Adaptation to hypocaloric feeding: Physiologic significance of the fall in serum T3 as measured by the pulse wave arrival time (QKd)

We have investigated the physiologic significance of the decline in serum triiodothyronine (T₃) occurring during hypocaloric feeding by measurement of changes in cardiovascular function. The QKd interval, the interval between the Q wave of the electrocardiogram and the onset of Korotkoff sounds at diastolic pressure at the brachial artery, is the sum of the preejection period and pulsetransmission time, and has proven to be a sensitive and effective measure of the effect of thyroid hormones on the cardiovascular system. Fifteen euthyroid obese volunteers underwent successive 2 wk periods of hypocaloric feeding (200–400 calories per day) interspersed with periods of at least 2 wk of re-feeding on a weight-maintaining diet (1500 calories). In a later phase subjects received oral supplementation of triiodothyronine (T₃) in addition to the diet to prevent the fall in serum T₃. In the last study phase, subjects on the diet received supplementation with oral thyroxine (T₄), which prevented the fall in serum T₃ and resulted in a slight increase in serum T₄. During the first 2 wk period of hypocaloric feeding, there was a statistically significant increase in QKd, and a decrease in pulse rate, compatible with a hypothyroid state relative to initial measurements. When oral T₃ supplementation was given, the rise in QKd and fall in pulse rate were prevented. Likewise, with oral T₄ supplementation, the changes in QKd and pulse were prevented. Thus, the fall in serum T₃ occurring during hypocaloric feeding is associated with changes in the cardiovascular system which are qualitatively similar to those observed during hypothyroidism. The present data, taken with other data in the literature, suggest that the decline in serum T₃ during hypocaloric feeding may be an adaptive mechanism to conserve energy during caloric deprivation.     

Evidence for heterogeneity in hereditary hemochromatosis: Evaluation of 174 persons in nine families

Hereditary hemochromatosis is an autosomal recessive disease in which the gene is linked to the HLA system. Investigation of nine unrelated probands and their family members has revealed distinct groups based on biochemical and clinical manifestations of the disease. Four different types of disease expression were identified: Group I—classic hereditary hemochromatosis with elevated transferrin saturation, serum ferritin levels, and liver iron content; Group II—severe iron overload, accelerated disease manifesting at an early age; Group III—elevated total body iron stores, normal transferrin saturation and serum ferritin levels; Group IV—markedly elevated findings on serum biochemical tests, e.g., transferrin saturation, serum ferritin levels, with minimal elevation in total body iron stores. This evidence for several clearly distinguishable modes of expression in different families suggests that more than one genetic lesion in iron metabolism may be responsible for iron overload in hereditary hemochromatosis. This genetic heterogeneity may be helpful in delineating the fundamental abnormalities in iron metabolism in this group of disorders.     

Effects of mazindol on carbohydrate and insulin metabolism in obesity

Oral administration of a single dose of the anorectic agent mazindol to obese subjects led to a significant improvement in oral glucose tolerance and a concomitant reduction in insulin secretion, but had no effect on the blood glucose and plasma insulin responses to glucose given intravenously. Mazindol, when given to obese subjects in conjunction with a hypocaloric diet, was associated with progressive weight loss and reduction in the fasting levels of blood glucose, plasma insulin, serum triglyceride, and serum cholesterol. When oral glucose tolerance was retested after 16-20 wk, blood glucose and plasma insulin responses were significantly decreased compared with initial control values. It is concluded that one effect of mazindol, when given acutely, is to impair absorption of glucose from the gut. Changes in carbohydrate metabolism after chronic administration of mazindol are entirely consistent with weight loss, although a separate effect of the drug cannot be excluded.     

The effects of dietary cholesterol upon the hypercholesterolemia of pregnancy

The hypercholesterolemia which accompanies the normal human pregnancy is not known to be influenced by diet or other factors. The present experiment in fourteen pregnant women was designed to document this phenomenon under controlled metabolic conditions and to study the effect of dietary cholesterol upon this usual increase in serum cholesterol. The subjects included twelve normal subjects, one juvenile diabetic, and one type II familial hypercholesterolemic subject. They were fed controlled, nutritionally adequate diets which were equivalent except for the cholesterol content, which was cholesterol-free or 600–1000 mg from egg yolk daily. Calories were adjusted to permit weight gain of 1.4 kg per mo. The cholesterol-free diet lowered the mean serum cholesterol level in the 12 normal pregnant women from 234-187 mg/dl, a 20% decrease (?47 ± 37 S.D.) (p < 0.005). The addition of cholesterol to the diet invariably elevated the mean serum cholesterol concentrations to 223 mg/dl, a 19% increase (+36 ± 12) (p < 0.001). The mean serum triglyceride levels increased steadily throughout pregnancy regardless of diet, up to 198 ± 43 (S.D.) mg/dl at term. Both serum cholesterol and triglyceride concentrations decreased strikingly 1 wk after parturition. These serum cholesterol and triglyceride responses occurred similarly in the familial hypercholesterolemic and the diabetic women. The increased serum cholesterol levels during the high cholesterol diets occurred largely in the low density lipoprotein (LDL) fraction. Despite the inevitable alterations of cholesterol and lipooprotein homeostasis which occur in pregnancy, the results of this study indicated that the usual hypercholesterolemia of pregnancy in women eating the general American diet was greatly ameliorated by a very low cholesterol, nutritionally adequate diet.     

A study of the iron and HFE status of blood donors, including a group who failed the initial screen for anaemia

A complete data set (age, weight, diet and recent donation history; venous blood cell count, serum ferritin and soluble transferrin receptor concentrations and transferrin saturation; HFE genotype) was obtained from 113 male and 122 female blood donors. Progressive iron depletion and deficiency - most apparent from serum concentrations of soluble transferrin receptor divided by the logarithm of ferritin concentrations (the TfR-F index) - developed in men donating up to six times in 2 years, although the serum ferritin alone was also informative; however, no prediction could be made for those iron-depleted individuals who will develop iron deficiency after donation. Iron stores in the groups of donors with 'low-normal' haemoglobin (Hb) concentrations were indistinguishable from those in donors with higher Hb values, whereas donors failing the anaemia screen had reduced stores. This supports the UK policy of accepting donations from people whose Hb concentration is up to 0. 5 g/dl below the recommended European threshold. Women eating red meat once a week sustained higher ferritin concentrations, and the iron status of first-time women donors resembled that of men donating twice each year. Homozygosity for either HFE variant allowed greater iron retention in the face of regular donation, but among heterozygotes the findings were inconclusive.     

The effects of two different hypocaloric diets on glucagon-like peptide 1 in obese adults, relation with insulin response after weight loss

ObjectiveFew studies have investigated the effect of type of diets on GLP-1 concentrations. The aim of this study was to compare the effect of two diets on circulating GLP-1 levels and the relation with insulin response after weight loss.MethodsA population of 118 obese patients were analyzed. Patients were randomly allocated to two groups: (a) Diet I (low carbohydrate) and (b) Diet II (low fat). Biochemical and anthropometric parameters were measured before and after 3 months of hypocaloric diet.ResultsFifty-two patients (12 male/40 female) were treated with Diet I and 66 patients (21 male/45 female) with Diet II. In Group I, basal GLP-1 levels did not change after dietary treatment (9.4±3.3 vs. 9.9±3.1 ng/ml; ns). In Group II, GLP-1 levels decreased significantly (8.4%) (9.2±3.3 vs 8.7±3.1 ng/ml; P<.05). In the multivariate analysis with a dependent variable (levels of GLP-1), only insulin levels remained as an independent predictor in the model (F=5.9; P<.05), with an increase of 0.6 ng/ml (95% CI 0.1–1.1) GLP-1 concentrations with each increase of 1 mUI/ml of insulin.ConclusionA hypocaloric diet with a low fat percentage decreased GLP-1 levels with a direct correlation with insulin levels. Nevertheless, patients with a hypocaloric diet with a low carbohydrate percentage treatment did not change GLP-1 levels. Diet macronutrient manipulation on GLP-1 response could be useful in an obesity nutrition therapy.     

THE EFFECT OF CALORIE RESTRICTION ON SERUM THYROID HORMONE BINDING PROTEINS AND FREE HORMONE IN OBESE PATIENTS

In ten obese euthyroid subjects the concentration of thyroxine (T4), tri-iodothyronine (T3) and reverse T3 (rT3) were assayed in serum and of T4 and T3 in urine before and after 2 weeks of 2.1 MJ (500 Kcal) per day diet. Mean serum T4 was unchanged, while T3 decreased and rT3 increased. Urinary excretion of both T4 and T3 decreased after diet. In six subjects the concentrations of serum thyroxine binding globulin (TBG), thyroxine binding prealbumin (TBPA) and albumin were measured before and after diet. Free T4 and T3 were calculated using a formula based on measured concentration of hormones and their binding proteins. Calorie restriction resulted in a significant decrease in TBG and a greater decrease in TBPA, while albumin was unchanged. Calculation of free hormones showed a fall in absolute free T3 and rise in percentage free T3, but a rise in both absolute and per cent free T4. Our data indicate a selective effect of calorie restriction on the concentrations of TBPA and to a lesser extent TBG and confirm previous reports of altered peripheral monodeiodination of T4. Decreased urinary excretion of T4, despite a calculated increase of free T4 in serum, suggests intrarenal metabolic adjustment, the mechanism of which awaits elucidation.     

Reduced affinity for thyroxine in two of three structural thyroxine-binding prealbumin variants associated with familial amyloidotic polyneuropathy

T4-binding prealbumin (TBPA), a protein synthesized by the liver, circulates as a tetramer and transports 15-20% of T4. We studied 3 variants of the TBPA monomer recently identified in serum and amyloid fibrils of patients affected by familial amyloidotic polyneuropathy (FAP). They represent single amino acid substitutions at positions 30 (type I), 60 (Appalachian), and 84 (type II). Tests of thyroid function and the apparent association constant (Ka) of T4 binding to TBPA were measured in whole serum from 14 carriers of FAP identified clinically, by amino acid sequence analysis, or by DNA restriction fragment analysis. Significant reduction of Ka was found in subjects with FAP types I and II, but not in subjects with the Appalachian type. Mean (+/- SD) values of 0.24 +/- 0.08 X 10(7) M-1 for type I and 0.26 +/- 0.10 X 10(7) M-1 for type II were significantly (P less than 0.0001) lower than those for normal relatives (1.39 +/- 0.30 X 10(7) M-1) or unrelated normal subjects (1.41 +/- 0.18 X 10(7) M-1). The mean Ka value for the five subjects with FAP of the Appalachian type was slightly but not significantly reduced (1.08 +/- 0.11 X 10(7) M-1). There was no overlap of individual Ka values of subjects with types I and II TBPA with those of subjects from all other groups. Abnormalities of thyroid function included slight but significant reductions of the mean total serum T4 concentration in the subjects with type II FAP and the mean serum total T3 concentration in those with type I FAP. Four subjects with FAP (two type II and two of the Appalachian type) had biochemical evidence of hypothyroidism. The three subjects with total serum T3 levels below the limit of normal had amyloid cardiomyopathy. These results indicate that TBPAs from subjects with FAP types I and II have relatively lower affinity for T4. Although none of the substituted amino acids in these variant TBPAs contribute directly to the surface of the putative T4-binding site, the side chains of amino acids 30 and 84, but not 60, interact with internal residues of the beta-structure which forms the presumed binding site, in agreement with our results of Ka measurements. The high incidence of hypothyroidism is due to the probably fortuitous occurrence of Hashimoto's thyroiditis as well as to partial destruction of the thyroid gland by amyloid deposits.     

Erythrocyte Na-K-ATPase membrane activity in obese patients fed over a long-term period with a very-low-calorie diet

In a search for the role of long-term hypocaloric feeding on the expression of the erythrocyte Na pump in obesity, we examined three groups of subjects. Group 1 consisted of 10 obese subjects who had been under treatment for a long period of time with a very-low-calorie diet (500 kcal/d) while group 2 consisted of 10 age-, sex-, and body mass index-matched obese subjects on their usual diet; in the third group, 12 normal-weight subjects on a free diet served as controls. There was no difference between the groups in the number of erythrocyte binding sites per cell. On the contrary, the Na-K-ATPase activity was significantly lower in the obese group 1 (0.35 +/- 0.09 mumol Pi x mg protein-1 x h-1) compared to that observed in the obese group 2 (0.42 +/- 0.07, P less than .05) and in control subjects (0.45 +/- 0.06, P less than .05). Sex, duration of hypocaloric feeding, and the amount of weight loss before the study in the obese group 1 seemed not to be related to the Na pump parameters. We conclude that long-term severe hypocaloric feeding may be a factor in altered erythrocyte Na-K-ATPase in obese individuals.     

PLASMA GLUCAGON RESPONSE TO ARGININE INFUSION IN CHILDREN AND ADOLESCENTS WITH DIABETES MELLITUS

Plasma glucagon response to an arginine infusion was studied in children and adolescents belonging to the following groups: (I) twenty-two controls; (II) six subjects with delayed insulin peak during oral GTT; (III) ten diabetics on diet and/or oral therapy; (IV) six newly diagnosed uncompensated diabetics; and (V) eight diabetics on insulin therapy. The fasting glucagon concentrations and rise of glucagon in response to arginine in the patients of Groups II, III and V were similar to those of the controls (Group I). The basal levels and rise of glucagon in the newly diagnosed, uncompensated dibetic children (Group IV) was elevated compared to the other groups but the difference was statistically not significant. The results of this investigation favour the hypothesis that the hyperglucagonaemia in diabetes is a secondary effect to the metabolic derangement, bearing a direct relationship to the degree of homeostastic decompensation.     

Carbohydrate restriction favorably alters lipoprotein metabolism in Emirati subjects classified with the metabolic syndrome

Background and aimsCarbohydrate restriction (CR) has been shown to improve dyslipidemias associated with metabolic syndrome (MetS). We evaluated the effects of CR on lipoprotein subfractions and apolipoproteins in Emirati adults classified with the MetS.Methods and results39 subjects (15 men/24 women) were randomly allocated to a CR diet [20–25% energy from carbohydrate (CHO)] for 12 wk (CRD group) or a combination treatment consisting of CRD for 6 wk followed by the American Heart Association diet (50–55% CHO, AHA group) for an additional 6 wk. All subjects reduced body weight, LDL cholesterol and triglycerides (P < 0.01). At baseline all subjects had low concentrations of medium VLDL and total HDL particles associated with the very low plasma triglycerides and HDL cholesterol in this population. After 12 wk, the large VLDL subfraction was decreased over time for subjects in the CRD group (P < 0.01) while these changes were not observed in those subjects who changed to the AHA diet. The number of medium and small LDL particles decreased for all subjects rendering a less atherogenic lipoprotein profile. In agreement with these results, a significant decrease in apolipoprotein (apo) B was observed (P < 0.01). The medium HDL subfraction and apo A-II, which can be considered pro-atherogenic, were also decreased over time in the CRD group only.ConclusionsThese results suggest that weight loss favorably affects lipoprotein metabolism and that the CRD had a better effect on atherogenic VLDL and HDL than the low fat diet recommended by AHA.     

The effect of ethanol extract of Hypericum lysimachioides on lipid profile in hypercholesterolemic rabbits and its in vitro antioxidant activity

Hypercholesterolemia, high cholesterol diet and oxidative stress increase serum total cholesterol and LDL cholesterol levels resulting in increased risk for development of atherosclerosis. Antioxidants play an important role in inhibiting and scavenging radicals, thus providing protection to humans against infectious and degenerative diseases. Literature shows that the antioxidant activity is high in medicinal plants. Realizing the fact that, this study was carried out to determine the effect of ethanol extract of Hypericum lysimachioides Boiss var lysimachioides (Guttifera) on serum lipid levels and serum lipid peroxidation in hypercholesterolemic rabbits. The rabbits were divided into four groups and these groups were fed with diets containing standard laboratory diet (Group I), standard laboratory diet and ethanol extracts of H. lysimachioides (HL) (50mg/kg body weight) (Group II), standard laboratory diet, ethanol extracts of HL (50mg/kg body weight) and cholesterol (100mg/kg body weight) (Group III), and finally standard laboratory diet and cholesterol (100mg/kg body weight) (Group IV), for 5 weeks. Feeding cholesterol increased serum cholesterol and LDL cholesterol levels significantly in Group IV as compared to the other groups. Ethanol extract of HL with high cholesterol diet significantly lowered LDL cholesterol and total cholesterol levels in the rabbits of Group III as compared to the Group IV. The level of serum triacylglycerol was found to be similar to all comparison groups. HDL cholesterol levels were also increased significantly in Groups II and III as compared to Group IV. Statistically significant difference was found in Group IV as compared to all other groups. The ethanol extract of HL with high cholesterol diet significantly lowered the serum MDA levels in the rabbits of Group III compared to the Group IV. The histopathological findings confirmed that the ethanol extract of HL restrained the progression of the hydropic degeneration and fatty changes in the liver and some atherosclerotic lesions in the aorta. The in vitro antioxidant activities of ethanol extract of HL was also evaluated. The free radical-scavenging properties of HL (IC(50)=28 microg/ml) were studied using 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay system. Since plant phenolic compound is one of the phytochemicals possessing radical scavenging activity, the amount of total phenolic compound was also determined in ethanol extract of HL and total phenolic content of one-milligram HL ethanol extract was equivalent to 307 microg of gallic acid. Total antioxidant activity of ethanol extract of HL was tested by using ferric thiocyanate (FTC) and thiobarbituric acid (TBA) methods. Antioxidative activities of ethanol extract of HL was found to be comparable with Vitamin E. In conclusion, the use of this extract could be useful in the management of cardiovascular disease in which atherosclerosis is important.     

Regression of hypercholesterolemic atherosclerosis in rabbits by secoisolariciresinol diglucoside isolated from flaxseed

Secoisolariciresinol diglucoside (SDG) isolated from flaxseed is a lipid-lowering and antioxidant agent. It suppresses the development of hypercholesterolemic atherosclerosis in rabbits. It is however not known if SDG would produce regression of atherosclerosis. The objectives of this study were to determine (i) if SDG produces regression of atherosclerosis; (ii) if regression is associated with reduction in serum lipids, oxidative stress or both; and (iii) if the duration of treatment has an effect on regression. Rabbits were assigned to five groups: Group I, regular diet (control); Group II, 0.5% cholesterol diet for 2 months (mo); Group III, same as Group II but followed by regular diet for 2 mo; Group IV, same as Group II and followed by regular diet with SDG (20mg x kg body wt(-1) x day(-1) PO) for 2 mo; and Group V, same as Group IV but SDG treatment for an additional 2 mo. Blood samples were collected from rabbits before and at monthly intervals thereafter on their respective diet regimen for measurement of triglycerides (TG), total cholesterol (TC), LDL-C, HDL-C and malondialdehyde (MDA), a lipid peroxidation product. At the end of the protocol, the aorta was removed for assessment of atherosclerotic lesions, aortic MDA and aortic chemiluminescence (Aortic-CL), a measure of antioxidant reserve. MDA and Aortic-CL provide an index of oxidative stress. Increases in serum TG, TC, LDL-C, HDL-C and the risk ratio TC/HDL-C in Group II were associated with an increase in oxidative stress and development of atherosclerosis (57% of aortic intimal surface covered with lesions). Serum lipids decreased to a similar extent in Groups III-V, however atherosclerotic lesions were 84%, 63% and 44%, respectively in Groups III-V. There were more atherosclerotic lesions in Group III (+48.9%) as compared to Group II. The atherosclerotic lesions decreased by 24% and 45%, respectively in Groups IV and V compared to Group III. The reduction in atherosclerotic lesions was associated with a reduction in oxidative stress. These results suggest that (i) regular diet following a high cholesterol diet accelerates atherosclerosis in spite of a decrease in serum lipids; (ii) SDG treatment prevents the progression of atherosclerosis on a regular diet following a high cholesterol diet; (iii) prevention of progression is associated with a reduction of aortic oxidative stress and not with reductions in serum lipids; (iv) a longer duration of treatment reduces the progression of atherosclerosis to a greater extent, and tends to regress the atherosclerosis.     

Changes in lactate dehydrogenase, LDH isoenzymes, lactate, and pyruvate as a result of feeding low fat diets to healthy men and women.

A study was conducted to evaluate the effects on blood lipids and lipoproteins of feeding 21 healthy volunteers, 40-60 yr old, foods commonly eaten in the United States for two 40-day periods. Activities of lactate dehydrogenase (LDH) and LDH isoenzymes, lactate, and pyruvate were monitored. Results showed that LDH activity was significantly lower in all subjects at the end of the 25% fat-calorie period (period I) than at the beginning of the study, but rose above initial levels at the end of the 35% fat-calorie period (period II). While total LDH fell during period I, relative activity of M type subunits of LDH rose significantly in relation to H type in both sexes. This rise is probably indicative of an increase in glycolytic activity as a consequence of the increased intake of dietary carbohydrate. In period I, lactate and pyruvate decreased significantly in males (pyruvate greater than lactate) but not in females. Values for males returned to near initial levels in period II. The ratio of lactate/pyruvate was elevated in both sexes after period I. The greater change in pyruvate relative to lactate with increased dietary carbohydrate suggests increased Krebs Cycle activity. There was a statistically significant positive correlation between lactate, pyruvate, and serum triglyceride for males after they ate the 25% and 35% fat-calorie diets and for females after they ate the 35% fat-calorie diet, but not between lactate, pyruvate, and serum cholesterol for either sex.     

Retinol binding protein-4 levels and clinical features of type 2 diabetes patients

CONTEXT: Retinol binding protein (RBP)-4 is a recently identified adipocytokine that is associated with insulin resistance. OBJECTIVES: The aim was to investigate the association between RBP4 and various markers related to insulin resistance and diabetic complications in type 2 diabetic patients. The effect on RBP4 of the addition of pioglitazone to other diabetic medications was also examined. DESIGN, SETTING, PATIENTS, INTERVENTION, AND MAIN OUTCOME MEASURES: RBP4 levels were measured in 101 hospitalized patients with type 2 diabetes and in 22 nonhospitalized control subjects. Endothelial function was evaluated using flow-mediated vasodilatation. In a further 22 nonhospitalized type 2 diabetic patients, pioglitazone (30 mg/d) was administered for 12 wk while other medications for diabetes were continued. RESULTS: There was a significant elevation of RBP4 levels in diabetic patients compared with healthy subjects. RBP4 showed significant positive correlations with triglyceride, systolic blood pressure, and log urinary albumin excretion, and significant negative correlations with high-density lipoprotein cholesterol and flow-mediated vasodilatation. In stepwise regression analysis, log urinary albumin excretion, triglyceride, and gender showed a significant association with RBP4. RBP4 was significantly elevated in patients with proliferative-diabetic retinopathy compared with nondiabetic retinopathy and simple-diabetic retinopathy patients. The addition of pioglitazone for 12 wk to other diabetic medications the patients were already taking did not affect the serum RBP4 concentration. CONCLUSIONS: The current study shows that RBP4 is associated with variables related to insulin resistance and diabetic complications. The addition of pioglitazone for 12 wk to other diabetic medications the patients were already taking did not affect serum RBP4 levels.     

Thyroid hormone binding in serum of 15 vertebrate species: isolation of thyroxine-binding globulin and prealbumin analogs

The binding of [125I]T4 to serum proteins was studied in human, monkey, cattle, sheep, goat, water buffalo, horse, swine, dog, cat, rabbit, rat, chicken, frog, and salmon. Attempts were made to isolate thyroxine-binding globulin (TBG) and thyroxine-binding prealbumin (TBPA) from serum of all species, utilizing purification methods based on the specific properties of these proteins. TBPA was found to exist in all species examined. The protein was found anodal to albumin only in human, monkey, horse, and chicken. In cattle, swine, dog, cat, rabbit, frog, and salmon, TBPA was found cathodal to albumin, while sheep, goat, water buffalo, and rat had identical mobility of albumin and TBPA. The presence of TBG was demonstrated in larger mammals. In cat, rabbit, rat, chicken, frog, and salmon, TBG could not be demonstrated. The thyroxine-binding capacity of TBPA in serum varied from 1000 to greater than 6000 nmol/l and that of TBG between 150 and 600 nmol/l. TBPA from all species except salmon showed affinity to human retinol-binding protein. The presence of TBPA in all vertebrates suggests prealbumin to be a far more important thyroxine carrier than earlier anticipated.     

Twenty-four hour variation of transferrin saturation in treated and untreated haemochromatosis homozygotes

We studied 43 haemochromatosis homozygotes and seven normal individuals to test the hypothesis that there is an almost continuous relative deficiency of apotransferrin in treated and untreated homozygotes. Transferrin saturation was measured at 2-h intervals for 24 h while all subjects ate their usual diet. Subjects with haemochromatosis were separated into four groups based on sex and whether or not they had been iron-depleted. Nineteen treated and 11 untreated male homozygotes had mean transferrin saturation values of 70 and 81%, respectively. Five treated and eight untreated female homozygotes had mean transferrin saturation values of 71 and 69%. Normal subjects had mean transferrin saturation values of 29% (3 males) and 21% (4 females). These data demonstrate continuously high transferrin saturation values, greater than 69% in most treated and untreated male and female homozygotes, resulting in hepatic iron accumulation of non-transferrin-bound iron from the portal circulation.     

Effects of postextrasystolic potentiation on systolic time intervals

The changes in systolic time intervals associated with postextrasystolic potentiation were studied in 48 patients whose left ventricular function was categorized angiographlcally into four groups—normal function (I) and mlld (II), moderate (III) and severe (IV) left ventricular dysfunction. Postectopic potentiation in all groups caused a decrease in preejection period/left ventricular ejection time (PEP/LVET) ratio. The greatest potentiation and decreases in PEP/LVET ratio were noted in beats where the difference in compensatory pause and coupling interval (both expressed as percent of basic cycle length [CP percent — CI percent]) exceeded 40. The decrease in the ratio was least in the normal subjects (Group I) and maximal in Group IV patients. The pattern of response of the rate-corrected left ventricular ejection time and preejectlon period was also different at the four levels of ventricular function. Marked shortening of ejection time with minimal shortening of preejection period occurred in Group I, but in Group IV patients there was marked shortening of preejection period and minimal shortening of ejection time. An intermediate response was seen in Group II and III patients. The amount of shortening of ejection time exceeded that of preejection period in Group II patients; the reverse was true in Group III patients. The group responses differed with a significance of 2P <0.001 except when Group II was compared with Group III, when the significance was 2P <0.025. Thus, measurement of changes in systolic time intervals associated with postextrasystolic potentiation is of value as a noninvasive means of assessing resting left ventricular function.     

Serum retinol-binding protein 4 is associated with insulin secretion in Chinese people with normal glucose tolerance

Background:  Serum levels of retinol‐binding protein 4 (RBP4) are associated with insulin resistance and type 2 diabetes mellitus (T2DM) and may impact on β‐cell function. Thus, the present study investigated the relationship between serum RBP4 and insulin secretion in Chinese people with and without T2DM. Methods:  A 75 g oral glucose tolerance test was administered to all 867 subjects and serum RBP4 concentrations were determined. Insulin secretion was assessed by ΔI/ΔG (increment in plasma insulin concentration/plasma glucose concentration 30 min after the oral administration of 75 g glucose) and the total area under the curve for insulin over 180 min (AUC‐I). Magnetic resonance imaging was used to measure visceral fat area (VFA) at L4–L5; subjects with VFA ≥80 cm² were considered to have visceral obesity (VO). Results:  Serum RBP4 concentrations were significantly higher in subjects with VO than without, regardless of the presence of T2DM. In addition, in the entire group with normal glucose tolerance (NGT), serum RBP4 was positively correlated with ΔI/ΔG (r = 0.152; P < 0.01) and AUC‐I (r = 0.218; P < 0.01) after adjustment for gender. The correlation between RBP4 and ΔI/ΔG (r = 0.162; P < 0.05) and AUC‐I (r = 0.195; P < 0.01) remained in NGT non‐VO subjects. No correlation was found between serum RBP4 and ΔI/ΔG or AUC‐I in T2DM patients. Stepwise multiple regression analysis showed that serum RBP4 is an independent factor that contributes to ΔI/ΔG (β = 0.176) and AUC‐I (β = 0.204) in NGT non‐VO subjects. Conclusions:  Serum RBP4 is correlated with glucose‐stimulated insulin secretion in NGT non‐VO subjects, but not in NGT VO subjects and T2DM patients.