Real-world weight change among patients treated with glucagon-like peptide-1 receptor agonist, dipeptidyl peptidase-4 inhibitor and sulfonylureas for type 2 diabetes and the influence of medication adherence.

AIMS: The study aims to examine real-world weight change and the role of medication adherence among patients with type 2 diabetes who initiated one of three drug classes: glucagon-like peptide-1 receptor agonist (GLP-1RA), dipeptidyl peptidase-4 inhibitor (DPP4) and sulfonylureas (SUs). MATERIALS AND METHODS: A cohort of patients initiating one of the three drug classes was selected from a large US database of integrated electronic medical record and administrative claims. Adherence was defined as per cent of days covered ≥80% during the year following drug initiation. Weight change was calculated from drug initiation (-180, +30 d) to 1 year (±90 d) later. Multivariate regression controlled for baseline differences between adherent and poorly adherent patients and the addition of another drug class during follow-up. RESULTS: The study included 833 GLP-1RA, 2,272 DPP4 and 2,713 SU patients who contributed 2,279, 6,602 and 7,429 observations respectively. Patients initiating a GLP-1RA achieved the largest weight change (-2.46 kg of GLP-1RA, -1.26 kg of DPP4 and 0.18 kg of SU, P < 0.01). Adherent GLP-1 patients lost 1.73 kg more than poorly adherent patients, and adherent SU patients gained 1.11 kg more than poorly adherent patients (all P < 0.01). Adherent and poorly adherent DPP4 patients experienced approximately the same amount of weight loss. CONCLUSIONS: Medication adherence can mediate observed weight loss in patients treated with a GLP1-RA or weight gain in those treated with an SU. Medication adherence was low in a real-world population, particularly for GLP-1RA, which displayed the strongest weight loss benefit. Because recent American Diabetes Association guidelines recommend selecting drug therapies that have a weight loss or weight neutral effect for the management of type 2 diabetes patients, patients should be encouraged to enhance their adherence to benefit the most from therapies that have weight loss properties.

Challenges faced by physicians when discussing the Type 2 diabetes diagnosis with patients: insights from a cross-national study (IntroDia® ).

AIMS: To investigate physicians' recalled experiences of their conversations with patients at diagnosis of Type 2 diabetes, because physician-patient communication at that time may influence the patient's subsequent self-care and outcomes. METHODS: As part of a large cross-national study of physician-patient communication during early treatment of Type 2 diabetes (IntroDia® ), we conducted a cross-sectional survey of physicians treating people with Type 2 diabetes in 26 countries across Africa, Asia, Europe, Latin America, the Middle East, North America and Oceania. The survey battery was designed to evaluate physician experiences during diagnosis conversations as well as physician empathy (measured using the Jefferson Scale of Physician Empathy). RESULTS: A total of 6753 of 9247 eligible physicians completed the IntroDia® survey (response rate 73.0%). Most respondents (87.5%) agreed that the conversation at diagnosis of Type 2 diabetes impacts the patient's acceptance of the condition and self-care. However, almost all physicians (98.9%) reported challenges during this conversation. Exploratory factor analysis revealed two related yet distinct types of challenges (r = 0.64, P < 0.0001) associated with either patients (eight challenges, α = 0.87) or the situation itself at diagnosis (four challenges, α = 0.72). There was a significant inverse association between physician empathy and overall challenge burden, as well as between empathy and each of the two types of challenges (all P < 0.0001). Study limitations include reliance on accurate physician recall and inability to assign causality to observed associations. CONCLUSIONS: Globally, most physicians indicated that conversations with patients at diagnosis of Type 2 diabetes strongly influence patient self-care. Higher physician empathy was associated with fewer challenges during the diagnosis conversation.

Evaluation of immunogenicity of LY2963016 insulin glargine compared with Lantus® insulin glargine in patients with type 1 or type 2 diabetes mellitus.

AIMS: To compare the immunogenicity profiles and the potential effects on clinical outcomes of LY2963016 insulin glargine (LY IGlar) and Lantus® insulin glargine (IGlar), products with identical primary amino acid sequences, in patients with type 1 or type 2 diabetes mellitus (T1DM or T2DM). METHODS: To assess immunogenicity, anti-insulin glargine antibodies (measured as percent binding) were compared between treatments in 52-week (open-label) and 24-week (double-blind) randomized studies in total study populations of patients with T1DM (N = 535) and T2DM (N = 756), respectively, and two subgroups of patients with T2DM: insulin-naïve patients and those reporting prestudy IGlar treatment (prior IGlar). Relationships between insulin antibody levels and clinical outcomes were assessed using analysis of covariance and partial correlations. Insulin antibody levels were assessed using Wilcoxon rank sum. Treatment comparisons for treatment-emergent antibody response (TEAR) and incidence of detectable antibodies were analysed using Fisher's exact test. RESULTS: No significant treatment differences were observed for insulin antibody levels, incidence of detectable anti-insulin glargine antibodies, or incidence of TEAR [overall and endpoint, by last-observation-carried-forward (LOCF)] in patients with T1DM or patients with T2DM, including the insulin-naïve subgroup. A statistically significant difference was noted in the overall incidence of detectable antibodies but not at endpoint (LOCF) nor in TEAR for the prior IGlar subgroup of patients with T2DM. Insulin antibody levels were low (<5%) in both treatment groups. Insulin antibody levels or developing TEAR was not associated with clinical outcomes. CONCLUSIONS: LY IGlar and IGlar have similar immunogenicity profiles; anti-insulin glargine antibody levels were low for both treatments, with no observed effect on efficacy and safety outcomes.

Identifying the worries and concerns about hypoglycemia in adults with type 2 diabetes.

AIMS: To identify the hypoglycemic concerns of adults with type 2 diabetes (T2D) and examine how these concerns are associated with key patient characteristics. METHODS: Qualitative interviews with 16 T2D adults and 11 diabetes care providers were conducted. Survey items were then developed and submitted to exploratory factor analyses (EFAs). Construct validity was assessed by correlations with diabetes distress, anxiety and depressive symptoms, well-being, hypoglycemic fear, hypoglycemia history and glycemic control (A1C). RESULTS: An EFA with 226 insulin users and 198 non-insulin users yielded 3 factors (14 items): Hypoglycemia Anxiety, Avoidance and Confidence. For both T2D groups, higher Anxiety and Avoidance were significantly associated with more hypoglycemia, lower well-being, and greater diabetes distress, depressive symptoms and hypoglycemic fear. Similar associations, in the converse direction, were found for Confidence. Among insulin users only, Anxiety was independently associated with greater emotional distress and more hypoglycemia, while Confidence was independently linked to less emotional distress and lower A1C. Avoidance was independently associated with greater emotional distress in both groups. CONCLUSIONS: Using the new 14-item Hypoglycemic Attitudes and Behavior Scale (HABS), we found that hypoglycemic concerns are significant in T2D adults, are linked to emotional distress and A1C, and merit attention in clinical practice.

Oxytocin receptor and vasopressin receptor 1a genes are respectively associated with emotional and cognitive empathy.

Empathy is the ability to recognize and share in the emotions of others. It can be considered a multifaceted concept with cognitive and emotional aspects. Little is known regarding the underlying neurochemistry of empathy and in the current study we used a neurogenetic approach to explore possible brain neurotransmitter pathways contributing to cognitive and emotional empathy. Both the oxytocin receptor (OXTR) and the arginine vasopressin receptor 1a (AVPR1a) genes contribute to social cognition in both animals and humans and hence are prominent candidates for contributing to empathy. The following research examined the associations between polymorphisms in these two genes and individual differences in emotional and cognitive empathy in a sample of 367 young adults. Intriguingly, we found that emotional empathy was associated solely with OXTR, whereas cognitive empathy was associated solely with AVPR1a. Moreover, no interaction was observed between the two genes and measures of empathy. The current findings contribute to our understanding of the distinct neurogenetic pathways involved in cognitive and emotional empathy and underscore the pervasive role of both oxytocin and vasopressin in modulating human emotions.

Control of type 2 diabetes after 1 year of laparoscopic adjustable gastric banding in the helping evaluate reduction in obesity (HERO) study.

AIMS: The 5-year, open-label, prospective, observational helping evaluate reduction in obesity (HERO) study (N = 1106) examines efficacy and safety of the LAP-BAND AP(®) laparoscopic adjustable gastric band (LAGB) in obese patients. This interim analysis assessed the control of type 2 diabetes (T2D), 1 year after the implantation of the LAGB. METHODS: Baseline T2D was defined by chart review or use of antidiabetic medications or haemoglobin A1c (HbA1c) ≥ 7.0%. Control of T2D at 1 year was defined as A1c <7.0% (with or without antidiabetic medications). RESULTS: After 1 year, 187 of 273 patients with T2D at baseline had adequate data available to assess T2D status, of which 135 patients (72.2%) achieved target control of T2D compared with 42.8% control rate at baseline. Independent predictors of achieving target control at 1 year included the following: (i) shorter diabetes duration odds ratio (OR) 0.914 [95% confidence interval (CI), 0.839, 0.995, p = 0.038], (ii) not using insulin therapy OR 0.16 (95% CI, 0.06, 0.47, p < 0.001) and (iii) greater mean % weight loss OR 1.176 (95% CI, 1.093, 1.266, p < 0.001). Patients using insulin at baseline were 84% less likely to achieve control of T2D after 1 year; each additional year of diabetes at baseline reduced the likelihood of good control by 9%; and each 1% of weight loss increases the likelihood of good control by 18%. Rates of device-related adverse events and reoperations were low and were not significantly different between patients with and without baseline T2D at 1 year. CONCLUSIONS: Greater % weight loss, not using insulin therapy, and shorter disease duration predicted increased likelihood of target control of T2D, 1 year after implantation of the LAGB.

Frailty and osteoporosis in older women--a prospective study.

UNLABELLED: Despite sharing common risk factors and biological pathways, the relationship between frailty and osteoporosis (OP) is not clear. This prospective study has shown that frailty defined by the Vulnerable Elders Survey can predict a decrease in bone mineral density after 1 year. Thus, frail older women should be assessed for osteoporosis. INTRODUCTION: Frailty and OP share common risk factors such as age, sarcopenia, lack of physical activity, low body weight, and smoking. Despite shared risk factors and biological pathways, the relationship between frailty and OP is not clear. The purpose of our prospective study was to examine this relationship in a community sample of older women. METHODS: A sample of 235 community-dwelling women was assessed for demographic, medical, frailty and OP status at baseline, and after at least 1 year. Frailty was assessed using the Cardiovascular Health study (CHS) frailty phenotype and using the Vulnerable Elders Survey (VES-13). OP was measured using dual photon absorptiometry bone mineral density (BMD). Descriptive statistics and regression models were used. RESULTS: At baseline, 235 women with a mean age of 77.6 (SD = 5.4), body mass index (BMI) of 28.3 (SD = 5.2) kg/m(2), and BMD of 0.7 (SD = 0.2) g/cm(2)were assessed. No correlation was found between BMD and the CHS (BMD spine, r = 0.009, p = 0.889; BMD hips, r = 0.050, p = 0.473) or the VES-13 (BMD spine, r = 0.034, p = 0.605; BMD hips, r = -0.042, p = 0.537) frailty scales. One hundred fifty-two (63.9 %) women were assessed after 1 year. In a regression model, women who were frail at baseline (VES-13) were found to have a statistically significantly lower hip and spine BMD at follow-up (controlling for BMI) than women who were non-frail at baseline (p = 0.0393, hip; p = 0.0069, spine). CONCLUSIONS: Frailty status as defined by the VES-13 predicts a decrease in BMD after 1 year.

What is so tough about self-monitoring of blood glucose? Perceived obstacles among patients with Type 2 diabetes.

AIMS: To identify patient-reported obstacles to self-monitoring of blood glucose among those with Type 2, both insulin users and non-insulin users, and to investigate how obstacles are associated with frequency of self-monitoring and use of self-monitoring data. METHODS: Patients with Type 2 diabetes (n = 886, 65% insulin users) who attended a 1-day diabetes education conference in cities across the USA completed a survey on current and recommended self-monitoring of blood glucose frequency, how they used self-monitoring results and perceived obstacles to self-monitoring use. Exploratory factor analysis examined 12 obstacle items to identify underlying factors. Regression analyses examined associations between self-monitoring of blood glucose use and the key obstacle factors identified in the exploratory factor analysis. RESULTS: Three obstacle factors emerged: Avoidance, Pointlessness and Burden. Avoidance was the only significant independent predictor of self-monitoring frequency (ß = -0.23, P < 0.001). Avoidance (ß = -0.12, P < 0.01) and Pointlessness (ß = -0.15, P < 0.001) independently predicted how often self-monitoring data were shared with healthcare professionals and whether or not data were used to make management adjustments (Avoidance: odds ratio = 0.74, P < 0.001; Pointlessness: odds ratio = 0.75, P < 0.01). Burden was not associated with any of the self-monitoring behavioural measures. Few differences between insulin users and non-insulin users were noted. CONCLUSIONS: Obstacles to self-monitoring of blood glucose use, both practical and emotional, were common. Higher levels of Avoidance and Pointlessness, but not Burden, were associated with less frequent self-monitoring use. Addressing patients' self-monitoring-related emotional concerns (Avoidance and Pointlessness) may be more beneficial in enhancing interest and engagement with self-monitoring of blood glucose than focusing on day-to-day, behavioural issues (Burden).

Pramlintide in the treatment of diabetes.

Diabetes treatment has traditionally focused on correcting insulin deficiency with exogenous insulin and oral agents designed to enhance insulin secretion or insulin sensitivity in peripheral tissues. The more recent view of diabetes as a disease that affects multiple hormones in addition to insulin has led to the development of new therapies more broadly aimed at restoring glucose homeostasis by correcting abnormalities in additional glucoregulatory hormones. Pramlintide, a synthetic analogue of the beta-cell hormone amylin, regulates the appearance of glucose in the circulation following meals through several mechanisms of action: slowing gastric emptying, preventing inappropriate postprandial secretion of glucagon and increasing satiety. Long-term studies have demonstrated that pramlintide improves postprandial glucose fluctuations and A1C while reducing insulin dose and body weight. This combination of benefits associated with pramlintide makes it an attractive new treatment option for patients with diabetes. Clinical Trial Registry Numbers: 137-155 open-label clinical trial: NCT00108004 (Pramlintide long-term, placebo-controlled clinical trials were completed prior to the requirement for NCT registry).

Home testing of fructosamine improves glycemic control in patients with diabetes.

OBJECTIVE: To determine whether weekly fructosamine testing at home by patients with type 2 diabetes, combined with therapeutic intervention when necessary on the basis of the results, would lead to improved glycemic control in comparison with usual care during a 3-month period. METHODS: In a prospective study, 25 patients with glycosylated hemoglobin (HbA1c) values above 8.0% were randomized into 2 groups. Both groups, a glucose-only testing group (14 patients with an initial mean HbA1c of 9.4 +/- 0.9%) and a combined glucose plus fructosamine testing group (11 patients with an initial mean HbA1c of 9.2 +/- 0.7%), received therapeutic intervention at the time of randomization. Both groups were instructed to perform blood glucose testing up to four times per day. The combined glucose plus fructosamine testing group was also instructed to perform weekly fructosamine testing in addition to the glucose testing and to telephone the investigator if their home-testing fructosamine value exceeded 350 mmol/L (approximately equivalent to HbA1c of 7.8%), whereupon the investigator implemented further interventions. Both groups returned in 3 months, at which time HbA1c testing was repeated in order to determine whether glycemic control had changed. RESULTS: The study results after 3 months showed that the HbA1c values in the combined glucose plus fructosamine testing group decreased from 9.2 +/- 0.7% to 8.0 +/- 0.5% (P<0.0001). In contrast, the HbA1c values in the glucose-only testing group declined from 9.4 +/- 0.9% to 9.1 +/- 1.3%, a difference that was not significant. CONCLUSION: In the 3 months after a change in therapy for type 2 diabetes, weekly home testing of fructosamine, combined with therapeutic interventions based on the results, led to a more rapid and significant improvement in glycemic control than did the usual regimen of glucose-only testing.

Insulin therapy in type 2 diabetes.

Type 2 diabetes is a common disorder often accompanied by numerous metabolic abnormalities leading to a high risk of cardiovascular morbidity and mortality. Results from the UKPDS have confirmed that intensive glucose control delays the onset and retards the progression of microvascular disease and possibly of macrovascular disease in patients with type 2 diabetes. In the early stages of the disease, insulin resistance plays a major role in the development of hyperglycemia and other metabolic abnormalities, and patients with type 2 diabetes often benefit from measures to improve insulin sensitivity such as weight loss, dietary changes, and exercise. Later, the use of oral insulin secretagogues and insulin sensitizers as monotherapy and in combination helps maintain glycemia for varying periods of time. Ultimately, because of the progressive nature of the disease and the progressive decline in pancreatic beta-cell function, insulin therapy is almost always obligatory to achieve optimal glycemic goals. Not all patients are candidates for aggressive insulin management; therefore, the goals of therapy should be modified, especially in elderly individuals and those with co-morbid conditions. Candidates for intensive management should be motivated, compliant, and educable, without other major medical conditions and physical limitations that would preclude accurate and reliable HGM and insulin administration. In selected patients, combination therapy with insulin and oral antidiabetic medications can be an effective method for normalizing glycemia without the need for rigorous multiple-injection regimens. The patients for whom combination therapy is most commonly successful are those who do not achieve adequate glycemic control using daytime oral agents but who still show some evidence of responsiveness to the medications. Bedtime intermediate-acting or predinner premixed intermediate- and rapid-acting insulin is administered and progressively increased until the FPG concentration is normalized. If combination therapy is not successful, a split-mixed regimen of intermediate- and rapid-acting insulin equally divided between the prebreakfast and pre-dinner periods is advised for oese patients, and more intensive regimens are advised for thin patients. Insulin therapy is invariably associated with weight gain and hypoglycemia. The use of metformin or glitazones in combination with insulin has been demonstrated to have insulin-sparing properties. Also, metformin use may ameliorate weight gain. The use of continuous subcutaneous insulin infusion pumps can be particularly beneficial in treating patients with type 2 diabetes mellitus who do not respond satisfactorily to more conventional treatment strategies. Intraperitoneal insulin delivery systems hold considerable promise in type 2 diabetes because of their more physiologic delivery of insulin and their ability to inhibit hepatic glucose production selectively, with less peripheral insulinemia than with subcutaneous insulin injections. Newer insulin analogues such as the rapidly acting Lispro insulin and the peakless, long-acting glargine insulin are increasingly being used because of their unique physiologic pharmacokinetics. New developments such as inhaled and buccal insulin preparations will also make it easier for many patients to initiate and maintain a proper insulin regimen. Finally, a new generation of gut peptides such as amylin and GLP-1 will add a new dimension to glycemic control through modification of nutrient delivery and other mechanisms; however, the ultimate goal in the management of type 2 diabetes is the primary prevention of the disease. The Diabetes Prevention Program (DPP) sponsored by the National Institutes of Health has currently randomly assigned more than 3000 persons with impaired glucose tolerance and at high risk of developing diabetes into three treatment arms: metformin arm, an intensive lifestyle-modification arm, and a placebo arm. The study will conclude in 2002 after all participants have been followed for 3 to 6 years.

The dental prosthesis used for intraoral muscle therapy in the rehabilitation of the stroke patient. A preliminary research study.

The dentist can maximize the oral rehabilitation of the stroke patient's weak or paralyzed oral musculature, resulting in dysfunctional speech, swallowing and deglutition, with the use of palatal lift and palatal augmentation prostheses. The study described here evaluates functional changes using these prostheses for three post-stroke patients with left hemiparesis. Clinical tests indicated decreased nasal emission and hypernasality, and improved speech articulation. Videofluoroscopy evaluation showed improvement in the oral phase of swallowing. Patient self-assessment indicated improved satisfaction with treatment.

Imperfect invariance to object translation in the discrimination of complex shapes.

The positional specificity of short-term visual memory for a variety of 3-D shapes was investigated in a series of 'same'/'different' discrimination experiments, with computer-rendered stimuli displayed either at the same or at different locations in the visual field. For animal-like shapes, we found complete translation invariance, regardless of the interstimulus similarity, and irrespective of direction and size of the displacement (experiments 1 and 2). Invariance to translation was obtained also with animal-like stimuli that had been 'scrambled' by randomizing the relative locations of their parts (experiment 3). The invariance broke down when the stimuli were made to differ in their composition, but not in the shapes of the corresponding parts (experiments 4 and 5). We interpret this pattern of findings in the context of several current theories of recognition, focusing in particular on the issue of the representation of object structure.

Detection of hypoglycemia with the GlucoWatch biographer.

OBJECTIVE: Hypoglycemia is a common acute complication of diabetes therapy. The GlucoWatch biographer provides frequent and automatic glucose measurements with an adjustable low-glucose alarm. We have analyzed the performance of the biographer low-glucose alarm relative to hypoglycemia as defined by blood glucose < or = 3.9 mmol/l. RESEARCH DESIGN AND METHODS: The analysis was based on 1,091 biographer uses from four clinical trials. which generated 14,487 paired (biographer and blood glucose) readings. RESULTS: The results show that as the low-glucose alert level of the biographer is increased, the number of true positive alerts (alarm sounds and blood glucose < or = 3.9 mmol/l) and false positive alerts (alarm sounds but blood glucose >3.9 mmol/l) increased. When analyzed as a function of varying low-glucose alert levels, the results show receiver operator characteristic curves consistent with a highly useful diagnostic tool. Setting the alert level from 1.1 to 1.7 mmol/l above the level of concern is likely to optimize the trade-off between true positives and false positives for each user. When the same blood glucose data are analyzed for typical monitoring practices (two or four measurements per day), the results show that fewer hypoglycemic events are detected than those detected with the biographer.

Benchmark data from the literature for evaluation of new glucose sensing technologies.

New glucose sensors based on various technologies are being developed to provide information for improved therapy in diabetes. There is a need to establish rational performance standards for these sensors. Frequently sampled, direct blood glucose recordings representative of blood glucose excursions in diabetes are the "gold standard." An extensive literature search revealed a limited number of diabetic and nondiabetic blood glucose recordings suitable for this purpose. Certain blood glucose recordings reflect the diversity of glycemic dynamics and provide sufficient challenge for evaluation of sensor systems. These recordings were converted into an accessible electronic format. An example is given of the use of these benchmark data to estimate aliasing error, or the error due to insufficient sampling frequency, based on a hypothetical sensor system having some properties of conventional "fingerstick" systems. Discrete sampling systems accumulate substantial aliasing error as the sampling period increases.

Can psycotherapy increase the survival time of cancer patients?

OBJECTIVE: The aim of this paper was to review the evidence regarding the possibility of a relationship between psychological intervention and survival time of cancer patients. METHOD: A literature search was conducted using CD ROM databases to identify studies which have evaluated the effects of psychological interventions on the survival time of cancer patients. The identified studies were critically reviewed. RESULTS: Eight studies which used scientifically acceptable methodology to examine this question were identified. Three of these studies found evidence for a relationship between psychological intervention and patients' survival time, while five did not. Methodological issues and potentially confounding factors are discussed. CONCLUSION: To date, a direct relationship between psychological intervention and patient survival time has not been conclusively demonstrated. Large-scale replication studies which are currently under way will provide more conclusive evidence on this question within the next few years.