55% (1.4%) at 6 to 12 months (P < 0.001); -0.54% (1.83%) at 12 to 18 months (P = 0.019); and -0.54% (1.37%) at 18 to 27 months (P = 0.020). Mean weight significantly declined with increasing treatment duration. Mean changes in weight were: -2.4 (5.1) kg at 0 to 6 months (P < 0.001); -4.3 (7.2) kg at 6 to 12 months (P < 0.001); -6.2 (9.7) kg at 12 to 18 months (P < 0.001); and -5.5 (10.8) kg at 18 to 27 months (P < 0.01). After 18 months, an increase in weight was observed; but the increase remained lower than baseline. The mean insulin total daily dose (TDD) was decreased in all patients at the 0- to 6-month (-18.0 [49.9] U; P < 0.001) and the 6- to 12-month (-14.8 [35.3] U; P < 0.001) intervals. Mean changes in insulin TDD during the 12- to 18-month and 18- to 27-month intervals were not statistically significant. The mean percent change from baseline in the basal insulin dose at 0 to 6 months, 6 to 12 months, 12 to 18 months, and 18 to 27 months was not statistically significant. For the 4 intervals, the mean percent change from baseline in the prandial insulin dose was -33.5% (56.2%) at 0 to 6 months (P < 0.001); -25.9% (59.7%) at 6 to 12 months (P = 0.002); -29.7% (74.8%) at 12 to 18 months (P = 0.02); and -55.7% (56.8%) at 18 to 27 months (P = 0.005). Of the 226 patients who were treated with exenatide + insulin for any length of time (including within the first 2 months), 59 (26.1%) discontinued exenatide because of adverse events. The adverse events were largely considered mild and included nausea (n = 51 [22.6% of patients]), vomiting (22 [9.7%]), hypoglycemia (9 [4.0%]), heartburn (2 [0.9%]), diarrhea (1 [0.4%]), constipation (1 [0.4%]), malaise (1 [0.4%]), and generalized edema (1 [0.4%]). Two serious adverse events occurred during the study period: acute renal failure not attributed to exenatide (1 [0.4%]); and pancreatitis (1 [0.4%]), both of which required hospitalization 1 month after the start of exenatide therapy. CONCLUSION: In this retrospective review of patients with T2DM treated in an outpatient setting, the addition of exenatide to insulin-based therapy was associated with reductions in mean HbA(1c), weight, and prandial insulin requirements for treatment periods of up to 27 months, and in total insulin requirements for treatment periods of up to 12 months.

New insulin analogues and routes of delivery: pharmacodynamic and clinical considerations.

Analogues of human insulin have been developed to more closely replicate the physiology of meal-related and basal insulin secretion. Three rapid-acting analogues and two basal analogues are available for clinical use. Insulin aspart and insulin lispro have nearly identical pharmacokinetic and pharmacodynamic profiles and provide better postprandial glucose control and less hypoglycaemia (primarily nocturnal and severe hypoglycaemia in type 1 diabetes mellitus) than regular insulin. Insulin glulisine is a new rapid-acting analogue and has characteristics nearly identical to those of its predecessors. Insulin glargine was the first basal analogue approved for clinical use and has shown better fasting glucose control and less risk of hypoglycaemia than conventional human neutral protamine Hagedorn (NPH) insulin. More recent studies have indicated that insulin glargine may not be truly 'peakless' at higher doses and that the adjustment of dose timing and frequency may have favourable effects on the risk of hypoglycaemia and the duration of the effect. Insulin detemir is a new basal insulin analogue with superiority to NPH insulin similar to that demonstrated by insulin glargine, though its duration of action appears to be shorter. The intraindividual variability in the response to a given dose is lower for insulin detemir than for both NPH insulin and insulin glargine. The clinical significance of this finding is not clear, though it may contribute to the lower rate of hypoglycaemia seen with insulin detemir. A number of 'alternative routes' of insulin administration have been studied, the most promising of which has been the pulmonary route. The time-action profile of inhaled insulins is generally characterized by a rapid onset of action similar to those of rapid-acting analogues and a slightly protracted duration of action similar to that of regular insulin. Inhaled insulin is similar to regular insulin with respect to efficacy and safety, though small reversible changes in pulmonary function have been noted. For technical and practical reasons, other alternative routes have generally not met with clinical success.

A critical dialogue: communicating with type 2 diabetes patients about cardiovascular risk.

Patients with type 2 diabetes mellitus (DM) are at increased risk for cardiovascular disease (CVD), and many patients are inadequately treated for risk factors such as hyperglycemia, hyperlipidemia, hypertension, and smoking. Providing individualized risk information in a clear and engaging manner may serve to encourage both patients and their physicians to intensify risk-reducing behaviors and therapies. This review outlines simple and effective methods for making CVD risk information understandable to persons of all levels of literacy and mathematical ability. To allow the patient to understand what might happen and how, personal risk factors should be clearly communicated and the potential consequences of a CVD event should be presented in a graphic but factual manner. Risk calculation software can provide CVD risk estimates, and the resulting information can be made understandable by assigning risk severity (eg, "high") by comparing clinical parameters with accepted treatment targets and by comparing the individual's risk with that of the "average" person. Patients must also be informed about how they might reduce their CVD risk and be supported in these efforts. Thoughtful risk communication using these techniques can improve access to health information for individuals of low literacy, especially when interactive computer technology is employed. Research is needed to find the best methods for communicating risk in daily clinical practice.

Effects of multiple daily injection therapy with Humalog mixtures versus separately injected insulin lispro and NPH insulin in adults with type I diabetes mellitus.

BACKGROUND: Injection of insulin lispro (LP) before meals provides a more physiologic insulin activity profile than regular human insulin, but the relatively short duration of action of LP may allow the blood glucose (BG) level to increase during the late postprandial period (4-7 hours after meals) unless basal insulin is optimally replaced. One approach to basal insulin optimization has been to combine small doses of NPH with LP before meals. When used in a similar fashion, premixed, fixed-ratio insulin preparations containing LP and NPL (an LP-based intermediate-acting insulin) may provide the basis for an optimized basal-bolus insulin regimen. OBJECTIVE: This study assessed mean late postprandial glycemic control during treatment with a premixed formulation consisting of a high proportion of LP (75% LP/25% NPL; H) and a premixed formulation consisting of a medium proportion of LP (50% LP/50% NPL; M). The H/M formulation was given before meals and was compared with treatment with preprandial LP + NPH (LP + N) in patients with type 1 diabetes mellitus (DM). METHODS: This multicenter, randomized, open-label, 2-period crossover study was conducted at 4 centers in Italy and 1 center in France. Patients eligible for the study had type 1 DM, were > or = 18 years of age, and had a glycosylated hemoglobin (HbA(1c)) <150% of the upper limit of normal. Patients were randomly assigned to 1 of 2 treatment sequences: LP self-mixed with NPH before meals plus NPH alone at bedtime for 8 weeks (LP + N) followed by preprandial H or M, plus NPH alone at bedtime for 8 weeks (H/M), or the opposite sequence. Assessments included 8-point self-monitored BG profiles, HbA(1c), and hypoglycemia (any sign or symptom of hypoglycemia or BG < 3.0 mmol/L [<54.0 mg/dL]). The primary outcome measure was the late postprandial BG value, calculated as the mean of the combined prelunch (late postbreakfast), predinner (late postlunch), and bedtime (late postdinner) values. RESULTS: A total of 89 patients with type 1 DM were enrolled (44 men, 45 women; mean [SD] age, 38.3 [12.8] years; mean [SD] body weight, 70.8 [11.6] kg; mean [SD] body mass index, 24.6 [3.0] kg/m(2); mean [SD] duration of diabetes, 17.8 [10.5] years; mean HbA(1c), 7.9% [0.88%]). The mean (SD) late postprandial BG values were similar between treatments (8.9 [2.1] mmol/L [160.3 (37.8) mg/dL] for H/M vs 9.0 [1.8] mmol/L [162.1 (32.4) mg/dL] for LP + N), as were the end point HbA(1c) values (7.8% [0.9%] for H/M vs 7.9% [0.8%] for LP + N). The rate of hypoglycemia was significantly higher during treatment with H/M, primarily because of episodes occurring between 12 PM and 6 PM, but was relatively low in both groups (mean/median rate per patient per 30 days: 2.87/2.14 for H/M and 2.11/1.07 for LP + N; P < 0.05). CONCLUSIONS: In this population of patients with type 1 DM, preprandial H/M provided an effective alternative regimen for prandial and basal insulin replacement. Late postprandial BG control, an indicator of basal insulin sufficiency, was similar to that achieved with an intensified regimen of LP + N injected separately before meals, and the end point HbA(1c) was similar between the 2 treatments.

Clinical pharmacokinetics and pharmacodynamics of insulin lispro mixtures.

Rapid-acting insulin analogues such as insulin lispro and insulin aspart produce a more physiological profile of insulin activity than does conventional regular human insulin because of their unique pharmacokinetics. These insulin analogues are absorbed rapidly from the subcutaneous injection site, resulting in a better matching of the appearance of insulin in the circulation with nutrient absorption from the intestine. In addition, they are shorter-acting than regular human insulin, thus decreasing the risk of late postprandial hypoglycaemia due to inappropriate hyperinsulinaemia. Because self-prepared mixtures of these rapid-acting insulin analogues with longer-acting insulins such as neutral protamine Hagedorn (NPH) insulin have been shown to be clinically useful, and because manufactured fixed-ratio mixtures of regular human insulin and NPH already represent a large proportion of insulin use, manufactured fixed-ratio mixtures of insulin lispro and a sustained-release insulin known as NPL have been developed (insulin lispro mixtures). NPL is a protamine-based insulin lispro formulation with pharmacokinetics and glucodynamics comparable to those of human NPH insulin. NPL was developed for use within insulin lispro mixtures because an exchange between soluble insulin lispro and protamine-bound human insulin within human NPH precludes prolonged storage of mixtures of these insulins. An insulin lispro mixture consisting of 25% insulin lispro and 75% NPL is now commercially available. This preparation is intended primarily as an alternative to human insulin 30/70, which is commonly used within a twice-daily injection regimen. A mixture containing 50% insulin lispro and 50% NPL is also available. The rapid activity of insulin lispro is maintained within insulin lispro mixtures, allowing injection just prior to a meal, a convenience that is not available with commercial mixtures of regular human insulin and human NPH insulin, which should be injected 30 to 45 minutes prior to meals. As with insulin lispro itself, the rapid action of insulin lispro within the insulin lispro mixtures also results in a smaller increase in blood glucose levels after meals than with comparable human insulin mixtures. In addition, data from two studies have shown that when Mix25 is injected prior to the evening meal the incidence of nocturnal hypoglycaemia is decreased in comparison with the same dose of human insulin 30/70. The combined rapid and prolonged insulin activity provided by insulin lispro mixtures has been defined both in healthy subjects without diabetes and in patients with diabetes.