Cunegundo Vergara

Insulin Glargine: A Systematic Review of a Long-Acting Insulin Analogue

BACKGROUND Insulin glargine is the first long-acting basal insulin analogue indicated for subcutaneous administration once daily at bedtime in adults with type 1 or type 2 diabetes mellitus and pediatric patients aged > or = 6 years with type 1 diabetes. It differs in structure from native human insulin by 3 amino acids, a structural modification that provides a delayed onset of action and a constant, peakless effect that has a duration of at least 24 hours. OBJECTIVE The goal of this article was to help determine the current place in therapy of insulin glargine by reviewing all available efficacy and tolerability data published since its introduction onto the market. METHODS Relevant English-language articles were identified through searches of MEDLINE, PubMed, and EMBASE from 1966 to October 2002 and PREMEDLINE for November 2002. The search terms used were insulin, analogs, analogues, diabetes mellitus, glargine, HOE901, HOE-901, efficacy, safety, comparative study, treatment outcome, and case report. The reference lists of the identified articles were searched for additional relevant publications. Pharmacokinetic and pharmacodynamic data were reviewed and summarized. All large clinical trials (> or = 100 patients) evaluating the efficacy and tolerability of insulin glargine in patients with type 1 or type 2 diabetes were included in the review. Studies were compared in terms of their designs, primary and secondary efficacy parameters (glycosylated hemoglobin [HbA(1c)], fasting plasma glucose [FPG] and/or fasting blood glucose [FBG] level, incidence of hypoglycemia), and tolerability assessments. RESULTS Fourteen trials met the criteria for inclusion in this review, 7 of them published only in abstract form. All were multicenter, randomized, open-label, parallel-group trials conducted in Europe or the United States, and ranged in duration from 4 to 52 weeks. They compared insulin glargine with neutral protamine Hagedorn (NPH) insulin given once or twice daily in >5000 patients with type 1 or type 2 diabetes, or in insulin-naive patients with type 2 diabetes that was poorly controlled by oral antidiabetic agents. Insulin doses were individually titrated to achieve a target FBG level < or =120 mg/dL (6.7 mmol/L). The studies were typically statistically underpowered to detect a significant difference in HbA(1c) between treatment groups; only 3 trials were of an adequate size to have 90% statistical power to detect a mean 0.5% difference in HbA(1c). Furthermore, analysis of the data from these trials was associated with a number of methodologic problems relating to inconsistencies in reporting. Given these limitations, the available data suggest that insulin glargine treatment produces statistically significant reductions in FPG or FBG levels at end point both compared with baseline and compared with NPH insulin (P < 0.001) without achieving overall significant improvements in HbA(1c) values. However, a recent abstract of a small 52-week trial in patients with type 1 diabetes reported a 0.4% additional decrease in HbA(1c) with insulin glargine treatment compared with NPH insulin. Patients have reported greater treatment satisfaction with insulin glargine compared with NPH insulin. The findings varied regarding weight gain, overall incidence of hypoglycemia, and incidence of nocturnal hypoglycemia. Currently, the cost of insulin glargine is twice that of NPH insulin on a per-unit basis. CONCLUSIONS As a basal insulin replacement, insulin glargine administered once daily demonstrates a steady time-action profile over 24 hours without a pronounced peak. Based on the evidence from published clinical trials, insulin glargine appears to have equal clinical efficacy to NPH insulin, produces similar reductions in HbA(1c), and is associated with lower FPG and FBG levels and a consistent and significant reduction in the incidence of nocturnal hypoglycemia in patients with type 2 diabetes.

Management of rosiglitazone-induced edema: two case reports and a review of the literature.

The thiazolidinediones are an important class of insulin-sensitizing agents used for the treatment of type 2 diabetes. Similar to other antidiabetic agents, use of the thiazolidinediones is limited by adverse drug reactions. Specifically, use of the thiazolidinediones is associated with a triad of fluid retention, edema, and weight gain. In premarketing clinical trials, edema was reported to occur infrequently with minimal severity. However, several published cases from postmarketing data demonstrate that thiazolidinedione-induced fluid retention, exhibited by the initial onset of peripheral edema and weight gain, can progress to a more severe form of pulmonary edema that is refractory to diuretic therapy with resolution of symptoms only through discontinuation of the offending thiazolidinedione. In clinical practice, the occurrence of edema secondary to a thiazolidinedione drug may occur more frequently than reported. Two cases presented in this report illustrate a different outpatient management approach that enables both desired glycemic control and minimal fluid retention while using the thiazolidinediones.

A randomized, controlled trial of a stress management intervention for Latinos with type 2 diabetes delivered by community health workers: Outcomes for psychological wellbeing, glycemic control, and cortisol.

AIMS To test the efficacy of a community health worker (CHW) delivered stress management (SM) intervention on psychosocial, glycemic, and cortisol outcomes among U.S. Latinos with type 2 diabetes. METHODS A randomized, controlled trial compared CHW-delivered diabetes education (DE; one group session) to DE plus CHW-delivered SM (DE+SM; 8 group sessions). Psychosocial variables and urinary cortisol were measured at baseline and posttreatment. HbA1c was measured at baseline, posttreatment, and 3-month follow-up. RESULTS In intent to treat analysis, compared to DE (n=46), DE+SM (n=61) showed significantly improved symptoms of depression, anxiety, and self-reported health status. There were no significant group effects for HbA1c, diabetes distress, or urinary cortisol. However, there was a dose response effect for HbA1c and diabetes distress; increasing attendance at SM sessions was associated with greater improvements in HbA1c and diabetes distress. CONCLUSIONS This is the first randomized, controlled trial demonstrating that CHWs can improve psychological symptoms and self-reported health among Latinos with type 2 diabetes. Efforts to increase intervention attendance may improve HbA1c and diabetes distress.

Breast self-examination beliefs and practices, ethnicity, and health literacy: Implications for health education to reduce disparities.

Objective: This study aimed to quantitatively and qualitatively examine breast cancer screening practices, including breast self-examination (BSE), and health literacy among patients with chronic disease. Design: A prospective, multi-method study conducted with a targeted purposive sample of 297 patients with diabetes and/or hypertension from four ethnic groups (Latino, Vietnamese, African American, White-American) at an urban community health center. Setting: A federally qualified health center in Western Massachusetts. Methods: In our four-year study, 297 participants completed cancer knowledge, beliefs, attitudes and screening utilization scales and measures of health literacy. In addition to survey data collection, we conducted in-depth interviews, focus groups, home visits, and chronic disease diaries (n = 71). Results: In focus groups, African American, Vietnamese and Latina participants offered interviewers an unprompted demonstration of BSE, reported regular BSE use at particular times of the month, and shared positive feelings about the screening method. In a sample where approximately 93% of women have had a mammogram, many also had performed BSE (85.2%). Women with adequate health literacy were more likely than those with inadequate health literacy to rely on it. Despite being positively inclined toward BSE, Vietnamese women, who had the lowest health literacy scores in our sample, were less likely to perform BSE regularly. Conclusions: BSE seemed to be an appealing self-care practice for many women in our study, but we conclude that proper BSE practices may not be reinforced equally across ethnic groups and among patients with low health literacy.

A Novel Admixture-Based Pharmacogenetic Approach to Refine Warfarin Dosing in Caribbean Hispanics.

Aim This study is aimed at developing a novel admixture-adjusted pharmacogenomic approach to individually refine warfarin dosing in Caribbean Hispanic patients. Patients & Methods A multiple linear regression analysis of effective warfarin doses versus relevant genotypes, admixture, clinical and demographic factors was performed in 255 patients and further validated externally in another cohort of 55 individuals. Results The admixture-adjusted, genotype-guided warfarin dosing refinement algorithm developed in Caribbean Hispanics showed better predictability (R2 = 0.70, MAE = 0.72mg/day) than a clinical algorithm that excluded genotypes and admixture (R2 = 0.60, MAE = 0.99mg/day), and outperformed two prior pharmacogenetic algorithms in predicting effective dose in this population. For patients at the highest risk of adverse events, 45.5% of the dose predictions using the developed pharmacogenetic model resulted in ideal dose as compared with only 29% when using the clinical non-genetic algorithm (p<0.001). The admixture-driven pharmacogenetic algorithm predicted 58% of warfarin dose variance when externally validated in 55 individuals from an independent validation cohort (MAE = 0.89 mg/day, 24% mean bias). Conclusions Results supported our rationale to incorporate individual’s genotypes and unique admixture metrics into pharmacogenetic refinement models in order to increase predictability when expanding them to admixed populations like Caribbean Hispanics. Trial Registration ClinicalTrials.gov NCT01318057

Community health workers assisting Latinos manage stress and diabetes (CALMS-D): rationale, intervention design, implementation, and process outcomes.

Latinos have high rates of diabetes and mental distress, but lack appropriate services. A study was designed to compare enhanced standard diabetes care with enhanced standard care plus community health worker (CHW) delivered stress management for Latinos with type 2 diabetes. This paper reports intervention design and process outcomes. A formative process was used to develop and implement an eight-session, group stress management intervention. One hundred twenty-one participants completed baseline assessments; n = 107 attended diabetes education and were then randomized. Recruits reported high credibility and treatment expectancies. Treatment fidelity was high. Participants reported high treatment satisfaction and therapeutic alliance and their diabetes knowledge and affect improved over the short term. Retention and attendance at group sessions was challenging but successful relative to similar trials. This comprehensive and culturally sensitive stress management intervention, delivered by a well-trained CHW, was successfully implemented.

The effect of a Spanish virtual pain coach for older adults: a pilot study.

OBJECTIVE To pilot test the effects of a virtual pain coach on ambulatory Spanish-speaking older adults with pain from osteoarthritis. METHODS A randomized, controlled design was used. Eighteen Spanish-speaking older adults were randomly assigned to the virtual pain coach and pain communication education group, or to the pain communication education-only group. All participants viewed the pain communication videotape. Participants in the virtual pain coach group practiced talking about their osteoarthritis pain with the virtual pain coach. Immediately after the respective intervention, participants had their ambulatory medical visit. Pain intensity and pain interference with activities were measured with the Brief Pain Inventory, and depressive symptoms were measured with the Beck Depression Inventory II at baseline and 1 month later. RESULTS No significant group difference emerged for pain intensity, pain interference with activities, or depressive symptoms 1 month later. More older adults in the virtual pain coach group reported a change from nonuse to use of opioids at 1 month, 50% vs 0% of the education only group, Fishers exact test, P = 0.023. CONCLUSIONS  Preliminary data indicate that the Spanish virtual pain coach might assist Spanish-speaking older adults to talk with their practitioner about their osteoarthritis pain and obtain opioid treatment changes, but that pain and depressive symptoms continue unchanged 1 month later. Additional refinement and testing is required for the Spanish-speaking virtual pain coach to determine acceptability and outcomes for assisting Spanish-speaking older adults to communicate about their pain with their primary care practitioner.