Effect of Low-Dose Progesterone on Glycemic Metabolism, Morphology and Function of Adipose Tissue and Pancreatic Islets in Diet-Induced Obese Female Mice.

BACKGROUND: Obesity is a worldwide concern due to its global rapid expansion and remarkable impact on individual's health by predisposing to several other diseases. About twice as many women as men suffer from severe obesity and, in fact, there are stages in a woman's life when weight gain and adiposity can result in greater damage to health. For example, obesity triples the chance of a woman developing gestational diabetes. Many hormones promote the metabolic adaptations of pregnancy, including progesterone, whose role in female obesity is still not well known despite being involved in many physiological and pathological processes. METHODS: Here we investigated whether progesterone treatment at low dose can worsen the glucose metabolism and the morpho functional aspects of adipose tissue and pancreas in obese females. Mice were assigned into four groups: normocaloric diet control (NO-CO), high-fat and -fructose diet control (HFF-CO), normocaloric diet plus progesterone (NO-PG) and high-fat and -fructose diet plus progesterone (HFF-PG) for 10 weeks. Infusion of progesterone (0.25 mg/kg/day) was done by osmotic minipump in the last 21 days of protocol. RESULTS: Animals fed a hypercaloric diet exhibited obesity with increased body weight (p < 0.0001), adipocyte hypertrophy (p < 0.0001), hyperglycemia (p = 0.03), and glucose intolerance (p = 0.001). HFF-CO and HFF-PG groups showed lower adiponectin concentration (p < 0.0001) and glucose-stimulated insulin secretion (p = 0.03), without differences in islet size. Progesterone attenuated glucose intolerance in the HFF-PG group (p = 0.03), however, did not change morphology or endocrine function of adipose tissue and pancreatic islets. CONCLUSIONS: Taken together, our results showed that low dose of progesterone does not worsen the effects of hypercaloric diet in glycemic metabolism, morphology and function of adipose tissue and pancreatic islets in female animals. These results may improve the understanding of the mechanisms underlying the pathogenesis of obesity in women and eventually open new avenues for therapeutic strategies and better comprehension of the interactions between progesterone effects and obesity.

Real-World Diagnosis and Treatment of Diabetic Kidney Disease.

INTRODUCTION: People with type 2 diabetes mellitus (T2DM) and diabetic kidney disease (DKD) have increased morbidity and mortality risk. Angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARB) are recommended to slow kidney function decline in DKD. This representative, real-world data analysis of patients with T2DM was performed to detect onset of DKD and determine methods and timing of DKD diagnosis and time to initiation of ACEi/ARB therapy. METHODS: Patients diagnosed with T2DM before January 1, 2016 who developed DKD between January 1, 2017 and June 30, 2019 were identified from a longitudinal ambulatory electronic health record (EHR) dataset (Veradigm Inc). Each record was analyzed using the CLinical INTelligence engine (CLINT™, HealthPals, Inc.) to identify delays and gaps in diagnosing DKD. DKD was diagnosed through two reduced estimated glomerular filtration rate (eGFR; < 60 mL/min/1.73 m2) measurements at least 90 days apart, a single elevated urine albumin-to-creatinine ratio (UACR; > 30 mg/g) measurement, or ICD-9/10 diagnosis codes for DKD and/or albuminuria. Time to diagnose (TTD), time to treat (TTT), and diagnosis to treatment time were assessed. RESULTS: Of 6,499,409 patients with T2DM before January 2016, 245,978 developed DKD between January 1, 2017 and June 30, 2019. In this DKD cohort, ca. 50% were first identified through EHR diagnosis and ca. 50% by UACR or eGFR lab-based diagnosis. In patients who had UACR/eGFR assessed, more than 90% exhibited DKD-level results on the first diagnostic test. Average TTD after eGFR labs was 2 years; average TTT with ACEi/ARB was 6-9 months after DKD lab evidence. The majority of patients who developed DKD received ACEi/ARB therapy 6-7 months after diagnosis. CONCLUSION: In a contemporary, large national cohort of patients with T2DM, progression to DKD was common but likely underrepresented. The low rate of DKD-screening labs, along with sizable delays in diagnosis of DKD and initiation of ACEi/ARB therapy, indicates that many patients who progress to DKD are not being properly treated.

Diabetic kidney disease is kidney disease that occurs in patients with type 2 diabetes and is associated with greater risk of death and other adverse cardiovascular and kidney outcomes. Unfortunately, diabetic kidney disease is underdiagnosed because of lack of awareness and its early asymptomatic presentation. Early detection and treatment of diabetic kidney disease with medicines such as angiotensin-converting enzyme inhibitors (also known as ACE inhibitors) or angiotensin II receptor blockers (also known as ARBs) is important for the prevention of disease progression and the development of other serious conditions. This real-world analysis evaluated electronic health record data from more than 6 million patients with diabetes to detect the onset of diabetic kidney disease and to determine timing of treatment and gaps in medical care. Results from the study show that there are often significant delays in the diagnosis of diabetic kidney disease, even when laboratory evidence is available. Furthermore, many patients are not undergoing regular renal function testing, thus missing the opportunity for diagnosis (and subsequent treatment) of earlier onset, less severe disease. After diagnosis, patients with diabetic kidney disease experience significant delay until they receive appropriate treatment with an ACE inhibitor or ARB. The low rate of kidney function screening coupled with delays in diagnosis and treatment initiation suggest that many patients who progress to diabetic kidney disease are not being properly treated. The results from this study highlight the need to improve diagnostic and treatment protocols to address these significant gaps in care.

Brazilian norms for the Bank of Standardized Stimuli (BOSS).

Norms for visual stimuli are critical for designing reliable psychological and neuroscientific studies. However, such normative sets of stimuli are scarce for the Brazilian population. Here, we report norms for the Bank of Standardized Stimuli (BOSS) for Brazilian college students. Sixty-five Brazilian university students rated the initial normative set of BOSS images for familiarity and visual complexity, and produced a name for each object. Data analysis focused on comparing the present norms to prior BOSS norms (English-Canadian, French-Canadian, and Thai) across four normative dimensions: familiarity, visual complexity, modal name agreement, and H value, and considered these dimensions according to whether items pertained to living or non-living domains. Correlation analyses revealed that the present norms show strong similarities to prior BOSS norms, although objects were scored as more familiar in the Brazilian relative to all prior norms, especially relative to the Thai norms. In addition, familiarity was greater for living than for non-living items in the English- and French-Canadian norms, but such difference was absent in the Brazilian and Thai norms, suggesting that familiarity is more strongly affected by culture than by semantic domain. In sum, even when cultural differences are considered, the current study reveals that the images of the BOSS data set are in general well known for Brazilians, demonstrating that they can be useful for psychological and neuroscientific research in Brazil.

Streptococcus mutans in Mother-Child Dyads and Early Childhood Caries: Examining Factors Underlying Bacterial Colonization.

This study investigated the association between colonization of mother-child dyads with Streptococcus mutans (SM) and early childhood caries (ECC), with consideration of the mediator and confounders, using a theoretical model. Four hundred mothers and their children from São Luís, Brazil, were included in the study. A diagram based on directed acyclic graphs was elaborated to analyze the association between SM colonization of the mother, mediated by child SM, and ECC. Other maternal (socioeconomic, waist circumference, sugar consumption, DMFT index, and visible plaque) and child factors (sugar consumption, visible plaque, and child age) composed the theoretical model. A total effect model (maternal SM on ECC) and a direct effect model, adjusted by the mediation effect of child SM (maternal SM via child SM) on ECC, were analyzed. The outcome of interest in this study was ECC (number of teeth with caries experience, dmft), which was analyzed as a discrete variable by Poisson regression. The Paramed test was used to analyze mediation. The following variables were associated with ECC in the total effect model: maternal SM, maternal waist circumference ≥80 cm, DMFT, maternal visible plaque, child age ≥4 years, and increased sugar consumption of the child (>3 times/day). In the direct effect model, high maternal SM levels remained associated with ECC, while moderate and high colonization of the child with SM was also associated with ECC. Child SM colonization just partially mediated the effect of maternal SM on ECC (33%). Thus, factors other than the mechanism of bacterial colonization should be considered in mother-child dyads, including eating habits, oral hygiene practices, and a family history of caries.