EARLIER INTERVENTION IN TYPE 2 DIABETES

In type 2 diabetes, the onset and progression of complications is significantly delayed by improving glycaemic control. However, the proportion of patients reaching and sustaining guideline recommendations for glycaemic targets remains unacceptably low. Recent clinical trials and predictive physiologically based mathematical simulations (Archimedes model) indicate that benefits can be enhanced with earlier intervention and timely achievement of glycaemic targets. This article reviews the evidence for early intervention, showing that intensive approaches, including earlier introduction of combination therapy, allow more patients to achieve glycaemic targets and hence reduce complications and delay disease progression

Insulin degludec results in lower rates of nocturnal hypoglycaemia and fasting plasma glucose vs. insulin glargine: A meta-analysis of seven clinical trials *

AbstractBackground and aimsBasal insulin analogues have a reduced risk of hypoglycaemia compared with NPH insulin, but hypoglycaemia still remains a major impediment to achieving recommended fasting plasma glucose (FPG) targets in patients with diabetes. Insulin degludec (IDeg) is a new basal insulin that forms soluble multihexamers after subcutaneous injection resulting in an ultra-long duration of action and stable glucose-lowering effect. The aim of this analysis was to compare the effect of IDeg on FPG and nocturnal confirmed hypoglycaemia as compared to insulin glargine (IGlar).Methods and resultsData were included from seven phase 3a, randomised, open-label, treat-to-target clinical trials in which once-daily IDeg was compared with once-daily IGlar. Two trials included a total of 957 patients with type 1 diabetes (T1D) and five trials included a total of 3360 patients with type 2 diabetes (T2D); all trials were 26 or 52 weeks in duration. Confirmed hypoglycaemia was defined as plasma glucose <3.1 mmol/L or severe episodes requiring assistance, and nocturnal hypoglycaemia occurred between 00:01 and 05:59. In all trials, the mean end-of-trial FPG was lower for IDeg than IGlar, reaching statistical significance in three trials. Similarly, IDeg was associated with a lower rate of nocturnal confirmed hypoglycaemia vs. IGlar, which was statistically significant in three trials, regardless of type of diabetes or background therapy.ConclusionThis analysis shows that the lower rate of nocturnal confirmed hypoglycaemia seen with IDeg relative to IGlar is accompanied by a reduced mean FPG, in particular in patients with T2D

Efficacy and safety of dapagliflozin in patients with type 2 diabetes and moderate renal impairment (chronic kidney disease stage 3A): The DERIVE Study

Aims: Dapagliflozin is a selective inhibitor of sodium glucose co-transporter 2 (SGLT2). This study assessed the efficacy and safety of dapagliflozin 10 mg vs placebo in patients with type 2 diabetes (T2D) and moderate renal impairment (estimated glomerular filtration rate [eGFR], 45-59mL/min/1.73m2; chronic kidney disease [CKD] stage 3A). Materials and methods: In this double-blind, parallel group, Phase 3 study (NCT02413398, clinicaltrials.gov) patients with inadequately controlled T2D (HbA1c 7.0%-11.0%) were randomized (1:1) to dapagliflozin 10 mg once daily (N=160) or matching placebo (N=161) for 24weeks. Randomization was stratified by pre-enrolment glucose-lowering therapy. The primary endpoint was change from baseline in HbA1c at Week 24. Results: At Week 24, compared with placebo, dapagliflozin significantly decreased HbA1c (difference [95% CI], -0.34% [-0.53, -0.15]; P < 0.001), body weight (difference [95% CI], -1.25kg [-1.90, -0.59]; P < 0.001), fasting plasma glucose (difference [95% CI], -0.9 mmol/L [-1.5, -0.4]; P = 0.001) and systolic blood pressure (difference [95% CI], -3.1 mmHg [-6.3, 0.0]; P < 0.05). Decreases from baseline in eGFR were greater with dapagliflozin than placebo at Week 24 (-2.49mL/min/1.73m2[-4.96, -0.02]), however, eGFR returned to baseline levels at Week 27 (3 weeks post-treatment) (0.61mL/min/1.73m2[-1.59, 2.81]). No increase in adverse events (AEs; 41.9% vs 47.8%) or serious AEs (5.6% vs 8.7%) were reported with dapagliflozin versus placebo. No AEs of bone fractures, amputations or DKA were reported. Conclusions: The findings of this study (NCT02413398, clinicaltrials.gov) support the positive benefit/risk profile of dapagliflozin for the treatment of patients with T2D and CKD 3A

Cardiovascular risk assessment beyond Systemic Coronary Risk Estimation: a role for organ damage markers

BACKGROUND: Cardiovascular risk assessment in the clinical practice is mostly based on risk charts, such as Framingham risk score and Systemic Coronary Risk Estimation (SCORE). These enable clinicians to estimate the impact of cardiovascular risk factors and assess individual cardiovascular risk profile. Risk charts, however, do not take into account subclinical organ damage, which exerts independent influence on risk and may amplify the estimated risk profile. Inclusion of organ damage markers in the assessment may thus contribute to improve this process. OBJECTIVE: Our aim was to evaluate the influence of implementation of SCORE charts with widely available indexes of organ damage, with the purpose to ameliorate individual risk assessment. METHODOLOGY: We searched www.Pubmed.gov for evidence about the predictive value of left ventricular hypertrophy (LVH), estimated glomerular filtration rate (eGFR), microalbuminuria (MAU) and metabolic syndrome on different risk profiles estimated by SCORE. Interventional and observational trials including at least 200 patients and published after 2000 were selected. RESULTS: The presence of organ damage as well as the number of abnormal parameters indicating organ damage is associated with increased cardiovascular risk, independently of SCORE. In the area of high risk, the impact of different markers of organ damage is heterogeneous. Combined risk models of SCORE and subclinical organ damage have major impact on risk stratification and may impact on recommendation in primary prevention in all SCORE categories. CONCLUSION: Available evidence suggests a tangible clinical advantage of adding the evaluation of simple organ damage markers to risk charts in cardiovascular risk prediction

The Place and Value of Sodium-Glucose Cotransporter 2 Inhibitors in the Evolving Treatment Paradigm for Type 2 Diabetes Mellitus: A Narrative Review

Over recent years, the expanding evidence base for sodium-glucose cotransporter-2 inhibitor (SGLT2i) therapies has revealed benefits beyond their glucose-lowering efficacy in the treatment of Type 2 diabetes mellitus (T2DM), resulting in their recognition as cardiorenal medicines. While SGLT2is continue to be recommended among the second-line therapies for the treatment of hyperglycaemia, their true value now extends to the prevention of debilitating and costly cardiovascular and renal events for high-risk individuals, with particular benefit shown in reducing major adverse cardiac events and heart failure (HF) and slowing the progression of chronic kidney disease. However, SGLT2i usage is still suboptimal among groups considered to be at greatest risk of cardiorenal complications. The ongoing coronavirus disease 2019 (COVID-19) pandemic has intensified financial pressures on healthcare systems, which may hamper further investment in newer effective medicines. Emerging evidence indicates that glycaemic control should be prioritised for people with T2DM in the era of COVID-19 and practical advice on the use of T2DM medications during periods of acute illness remains important, particularly for healthcare professionals working in primary care who face multiple competing priorities. This article provides the latest update from the Improving Diabetes Steering Committee, including perspectives on the value of SGLT2is as cost-effective therapies within the T2DM treatment paradigm, with particular focus on the latest published evidence relating to the prevention or slowing of cardiorenal complications. The implications for ongoing and future approaches to diabetes care are considered in the light of the continuing coronavirus pandemic, and relevant aspects of international treatment guidelines are highlighted with practical advice on the appropriate use of SGLT2is in commonly occurring T2DM clinical scenarios. The ‘SGLT2i Prescribing Tool for T2DM Management’, previously published by the Steering Committee, has been updated to reflect the latest evidence and is provided in the Supplementary Materials to help support clinicians delivering T2DM care

Beyond Metformin: Safety Considerations in the Decision-Making Process for Selecting a Second Medication for Type 2 Diabetes Management: Reflections From aDiabetes CareEditors’ Expert Forum

The trend toward personalized management of diabetes has focused attention on the differences among available pharmacological agents in terms of mechanisms of action, efficacy, and, most important, safety. Clinicians must select from these features to develop individualized therapy regimens. In June 2013, a nine-member Diabetes Care Editors’ Expert Forum convened to review safety evidence for six major diabetes drug classes: insulin, sulfonylureas (SUs), thiazolidinediones (TZDs), glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, and sodium glucose cotransporter 2 inhibitors. This article, an outgrowth of the forum, summarizes well-delineated and theoretical safety concerns related to these drug classes, as well as the panelists’ opinions regarding their best use in patients with type 2 diabetes. All of the options appear to have reasonably wide safety margins when used appropriately. Those about which we know the most—metformin, SUs, insulin, and perhaps now also TZDs—are efficacious in most patients and can be placed into a basic initial algorithm. However, these agents leave some clinical needs unmet. Selecting next steps is a more formidable process involving newer agents that are understood less well and for which there are unresolved questions regarding risk versus benefit in certain populations. Choosing a specific agent is not as important as implementing some form of early intervention and advancing rapidly to some form of combination therapy as needed. When all options are relatively safe given the benefits they confer, therapeutic decision making must rely on a personalized approach, taking into account patients’ clinical circumstances, phenotype, pathophysiological defects, preferences, abilities, and costs

Kadun eri ratkaisujen vaikutukset ylläpitokustannuksiin

Tässä opinnäytetyössä tarkastellaan katujen ylläpitokustannuksia Helsingin kaupungissa. Työn toimeksiantajana on Helsingin kaupunki. Ohjaajina toimivat Helsingin kaupungin ylläpitoinsinööri Tuomas Lautaniemi ja Hämeen ammattikorkeakoulun liikennealan lehtori Rami Tervo. Työn tavoitteena oli kehittää Helsingin kaupungille apuväline ylläpitokustannusten arviointiin katusuunnittelun yhteydessä. Apuvälineeksi on toteutettu Excel-taulukko, joka laskee kadun eri ratkaisujen ja ominaisuuksien perusteella arvion vuosittaisista ylläpitokustannuksista. Tämän taulukon on tarkoitus antaa tarkempaa arviota katusuunnitelman yhteydessä ilmoitettaviin ylläpitokustannuksiin kuin ennen. Suurimmat katujen ylläpitoa hankaloittavat ratkaisut ovat kadunvarsipysäköinti, kolmitasoratkaisut (jalankulun, pyöräilyn ja ajoradan erottaminen eri tasoihin) ja ahtaat katutilat. Kadun ylläpitokustannuksiin vaikuttavat myös monet sellaiset asiat, joihin ei suunnittelulla voida vaikuttaa. Kadun eri rakenteellisten ominaisuuksien vaikutuksetkin ovat hyvin moninaisia ja usein vaikutukset vaihtelevat kohteittain. Näiden takia taulukon antama ylläpitokustannusarvio on vain karkea arvio kadun vuosittaisista ylläpitokustannuksista.In this thesis project maintenance costs of streets were examined by the perspective of the city of Helsinki. The commissioner of this thesis was the city of Helsinki. The supervisors included maintenance engineer Tuomas Lautaniemi from the city of Helsinki and traffic and transport management lecturer Rami Tervo from Häme University of Applied Sciences. The goal of this project was to develop an assistive device to the city of Helsinki which would help estimate the maintenance costs of streets. The assistive device was implemented using an Excel-table which calculates estimated annual maintenance costs for a specific street based on solutions and features of the street. The function of this Excel-table is to provide more exact maintenance costs shown in the street plan than before. The biggest challenges in the maintenance of streets are street parking, three-level solutions (walking, cycling and roadway are separated into different levels) and the narrow street space. The maintenance costs of streets are influenced by many factors which cannot be affected by planning. The effects of structural solutions on streets are multifold and often they change by location. This is why the estimated annual maintenance costs of a street are only a very rough estimates