We describe the unique case of a patient in whom two ciliopathies with autosomal recessive transmission were clinically and molecularly diagnosed: Nephronophthisis type1 (NPHP1) and Alström Syndrome (AS). NPHP1 is one of the main genetic causes of terminal kidney failure in childhood. AS is an ultra-rare multi-systemic disease, characterized by progressive kidney disease, hepatic failure, dystrophy of the rods and cones to blindness, slowly progressive neuro-sensory deafness, dilated cardiomyopathy, obesity, insulin resistance / type 2 diabetes mellitus. The coexistence in the same patient of two rare syndromes with overlapping clinical manifestations but genetically different is an eventuality to be considered. This case report would describe the onset and progression of the multi-organ manifestations of both syndromes to highlight that ciliopathies present a strong phenotype overlap but also specific peculiarities. Therefore, to make a correct diagnosis, that is essential to achieve the best clinical management, could be challenging.

This systematic review provides a high-quality, comprehensive summary of recommendations on hypertension (HT) and type 2 diabetes mellitus (T2DM), accentuating patient blood pressure, HbA1c levels, patterns of drug treatment, management, and screening of these diseases. The overall objective of the review is to support adapting existing clinical practice guidelines in Indonesia, Vietnam, and Myanmar. The database PubMed and the web search engines Google and Google Scholar were searched from October to December 2019 for evidence-based guidelines covering the overall disease management in Europe, the United States of America, and low and middle-income countries (Indonesia, Vietnam, and Myanmar-IVM later on). Nine studies were selected for the review, seven concerning HT and five T2DM. Guidelines in IVM and Europe identified HT as increased blood pressure (BP; ≥140/90 mmHg). IVM guidelines also recommended commencing drug treatment if lifestyle interventions were not successful. Four international HT guidelines recommended monitoring BP every few months, and the other three guidelines gave recommendations based on the patient's current BP levels. All five T2DM guidelines recommended target HbA1c levels below 7%-6.5%, but only IVM guidelines included re-examination every 3-6 months. Metformin was recommended as the first choice of medical treatment, if not contraindicated. Amid the guidelines' recommendations, there were no major variations in the Class of recommendation and Level of evidence (except IVM guidelines where COR and LOE were missing). Revision and completion of IVM guidelines by this grading system would enhance evidence-based and informed decisions in clinical care.

Dyslipidemia is a hallmark of T2DM, and as such, analyses of lipid metabolic profiles in affected patients have the potential to permit the development of an integrated lipid metabolite-based biomarker model that can facilitate early patient diagnosis and treatment.

MicroRNAs (miRNAs) are critical regulators of gene expression in healthy and diseased states, and numerous studies have established their tremendous potential as a tool for improving the diagnosis of Type 2 Diabetes Mellitus (T2D) and its comorbidities. In this regard, we computationally identify novel top-ranked hub miRNAs that might be involved in T2D. We accomplish this via two strategies: 1) by ranking miRNAs based on the number of T2D differentially expressed genes (DEGs) they target, and 2) using only the common DEGs between T2D and its comorbidity, Alzheimer's disease (AD) to predict and rank miRNA. Then classifier models are built using the DEGs targeted by each miRNA as features. Here, we show the T2D DEGs targeted by hsa-mir-1-3p, hsa-mir-16-5p, hsa-mir-124-3p, hsa-mir-34a-5p, hsa-let-7b-5p, hsa-mir-155-5p, hsa-mir-107, hsa-mir-27a-3p, hsa-mir-129-2-3p, and hsa-mir-146a-5p are capable of distinguishing T2D samples from the controls, which serves as a measure of confidence in the miRNAs' potential role in T2D progression. Moreover, for the second strategy, we show other critical miRNAs can be made apparent through the disease's comorbidities, and in this case, overall, the hsa-mir-103a-3p models work well for all the datasets, especially in T2D, while the hsa-mir-124-3p models achieved the best scores for the AD datasets. To the best of our knowledge, this is the first study that used predicted miRNAs to determine the features that can separate the diseased samples (T2D or AD) from the normal ones, instead of using conventional non-biology-based feature selection methods.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic disorder and an important cause of end stage renal disease (ESRD). Tolvaptan (a V2R antagonist) is the first disease modifier drug for treatment of ADPKD, but also causes severe polyuria. AMPK activators have been shown to attenuate cystic kidney disease. Methods: In this study, we tested the efficacy of the combined administration of salsalate (a direct AMPK activator) and tolvaptan using clinically relevant doses in an adult-onset conditional Pkd1 knock-out (KO) mouse model. Results: Compared to untreated Pkd1 mutant mice, the therapeutic effects of salsalate were similar to that of tolvaptan. The combined treatment tended to be more effective than individual drugs used alone, and was associated with improved kidney survival (p < 0.0001) and reduced kidney weight to body weight ratio (p < 0.0001), cystic index (p < 0.001) and blood urea levels (p < 0.001) compared to untreated animals, although the difference between combination and single treatments was not statistically significant. Gene expression profiling and protein expression and phosphorylation analyses support the mild beneficial effects of co-treatment, and showed that tolvaptan and salsalate cooperatively attenuated kidney injury, cell proliferation, cell cycle progression, inflammation and fibrosis, and improving mitochondrial health, and cellular antioxidant response. Conclusion: These data suggest that salsalate-tolvaptan combination, if confirmed in clinical testing, might represent a promising therapeutic strategy in the treatment of ADPKD.

Nonalcoholic steatohepatitis (NASH), also known as metabolic steatohepatitis, is a clinical syndrome with pathological changes like alcoholic hepatitis but without a history of excessive alcohol consumption. NASH is closely related to metabolic disorders such as obesity, insulin resistance, type 2 diabetes mellitus, and hyperlipidemia. Its main characteristics are hepatocyte steatosis with hepatocyte injury and inflammation. In severe cases, it can develop into liver cirrhosis. At present, there is no special treatment for NASH. Theabrownin (TB) is the main pigment substance in fermented tea. Theabrownin has beneficial effects on lipid metabolism and intestinal flora. However, the effect of theabrownin on NASH has not been studied.

Post-viral new-onset diabetes has been an important feature of the COVID-19 pandemic. It is not always clear if new-onset diabetes is the unmasking of a previously undiagnosed condition, the acceleration of prediabetes, or new-onset diabetes that would not have otherwise occurred. Even asymptomatic cases of COVID-19 have been associated with new-onset diabetes. Diabetes that emerges during acute COVID-19 infection tends to have an atypical presentation, characterized by hyperglycemia and potentially life-threatening diabetic ketoacidosis. It is not always clear if new-onset diabetes is type 1 or type 2 diabetes mellitus. Many cases of COVID-associated diabetes appear to be type 1 diabetes, which is actually an autoimmune disorder. The clinical course varies temporally and with respect to outcomes; in some cases, diabetes resolves completely or improves incrementally after recovery from COVID-19. Disruptions in macrophagy caused by COVID-19 infection along with an exaggerated inflammatory response that can occur in COVID-19 also play a role. Those who survive COVID-19 remain at a 40% elevated risk for diabetes in the first year, even if their case of COVID-19 was not particularly severe. A subsequent post-pandemic wave of new diabetes patients may be expected.

Objective: To investigate the risk factors of diabetic nephropathy (DN) in primary type 2 diabetes mellitus (T2DM) patients and to quantitatively analyze the risk of DN by nomogram modeling. Methods: A total of 1 588 primary T2DM patients from 17 townships and streets in Zhejiang Province were enrolled from June 2018 to August 2018 in this cross-sectional study, with an average age of (56.8±10.1) years (50.06% male) and a mean disease duration of 9 years. The clinical data, biochemical test results, and fundus photographs of all T2DM patients were collected, and logistic regression analysis was used to screen the risk factors of DN. Then, a nomogram model was used to quantitatively analyze the risk of DN. Results: DN occurred in 27.71% (440/1 588 cases) primary type 2 diabetes patients. Hemoglobin A1c (HbA1c) (OR=1.159, 95%CI 1.039-1.292), systolic blood pressure (OR=1.041, 95%CI 1.031-1.051), serum creatinine (Scr) (OR=1.011, 95%CI 1.004-1.017), serum globulin (GLOB) (OR=1.072, 95%CI 1.039-1.105), diabetic retinopathy (DR) (OR=1.463, 95%CI 1.073-1.996), education level of more than junior high school (OR=2.018, 95%CI 1.466-2.777), and moderate-intensity exercise (OR=0.751, 95%CI 0.586-0.961) were influencing factors of DN. Nomogram model analysis showed that the total score of each factor of DN ranged from 64-138 points, and the corresponding risk rate ranged from 0.1-0.9. The nomogram model also predicted a C-index value of 0.753 (95%CI 0.726-0.781) and an area under the receiver operating characteristic curve of DN of 0.753. Internal verification of the C-index reached 0.738. The model displayed medium predictive power and could be applied in clinical practice. Conclusions: HbA1c, systolic blood pressure, Scr, GLOB, DR, and more than a junior high school education are independent risk factors of DN. Nomogram modeling can more intuitively evaluate the risk of DN in primary T2DM patients.

Achondroplasia is a rare skeletal dysplasia characterized by rhizomelic short stature, whose prevalence is about 1 per 25,000 births. For some patients with achondroplasia, excess body weight is one of the major concerns due to an impaired linear growth. Epidemiological studies revealed a premature onset of cardiovascular or cerebrovascular events in achondroplasia. An association between obesity and cardiometabolic risk factors related to cardiovascular events remains unknown in patients with achondroplasia/hypochondroplasia. This cross-sectional study investigated anthropometric measurements, body compositions and cardiometabolic risk factors in pediatric patients with achondroplasia/hypochondroplasia. Thirty-two patients with achondroplasia and ten with hypochondroplasia aged between 1.9 and 18.7 years were enrolled in this study. Half of the participants presented at least one cardiometabolic abnormality. Elevated systolic blood pressure was the most common abnormality. None of the participants developed metabolic syndrome or type 2 diabetes mellitus. Body mass index-standard deviation score and hip/height ratio were strongly correlated with percent body fat assessed by dual energy X-ray absorptiometry although no significant association was found between anthropometric measurements or body fat mass and any cardiometabolic risk factors. No significant difference in body fat mass, as well as body mass index-standard deviation score and hip/height, was found between cardiometabolically normal group and cardiometabolically abnormal groups. These results suggest that not only weight gain and hip/height changes should be monitored but also individual cardiometabolic risk factors should be evaluated to avoid cardiometabolic events in the healthcare management of pediatric patients with achondroplasia/hypochondroplasia.

Diabetic gastroparesis (DGP) is characterized by delayed gastric emptying of solid food without mechanical obstruction. Nitrergic neuron-mediated fundus relaxation and intragastric peristalsis are pivotal for gastric emptying and are impaired in patients with DGP. Transient receptor potential vanilloid 1 (TRPV1) ion channels are expressed in gastrointestinal vagal afferent nerves and have potential role in relevant gastrointestinal disorders. In this study, mice with high fat diet (HFD)-induced type 2 diabetes mellitus (T2DM), associated with gastroparesis, were used to determine the role of TRPV1 in DGP. After feeding with HFD, mice exhibited obesity, hyperglycemia, insulin resistance, and delayed gastric emptying. Cholinergic- and nitrergic-mediated neuromuscular contractions and relaxation were impaired. The antral tone of the DGP mice was also attenuated. Interestingly, activating or suppressing TRPV1 facilitates or inhibits gastric fundus relaxation in normal mice. These effects were neutralized using a nitric oxide synthase (NOS) inhibitor. Activation or suppression of TRPV1 also increases or reduces NO release. TRPV1 is specifically localized with nNOS in the gastric fundus. These data suggested that TRPV1 activation facilitates gastric fundus relaxation by regulating nNOS and promoting NO release. However, these effects and mechanisms disappeared in HFD diet induced DGP mice. TRPV1 expression was only marginally decreased in the fundus of DGP mice. TRPV1 dysfunction may be a potential mechanism underlying the dysfunction of DGP gastric nitrergic neuromuscular relaxation.

The intestine is responsible for efficient absorption and packaging of dietary lipids before they enter the circulatory system. This review provides a comprehensive overview of how intestinal enterocytes from diverse model organisms absorb dietary lipid and subsequently secrete the largest class of lipoproteins (chylomicrons) to meet the unique needs of each animal. We discuss the putative relationship between diet and metabolic disease progression, specifically Type 2 Diabetes Mellitus. Understanding the molecular response of intestinal cells to dietary lipid has the potential to undercover novel therapies to combat metabolic syndrome.

Islet β-cell dysfunction is a basic pathophysiological characteristic of type 2 diabetes mellitus. Appropriate assessment of islet β-cell function is beneficial to better management ofT2DM. Protecting islet β-cell function is vital to delay the progress of type 2 diabetes mellitus. Therefore, the Pancreatic Islet β-cell Expert Panel of the Chinese Diabetes Society and Endocrinology Society of Jiangsu Medical Association organized experts to draft the "Clinical expert consensus on the assessment and protection of pancreatic islet β-cell function in type 2 diabetes mellitus." This consensus suggests that β-cell function can be clinically assessed using blood glucose-based methods or methods that combine blood glucose and endogenous insulin or C-peptide levels. Some measures, including weight loss and early and sustained euglycemia control, could effectively protect islet β-cell function, and some newly developed drugs, such as Sodium-glucose cotransporter-2 inhibitor and Glucagon-like peptide-1 receptor agonists, could improve islet β-cell function, independent of glycemic control.