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Greater Glycemic Burden Is Associated with Further Poorer Glycemic Control in Newly-Diagnosed Type 2 Diabetes Mellitus Patients.
Wen, WL, Huang, HC, Lin, HC, Lo, WC, Chen, SC, Lee, MY
Nutrients. 2022;(2)
Abstract
Aims: hyperglycemia impairs pancreatic β-cell function instantly, also known as glucotoxicity. It is unknown whether this insult is temporary or sustained, and little real-world evidence needs to reflect the relationship between hyperglycemic burden, per se, and glycemic durability. Materials and Methods: a retrospective observational cohort study was conducted to recruit newly-diagnosed type 2 diabetes mellitus (T2DM) patients. Durability was defined as the episode from first glycated hemoglobin A1c (HbA1c) below 7.0% to where it exceed 8.0% (with treatment failure) or where study ended (without treatment failure). Glycemic burden was defined with the area above a burden value line (HbA1c = 6.5%) but under the HbA1c curve (AUC), and it was then divided into two compartments with the demarcation timepoint once HbA1c was treated below or equal to 7.0%; the former AUC' represented the initial insult; the latter AUC" represented the residual part. Multivariable regression models assessed factors associated with durability in whole participants and two distinct subgroups: patients with baseline HbA1c > 7.0% or ≤7.0%. Results: 1048 eligible participants were recruited and analyzed: 291 patients with treatment failure (durability 26.8 ± 21.1 months); 757 patients without treatment failure (durability 45.1 ± 31.8 months). Besides age, glycemic burden was the only constant determinant in the two subgroups. AUC' or AUC" increased treatment failure, respectively, in baseline HbA1c > 7.0% or ≤7.0% subgroup [per 1%/90 days hazard ratio (95% confidence interval): 1.026 (1.018-1.034) and 1.128 (1.016-1.253)]. Other determinants include baseline HbA1c, initial OAD, and education level. Conclusions: in patients with newly-diagnosed T2DM, glycemic durability was negatively associated with greater glycemic burden.
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Duodenal mucosal resurfacing with a GLP-1 receptor agonist increases postprandial unconjugated bile acids in patients with insulin-dependent type 2 diabetes.
Meiring, S, Meessen, ECE, van Baar, ACG, Holleman, F, Nieuwdorp, M, Olde Damink, SW, Schaap, FG, Vaz, FM, Groen, AK, Soeters, MR, et al
American journal of physiology. Endocrinology and metabolism. 2022;(2):E132-E140
Abstract
Duodenal mucosal resurfacing (DMR) is a new endoscopic ablation technique aimed at improving glycemia and metabolic control in patients with type 2 diabetes mellitus (T2DM). DMR appears to improve insulin resistance, which is the root cause of T2DM, but its mechanism of action is largely unknown. Bile acids function as intestinal signaling molecules in glucose and energy metabolism via the activation of farnesoid X receptor and secondary signaling [e.g., via fibroblast growth factor 19 (FGF19)], and are linked to metabolic health. We investigated the effect of DMR and glucagon-like peptide-1 (GLP-1) on postprandial bile acid responses in 16 patients with insulin-dependent T2DM, using mixed meal tests performed at the baseline and 6 mo after the DMR procedure. The combination treatment allowed discontinuation of insulin treatment in 11/16 (69%) of patients while improving glycemic and metabolic health. We found increased postprandial unconjugated bile acid responses (all P < 0.05), an overall increased secondary bile acid response (P = 0.036) and a higher 12α-hydroxylated:non-12α-hydroxylated ratio (P < 0.001). Total bile acid concentrations were unaffected by the intervention. Postprandial FGF19 and 7-α-hydroxy-4-cholesten-3-one (C4) concentrations decreased postintervention (both P < 0.01). Our study demonstrates that DMR with GLP-1 modulates the postprandial bile acid response. The alterations in postprandial bile acid responses may be the result of changes in the microbiome, ileal bile acid uptake and improved insulin sensitivity. Controlled studies are needed to elucidate the mechanism linking the combination treatment to metabolic health and bile acids.NEW & NOTEWORTHY Glycemic and metabolic improvements are seen in patients with type 2 diabetes after replacing their insulin therapy with DMR and GLP-1. These changes are accompanied by changes in postprandial bile acid concentrations: increased unconjugated and secondary bile acids.
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Low fasting glucose-to-estimated average glucose ratio was associated with superior response to insulin degludec/aspart compared with basal insulin in patients with type 2 diabetes.
Jang, HN, Yang, YS, Oh, TJ, Koo, BK, Lee, SO, Park, KS, Jang, HC, Jung, HS
Journal of diabetes investigation. 2022;(1):85-93
Abstract
AIMS/INTRODUCTION The benefits of once-daily insulin degludec/aspart (IDegAsp) compared with basal insulin in type 2 diabetes patients have not been established. MATERIALS AND METHODS This was a retrospective observational study. From a basal insulin cohort from three referral hospitals, patients were enrolled who initiated once-daily IDegAsp. A control group maintaining basal insulin was selected by propensity score matching. Glycated hemoglobin (HbA1c) changes over a period of 6 months and associated clinical factors were evaluated. RESULTS The IDegAsp group and the control group comprised of 87 patients, respectively. Baseline HbA1c was comparable between the two groups (8.7 ± 0.9 vs 8.6 ± 0.9%, mean and standard deviation). After 6 months with matched insulin doses, HbA1c in the IDegAsp group was lower than that in the control group (8.1 ± 1.0 vs 8.4 ± 1.1%, P = 0.029). Among baseline variables, fasting plasma glucose (FPG) and fasting C-peptide in the IDegAsp were lower than that in the control (FPG 124.2 ± 38.4 vs 148.0 ± 50.6 mg/dL, P < 0.001). Considering that the lower FPG despite the comparable HbA1c could be related with the efficacy of IDegAsp, subgroup analysis was carried out according to a ratio of FPG-to-estimated average glucose, which is calculated from HbA1c. When compared with each control group, the superiority of IDegAsp in the reduction of HbA1c was significant only in the patients with a lower FPG-to-estimated average glucose ratio (0.49 ± 0.09), but not in those with a higher FPG-to-estimated average glucose ratio (0.79 ± 0.20). CONCLUSIONS We observed that IDegAsp was more effective than basal insulin in patients with an FPG lower than predicted by HbA1c, which might be related with insulin deficiency and postprandial hyperglycemia in patients on basal insulin therapy.
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Suppression of serum lipid transfer proteins involved in high-density lipoprotein cholesterol metabolism by intensive insulin therapy in the first year of type 1 diabetes mellitus: Prospective InLipoDiab1 study.
Cieluch, A, Uruska, A, Nowicki, M, Wysocka, E, Grzelka-Woźniak, A, Flotyńska, J, Niedźwiecki, P, Zozulińska-Ziółkiewicz, D
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2021;(4):1219-1226
Abstract
BACKGROUND AND AIMS Cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP) are crucial proteins in reverse cholesterol transport. There are insufficient data on regulating these proteins by insulin therapy in type 1 diabetes mellitus (T1DM). We aimed to assess prospectively the impact of insulin therapy initiation on transfer proteins serum levels in adults with newly diagnosed T1DM. METHODS AND RESULTS 57 adults with newly diagnosed T1DM were enrolled in the InLipoDiab1 Study. All participants were treated with subcutaneous insulin in the model of intensive insulin therapy since the diagnosis of diabetes. Serum PLTP and CETP concentrations were measured at diagnosis, after three weeks, six months, and after one year of insulin treatment, using the immunoenzymatic method ELISA. A significant decrease in PLTP and CETP concentrations were demonstrated during twelve months of insulin therapy in newly diagnosed T1DM. The dynamics of changes in the level of these proteins varied depending on the occurrence of remission after a year of the disease. In the group without remission, a significant decrease in PLTP and CETP levels appeared after six months of follow-up. The remission group was characterized by a decrease in proteins concentration only after one year of treatment. In the non-remission group, significant negative correlations were found between the daily dose of insulin and levels of PLTP and CETP. CONCLUSION Exogenous insulin is an inhibitor of lipid transfer proteins involved in high-density lipoprotein cholesterol metabolism in the first year of treatment.
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Prescribing Trend of Inappropriate Medications in Outpatient Clinics for Older Adults With Heart Failure in the United States: NAMCS 2012 to 2016.
Kobayashi, M, Kwak, MJ, Aguilar, D, Goyal, P, Holmes, HM, Deshmukh, AA, Aparasu, RR
The American journal of cardiology. 2021;:168
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Real-world study on the effectiveness and safety of basal insulin IDegLira in type 2 diabetic patients previously treated with multi-injective insulin therapy.
Persano, M, Nollino, L, Sambataro, M, Rigato, M, Negro, I, Marchetto, S, Paccagnella, A
European review for medical and pharmacological sciences. 2021;(2):923-931
Abstract
OBJECTIVE Achieving glycemic target is paramount to control diabetes mellitus (DM) and reduce micro-vascular and macro-vascular complications. Despite the mostly recent-developed drugs, most patients still show an above desired glycated hemoglobin (HbA1c) level due to DM complex pathophysiology, therapeutic and dietary compliance and clinical inertia in introducing or intensifying insulin therapy. To support the promising results of clinical trials on the effectiveness and safety of the degludec/liraglutide combination (IDegLira) in type 2 DM patients with C-peptide values >1 ng/ml who were previously treated with basal-bolus multiple daily-dose insulin injections. PATIENTS AND METHODS This observational, prospective and non-randomized trial enrolled type 2 DM patients referred to our outpatient clinic between January 2019 and December 2019, who were shifted from multiple daily-dose insulin injection therapy to degludec/liraglutide combination as per the physician's decision. The main assessment was HbA1c variation at 6 months from baseline. Secondary assessments included variation in fasting glycemia, routine anthropometric assessments, blood chemistry, blood pressure and patients' quality of life (measured by the Diabetes Treatment Satisfaction Questionnaire [DTSQ]), from baseline to 6 months. RESULTS HbA1c (8.4 vs. 7.4%; p<0.0001) and body weight (94.1 vs. 93 kg; p<0.0001) were significantly lower after 6 months for patients on the degludec/liraglutide combination. A similar trend was observed in fasting glycemia levels (159 vs. 125 mg/dl; p<0.0001). An improved glycemic control was achieved with degludec/liraglutide despite a reduction in total daily insulin units (42 U at 6 months vs. 22 U at baseline; p<0.0001). In addition, higher scores in the DTSQ were registered after 6 months on degludec/liraglutide (mean score: 27 vs. 20; p<0.0001). The combination therapy also proved more convenient than basal-bolus therapy in terms of costs, with an average per-patient cost difference of €-0.41±0.59/die (p<0.0001). CONCLUSIONS These real-world findings show that degludec/liraglutide seems to be more effective than basal-bolus insulin in achieving glycemic control, allowing cost sustainability and improving patient satisfaction.
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Effect of newer antihyperglycemic drugs on liver steatosis indices in patients with diabetes and obesity.
Carretero Gómez, J, Ena, J, Seguí Ripoll, JM, Carrasco-Sánchez, FJ, Gómez Huelgas, R, Casas Rojo, JM, Suárez Tembra, M, Carabantes Rueda, JJ, Arévalo Lorido, JC
Current medical research and opinion. 2021;(11):1867-1873
Abstract
AIM: To assess the efficacy of sodium-glucose cotransporter-2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptors agonist (GLP-1RA) therapy on liver steatosis measured by fatty liver index (FLI) and hepatic steatosis index (HSI) at 26 weeks in outpatients with diabetes and obesity. METHODS Observational, prospective, multicenter study. Patients with steatosis determined by FLI (values <30 rule out and >60 indicate steatosis) and HIS (values <30 rule out and >36 indicate steatosis) who received combination therapy were included. Patients were stratified into three groups according to the sequential order of treatment. We used robust statistical methods. RESULTS In our final report we included 174 patients (58.6% males), mean age 61.9 (10) years. Baseline body mass index, waist circumference and weight were 36.5 (6.8) kg/m2, 117.5 (15.1) cm and 99.4 (20.5) kg, respectively. One hundred percent of patients had altered biomarkers of fatty liver scores (FLI 96 [13] and HSI 49.2 [8.5]). At 26 weeks, significant reductions in FLI (-4.5 [95% CI 3.5-5.9] p < .001) and HSI (-2.4 [95% CI 1.6-3.2] p < .001) were found in the total sample and pre-specified treatment and FLI cut-off point subgroups. CONCLUSION Our results show a beneficial effect of the combination of GLP-1RAs plus SGLT2is on liver steatosis that goes beyond glucose control, and it is related mainly to weight loss, a decline in biomarkers and reductions in abdominal circumference. For many patients, early detection is essential to improving outcomes in NAFLD and could allow us to select the most efficient treatment options.
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Prescribing in Type 2 Diabetes Patients With and Without Cardiovascular Disease History: A Descriptive Analysis in the UK CPRD.
Farmer, RE, Beard, I, Raza, SI, Gollop, ND, Patel, N, Tebboth, A, McGovern, AP, Kanumilli, N, Ternouth, A
Clinical therapeutics. 2021;(2):320-335
Abstract
PURPOSE Some classes of glucose-lowering medications, including sodium-glucose co-transporter 2 inhibitors (SGLT2is) and glucagon-like peptide 1-receptor agonists (GLP1-RAs) have cardio-protective benefit, but it is unclear whether this influences prescribing in the United Kingdom (UK). This study aims to describe class-level prescribing in adults with type 2 diabetes mellitus (T2DM) by cardiovascular disease (CVD) history using the Clinical Practice Research Datalink (CPRD). METHODS Four cross-sections of people with T2DM aged 18-90 and registered with their general practice for >1 year on 1st January 2017 (n = 166,012), 1st January 2018 (n = 155,290), 1st January 2019 (n = 152,602) and 31st December 2019 (n = 143,373) were identified. Age-standardised proportions for class use through time were calculated separately in those with and without CVD history and by total number of medications prescribed (one, two, three, four+). An analysis by UK country was also performed. FINDINGS Around 31% of patients had CVD history at each cross-section. Metformin was the most common treatment (>70% of those with and without CVD had prescriptions across all treatment lines). Overall use of SGLT2is and GLP1-RAs was low, with slightly less use in patients with CVD (SGLT2i: 9.8% and 13.8% in those with and without CVD respectively; GLP1-RA: 4.3% and 4.9%, December 2019). Use of SGLT2is as part of dual therapy was low but rose throughout the study. In January 2017, estimated use was 8.0% (95% CI 6.9-9.1%) and 8.9% (8.6-9.3%) in those with and without CVD. By December 2019 this reached 18.3% (17.0-19.5%) and 21.2% (20.6-21.7%) for those with and without CVD respectively. SGLT2i use as triple therapy increased: 22.7% (21.0-24.4%) and 25.9% (25.2-26.6%) in January 2017 to 41.3% (39.5-43.0%) and 45.5% (44.7-46.3%) in December 2019. GLP1-RA use also increased, but observed usage remained lower than SGLT2 inhibitors. Insulin use remained stable throughout, with higher use observed in those with CVD (16% vs 9.7% Dec 2019). Time trends in England, Wales, Scotland and Northern Ireland were similar, although class prevalence varied. IMPLICATIONS Although use of SGLT2is and GLP1-RAs has increased, overall usage remains low with slightly lower use in those with CVD history, suggesting there is opportunity to optimise use of these medicines in T2DM patients to manage CVD risk. Insulin use was substantially more prevalent in those with CVD despite no evidence of CVD benefit. Further investigation of factors influencing this finding may highlight strategies to improve patient access to the most appropriate treatments, including those with evidence of cardiovascular benefit.
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Characteristics of patients with emergency attendance for severe hypoglycemia and hyperglycemia in a general hospital in Japan.
Endo, K, Itoh, T, Tanno, M, Ohno, K, Hotta, H, Kato, N, Matsumoto, T, Ooiwa, H, Kubo, H, Miki, T
Medicine. 2021;(25):e26505
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Abstract
Despite advances in treatments for diabetes mellitus (DM), severe acute glycemic crises still occur. In this study, the characteristics of patients who were transported to an emergency department due to acute glycemic crises were investigated.We enrolled patients who were transported to our hospital by ambulance due to hypoglycemia or hyperglycemia during the period from January 2015 to December 2019. Initial glucose levels below 70 mg/dL and above 250 mg/dL were defined as hypoglycemia and hyperglycemia, respectively.In the 5-year period, 16,910 patients were transported to our hospital by ambulance. Of those patients, 87 patients (0.51%) were diagnosed with hypoglycemia, 26 patients (0.15%) were diagnosed with hyperglycemia and 1 patient was diagnosed with lactic acidosis. Compared to patients with hypoglycemia, blood urea nitrogen, serum potassium and hemoglobin levels were higher in patients with hyperglycemia. Systolic blood pressure was lower and pulse rate was higher in patients with hyperglycemia, possibly reflecting dehydration in hyperglycemia. Patients with hyperglycemia were younger (63 vs 70 years old, median), more likely to be hospitalized (92.3% vs 23.0%) with poorer prognosis (23.1% vs 4.6%) than those with hypoglycemia. In 64 DM patients with hypoglycemia, 34 patients were treated with insulin and 24 patients were treated with sulfonylurea or glinide, and their medication was often inappropriate. Excessive alcohol intake and malnutrition were the main causes of hypoglycemia in 23 non-DM patients. The main reasons for hyperglycemia were interrupted treatment, forgetting insulin injection and infection.To avoid acute glycemic crises, optimization of anti-DM therapy and education of patients are needed.
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Metformin use is associated with a reduced risk of mortality in patients with diabetes hospitalised for COVID-19.
Lalau, JD, Al-Salameh, A, Hadjadj, S, Goronflot, T, Wiernsperger, N, Pichelin, M, Allix, I, Amadou, C, Bourron, O, Duriez, T, et al
Diabetes & metabolism. 2021;(5):101216
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AIMS: Metformin exerts anti-inflammatory and immunosuppressive effects. We addressed the impact of prior metformin use on prognosis in patients with type 2 diabetes hospitalised for COVID-19. METHODS CORONADO is a nationwide observational study that included patients with diabetes hospitalised for COVID-19 between March 10 and April 10, 2020 in 68 French centres. The primary outcome combined tracheal intubation and/or death within 7 days of admission. A Kaplan-Meier survival curve was reported for death up to day 28. The association between metformin use and outcomes was then estimated in a logistic regression analysis after applying a propensity score inverse probability of treatment weighting approach. RESULTS Among the 2449 patients included, 1496 were metformin users and 953 were not. Compared with non-users, metformin users were younger with a lower prevalence of diabetic complications, but had more severe features of COVID-19 on admission. The primary endpoint occurred in 28.0% of metformin users (vs 29.0% in non-users, P = 0.6134) on day 7 and in 32.6% (vs 38.7%, P = 0.0023) on day 28. The mortality rate was lower in metformin users on day 7 (8.2 vs 16.1%, P < 0.0001) and on day 28 (16.0 vs 28.6%, P < 0.0001). After propensity score weighting was applied, the odds ratios for primary outcome and death (OR [95%CI], metformin users vs non-users) were 0.838 [0.649-1.082] and 0.688 [0.470-1.007] on day 7, then 0.783 [0.615-0.996] and 0.710 [0.537-0.938] on day 28, respectively. CONCLUSION Metformin use appeared to be associated with a lower risk of death in patients with diabetes hospitalised for COVID-19.