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Alzheimer's disease: pathophysiological implications of measurement of plasma cortisol, plasma dehydroepiandrosterone sulfate, and lymphocytic corticosteroid receptors.

Alzheimer's disease is often characterized by an increase in plasma cortisol without clinical evidence of hypercorticism. Twenty-three consecutive patients with Alzheimer's disease and 23 age- and sex-matched healthy controls were studied by measuring plasma cortisol and dehydroepiandrosterone sulfate (DHEAS) (by enzyme immunoassay), the number of type I and type II corticosteroid receptors in mononuclear leukocytes (by radio-receptor-assay), and the lymphocyte subpopulations (by cytofluorimetry). Results are expressed in terms of median and range. In Alzheimer's disease, plasma cortisol was higher than in controls (median 0.74, range 0.47-1.21 vs 0.47, 0.36-0.77 mmol/L; p < 0.001). Plasma DHEAS, the DHEAS/cortisol ratio, and the number of type II corticosteroid receptors were significantly lower in AD than in controls (DHEAS: median 1.81, range 0.21-3.69 vs 3.51, 1.35-9.07 micromol/L; DHEAS/ cortisol: 2.04, range 0.3-5.8 vs 6.8, range 2.7-24 and type II receptors: 1219, 1000-2700 vs 1950, 1035- 2750 receptors per cell; p < 0.001). No correlation was found between the hormonal parameters, age, and mini-mental test score. These data support the hypothesis of a dysregulation of the adrenal pituitary axis in Alzheimer's disease, which is probably the consequence of damage to target tissues by corticosteroids.

Aged↗

Effects of an olive oil-enriched diet on plasma GLP-1 concentration and intestinal content, plasma insulin concentration, and glucose tolerance in normal rats.

The present study aims mainly at measuring, in normal rats, the GLP-1 response to oral intake of an olive oil-enriched diet (OO), and at assessing the long-term effects of such a diet on the GLP-1 content of the intestinal tract, as well as the plasma D-glucose, insulin, and GLP-1 pattern during an oral glucose tolerance test. In meal-trained rats, the mean increment in plasma GLP-1 concentration at min 10 and 20 was 1.39 +/- 0.23 ng/mL higher (p < 0.001) in the rats given access to the OO diet rather than control diet. Relative to the initial value (d 0), the gain in body weight at d 50 was also higher in the animals fed the OO rather than control diet. At d 50, the GLP-1 content of the jejunum, ileum, colon, and cecum were not significantly different in the two groups of rats. At d 19 and 36, the increment in both plasma insulin concentration and paired ratio between plasma insulin and D-glucose concentrations were again higher, during an oral glucose tolerance test conducted in overnight fasted animals, in the rats otherwise fed the OO, as distinct from control, diet. The intake of an olive oil-enriched diet thus increases, in normal rats, GLP-1 release, this coinciding during long-term exposure to the OO diet with higher body weight gain, increased secretory response of insulin-producing cells to oral glucose administration, and, after 36 d, improved glucose tolerance.

Animals↗

[The effect of trilostane, a new inhibitor of adrenal steroid biosynthesis, on blood pressure, plasma aldosterone and other steroid hormones, serum potassium and plasma renin activity in primary aldosteronism (author's transl)].

Six patients with primary aldosteronism (PA), one with idiopathic hyperaldosteronism (IHA), one with glucocorticoid responsible hyperaldosteronism (GRHA) and eight with essential hypertension (EH) were treated with trilostane (MWD-1822) (4 alpha, 5-epoxy-17 beta-hydroxy-3-oxo-5 alpha-androstane-2 alpha-carbonitrile), an inhibitor of adrenal steroid biosynthesis, for 9-47 days with a daily dose of 30-960 mg. Blood pressure decreased slightly and gradually from 30 min. to 360 min, plasma aldosterone (PAC) and cortisol concentration (F) decreased, and plasma dehydroepiandrosterone concentration (DHEA) increased 120 min. after the administration of a single dose of 120 mg of trilostane. In the patients with PA, IHA and GRHA on long term therapy with trilostane, blood pressure decreased, PAC and F were depleted, serum improved within normal limits and DHEA increased, but plasma progesterone concentration (Prog.) changed variously and plasma renin activity (PRA) remained suppressed. In the patients with EH, systolic pressure decreased in 5 out of 8 (under - 20 mmHg), and diastolic pressure decreased in 3 out of 8 (under - 10 mmHg), DHEA increased in all, but the changes in serum potassium, PAC, F, Prog. and PRA were various. There was no remarkable reaction after the administration of trilostane. It is concluded that trilostane is an effective inhibitor of 3-hydroxysteroid dehydrogenase in vivo and that it is useful in the treatment of primary aldosteronism and other hypertension due to hyperproduction of aldosterone.

Adult↗

Plasma prostaglandin F2 alpha and plasma 13,14-dihydro-15-keto-prostaglandin F2 alpha levels in women during induction of labor with i.v. infusion of prostaglandin F2 alpha in relation to uterine contractions.

The concentrations of plasma PGF2 alpha and its main metabolite, 13,14-dihydro-15-keto-PGF2 alpha (PGFM) were measured in serial samples of blood collected in 10 pregnant women at term who were given iv infusions of low doses of PGF2 alpha for induction of labor. Six other women served as controls and were given saline infusions. Uterine contractions began with a mean latency of 62 min in the PGF2 alpha infused women, in controls uterine activity remained unchanged. Plasma PGFM levels had increased significantly 30 min after PGF2 alpha infusion began, rising thereafter in a dose dependent manner. Plasma PGF2 alpha also rose reaching a steady state at 2 hours. No significant changes were observed in the controls. The 6-h infusion resulted in delivery in 5 of the 10 women, in the 5 others the cervical scores increased only by 1.25 points on the average and further treatment was needed to achieve delivery, although prostanoid levels rose to similar levels in all. The data show that when uterine contractions are induced by systemic PGF2 alpha, the levels of PGFM are significantly raised. In spontaneous labor uterine contractions begin long before plasma PGFM rises. Thus, if endogenous PGF2 alpha generation is involved in the initiation of uterine contractions during spontaneous labor, it must be synthetized in the myometrium at quantities too low to raise the levels of circulating PGFM.

Adult↗

Immunoextracted calcitonin in milk and plasma from totally thyroidectomized women. Evidence of monomeric calcitonin in plasma during pregnancy and lactation.

The level of immunoreactive calcitonin in the first produced breast milk was in totally thyroidectomized (TX) women 713 +/- 307 pg-eq/ml (mean +/- SD, N = 7) and in control women 772 +/- 329 pg-eq/ml (N = 33), i.e. about 45 times higher than in plasma (see below). On gel chromatography of immunoextracted milk from TX women, immunoreactive calcitonin appeared as high molecular weight forms in the same pattern as in milk from healthy women when the same antiserum was used for immunoextraction and radioimmunoassay (RIA). In another series of experiments, a new antiserum raised in rabbits was used for measurement of immunoreactive calcitonin after immunoextraction with 1. Plasma levels of immunoreactive calcitonin in the TX women during pregnancy were 16 +/- 6 pg-eq/ml (N = 6) and during lactation 14 +/- 7 pg-eq/ml (N = 5). Immunoreactive calcitonin was undetectable (less than 8 pg/ml) in plasma from those TX women in whom lactation had stopped (N = 5). Immunoextraction and gel chromatography of plasma collected during pregnancy and lactation from the TX women showed that the immunoreactive calcitonin present eluted in the region of monomeric calcitonin with both antiserum 1 and 2. In conclusion, high concentrations of high molecular weight forms of of immunoreactive calcitonin have been demonstrated in milk from TX patients, most probably devoid of any calcitonin-producing thyroid C-cells. This points to a local production site in the mammary gland.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcitonin↗

[Functions of the sympathetic-adrenomedullar system and adrenocortex in patients with vibration syndrome. Investigations of plasma and urine catecholamine and plasma cortisol during cold exposure].

Much discussion has been made as to whether vibration syndrome is a peripheral or systemic disorder. We studied plasma and urine norepinephrine and epinephrine, and plasma cortisol under resting and cold exposure conditions (7 degrees C cold room for 30 min). The subjects were 20 patients with vibration syndrome and with a history of Raynaud's phenomenon, 20 patients with vibration syndrome without a history of Raynaud's phenomenon, and 20 healthy controls. They were all males and the three groups were matched by age. The following results were obtained. 1. Mean temperatures of finger skin in the patient groups under resting and cold exposure conditions were lower than in the control group. Mean systolic and diastolic blood pressures in the patient groups under both conditions were higher than in the control group. Mean values of blood pressure change produced by cold exposure in the patient groups were lower than in the control group. Some of these differences were statistically significant (p less than 0.05 or p less than 0.01). 2. Mean levels of plasma norepinephrine in the patient groups under resting and cold exposure conditions were significantly higher (p less than 0.01 or p less than 0.05) than in the control group. This finding indicates that the patients with vibration syndrome had hyperfunction of the sympathetic nervous system. Mean levels of urine norepinephrine in the patient groups were not significantly different from the control group. 3. Mean levels of plasma epinephrine in the patient groups under resting and cold exposure conditions were lower than in the control group. The differences between the patient groups and the control group were significant (p less than 0.05 or p less than 0.01) in the cold exposure condition. This finding suggests that the patients with vibration syndrome had hypofunction of the adrenomedullar system. Urine epinephrine in the patient groups was not significantly different from the control group. 4. Mean levels of cortisol in the patient groups were higher than in the control group. The difference in cortisol level between the group of patients without Raynaud's phenomenon and the control group was significant (p less than 0.01) in the resting condition. This finding may suggest that the patients with vibration syndrome had hyperfunction of the adrenocortex. The foregoing data support the hypothesis that vibration syndrome is a systemic dysfunction, which includes disorders of the sympathetic-adrenomedullar system and adrenocortex.

Adrenal Cortex↗

Change in plasma renin activity by cold storage of plasma in normal subjects and patients with essential hypertension and primary aldosteronism.

The time courses of change in renin activity after cold storage of human plasma at -5 degrees C and pH 7.4 were examined in 5 normal subjects, 6 patients with essential hypertension and one female patient with primary aldosteronism before and after extirpation of the adrenal tumor. In the 5 normal subjects and 6 essential hypertensives, the gradual increase in plasma renin activity was observed until 10 days of cold storage. The same result was obtained in the case of primary aldosteronism. However, there was no increase in renin activity despite of cold storage for 10 days in plasma which was sampled from this patient 45 days after operation. These data indicate that a period of 4 days for cryoactivation of human plasma renin as has been reported by Sealey et al. is not sufficient to accomplish activation of renin by cold storage.

Adolescent↗

Elevation of circulating plasma cytokines in cancer patients with high plasma parathyroid hormone-related protein levels.

Parathyroid hormone (PTH) and PTH-related protein/peptide (PTHrP) bind to the same PTH/PTHrP receptor and stimulate osteoblasts to secrete pro-inflammatory cytokines like interleukin (IL)-6. In patients with primary hyperparathyroidism, elevation of plasma levels of tumor necrosis factor (TNF)-alpha and IL-6 was also described. We, therefore, postulated that PTHrP secreted from cancer cells stimulates the secretion of cytokines and causes increases in their blood levels. Blood concentrations of several cytokines (TNF-alpha, IL-1beta, IL-5, IL-6, IL-8, IL-11 and IL-12) in cancer-bearing patients with or without elevation of blood PTHrP were measured by ELISA. The patients with high plasma PTHrP levels (n=29, intact PTHrP: 8.5 +/- 1.4 pmol/l, normal: <1.1) had higher serum type 1 collagen C-telopeptide (ICTP). Twenty of the patients were hypercalcemic. Plasma concentrations of TNF-alpha, IL-6 and IL-8 were significantly increased in patients with high PTHrP, in either the presence or absence of hypercalcemia. The concentrations of TNF-alpha and IL-6 were also significantly correlated with those of PTHrP. Our observations indicate that high plasma levels of PTHrP in cancer-bearing patients contribute not only to the development of hypercalcemia, but also to the development of the syndrome caused by an excess of pro-inflammatory cytokines.

Adult↗

Levels of alpha-melanotrophin in the plasma and pituitary glands of fetal and juvenile rats, and in the plasma of adult female rats during pregnancy and lactation.

alpha-Melanotrophin was detected by radioimmunoassay in the pituitary glands of fetal rats from day 17 of gestation. The pituitary content of alpha-melanotrophin increased regularly, at a gradually decreasing rate, throughout gestation and in the postnatal period. Concentrations of alpha-melanotrophin in the plasma of fetal and newborn rats were below the detection limit of the radioimmunoassay (10 pmol/l). Detectable concentrations were first found in young rats on day 3 after birth and did not differ significantly from those in their mothers throughout the period of suckling. Plasma concentrations of alpha-melanotrophin were raised in pregnant rats during the last 4 days of gestation and after parturition. They returned to basal levels in the 2 weeks after delivery. After weaning at 3 weeks of age, a large increase in the plasma concentration of alpha-melanotrophin was detected in juvenile rats. Plasma levels had returned to the normal adult range by 6 weeks of age. The increases in alpha-melanotrophin in the blood were thought to be the result of non-specific stress effects. The data did not provide evidence for a role of alpha-melanotrophin in reproductive processes in the rat.

Animals↗

Identification of the major steroids in ovarian and adrenal venous plasma of the brush-tail possum (Trichosurus vulpecula) and changes in the peripheral plasma levels of oestradiol and progesterone during the reproductive cycle.

The quantitatively major steroid hormones in ovarian and adrenal venous plasma of the female brush-tail possum were identified by gas chromatography-mass spectrometry. The ovarian vein plasma samples all contained oestradiol and its concentration was highest during the pro-oestrous phase of the reproductive cycle. During this phase the concentration of progesterone was below the limit of detection but at day 13 of the oestrous cycle and pregnancy, the concentration of progesterone exceeded that of oestradiol. Cortisol and corticosterone were the major steroid hormones found in all adrenal vein samples with cortisol predominant. Androgens with a 3-oxo structure, if present, were below the limits of detection in all plasma samples. Radioimmunoassays for the measurement of progesterone and oestradiol in peripheral plasma were used to follow changes in the concentrations of these steroids during the reproductive cycle. Progesterone in serial blood samples was low at oestrus, rose gradually until day 7 and then increased more rapidly to reach a peak level of 21-29 nmol/l at around day 13. Any differences between the pregnant and non-pregnant cycles were minor. Oestradiol was only detected around oestrus when levels were variable (53.3 +/- 20.92 (S.E.M.) pmol/l; n = 4). The results indicate that the reproductive cycle of the brush-tail possum is characterized by a single peak of oestradiol at around pro-oestrus followed by gradually increasing levels of progesterone. Pregnancy appears to have no influence on the circulating concentrations of oestradiol or progesterone.

Adrenal Glands↗

Effect of pulsatile infusion of gonadotropin-releasing hormone on plasma oestradiol-17 beta concentrations and follicular development during naturally and artificially maintained high levels of plasma progesterone in heifers.

To stimulate a follicular-phase pattern of pulsatile LH release, gonadotrophin-releasing hormone (GnRH; 5 micrograms) was infused (i.v.) hourly into heifers for periods of 5-11 days during the luteal phase of the oestrous cycle, and also when plasma progesterone levels were increased artificially by means of a progesterone-releasing intravaginal device. Plasma oestradiol-17 beta concentrations increased from basal (less than or equal to 2.5 pmol/l) to preovulatory peak levels (20-30 pmol/l) during the first 3 days of GnRH treatment. They were maintained at these values before returning to basal levels within 24 h of cessation of infusion. This response occurred regardless of the source of progesterone (endogenous or administered). Follicular development was observed by ovarian palpation (per rectum) in some heifers at the time of maximum secretion of oestradiol-17 beta. There was no detectable cervical mucus secretion or oestrous behaviour during these periods of high oestradiol-17 beta levels and ovulation did not occur. Treatment with GnRH did not affect plasma progesterone concentrations or oestrous cycle length. The study shows that oestradiol-17 beta secretion and follicular development (and the accompanying oestrus and ovulation) are suppressed during the luteal phase of the cycle by high concentrations of plasma progesterone, and provides strong indirect evidence that such inhibition is associated with a reduction in the pulse frequency of LH release.

Animals↗

Developmental patterns of plasma insulin-like growth factor-I (IGF-I) and body growth in mice from lines divergently selected on the basis of plasma IGF-I.

A study was conducted to investigate developmental patterns of plasma concentrations of insulin-like growth factor-I (IGF-I), body growth and body composition in mice from lines selected for seven generations on the basis of low (L) or high (H) plasma IGF-I, and in a random-bred control (C) line. Litter size was standardized to eight individuals with equal sex ratios (as far as possible) within 48 h of birth. Pups were weaned at an average of 21 days and separated on the basis of sex. Blood samples were collected from one male and one female of each litter on days, 21, 42, 63 and 105 for analysis of plasma concentrations of IGF-I. The animals were then killed and analysed for water, fat and crude protein content. The plasma concentration of IGF-I was influenced by line (P less than 0.05) but not by sex. Significant (P less than 0.001) differences in liveweight between mice from L and H lines were first evident at 21 days of age. From 28 until 105 days of age the H line was significantly (P less than 0.001) heavier than both L and C lines, but differences between C and L lines were inconsistent and mostly non-significant. The growth velocity of the H line was significantly greater than that of C or L lines between 14 and 42 days of age, but differences in growth velocities of C compared with L lines were generally non-significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of fasting, elevated plasma glucose and plasma insulin concentrations on milk secretion in women.

In order to determine whether short term variations in plasma glucose and/or insulin influence milk lactose secretion in women, the effects of fasting and increased blood insulin and glucose on milk volume and composition were studied with glucose clamp methodology in exclusively and partially breast-feeding women. Twenty hours of fasting had no discernable effect on the output of milk or its macronutrient composition. Four hours of increased plasma insulin, studied under conditions where plasma glucose was maintained at the fasting level, had no effect on milk volume, milk glucose concentration, total fat content or lactose secretion rate. Increased plasma glucose, maintained at twice fasting levels for 4 to 6 h, produced a threefold increase in milk glucose concentration but had no significant effect on the rate of lactose synthesis. In partially breast-feeding women producing no more than 200 ml milk per day, a similar degree of hyperglycaemia increased milk glucose more than fourfold but did not significantly increase the milk secretion rate. It is concluded that human milk production is isolated from the homeostatic mechanisms that regulate glucose metabolism in the rest of the body, in part because the lactose synthetase system has a Km for glucose lower than the concentration available in the Golgi compartment.

Adult↗

Glutamate concentration in plasma, erythrocyte and muscle in relation to plasma levels of insulin-like growth factor (IGF)-I, IGF binding protein-1 and insulin in patients on haemodialysis.

Elevated insulin-like growth factor binding protein (IGFBP) levels, including IGFBP-1, occur in renal failure, and may contribute towards reduced IGF bioactivity in uraemia. The reduced IGF bioactivity may, in turn, contribute towards the disturbances in protein metabolism present in renal failure. In this study, the relationships between intra- and extracellular amino acid (AA) levels and IGF-I and/or IGFBP-1 levels were studied in 30 adult patients (aged 24-70 years) on haemodialysis who had no clinical signs of malnutrition. Blood samples (n = 30) and muscle biopsies (n = 13) were collected for determination of free AA in erythrocytes (RBC), plasma and muscle by reverse-phase HPLC while IGFBP-1, IGF-I and insulin plasma levels were determined by radioimmunoassay The patients on haemodialysis had elevated glutamate concentrations in RBC and plasma compared with healthy controls (524 +/- 26 vs 448 +/- 17 mumol/l, P < 0.05 and 45 +/- 4 vs 32 +/- 4 mumol/l, P < 0.01 respectively), although glutamate levels in muscle were within the normal range. The mean IGF-I level was slightly increased (s.d. score +0.74 +/- 0.30) but insulin levels were within the normal range. IGFBP-1 levels, which were inversely correlated to insulin (r = -0.40, P < 0.02), were elevated threefold compared with controls. No plasma AA level displayed a significant correlation with IGF-I, IGFBP-1 or insulin levels. However, glutamate concentrations in RBC were positively correlated to IGFBP-1 (r = 0.51, P < 0.01) and inversely correlated to IGF-I (r = -0.46. P < 0.01), although unrelated to insulin. Muscle glutamate, which was inversely related to RBC glutamate, displayed an opposite pattern with an inverse relation to IGFBP-1 levels (r = - 0.73, P < 0.01) and a positive correlation to IGF-I levels (r = 0.64, P < 0.02). Glutamate was the only AA to display an inverse correlation between RBC and muscle (r = -0.65, P < 0.02, n = 12). These findings lead us to propose that, in uraemia, the elevated IGFBP-I levels, which reduce the bioavailability of IGFs, are linked to glutamate uptake in muscle, resulting in accumulation of RBC glutamate. Whether there is a causal relationship or the correlation is due to some common regulator is not clarified in the present study.

Adult↗

Relationship of postload plasma glucose to mortality with 19-yr follow-up. Comparison of one versus two plasma glucose measurements in the Chicago Peoples Gas Company Study.

OBJECTIVE: To explore the relationship of one versus two postload plasma glucose measurements to 19-yr mortality in men in the Chicago Peoples Gas Company Study. RESEARCH DESIGN AND METHODS: One-hour postload plasma glucose was measured twice (1.4 yr apart, 1965-1967) for 873 nondiabetic men 34-65 yr of age. Serum cholesterol, blood pressure, height, and weight were measured. Data on smoking habits were obtained. Mortality follow-up was complete through July 1986, 19 yr after second glucose load. RESULTS: In prospective analyses, with each of three glucose values--first, second, and mean of first and second--coronary, cardiovascular, and all-cause age-adjusted mortality rates were higher in quintiles 3, 4, and 5 compared with quintile 1, with a significant linear trend. Multivariate analyses with glycemia as a continuous variable confirmed a positive independent association between plasma glucose and mortality endpoints with first measurement and mean of two values but not with second. With dichotomization of plasma glucose (greater than or equal to 11.2 mM [greater than or equal to 200 mg/dl]) for 30 men hyperglycemic both times, CHD and CVD death rates were significantly higher (odds ratios 2.3-2.7) compared with those for 758 men consistently nonhyperglycemic. In contrast, for those hyperglycemic once only, death rates were not significantly higher. Results of multivariate analyses were consistent with these findings. CONCLUSIONS: These data indicate a significant relationship of asymptomatic hyperglycemia on repeat examinations to coronary and cardiovascular mortality independent of other factors measured in the study.

Adult↗

Plasma cholesteryl ester transfer protein and its relationship to plasma lipoproteins and apolipoprotein A-I-containing lipoproteins in IDDM patients with microalbuminuria and clinical nephropathy.

OBJECTIVE: To study the distribution of high-density lipoprotein (HDL) subclasses in insulin-dependent diabetes mellitus (IDDM) patients with nephropathy and factors involved in the regulation of HDL, including plasma cholesteryl ester transfer protein (CETP) and postheparin plasma lipoprotein lipase (LPL) and hepatic lipase (HL) activities. RESEARCH DESIGN AND METHODS: Participants included 52 microalbuminuric IDDM patients (with a urinary albumin excretion rate [UAER] of 20-200 micrograms/min), 37 macroalbuminuric IDDM patients (UAER > 200 micrograms/min), and 64 normoalbuminuric IDDM patients (UAER < 20 micrograms/min). Groups were matched for age, body mass index, duration of diabetes, and glycemic control (HbA1). RESULTS: Median concentrations of HDL and HDL2 cholesterol were 11.6 (P = 0.01) and 22.7% (P = 0.01) less in microalbuminuric patients and 5.1 and 15.5% less in macroalbuminuric patients compared with normoalbuminuric patients. No significant differences were observed in the concentrations of apoA-I, apoA-II (apolipoprotein) or LpA-I or LpA-I:A-II (lipoprotein) particles between the groups. HDL cholesterol: apoA-I+apoA-II ratio was significantly lower in micro- (19.7 +/- 4.2 (+/- SD); P < 0.01) and macroalbuminuric patients (20.0 +/- 3.7, P < 0.05) than in normoalbuminuric patients (22.1 +/- 4.4). Postheparin plasma LPL:HL ratio was lower in microalbuminuric patients compared with normoalbuminuric patients (1.65 vs. 1.05 [median], P < 0.01). Plasma CETP activity was higher in the macroalbuminuric patients than in micro- (P < 0.05) and normoalbuminuric patients (P < 0.05) but did not correlate with HDL, HDL2, or HDL3 cholesterol. LPL:HL ratio correlated positively with HDL cholesterol (r = 0.372, P < 0.001), HDL2 cholesterol (r = 0.413, P < 0.001) and with LpA-I particles (r = 0.355, P < 0.001) but not with LpA-I:A-II particles (r = -0.065, NS). CONCLUSIONS: IDDM patients with micro- and macroalbuminuria show only trivial changes in concentrations of different HDL parameters, which cannot explain the excess risk of coronary heart disease in these patients. Data also indicate that elevation of CETP activity in IDDM patients with nephropathy is probably not responsible for the lowering of HDL cholesterol.

Adult↗

The relationship of fasting plasma glucose values and other variables to 2-h postload plasma glucose in Japanese subjects.

OBJECTIVE: To investigate the relationship between fasting plasma glucose (FPG) values and other variables (e.g., age, sex, and BMI) to 2-h post-75-g oral glucose load glycemia (PG) in Japanese subjects. RESEARCH DESIGN AND METHODS: Subjects included 13,694 Japanese subjects between 20 and 83 years of age (10,677 men and 3,017 women) who were undergoing a 75-g oral glucose tolerance test (OGTT) during a health screening performed at our hospital. The influences of age for 2-h PG at a fixed fasting plasma glucose (FPG) level of 126 mg/dl were analyzed. Multiple linear regression analysis was performed using a model in which the dependent variable was 2-h PG using the following explanatory variables: FPG, age, sex, BMI, blood pressure, plasma cholesterol, and triglyceride (TG) levels. RESULTS: The 2-h PG at a fixed FPG of 126 mg/dl increased by 0.94 mg/dl per year in patients aged between 30 and 78 years (r = 0.68, P < 0.0001). In multiple regression, five explanatory variables (FPG, age, BMI, plasma TG levels, and systolic blood pressure levels) were all positively associated with 2-h PG. The percentages of patients with 2-h diabetes (isolated postchallenge hyperglycemia [IPH]) versus fasting plus 2-h diabetes by the World Health Organization criteria significantly (P = 0.005) increased as the patients' decades increased, whereas the impact of BMI on the percentages was significant only in young patients (P = 0.001). CONCLUSIONS: Aging was found to be the second best predictor of 2-h PG on multiple regression. Therefore, OGTT should be performed especially in elderly patients because they show IPH more frequently.

Adult↗

Comparison of plasma glucose and plasma free insulin during CSII and intensified conventional insulin therapy.

The plasma glucose and plasma free insulin profiles of six totally insulin-dependent diabetic patients were compared during periods of 4 days in hospital under a conventional insulin therapy (ICIT) comprising 4 daily injections of regular insulin and under continuous subcutaneous insulin infusion (CSII). Two profiles of prandial insulin administration with CSII were compared: a rectangular (R) and an exponential wave (E) in which 50% of the dose was given rapidly followed by an exponential decrease. In both cases, the basal infusion rate was increased by 30-50% between 5 a.m. and 8 a.m. Mean circadian blood glucose was equally good with ICIT: R and E: 7.0 +/- 0.9, 7.3 +/- 1.0, and 7.1 +/- 1.0 mmol/L, respectively. In five patients, fasting plasma glucose was higher with ICIT than with R and E (12.7 +/- 1.8 versus 6.9 +/- 1.0 and 6.8 +/- 0.8 mmol/L, respectively; t test: P less than 0.05; Wilcoxon: P = 0.06). Mean plasma free insulin level was significantly higher (t test: P less than 0.005; Wilcoxon: P less than 0.05) with ICIT (0.46 +/- 0.04 nmol/L) than with R (0.37 +/- 0.04 nmol/L) or E (0.36 +/- 0.05 nmol/L), although the daily doses were similar. In conclusion, CSII leads to a better glycemic control than ICIT, since it appears to prevent the morning rise of blood glucose.

Adult↗