Brain Structure Among Middle-aged and Older Adults With Long-standing T1DM

It was observed a high percentage of SGA births among women with type 2 diabetes and chronic hypertension and/or nephropathy who were treated with metformin.

source: Diabetes Care

Summary

[Posted 26/Jul/2022]

AUDIENCE: Endocrinology, Neurology, Family Medicine

KEY FINDINGS: Middle-aged and older adults with T1DM showed brain volume loss and increased vascular injury in comparison with control subjects without diabetes, equivalent to 4-9 years of brain aging.

BACKGROUND: Individuals with type 1 diabetes mellitus (T1DM) are living to ages when neuropathological changes are increasingly evident. Hypothesized that middle-aged and older adults with long-standing T1DM will show abnormal brain structure in comparison with control subjects without diabetes.

DETAILS: MRI was used to compare brain structure among 416 T1DM participants in the Epidemiology of Diabetes Interventions and Complications (EDIC) study with that of 99 demographically similar control subjects without diabetes at 26 U.S. and Canadian sites. Assessments included total brain (TBV) (primary outcome), gray matter (GMV), white matter (WMV), ventricle, and white matter hyperintensity (WMH) volumes and total white matter mean fractional anisotropy (FA). Biomedical assessments included HbA1c and lipid levels, blood pressure, and cognitive assessments of memory and psychomotor and mental efficiency (PME). Among EDIC participants, HbA1c, severe hypoglycemia history, and vascular complications were measured longitudinally. Mean age of EDIC participants and control subjects was 60 years. T1DM participants showed significantly smaller TBV (least squares mean ± SE 1,206 ± 1.7 vs. 1,229 ± 3.5 cm3, P < 0.0001), GMV, and WMV and greater ventricle and WMH volumes but no differences in total white matter mean FA versus control subjects. Structural MRI measures in T1DM were equivalent to those of control subjects who were 4-9 years older. Lower PME scores were associated with altered brain structure on all MRI measures in T1DM participants.

Our Most Popular Resources

Copyright © American Diabetes Association. All rights reserved.

Source: Jacobson, A. M., Braffett, B. H., Erus, G., et al. (2022). Brain Structure Among Middle-aged and Older Adults With Long-standing Type 1 Diabetes in the DCCT/EDIC Study. Diabetes Care. 2022; 45(8): 1779-1787. Published: July 26, 2022. DOI: 10.2337/dc21-2438.



Phase II Trial of Cabozantinib Plus Nivolumab in Patients With Non-Clear-Cell Renal Cell Carcinoma and Genomic Correlates

Cabozantinib plus nivolumab showed promising efficacy in most non-clear-cell RCC variants tested in this trial, particularly those with prominent papillary features, whereas treatment effects were limited in chromophobe RCC.

source: J Clinical Oncology

Summary

[Posted 26/Jul/2022]

AUDIENCE: Oncology, Nephrology

KEY FINDINGS: Cabozantinib plus nivolumab showed promising efficacy in most non–clear-cell RCC variants tested in this trial, particularly those with prominent papillary features, whereas treatment effects were limited in chromophobe RCC. Genomic findings in non–clear-cell RCC variants warrant further study as predictors of response.

BACKGROUND: Objective of this trial is to assess the efficacy and safety of cabozantinib plus nivolumab in a phase II trial in patients with non–clear-cell renal cell carcinoma (RCC).

DETAILS: Patients had advanced non–clear-cell renal carcinoma who underwent 0-1 prior systemic therapies excluding prior immune checkpoint inhibitors. Patients received cabozantinib 40 mg once daily plus nivolumab 240 mg once every 2 weeks or 480 mg once every 4 weeks. Cohort 1 enrolled patients with papillary, unclassified, or translocation-associated RCC; cohort 2 enrolled patients with chromophobe RCC. The primary end point was objective response rate (ORR) by RECIST 1.1; secondary end points included progression-free survival, overall survival, and safety. Next-generation sequencing results were correlated with response. A total of 47 patients were treated with a median follow-up of 13.1 months. Objective response rate for cohort 1 (n= 40) was 47.5% (95% CI, 31.5 to 63.9), with median progression-free survival of 12.5 months (95% CI, 6.3 to 16.4) and median overall survival of 28 months (95% CI, 16.3 to not evaluable). In cohort 2 (n= 7), no responses were observed; one patient had stable disease > 1 year. Grade 3/4 treatment-related adverse events were observed in 32% treated patients. Cabozantinib and nivolumab were discontinued because of toxicity in 13% and 17% of patients, respectively. Common mutations included NF2 and FH in cohort 1 and TP53 and PTEN in cohort 2. Objective responses were seen in 10/12 patients with either NF2 or FH mutations.

Our Most Popular Resources

Copyright © American Society of Clinical Oncology. All rights reserved.

Source: Lee, C., Voss, M. H., Carlo, M. I., et al. (2022). Phase II Trial of Cabozantinib Plus Nivolumab in Patients With Non–Clear-Cell Renal Cell Carcinoma and Genomic Correlates. Journal of Clinical Oncology. 2021; 40(21): 2333-2341. Published: July 20, 2022. DOI: 0.1200/JCO.21.01944.



Determinants of Small for Gestational Age in Women with Type 2 Diabetes in Pregnancy

It was observed a high percentage of SGA births among women with type 2 diabetes and chronic hypertension and/or nephropathy who were treated with metformin.

source: Diabetes Care

Summary

Who Should Receive Metformin?

[Posted 18/Jul/2022]

AUDIENCE: Endocrinology, Ob/Gyn

KEY FINDINGS: In this study, it was observed a high percentage of SGA births among women with type 2 diabetes and chronic hypertension and/or nephropathy who were treated with metformin. Therefore, with the aim of reducing SGA, it is reasonable to be cautious in our use of metformin in those with type 2 diabetes and chronic hypertension or nephropathy in pregnancy.

BACKGROUND: In the MiTy (Metformin in Women With Type 2 Diabetes in Pregnancy) randomized trial of metformin versus placebo added to insulin, found numerous benefits with metformin but identified an increased proportion of infants who were small for gestational age (SGA). Study was aimed to determine the predictors of SGA in order to individualize care.

DETAILS: Using logistic regression, we assessed baseline maternal characteristics as predictors of SGA. Compared maternal/neonatal outcomes in SGA metformin and placebo groups using the t, x2, or Fisher exact test, as appropriate. Among the 502 mothers, 460 infants were eligible for this study. There were 30 infants with SGA in the metformin group (12.9%) and 15 in the placebo group (6.6%) (P = 0.026). Among SGA infants, those in the metformin group were delivered significantly later than those in the placebo group (37.2 vs. 35.3 weeks; P = 0.038). In adjusted analyses, presence of a comorbidity (chronic hypertension and/or nephropathy) (odds ratio [OR] 3.05; 95% CI 1.58-5.81) and metformin use (OR 2.26; 95% CI 1.19-4.74) were predictive of SGA. The absolute risk of SGA was much higher in women receiving metformin with comorbidity compared with women receiving metformin without comorbidity (25.0% vs. 9.8%).

Our Most Popular Resources

Copyright © American Diabetes Association. All rights reserved.

Source: Feig, D. S., Zinman, B., Asztalos, E., et al. (2022). Determinants of Small for Gestational Age in Women With Type 2 Diabetes in Pregnancy: Who Should Receive Metformin? Diabetes Care . 2022;45(7):1532-1539. Published: July 6, 2022. DOI: 10.2337/dc22-0013.



Dapagliflozin Impairs the Suppression of Endogenous Glucose Production in T2D Following Oral Glucose

Findings provide novel evidence that the increase in EGP induced by SGLT2i is present during an oral glucose load.

source: Diabetes Care

Summary

[Posted 20/Jun/2022]

AUDIENCE: Endocrinology

KEY FINDINGS: These findings provide novel evidence that the increase in EGP induced by SGLT2i is present during an oral glucose load. The fact that stimulation of EGP occurs despite elevated plasma insulin and glucagon suggests that additional factors must be involved.

BACKGROUND: Purpose of this trial is to examine the effect of SGLT2 inhibitors (SGLT2i) on endogenous glucose production (EGP) in patients with type 2 diabetes after an oral glucose load.

DETAILS: Forty-eight patients with type 2 diabetes received an 8-h [3-3H]-glucose infusion (protocol I) to assess EGP response to: 1) dapagliflozin (DAPA), 10 mg; 2) exenatide (EXE), 5 μg s.c.; 3) DAPA/EXE; and 4) placebo (PCB). After 2 weeks (protocol II), patients were restudied with a 5-h double-tracer (i.v. [3-3H]-glucose and oral [1-14C]-glucose) oral glucose tolerance test (OGTT) preceded by PCB, DAPA, EXE, or DAPA/EXE. Protocol I: EGP decreased (P < 0.01) with PCB (2.16 ± 0.15 to 1.57 ± 0.08 mg/kg/min) and EXE (2.13 ± 0.16 to 1.58 ± 0.03) and remained unchanged (P = NS) with DAPA (2.04 ± 0.17 vs. 1.94 ± 0.18) and DAPA/EXE (2.13 ± 0.10 vs. 2.09 ± 0.03). During OGTT, EGP decreased (P < 0.01) with PCB (2.30 ± 0.05 to. 1.45 ± 0.06 mg/kg/min) and EXE (2.53 ± 0.08 to 1.36 ± 0.06); with DAPA (2.20 ± 0.04 vs. 1.71 ± 0.07) and DAPA/EXE (2.48 ± 0.05 vs. 1.64 ± 0.07), the decrease in EGP was attenuated (both P < 0.05). During OGTT, the insulin/glucagon (INS/GCN) ratio increased in PCB (0.26 ± 0.03 vs. 0.71 ± 0.06 μU/mL per pg/mL), whereas in DAPA (0.26 ± 0.02 to 0.50 ± 0.04), the increase was blunted (P < 0.05). In EXE, INS/GCN increased significantly (0.32 ± 0.03 to 1.31 ± 0.08) and was attenuated in DAPA/EXE (0.32 ± 0.03 vs. 0.78 ± 0.08) (P < 0.01).

Our Most Popular Resources

Copyright © American Diabetes Association. All rights reserved.

Source: Alatrach, M., Agyin, C., Solis-Herrera, C., et al. (2022). Dapagliflozin Impairs the Suppression of Endogenous Glucose Production in Type 2 Diabetes Following Oral Glucose. Diabetes Care . 2022; 45(6): 1372-1380. Published: June 6, 2022. DOI: 10.2337/dc21-1798.



SGLT2 Inhibitors and the Risk of AKI

Among older adults with type 2 diabetes, initiation of an SGLT2 inhibitor was associated with a reduced risk of AKI compared with initiation of a DPP-4 inhibitor or a GLP-1RA.

source: Am J Kidney Dis

Summary

SGLT2 Inhibitors and the Risk of Acute Kidney Injury in Older Adults With Type 2 Diabetes

[Posted 30/May/2022]

AUDIENCE: Nephrology, Internal Medicine

KEY FINDINGS: Among older adults with type 2 diabetes, initiation of an SGLT2 inhibitor was associated with a reduced risk of AKI compared with initiation of a DPP-4 inhibitor or a GLP-1RA.

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been found to have many benefits for patients with type 2 diabetes. However, whether SGLT2 inhibitors increase the risk of acute kidney injury (AKI) remains unknown. We examined the association of AKI hospitalization with prior initiation of an SGLT2 inhibitor compared with initiation of a dipeptidyl peptidase 4 (DPP-4) inhibitor or a glucagon-like peptide 1 receptor agonist (GLP-1RA) among older adults with type 2 diabetes in routine practice.

DETAILS: Older adults aged at least 66 years with type 2 diabetes enrolled in Medicare fee-for-service and who were new users of SGLT2 inhibitor, DPP-4 inhibitor, or GLP-1RA agents in the interval from March 2013 to December 2017. New users of SGLT2 inhibitors were matched at a 1:1 ratio to new users of DPP-4 inhibitors or GLP-1RAs using propensity scores in 2 pairwise comparisons. Cox proportional hazards regression models generated hazard ratios (HRs) with 95% CIs in propensity score–matched groups. Totals of 68,130 and 71,477 new users of SGLT2 inhibitors were matched to new users of DPP-4 inhibitors or GLP-1RAs, respectively. Overall, the mean age of study participants was 72 years. The risk of AKI was lower in the SGLT2 inhibitor group than in the DPP-4 inhibitor group (HR, 0.71 [95% CI, 0.65-0.76]) or the GLP-1RA group (HR, 0.81 [95% CI, 0.75-0.87]).

Our Most Popular Resources

Copyright © Elsevier Ltd. All rights reserved.

Source: Zhuo, M., Paik, J. M., Wexler, D. J., et al. (2022). SGLT2 Inhibitors and the Risk of Acute Kidney Injury in Older Adults With Type 2 Diabetes. Am J Kidney Dis. 2022; 79(6): 858-867. Published: June, 2022. DOI: 10.1053/j.ajkd.2021.09.015.



Offloading Devices For Neuropathic Foot Ulcers In Adult Persons With T1D Or T2D

There is limited evidence from RCTs to suggest that F-TCC has a shorter ulcer healing time compared with RCW among adults with diabetic NPFUs.

source: BMJ DRC

Summary

A Rapid Review With Meta-Analysis And Trial Sequential Analysis Of Randomized Controlled Trials

[Posted 13/May/2022]

AUDIENCE: Endocrinology

KEY FINDINGS: There is limited evidence from RCTs to suggest that F-TCC has a shorter ulcer healing time compared with RCW among adults with diabetic NPFUs. Properly designed and conducted RCTs are still required for a stronger evidence base.

BACKGROUND: Healing time for neuropathic planter foot ulcers (NPFUs) in persons with diabetes may be reduced through use of non-removable fiberglass total contact casting (F-TCC) compared with removable cast walkers (RCWs), although the evidence base is still growing.

DETAILS: A rapid review was conducted and systematically searched for, and critically assessed, randomized controlled trials (RCTs) that compared the efficacy of F-TCC versus RCW, focusing on the time to ulcer healing in adult persons (18+ years) with NPFUs and type 1 or type 2 diabetes. We meta-analysed the mean differences and associated 95% CIs using an inverse variance, random-effects model. Also conducted a trial sequential analysis (TSA) to assess if the available evidence is up to the required information size for a robust conclusion. Assessed and quantified statistical heterogeneity between the included studies using the I2 statistic. Out of 102 retrieved citations, five RCTs met the eligibility criteria. Participants' inclusion in relation to stage of ulcer was highly variable as was peripheral neuropathy complicating comparisons. F-TCC appeared to present a shorter ulcer healing time (-5.42 days, 95% CI -9.66 days to -1.17 days; I2 9.9%; 5 RCTs; 169 participants) compared with RCW. This finding was supported by the TSA.

Our Most Popular Resources

Copyright © BMJ Publishing Group Ltd. All rights reserved.

Source: Okoli GN, Rabbani R, Lam OLT, et al. (2022). Offloading Devices For Neuropathic Foot Ulcers In Adult Persons With Type 1 Or Type 2 Diabetes: A Rapid Review With Meta-Analysis And Trial Sequential Analysis Of Randomized Controlled Trials. BMJ DRC. 2022; 10(3): e002822. Published: May 12, 2022. DOI: 10.1136/bmjdrc-2022-002822.



Specialty: 

Breaking Medical News Cardiology Emergency Medicine Endocrinology Family Medicine Gastroenterology General Interests General Surgery Hematology/Oncology Infectious Disease Internal Medicine Nephrology Neurology Nursing Ob/Gyn Ophthalmology Pediatrics Pharmacy Psychiatry