Diabetes Therapy

Differential Effect of Hypoalbuminemia on Hypoglycemia on Type 2 Diabetes Patients Treated with Insulin Glargine 300 U/ml and Insulin Degludec Abstract Introduction Hypoglycemia resulting from insulin therapy for treatment of diabetes increases the risk of adverse cardiovascular events. Determining biomarkers that provide accurate estimation of hypoglycemia risk may allow for more accurate patient management and care. The purpose of this study was to determine the cutoff value of serum albumin (s-alb) that increases the risk of hypoglycemia in patients treated with insulin degludec. Methods This study used a crossover design and randomized 30 patients admitted for glycemic control to compare differences between insulin glargine 300 U/ml (Gla300) and degludec treatments. Results The cutoff value of s-alb associated with 24-h hypoglycemia and nocturnal hypoglycemia in patients treated with degludec was 3.8 g/dl. In patients with s-alb levels < 3.8 g/dl, mean percentages of time with hypoglycemia, clinically important hypoglycemia, and nocturnal hypoglycemia were significantly lower in those treated with Gla300 compared with patients treated with degludec. Conclusion This study identified a cutoff value for s-alb levels that indicates risk of hypoglycemia in patients treated with degludec. Monitoring s-alb levels in patients treated with degludec will help to mitigate the risk of hypoglycemia. Trial Registration University Hospital Medical Information Network (UMIN 000031044).

Maturity Onset Diabetes of the Young is Not Necessarily Associated with Autosomal Inheritance: Case Description of a De Novo HFN1A Mutation Abstract Maturity onset diabetes of the young (MODY) accounts for up to 4% of all cases of diabetes in pediatric patients. MODY is usually characterized by autosomal dominant inheritance, impaired insulin secretion, and an average age at diagnosis of 18–26 years. Mutations in the hepatocyte nuclear factor 1-alpha (HNF1A), glucokinase, hepatocyte nuclear factor 4-alpha, and hepatocyte nuclear factor 1-beta genes are the mutations most frequently observed in cases of MODY. We herein report a case of HNF1A-MODY characterized by an early onset of diabetes. Genetic investigations revealed a de novo heterozygous substitution, N237D (HNF1A c.709A>G), in exon 3 of the HNF1A gene. Our case supports the hypothesis that de novo mutations are more frequent than expected. This recent evidence may suggest that conventional clinical diagnostic criteria for MODY should be revised and personalized according to the individual patient.

American Diabetes Association 2019 Conference Podcast With the Editor-in-Chief: What Are the Outcomes from ADA This Year and What Are the Future Developments in Diabetes? Podcast recording of Fernando Ovalle live from the ADA 2019 conference in San Francisco (MP4 177883 kb)

Correction to: Management of Patients with Type 2 Diabetes with Once-Weekly Semaglutide Versus Dulaglutide, Exenatide ER, Liraglutide and Lixisenatide: A Cost-Effectiveness Analysis in the Danish Setting In the original publication, Figs. 3 and 5 and the final sentence in the final paragraph of Results/Sensitivity Analyses were incorrectly published. The corrected statement and the figures are given below.

Clinical Efficacy and Parameters Affecting the Response to Dulaglutide Treatment in Patients with Type 2 Diabetes: A Retrospective, Real-World Data Study Abstract Introduction This study aimed to investigate the efficacy and clinical factors affecting the glycemic response to dulaglutide in type 2 diabetes (T2D) in a real-world clinical setting. Methods We conducted a retrospective study of 234 patients at the Asan Medical Center, Republic of Korea, who had T2D and initiated dulaglutide from June 2016 to December 2017. The primary outcome was the change in glycated hemoglobin (HbA1c) concentration between baseline and 6 months after the initiation of therapy. Multivariate regression analysis was used to determine the clinical parameters contributing to a superior glycemic response to dulaglutide. Results The mean age of the patients was 53, and 50% were male. Their mean baseline HbA1c, body mass index and duration of diabetes were 8.8%, 27.6 kg/m2 and 10.2 years, respectively. The change in HbA1c between baseline and 6 months was − 0.92% (95% CI: − 1.1% to − 0.74%, p < 0.001). The reduction in body weight over the same period was −2.1 kg (95% CI: − 2.9 to − 1.3 kg, p < 0.001). Using multivariate regression analysis, baseline HbA1c was found to be a significant predictor of superior glycemic response to dulaglutide. Conclusion The use of dulaglutide was associated with a significant reduction in HbA1c and body weight over a 6-month period in a real-world clinical setting. T2D patients with higher baseline HbA1c concentrations were more likely to demonstrate good clinical responses to dulaglutide.

Lower Renal Threshold for Glucose Reabsorption in Type 1 Diabetes Mellitus (T1DM) May Explain the Smaller Contribution of SGLT2 Inhibitors to the Improvement of Plasma Glucose Control Compared with T2DM Abstract Introduction Previously, we reported that the renal threshold for glucose reabsorption can be measured as the lowest plasma glucose level that correlates with the first detectable appearance of urine glucose. These data revealed significant variations among patients with type 2 diabetes mellitus (T2DM), and there was a significant negative correlation between the renal threshold for glucose reabsorption and HbA1c levels following treatment with the sodium-glucose co-transporter 2 (SGLT2) inhibitor ipragliflozin. Recently approved SGLT inhibitors may not show the same efficacy in patients with T1DM as in those with T2DM unless the renal threshold for glucose reabsorption shows similar levels between the two groups. SGLT2 inhibitors improve plasma glucose control in patients with T2DM by reducing glucose reabsorption via the epithelial cells of the proximal tubule. Methods The renal threshold for glucose reabsorption was defined as the minimum blood glucose concentration that results in the presence of measurable glycosuria in at least 12 measurements. Results The renal threshold for glucose reabsorption in patients with T2DM [n = 64; 201.8 ± 33.6 (range 121–268) mg/dL] was significantly higher than that in patients with T1DM [n = 33; 171.0 ± 33.0 (range 76–259) mg/dL; p = 0.00022]. Conclusion The renal threshold for glucose reabsorption in patients with T1DM was near the normal range and significantly lower than that in patients with T2DM. The efficacy of the SGLT2 inhibitor was better in patients with a higher renal threshold for glucose reabsorption. Thus, these results indicate that it is advisable to estimate the renal threshold for glucose reabsorption prior to initiating SGLT2 inhibitor therapy in patients with T1DM.

Effect of Intravitreal Anti-Vascular Growth Factor Agents With or Without Macular Photocoagulation on Diabetic Macular Edema: A Systematic Review and Meta-Analysis Abstract Introduction Diabetes is a common cause of new sight loss in populations world-wide, and diabetic macular edema (DME) is a major cause of visual deficits in the diabetic populations of developed countries. We have performed a meta-analysis to evaluate whether combined treatment with anti-vascular endothelial growth factor (VEGF) injections and macular photocoagulation (MPC) is more efficacious than primary monotherapy with anti-VEGF injections in patients with DME. Methods We systematically searched the PubMed and Web of Science databases for studies providing sufficient information for a comparison of pre- and post-treatment of central macular thickness (CMT) and best-corrected visual acuity (BCVA) between two groups of patients with DME given interventional therapies (monotherapy with an anti-VEGF agent vs. combination therapy with an anti-VEGF agent and MPC) before January 2019. A meta-analysis was performed to summarize the results of the studies included in the systematic review. Results The results of our meta-analysis indicated that post-treatment CMT was significantly lower at 3 months in DME patients receiving combination therapy with bevacizumab, a humanized anti-VEGF antibody, and MPC than in those receiving monotherapy with bevacizumab. The results also showed that post-treatment CMT was lower in DME patients given ranibizumab, an anti-VEGF agent, in combination with MPC at 6, 9 and 12 months than in those treated with ranibizumab alone. However, no significant differences were found in post-treatment BCVA at 1, 3, 6, 9 and 12 months between DME patients receiving combination therapy with an anti-VEGF agent (bevacizumab or ranibizumab) and MPC and those receiving monotherapy with an anti-VEGF agent. Conclusion In conclusion, the results of our meta-analysis demonstrate a transiently synergistic effect of MPC on CMT when this treatment is combined with anti-VEGF agents, whereas no similar synergistic effect could be detected on the BCVA. A relatively longer follow-up was essential to be able to evaluate the long-term existence of this synergistic effect.

Short-Term Versus Long-Term Adverse Cardiovascular Outcomes Post Percutaneous Coronary Intervention in Patients with Insulin-Treated Type 2 Diabetes Mellitus: A Simple Meta-Analysis Abstract Introduction Type 2 diabetes mellitus (T2DM) is a major health issue, especially in patients with coexisting coronary artery disease (CAD). Patients with insulin-treated T2DM (ITDM) have worse outcomes than those with non-insulin-treated T2DM. Very few studies have compared short-term to long-term adverse cardiovascular outcomes following percutaneous coronary intervention (PCI) in patients on insulin therapy. Therefore, in this meta-analysis, we systematically compared short-term to long-term adverse cardiovascular outcomes in a population of patients with ITDM following PCI. Methods We searched for English-language publications focusing on PCI in patients with ITDM using specific search terms/phrases. All the participants accepted for inclusion in this meta-analysis were treated with a drug-eluting stent. Post-intervention adverse cardiovascular outcomes observed during short-term and long-term follow-up periods were assessed and compared. Statistical analysis was carried out using the popular RevMan 5.3 software. Odd ratios (OR) with 95% confidence intervals (CI) were calculated. Results Six studies comprising 1568 participants with ITDM in total were included in this simple meta-analysis. Patient enrollment periods varied but enrollment occurred during the years 1993–2012. When a fixed-effects statistical model was used, post-PCI adverse cardiovascular outcomes—such as major adverse cardiac events (MACEs) (OR 3.33, 95% CI 2.64–4.21; P = 0.00001), all-cause mortality (OR 5.73, 95% CI 3.37–9.73; P = 0.00001), myocardial infarction (MI) (OR 1.47, 95% CI 1.05–2.07; P = 0.02), and repeated revascularization (OR 4.78, 95% CI 3.29–6.94; P = 0.00001)—were found to be significantly more likely during the long-term follow-up period. A similar result was observed with a random-effects statistical model. Conclusion Adverse cardiovascular outcomes post PCI were significantly more likely during the long-term follow-up period than during the short-term follow-up period in these patients with T2DM on insulin therapy. This hypothesis requires confirmation via new comparative trials that consider short-term and long-term follow-up periods.

Effects of Diabetes Numeracy on Glycemic Control and Diabetes Self-Management Behaviors in Patients on Insulin Pump Therapy Abstract Introduction Diabetes numeracy (DN) skills are crucial in patients on insulin pump therapy. Little evidence exists regarding DN in this patient population. Methods This exploratory, observational, cross-sectional study assessed the DN levels of patients on insulin pump therapy and potential relationships with glycemic control and self-management behaviors. Seventy-two patients on insulin pump therapy were recruited from one specialty endocrinology clinic. Subjects completed validated tools to measure DN [Diabetes Numeracy Test (DNT-15)] and self-management behaviors [Diabetes Self-Management Questionnaire (DSMQ)]. A general diabetes questionnaire assessed socioeconomic information and self-efficacy. Additional self-management behaviors and glycemic control data were collected from patients' medical records. Patients were categorized into two groups based on DNT-15 scores to explore potential relationships between DN scores and patient characteristics, glycemic control, and self-management behaviors. Results Average age was 52 ± 15 years, glycosylated hemoglobin (A1C) was 7.7% ± 1.2% (61 mmol/mol), duration of diabetes was 28 ± 15 years, and duration of pump use was 3.4 ± 1.3 years. The average DNT-15 score was 87.5% ± 18%. Forty-three participants (60%) scored ≥ 90% and 29 participants (40%) scored < 90%. Eighteen percent were unable to calculate the carbohydrate content from a nutrition label. Participants with lower DNT-15 scores had higher A1C levels (8.0% vs. 7.5%, p = 0.04), were older (58.3 vs. 47.7, p = 0.003), were more likely to describe their diabetes self-care as poor (p = 0.04), and were less confident in using their pump features (p = 0.02) than those with higher DNT-15 scores. Conclusion Many patients on insulin pump therapy have deficiencies with DN which may be associated with older age and higher A1C levels.

Retrospective Database Analysis Evaluating the Clinical Outcomes of Changing Treatment of People with Type 2 Diabetes Mellitus (T2DM) from Other DPP-4 Inhibitor Therapy to Alogliptin in a Primary Care Setting Abstract Introduction Although some differences between individual dipeptidyl peptidase-4 (DPP-4) inhibitors may exist, the National Institute for Health and Clinical Excellence (NICE) have recommended that 'prescribers should be encouraged to select the individual DPP-4 inhibitor with the lowest acquisition cost available to them, where all other factors are equal'. We aimed to determine whether or not 'within class' switching to alogliptin, the DPP-4 inhibitor with lowest acquisition cost, is a clinically appropriate strategy. Methods This study evaluated people with type 2 diabetes taking DPP-4 inhibitor therapy in addition to at least one other diabetes therapy. Primary care records were reviewed from six clinical commissioning groups (CCGs). For people who had been switched from other DPP-4 inhibitors to alogliptin, an assessment of the impact of switch on both absolute haemoglobin A1c (HbA1c) levels and on HbA1c trajectory was undertaken. Persistence on alogliptin and the need for therapy intensification was also assessed. Results Overall, 865 people with diabetes met the eligibility criteria for the study. There was no significant difference between pre- and post-switch mean HbA1c level [8.44% (SD 1.52%) vs 8.42% (1.62%), p = 0.6]. Similarly, for patients where there was sufficient data to assess the impact of switching on HbA1c trajectory (n = 319) minimal impact was identified (actual HbA1c at 3 months 8.33% vs projected 8.31%). The majority of people with diabetes (80.76%) remained on alogliptin treatment at 6 months and only 4.54% required additional diabetes therapies. Switching to alogliptin resulted in a median saving of £7.24 per patient-month. Conclusion Switching United Kingdom (UK) primary care patients from other DPP-4 inhibitors to alogliptin did not result in a statistically significant or clinically meaningful change in HbA1c level and few required the addition of further diabetes therapies, suggesting that therapy change or intensification was not considered necessary in most patients who were switched to alogliptin. Trial Registration ENCePP clinical trial registration number EUPAS29153. Funding Takeda UK Ltd.

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00306932607174,00302841026182,alsfakia@gmail.com