Normal TG Levels Research Articles

Association Between the Hepatic Steatosis Index and Risk of Incident Type 2 Diabetes Mellitus in the Normoglycemic Population:A Longitudinal Prospective Study in Japan.

The Hepatic Steatosis Index (HSI) is a reliable predictor of non-alcoholic fatty liver disease (NAFLD), which can increase the risk of type 2 diabetes mellitus (T2DM). However, limited research has directly predicted HSI's association with T2DM occurrence at normal blood glucose levels. Hence, this study aimed to assess the link between baseline HSI and T2DM development under euglycemic conditions while also exploring potential sex differences. Using data from the NAGALA cohort study, a Cox regression model analyzed the relationship between HSI and T2DM risk, calculating hazard ratios (HR) and 95% confidence intervals (CI). Subgroup analyses were conducted to investigate factors influencing HSI's prediction of incident T2DM. During a mean 6.1-year follow-up, 238 individuals (1.65% of participants) developed T2DM. After adjusting for age, ethanol consumption, smoking status, SBP, DBP, TG, and TC, HSI showed a significant association with incident T2DM in individuals with normal glucose levels, consistent across sexes. Compared to the lowest quartile group (Q1), the HR and 95% CI for Q2, Q3, and Q4 were 1.09 (0.61, 1.93), 1.16 (0.68, 1.98), and 3.30 (2.04, 5.33), respectively (P for trend < 0.001). Subgroup analysis indicated that elevated HSI significantly increased the risk of incident T2DM in individuals with normal TG levels (P for interaction = 0.0170). This study highlights the significant association between elevated HSI levels and the likelihood of developing incident T2DM in individuals with normal glucose levels. Furthermore, it offers a simple and valuable screening tool for predicting T2DM.

The association between platelet reactivity and lipoprotein levels in Framingham Heart Study participants

BackgroundHypertriglyceridemia is an independent risk factor for major adverse cardiovascular events, though the mechanisms linking triglycerides and platelet function with thrombosis, remain elusive. The aim of this study was to assess the association between platelet function and triglyceride levels. MethodsWe included participants from the Framingham Heart Study Third Generation cohort, OMNI, and New Offspring Spouse cohort who attended the third examination cycle (2016–2019). Eligible participants were categorized into four triglyceride subgroups. ResultsThe study comprised a total of 1897 (55.53 %) participants with normal TG levels; 883 (25.85 %) participants with high-normal TGs; 378 (11.07 %) with borderline high TGs; and 258 (7.55 %) participants with hypertriglyceridemia. After adjusting for age, sex, alcohol consumption, aspirin, statin and P2Y12 inhibitors, the levels of ADP-induced platelet aggregation were inversely associated with total cholesterol levels (P < 0.0001). Platelet disaggregation was associated with low-density lipoprotein and high-density lipoprotein cholesterol levels (P < 0.0001). Lastly, in a shear-stress chamber assay mimicking arterial flow velocities, TG levels in the normal-high group were associated with increased levels of collagen-dependent thrombogenicity (β = 24.16, SE = 6.65, P < 0.0001). ConclusionTriglyceride levels are associated with altered platelet activation and aggregation. Furthermore, increased platelet-driven thrombogenicity is directly associated with triglyceride levels after adjusting for medications and other covariates.

Subacute Thyroiditis With Very Elevated Thyroglobulin Level in a Patient on Chronic Adalimumab Therapy

Background: Viral infections are a well-recognized cause of subacute thyroiditis (SAT), but other etiologies are occasionally seen. Here we present a case of SAT in a patient receiving chronic tumor necrosis factor inhibitor (TNF-i) therapy. Serum thyroglobulin (Tg) levels in healthy individuals have been reported and range 1.40-29.2ng/mL in males and 1.50-38.5ng/mL. There are no known serum Tg levels of reference in SAT. Clinical Case: A 43-year-old woman with a history of psoriasis treated with adalimumab presented to her primary care physician (PCP) 2 months after her mother had noticed the patient’s new goiter. Patient recalled upper respiratory infection symptoms lasting 1.5 weeks, and subsequent agitation, insomnia, and a low-grade fever preceding the development of goiter. She denied neck compressive symptoms aside from mild dysphagia. She has been treated with adalimumab 40mg subcutaneous injection weekly for psoriasis with good results for the past 3.5 years and was on norethindrone 0.35mg daily for contraception. Her thyroid exam with her PCP revealed a diffuse painless goiter and she was clinically euthyroid. Labs revealed a TSH 1.44mIU/L [0.45-5.33], TT3 104ng/dL [60-181], fT3 3.3pg/mL [2.3-4.2], fT4 0.83ng/dL [0.89-1.76], and Tg 288.7ng/mL [1.6-50]. Thyroid antibodies (Tg, thyroid peroxidase and thyroid stimulating immunoglobulin) were negative. She tested negative for COVID-19. The neck ultrasound showed an enlarged pseudonodular thyroid gland with a heterogenous parenchyma and diffuse hypervascularity bilaterally (right lobe, 7.4 x 2.8 x 3.0 cm; left lobe, 8.4 x 3.2 x 3.6 cm; isthmus, 9 mm). A month later, repeat labs showed TSH 1.56 mIU/L, TT3 85 ng/dL, fT4 0.74 ng/dL, and Tg 231.2 ng/mL. She was subsequently referred to Endocrine Clinic 4 months after her initial presentation. She had a persistent diffuse painless goiter, minimally decreased in size, and she remained clinically euthyroid. Labs included a TSH 1.75 mIU/L and fT4 0.78 ng/dL. Conclusion: There are known associations of SAT with chronic TNF-i therapy in patients with psoriasis. Viral infections are an identified cause, but other triggers in chronic TNF-i therapy may exist. Serum Tg is elevated during SAT, but in this case Tg elevation was very significant. Although normal serum Tg levels are established in healthy individuals, there are no known reference values during SAT. Tg levels should not be used in acute illness period to evaluate illness severity or the resolution of SAT.

The spectrum of thyroid function tests during hospitalization for SARS COV-2 infection.

ObjectiveAlterations in thyroid function tests (TFTs) have been recorded during SARS-CoV-2 infection as associated to either a destructive thyroiditis or a non-thyroidal illness.MethodsWe studied 144 consecutive COVID-19 patients admitted to a single center in intensive or subintensive care units. Those with previous thyroid dysfunctions or taking interfering drugs were excluded. Differently from previous reports, TSH, FT3, FT4, thyroglobulin (Tg), anti-Tg autoantibodies (TgAb) were measured at baseline and every 3–7 days. C-reacting protein (CRP), cortisol and IL-6 were also assayed.ResultsThe majority of patients had a normal TSH at admission, usually with normal FT4 and FT3. Low TSH levels were found either at admission or during hospitalization in 39% of patients, associated with low FT3 in half of the cases. FT4 and Tg levels were normal, and TgAb-negative. TSH and FT3 were invariably restored at the time of discharge in survivors, whereas were permanently low in most deceased cases, but only FT3 levels were predictors of mortality. Cortisol, CRP and IL-6 levels were higher in patients with low TSH and FT3 levels.ConclusionsAlmost half of our COVID-19 patients without interfering drugs had normal TFTs both at admission and during follow-up. In this series, the transient finding of low TSH with normal FT4 and low FT3 levels, inversely correlated with CRP, cortisol and IL-6 and associated with normal Tg levels, is likely due to the cytokine storm induced by SARS-Cov-2 with a direct or mediated impact on TSH secretion and deiodinase activity, and likely not to a destructive thyroiditis.

Is APOC3 the driver of cardiovascular disease in people with type I diabetes mellitus?

In this issue of the JCI, Kanter et al. make a strong case for implicating apolipoprotein C3 (APOC3) as a central player in atherosclerotic cardiovascular disease that is commonly seen in individuals with type 1 diabetes mellitus (T1DM). Kanter and colleagues suggest that insulin deficiency elevates plasma APOC3 as well as atherogenic triglyceride-rich (TG-rich) lipoproteins (TRLs). Using two mouse models of T1DM, the authors investigated APOC3-mediated inhibition of both TG hydrolysis by lipoprotein lipase and hepatic uptake of remnant lipoproteins. They suggest that poorly catabolized lipoproteins, enriched in both APOC3 and APOE content, are particularly atherogenic. Notably, treating both mouse models with an APOC3 antisense oligonucleotide lowered both plasma APOC3 and TRLs, and prevented atherosclerosis. These impactful mouse studies were supported by the initial finding that APOC3 predicted coronary artery disease events in participants of the prospective Coronary Artery Calcification in Type 1 Diabetes study with normal TG levels.

Abstract 24056: Longitudinal Evaluation of the Associations between Severe Hypertriglyceridemia and Cardiovascular Features

Introduction: For at least 35 years the associations between insulin resistance, hyperinsulinemia, hypertriglyceridemia and hypertension have been described. Nevertheless, the existence of an independent association between hypertriglyceridemia (HTG) and cardiovascular diseases (CVD) remains controversial. This may be due to the insufficiency of longitudinal study data that include severe elevations of TG. The purpose of this study was to characterize the associations between systolic blood pressure and various cardiovascular features under different degrees of naturally-occurring HTG severity and to determine the independent effect of severe HTG. Methods: We characterized TG in a large cohort of longitudinally studied nonhuman primates (n=227; 164 males) maintained for their lifetimes under constant environmental and dietary conditions. The TG ranged from normal TG levels &lt;100 mg/dl, to mild HTG 100-200 mg/dl, high HTG 200-500 mg/dl, very high 500-1000 mg/dl and severe &gt;1000 mg/dl. The Kruskal Wallis H test was applied, as the data samples were not normally distributed. Results: Severe hypertriglyceridemia was statistically significantly related to systolic blood pressure and was significantly higher (p&lt;0.0001) at the severe HTG levels of 500-1000 mg/dl and ≥1000 mg compared to all other TG levels. Diastolic blood pressure and mean arterial blood pressure were not significantly different among the normal to severe HTG groups. HDL cholesterol was significantly lower (p&lt;0.0001) at all levels of HTG (TG 100-200, 200-500, 500-1000 and ≥1000mg/dl) compared to normal TG &lt;100 mg/dl, and was not related to the severity of the HTG, a finding similar to the relationship with body weight. By contrast, LDL cholesterol was significantly higher (p&lt;0.05) in monkeys with severe HTG &gt;500-1000 mg/dl, as was systolic blood pressure. Conclusions: In conclusion, much of the association between triglyceride levels and cardiovascular features, including blood pressure, may be principally determined by the severely elevated triglyceride levels, possibly highlighting the importance of longitudinal within subject evaluation of such associations for break points in the interactions of these features.

DOES LOW HDL-C INCREASE CHD RISK WHEN TG & LDL-C ARE NORMAL? THE FRAMINGHAM OFFSPRING STUDY

Low levels of HDL-C are inversely correlated with risk of coronary heart disease (CHD). However, the association between low HDL-C and CHD risk in subjects with normal TG and LDL-C levels has not been well studied. We hypothesized that low HDL-C raises CHD risk in subjects with elevated levels of TG

Ultrasensitive serum thyroglobulin measurement is useful for the follow-up of patients treated with total thyroidectomy without radioactive iodine ablation

Thyroglobulin (Tg) measurement is a major tool for the follow-up of differentiated thyroid cancer (DTC) patients; however, in patients who do not undergo radioactive iodine (RAI) ablation, normal ultrasensitive Tg levels measured under levothyroxine treatment (usTg/l-T4) are not well defined. This single-center retrospective study assessed usTg/l-T4 level in 86 consecutive patients treated with total thyroidectomy without RAI ablation for low-risk DTC (n=77) or for tumors of uncertain malignant potential (TUMP) (n=9). DTCS were classified as PT1, PT2, and PT3 in 75, 1, and 1 case respectively and PN0, PN1, and PNX in 40, 6, and 31 respectively. following surgery, ten patients had TG antibodieS (TGAB). Among those without TGAB, the first USTG/L-T4 determination obtained at a mean time of 9 months after surgery was 0.1NG/ML in 62% of cases, 0.3NG/ML in 82% of cases, 1NG/ML in 91%, and 2NG/ML in 96% of cases. after a median follow-up of 2.5 years (range: 0.6-7.2 years), one patient had persistent disease with an usTg/l-T4 at 11 ng/ml and an abnormal neck ultrasonography (US) and two patients had usTg/l-T4 level >2 ng/ml (3.9 and 4.9 ng/ml) with a normal neck US. Within the first 2 years following total thyroidectomy without RAI ablation, usTg/l-T4 level is ≤2 ng/ml in 96% of the cases. After total thyroidectomy, sensitive serum Tg/l-T4 level is ≤2 ng/ml in most patients and can be used for patient follow-up.

Baseline Lipid Levels and Acute Treatment Response to Paroxetine and Tianeptine in Depressed Women

Mück-Seler, Dorotea BSc, PhD1; Sagud, Marina MD, PhD2; Mihaljevi-Peles, Alma MD, PhD2; Jakovljevi, Miro MD, PhD2; Pivac, Nela DVM, PhD3 Author Information

Increased Remnant Lipoprotein in Patients with Coronary Artery Disease-Evaluation Utilizing a Newly Developed Remnant Assay, Remnant Lipoproteins Cholesterol Homogenous Assay (RemL-C)

Remnant lipoprotein is an emerging risk factor for coronary artery disease (CAD); however, the development of a specific remnant lipoprotein assay has struggled due to its heterogeneous nature. This study aimed to evaluate the clinical importance of a newly developed assay for remnant lipoprotein, RemL-C, in patients with CAD. This assay utilizes surfactant and phospholipase-D to selectively degrade and solubilize remnant lipoprotein. One hundred and sixty consecutive CAD patients who underwent coronary catheterization were recruited. Remnant liporotein, RemL-C, was significantly higher in CAD patients (p< 0.001). Additionally, TG, hs-CRP, ICAM-1, VCAM-1, and homocysteine were significantly higher, but HDL-C and adiponectin were lower with LDL-C unchanged. Since RemL-C levels correlated with plasma TG levels, two subgroups, normotriglycedemic and normolipidemic CAD groups, were extracted. In both groups, RemL-C was still significantly higher than controls. HDL-C, but not RemL-C, was associated with the severity of CAD. RemL-C significantly correlated with TG-rich lipoproteins, in particular VLDL and IDL, when limited to normolipidemic CAD patients. Remnant lipoprotein, measured by RemL-C, was increased in CAD patients independent of TG levels, indicating impaired remnant lipoprotein metabolism in these patients. CAD severity was associated with HDL-C, but not with remnant lipoprotein, indicating differential roles of lipoproteins in the development of coronary atherosclerosis. This study therefore provides clinical significance to assess coronary risk by measuring RemL-C, particularly among patients with normal TG levels.

Improvement of graft function and animal survival by fat emulsion in liver transplant rats

Nutritional supports are required for liver transplant patients. However, no systematical assessment has been made of the optimal composition of energy yielding substrates in these patients. This study is to evaluate whether mixed energy system consisting of carbohydrate and lipid emulsions is more advantageous over single energy source of glucose for nutritional support in liver transplant recipients and whether structured lipid emulsion (STG) is superior to medium-chain triglyceride/long-chain triglycerides (MCT/LCT) and long-chain triglycerides (LCT) using a total parenteral nutrition model. Liver transplant rats were randomly divided to four groups according to the energy source, i.e. glucose (GLU), MCT/LCT, STG and LCT groups. Sham operated rats served as control. Hepatic function and lipid profile were determined to investigate the roles of lipid emulsion in hepatic function and lipid metabolism. Morphological changes of liver were observed, and nitrogen balance was determined. The results showed that infusion of lipid emulsion was well tolerated. The 1-week survival rate in the lipid emulsion groups was significantly higher than in the GLU group (100% versus 50%, P < 0.05); compared with the GLU group, hepatic function recovered quickly and returned to normal level, and morphological alterations were less severer in the lipid emulsion groups, especially in the STG group; the lipid emulsions groups had normal serum TG and TC levels, especially STG and MCT/LCT groups; the lipid emulsions groups achieved a positive nitrogen balance on day 7 compared with the GLU group, and the STG group had the highest nitrogen balance. In conclusion, lipid emulsion is beneficial in improving hepatic function and the recipients’ survival and does not influence the lipid metabolism. Mixed energy system consisting of carbohydrate and lipid is more advantageous over single energy source of glucose after liver transplantation, and STG is superior to MCT/LCT and LCT.

Maternal triglyceride levels and newborn weight in pregnant women with normal glucose tolerance

To determine the predictive value of serum triglyceride levels (TG) for neonatal weight in pregnant women with positive diabetic screening but normal glucose tolerance. We enrolled 180 pregnant Caucasian women with positive diabetic screening. All women underwent a 3-h 100-g oral glucose tolerance test (OGTT) at 27th +/- 4 week of gestation. At the time of OGTT, we measured: fasting plasma glucose, fasting lipids profile and determined ApoE polymorphisms to evaluate the effects on lipid levels. In 83 women with normal glucose tolerance and at term delivery we evaluated the association between maternal serum TG, specific maternal parameters known to affect fetal growth and newborn weight. Based on OGTT, gestational diabetes mellitus (GDM) was diagnosed in 36 women (20%), impaired glucose tolerance (IGT) in 23 (13%), and normal glucose tolerance (NGT) in 121 (67%). Serum TG concentration was significantly higher in women with GDM (2.47 +/- 0.77 mmol/l) as compared with NGT (1.99 +/- 0.64 mmol/l) or IGT (1.98 +/- 0.81 mmol/l) (P < 0.01). ApoE3 allelic frequency was 86%, ApoE2 and ApoE4 were 5 and 9%, respectively. We found no clear-cut association between apoE genotype and serum TG concentration. Macrosomia and LGA newborns were more frequent in IGT than in GDM or NGT (P < 0.01). In the 83 women with positive diabetic screening but normal glucose tolerance who delivered at term, the incidence of LGA infants was significantly higher in those with TG levels higher than the 75th percentile (> 2.30 mmol/l) (21%) than in mothers who had normal TG levels (4.5%) (P < 0.05). Pre-pregnancy BMI (r(2) = 0.067), weight gain during pregnancy (r(2) = 0.062), fasting serum TG (r(2) = 0.09), and 2-h post-OGTT glucose levels (r(2) = 0.044) were all associated with neonatal body weight (all P < 0.05 or less). However, on a multiple regression analysis, only pre-pregnancy BMI (F-test = 7.26, P < 0.01), and fasting serum TG (F-test = 4.07, P < 0.01) were independently associated with birth weight. Pre-pregnancy BMI and fasting maternal serum TG determined in the last trimester of gestation were independently associated with neonatal birth weight in women with normal glucose tolerance, but positive screening test. TG levels measured in the third trimester of pregnancy are independent of the genetic polymorphism of ApoE.

Daytime triglyceridemia in normocholesterolemic patients with premature atherosclerosis and in their first-degree relatives

Postprandial hypertriglyceridemia tested under metabolic ward conditions with unphysiological high fat loads has been reported in CAD patients and their relatives even in the presence of normal fasting lipids. It is unclear whether this also occurs in the daytime situation. Twenty-seven normocholesterolemic, non-obese and nondiabetic patients with premature coronary artery disease (CAD) and 56 first-degree relatives without CAD measured daytime capillary triglyceride profiles (TGc-AUC) as an estimate of postprandial lipemia. Fasting capillary triglycerides (TGc) were not significantly different between CAD index patients and their relatives (1.68 ± 0.63 and 1.54 ± 0.71 mmol/L, respectively). In contrast, daytime triglyceridemia was significantly higher in CAD patients (30.7 ± 13.6 mmol · h/L) compared to their relatives (24.4 ± 9.4 mmol · h/L) and this was also the case after correction for fasting TGc (7.24 ± 7.41 and 2.79 ± 6.89 mmol · h/L; P < .05). The best predictors of TGc-AUC by multiple regression analysis in CAD families were fasting TGc, systolic blood pressure, and high-density lipoprotein cholesterol (HDL-C), which are all components of the metabolic syndrome, explaining 65% of the variation. Since there were no major differences in nutritional intake between index patients and their relatives, this could not explain the differences Daytime triglyceridemia, measured under physiological conditions, is increased in patients with premature atherosclerosis and normal fasting TG levels, when compared to their non-CAD relatives. This study confirms previous observations using standardized oral fat loading tests and underlines the importance of postprandial hyperlipidemia in CAD.

Role of Thyroglobulin Measurement in Fine-Needle Aspiration Biopsies of Cervical Lymph Nodes in Patients with Differentiated Thyroid Cancer

The identification of metastatic neck lymph nodes in patients awaiting surgery for differentiated thyroid tumor permits their excision during thyroidectomy. In order to detect thyroid cancer lymphatic metastasis before surgery, we measured thyroglobulin (Tg) in the needle wash-out of fine-needle aspiration biopsy (FNAB). Ultrasound-guided FNAB on enlarged neck nodes was performed in 23 patients awaiting surgery for differentiated thyroid tumor (n = 33 lymph nodes), 47 patients previously thyroidectomized for thyroid tumor (n = 89 lymph nodes), and 60 patients without thyroid disease (n = 94 lymph nodes). Immediately after aspiration biopsy, the needle was rinsed with 1 mL of normal saline solution and Tg levels were measured on the needle wash-out (FNAB-Tg). FNAB-Tg levels were markedly elevated in metastatic lymph nodes both in patients awaiting thyroidectomy (metastatic vs. negative lymph nodes, mean +/- SEM, 16,593 +/- 7,050 ng/mL vs. 4.91 +/- 1.61 ng/mL; p < 0.001) and in thyroidectomized patients (11,541 +/- 7,283 ng/mL vs. 0.45 +/- 0.07 ng/mL; p < 0.001). FNAB-Tg sensitivity, evaluated through histological examination in 69 lymph nodes, was 84.0%. The combination of cytology plus FNAB-Tg increased FNAB sensitivity from 76% to 92.0%. In conclusion, FNAB-Tg measurement is a useful technique for early diagnosis of lymph node metastasis originating from differentiated thyroid cancer.

Effects of ionic and non-ionic contrast media on platelet function as evaluated by plasma concentration of beta-thromboglobulin.

The aim of the study was to evaluate the effects of ionic and non-ionic contrast media on platelet function. In 44 patients who underwent angiography, the plasma concentration of beta-thromboglobulin (beta TG) was measured before and after ionic contrast medium (diatrizoate) administration in 22 patients and non-ionic contrast medium (iopromide) in the other 22 patients. A significant decrease in the plasma beta TG levels after intraarterial contrast medium injection occurred in both groups of patients. No significant beta TG level changes occurred in patients with normal pre-examination beta TG levels in both groups. In patients with elevated beta TG levels before arteriography, beta TG returned to normal values after contrast medium injection in both groups. There was no significant correlation between the amount of administered contrast medium and beta TG concentration after angiography. These results suggest that platelet function is not affected by either ionic or non-ionic contrast medium in patients with normal platelet activation. In patients with enhanced platelet activation, the activation became normal after contrast medium administration.

Effect of Hypertriglyceridemia Correction by Omega-3 Fatty Acids on Peritoneal Transport in Continuous Ambulatory Peritoneal Dialysis Patients

Lipid abnormalities, both hypercholesterolemia and particularly hypertriglyceridemia (hyperTg), are common in long-term continuous ambulatory peritoneal dialysis (CAPD) patients. Hyperviscosity and rheological alterations have been proposed as major hemodynamic problems in hyperTg patients. The aim of this study was to evaluate whether a hyperTg correction by employing omega-3 fatty acids (omega-3) affects peritoneal transport. Six hyperTg (> 700 mg/dL) CAPD patients were treated with 2-3 g/day of omega-3 until normal Tg values were achieved. The assessment of peritoneal dialysis efficacy was performed by evaluating the peritoneal equilibration test (PET) before omega-3 supplementation, when normal Tg levels were reached, and 3 weeks after stopping therapy when hyperTg returned. When normal Tg levels were reached, a small but significant improvement of urea and creatinine D/P was noted: 0.85 +/- 0.05 versus 0.93 +/- 0.03 (p < 0.05) and 0.78 +/- 0.03 versus 0.86 +/- 0.05 (p < 0.05), respectively, with negative correlation between D/P of urea and Tg. These preliminary data demonstrate that a hyperTg correction with omega-3 may induce an increase in peritoneal transport of small molecules in CAPD.

Increased apo A-I and apo A-II fractional catabolic rate in patients with low high density lipoprotein-cholesterol levels with or without hypertriglyceridemia.

Low HDL-cholesterol (HDL-C) levels may elevate atherosclerosis risk, and often associate with hypertriglyceridemia (HTG); however, the metabolic causes of low HDL-C levels with or without HTG are poorly understood. We studied the turnover of radioiodinated HDL apolipoproteins, apo A-I and apo A-II, in 15 human subjects with low HDL-C, six with normal plasma TG levels (group 1) and nine with high TG (group 2), and compared them to 13 control subjects with normal HDL-C and TG levels (group 3). The fractional catabolic rate (FCR) was equally elevated in groups 1 and 2 vs. group 3 for both apo A-I (0.313 +/- 0.052 and 0.323 +/- 0.063 vs. 0.245 +/- 0.043 pools/d, P = 0.003) and apo A-II (0.213 +/- 0.036 and 0.239 +/- 0.037 vs. 0.185 +/- 0.031 pools/d, P = 0.006). Thus, high FCR characterized low HDL-C regardless of the presence or absence of HTG. In contrast, transport rate (TR) of apo A-I did not differ significantly among the groups and the apo A-II TR differed only between groups 2 and 3 (2.15 +/- 0.57, 2.50 +/- 0.39, and 1.83 +/- 0.48 mg/kg per d for groups 1 to 3, respectively, P = 0.016). Several HDL-related factors were similar in groups 1 and 2 but differed in group 3, as with FCR, including the ratio of lipoprotein lipase to hepatic lipase activity (LPL/HL) in post-heparin plasma, the ratio of the HDL-C to apo A-I plus apo A-II levels, and the percent of tracer in the d greater than 1.21 fraction. In linear regression analysis HDL-C levels correlated inversely with the FCR of apo A-I and apo A-II (r = -0.74, P less than 0.0001 for both). Major correlates of FCR were HDL-C/apo A-I + apo A-II, LPL/HL, and plasma TG levels. We hypothesize that lipase activity and plasma TG affect HDL composition which modulates FCR, which in turn regulates HDL-C. Thus, HTG is only one of several factors which may contribute to elevated FCR and low HDL-C. Given the relationship of altered HDL composition with high FCR and low HDL-C levels, factors affecting HDL composition may increase atherosclerosis susceptibility.

Development of a highly sensitive assay for serum thyroglobulin using avidin-biotin system and its clinical application

The authors have developed a highly sensitive sandwich-type enzyme immunoassay (EIA) for serum thyroglobulin using the biotin-avidin system. The sensitivity of this EIA was 0.1 ng/ml. The intra- and inter-assay coefficient of variation was 4-15% and 4-11%, respectively. Human Tg in serum was detectable in 100% of 63 normal subjects, and the normal range was from 2.3 ng/ml to 47.4 ng/ml. The recovery rate was very good. Then we applied this EIA to the follow-up study of patients with thyroid cancer. Serum Tg levels were serially determined in 15 patients with thyroid cancer who had undergone thyroidectomy (n = 9 subtotal, n = 6 total) and were receiving thyroid hormone suppression therapy. It was found that there were three groups in regard to the relationship between serum TSH and Tg. The first group showed normal TSH and normal Tg levels (n = 4). The second group showed TSH levels that were lower than the lower limit of the assay, whereas Tg levels were within the normal limit (n = 5). The last group showed both TSH and Tg that were lower than the lower limit (n = 6). In one case in the last group, recurrence of thyroid cancer was forecast by the change of Tg levels (from below 0.1 ng/ml to 5.9 ng/ml). Therefore, it is important to suppress serum Tg and TSH levels as much as possible in order to obtain the best usefulness of serum Tg determination in the follow-up study of thyroid cancer in patients who have undergone subtotal thyroidectomy or have residual thyroid tissue. We also measured Tg levels in patients with untreated Graves' disease. Twelve patients were negative for anti-Tg antibody and 18 were positive for anti-Tg antibody. Even in the antibody positive cases, serum Tg could be detected and their levels could be calculated from the recovery studies. The mean serum Tg levels in antibody positive cases were lower than in negative cases. These studies showed that our sensitive EIA for serum Tg determination was useful in practice in patients with thyroid disease.

T lymphocyte subpopulations in Graves' disease: relationship with clinical conditions.

T lymphocytes were fractionated according to their receptors for IgG (TG) or IgM (TM) and scored in 37 patients with Graves' disease (17 hyperthyroid and untreated. 10 euthyroid on antithyroid drugs, 10 in long-term remission after radioiodine therapy). TG percentages were very low both in untreated and in drug-treated patients. By contrast, normal TG levels were observed in patients in long-term remission. These data are consistent with the hypothesis of a defective suppressor cell activity in Graves' disease.

Platelets, Coagulation and Fibrinolysis in Patients with Diabetic Retinopathy

Twenty control subjects, 12 insulin treated and 10 non-insulin treated diabetics were studied. All diabetics had retinopathy documented by fluorescein angiography and fluorophotometry. Factor VIIIR:Ag and plasma fibrinogen concentrations were elevated in both diabetic groups, but more so in the insulin treated patients. Within this latter group the plasma fibrinogen was also correlated with the degree of retinopathy. Platelets separated on linear isosmolar Percoll gradients showed an increase in intraplatelet beta TG content and concentration and a slight increase in volume of the lightest platelets in the insulin treated diabetics. Plasma platelet factor 4 and antithrombin III concentrations were normal and plasma beta TG levels were elevated only in those patients with renal insufficiency. Platelet aggregometry was performed in 18 diabetic subjects and found to be normal. It is concluded that abnormalities of coagulation and platelets in diabetes are determined by metabolic factors rather than the severity of microvascular disease per se.