Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

Familial hypercholesterolaemia in children and adolescents from 48 countries : a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11848 individuals. Median age at registry entry was 9·6 years (IQR 5·8–13·2). 10 099 (89·9%) of 11235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05–6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50–75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life.peer-reviewe

CETP deficiency due to a novel mutation in the CETP gene promoter and its effect on cholesterol efflux and selective uptake into hepatocytes

International audienc

Salivary and serum interleukin-17A and interleukin-18 levels in patients with type 2 diabetes mellitus with and without periodontitis.

OBJECTIVE:Interleukin (IL)-17A and IL-18 have been proposed to play important roles in periodontitis and type 2 diabetes mellitus (DM), but human data are conflicting. The present study aimed to investigate the roles of IL-17A and IL-18 in periodontitis and DM by measuring salivary and serum levels, respectively. MATERIALS AND METHODS:A total of 49 participants with type 2 DM and 25 control subjects without type 2 DM were recruited. A periodontal screening and recording (PSR) index (0, 1-2, 3, and 4) was used to classify whether these subjects had periodontitis. Salivary and serum IL-17A and IL-18 levels were measured by enzyme-linked immunosorbent assay. Multiple linear regression analyses were used to evaluate the associations between these cytokines and clinical parameters. RESULTS:Salivary IL-17A levels were not significantly different between patients with DM and controls, however, the levels were significantly higher in controls with periodontitis than those without periodontitis (p = 0.031). Salivary IL-17A levels were significantly associated with the PSR index (β = 0.369, p = 0.011). Multiple linear regression analyses revealed the association of salivary IL-18 levels and fasting plasma glucose (β = 0.270, p = 0.022) whereas serum IL-18 levels were associated with HbA1C (β = 0.293, p = 0.017). No correlation between salivary and serum levels of IL-17A and IL-18 was found. CONCLUSION:Salivary IL-17A was strongly associated with periodontitis, whereas salivary IL-18 was associated with FPG and serum IL-18 was associated with HbA1C. These results suggest the role of these cytokines in periodontal inflammation and DM

Immediate and long‐term effects of a very‐low‐calorie diet on diabetes remission and glycemic control in obese Thai patients with type 2 diabetes mellitus

AIM A very‐low‐calorie diet (VLCD) can reverse the underlying defects of type 2 diabetes mellitus (DM) in obese subjects. We determined the efficacy, safety, and durability of VLCD in Thai patients with DM and obesity. METHODS Twenty Thai patients with DM and obesity were enrolled. After a 2‐week trial, VLCD (600 kcal/day) was continued for 8 weeks, followed by a 4‐week transition period. Data on diabetes remission (fasting plasma glucose level <126 mg/dl and HbA1c <6.5% without the use of glucose‐lowering medications), glycemic control, metabolic parameters, and quality of life (QOL) were collected along with indices of insulin resistance (IR) and beta cell function. Glycemic control 12 months after discontinuation of VLCD was also examined. RESULTS Among 19 patients (age 48 ± 2 years, BMI 27.7 kg/m2) who completed the study, rapid improvement in glycemic control was observed in the first 2 weeks of VLCD. At both 8 and 12 weeks, diabetes remission was achieved in 79%. Significant weight loss was accompanied by a significant reduction in IR and an increase in beta cell function, starting at 4 weeks of VLCD. QOL also significantly increased. At 12 months after VLCD, however, DM remission was achieved in approximately 30%. CONCLUSION Very‐low‐calorie diet was effective and safe in inducing short‐term diabetes remission in Thai subjects by ameliorating beta cell function and IR. Optimal long‐term glycemic control was potentially durable as one‐third of subjects remained without diabetes medication 12 months after VLCD

Immediate and long‐term effects of a very‐low‐calorie diet on diabetes remission and glycemic control in obese Thai patients with type 2 diabetes mellitus

AIM A very‐low‐calorie diet (VLCD) can reverse the underlying defects of type 2 diabetes mellitus (DM) in obese subjects. We determined the efficacy, safety, and durability of VLCD in Thai patients with DM and obesity. METHODS Twenty Thai patients with DM and obesity were enrolled. After a 2‐week trial, VLCD (600 kcal/day) was continued for 8 weeks, followed by a 4‐week transition period. Data on diabetes remission (fasting plasma glucose level <126 mg/dl and HbA1c <6.5% without the use of glucose‐lowering medications), glycemic control, metabolic parameters, and quality of life (QOL) were collected along with indices of insulin resistance (IR) and beta cell function. Glycemic control 12 months after discontinuation of VLCD was also examined. RESULTS Among 19 patients (age 48 ± 2 years, BMI 27.7 kg/m2) who completed the study, rapid improvement in glycemic control was observed in the first 2 weeks of VLCD. At both 8 and 12 weeks, diabetes remission was achieved in 79%. Significant weight loss was accompanied by a significant reduction in IR and an increase in beta cell function, starting at 4 weeks of VLCD. QOL also significantly increased. At 12 months after VLCD, however, DM remission was achieved in approximately 30%. CONCLUSION Very‐low‐calorie diet was effective and safe in inducing short‐term diabetes remission in Thai subjects by ameliorating beta cell function and IR. Optimal long‐term glycemic control was potentially durable as one‐third of subjects remained without diabetes medication 12 months after VLCD

Multiplex recombinase polymerase amplification for high-risk and low-risk type HPV detection, as potential local use in single tube

Abstract High rates of new cervical cancer cases and deaths occur in low- and middle-income countries yearly, and one reason was found related to limitation of regular cervical cancer screening in local and low-resource settings. HPV has over 150 types, yet certain 14–20 high-risk and 13–14 low-risk types are common, and, thus, most conventional HPV nucleic acid assays, for examples, Cobas 4800 HPV test (Roche Diagnostics, New Jersey, USA) and REBA HPV-ID (Molecules and Diagnostics, Wonju, Republic of Korea) were developed to cover these types. We thereby utilized bioinformatics combined with recent isothermal amplification technique at 35–42 °C to firstly describe multiplex recombinase polymerase amplification assay that is specific to these common 20 high-risk and 14 low-risk types, and also L1 and E6/E7 genes that target different stages of cervical cancer development. Multiplex primer concentrations and reaction incubation conditions were optimized to allow simultaneous two gene detections at limit of detection of 1000 copies (equivalent to 2.01 fg) for L1 and 100 copies (0.0125 fg) for E6/E7, respectively. The assay was validated against urogenital and other pathogens, normal flora, and human control. In 130 real clinical sample tests, the assay demonstrated 100% specificity, 78% diagnostic accuracy, and 75% sensitivity compared with REBA HPV-ID test, and is much more rapid (15–40 min), less expensive (~ 3–4 USD/reaction) and does not require instrumentation (35–42 °C reaction condition so hand holding or tropical temperature is possible). Hence, the developed novel assay provides alternative screening tool for potential local screening. Furthermore, as this assay uses safe chemical reagents, it is safe for users