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Biomedical subjects

D R Matthews

Publications and source records attributed to D R Matthews.

At least 19 recordsLinked to original sources
PubMed1998

Risk factors for coronary artery disease in non-insulin dependent diabetes mellitus: United Kingdom Prospective Diabetes Study (UKPDS: 23)

OBJECTIVE: To evaluate baseline risk factors for coronary artery disease in patients with type 2 diabetes mellitus. DESIGN: A stepwise selection procedure, adjusting for age and sex, was used in 2693 subjects with complete data to determine which risk factors for coronary artery disease should be included in a Cox proportional hazards model. SUBJECTS: 3055 white patients (mean age 52) with recently diagnosed type 2 diabetes mellitus and without evidence of disease related to atheroma. Median duration of follow up was 7.9 years. 335 patients developed coronary artery disease within 10 years. OUTCOME MEASURES: Angina with confirmatory abnormal electrocardiogram; non-fatal and fatal myocardial infarction. RESULTS: Coronary artery disease was significantly associated with increased concentrations of low density lipoprotein cholesterol, decreased concentrations of high density lipoprotein cholesterol, and increased triglyceride concentration, haemoglobin A1c, systolic blood pressure, fasting plasma glucose concentration, and a history of smoking. The estimated hazard ratios for the upper third relative to the lower third were 2.26 (95% confidence interval 1.70 to 3.00) for low density lipoprotein cholesterol, 0.55 (0.41 to 0.73) for high density lipoprotein cholesterol, 1.52 (1.15 to 2.01) for haemoglobin A1c, and 1.82 (1.34 to 2.47) for systolic blood pressure. The estimated hazard ratio for smokers was 1.41 (1.06 to 1.88). CONCLUSION: A quintet of potentially modifiable risk factors for coronary artery disease exists in patients with type 2 diabetes mellitus. These risk factors are increased concentrations of low density lipoprotein cholesterol, decreased concentrations of high density lipoprotein cholesterol, raised blood pressure, hyperglycaemia, and smoking.

Adult↗
PubMed1998

United Kingdom Prospective Diabetes Study, 30: diabetic retinopathy at diagnosis of non-insulin-dependent diabetes mellitus and associated risk factors.

OBJECTIVES: To report on the prevalence of retinopathy in patients with newly diagnosed non-insulin-dependent diabetes mellitus (NIDDM) and to evaluate the relationship of retinopathy to clinical and biochemical variables. DESIGN: A multicenter, randomized, controlled clinical study of therapy in patients with NIDDM. SETTING AND PATIENTS: Patients were part of the United Kingdom Prospective Diabetes Study, a 23-center study of 2964 white patients who had both eyes photographed and assessed. OUTCOME MEASURES: The presence and severity of diabetic retinopathy were evaluated by sex, and the relationship of retinopathy to medical and biochemical parameters was assessed. RESULTS: Retinopathy, defined as microaneurysms or worse lesions in at least 1 eye, was present in 39% of men and 35% of women. Marked retinopathy with cotton wool spots or intraretinal microvascular abnormalities was present in 8% of men and 4% of women. The severity of retinopathy was related in both sexes to higher fasting plasma glucose levels, higher systolic and diastolic blood pressure, lower serum insulin levels, and reduced beta-cell function. In addition, in men, increased alcohol consumption was related to increased severity of retinopathy, while leaner women had more severe eye lesions. Visual acuity was normal in most patients, but in men there was a trend for those with more severe retinal lesions to have worse visual acuity. CONCLUSIONS: Diabetic retinopathy is common in patients with newly diagnosed NIDDM. Careful ophthalmic assessment at diagnosis is important.

Alcohol Drinking↗
PubMed1998

UKPDS 26: Sulphonylurea failure in non-insulin-dependent diabetic patients over six years. UK Prospective Diabetes Study (UKPDS) Group.

Patients with Type 2 (non-insulin-dependent) diabetes mellitus (DM) on sulphonylurea therapy convert to insulin progressively as the sulphonylureas 'fail'. The rate of failure and the features of those who fail have been poorly described. To assess secondary failure rates of sulphonylureas, we report on the responses in 1305 patients with newly diagnosed Type 2 DM randomly allocated to therapy with either chlorpropamide or glibenclamide in the UK Prospective Diabetes Study (UKPDS). These patients were initially treated by diet for 3 months and had a fasting plasma glucose > 6 mmol l(-1); mean age 53 (SD 9) years; BMI 26.8 (SD 5.0) kg m(-2); and median fasting plasma glucose 9.1 (7.6-12.5 quartiles) mmol l(-1). If their fasting plasma glucose subsequently rose above 15.0 mmol l(-1), or they developed hyperglycaemic symptoms, additional hypoglycaemic therapy was given: metformin, ultratard insulin, and soluble insulin as required. By 6 years, 44% had required additional therapy. Of those randomized to glibenclamide, 48% required additional therapy by 6 years, compared with 40% of those allocated to chlorpropamide (p < 0.01). Sixty-one per cent, 39%, and 23%, respectively, of patients with fasting plasma glucose > or = 10.0 mmol l(-1), > or = 7.8 mmol l(-1) to < 10.0 mmol l(-1) and < 7.8 mmol l(-1) at randomization required additional therapy (p < 0.001). In the initial 3 years, non-obese subjects (BMI < 30 kg m(-2)) were more likely to require additional therapy than obese patients (BMI > or = 30 kg m(-2)) (43% vs 53% at 6 years; p < 0.001). Modelled beta-cell function showed that those with lower function were more likely to fail (p < 0.0001). Thus sulphonylureas fail as a therapeutic agent at rates which are dependent both on the phenotype at presentation and perhaps on the agent used initially. Higher failure rates were found in those with higher glucose concentrations, those who were younger, those with lower beta-cell reserve and those randomized to glibenclamide compared with chlorpropamide.

Adult↗
PubMed1998

Insulin, insulin-like growth factor I (IGF-I), IGF-binding protein-1, growth hormone, and feeding in the newborn.

The relationship between GH, insulin-like growth factor I (IGF-I), IGF-binding protein-1 (IGFBP-1), and insulin may be critical to the understanding of variation in early growth, especially in the small for gestational age (SGA) baby. To investigate these relationships, we have undertaken 12-h hormone profiles in 26 babies (13 SGA) at a median of 4.5 days of age. GH levels were measured every 10 min; insulin and IGFBP-1 were measured every 20 min. Mean levels of these hormones and IGF-I levels (from a single sample) were related to size at birth. The GH data were analyzed by Pulsar and time series analysis to characterize hormone pulsatility and relationship with feeds. IGF-I levels correlated with birth weight and length (r2 = 0.47; P = 0.004, and r2 = 0.5; P = 0.0005, respectively, after allowing for gestation), whereas mean GH levels were negatively related to birth size (r2 = -0.18; P = 0.04 and r2 = -0.2; P = 0.03 for weight and length, respectively). No direct relationship between mean GH levels and IGF-I was identified. IGF-I levels were higher in appropriate for gestational age (AGA; mean +/- SD, 82+/-61 ng/mL) than in SGA (34+/-22 ng/mL; P = 0.03) babies. Baseline (mean +/- SD, 25.9+/-11.9), mean (33.9+/-14.0), and peak (45.0+/-18.1 microg/L) GH levels were higher in SGA than in AGA babies [17.1+/-8.2 (P = 0.04), 22.5+/-10.4 (P = 0.03), and 30.7+/-15.4 microg/L (P = 0.04), respectively]. Mean IGFBP-1 levels were also higher in SGA than AGA babies (157.4+/-90.7 vs. 62.7+/-43.8 ng/mL; P = 0.01). A positive correlation was identified between changes in insulin and coincident pulses of GH (r = 0.147; P < 0.01), whereas there was an inverse relationship between insulin and IGFBP-1, with a lag time 120 min (r = -0.33; P < 0.0001). In conclusion, these studies indicate that the GH-IGF-I axis is closely related to feeding in the newborn. In SGA babies, low IGF-I and elevated IGFBP-1 reflect the slow growth, but elevated GH and rapid GH pulsatility may be a signal for lipolysis.

Eating↗
PubMed1998

Mid-follicular phase pulses of inhibin B are absent in polycystic ovarian syndrome and are initiated by successful laparoscopic ovarian diathermy: a possible mechanism regulating emergence of the dominant follicle.

The hypothalamic pulse generator of GnRH is recognized to be central to ovulatory function as evidenced by the anovulation of women with hypogonadotrophic hypogonadism due to Kallmann's syndrome or severe anorexia nervosa. LH is released from the anterior pituitary in pulses, the frequency of which is closely entrained with those of GnRH. In contrast, secretion of FSH is influenced by a number of regulatory molecules, including GnRH, estradiol, inhibin, and activin. The close temporal relationship between changes in levels of inhibin B and FSH in the mid-follicular phase suggests that the release of inhibin B by the preovulatory follicle critically regulates pituitary FSH secretion. Polycystic ovarian syndrome (PCOS) is one of the most common endocrine disorders affecting ovulation, and abnormal ovarian morphology as detected by ultrasonography remains the most sensitive diagnostic marker for this disorder. The etiology of PCOS is unclear, but its effective treatment by both anti-estrogens and by exogenous FSH suggests that a primary disorder of FSH regulation may be central. To investigate the possible role of inhibin B in the pathology of PCOS, serum inhibin B levels were measured in 10 women with PCOS on cycle day 5 of a spontaneous or progestrogen-provoked bleed and compared with levels on cycle day 5 of 10 women with regular ovulatory cycles. The mean serum inhibin B levels in the PCOS patients were significantly higher at 248 (+/- 43.4) pg/mL compared with normal controls, 126 (+/- 18.6) pg/mL (P < 0.01). Ten women with clomiphene resistant PCOS and 5 normal controls consented to undergo serial blood sampling on cycle day 5. Time Series Analysis using a Fourier Transformation to analyze the power spectrum of the data revealed that in normal women there is a distinct periodicity in inhibin B levels with a clear peak detectable every 60-70 min (P < 0.05), whereas in women with ovulatory dysfunction due to PCOS, no such pattern of regular pulsatility was seen. Four women with PCOS whose anovulation was successfully treated with laparoscopic ovarian diathermy (LOD) underwent repeat venous sampling following LOD. Their serum inhibin B levels fell to the upper limit of the normal range (160 +/- 38.5) pg/mL, and pulsatility was initiated. It is possible that inhibin B pulses are being generated directly by the ovary in response to pulses of GnRH in the peripheral circulation, or indirectly in response to FSH pulses arising in the pituitary. The function of inhibin B pulses in the mid-follicular phase of the normal cycle remains to be elucidated, but the absence of the normal pulsatile pattern in women with PCOS, in conjunction with high basal levels of inhibin B arising from the multiple small follicles characteristic of the PCOS ovary, appears to reinforce the development of a large cohort of small, developmentally arrested, and ultimately atretic follicles in these patients. Initiation of normal inhibin B pulsatility by LOD in patients with polycystic ovaries appears to correlate with the post-operative onset of ovular cycles.

Diathermy↗
PubMed1998

Acute effect of fructose on postprandial lipaemia in diabetic and non-diabetic subjects.

We investigated whether the potentiation of postprandial lipaemia by fructose occurs in both non-diabetic subjects and those with non-insulin-dependent diabetes mellitus. Six non-diabetic and six diabetic subjects were studied on two occasions. They were given a meal containing 1 g fat/kg body weight with, on one occasion, 0.75 g fructose/kg body weight, on the other occasion 0.75 g starch/kg body weight. In both groups, plasma glucose and insulin concentrations rose more after starch than after fructose. At 1-2 h after the meal, plasma non-esterified fatty acid concentrations were suppressed more after fructose than after starch, but later they rose more after fructose than after starch. Plasma triacylglycerol concentrations rose more slowly after fructose, but were considerably higher than those after starch from 4-6 h after the meal. There were no differences in post-heparin plasma lipoprotein lipase (EC 3.1.1.34) activity at the end of the test. The potentiation of postprandial lipaemia by fructose was positively related to the fasting plasma insulin concentration, suggesting that insulin-resistant subjects are more prone to this effect. We conclude that the potentiation of postprandial lipaemia by fructose is seen in both diabetic and non-diabetic subjects. Our results suggest that alterations in the dynamics of plasma non-esterified fatty acids might underlie the effects of fructose on triacylglycerol metabolism.

Adult↗
PubMed1997

The stimulation of insulin secretion in non-insulin-dependent diabetic patients by amino acids and gliclazide in the basal and hyperglycemic state.

Sulfonylureas stimulate insulin secretion as their predominant contribution toward decreasing blood glucose in diabetic patients. We studied eight gliclazide-treated, non-insulin-dependent diabetic patients on two occasions with a protocol of basal observation for 30 minutes, a 60-minute infusion of randomized leucine or arginine, and a further 90-minute hyperglycemic clamp. Basal glucose was the same on both occasions (mean, 7.82 mmol/L for leucine v 7.79 for arginine, P = NS), and glucose levels declined to 7.50 and 7.25 mmol/L, respectively, by 30 minutes. After leucine infusion, the decline of glucose continued, but stabilized or reversed with arginine such that by the end of the infusions, glucose levels were 6.63 +/- 0.69 mmol/L for leucine and 7.62 +/- 0.67 for arginine (P < .02). Arginine caused a sharp increase in insulin secretion (from 17.8 mU/L to 43.8 mU/L in 6 minutes) at the onset of the infusion, and thereafter insulin secretion was not significantly different throughout either the amino acid or hyperglycemic clamp periods (mean, 42.1 v 44.7 mU/L, respectively, P = NS). By contrast, the leucine infusion caused little acute change in secretion, but augmented it with time from the basal period (17.2 mU/L) to the end of the infusion (29.4 mU/L). During the hyperglycemic clamp period, there was significant further augmentation of insulin secretion, increasing to 81.6 +/- 16 mU/L at the end of the study. Leucine significantly augmented insulin secretion compared with arginine (81.6 +/- 16 v 54.0 +/- 8.4 mU/L, respectively, P < .002). These data suggest that leucine is a better priming agent for sulfonylurea than arginine. Additive effects on insulin secretion may allow the use of combinations of branched chain amino acids (BCAAs) and sulfonylureas to augment insulin secretion in the presence of hyperglycemia.

Aged↗
PubMed1997

The use of an automated microsampling system for the characterization of growth hormone pulsatility in newborn babies.

To overcome the difficulties of studying hormone pulsatility in the newborn, we have developed an automated microsampling system that permits the measurement of hormones in small prediluted samples of blood (40 microL) taken at 10-min intervals over 12 h. The system has been validated in adult volunteers, and the error attributable to the dilution was <4%. Using this method in 10 preterm babies, we have been able to describe pulsatile changes in GH and have demonstrated a clear postprandial elevation in GH levels peaking 60 min after a feed. Fourier transform analysis indicated a pulse periodicity of 180 min in babies who were appropriate for gestational age (n = 6), but faster, co-dominant pulse periodicities of 90-100 and 140 min in babies who were small for gestational age (weight and length below the 10th centile) (n = 4). There was no significant difference between mean, peak, and baseline GH levels between the two groups.

Adult↗
PubMed1997

Approach to maintaining comparability of biochemical data during long-term clinical trials.

Our objective was to design a structured approach to maintaining comparability of biochemical data during a long clinical trial. Maintaining the comparability of clinical and biochemical data obtained in long-term studies is essential, even though analytical methods in the laboratory may be changed, conventions on specimen handling and storage revised, calibration procedures updated, quality-control systems replaced, and secular changes may occur. The United Kingdom Prospective Diabetes Study (UKPDS), a large randomized control trial investigating therapy for type 2 diabetes, was the setting for the study. Data were collected from 5102 subjects randomized since 1977. Our techniques included quality control, external quality assurance, direct comparison of laboratory methods when updating assays and statistical techniques for the detection of unsuspected changes in assay bias, laboratory comparisons of new with old assay methodologies, the realigning of data to current methods, the use of a suitable reference population for long-term monitoring, and rules to aid decision-making about clinical vs statistical significance. Procedures by which comparability of data is assured should be specified for all long-term trials and, where possible, comparison with reference methods should be detailed to allow results from different laboratories to be compared.

Diabetes Mellitus, Type 2↗
PubMed1996

Brain serotonin (5-HT) neuroendocrine function in patients taking cholesterol-lowering drugs.

Brain serotonin (5-HT) neuroendocrine function, plasma tryptophan, and platelet 5-HT content were examined in 20 patients treated in a lipid clinic for hypercholesterolaemia with combined drug and diet therapy and in 20 healthy matched controls. Treatment had produced a substantial decrease in total cholesterol concentrations in the patients, but they still had higher cholesterol and triglyceride levels than control subjects. The patients were somewhat more depressed than controls but did not differ from them in degree of hostility, free or total plasma tryptophan, or prolactin response to 30 mg of d-fenfluramine. This study does not reveal evidence of abnormal brain 5-HT neuroendocrine function in hypercholesterolaemic patients receiving cholesterol-lowering medications and diet.

Analysis of Variance↗
PubMed1996

The effect of repeated administration of hexarelin, a growth hormone releasing peptide, and growth hormone releasing hormone on growth hormone responsivity.

OBJECTIVE: Hexarelin is a synthetic six-amino-acid compound capable of releasing GH in animals and in man. Its mechanism of action is not understood and little is known about the GH response after repeated administration. The aim of this study was to determine the GH response to the administration of two intravenous boluses of hexarelin, growth hormone releasing hormone (GHRH) or hexarelin with GHRH. DESIGN: Single boluses of hexarelin (1 microgram/kg), GHRH-(1-29)-NH2 (1 microgram/kg) or hexarelin with GHRH-(1-29)-NH2 were administered intravenously. Each study was performed on two further occasions, with a second bolus being administered 60 or 120 minutes after the first. A control study was performed giving saline intravenously. Studies were performed in a random order. SUBJECTS: Six healthy adult males (25.4-34.1 years) were studied. MEASUREMENTS: Serum GH was measured by radioimmunoassay. GH secretion rates were derived from the measured serum GH concentrations using the technique of deconvolution analysis. RESULTS: The peak GH secretion rate following the first intravenous bolus of hexarelin was greater than that following the first bolus of GHRH-(1-29)-NH2 (P < 0.001), and was greatest following the administration of hexarelin with GHRH-(1-29)-NH2 (P < 0.001). The coadministration of the two secretagogues resulted in peak GH secretion rates significantly greater than the arithmetic sum of those following their isolated administration (P = 0.001), demonstrating synergism. Compared to saline, the administration of a second bolus of hexarelin, GHRH-(1-29)-NH2 or both resulted in significant further GH secretion (P = 0.02, P = 0.002, P = 0.03, respectively). The administration of a second bolus of hexarelin or hexarelin with GHRH-(1-29)-NH2 120 minutes after the first bolus resulted in lower peak GH secretion rates (P = 0.03). The reductions in peak GH secretion rates following the 60-minute boluses were not statistically significant. The peak GH secretion rates following the first GHRH-(1-29)-NH2 boluses were similar to those following the 60 and 120-minute GHRH-(1-29)-NH2 boluses (P = NS). Irrespective of the interval between the boluses of hexarelin with GHRH-(1-29)-NH2, the peak GH secretion rates following the second boluses were not significantly different from the arithmetic sum of those following the administration of the second boluses of hexarelin or GHRH-(1-29)-NH2, indicating loss of synergism on repeated administration. CONCLUSION: This study shows that hexarelin is a potent GH secretagogue active after two successive doses; the magnitude of the GH response to the second dose was influenced by the dosing interval. Hexarelin and GHRH-(1-29)-NH2 are synergistic, a property which is lost after repeated administration. These findings may help our understanding of GHRPs and may have implications for the potential use of hexarelin and other GHRPs as therapeutic agents.

Adult↗
PubMed1996

Is the growth hormone concentration regulated by the morning rise in the plasma cortisol concentration?

Exogenous steroids affect plasma growth hormone (GH) concentrations and hypothalamic somatostatin levels either directly, by stimulating the anterior pituitary gland, or indirectly by partially inhibiting the response of the pituitary gland to stimuli. The effect of the circadian rhythm of cortisol on plasma GH concentrations is unknown. In normal subjects, highest plasma GH concentrations are recorded within the first two hours of onset of sleep. During the early morning the plasma GH concentration decreases and the plasma cortisol concentration increases. We investigated the effect of the early morning rise in plasma cortisol concentration on plasma GH concentrations. We studied 12 healthy volunteers on two occasions. On one occasion the early morning rise in plasma cortisol concentrations was reduced by administering metyrapone (750 mg, 4 hourly from 03.00), while on the other occasion no intervention was made. Plasma GH and cortisol concentrations were measured every 30 and 60 minutes respectively from 22.00 until 14.00. Metyrapone caused a significant reduction in the rise of plasma cortisol concentration, but the GH concentration was identical on both occasions. We conclude that the morning rise in cortisol concentration has no acute regulatory effect on the plasma GH concentration.

Adult↗
PubMed1996

The effect of glimepiride on pancreatic beta-cell function under hyperglycaemic clamp and hyperinsulinaemic, euglycaemic clamp conditions in non-insulin-dependent diabetes mellitus.

The comparative effects of glimepiride (Amaryl; HOE 490) and glibenclamide on insulin and glucose metabolism under hyperglycaemic and hyperinsulinaemic, euglycaemic clamp conditions were studied in a double-blind, placebo-controlled, cross-over trial. Patients with sulfonylurea-controlled non insulin-dependent diabetes were allocated in random order to placebo, glimepiride (5 mg) or glibenclamide (5 mg) and received one week treatment of each with no wash-out period. At the end of each treatment week a clamp study was performed. Two protocols were used. Protocol 1 used a 5 h hyperglycaemic clamp at 10.9 mmol/l whole blood glucose concentration and Protocol II used a 3 h hyperinsulinaemic, euglycaemic damp at 3.5 mmol/l whole blood glucose concentration. Both glimepiride and glibenclamide exhibited a hypoglycaemic effect. A significant reduction in fasting whole blood glucose concentration was observed after one-week treatment of each active agent (fasting glucose: glimepiride v. placebo, 9.3 +/- 0.7 v. 10.7 +/- 0.8 mmol/l, p < 0.02; glibenclamide v. placebo, 8.9 +/- 0.9 v. 10.7 +/- 0.8 mmol/l, p < 0.005). This hypoglycaemic action of both preparations administered in equivalent daily dose appeared comparable. Glimepiride and glibenclamide stimulated beta-cell secretion and in the basal state both beta-cell secretory products insulin and C-peptide, were elevated in the plasma (basal C-peptide concentration: glimepiride v. placebo, 0.79 +/- 0.08 v. 0.68 +/- 0.07 nmol/l, p < 0.01; glibenclamide v. placebo, 0.79 +/- 0.07 v. 0.68 +/- 0.07 nmol/l, p < 0.004). This insulinotropic effect appeared to be comparable with no demonstrable difference in the efficacy of the two preparations. Under steady-state hyperglycaemic conditions both agents promoted insulin release (stimulated C-peptide concentration; glimepiride v. placebo, 1.39 +/- 0.16 v. 1.11 +/- 0.20 nmol/l, p < 0.006; glibenclamide v. placebo. 1.60 +/- 0.18 v. 1.11 +/- 0.20 nmol/l, p < 0.001) and there was no statistically significant difference between active treatments. Under steady-state euglycaemia both preparations continued to stimulate insulin release as evidenced by the mean plasma C-peptide concentrations (glimepiride v. placebo, 0.69 +/- 0.10 v. 0.28 +/- 0.06 nmol/l, p < 0.01; glibenclamide v. placebo, 0.76 +/- 0.12 v. 0.28 +/- 0.06 nmol/l, p < 0.01). Both glimepiride and glibenclamide had a comparable and significant enhancing effect on glucose metabolism (Protocol II: M: glimepiride v. placebo 4.4 +/- 1.3 v. 1.3 +/- 0.7 mg/kg.min, p < 0.05; glibenclamide v. placebo 4.7 +/- 1.3 v. 1.3 +/- 0.7 mg/kg min, p < 0.03) and improved tissue sensitivity to the action of insulin as determined by the quantity of glucose metabolised per unit insulin (Protocol II: M/l ratio: glimepiride v. placebo, 0.09 +/- 0.03 v. 0.03 +/- 0.01 kg.min per mU/l, p < 0.02; glibenclamide v. placebo, 0.1 +/- 0.03 v. 0.03 +/- 0.01 kg.min per mU/l, p < 0.01). In conclusion, glimepiride is a "second-generation" sulfonylurea agent which stimulates pancreatic beta-cell insulin secretion, lowers blood glucose and improves tissue insulin sensitivity in non-insulin-dependent diabetic subjects. Its insulinotropic effect is comparable with that of glibenclamide but may diminish in the presence of normoglycaemia. The magnitude and hence, the clinical relevance of a selective beta-cytotropic action, determined by blood glucose concentration, remains to be demonstrated.

Blood Glucose↗
PubMed1996

Postprandial lipemia: the origin of an early peak studied by specific dietary fatty acid intake during sequential meals.

Previous studies have noted the presence of an early postprandial peak in plasma triacylglycerol concentration, particularly when successive meals have been consumed. We tested the hypothesis that fat from a previous meal contributes to this early postprandial lipemia. We investigated the effect of consuming a lunch containing 61 g fat 5 h after a breakfast containing 54 g fat. The predominant fatty acids in the first meal, expressed as % by wt of total fatty acids, were 18:2 (linoleic acid), 68%, and 18:1 (oleic acid), 19%. The main fatty acids in the second meal were 18:1 (75%) and 18:2 (8%). After lunch, the early peak (at 50-60 min) in chylomicron triacylglycerol was found to contain a large proportion of 18:2, the main constituent of the first meal, whereas at later time points the chylomicron triacylglycerol fatty acid profile more closely resembled that of the second meal. Control studies in three subjects showed the complete absence of the early peaks in plasma and chylomicron triacylglycerol concentrations when either the lunch was omitted or the first meal was low in fat. The plasma nonesterified fatty acid profile also showed a corresponding peak in 18:2 at 50-60 min, which may represent the release into the plasma of fatty acids arising from the hydrolysis of chylomicron triacylglycerol by adipose tissue lipoprotein lipase.

Adult↗
PubMed1996

Effects of morning rise in cortisol concentration on regulation of lipolysis in subcutaneous adipose tissue.

Cortisol has a well-defined circadian rhythm. The aim of the study was to examine the effect of the morning rise in cortisol concentration on lipolysis in adipose tissue. Ten healthy subjects were studied on two occasions, and six of these were studied on three occasions. During the first two occasions, either a control or cortisol suppression study was performed by using metyrapone, and on the third occasion exogenous cortisol replacement was given in addition to metyrapone. Lipolysis in the subcutaneous adipose tissue of the anterior abdominal wall was studied by measurement of arteriovenous differences. Reduction in the early morning rise in cortisol led to significantly decreased venoarterialized differences for nonesterified fatty acids (P < 0.05) and glycerol (P < 0.01), attributable in part to decreased hormone-sensitive lipase (EC 3.1.1.3) action (P < 0.05) in adipose tissue. At the same time the arterialized plasma triacylglycerol concentration increased (P < 0.005) with a significant reduction in the adipose lipoprotein lipase (EC 3.1.1.34) rate of action (P < 0.05). In the replacement study, values were identical to those of the control study, showing that metyrapone had no nonspecific effects on lipolysis. We conclude that the morning rise in plasma cortisol concentration plays an important role in the regulation of lipolysis in adipose tissue in normal healthy adults.

Adipose Tissue↗