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Patients with type 2 diabetes at high cardiovascular risk received either once-weekly semaglutide, a glucagon-like peptide 1 analogue, or placebo. The rate of a first occurrence of cardiovascular death, nonfatal MI, or nonfatal stroke was significantly lower with semaglutide. Cardiovascular disease is the leading cause of death and complications in patients with type 2 diabetes. 1 Recently, trials evaluating a sodium–glucose cotransporter 2 inhibitor (empagliflozin) and a glucagon-like peptide 1 (GLP-1) analogue (liraglutide) have shown improved cardiovascular outcomes in patients with type 2 diabetes who were at high risk for cardiovascular events. 2 , 3 Semaglutide, a GLP-1 analogue with an extended half-life of approximately 1 week (which permits once-weekly subcutaneous administration), 4 is currently in development but not yet approved for the treatment of type 2 diabetes. Regulatory guidance specifies the need to establish the cardiovascular safety of new therapies for type . . .

As compared with standard glucose control in patients with type 2 diabetes, intensive glucose control in the ADVANCE trial reduced the risk of nephropathy but not the risk of macrovascular events. There was no significant difference between the two groups in overall mortality. These findings, along with those of the ACCORD trial, raise complex questions about the role of intensive glucose control in type 2 diabetes. As compared with standard glucose control in patients with type 2 diabetes, intensive glucose control reduced the risk of nephropathy but not the risk of macrovascular events. There was no significant difference between the two groups in overall mortality. The prevalence of diabetes is increasing worldwide, and most people with diabetes will die or be disabled as a consequence of vascular complications. 1 , 2 Prospective studies have shown continuous associations of blood glucose and glycated hemoglobin levels with the risks of major vascular events. 3 , 4 However, previous randomized trials evaluating the effects of glycemic control in patients with diabetes have provided inconsistent evidence of effects on vascular disease. 5 – 11 Nevertheless, current guidelines recommend a target glycated hemoglobin level of 7.0% or less for most patients with diabetes. 12 – 14 The Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release . . .

Among adolescents with type 2 diabetes, there is limited information regarding incidence and progression of hypertension and microalbuminuria. Hypertension and microalbuminuria assessments made during the TODAY clinical trial were analyzed for effect of treatment, glycemic control, sex, and race/ethnicity. A cohort of 699 adolescents, 10-17 years of age, <2 years duration of type 2 diabetes, BMI ≥ 85%, HbA1c ≤ 8% on metformin therapy, controlled blood pressure (BP), and calculated creatinine clearance >70 mL/min, were randomized to metformin, metformin plus rosiglitazone, or metformin plus intensive lifestyle intervention. Primary study outcome was loss of glycemic control for 6 months or sustained metabolic decompensation requiring insulin. Hypertension and microalbuminuria were managed aggressively with standardized therapy to maintain BP <130/80 or <95th percentile for age, sex, and height and microalbuminuria <30 μg/mg. In this cohort, 319 (45.6%) reached primary study outcome, and 11.6% were hypertensive at baseline and 33.8% by end of study (average follow-up 3.9 years). Male sex and higher BMI significantly increased the risk for hypertension. Microalbuminuria was found in 6.3% at baseline and rose to 16.6% by end of study. Diagnosis of microalbuminuria was not significantly different between treatment arms, sex, or race/ethnicity, but higher levels of HbA1c were significantly related to risk of developing microalbuminuria. Prevalence of hypertension and microalbuminuria increased over time among adolescents with type 2 diabetes regardless of diabetes treatment. The greatest risk for hypertension was male sex and higher BMI. The risk for microalbuminuria was more closely related to glycemic control.

This observational study examined the association between modifiable lifestyle and social factors on the incidence and progression of early chronic kidney disease (CKD) among those with type 2 diabetes. All 6972 people from the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) with diabetes but without macroalbuminuria were studied. CKD progression was defined as decline in GFR of more than 5% per year, progression to end-stage renal disease, microalbuminuria, or macroalbuminuria at 5.5 years. Lifestyle/social factors included tobacco and alcohol use, physical activity, stress, financial worries, the size of the social network and education. Adjustments were made for known risks such as age, diabetes duration, GFR, albuminuria, gender, body mass index, blood pressure, fasting plasma glucose, and angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers use. Competing risk of death was considered. At study end, 31% developed CKD and 15% had died. The social network score (SNS) was a significant independent risk factor of CKD and death, reducing the risk by 11 and 22% when comparing the third to the first tertile of the SNS (odds ratios of CKD 0.89 and death 0.78). Education showed a significant association with CKD but stress and financial worries did not. Those with moderate alcohol consumption had a significantly decreased CKD risk compared with nonusers. Regular physical activity significantly decreased the risk of CKD. Thus, lifestyle is a determinant of kidney health in people at high cardiovascular risk with diabetes.

OBJECTIVE: This multicenter study examined the impact of albumin excretion rate (AER) on the course of estimated glomerular filtration rate (eGFR) and the incidence of sustained eGFR <60 ml/min/1.73 m² in type 1 diabetes up to year 14 of the Epidemiology of Diabetes Interventions and Complications (EDIC) study (mean duration of 19 years in the Diabetes Control and Complications Trial [DCCT]/EDIC). RESEARCH DESIGN AND METHODS: Urinary albumin measurements from 4-h urine collections were obtained from participants annually during the DCCT and every other year during the EDIC study, and serum creatinine was measured annually in both the DCCT and EDIC study. GFR was estimated from serum creatinine using the abbreviated Modification of Diet in Renal Disease equation. RESULTS: A total of 89 of 1,439 subjects developed an eGFR <60 ml/min/1.73 m² (stage 3 chronic kidney disease on two or more successive occasions (sustained) during the DCCT/EDIC study (cumulative incidence 11.4%). Of these, 20 (24%) had AER <30 mg/24 h at all prior evaluations, 14 (16%) had developed microalbuminuria (AER 30-300 mg/24 h) before they reached stage 3 chronic kidney disease, and 54 (61%) had macroalbuminuria (AER >300 mg/24 h) before they reached stage 3 chronic kidney disease. Macroalbuminuria is associated with a markedly increased rate of fall in eGFR (5.7%/year vs. 1.2%/year with AER <30 mg/24 h, P < 0.0001) and risk of eGFR <60 ml/min/1.73 m² (adjusted hazard ratio 15.3, P < 0.0001), whereas microalbuminuria had weaker and less consistent effects on eGFR. CONCLUSIONS: Macroalbuminuria was a strong predictor of eGFR loss and risk of developing sustained eGFR <60 ml/min/1.73 m². However, screening with AER alone would have missed 24% of cases of sustained impaired eGFR.

Persons with type 1 diabetes are at high risk for kidney disease. In this study, intensive diabetes therapy administered early in the course of type 1 diabetes reduced the long-term risk of an impaired glomerular filtration rate. An impaired glomerular filtration rate (GFR) is the final common pathway of diabetic kidney disease. Once the GFR is impaired, cardiovascular disease events and progression to end-stage renal disease occur at unacceptably high rates, even with proven medical management. 1 – 3 This underscores the need for the primary prevention of impaired GFR in persons with diabetes. The Diabetes Control and Complications Trial (DCCT) and the observational study that followed it, the Epidemiology of Diabetes Interventions and Complications (EDIC) study, showed that intensive diabetes therapy that lowered glycated hemoglobin levels reduced the risk of microalbuminuria and macroalbuminuria among persons with type 1 . . .

Background Individuals with diabetic kidney disease (DKD) often suffer cardiac and kidney events. We sought to develop an accurate means by which to stratify risk in DKD. Methods Clinical variables and biomarkers were evaluated for their ability to predict the adjudicated primary composite endpoint of CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) by 3 years. Using machine learning techniques, a parsimonious risk algorithm was developed. Results The final model included age, body-mass index, systolic blood pressure, and concentrations of N-terminal pro-B type natriuretic peptide, high sensitivity cardiac troponin T, insulin-like growth factor binding protein-7 and growth differentiation factor-15. The model had an in-sample C-statistic of 0.80 (95% CI = 0.77–0.83; P  < 0.001). Dividing results into low, medium and high risk categories, for each increase in level the hazard ratio increased by 3.43 (95% CI = 2.72–4.32; P  < 0.001). Low risk scores had negative predictive value of 94%, while high risk scores had positive predictive value of 58%. Higher values were associated with shorter time to event (log rank P  < 0.001). Rising values at 1 year predicted higher risk for subsequent DKD events. Canagliflozin treatment reduced score results by 1 year with consistent event reduction across risk levels. Accuracy of the risk model was validated in separate cohorts from CREDENCE and the generally lower risk Canagliflozin Cardiovascular Assessment Study. Conclusions We describe a validated risk algorithm that accurately predicts cardio-kidney outcomes across a broad range of baseline risk. Trial registration CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation; NCT02065791) and CANVAS (Canagliflozin Cardiovascular Assessment Study; NCT01032629/NCT01989754). Graphical abstract Persons with diabetic kidney disease (DKD) are at riskfor progressive kidney failure and cardiovascular (CV) events. Using datafrom the CREDENCE trial of patients with type 2 diabetes and DKD,machine learning techniques were applied to create a highly accuratealgorithm to predict progressive DKD and adverse CV outcomes. Thealgorithm was validated both within an internal CREDENCE cohort andexternally in the CANVAS trial.

BackgroundWe conducted exploratory analyses to identify distinct trajectories of estimated glomerular filtration rate (eGFR) and their relationship with hyperfiltration, subsequent rapid eGFR decline, and albuminuria in participants with youth-onset type 2 diabetes enrolled in the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) study.MethodsAnnual serum creatinine, cystatin C, urine albumin, and creatinine measurements were obtained from 377 participants followed for ≥ 10 years. Albuminuria and eGFR were calculated. Hyperfiltration peak is the greatest eGFR inflection point during follow-up. Latent class modeling was applied to identify distinct eGFR trajectories.ResultsAt baseline, participants’ mean age was 14 years, type 2 diabetes duration was 6 months, mean HbA1c was 6%, and mean eGFR was 120 ml/min/1.73 m2. Five eGFR trajectories associated with different rates of albuminuria were identified, including a “progressive increasing eGFR” group (10%), three “stable eGFR” groups with varying starting mean eGFR, and an “eGFR steady decline” group (1%). Participants who exhibited the greatest peak eGFR also had the highest levels of elevated albuminuria at year 10. This group membership was characterized by a greater proportion of female and Hispanic participants.ConclusionsDistinct eGFR trajectories that associate with albuminuria risk were identified, with the eGFR trajectory characterized by increasing eGFR over time associating with the highest level of albuminuria. These descriptive data support the current recommendations to estimate GFR annually in young persons with type 2 diabetes and provide insight into eGFR-related factors which may contribute to predictive risk strategies for kidney disease therapies in youth with type 2 diabetes.Trial registrationClinicalTrials.gov Identifier: NCT00081328, date registered 2002.

The Japan Diabetes Complications Study (JDCS), a nation-wide, multicenter, prospective study of patients with type 2 diabetes, reported that hemoglobin A1c (HbA1c), systolic blood pressure, and smoking were risk factors for the onset of macroalbuminuria. This study explored the risk factors for glomerular filtration rate (GFR) decline in the JDCS patients. We examined the 1407 JDCS patients (667 women, mean age 59years, 974 normoalbuminuria, 433 microalbuminuria) whose urinary albumin-to-creatinine ratio (UACR) and estimated GFR (eGFR) were determined at baseline with an 8-year follow-up. We divided all the patients into four groups according to baseline eGFR: G1 (120≤eGFR), G2 (90≤eGFR<120), G3 (60≤eGFR<90), G4 (eGFR<60). The eGFRs in groups G1 and G2 decreased at follow-up compared to those at the baseline. The risk of annual eGFR decline rate≥3ml/min/1.73m2 (rapid decliners) increased as the baseline eGFR increased. Advanced age, high HbA1c, and UACR, or diabetic retinopathy at baseline were risk factors for the rapid decliners. Especially the G1 group had a significant risk for the rapid decliners. The frequency of the patients with GFR<60ml/min/1.73m2 at the follow-up amounted to 31.1% in the rapid decliners, which was higher than 12% in the non-rapid decliners. In normo- and microalbuminuric patients with type 2 diabetes, extra careful attention should be paid to patients with eGFR ≥120ml/min/1.73m2 to detect cases with rapidly decreased GFR under the normal range.

BackgroundPatients with diabetic kidney disease (DKD) often struggle with blood pressure control. In team-based models of care, pharmacists and primary care providers (PCPs) play important roles in supporting patients’ blood pressure management.ObjectiveTo describe whether PCPs’ acceptance of pharmacists’ recommendations impacts systolic blood pressure (SBP) at 36 months.DesignAn observational analysis of a subset of participants randomized to the intervention arm of the Simultaneous risk factor control using Telehealth to slOw Progression of Diabetic Kidney Disease (STOP-DKD) study.ParticipantsSTOP-DKD participants for whom (1) the pharmacist made at least one recommendation to the PCP; (2) there were available data regarding the PCP’s corresponding action; and (3) there were SBP measurements at baseline and 36 months.InterventionParticipants received monthly telephone calls with a pharmacist addressing health behaviors and medication management. Pharmacists made medication-related recommendations to PCPs.Main MeasuresWe fit an unadjusted generalized linear mixed model to assess the association between the number of pharmacists’ recommendations for DKD and blood pressure management and PCPs’ acceptance of such recommendations. We used a linear regression model to evaluate the association between PCP acceptance and SBP at 36 months, adjusted for baseline SBP.Key ResultsPharmacists made 176 treatment recommendations (among 59 participants), of which 107 (61%) were accepted by PCPs. SBP significantly declined by an average of 10.5 mmHg (p < 0.01) among 47 of 59 participants who had valid measurements at baseline and 36 months. There was a significant association between the number of pharmacist recommendations and the odds of PCP acceptance (OR 1.19; 95%CI 1.00, 1.42; p < 0.05), but no association between the number of accepted recommendations and SBP.ConclusionsPharmacists provided actionable medication-related recommendations. We identified a significant decline in SBP at 36 months, but this reduction was not associated with recommendation acceptance.Trial RegistrationNCT01829256