2 Minute Medicine Rewind April 4, 2022

Diabetic kidney disease and risk of incident stroke among adults with type 2 diabetes

1. Diabetic kidney disease, as determined by high urine albumin-to-creatinine ratio and low estimated glomerular filtration rate in diabetic patients, was associated with an elevated risk of incident stroke.

Evidence Rating Level: 2 (Good)

Atherosclerotic cardiovascular disease presents a significant health burden among individuals with type 2 diabetes.  Diabetes-related microvascular complications have been associated with a higher risk of stroke; however, the impact of diabetic kidney disease on stroke is currently not well-elucidated in literature. In this post-hoc analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study, 9170 patients with type 2 diabetes and no prior history of stroke were assessed for kidney function using urine albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR). Participants were followed over a median of five years to identify the incidence of stroke and mortality. The moderate (30-300 mg/g) and severe UACR (>300 mg/g) groups were associated with elevated risk of stroke incidence compared to the normal UACR (<30 mg/g) group (HR 1.61, 95%CI 1.12-2.32 and HR 2.29, 95%CI 1.39-3.80, respectively). Using an eGFR of 60 mL/min as a cut-off, participants with a decreased eGFR had a 50% increased stroke risk compared to individuals with a normal eGFR (HR 1.50, 95%CI 0.98-2.29). As such, diabetic kidney disease, as determined by increased UACR and decreased eGFR in diabetic patients, is associated with an elevated risk of stroke. Given that a significant proportion of patients with diabetes mellitus present with chronic kidney disease (CKD), these results warrant further investigation into strategies targeting the progression of CKD to ultimately reduce the subsequent burden of stroke.

Analysis of Adverse Events and Intravenous Iron Infusion Formulations in Adults With and Without Prior Infusion Reactions

1. The iron sucrose formulation of intravenous iron was associated with an increased rate of post-infusion reaction compared to low molecular weight iron dextran, ferumoxytol, and ferric carboxymaltose.

Evidence Rating Level: 2 (Good)

Intravenous (IV) iron has been known to be more effective in the management of iron deficiency than oral iron. However, the overall safety among various IV iron administration methods remains ambiguous, especially with the development of newer infusion formulations. In this multi-center cohort study, 12 237 adult patients who received at least one infusion of IV iron formulation (iron sucrose (IS), low molecular weight iron dextran (LMWID), ferumoxytol, or ferric carboxymaltose) were assessed for adverse events (AEs) which were defined as the administration of diphenhydramine, epinephrine, famotidine, or hydrocortisone within 24-hours following an iron infusion. The cumulative incidence of infusion-related AE over the 6.5-year study period was 3.9% (95%CI, 3.7-4.1). In patients who received IS, the reaction rate was 4.3% (95%CI, 1.4-2.3), 3.8% (95%CI, 3.4-4.2) in LMWID, 1.8% (95%CI, 1.4-2.3) in ferumoxytol, and 1.4% (95%CI, 0.8-2.3) in ferric carboxymaltose. Of note, an increased rate of AEs was observed in individuals with a history of allergy compared to individuals without (4.2%, 95%CI 4.1-4.6). As the highest AE rate was associated with the oldest iron formulation (IS), this study suggests that infusion reactions have decreased with the emergence of newer IV iron formulations. However, the use of post-infusion medication administration may not be an accurate indicator of an adverse event, reducing the validity of these results. Nonetheless, these findings still support future investigation of adverse reactions in newer iron IV formulations and mechanisms involved in the prevention of AEs post-infusion.

Empirically derived dietary pattern and odds of non-alcoholic fatty liver diseases in overweight and obese adults: a case-control study

1. Adherence to a “western” dietary pattern was associated with an increased risk of non-alcoholic fatty liver disease.

Evidence Rating Level: 3 (Average)

Non-alcoholic fatty liver disease (NAFLD), characterized by hepatic steatosis and the accumulation of triglycerides in the liver, can give rise to cirrhosis, hepatocellular carcinoma, and liver failure if left to worsen. Nutrition and dietary patterns are known to contribute heavily to NAFLD development and its management; however, this is not currently well-elucidated in literature. In this age- and gender-matched case-control study conducted in Iran, the dietary intake of 217 Iranian participants with a BMI of greater than 25 was assessed using a semi-quantitative food frequency questionnaire. Food items were categorized under 24 food groups and three broad dietary patterns were established which included “western”, “traditional”, and “snack and sweets”. The western dietary pattern included fast foods, refined grains, high-fat dairy, and processed meats; the traditional dietary pattern consisted of vegetables, fruits, low-fat dairy, and poultry; snack and sweets included soft drinks, sugars, and sweet desserts. In participants that adhered to a “western” dietary pattern, the risk of NAFLD was 3.52 higher (OR 3.52, 95%CI 1.64-8.61) compared to participants who did not. This relationship remained significant after adjusting for energy intake, education, occupation, history of diabetes, medications, and physical activity (OR 3.30, 95%CI 1.06-10.27). However, as this study only included Iranian participants, these results may not be generalizable to other cultures with varying dietary patterns and food availability. Nonetheless, these findings still warrant further research in the association between diet and NAFLD in various age groups, cultures, and populations.

Association of Lithium Treatment with the Risk of Osteoporosis in Patients With Bipolar Disorder

1. The risk of osteoporosis was elevated in patients with bipolar disorder.

2. Lithium treatment for bipolar disorder was associated with a decreased risk of osteoporosis.

Evidence Rating Level: 2 (Good)

Osteoporosis is known to present a substantial burden of morbidity and mortality on healthcare systems globally. While characteristics such as advanced age and female sex are commonly associated with an elevated risk of osteoporosis, recent evidence suggests that bipolar disorder and its pharmacological therapies may pose an additional risk. In a nationwide longitudinal register-based study conducted in Denmark, 22 912 individuals with bipolar disorder, as well their age- and sex- matched references were followed for a median of seven years for onset of osteoporosis. The incidence of osteoporosis was elevated in patients with bipolar disorder (HRR 1.14, 95%CI 1.08-1.20). Additionally, individuals with bipolar disorder that underwent lithium therapy demonstrated a decreased risk of osteoporosis (HRR 0.62, 95%CI 0.53-0.72) compared to patients who did not receive lithium. Interestingly, management with antipsychotics, valproate, and lamotrigine depicted no statistically significant association with the risk of osteoporosis. The results of this study highlight the importance of prioritizing bone health in individuals diagnosed with bipolar disorder to reduce the risk of osteoporosis and investigate mechanisms involved in the protective function of lithium. However, as the study sample only used Danish participants, results may not be generalized to a wider population. Moreover, it is unclear whether bipolar disorder is directly contributing to an increased osteoporosis risk or if there are other comorbidities involved in the disease process.

Avocado Consumption and Risk of Cardiovascular Disease in US Adults

1. Avocado consumption was associated with a reduced risk of cardiovascular disease.

Evidence Rating Level: 2 (Good)

Cardiovascular disease (CVD) remains the leading cause of death globally, but evidence suggests that modifiable factors such as adhering to a healthy diet and lifestyle may significantly reduce its health burden. Recent studies have investigated the protective factors of avocados on cardiovascular health. In this prospective cohort study, dietary intake of 68 786 women from the Nurses’ Health Study (NHS) and 41 701 men from the Health Professionals Follow-up Study (HPFS) was evaluated for avocado consumption using a semi-quantitative food-frequency questionnaire. These participants were followed over 30 years for incidence of cardiovascular events. Avocado intake was divided into four categories: no avocado intake, 1-3 times a month, once per week, and twice or more per week. Individuals with avocado consumption twice or more per week demonstrated a 16% decreased risk of CVD compared to all other groups (pooled HR 0.84, 95%CI 0.75-0.95). Additionally, this group had a 21% lower risk of coronary heart disease (pooled HR 0.79, 95%CI 0.68-0.91). No significant associations between avocado consumption and stroke were identified. The results of this study highlight the impact of dietary changes such as increasing avocado consumption on reducing cardiovascular disease risk. However, as the dietary information provided was self-reported, the accuracy of the data is in question. As well, given the predominantly White population represented in the study sample, there is reduced generalizability to other cultures and ethnicities. Nonetheless, these findings warrant further research into additional nutritional modifications contributing to cardiovascular health.

Image: PD

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