Comparing the efficacy, safety, and utility of intensive insulin algorithms for a primary care practice

Diabetes management is firmly based within the primary care community. Landmark randomized, controlled trials have demonstrated that even modest reductions in glycated hemoglobin (HbA1c) can yield improvements in economic and medical end-points. Diabetes is a chronic, progressive disease associated with loss of pancreatic β-cell function. Therefore, most patients will eventually require insulin therapies in order to achieve their individualized targeted HbA1c as their β-cell function and mass wanes. Although clinicians understand the importance of early insulin initiation, there is little agreement as to when to introduce insulin as a therapeutic option. Once initiated, questions remain as to whether to allow the patients to self-titrate their dose or whether the dosing should be tightly regulated by the clinician. Physicians have many evidence-based basal insulin protocols from which to choose, all of which have been shown to drive HbA1c levels to the American Diabetes Association target of ≤7%. This article will discuss ways by which insulin therapies can be effectively introduced to patients within busy primary care practices. Published evidence-based basal insulin protocols will be evaluated for safety and efficacy

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Glycaemic control and the risk of mortality in elderly type 2 diabetic patients (ZODIAC-20)

P>Aims: Studies on macrovascular consequences of glucose control in elderly patients (> 75 years) with type 2 diabetes mellitus (T2DM) are lacking. The present study aimed to investigate the relationship between HbA(1c) and mortality in this specific population. Methods: Between 1998 and 1999, 374 primary care patients with T2DM aged older than 75 years participated in the Zwolle Outpatient Diabetes project Integrating Available Care study, a prospective observational study. Early 2009, data on mortality were collected. Updated means for annually measured HbA(1c) values were calculated after a follow-up time of 10 years. Updated mean HbA(1c) was used as a time-dependent covariate in a Cox proportional hazard model. Main outcome measures were all-cause and cardiovascular disease (CVD) mortality. Analyses were performed in strata according to diabetes duration (< 5, 5-11 and >= 11 years). Results: In the group with a diabetes duration < 5 years, an increase of 1% in the updated mean HbA(1c) level was associated with an increase in all-cause and CVD mortality risk of 51% (95% CI 17-95%) and 72% (95% CI 19-148%), respectively. Glycaemic control was not related to mortality for patients with a diabetes duration >= 5 years. Conclusion: Poor glycaemic control is related to increased all-cause and CVD mortality in patients > 75 years with T2DM of short duration (< 5 years). Discussion: Because of the observational study design, our results should be interpreted with caution. Nevertheless, they are suggestive that improving glycaemic control may be beneficial in elderly patients with T2DM, especially in those with recently diagnosed T2DM. Randomised-controlled trials are necessary to investigate whether this holds true

Lower blood pressure associated with higher mortality in elderly diabetic patients (ZODIAC-12)

Objective: to investigate the relationship between blood pressure over time and mortality in elderly patients with type 2 diabetes mellitus (T2DM). Design: prospective observational cohort stud). Setting: primary care, Zwolle, The Netherlands. Subjects: patients with T2DM aged 60 years and older (n = 881). The cohort was divided into two age categories: 60-75 years and older than 75 years. Methods: updated means for systolic, diastolic and pulse pressures were calculated after a median follow-up time of 9.8 years. These values were used as time-dependent covariates in a Cox proportional hazard model. Main outcome measures were all-cause and cardiovascular mortality. Results: all of the blood pressure measures were inversely related to all-cause mortality in elderly diabetic patients (>75 years). Furthermore, these relationships were specifically found in elderly patients treated with antihypertensive medication at baseline. A decrease of 10 mm Hg in systolic blood pressure, diastolic blood pressure and pulse pressure led to a mortality increase of 20% [95% confidence interval (95% CI): 12-27%], 26% [95% CI: 12%-38%] and 20% [95% CI: 10%-29%], respectively. In the low age group (60-75 years), no relationship was found between blood pressure and mortality. Conclusions: blood pressure is a marker for mortality in elderly T2DM patients; however, the relationship is inverse

Prediction of mortality in type 2 diabetes from health-related quality of life (ZODIAC-4)

Abstract: OBJECTIVE - To investigate the relationship between health-related quality of life (HRQOL) and mortality in type 2 diabetes. RESEARCH DESIGN AND METHODS - In 1998,1,143 primary care patients with type 2 diabetes participated in the Zwolle Outpatient Diabetes project Integrating Available Care (ZODIAC) study. At baseline, HRQOL was assessed with the RAND-36 and, after almost 6 years, life status was retrieved. Cox proportional hazards modeling was used to investigate the association between HRQOL (continuous data) and mortality with adjustment for selected confounders (smoking, age, sex, diabetes duration, AlC, renal function, BMI, blood pressure, HDL cholesterol, and macrovascular complications). RESULTS - The Physical Component Summary of the RAND-36 was inversely associated with mortality (hazard ratio [HR] 0.979 [95% CI 0.966-0.992]), as were two separate RAND-36 dimensions. CONCLUSIONS - This study found that HRQOL is; an independent marker of mortality and emphasizes the importance of looking beyond clinical parameters in patients wit type 2 diabetes.

Association between 9p21 genetic variants and mortality risk in a prospective cohort of patients with type 2 diabetes (ZODIAC-15)

The genomic region at 9p21 chromosome near the CDKN2A/CDKN2B genes is associated with type 2 diabetes(T2D) and cardiovascular disease(CVD). The effect of the 9p21 locus on long-term mortality in patients with T2D has yet to be determined. We examined three single nucleotide polymorphisms (SNPs) on 9p21, consistently and independently associated with T2D (rs10811661) or CVD (rs10757278, rs2383206), in relation to the risk of total and cardiovascular mortality in diabetic patients. We also aimed to replicate the previously observed interaction between rs2383206 and glycemic control on mortality. Genotypes for three SNPs were determined in 914 individuals from a prospective cohort of T2D patients of Dutch origin. Associations with mortality were assessed using Cox proportional hazard analyses. After a median follow-up of 9.5 years, 358 out of 914 patients had died. The hazard ratio (HR) for total mortality among individuals homozygous for the T2D-risk allele of rs10811661 compared to non-homozygous individuals was 0.74(95%CI 0.59-0.93). For the carriers of both CVD-risk alleles of rs10757278, the HR for total mortality was 1.31(95% CI 1.01-1.70). We found a significant interaction between rs2383206 and HbA1c on mortality, which was higher among patients with two CVD-risk alleles in the two lowest HbA1c tertiles (HR 1.68(95% CI 1.08-2.63); HR 1.48(95%CI 1.01-2.18). In conclusion, common variants on 9p21 were associated with mortality in patients with T2D in a Dutch population. The T2D SNP was inversely associated with mortality, while the CVD SNP increased the risk for mortality. We confirmed a possible, although different, synergistic relationship between HbA1c and rs2383206 on total mortality