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.

Genetic diagnosis for adult patients at a genetic clinic.

Clinical utility of genetic testing has rapidly increased in the past decade to identify the definitive diagnosis, etiology, and specific management. The majority of patients receiving testing are children. There are several barriers for genetic tests in adult patients; barriers may arise from either patients or clinicians. Our study aims to realize the detection rate and the benefits of genetic tests in adults. We conducted a prospective study of 10 adult patients who were referred to a genetic clinic. Exome sequencing (ES) was pursued in all cases, and chromosomal microarray (CMA) was performed for six cases. Our result is impressive; six cases (60%) received likely pathogenic and pathogenic variants. Four definitive diagnosis cases had known pathogenic variants in KCNJ2, TGFBR1, SCN1A, and FBN1, whereas another two cases revealed novel likely pathogenic and pathogenic variants in GNB1 and DNAH9. Our study demonstrates the success in genetic diagnosis in adult patients: four cases with definitive, two cases with possible, and one case with partial diagnosis. The advantage of diagnosis is beyond obtaining the diagnosis itself, but also relieving any doubt for the patient regarding any previous questionable diagnosis, guide for management, and recurrence risk in their children or family members. Therefore, this supports the value of genetic testing in adult patients.

Implementation of diabetes care and educational program via telemedicine in patients with COVID-19 in home isolation in Thailand: A real-worldexperience.

BACKGROUND: The coronavirus disease (COVID-19) outbreak in Bangkok led to a shortage of hospital capacity, and a home isolation system was set up. We described the process of diabetes self-management education and support (DSMES) and glycemic management via telemedicine, along with outcomes in home-isolated patients with COVID-19 infection. METHODS: A retrospective chart review of glucose values, insulin and corticosteroids use, and outcomes was performed. RESULTS: A volunteer group of 21 endocrinologists and 21 diabetes educators/nurses formed the consultation team. Patients with diabetes or at high-risk of diabetes and receiving corticosteroids were referred by primary volunteer physicians. Glucometers and related supplies, and insulin were donated, and delivered via same-day delivery services. A chat group of an individual patient/their caregiver, diabetes educator, endocrinologist, and primary physician was formed (majority via LINE® platform) to assess the patient's clinical status and need. Real-time virtual DSMES sessions were performed and treatments were adjusted via smartphone application or telephone. There were 119 patients (1,398 service days), mean (SD) age 62.0 (13.6) years, 85.7% had a history of type 2 diabetes, and 84.0% received corticosteroids. Insulin was used in 88 patients; 69 of whom were insulin-naïve. During the first 10 days, there were 2,454 glucose values. The mean glucose level on day 1 was 280.6 (122.3) mg/dL, and declined to 167.7 (43.4) mg/dL on day 10. Hypoglycemia occurred in 1.4% of the values. A majority of patients (79.5%) recovered at home. CONCLUSION: Diabetes care and DSMES delivered via telemedicine to patients on home isolation during COVID-19 pandemic was safe and effective.

Lack of Seasonal Differences in Basal Metabolic Rate in Humans: A Cross-Sectional Study.

Some studies indicate that basal metabolic rate is greater in winter than in the summer, suggesting a role for brown fat in human thermogenesis. We examined whether there are clinically meaningful differences in basal metabolic rate under thermoneutral conditions between winter and summer months in inhabitants of Rochester, Minnesota. We collated data from 220 research volunteers studied in the winter (December 1 - February 28) and 214 volunteers studied in the summer (June 1 - August 31), 1995-2012. Basal metabolic rate was measured by indirect calorimetry and body composition by dual-energy X-ray absorptiometry. The effect of season on basal metabolic rate was tested using multivariate regression analysis with basal metabolic rate as the dependent variable and fat-free mass, fat mass, age, sex, and season as the independent variables. The groups were comparable with respect to age, body mass index, fat mass, and fat-free mass. There was no significant difference in basal metabolic rate between winter and summer groups (1 667±322 vs. 1 669±330 kcal/day). Both winter and summer basal metabolic rates were strongly predicted by fat-free mass (Pearson's r=0.75 and r=0.77, respectively, p <0.0001). Using multiple linear regression analysis, basal metabolic rate was significantly, independently predicted by fat-free mass, fat mass, age, and sex, but not season. We conclude that the lack of seasonal variation of thermoneutral basal metabolic rate between winter and summer suggests that modern, Western populations do not engage thermogenically detectable brown fat activity during periods of living in a cold climate.

Does basal metabolic rate predict weight gain?

BACKGROUND: Some previous studies have indicated that a low basal metabolic rate (BMR) is an independent predictor of future weight gain, but low rates of follow-up and highly select populations may limit the ability to generalize the results. OBJECTIVE: We assessed whether adults with a low BMR gain more weight than do adults with a high BMR who are living in a typical Western environment. DESIGN: We extracted BMR, body-composition, demographic, and laboratory data from electronic databases of 757 volunteers who were participating in our research protocols at the Mayo Clinic between 1995 and 2012. Research study volunteers were always weight stable, had no acute illnesses and no confounding medication use, and were nonsmokers. The top and bottom 15th percentiles of BMR, adjusted for fat-free mass (FFM), fat mass, age, and sex, were identified. Follow-up electronic medical record system data were available for 163 subjects, which allowed us to determine their subsequent weight changes for ≥3 y (mean: ∼9.7 y). RESULTS: By definition, the BMR was different in the high-BMR group (2001 ± 317 kcal/d; n = 86) than in the low-BMR group (1510 ± 222 kcal/d; n = 77), but they were comparable with respect to age, body mass index, FFM, and fat mass. Rates of weight gain were not greater in the bottom BMR group (0.3 ± 1.0 kg/y) than in the top BMR group (0.5 ± 1.5 kg/y) (P = 0.17). CONCLUSION: Adults with low BMRs did not gain more weight than did adults with high BMRs, implying that habitual differences in food intake or activity counterbalance variations in BMR as a risk factor for weight gain in a typical Western population.

Diagnosis and treatment of high density lipoprotein deficiency.

Low serum high density lipoprotein cholesterol level (HDL-C) <40 mg/dL in men and <50 mg/dL in women is a significant independent risk factor for cardiovascular disease (CVD), and is often observed in patients with hypertriglyceridemia, obesity, insulin resistance, and diabetes. Patients with marked deficiency of HDL-C (<20 mg/dL) in the absence of secondary causes are much less common (<1% of the population). These patients may have homozygous, compound heterozygous, or heterozygous defects involving the apolipoprotein (APO)AI, ABCA1, or lecithin:cholesterol acyl transferase genes, associated with apo A-I deficiency, apoA-I variants, Tangier disease , familial lecithin:cholesteryl ester acyltransferase deficiency, and fish eye disease. There is marked variability in laboratory and clinical presentation, and DNA analysis is necessary for diagnosis. These patients can develop premature CVD, neuropathy, kidney failure, neuropathy, hepatosplenomegaly and anemia. Treatment should be directed at optimizing all non-HDL risk factors.

Moringa Oleifera Leaf Increases Insulin Secretion after Single Dose Administration: A Preliminary Study in Healthy Subjects.

BACKGROUND: Herbal medicine has long been used as an alternative medicine for treatment of type 2 diabetes mellitus (T2DM). Recently, Moringa oleifera (MO or ma-rum in Thai) leaf has been widely used in T2DM patients. Several studies in diabetes rat model have shown that MO had effect on glucose metabolism. However study in humans is lacking. OBJECTIVE: Examine effects of MO on plasma glucose and insulin secretion. MATERIAL AND METHOD: Ten healthy volunteers were enrolled in this study (mean age 29 ± 5 years; BMI 20.6 ± 1.5 kg/m2; FPG 81 ± 5 mg/dl). After an overnight fast and every two weeks, subjects received an oral dose of MO at increasing dosages of 0, 1, 2, and 4 g. Plasma glucose (PG) and insulin were collected at baseline and at 0.5, 1, 1.5, 2, 4, and 6 hours after each MO dosage administration. Insulin secretion rate was measured using area under the curve (AUC) of insulin and AUC of insulin/glucose ratio. RESULTS: After doses of 0, 1, 2, and 4 g MO, mean plasma insulin increased (2.3 ± 0.9, 2.7 ± 1.0, 3.3 ± 1.4, and 4.1 ± 1.7 µU/ml, respectively) despite there being no differences in mean PG (77 ± 6, 78 ± 5, 79 ± 6, and 79 ± 5 mg/dl, respectively). AUC of insulin was greater after high-dose MO (4 g) than after baseline or low-dose MO capsule (1 g) (24.0 ± 3.5 vs. 14.5 ± 1.8 or 16.1 ± 2.0, respectively; p = 0.03), while there was no difference in AUC of glucose. Accordingly, insulin secretion rate represented by AUC of insulin/glucose ratio after high-dose MO was significantly increased by 74% (P = 0.041), as compared with that of baseline. CONCLUSION: We concluded that high-dose (4 g) MO leaf powder capsules significantly increased insulin secretion in healthy subjects. These results suggest that MO leaf may be a potential agent in the treatment of type 2 diabetes. Further studies of MO in patients with T2DM are needed.

The Risk for New-Onset Diabetes Mellitus after Kidney Transplantation in Patients with Autosomal Dominant Polycystic Kidney Disease: A Systematic Review and Meta-Analysis.

OBJECTIVES: New-onset diabetes after kidney transplantation (NODAT) is associated with both renal allograft failure and increased rates of mortality. The objective of this meta-analysis was to evaluate the risk for NODAT in patients with autosomal dominant polycystic kidney disease (ADPKD). METHODS: A literature search was performed using MEDLINE, EMBASE and Cochrane Database of Systematic Reviews from inception through July 2015. Studies that reported relative risks, odd ratios or hazard ratios comparing the risk for NODAT in patients with ADPKD were included. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using a random-effect, generic inverse variance method. RESULTS: Included in the analysis were 12 cohort studies, which comprised 1379 patients with ADPKD of a total of 9849 patients who had undergone kidney transplants. The pooled RRs of NODAT in patients with ADPKD were 1.92 (95% CI, 1.36 to 2.70). When meta-analysis was limited only to studies with confounder-adjusted analysis, the pooled RRs for NODAT were 1.98 (95% CI, 1.33 to 2.94). However, the association between NODAT requiring insulin treatment was insignificant, with pooled RRs of 1.57 (95% CI, 0.75 to 3.27). CONCLUSIONS: Our meta-analysis demonstrates a significant association between ADPKD and NODAT in recipients of kidney transplants. The findings of this study may impact clinical management and follow up for patients with ADPKD after kidney transplantation.

The risk of kidney stones following bariatric surgery: a systematic review and meta-analysis.

BACKGROUND: With rising prevalence of morbid obesity, the number of bariatric surgeries performed each year has been increasing worldwide. The objective of this meta-analysis was to assess the risk of kidney stones following bariatric surgery. METHODS: A literature search was performed using MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews from inception through July 2015. Only studies reporting relative risks, odd ratios or hazard ratios (HRs) to compare risk of kidney stones in patients who underwent bariatric surgery versus no surgery were included. Pooled risk ratios (RR) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method. RESULTS: Four studies (One randomized controlled trial and three cohort studies) with 11,348 patients were included in analysis to assess the risk of kidney stones following bariatric surgery. The pooled RR of kidney stones in patients undergoing bariatric surgery was 1.22 (95% CI, 0.63-2.35). The type of bariatric surgery subgroup analysis demonstrated an increased risk of kidney stones in patients following Roux-en-Y gastric bypass (RYGB) with the pooled RR of 1.73 (95% CI, 1.30-2.30) and a decreased risk of kidney stones in patients following restrictive procedures including laparoscopic banding or sleeve gastrectomy with the pooled RR of 0.37 (95% CI, 0.16-0.85). CONCLUSIONS: Our meta-analysis demonstrates an association between RYGB and increased risk of kidney stones. Restrictive bariatric surgery, on the other hand, may decrease kidney stone risk. Future study with long-term follow-up data is needed to confirm this potential benefit of restrictive bariatric surgery.

Case report: A novel apolipoprotein A-I missense mutation apoA-I (Arg149Ser)Boston associated with decreased lecithin-cholesterol acyltransferase activation and cellular cholesterol efflux.

We report a novel heterozygous apolipoprotein A-I (apoA-I) missense mutation (c.517C>A, p.Arg149Ser, designated as apoA-IBoston) in a 67-year-old woman and her 2 sons, who had mean serum high-density lipoprotein (HDL) cholesterol, apoA-I, and apoA-I in very large α-1 HDL that were 10%, 35%, and 16% of normal, respectively (all P < .05). The percentage of HDL cholesterol in the esterified form was also significantly (P < .05) reduced to 52% of control values. Cholesteryl ester tranfer protein (CETP) activity was normal. The mean global, adenosine triphosphate (ATP)-binding cassette transporter A1 and scavenger receptor B type I-mediated cellular cholesterol efflux capacity in apoB-depleted serum from affected family members were 41%, 37%, 47%, 54%, and 48% of control values, respectively (all P < .05). lecithin-cholesterol acyltransferase (LCAT) activity in plasma was 71% of controls, whereas in the cell-based assay, it was 73% of control values (P < .05). The data indicate that this novel apoA-I missense is associated with markedly decreased levels of HDL cholesterol and very large α-1 HDL, as well as decreased serum cellular cholesterol efflux and LCAT activity, but not with premature coronary heart disease, similar to other apoA-I mutations that have been associated with decreased LCAT activity.

A novel ApoA-I truncation (ApoA-IMytilene) associated with decreased ApoA-I production.

OBJECTIVE: We report a novel apolipoprotein (apo) A-I truncation (apoA-IMytilene) due to a heterozygous nonsense mutation (c.718C > T, p.Gln216*) in a 68-year-old male proband with premature coronary heart disease (CHD), corneal arcus, and very low plasma concentrations of HDL cholesterol (HDL-C) and apoA-I. Two family members also had the same mutation. Our objectives were to characterize the kindred and to examine the kinetics of apoA-I, as well as cellular cholesterol efflux capacity in the proband. METHODS: We carried out the kinetic studies using a primed constant infusion of [5,5,5-D3]L-leucine and isotopic enrichment was determined by gas chromatography mass spectrometry in the proband and seven controls with low HDL-C. To assess cellular cholesterol efflux capacity, we used a validated ex vivo system that involved incubation of J774 macrophages with apoB-depleted serum from the proband, five controls with normal HDL-C, and two controls with low HDL-C. RESULTS: Stable isotope kinetic studies indicated that the proband had an apoA-I production rate (PR) that was 41% lower than the mean PR observed in low HDL-C controls (n = 7). The cellular cholesterol efflux capacity assessment showed normalized cholesterol efflux capacity in the proband was decreased by 36% compared to the mean normalized cholesterol efflux capacity of normal controls (n = 5). CONCLUSIONS: Our data indicate that this novel heterozygous apoA-I truncation is associated with markedly decreased levels of HDL-C, plasma apoA-I, and apoA-I in large α-1 HDL particles, as well as decreased total cellular cholesterol efflux and decreased apoA-I production.

High-density lipoprotein metabolism, composition, function, and deficiency.

PURPOSE OF REVIEW: To examine the recent advances in our knowledge of HDL metabolism, composition, function, and coronary heart disease (CHD), as well as marked HDL deficiency states because of mutations in the apolipoprotein (apo) A-I, ATP-binding cassette transfer protein A1 and lecithin cholesterol acyltransferase (LCAT) gene loci. RECENT FINDINGS: It has been documented that apoA-I, myeloperoxidase and paraoxonase 1 (PON1) form a complex in HDL that is critical for HDL binding and function. Myeloperoxidase has a negative impact on HDL function, whereas PON1 has a beneficial effect. Patients who lack apoA-I develop markedly premature CHD. Patients who lack ATP-binding cassette transfer protein A1 transporter function have only very small discoidal preß-1 HDL, and develop hepatosplenomegaly, intermittent neuropathy and premature CHD, although significant heterogeneity for these disorders has been reported. Patients with LCAT deficiency have abnormal small discoidal LDLs and HDL particles, and develop kidney failure. Enzyme replacement therapy is being developed for the latter disorder. SUMMARY: Recent data indicates that proteins other than apoA-I and apoA-II such as MPO and PON1 have important effects on HDL function. There has been considerable recent progress made in our understanding of HDL protein content and function.

Incidences and outcomes of hyperglycemic crises: a 5-year study in a tertiary care center in Thailand.

OBJECTIVE: To assess the incidences and outcomes of hyperglycemic crises. MATERIAL AND METHOD: A retrospective study of diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) in adults with type 1 or type 2 diabetes mellitus (DM) admitted to Thammasat Hospital between 2006 and 2010 was performed. Incidences, precipitating causes, clinical and laboratory characteristics, and treatment outcomes of hyperglycemic crises were obtained via medical record review Multivariate logistic regression analysis was used to determine predictors for mortality. RESULTS: Eighty-three patients were eligible and included. The mean age was 54.9 +/- 17.7 years old. Most subjects had type 2 DM (86.7%). The 5-year incidence of hyperglycemic crises was 7.46%. Diabetic ketoacidosis occurred more frequently than HHS (4.67% vs. 1.71%). During the hyperglycemic episodes, the mean plasma glucose level on admission was 741.3 +/- 320.8 mg/dL. Infections were the most common precipitating factor [61/83 (73.5%)], followed by non-compliance with treatments [35/83 (42.2%)]. Treatment complications included recurrent hyperglycemia (69.9%), hypokalemia (48.2%), hypernatremia (21.7%), and hypoglycemia (15.7%). The overall mortality rate of hyperglycemic crises was 8.4% (5.8% in DKA, 15.8% in HHS and 8.3% in the overlap of both conditions). The most common causes of death were infections [5/7 (71.4%)]. By multivariate analysis, serum sodium level on admission was independently associated with mortality (adjusted odds ratio 1.08, 95% CI 1.01-1.16, p = 0.03). CONCLUSION: Hyperglycemic crises were common in the authors' setting. Diabetic ketoacidosis occurred more frequently but had a lower mortality rate than HHS. Complications from hyperglycemic crisis treatment could be prevented by close monitoring, while high serum sodium level on admission was a predictor for mortality. Strategies to prevent infections and improve treatment compliance are needed to reduce the incidence of hyperglycemic crises among patients with DM.

Atypical avian influenza (H5N1).

We report the first case of avian influenza in a patient with fever and diarrhea but no respiratory symptoms. Avian influenza should be included in the differential diagnosis for patients with predominantly gastrointestinal symptoms, particularly if they have a history of exposure to poultry.