Management of familial hypercholesterolaemia (FH) may vary across different settings due to factors related to population characteristics, practice, resources and/or policies. We conducted a survey among the worldwide network of EAS FHSC Lead Investigators to provide an overview of FH status in different countries. Lead Investigators from countries formally involved in the EAS FHSC by mid-May 2018 were invited to provide a brief report on FH status in their countries, including available information, programmes, initiatives, and management. 63 countries provided reports. Data on FH prevalence are lacking in most countries. Where available, data tend to align with recent estimates, suggesting a higher frequency than that traditionally considered. Low rates of FH detection are reported across all regions. National registries and education programmes to improve FH awareness/knowledge are a recognised priority, but funding is often lacking. In most countries, diagnosis primarily relies on the Dutch Lipid Clinics Network criteria. Although available in many countries, genetic testing is not widely implemented (frequent cost issues). There are only a few national official government programmes for FH. Under-treatment is an issue. FH therapy is not universally reimbursed. PCSK9-inhibitors are available in ∼2/3 countries. Lipoprotein-apheresis is offered in ∼60% countries, although access is limited. FH is a recognised public health concern. Management varies widely across countries, with overall suboptimal identification and under-treatment. Efforts and initiatives to improve FH knowledge and management are underway, including development of national registries, but support, particularly from health authorities, and better funding are greatly needed.

Huntington disease (HD) is an autosomal dominant progressive neurodegenerative disorder characterized by involuntary movements, especially chorea; frank dementia; behavioral and psychiatric disturbances; and functional disability. It is caused by an unstable expanded CAG trinucleotide repeat in exon 1 on the huntingtin gene (HD [OMIM 143100) on the tip of the short arm of chromosome 4.¹

Type 2 diabetes (T2D), one of the most prevalent noncommunicable diseases, is often preceded by insulin resistance (IR), which underlies the inability of tissues to respond to insulin and leads to disturbed metabolic homeostasis. Mitochondria, as a central player in the cellular energy metabolism, are involved in the mechanisms of IR and T2D. Mitochondrial function is affected by insulin resistance in different tissues, among which skeletal muscle and liver have the highest impact on whole-body glucose homeostasis. This review focuses on human studies that assess mitochondrial function in liver, muscle and blood cells in the context of T2D. Furthermore, different interventions targeting mitochondria in IR and T2D are listed, with a selection of studies using respirometry as a measure of mitochondrial function, for better data comparison. Altogether, mitochondrial respiratory capacity appears to be a metabolic indicator since it decreases as the disease progresses but increases after lifestyle (exercise) and pharmacological interventions, together with the improvement in metabolic health. Finally, novel therapeutics developed to target mitochondria have potential for a more integrative therapeutic approach, treating both causative and secondary defects of diabetes.

Increased body weight as well as type 2 diabetes (T2D) are found to be associated with increased incidence of hypertension, although the mechanisms facilitating hypertension in T2D or nondiabetic individuals are not clear. Therefore, in this study we compared the levels of insulin resistance (IR:OGIS), plasma insulin (PI:RIA) levels, and pro-inflammatory cytokines (IL-6 and TNF-α: ELISA), being risk factors previously found to be associated with hypertension, in T2D patients showing increased body weight (obese and overweight, BMI ≥ 25 kg/m²) with hypertension (group A, N = 30), or without hypertension (group B, N = 30), and in nonobese (BMI < 25 kg/m²), normotensive controls (group C, N = 15). We found that OGIS index was the lowest (A: 267 ± 35.42 vs. B: 342.89 ± 32.0, p < 0.01) and PI levels were the highest (A: 31.05 ± 8.24 vs. B: 17.23 ± 3.23, p < 0.01) in group A. In addition, IL-6 levels were higher in group A (A: 15.46 ± 5.15 vs. B: 11.77 ± 6.09; p < 0.05) while there was no difference in TNF-α levels. Our results have shown that appearance of hypertension in T2D patients with increased body weight was dependent on further increase in IR which was associated with the rise in pro-inflammatory IL-6 cytokine. The results imply that lifestyle intervention aimed to decrease IR might be beneficial in reducing the risk for hypertension in those T2D individuals.

OBJECTIVE. Diabetes‐associated oxidative stress is a consequence of both increased production of free radicals and reduced capacity of antioxidative defense. Prolonged hyperglycemia is the major factor in the pathogenesis of atherosclerosis in diabetes which can lead to cardiovascular complications. The aim of this study was to test the parameters of antioxidative defense in type 2 diabetic patients. METHODS. A total of 117 type 2 diabetics with and without cardiovascular complications were examined in order to find out the influence of hyperglycemia, type and duration of complications and duration of diabetes on the extent of disorder of antioxidative parameter values: superoxide dismutase (SOD), glutathione peroxidase (GSH‐Px), glutathione reductase (GR) and total antioxidant status (TAS). RESULTS. Compared to healthy control subjects, type 2 diabetic patients with cardiovascular complications (CVC) had significantly lower SOD (P<0.0001), GSH‐Px (P<0.0001), GR ( P = 0.0002) and TAS values (P<0.0001). In type 2 diabetic subjects with CVC, males had significantly lower SOD (778.7±103.2 U/gHb, P<0.01) and GR activities (52.2±8.9 U/L, P<0.001) compared to females (839.3±94.9 U/gHb; 58.5±9.1 U/L). Significant and positive correlation was found between glucose levels and SOD (r = 0.375 for P<0.05) and GSH‐Px (r = 0.384, P<0.05 ) activity in the group of complications‐free diabetics, while significant negative correlation between glucose and GSH‐Px values (r = −0.382, P<0.05) was found in the group of type 2 diabetics with coronary artery disease (CAD) and hypertension (HTA) and with CAD and acute myocardial infarction (AMI) (r = −0.860 P<0.05), and highly negative correlation between glucose and SOD levels (r = −0.590, P<0.05) in the group of diabetic subjects with CAD, AMI and HTA. Likewise, there was highly significant negative correlation of SOD (r = −0.949, P<0.05) and TAS (r = −0.393 for P = 0.038) with duration of diabetes in the group of diabetics with CAD and HTA. CONCLUSION. Our results confirm the hypothesis that there is reduced antioxidative defense in type 2 diabetics with prominent cardiovascular complications, which negatively correlates with glucose concentrations and duration of diabetes and cardiovascular complications.

MTOR (mechanistic target of rapamycin) protein kinase acts as a central integrator of nutrient signaling pathways. Besides the immunosuppressive role after solid organ transplantations or in the treatment of some cancers, another promising role of mTOR inhibitor as an antiaging therapeutic has emerged in the recent years. Acute or intermittent rapamycin treatment has some resemblance to calorie restriction in metabolic effects such as an increased insulin sensitivity. However, the chronic inhibition of mTOR by macrolide rapamycin or other rapalogs has been associated with glucose intolerance and insulin resistance and may even provoke type II diabetes. These metabolic adverse effects limit the use of mTOR inhibitors. Metformin is a widely used drug for the treatment of type 2 diabetes which activates AMP‐activated protein kinase (AMPK), acting as calorie restriction mimetic. In addition to the glucose‐lowering effect resulting from the decreased hepatic glucose production and increased glucose utilization, metformin induces fatty acid oxidations. Here, we review the recent advances in our understanding of the metabolic consequences regarding glucose metabolism induced by mTOR inhibitors and compare them to the metabolic profile provoked by metformin use. We further suggest metformin use concurrent with rapalogs in order to pharmacologically address the impaired glucose metabolism and prevent the development of new‐onset diabetes mellitus after solid organ transplantations induced by the chronic rapalog treatment.