Diabetes for Doctors

Changes in Albuminuria Predict Cardiovascular and Renal Outcomes in Type 2 Diabetes: A Post Hoc Analysis of the LEADER Trial

OBJECTIVE

A post hoc analysis to investigate the association between 1-year changes in albuminuria and subsequent risk of cardiovascular and renal events.

RESEARCH DESIGN AND METHODS

LEADER was a randomized trial of liraglutide up to 1.8 mg/day versus placebo added to standard care for 3.5–5 years in 9,340 participants with type 2 diabetes and high cardiovascular risk. We calculated change in urinary albumin-to-creatinine ratio (UACR) from baseline to 1 year in participants with >30% reduction (n = 2,928), 30–0% reduction (n = 1,218), or any increase in UACR (n = 4,124), irrespective of treatment. Using Cox regression, risks of major adverse cardiovascular events (MACE) and a composite nephropathy outcome (from 1 year to end of trial in subgroups by baseline UACR [<30 mg/g, 30–300 mg/g, or ≥300 mg/g]) were assessed. The analysis was adjusted for treatment allocation alone as a fixed factor and for baseline variables associated with cardiovascular and renal outcomes.

RESULTS

For MACE, hazard ratios (HRs) for those with >30% and 30–0% UACR reduction were 0.82 (95% CI 0.71, 0.94; P = 0.006) and 0.99 (0.82, 1.19; P = 0.912), respectively, compared with any increase in UACR (reference). For the composite nephropathy outcome, respective HRs were 0.67 (0.49, 0.93; P = 0.02) and 0.97 (0.66, 1.43; P = 0.881). Results were independent of baseline UACR and consistent in both treatment groups. After adjustment, HRs were significant and consistent in >30% reduction subgroups with baseline micro- or macroalbuminuria.

CONCLUSIONS

A reduction in albuminuria during the 1st year was associated with fewer cardiovascular and renal outcomes, independent of treatment. Albuminuria monitoring remains an important part of diabetes care, with great unused potential.

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Erratum. Coronary Artery Disease and Type 2 Diabetes: A Proteomic Study. Diabetes Care 2020;43:843-851

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Effects of Lifestyle Intervention of Maternal Gestational Diabetes Mellitus on Offspring Growth Pattern Before Two Years of Age

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Novel Biochemical Markers of Glycemia to Predict Pregnancy Outcomes in Women With Type 1 Diabetes

OBJECTIVE

The optimal method of monitoring glycemia in pregnant women with type 1 diabetes remains controversial. This study aimed to assess the predictive performance of HbA1c, continuous glucose monitoring (CGM) metrics, and alternative biochemical markers of glycemia to predict obstetric and neonatal outcomes.

RESEARCH DESIGN AND METHODS

One hundred fifty-seven women from the CGM in Pregnant Women With Type 1 Diabetes Trial (CONCEPTT) were included in this prespecified secondary analysis. HbA1c, CGM data, and alternative biochemical markers (glycated CD59, 1,5-a nhydroglucitol, fructosamine, glycated albumin) were compared at ~12, 24, and 34 weeks’ gestation using logistic regression and receiver operating characteristic (ROC) curves to predict pregnancy complications (preeclampsia, preterm delivery, large for gestational age, neonatal hypoglycemia, admission to neonatal intensive care unit).

RESULTS

HbA1c, CGM metrics, and alternative laboratory markers were all significantly associated with obstetric and neonatal outcomes at 24 weeks’ gestation. More outcomes were associated with CGM metrics during the first trimester and with laboratory markers (area under the ROC curve generally <0.7) during the third trimester. Time in range (TIR) (63–140 mg/dL [3.5–7.8 mmol/L]) and time above range (TAR) (>140 mg/dL [>7.8 mmol/L]) were the most consistently predictive CGM metrics. HbA1c was also a consistent predictor of suboptimal pregnancy outcomes. Some alternative laboratory markers showed promise, but overall, they had lower predictive ability than HbA1c.

CONCLUSIONS

HbA1c is still an important biomarker for obstetric and neonatal outcomes in type 1 diabetes pregnancy. Alternative biochemical markers of glycemia and other CGM metrics did not substantially increase the prediction of pregnancy outcomes compared with widely available HbA1c and increasingly available CGM metrics (TIR and TAR).

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Comparative Effectiveness and Safety of Sodium-Glucose Cotransporter 2 Inhibitors Versus Glucagon-Like Peptide 1 Receptor Agonists in Older Adults

OBJECTIVE

Both sodium–glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1RA) demonstrated cardiovascular benefits in randomized controlled trials of patients with type 2 diabetes (T2D) generally <65 years old and mostly with cardiovascular disease. We aimed to evaluate the comparative effectiveness and safety of SGLT2i and GLP-1RA among real-world older adults.

RESEARCH DESIGN AND METHODS

Using Medicare data (April 2013–December 2016), we identified 90,094 propensity score–matched (1:1) T2D patients ≥66 years old initiating SGLT2i or GLP-1RA. Primary outcomes were major adverse cardiovascular events (MACE) (i.e., myocardial infarction, stroke, or cardiovascular death) and hospitalization for heart failure (HHF). Other outcomes included diabetic ketoacidosis (DKA), genital infections, fractures, lower-limb amputations (LLA), acute kidney injury (AKI), severe urinary tract infections, and overall mortality. We estimated hazard ratios (HRs) and rate differences (RDs) per 1,000 person-years, controlling for 140 baseline covariates.

RESULTS

Compared with GLP-1RA, SGLT2i initiators had similar MACE risk (HR 0.98 [95% CI 0.87, 1.10]; RD –0.38 [95% CI –2.48, 1.72]) and reduced HHF risk (HR 0.68 [95% CI 0.57, 0.80]; RD –3.23 [95% CI –4.68, –1.77]), over a median follow-up of ~6 months. They also had 0.7 more DKA events (RD 0.72 [95% CI 0.02, 1.41]), 0.9 more LLA (RD 0.90 [95% CI 0.10, 1.70]), 57.1 more genital infections (RD 57.08 [95% CI 53.45, 60.70]), and 7.1 fewer AKI events (RD –7.05 [95% CI –10.27, –3.83]) per 1,000 person-years.

CONCLUSIONS

Among older adults, those taking SGLT2i had similar MACE risk, decreased HHF risk, and increased risk of DKA, LLA, and genital infections versus those taking GLP-1RA.

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