Introduction to Personalized Medicine in Diabetes Mellitus

The world is facing an epidemic rise in diabetes mellitus (DM) incidence, which is challenging health funders, health systems, clinicians, and patients to understand and respond to a flood of research and knowledge. Evidence-based guidelines provide uniform management recommendations for ?average? patients that rarely take into account individual variation in susceptibility to DM, to its complications, and responses to pharmacological and lifestyle interventions. Personalized medicine combines bioinformatics with genomic, proteomic, metabolomic, pharmacogenomic (?omics?) and other new technologies to explore pathophysiology and to characterize more precisely an individual?s risk for disease, as well as response to interventions. In this review we will introduce readers to personalized medicine as applied to DM, in particular the use of clinical, genetic, metabolic, and other markers of risk for DM and its chronic microvascular and macrovascular complications, as well as insights into variations in response to and tolerance of commonly used medications, dietary changes, and exercise. These advances in ?omic? information and techniques also provide clues to potential pathophysiological mechanisms underlying DM and its complications

3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial

Background: Liraglutide 3·0 mg was shown to reduce bodyweight and improve glucose metabolism after the 56-week period of this trial, one of four trials in the SCALE programme. In the 3-year assessment of the SCALE Obesity and Prediabetes trial we aimed to evaluate the proportion of individuals with prediabetes who were diagnosed with type 2 diabetes. Methods: In this randomised, double-blind, placebo-controlled trial, adults with prediabetes and a body-mass index of at least 30 kg/m2, or at least 27 kg/m2 with comorbidities, were randomised 2:1, using a telephone or web-based system, to once-daily subcutaneous liraglutide 3·0 mg or matched placebo, as an adjunct to a reduced-calorie diet and increased physical activity. Time to diabetes onset by 160 weeks was the primary outcome, evaluated in all randomised treated individuals with at least one post-baseline assessment. The trial was conducted at 191 clinical research sites in 27 countries and is registered with ClinicalTrials.gov, number NCT01272219. Findings: The study ran between June 1, 2011, and March 2, 2015. We randomly assigned 2254 patients to receive liraglutide (n=1505) or placebo (n=749). 1128 (50%) participants completed the study up to week 160, after withdrawal of 714 (47%) participants in the liraglutide group and 412 (55%) participants in the placebo group. By week 160, 26 (2%) of 1472 individuals in the liraglutide group versus 46 (6%) of 738 in the placebo group were diagnosed with diabetes while on treatment. The mean time from randomisation to diagnosis was 99 (SD 47) weeks for the 26 individuals in the liraglutide group versus 87 (47) weeks for the 46 individuals in the placebo group. Taking the different diagnosis frequencies between the treatment groups into account, the time to onset of diabetes over 160 weeks among all randomised individuals was 2·7 times longer with liraglutide than with placebo (95% CI 1·9 to 3·9, p<0·0001), corresponding with a hazard ratio of 0·21 (95% CI 0·13–0·34). Liraglutide induced greater weight loss than placebo at week 160 (–6·1 [SD 7·3] vs −1·9% [6·3]; estimated treatment difference −4·3%, 95% CI −4·9 to −3·7, p<0·0001). Serious adverse events were reported by 227 (15%) of 1501 randomised treated individuals in the liraglutide group versus 96 (13%) of 747 individuals in the placebo group. Interpretation: In this trial, we provide results for 3 years of treatment, with the limitation that withdrawn individuals were not followed up after discontinuation. Liraglutide 3·0 mg might provide health benefits in terms of reduced risk of diabetes in individuals with obesity and prediabetes. Funding: Novo Nordisk, Denmark

Metabolic profiling in personalized medicine: bridging the gap between knowledge and clinical practice in Type 2 diabetes

Type 2 diabetes mellitus (DM2) is the most commonly diagnosed metabolic disease and its prevalence is expected to increase. Epidemiological studies clearly show excess mortality associated with DM2, as well as an increased risk of DM2-related complications. Advances in personalized medicine would greatly improve patient care in the field of diabetes and other metabolic diseases. Prediction of the disease in asymptomatic patients as well as its harsh complications in patients already diagnosed is becoming a necessity, with the considerable increase in the cost of the treatment. In the current article, we review the known clinical, molecular metabolic and genetic biomarkers that should be integrated in a future bioinformatic platform to be used at the point-of-care, and discuss the challenges we face in applying this vision of personalized medicine for diabetes into reality

Depressive symptoms prior to and following insulin initiation in patients with type 2 diabetes mellitus : Prevalence, risk factors and effect on physician resource utilization

Aims: To study the frequency and intensity of depressive symptoms and associations with physician resource utilisation following insulin initiation in patients with type 2 diabetes mellitus. Methods: SOLVE was a 24-week observational study. In this sub-analysis of data from Poland, depressive symptoms were evaluated using the Patient Health Questionnaire (PHQ)-9. Results: PHQ-9 was completed by 942 of 1169 patients (80.6%) at baseline, and 751 (64.2%) at both baseline and final (24-week) visit. PHQ-9 scores indicated depressive symptoms in 45.6% (n = 430) at baseline, and 27.2% (n = 223) at final visit. Mean PHQ-9 change was −2.38 [95% CI −2.73, −2.02], p < 0.001. Depressive symptoms at baseline (OR 6.32, p < 0.001), microvascular disease (OR 2.45, p = 0.016), number of physician contacts (OR 1.16, p = 0.009), and change in HbA1c (OR 0.60, p = 0.025) were independently associated with moderate/severe depressive symptoms at final visit. Patients with more severe depressive symptoms spent more time training to self-inject (p = 0.0016), self-adjust (p = 0.0023) and manage other aspects of insulin delivery (p < 0.0001). Patients with persistent depressive symptoms had more telephone contacts and dose changes at final visit than those without (both p < 0.05)

Effect of baseline glycosylated hemoglobin A1c on glycemic control and diabetes management following initiation of once-daily insulin detemir in real-life clinical practice

The SOLVE study investigated the initiation of basal insulin in patients with type 2 diabetes on oral antidiabetic (OAD) treatment and outcomes in patients with varying levels of glycemic control at baseline. This was an observational cohort study conducted in 10 countries using insulin detemir. Data were collected at 3 clinic visits (baseline, 12-week interim, and 24-week final visit). A total of 13,526 (77.9%) patients were included in the glycosylated hemoglobin A1c (HbA1c) subset analysis. Patients were grouped according to pre-insulin HbA1c values as follows: HbA1c 9% (n = 5,363). A total of 27 patients experienced serious adverse drug reactions (SADRs) and/or severe hypoglycemia (3, 10, and 11 patients with pre-insulin HbA1c 9.0%, respectively). All patient subgroups realized improvements in HbA1c, with the pre-insulin HbA1c >9% subgroup having the largest HbA1c reduction (-2.4% versus -0.9% and -0.2% for HbA1c subgroups 7.6-9% and <7.6%, respectively). In the total cohort (n = 17,374), the incidence of severe hypoglycemia decreased from 4 events per 100 person years to <1 event per 100 person years by final visit; the incidence of minor hypoglycemia increased from 1.6 to 1.8 events per person year. In this study, insulin initiation was delayed until late in disease course, and overall concordance with internationally recognized guidelines was low. The initiation of once-daily insulin detemir was associated with substantial improvements in glycemic control and was not associated with an increase in severe hypoglycemia or weight gain