2 Minute Medicine Rewind February 15, 2021

Risk of Progression to Diabetes Among Older Adults With Prediabetes

1. Older adults with prediabetes were more likely to regress to normoglycemia or pass away than progress to diabetes.

2. Prediabetes may be a weak indicator of risk for diabetes among older adults.

Evidence Rating Level: 2 (Good)

Prediabetes is known as a risk factor for progression to diabetes, often used to identify at-risk individuals. However, the progression of prediabetes among older adults is still unclear and may not be diagnostically robust. This prospective cohort study of 3,412 older adults without diabetes (M [SD] age = 75.6 [5.2] years, 60% female, 17% Black) from the Atherosclerosis Risk in Communities Study (baseline 2011-2013) sought to characterize risks of prediabetes and diabetes in older age. All participants were contacted semiannually through 2017, including a final follow-up in 2016 or 2017. Prediabetes was defined by a glycated hemoglobin (HbA1C level between 5.7% and 6.4% and impaired fasting glucose (IFG) level was an FG level of 100-125mg/dL. The main outcome of this study was incident total diabetes. Of the 3,412 initial participants without diabetes, 2,497 attended follow-up or passed away. Over the course of the 6.5 years, there were 156 incident total diabetes cases and 434 deaths. Approximately 44% had HbA1C levels in the diagnostic range and 59% had IFG, and 73% met either the IFG or HbA1C criteria – 29% met both criteria. Those with prediabetes based on HbA1C at baseline, 9% progressed to diabetes. A total of 13% regressed to normoglycemia and 19% passed away. Of participants with baseline IFG, 8% progressed to diabetes, while 44% regressed to normoglycemia and 16% passed away. Of participants who did not have prediabetes based on HbA1C and FG levels, 17% and 8% progressed to prediabetes, respectively, and 3% of each of these groups progressed to diabetes. Overall, this study suggests that, while the prevalence of prediabetes was relatively high, it was more common for participants to regress to normoglycemia or pass away than it was to progress to diabetes. Thus, this risk factor may not serve as a strong diagnostic predictor among older adults.


Association Between Proton Pump Inhibitor Use and Risk of Asthma in Children

1. Children and adolescents using proton pump inhibitors (PPIs) were at an increased risk of asthma, compared to matched controls who were not using PPIs.

2. Infants and toddlers less than 2 years of age were at the greatest risk of developing asthma after PPI initiation. 

Evidence Rating Level: 2 (Good)

There has been a major increase in the use of proton pump inhibitors (PPIs) in children, in spite of concerns that these medications may increase asthma risk in this age group. This nationwide cohort study used data from a Swedish registry from 2007 through 2016 to identify children and adolescents 17 years of age or younger, matching them by age and propensity score into pairs of children who were and were not new users of PPIs. Asthma incidence and hazard ratios (HRs) were determined among the 80,870 pairs (M [SD] age = 12.9 [4.8] years, 63.0% female). This study found that those who used PPIs had a higher incidence rate of asthma (21.8 events/1,000 person-years) compared to those who had not used PPIs (14.0 events/1,000 person-years; HR = 1.57, 95% CI 1.49 to 1.64). Though asthma risk was significantly elevated across all age groups, it was particularly high for infants and toddlers younger than 6 months (HR = 1.83, 95% CI 1.65 to 2.03) and between 6 months and 2 years (HR = 1.91, 95% CI 1.65 to 2.22; interaction p<.001). Individual PPIs also showed different HRs: esomeprazole (HR = 1.64, 95% CI 1.50 to 1.79), lansoprazole (HR = 1.49, 95% CI 1.25 to 1.78), omeprazole (HR = 1.43, 95% CI 1.35 to 1.51), and pantoprazole (HR = 2.33, 95% CI 1.30 to 4.18). Asthma onset was also investigated based on PPI initiation, with the HR being 1.62 (95% CI 1.42 to 1.85) for within 90 days, 1.73 (95% CI 1.52 to 1.98) for 91 to 180 days, and 1.53 (95% CI 1.45 to 1.62) for 181 days to end of follow-up. Overall, this study suggests that PPI use was associated with an increased risk of asthma in children and adolescents, compared to matched controls who were not using PPIs. This risk should be considered prior to the prescribing of PPIs among this age group.


Poor Cardiovascular Health Is Associated With Subclinical Atherosclerosis In Apparently Healthy Sub-Saharan African Populations: An H2Africa AWI-Gen Study

1. The American Heart Association’s cardiovascular health index has clinical utility with an understudied sub-Saharan African population.

2. The targets for preventing atherosclerosis in this population are smoking, obesity, hypertension, hyperglycemia, and physical activity.

Evidence Rating Level: 3 (Average)

The American Heart Association’s cardiovascular health index (CVHI) is known to be a simple, valid, and translatable metric for cardiovascular health monitoring. This metric includes seven risk factors: dietary intake, smoking, body mass index, physical activity, blood pressure, total cholesterol, and glucose. This cross-sectional study sought to expand evidence of the CVHI’s utility with an underrepresented sub-Saharan African population. Participants were residents of Burkina Faso, Ghana, Kenya, and South Africa. A total of 9,011 participants (M [SD] age = 51 [7] years, 51% female) were included and had a mean CVHI score of 10.3 (SD = 2.0) and common carotid intima-media thickness (CIMT) of 637 (SD = 117μm). CVHI and common CIMT were found to be inversely associated across the countries of Burkina Faso (B-coefficients = 6.51, 95% CI -9.83 to -3.20 μm), Ghana (-5.42, 95% CI -8.90 to -1.95 μm), Kenya (-6.58, 95% CI -9.05 to -4.10 μm), and South Africa (-7.85, 95% CI -9.65 to -6.05 μm). Men (-6.27, 95% CI -7.91 to -4.64) and women (-4.44, 95% CI -6.23 to -2.65) were inversely related. Interestingly, hyperglycemia (p<.001), physical activity (p<.001), and smoking (p<.001) were each related to CIMT in women while only obesity and blood pressure were related to CIMT in both women and men (p<.001). Overall, this study demonstrated the utility of the CVHI among this understudied population, with risk factors differing between men and women. In general, the prevention of atherosclerotic cardiovascular disease requires careful attention to smoking, obesity, hypertension, hyperglycemia, and physical activity.


Association of First Trimester Prescription Opioid Use With Congenital Malformations In the Offspring: Population Based Cohort Study

1. The use of opioid medications during the first trimester is not significantly associated with greater risk of congenital malformations.

2. Following adjustments, opioid use during the first trimester was associated with a greater relative risk of oral clefts.

Evidence Rating Level: 2 (Good)

Pregnant women experience pain to varying degrees, yet teratogenicity of opioids is still unclear in epidemiological studies. Approximately 14% of commercial insurance beneficiaries and 22% of Medicaid beneficiaries receive at least one opioid prescription during pregnancy. This nationwide population-based cohort study sought to investigate congenital malformations in the context of pregnant women who received at least two opioid prescriptions during their first trimesters. A total of 1,602,580 publicly-insured and 1,177,676 commercially-insured pregnant women were included in analyses, with insurance eligibility three months prior to pregnancy and one month after delivery. Through the use of the Medicaid Analytic eXtract (MAX) and the MarketScan Research Database (MarketScan), these women were matched to their liveborn infants. Approximately 4.4% of publicly-insured and 1.1% of commercially-insured pregnant women had at least two opioid prescriptions dispensed during the first trimester. The absolute risk of overall malformations was 41 (95% CI 39.5 to 42.5) per 1,000 pregnancies exposed to opioid medications, compared to 32 (95% CI 31.7 to 32.3) per 1,000 in the MAX cohort. Overall malformations risk was 42.6 (95% CI 39.0 to 46.1) compared to 37.3 (95% CI 37.0 to 37.7) per 1,000 in the MarketScan cohort. Unadjusted relative risk (RR) estimates were calculated for all outcomes: overall malformations (RR = 1.06, 95% CI 1.02 to 1.10), cardiovascular malformations (RR = 1.09, 95% CI 1.00 to 1.18), ventricular septal defect (RR = 1.07, 95% CI 0.95 to 1.21), atrial septal defect/patent foramen ovale (RR = 1.04, 95% CI 0.88 to 1.24), clubfoot (RR = 1.06, 95% CI 0.88 to 1.28), and neural tube defect (RR = 0.82, 95% CI 0.53 to 1.27). However, nearly all of these outcomes regressed to the null after adjustment. The RR of oral clefts remained relatively high after adjustment (RR = 1.21, 95% CI 0.98 to 1.50), including a high risk of cleft palate (RR = 1.62, 95% CI 1.23 to 2.14). Overall, this study found that opioid medications are not associated with a significant increase in risk of congenital malformations, though oral clefts may be more likely.



Acute Kidney Injury In Patients With Severe COVID-19 In Mexico

1. Acute kidney injury (AKI) was common among individuals in Mexico with COVID-19 pneumonia.

2. Risk factors for developing AKI were older age, obesity, and need for invasive mechanical ventilation upon admission.

Evidence Rating Level: 3 (Average)

Individuals testing positive for COVID-19 present with a wide range of comorbidities. COVID-19 pneumonia and its impact on acute kidney injury (AKI) may provide information related to the risks faced by this population and how COVID-19 may effect AKI progression. This retrospective cohort study reviewed medical records of individuals with severe COVID-19 pneumonia at a major institution in Mexico between March and April 2020. A total of 99 participants (M [SD] age = 52.9 [13.2] years, 25.3% female) were included in analyses, 58.6% of whom developed AKI. Several risk factors for AKI emerged: older age (OR = 1.07, 95% CI 1.01 to 1.13, p = .024), obesity (OR = 6.58, 95% CI 1.8 to 24.05, p = .040), and need for invasive mechanical ventilation (IMV; OR = 6.18, 95% CI 1.29 to 29.58, p = .023). Mortality-specific risk factors included AKI (OR = 8.61, 95% CI 2.24 to 33.1, p = .002), requirement of vasoactive drugs on admission (OR = 5.35, 95% CI 1.16 to 24.61, p = .031), and obesity (OR = 5.57, 95% CI 1.48 to 20.93, p = .011). Individuals with AKI stage 3 (79.3%) and stage 2 (68.7%) had greater odds of in-hospital mortality compared to those with stage 1 (25%; p = .004). This study went further and reviewed the 53 participants who underwent furosemide stress tests (FST) to predict AKI progression. A total of 12 (22%) progressed to AKI stage 3. The ROC curve for the FST proved to have predictive value related to progression (AUC = .681, p = .009; sensitivity = 81.6%, specificity = 54.5%). Overall, this study suggests that AKI is a common presentation among patients with COVID-19 pneumonia and that risk factors for AKI and its progression are obesity, older age, and the need for IMV on admission.

Image: PD

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