OBJECTIVE -Large prospective studies have demonstrated that optimum glycemic control is not routinely achieved in clinical practice. Barriers to optimal insulin therapy include hypoglycemia, weight gain, and suboptimal initiation and dose titration. This study compared two treatment algorithms for insulin glargine initiation and titration: algorithm 1 (investigator led) versus algorithm 2 (performed by study subjects). RESEARCH DESIGN AND METHODS-A prospective, multicenter (n ϭ 611), multinational (n ϭ 59), open-label, 24-week randomized trial in 4,961 (algorithm 1, n ϭ 2,493; algorithm 2, n ϭ 2,468) suboptimally controlled type 2 diabetic subjects.RESULTS -At baseline, mean diabetes duration was 12.3 Ϯ 7.2 years, and 72% of subjects were pretreated with insulin. At end point, there was no significant difference in the incidence of severe hypoglycemia between algorithms 1 and 2 (0.9 vs. 1.1%). There was a significant reduction in HbA 1c from 8.9 Ϯ 1.3 to 7.8 Ϯ 1.2%, with a greater decrease (P Ͻ 0.001) with algorithm 2 (Ϫ1.22%) versus algorithm 1 (Ϫ1.08%). Fasting blood glucose decreased from 170 to 110 mg/dl, with a greater decrease (P Ͻ 0.001) with algorithm 2 (Ϫ62 mg/dl) versus algorithm 1 (Ϫ57 mg/dl). Mean basal insulin dose increased from 22.9 Ϯ 15.5 to 43.0 Ϯ 25.5 IU, with a significant difference (P Ͻ 0.003) between algorithm 2 (21.6 IU) and algorithm 1 (18.7 IU).CONCLUSIONS -Glargine is safe and effective in improving glycemic control in a large, diverse population with longstanding type 2 diabetes. A simple subject-administered titration algorithm conferred significantly improved glycemic control with a low incidence of severe hypoglycemia compared with physician-managed titration.

Running title: Glargine initiation in insulin-naïve type 2 diabetes AT.LANTUS: A Trial comparing LANTUS Algorithms to achieve Normal blood glucose Targets in subjects with Uncontrolled blood Sugar 2 ABSTRACT Objective: For many patients with type 2 diabetes, oral antidiabetic agents (OADs) do not provide optimal glycemic control, necessitating insulin therapy. Fear of hypoglycemia is a major barrier to initiating insulin therapy. The AT.LANTUS study investigated optimal methods to initiate and maintain insulin glargine (LANTUS ® ; glargine) therapy using two treatment algorithms. This sub-group analysis investigated the initiation of once-daily glargine therapy in patients sub-optimally controlled on multiple OADs. Research design and methods:This was a 24-week, multinational (59 countries), multicenter (611), randomized study. Algorithm 1 was a clinic-driven titration and Algorithm 2 was a patient-driven titration. Titration was based on target fasting blood glucose ≤100 mg/dL (≤5.5 mmol/L). Algorithms were compared for incidence of severe hypoglycemia (requiring assistance and blood glucose <50 mg/dL [<2.8 mmol/L]) and baseline-to-endpoint change in HbA 1c . Results:Of the 4961 patients enrolled in the study, 865 were included in this sub-group analysis: 340 received glargine plus 1 OAD; 525 received glargine plus >1 OAD. Incidence of severe hypoglycemia was <1%. HbA 1c decreased significantly between baseline and endpoint for patients receiving glargine plus 1 OAD (-1.4%, p<0.001; Algorithm 1 -1.3% vs Algorithm 2 -1.5%; p=0.03) and glargine plus >1 OAD (-1.7%, p<0.001; Algorithm 1 -1.5%vs Algorithm 2 -1.8%; p=0.001). Conclusions:This study shows that initiation of once-daily glargine with OADs results in significant reduction of HbA 1c with a low risk of hypoglycemia. The greater reduction in HbA 1c was seen in patients randomized to the patient-driven algorithm (Algorithm 2) on one or more than one OAD. Following diagnosis, patients are generally advised to make a number of lifestyle changes, focussed on increasing physical activity levels [7] and diet [8]. However, such programs are usually insufficient by this stage of the diabetes [9]. The progressive nature of T2DM, characterized by a decline in β-cell function [10,11] and deterioration in glycemic control [12], means that pharmacologic interventions are usually required [13]. Oral antidiabetic agents (OADs), for example, sulfonylureas, metformin and glitazones are therapeutic interventions used in monotherapy or in combination. However, to achieve and maintain good glycemic control, OADs, even in combination, are insufficient [14] and insulin therapy is often required [13].Both patients and physicians may be reluctant to start insulin therapy [6,15,16]. The fear of hypoglycemia, needle anxiety and weight gain are among the reasons cited that actively discourage insulin therapy. Therefore, it is important that for insulin therapy to be effective in patients with type 2 diabetes, these barriers must be overcome.Insulin glargine (LANTUS ® , glargine) is...

This study provides a set of face- and content-valid PQI for pharmacological management of patients with T2DM. While outcomes of some PQI were limited to patients with registration of clinical values, the selected PQI had good operational validity to be used in practice for assessment of prescribing quality.

It has been hypothesized that the possible mechanism behind an accelerated ovarian ageing process in type 1 diabetes is prolonged poor glycaemic control and subsequent effects on vascular health. The improved glycaemic control during the last decades may have prevented vascular damage from occurring to an extent that would affect organ function. Nevertheless, the present findings are reassuring for reproductive health prospects in women with type 1 diabetes.

Potential role of glial cell linederived neurotrophic factor receptors in Mü ller glial cells during light-induced retinal degeneration.