Gaps in the Care of Subjects with Familial Hypercholesterolemia: Insights from the Thai Familial Hypercholesterolemia Registry.

AIMS: Familial hypercholesterolemia (FH) is currently underdiagnosed and undertreated. The establishment of a FH registry could facilitate a deeper understanding of this disease. We described the clinical characteristics of subjects with FH from the Thai FH Registry, compared our data with the regional and global data, and identified gaps in the care of these subjects. METHODS: A multicenter, nationwide prospective FH registry was established in Thailand. Our data were compared with those of the European Atherosclerosis Society-FH Studies Collaboration. Multiple logistic regression analyses were performed for variables associated with lipid-lowering medication (LLM) use and the attainment of low-density lipoprotein-cholesterol (LDL-C) goal. RESULTS: The study includes 472 subjects with FH (mean age at FH diagnosis: 46±12 years, 61.4% women). A history of premature coronary artery disease was found in 12%. The percentage of LLM use in subjects with a Dutch Lipid Clinic Network score of ≥ 6 (probable or definite FH) in our registry (64%) was slightly lower than the regional data but higher than the global data. Among those who received statins, 25.2% and 6.4% achieved LDL-C levels of ＜100 mg/dL and ＜70 mg/dL, respectively. Women with FH were less likely to achieve LDL-C ＜70 mg/dL (adjusted odds ratio: 0.22, 95% confidence interval: 0.06-0.71, p=0.012). CONCLUSIONS: FH in Thailand was diagnosed late, and treatment was inadequate for the majority of subjects. Women with FH were less likely to achieve LDL-C goals. Our insights could potentially help raise awareness and narrow the gap in patient care.

Effect of acute TLR4 inhibition on insulin resistance in humans.

BackgroundStudies in cell cultures and rodents suggest that TLR4 is involved in the pathogenesis of insulin resistance, but direct data in humans are limited. We tested the hypothesis that pharmacologic blockade of TLR4 with the competitive inhibitor eritoran would improve insulin resistance in humans.MethodsIn protocol I, 10 lean, healthy individuals received the following 72-hour i.v. infusions in a randomized crossover design: saline (30 mL/h) plus vehicle; Intralipid (30 mL/h) plus vehicle; or Intralipid (30 mL/h) plus eritoran (12 mg i.v. every 12 hours). In protocol II, also a randomized crossover design, 9 nondiabetic individuals with obesity received eritoran or vehicle for 72 hours. The effect of eritoran was assessed with euglycemic hyperinsulinemic clamps.ResultsIn protocol I, lipid infusion significantly decreased peripheral insulin sensitivity (M value) by 14% and increased fasting plasma glucose (FPG) concentrations, fasting plasma insulin (FPI) concentrations, and the homeostatic model assessment of insulin resistance (HOMA-IR) index by 7%, 22%, and 26%, respectively. Eritoran did not prevent lipid-induced alterations of these metabolic parameters. Eritoran also failed to improve any baseline metabolic parameters (M, FPG, FPI, HOMA-IR) in individuals with obesity and insulin resistance (protocol II).ConclusionsAcute TLR4 inhibition with eritoran did not protect against lipid-induced insulin resistance. Short-term eritoran administration also failed to improve obesity-associated insulin resistance. These data do not support a role for TLR4 in insulin resistance. Future studies with a different class of TLR4 inhibitors, longer drug exposure, and/or lipid-enhancing interventions richer in saturated fats may be needed to further clarify the role of TLR4 in metabolic dysfunction in humans.Trial registrationClinicalTrials.gov NCT02321111 and NCT02267317.FundingNIH grants R01DK080157, P30AG044271, P30AG013319, and UL1TR002645.

National trends in the prevalence of glycemic control among patients with type 2 diabetes receiving continuous care in Thailand from 2011 to 2018.

Diabetes is one of the largest global health problems and exhibits a constantly increasing trend. A series of nationwide hospital-based cross-sectional surveys of clinical outcomes was performed annually from 2011 to 2015 and 2018 among patients with type 2 diabetes aged ≥ 20 years receiving medical care for at least 12 months. A two-stage stratified cluster that was proportional to the size sampling technique was used to select a nationally and provincially representative sample of patients with type 2 diabetes in Thailand. A total of 186,010 patients with type 2 diabetes were enrolled in the study from 2011 to 2018. The prevalence of adequate glycemic control (hemoglobinA1c level < 7.0%) among patients with type 2 diabetes were estimated to be 34.5% (95%CI 33.8-35.2%) in 2011, 33.0% (95%CI 32.4-33.6%) in 2012, 34.7% (95%CI 34.1-35.4%) in 2013, 35.5 (95%CI 34.9-36.1%) in 2014, 35.6 (95%CI 35.0-36.2%) in 2015, and 35.6% (95%CI 35.0-36.2%) in 2018, respectively (p for trend < 0.001). Independent factors related to poor glycemic control (hemoglobinA1c ≥ 7%) were being female, younger aged, living in the northeastern region, received care form hospitals lower than regional level, under universal health coverage scheme, greater duration of diabetes, higher body mass index level and absence of hypertension comorbidity.

Apolipoprotein B level in patients with type 2 diabetes who achieved goal of low density lipoprotein cholesterol and non-high density lipoprotein cholesterol.

OBJECTIVE: To demonstrate an apolipoprotein B (apo B) level in type 2 diabetic patients who achieved goal of low density lipoprotein cholesterol (LDL-c) and non-high density lipoprotein cholesterol (non-HDL-c). To identify the percentage of type 2 diabetes patients who achieved goal of apo B level. MATERIAL AND METHOD: A cross-sectional study was carried out from 1 October to 31 December 2008. Type2 diabetes patients who attended at diabetes clinics in the Phramongkutklao hospitals have determined the risk for develop cardiovascular diseases (CVD) and set up the goal for lipid level according to consensus statement from the American Diabetes Association (ADA) and the American College of Cardiology (ACC) foundation. Blood test for apo B will be done only the patients who achieved goal of LDL-c and non-HDL-c. RESULTS: 133 of the 162 registered diabetic patients can achieve goal of lipid level In this population, 9.7 percent (%) (n = 13) had a history of CVD. ApoB level in diabetic patients with and without CVD is 61.72 +/- 12.63 and 67.2 +/- 12.92 milligram per deciliter (mg/dL), respectively. Nearly ninety-eight percent of patients without cardiovascular diseases (CVD) have achieved apo B (< 90 mg/dL) goal, and 92.3% of patients with CVD have achieved apo B (< 80 mg/dL) goal. The two most commonly used lipid-lowering agents were statins and fibrates. CONCLUSION: In patients with type 2 diabetes who achieved goal of LDL-c and non-HDL-c have also achieved apo B level. Thus, apo B measurement in addition to reached LDL-c and non-HDL-c targets may be not necessary especially in diabetic patients who did not previous CVD.

Beta Cell Function and Insulin Resistance After Conversion from Tacrolimus Twice-Daily to Extended-Release Tacrolimus Once-Daily in Stable Renal Transplant Recipients.

BACKGROUND Post-transplantation diabetes mellitus is a major metabolic adverse effect of tacrolimus (TAC). The objective of this study was to determine if the conversion from tacrolimus twice-daily (TAC-BID) to extended-release tacrolimus once-daily (TAC-OD) in stable renal transplant recipients had any effect on beta cell function (HOMA-b), insulin resistance (HOMA-IR), patient preference, and expense. MATERIAL AND METHODS Twenty-eight renal transplant recipients were recruited and converted from TAC-BID to TAC-OD at the same dose. Primary outcomes were beta cell function and insulin resistance in stable renal transplant recipients at 4, 8, and 16 weeks after conversion. Secondary outcomes were patient satisfaction and expense of medication. RESULTS No significant change in the HOMA-ß and HOMA-IR was found in any of the 28 renal transplant recipients. However, HOMA-ß increased from 60 (37.33, 109.71) to 78.5 (44.3, 108.4) (p=0.02) in 15 patients who had the conversion within 4 years after renal transplantation. In multivariate regression analysis, the conversion from TAC-BID to TAC-OD significantly increased HOMA-b at 4 months at 1.21 mIU/mmol (95%CI 0.54-1.88 mIU/mmol, p=0.01) in this subgroup. The renal transplant recipients reported the conversion was more satisfactory and cost of treatment was comparable. CONCLUSIONS In short-term follow-up, conversion from TAC-BID to TAC-OD is safe in stable renal transplant recipients and might be beneficial in term of improved beta cell function in the early years after renal transplantation. The conversion caused comparable cost and was preferred by renal transplant recipients.