Variable phenotype in HNF1B mutations: extrarenal manifestations distinguish affected individuals from the population with congenital anomalies of the kidney and urinary tract

Background: Mutations in hepatocyte nuclear factor 1B (HNF1B) have been associated with congenital anomalies of the kidney and urinary tract (CAKUT) in humans. Diabetes and other less frequent anomalies have also been described. Variable penetrance and intrafamilial variability have been demonstrated including severe prenatal phenotypes. Thus, it is important to differentiate this entity from others with similar clinical features and perform confirmatory molecular diagnosis. Methods: This study reports the results of HNF1B screening in a cohort of 60 patients from 58 unrelated families presenting with renal structural anomalies and/or non-immune glucose metabolism alterations, and other minor features suggesting HNF1B mutations. Results: This study identified a pathogenic variant in 23 patients from 21 families. The most frequent finding was bilateral cystic dysplasia or hyperechogenic kidneys (87% of patients). Sixty percent of them also fulfilled the criteria for impaired glucose metabolism, and these were significantly older than those patients with an HNF1B mutation but without diabetes or prediabetes (14.4 versus 3.3years, P<0.05). Furthermore, patients with HNF1B mutations had higher frequency of pancreatic structural anomalies and hypomagnesaemia than patients without mutations (P<0.001 and P = 0.003, respectively). Hyperuricaemia and increased liver enzymes were detected in some patients as well. Conclusions: Renal anomalies found in patients with HNF1B mutations are frequently unspecific and may resemble those found in other renal pathologies (CAKUT, ciliopathies). Active searching for extrarenal minor features, especially pancreatic structural anomalies or hypomagnesaemia, could support the indication for molecular diagnosis to identify HNF1B mutations

Long-term prevention of renal insufficiency, excess matrix gene expression, and glomerular mesangial matrix expansion by treatment with monoclonal antitransforming growth factor-ß antibody in \u3ci\u3edb/db\u3c/i\u3e diabetic mice

Emerging evidence suggests that transforming growth factor-(TGF-β) is an important mediator of diabetic nephropathy. We showed previously that short-term treatment with a neutralizing monoclonal anti-TGF-antibody (αT) in streptozotocin-diabetic mice prevents early changes of renal hypertrophy and increased matrix mRNA. To establish that overactivity of the renal TGF-system mediates the functional and structural changes of the more advanced stages of nephropathy, we tested whether chronic administration of αT prevents renal insufficiency and glomerulosclerosis in the db/db mouse, model of type 2 diabetes that develops overt nephropathy. Diabetic db/db mice and nondiabetic db/m littermates were treated intraperitoneally with α or control IgG, 300 µg three times per week for 8 wk. Treatment with αT, but not with IgG, significantly decreased the plasma TGF-β1 concentration without decreasing the plasma glucose concentration. The IgG-treated db/db mice developed albuminuria, renal insufficiency, and glomerular mesangial matrix expansion associated with increased renal mRNAs encoding α 1(IV) collagen and fibronectin. On the other hand, treatment with α completely prevented the increase in plasma creatinine concentration, the decrease in urinary creatinine clearance, and the expansion of mesangial matrix in db/db mice. The increase in renal matrix mRNAs was substantially attenuated, but the excretion of urinary albumin factored for creatinine clearance was not significantly affected by α treatment. We conclude that chronic inhibition of the biologic actions of TGF-with neutralizing monoclonal antibody in db/db mice prevents the glomerulosclerosis and renal insufficiency resulting from type diabetes

Bariatric Surgery Outcomes in Appalachia Influenced by Surgery Type, Diabetes, and Depression

Background Most effective treatment for morbid obesity and its comorbidities is bariatric surgery. However, research is limited on weight loss and associated outcomes among patients in Appalachia. The objective of this study was to examine demographic and comorbidity influence on surgical outcomes of this population including age, sex, race, state of residence, education, marital status, body mass index (BMI kg/m2), excess body weight (EBW), percent excess weight loss (%EWL), blood pressure, diagnosed depression, diagnosed type 2 diabetes (T2D), Beck Depression Inventory-II (BDI-II), and laboratory values (i.e., hemoglobin A1c). Methods A retrospective electronic medical record (EMR) data extraction was performed on N = 582 patients receiving bariatric surgery (laparoscopic Roux-en-Y gastric bypass [RYGB] and laparoscopic sleeve gastrectomy [SG]) between 10/2013 and 2/2017. Results Patient population was 92.5% Caucasian, 79.3% female, 62.8% married, 45 ± 11.1 years, 75.8% received RYGB, and 24.2% received SG. Average %EWL from baseline to 1-year follow-up was 68.5 ± 18.4% (n = 224). In final descriptive models, surgery type, diagnosed T2D, HbA1c, and depressive symptoms were significant covariates associated with lower %EWL. Conclusions Findings suggest patients completing surgery within an Appalachian region have successful surgical outcomes at 1-year post-surgery, as indicated by significant reductions of \u3e 50% EWL, regardless of other covariates. Results suggest that bariatric programs should consider paying special consideration to patients with T2D or depressive symptoms to improve outcomes. Results have potential to inform future prospective studies and aid in guiding specific interventions tailored to address needs of this unique population

Physical Education Matters: A Full Report

Examines the quantity and quality of California's physical education programs, compliance with requirements, and resources. Summarizes research on the benefits of PE and effective strategies to improve PE programs. Outlines policy recommendations

Основні принципи реабілітації дітей з діабетичною кардіо-міопатією

Приведены результаты клинико-инструментального обследования 80 детей с сахарным диабетом 1 типа. Установлена высокая частота вегетативной дисфункции (в 76,3% обследованных) и диабетической кардиомиопатии (в 57,3%). Выделены три стадии развития диабетической кардиомиопатии у детей и обоснованно критерии их диагностики. Предложен дифференцированный подход к назначению схемы реабилитационных мероприятий на клиническом и санаторном и адаптационном этапах с учетом стадии диабетической кардиомиопатии и вегетативного гомеостаза.The vegetative dysfunction has been found in 76,3 % and the diabetic cardiomyopathy – in 57,3% of children with type $ diabetes mellitus. Three stages of development of the diabetic cardiomyopathy in children has been selected and criteria of their diagnostics have been proposed. The differential use of rehabilitation factors has been recommended taking into account the stage of the diabetic cardiomyopathy and vegetative homeostasis in children

The role of mediterranean diet and gut microbiota in type- diabetes mellitus associated with obesity (diabesity)

The human body is made up of 10¹⁴ human cells and 10¹⁵ bacterial cells, forming a combined structure that is described as a “superorganism”. Commensal, symbiotic, and pathogenic microorganisms in the human body, many of which are located inside the intestine, affect health conditions and diseases. An important factor contributing to the development of chronic diseases is dysbiosis, which occurs when the number of pathogenic microorganisms increases. Dysbiosis is associated with increased intestinal permeability, endotoxemia (increased LPS), pro-inflammatory cytokine release, energy harvest, and adiposity, thus being involved in the pathogenesis of disorders like diabetes and obesity. Nutritional habits are the most important environmental factor that affects intestinal microbial composition. A dietary pattern that was proven successful in regulating gut microbiota is the renowned Mediterranean diet, which is characterized by high plant-based foods consumption, moderate fish and dairy products consumption, and low red meat consumption. There is an inverse relationship between adherence to the Mediterranean diet and chronic diseases like obesity and diabetes. In addition to the direct effects of the Mediterranean diet on the pathogenesis of these diseases, it can also be effective in preventing these diseases due to its effects on the intestinal microbiota. It is noted that the number of Bifidobacterium and Bacteroides increases the longer one’s eating habit adhere to the Mediterranean diet, and the number of Firmicutes decreases, accordingly, thus supporting the symbiotic distribution in the intestinal microbiota

Association between Caries, Obesity and Insulin Resistance in Mexican Adolescents

Aim: To determine the association among dental caries, obesity and insulin resistance in Mexican adolescents. Methods: Body Mass Index, obesity (OB) blood pressure, insulin level, insulin resistance (IR), triglycerides level, serum HDL-cholesterol (cHDL), DMFT index and salivary flow were measured. Results: Anthropometric measures showed a significant statistical difference (p \u3c 0.05). Insulin level was 8.98 for healthy subjects, whereas for OB-IR group was 25.35, there was a statistical significant difference (p \u3c 0.05). Triglycerides level was 88.50 for healthy subjects and 169.40 mg/dL for OB-IR; cHDL was 52.88 for healthy and 41.82 mg/dL for OB-IR group, both showed a statistically significant difference (p \u3c 0.05). Salivary flow was 4.30 for healthy and for OB-IR group was 5.48 ml/min showed a significant statistical difference (p \u3c 0.05). DMFT index was 3.02 for healthy and for OB-IR adolescents was 4.78, showed a significant statistical difference (p \u3c 0.05). The caries component of DMFT index was 1.84 for healthy and was 3.52 for OB-IR adolescents, showed a significant statistical difference (p \u3c 0.05). According to the multivariate analysis, DMFT (OR=3.10; IC95%=0.20-1.02, p=0.042) and decay (OR=3.30; IC95%=0.19-1.0, p=0.011) were associated with subjects with OB-IR. Conclusion: OB-IR Mexican adolescents showed a positive association with DMFT

LADA type diabetes, celiac diasease, cerebellar ataxia and stiff person syndrome. A rare association of autoimmune disorders.

Celiac disease--in its typical form--is a chronic immune-mediated enteropathy with typical clinical symptoms that develops against gliadin content of cereal grains, and is often associated with other autoimmune diseases. In cases of atypical manifestation classic symptoms may be absent or mild, and extra-intestinal symptoms or associated syndromes dominate clinical picture. The authors present a longitudinal follow-up of such a case. A 63-years old woman was diagnosed with epilepsy at the age of 19, and with progressive limb ataxia at the age of 36, which was initially thought to be caused by cerebellar atrophy, later probably by stiff person syndrome. At the age 59, her diabetes mellitus manifested with type 2 diabetic phenotype, but based on GAD positivity later was reclassified as type 1 diabetes. Only the last check-up discovered the celiac disease, retrospectively explaining the entire disease course and neurological symptoms. By presenting this case, the authors would like to draw attention to the fact that one should think of the possibility of celiac disease when cerebellar ataxia, progressive neurological symptoms and diabetes are present at the same time. An early diagnosis may help to delay the progression of disease and help better treatment