Variants of the HNF4A and HNF1A genes in patients with impaired glucose metabolism and dyslipidemia

Maturity onset diabetes of the young is a dominantly inherited form of monogenic diabetes, diagnosed mainly before the age of 35 years. Mutations in the HNF1A and HNF4A genes are associated with diabetes mellitus of the HNF1A-MODY and HNF4A-MODY subtypes, respectively. These two forms of MODY are characterized by dyslipidemia in addition to impaired glucose metabolism due to the altered function HNF1A and HNF4A proteins. The aim of this study was a genetic analysis of young patients with the MODY phenotype and dyslipidemia with a burdened family history. Material and methods. The probands underwent targeted DNA sequencing using the Illumina MiSeq NGS System. The target panel included the coding regions and splicing sites of MODY-associated genes: HNF4A, GCK, HNF1A, PDX1, HNF1B, NEUROD1, KLF11, CEL, PAX4, INS, BLK, KCNJ11, ABCC8, and APPL1. Results. A heterozygous single nucleotide deletion NM_000457.4: c.153del (3’rule) was found in proband P1 in the HNF4A gene. In proband P2, single nucleotide deletion NM_000545.8: c.335del (3 ‘rule) in the HNF1A gene was detected in a heterozygous state. Both variants are located in the coding parts of the genes, led to a shift in the reading frame and have not been described in the literature and databases earlier. Conclusions. Taking into account the phenotypic features of probands, we assume that the variants NM_000545.8: c.335del (rule 3) in the HNF1A gene and NM_000457.4: c.153del (rule 3) of the HNF4A gene are associated with different MODY subtypes in these individuals. After verification of MODY-HNF1A and MODY-HNF4A diagnosis, it is necessary to monitor the lipid profile parameters (total cholesterol, low and high density lipoprotein cholesterol, triglycerides) and prescribe appropriate drug therapy.

Impact of Impaired Glucose Metabolism on Periodontitis Progression over Three Years

We evaluated the relationship between glucose abnormalities and periodontitis in overweight/obese individuals. Eight hundred and seventy (870) diabetes-free participants aged 40–65 years completed the three-year follow-up in the San Juan Overweight Adults Longitudinal Study. The ADA thresholds for fasting and 2-h post-load glucose and HbA1c were used to define prediabetes. The NHANES methods were used to assess periodontitis. Multivariable linear regression was used to evaluate the relationship between baseline glucose metabolism measures and periodontitis at follow-up, adjusting for potential confounders. There was no association between impaired glucose measures and mean pocket depth (PD), mean clinical attachment loss (CAL), or mean percent of sites ≥5 mm PD. Impaired glucose tolerance (IGT) was associated with a lower mean percent of sites ≥5 mm CAL (β = −1.6, p = 0.037). Prediabetes and impaired fasting glucose (IFG) were associated with improvement in mean percent of sites ≥5 mm PD (β = −1.4, p = 0.022; β = −1.6, p = 0.032; respectively). IFG and IGT were associated with improvement in mean percent of sites with ≥5 mm CAL (β = −1.6, p = 0.038; β = −1.9, p = 0.020; respectively). In conclusion, there were no consistent associations between baseline prediabetes or insulin resistance and periodontitis progression over a three-year period.

Extreme Birth Weight and Metabolic Syndrome in Children

Small and large birth weights (BWs) for gestational age (GA) represent extremes, but the correlation between extreme BW and metabolic syndrome (MetS) has not been fully elucidated. In this study, we examined this correlation in obese children based on changes in their metabolic profile from childhood to adolescence. A retrospective observational study was performed on 535 obese patients aged 0–18 years in the Clinical and Emergency Hospital for Children “Louis Turcanu” in Timisoara, Romania, based on clinical and biological data from January 2015 to December 2019. We emphasized the links between extreme BW and obesity, extreme BW and cardiometabolic risk, obesity and cardiometabolic risk, and extreme BW, obesity and MetS. Children born large for gestational age (LGA) predominated over those born small for gestational age (SGA). Our findings showed that BW has an independent effect on triglycerides and insulin resistance, whereas obesity had a direct influence on hypertension, impaired glucose metabolism and hypertriglyceridemia. The influences of BW and obesity on the development of MetS and its components are difficult to separate; therefore, large prospective studies in normal-weight patients are needed.

Early insulin-resistance, T2D and treatment options in childhood

Background T2D (Type 2 Diabetes) represents just the tip of the iceberg of the complex metabolic alterations associated with obesity and other clinical conditions associated to impaired adipose tissue storage. Summary Available data have suggested the presence of a continuous spectrum of metabolic alterations developed in the progression from IR to T2D, most of which are likely preventable through the early characterization of all the multiple risk factors involved. Therefore, the complete characterization of the natural history of the disease and the major modifiable factors represents a milestone in the daily care of young subject at risk for the development of impaired glucose metabolism early in life. This review will focus on the main components defining the risk of IR and T2D in childhood with a specific focus on the main aspects of treatment options available in children and adolescents. Key messages Impaired adipose tissue storage documented in obesity results in a continuous spectrum of metabolic alterations ranging from IR to T2DM. These metabolic alterations are mostly likely preventable through the early characterization of all the multiple risk factors involved. The complete characterization of the disease and of the major modifiable factors represent a milestone in the daily care of young subject at risk for the development of impaired glucose metabolism early in life.

Irizin: a new myokine and its effect on metabolism

Muscles release hormones (myokines) into the bloodstream, which affect the production of cytokines and their metabolism in various organs and tissues. One of them is irisin, a new adipokine with important autocrine and endocrine functions. It is produced not only by muscle tissue, but also by lymphoid organs, adipose and nervous tissue. It has been proven that this myokine can play a role in the pathogenesis of metabolic and oncological diseases, inflammation, aging and neurogenesis. The content of irisin in the blood is regulated not only by physical activity, but also by diet, changes in body weight, and drugs. The increased interest in studying the relationship of irisin with metabolic diseases is due to the search for a potentially new point of application for overcoming type 2 diabetes mellitus and insulin resistance. Irisin plays a major role in the interaction of the muscle­adiposetissue­bone­brain axis. It has been found that exercise has a positive effect on the functioning of the nervous system. Irisin has an anabolic effect on the skeleton and plays a significant role in bone metabolism. It has been established that exercise is a protective factor in people with cancer, reduces the toxicity of chemotherapy and improves the quality of life of patients, although the mechanisms of this phenomenon require further study. The relationship between circulating irisin levels and impaired glucose metabolism in children is discussed. It is proposed to use irisin as one of the predictors of childhood obesity. Its protective role in pregnancy and in newborns is being studied. A decrease in serum irisin levels is considered a marker of gestational diabetes. It has been suggested that cord blood irisin levels may be a reliable predictor of obesity in the future. Further research is needed to better understand the mechanism of action of this myokine in various diseases in children and to identify the relationship between circulating irisin levels and the amount of brownadipose tissue in newborns of different gestational age and with different birth weights.

Anti-Obesity Effects of Combined Cornus officinalis and Ribes fasciculatum Extract in High-Fat Diet-Induced Obese Male Mice

Medicinal plants are widely used as supplements for the treatment of various diseases because of their few side-effects. Here, we examined the anti-obesity effects of a mixture extract of Cornus officinalis and Ribes fasciculatum (CR) in high-fat diet (HFD)-induced obese male mice. Four week old male C57BL/6J mice were fed a normal diet (ND) or 60% high-fat diet (HFD) with different concentrations of CR extracts (75, 150, and 300 mg/kg/day) by oral administration for 12 weeks. CR extract administration prevented HFD-induced weight gain, hepatic steatosis, and adipocyte enlargement through the downregulation of adipogenesis-associated genes in obese male mice. In addition, CR administration improved the impaired glucose metabolism, insulin action, biochemical obesity parameters, and metabolic profiles in HFD-induced male mice. Consequently, the CR extract exhibited beneficial effects on HFD-induced systemic metabolic challenges. Taken together, our findings suggest that CR extract may be a potent therapeutic supplement for the treatment and prevention of obesity.

Type 2 Diabetes Mellitus and Alzheimer Disease: A Review of the Potential Links

: Diabetes mellitus and Alzheimer’s disease are considered the most prevalent diseases in older ages worldwide. The main pathology of Alzheimer’s disease is highly related with accumulation of misfolded proteins that lead to neuronal dysfunction in the brain. On the other hand, diabetes mellitus is associated with alteration of insulin signaling, which could cause the reduction of glu-cose uptake, metabolic prohibition of energy consuming cells, as well as suppression of glucose to fat conversion in the liver. In spite of having seemingly different pathological features, both dis-eases share common underlying biological mechanisms. Besides, the epidemiological and envi-ronmental links between these two diseases should not be overlooked. In this study, we aim to review shared pathological mechanisms of Alzheimer’s disease and diabetes mellitus, including impaired glucose metabolism, increased Amyloid-Beta (Aβ) production, impaired lipid metabo-lism, mitochondrial dysfunction, increased inflammation and elevated oxidative stress. Further-more, we discuss epidemiological/environmental association between these two diseases and also review animal investigations, which have evaluated the potential links between the two diseases.