-
1.
Incidence and predictors of chronic kidney disease in type-II diabetes mellitus patients attending at the Amhara region referral hospitals, Ethiopia: A follow-up study.
Ahmed, MA, Ferede, YM, Takele, WW
PloS one. 2022;(1):e0263138
Abstract
BACKGROUND Chronic kidney disease (CKD) is the severest form of kidney disease characterized by poor filtration. The magnitude of chronic kidney disease is trending upward in the last few years linked with the rapidly escalating cases of non-communicable chronic diseases, particularly diabetes mellitus. However, little is known about when this problem may occur, the incidence as well as predictors of chronic kidney disease among type-II diabetes mellitus patients. Thus, this study was conducted to determine the incidence, time to the occurrence, and predictors of chronic kidney disease in type-II diabetic patients attending the Amhara region referral hospitals, Ethiopia. METHODS A retrospective follow-up study was conducted involving 415 participants with type-II diabetes mellitus that enrolled in the chronic follow-up from 2012 to 2017. Multivariable shared Frailty Weibull (Gamma) survival model was employed considering the hospitals as a clustering variable. Model fitness was checked by both the Akaike information criteria (AIC) and log-likelihood. Factors having a p-value of ≤0.2 in the bi-variable analysis were considered to enter the multivariable model. Variables that had a p-value of <0.05 with its corresponding 95% confidence level were deemed to be significant predictors of chronic kidney disease. RESULTS The overall cumulative incidence of chronic kidney disease was 10.8% [95%; CI: 7.7-14.0%] with a median occurrence time of 5 years. The annual incidence rate was 193/10,000 [95%; CI: 144.28-258.78]. Having cardiovascular disease/s [AHR = 3.82; 95%CI: 1.4470-10.1023] and hypercholesterolemia [AHR = 3.31; 95% CI: 1.3323-8.2703] were predictors of chronic kidney disease. CONCLUSION One out of every ten diabetic patients experienced chronic kidney disease. The median time to develop chronic kidney disease was five years. Hypercholesterolemia and cardiovascular diseases have escalated the hazard of developing CKD. Thus, health promotion and education of diabetic patients to optimize cholesterol levels and prevent cardiovascular disease is recommended to limit the occurrence of this life-threatening disease.
-
2.
Duodenal-Jejunal Bypass Liner for the management of Type 2 Diabetes Mellitus and Obesity: A Multicenter Randomized Controlled Trial.
Ruban, A, Miras, AD, Glaysher, MA, Goldstone, AP, Prechtl, CG, Johnson, N, Chhina, N, Al-Najim, W, Aldhwayan, M, Klimowska-Nassar, N, et al
Annals of surgery. 2022;(3):440-447
-
-
Free full text
-
Abstract
OBJECTIVE The aim of this study was to examine the clinical efficacy and safety of the duodenal-jejunal bypass liner (DJBL) while in situ for 12 months and for 12 months after explantation. SUMMARY BACKGROUND DATA This is the largest randomized controlled trial (RCT) of the DJBL, a medical device used for the treatment of people with type 2 diabetes mellitus (T2DM) and obesity. Endoscopic interventions have been developed as potential alternatives to those not eligible or fearful of the risks of metabolic surgery. METHODS In this multicenter open-label RCT, 170 adults with inadequately controlled T2DM and obesity were randomized to intensive medical care with or without the DJBL. Primary outcome was the percentage of participants achieving a glycated hemoglobin reduction of ≥20% at 12 months. Secondary outcomes included weight loss and cardiometabolic risk factors at 12 and 24 months. RESULTS There were no significant differences in the percentage of patients achieving the primary outcome between both groups at 12 months [DJBL 54.6% (n = 30) vs control 55.2% (n = 32); odds ratio (OR) 0.93, 95% confidence interval (CI): 0.44-2.0; P = 0.85]. Twenty-four percent (n = 16) patients achieved ≥15% weight loss in the DJBL group compared to 4% (n = 2) in the controls at 12 months (OR 8.3, 95% CI: 1.8-39; P = .007). The DJBL group experienced superior reductions in systolic blood pressure, serum cholesterol, and alanine transaminase at 12 months. There were more adverse events in the DJBL group. CONCLUSIONS The addition of the DJBL to intensive medical care was associated with superior weight loss, improvements in cardiometabolic risk factors, and fatty liver disease markers, but not glycemia, only while the device was in situ. The benefits of the devices need to be balanced against the higher rate of adverse events when making clinical decisions. TRIAL REGISTRATION ISRCTN30845205. isrctn.org; Efficacy and Mechanism Evaluation Programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership reference 12/10/04.
-
3.
Type 2 diabetes prevention diet and the risk of pancreatic cancer: A large prospective multicenter study.
Huang, Y, Liu, F, Chen, AM, Yang, PF, Peng, Y, Gong, JP, Li, Z, Zhong, GC
Clinical nutrition (Edinburgh, Scotland). 2021;(11):5595-5604
Abstract
BACKGROUND & AIMS Type 2 diabetes prevention diet confers a lower risk of type 2 diabetes, which exhibits overlapping mechanisms with pancreatic cancer. We performed a prospective study to examine whether adherence to this dietary pattern is associated with a reduced risk of pancreatic cancer. METHODS A population-based cohort of 101,729 American adults was identified. A dietary diabetes risk reduction score was computed to reflect adherence to this dietary pattern, with higher scores representing greater adherence. Cox regression was used to compute hazard ratios (HRs) for pancreatic cancer incidence. Prespecified subgroup analyses were used to identify the potential effect modifiers. RESULTS After an average follow-up of 8.86 years (900,871.67 person-years), a total of 402 pancreatic cancer cases were observed. In the fully adjusted model, participants in the highest quartile of dietary diabetes risk reduction score were found to have a reduced risk of pancreatic cancer compared with those in the lowest quartile [HRquartiles 4versus1: 0.62; 95% confidence interval (CI): 0.44, 0.86; Ptrend = 0.004], which remained in a series of sensitivity analyses. Subgroup analyses further found that this favorable association was more pronounced in current or former smokers (HRquartiles 4versus1: 0.48; 95% CI: 0.30, 0.77) than in never smokers (HRquartiles 4versus1: 0.71; 95% CI: 0.44, 1.15), although the interaction test did not reach statistical significance (Pinteraction = 0.095). CONCLUSIONS Greater adherence to type 2 diabetes prevention diet is associated with a lower risk of pancreatic cancer in this US population. More studies are needed to confirm our findings.
-
4.
Screening cardiovascular risk factors of diabetes patients in the primary diabetes clinics.
An, L, Wang, Y, Cao, C, Chen, T, Zhang, Y, Chen, L, Ren, S, Tang, M, Ma, F, Li, X, et al
Medicine. 2021;(30):e26722
-
-
Free full text
-
Abstract
To evaluate the atherosclerotic cardiovascular diseases (ASCVD) risk factors in type 2 diabetes patients from the primary diabetes clinics for further comprehensive intervention in China.A cross-sectional study was conducted in 5 primary diabetes chain hospitals in Beijing, Lanzhou, Harbin, Chengdu, and Taiyuan in continuous patients with type 2 diabetes from March 2016 to December 2019. The data collected at the first visit were analyzed, and proportions of patients reached the targets (glycosylated hemoglobin [HbA1c] < 7%, blood pressure < 130/80 mm Hg, and low-density lipoprotein cholesterol [LDL-C] < 2.6mmol/l) were calculated. The clinical characteristics and the associated factors with achievement in HbA1c, blood pressure, and LDL-C targets were analyzed.A total of 20,412 participants, including 11,353 men (55.6%), with an average age of (59.4 ± 10.4) years were enrolled. Nearly 95% diabetes had one or more ASCVD risk factors other than hyperglycemia. The control rates of HbA1c, blood pressure, and LDL-C were 26.5%, 27.8%, and 42.6%, respectively. Only 4.1% patients achieved all 3 targets. Nearly 95% patients had one or more ASCVD risk factors other than hyperglyciemia. Diabetes duration, family history, and overweight/obesity were associated with the number of aggregated ASCVD risk factors. The patients with older age, no overweight/obesity, not smoking, less ASCVD risk factors, and having special diabetes care insurance (Chengdu) were associated with a higher control rates.To deal with poor control status, global management of ASCVD risk factors, weight loss, and smoking cessation must be emphasized in the primary diabetes care settings. Special diabetes care insurance should be advocated.Current ClinicalTrial.gov protocol ID NCT03707379. Date of Registration: October 16, 2018. https://clinicaltrials.gov.
-
5.
Different Effects of Lifestyle Intervention in High- and Low-Risk Prediabetes: Results of the Randomized Controlled Prediabetes Lifestyle Intervention Study (PLIS).
Fritsche, A, Wagner, R, Heni, M, Kantartzis, K, Machann, J, Schick, F, Lehmann, R, Peter, A, Dannecker, C, Fritsche, L, et al
Diabetes. 2021;(12):2785-2795
Abstract
Lifestyle intervention (LI) can prevent type 2 diabetes, but response to LI varies depending on risk subphenotypes. We tested whether individuals with prediabetes with low risk (LR) benefit from conventional LI and individuals with high risk (HR) benefit from an intensification of LI in a multicenter randomized controlled intervention over 12 months with 2 years' follow-up. A total of 1,105 individuals with prediabetes based on American Diabetes Association glucose criteria were stratified into an HR or LR phenotype based on previously described thresholds of insulin secretion, insulin sensitivity, and liver fat content. LR individuals were randomly assigned to conventional LI according to the Diabetes Prevention Program (DPP) protocol or control (1:1) and HR individuals to conventional or intensified LI with doubling of required exercise (1:1). A total of 908 (82%) participants completed the study. In HR individuals, the difference between conventional and intensified LI in postchallenge glucose change was -0.29 mmol/L [95% CI -0.54; -0.04], P = 0.025. Liver fat (-1.34 percentage points [95% CI -2.17; -0.50], P = 0.002) and cardiovascular risk (-1.82 percentage points [95% CI -3.13; -0.50], P = 0.007) underwent larger reductions with intensified than with conventional LI. During a follow-up of 3 years, intensified compared with conventional LI had a higher probability of normalizing glucose tolerance (P = 0.008). In conclusion, it is possible in HR individuals with prediabetes to improve glycemic and cardiometabolic outcomes by intensification of LI. Individualized, risk phenotype-based LI may be beneficial for the prevention of diabetes.
-
6.
Effect of Empagliflozin on Left Ventricular Volumes in Patients With Type 2 Diabetes, or Prediabetes, and Heart Failure With Reduced Ejection Fraction (SUGAR-DM-HF).
Lee, MMY, Brooksbank, KJM, Wetherall, K, Mangion, K, Roditi, G, Campbell, RT, Berry, C, Chong, V, Coyle, L, Docherty, KF, et al
Circulation. 2021;(6):516-525
-
-
Free full text
-
Abstract
BACKGROUND Sodium-glucose cotransporter 2 inhibitors reduce the risk of heart failure hospitalization and cardiovascular death in patients with heart failure and reduced ejection fraction (HFrEF). However, their effects on cardiac structure and function in HFrEF are uncertain. METHODS We designed a multicenter, randomized, double-blind, placebo-controlled trial (the SUGAR-DM-HF trial [Studies of Empagliflozin and Its Cardiovascular, Renal and Metabolic Effects in Patients With Diabetes Mellitus, or Prediabetes, and Heart Failure]) to investigate the cardiac effects of empagliflozin in patients in New York Heart Association functional class II to IV with a left ventricular (LV) ejection fraction ≤40% and type 2 diabetes or prediabetes. Patients were randomly assigned 1:1 to empagliflozin 10 mg once daily or placebo, stratified by age (<65 and ≥65 years) and glycemic status (diabetes or prediabetes). The coprimary outcomes were change from baseline to 36 weeks in LV end-systolic volume indexed to body surface area and LV global longitudinal strain both measured using cardiovascular magnetic resonance. Secondary efficacy outcomes included other cardiovascular magnetic resonance measures (LV end-diastolic volume index, LV ejection fraction), diuretic intensification, symptoms (Kansas City Cardiomyopathy Questionnaire Total Symptom Score, 6-minute walk distance, B-lines on lung ultrasound, and biomarkers (including N-terminal pro-B-type natriuretic peptide). RESULTS From April 2018 to August 2019, 105 patients were randomly assigned: mean age 68.7 (SD, 11.1) years, 77 (73.3%) male, 82 (78.1%) diabetes and 23 (21.9%) prediabetes, mean LV ejection fraction 32.5% (9.8%), and 81 (77.1%) New York Heart Association II and 24 (22.9%) New York Heart Association III. Patients received standard treatment for HFrEF. In comparison with placebo, empagliflozin reduced LV end-systolic volume index by 6.0 (95% CI, -10.8 to -1.2) mL/m2 (P=0.015). There was no difference in LV global longitudinal strain. Empagliflozin reduced LV end-diastolic volume index by 8.2 (95% CI, -13.7 to -2.6) mL/m2 (P=0.0042) and reduced N-terminal pro-B-type natriuretic peptide by 28% (2%-47%), P=0.038. There were no between-group differences in other cardiovascular magnetic resonance measures, diuretic intensification, Kansas City Cardiomyopathy Questionnaire Total Symptom Score, 6-minute walk distance, or B-lines. CONCLUSIONS The sodium-glucose cotransporter 2 inhibitor empagliflozin reduced LV volumes in patients with HFrEF and type 2 diabetes or prediabetes. Favorable reverse LV remodeling may be a mechanism by which sodium-glucose cotransporter 2 inhibitors reduce heart failure hospitalization and mortality in HFrEF. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03485092.
-
7.
Metabolites and diabetes remission after weight loss.
Kwee, LC, Ilkayeva, O, Muehlbauer, MJ, Bihlmeyer, N, Wolfe, B, Purnell, JQ, Xavier Pi-Sunyer, F, Chen, H, Bahnson, J, Newgard, CB, et al
Nutrition & diabetes. 2021;(1):10
Abstract
There is marked heterogeneity in the response to weight loss interventions with regards to weight loss amount and metabolic improvement. We sought to identify biomarkers predictive of type 2 diabetes remission and amount of weight loss in individuals with severe obesity enrolled in the Longitudinal Assessment of Bariatric Surgery (LABS) and the Look AHEAD (Action for Health in Diabetes) studies. Targeted mass spectrometry-based profiling of 135 metabolites was performed in pre-intervention blood samples using a nested design for diabetes remission over five years (n = 93 LABS, n = 80 Look AHEAD; n = 87 remitters), and for extremes of weight loss at five years (n = 151 LABS; n = 75 with high weight loss). Principal components analysis (PCA) was used for dimensionality reduction, with PCA-derived metabolite factors tested for association with both diabetes remission and weight loss. Metabolic markers were tested for incremental improvement to clinical models, including the DiaRem score. Two metabolite factors were associated with diabetes remission: one primarily composed of branched chain amino acids (BCAA) and tyrosine (odds ratio (95% confidence interval) [OR (95% CI)] = 1.4 [1.0-1.9], p = 0.045), and one with betaine and choline (OR [95% CI] = 0.7 [0.5-0.9], p = 0.02).These results were not significant after adjustment for multiple tests. Inclusion of these two factors in clinical models yielded modest improvements in model fit and performance: in a constructed clinical model, the C-statistic improved from 0.87 to 0.90 (p = 0.02), while the net reclassification index showed improvement in prediction compared to the DiaRem score (NRI = 0.26, p = 0.0013). No metabolite factors associated with weight loss at five years. Baseline levels of metabolites in the BCAA and trimethylamine-N-oxide (TMAO)-microbiome-related pathways are independently and incrementally associated with sustained diabetes remission after weight loss interventions in individuals with severe obesity. These metabolites could serve as clinically useful biomarkers to identify individuals who will benefit the most from weight loss interventions.
-
8.
Phase III, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of teneligliptin monotherapy in Chinese patients with type 2 diabetes mellitus inadequately controlled with diet and exercise.
Ji, L, Ma, J, Lu, W, Liu, J, Zeng, J, Yang, J, Li, W, Zhang, X, Xiao, X, Takayanagi, G, et al
Journal of diabetes investigation. 2021;(4):537-545
Abstract
AIMS/INTRODUCTION Although the efficacy of teneligliptin, a highly selective dipeptidyl peptidase-4 inhibitor, has been amply studied for the treatment of type 2 diabetes, no clinical trials of teneligliptin have been carried out in China. We evaluated the efficacy and safety of teneligliptin monotherapy compared with a placebo in Chinese patients with type 2 diabetes mellitus inadequately controlled with diet and exercise. MATERIALS AND METHODS This multicenter, randomized, double-blind, placebo-controlled, parallel-group study, carried out at 42 sites, enrolled type 2 diabetes patients with glycosylated hemoglobin 7.0 to <10.0% and fasting blood glucose <270 mg/dL. Patients were randomly assigned, in a 1:1 ratio, to treatment with 20 mg teneligliptin or a placebo (n = 127, each) administered orally once daily before breakfast for 24 weeks. Change in glycosylated hemoglobin from baseline to week 24 was the primary efficacy end-point. Safety was assessed by the incidence of adverse events and adverse drug reactions. RESULTS The least square mean (LSM) change in glycosylated hemoglobin from baseline to week 24 was -0.95% with teneligliptin versus -0.14% with a placebo, yielding an LSM difference (teneligliptin vs placebo) of -0.80% (P < 0.0001). For the secondary end-point, from baseline to week 24, the LSM change in fasting blood glucose was -21.9 mg/dL with teneligliptin versus -1.4 mg/dL with a placebo, yielding an LSM difference (teneligliptin vs placebo) of -20.5 mg/dL (P < 0.0001). The adverse event and adverse drug reaction incidence rates, including hypoglycemia, were similar in both groups. CONCLUSIONS At 24 weeks, teneligliptin was generally well tolerated and effective in Chinese patients with type 2 diabetes mellitus inadequately controlled with diet and exercise.
-
9.
Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, multicentre, phase 3 trial.
Del Prato, S, Kahn, SE, Pavo, I, Weerakkody, GJ, Yang, Z, Doupis, J, Aizenberg, D, Wynne, AG, Riesmeyer, JS, Heine, RJ, et al
Lancet (London, England). 2021;(10313):1811-1824
Abstract
BACKGROUND We aimed to assess efficacy and safety, with a special focus on cardiovascular safety, of the novel dual GIP and GLP-1 receptor agonist tirzepatide versus insulin glargine in adults with type 2 diabetes and high cardiovascular risk inadequately controlled on oral glucose-lowering medications. METHODS This open-label, parallel-group, phase 3 study was done in 187 sites in 14 countries on five continents. Eligible participants, aged 18 years or older, had type 2 diabetes treated with any combination of metformin, sulfonylurea, or sodium-glucose co-transporter-2 inhibitor, a baseline glycated haemoglobin (HbA1c) of 7·5-10·5% (58-91 mmol/mol), body-mass index of 25 kg/m2 or greater, and established cardiovascular disease or a high risk of cardiovascular events. Participants were randomly assigned (1:1:1:3) via an interactive web-response system to subcutaneous injection of either once-per-week tirzepatide (5 mg, 10 mg, or 15 mg) or glargine (100 U/mL), titrated to reach fasting blood glucose of less than 100 mg/dL. The primary endpoint was non-inferiority (0·3% non-inferiority boundary) of tirzepatide 10 mg or 15 mg, or both, versus glargine in HbA1c change from baseline to 52 weeks. All participants were treated for at least 52 weeks, with treatment continued for a maximum of 104 weeks or until study completion to collect and adjudicate major adverse cardiovascular events (MACE). Safety measures were assessed over the full study period. This study was registered with ClinicalTrials.gov, NCT03730662. FINDINGS Patients were recruited between Nov 20, 2018, and Dec 30, 2019. 3045 participants were screened, with 2002 participants randomly assigned to tirzepatide or glargine. 1995 received at least one dose of tirzepatide 5 mg (n=329, 17%), 10 mg (n=328, 16%), or 15 mg (n=338, 17%), or glargine (n=1000, 50%), and were included in the modified intention-to-treat population. At 52 weeks, mean HbA1c changes with tirzepatide were -2·43% (SD 0·05) with 10 mg and -2·58% (0·05) with 15 mg, versus -1·44% (0·03) with glargine. The estimated treatment difference versus glargine was -0·99% (multiplicity adjusted 97·5% CI -1·13 to -0·86) for tirzepatide 10 mg and -1·14% (-1·28 to -1·00) for 15 mg, and the non-inferiority margin of 0·3% was met for both doses. Nausea (12-23%), diarrhoea (13-22%), decreased appetite (9-11%), and vomiting (5-9%) were more frequent with tirzepatide than glargine (nausea 2%, diarrhoea 4%, decreased appetite <1%, and vomiting 2%, respectively); most cases were mild to moderate and occurred during the dose-escalation phase. The percentage of participants with hypoglycaemia (glucose <54 mg/dL or severe) was lower with tirzepatide (6-9%) versus glargine (19%), particularly in participants not on sulfonylureas (tirzepatide 1-3% vs glargine 16%). Adjudicated MACE-4 events (cardiovascular death, myocardial infarction, stroke, hospitalisation for unstable angina) occurred in 109 participants and were not increased on tirzepatide compared with glargine (hazard ratio 0·74, 95% CI 0·51-1·08). 60 deaths (n=25 [3%] tirzepatide; n=35 [4%] glargine) occurred during the study. INTERPRETATION In people with type 2 diabetes and elevated cardiovascular risk, tirzepatide, compared with glargine, demonstrated greater and clinically meaningful HbA1c reduction with a lower incidence of hypoglycaemia at week 52. Tirzepatide treatment was not associated with excess cardiovascular risk. FUNDING Eli Lilly and Company.
-
10.
Improved time in range and postprandial hyperglycemia with canagliflozin in combination with teneligliptin: Secondary analyses of the CALMER study.
Cho, KY, Nomoto, H, Nakamura, A, Kawata, S, Sugawara, H, Takeuchi, J, Nagai, S, Omori, K, Tsuchida, K, Miya, A, et al
Journal of diabetes investigation. 2021;(8):1417-1424
Abstract
AIMS/INTRODUCTION We recently reported the beneficial effect of the combination of sodium-glucose cotransporter 2 inhibitor and dipeptidyl peptidase-4 inhibitor on daily glycemic variability in patients with type 2 diabetes mellitus. Additional favorable effects of combination therapy were explored in this secondary analysis. MATERIALS AND METHODS The CALMER study was a multicenter, open-label, prospective, randomized, parallel-group comparison trial for type 2 diabetes mellitus involving continuous glucose monitoring under meal tolerance tests. Patients were randomly assigned to switch from teneligliptin to canagliflozin (SWITCH group) or to add canagliflozin to teneligliptin (COMB group). The continuous glucose monitoring metrics, including time in target range, were investigated. RESULTS All 99 participants (mean age 62.3 years; mean glycated hemoglobin 7.4%) completed the trial. The time in target range was increased in the COMB group (71.2-82.7%, P < 0.001). The extent of the reduction in time above target range was significantly larger in the COMB group compared with the SWITCH group (-14.8% vs -7.5%, P < 0.01). Area under the curve values for glucose at 120 min after all meal tolerance tests were significantly decreased in the COMB group compared with the SWITCH group (P < 0.05). CONCLUSIONS Sodium-glucose cotransporter 2 inhibitor combined with dipeptidyl peptidase-4 inhibitor improved the quality of glycemic variability and reduced postprandial hyperglycemia compared with each monotherapy.