Biomedical subjects

W T Cefalu

Publications and source records attributed to W T Cefalu.

At least 37 records · Page 2Linked to original sources

PubMed1998

Insulin resistance and fat patterning with aging: relationship to metabolic risk factors for cardiovascular disease.

Both insulin resistance and abdominal fat patterning are related to aging, and have been related to cardiovascular disease (CVD) risk factors such as dyslipidemia and hypertension. However, previous studies have not used direct methods to quantify the independent strength of the association of each of these two putative primary factors with metabolic outcomes. We quantified overall obesity by the body mass index (BMI) and used a previously validated magnetic resonance imaging (MRI) method to quantify abdominal fat in 63 healthy nondiabetic individuals aged 22 to 83 years. We also measured the glucose and insulin response to an oral glucose tolerance test and the insulin sensitivity ([SI] by modified minimal model analysis). Body fat patterning was evaluated by the waist to hip ratio (WHR) and by MRI, which allowed direct measurement of subcutaneous (SCF) and intraabdominal (IAF) fat depots at the umbilicus in these subjects. These independent parameters were related to risk factors for CVD (blood pressure, lipids, and lipoproteins) and to plasma concentrations of free fatty acids (FFAs). Measures of overall obesity (BMI), total fat [TF], and/or SCF measured at the abdomen by MRI), glucose/insulin metabolism and SI, and central fat patterning (WHR or IAF measured by MRI) were correlated with mean arterial pressure (MAP), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) levels in univariate analysis and after controlling for age and gender. An index of central fat patterning (WHR) added to the informativeness of the insulin area under the curve (IAUC) in explaining 24% of the variability in plasma TG concentration, but measures of overall obesity were not independently related. Both the BMI and TF contributed to the IAUC in explaining 32% to 34% of the variability in MAP, but central fat patterning was not independently related. No index of overall obesity, fat patterning, glucose/insulin metabolism, and/or SI, was independently related to the plasma concentration of HDL-C after controlling for any one of the other two. Direct measurement of glucose/insulin metabolism and SI, as well as fat patterning, provides information on their relative associations with CVD risk factors. The measures of glucose/insulin metabolism and SI were more consistently related to dyslipidemia and hypertension than were the overall obesity and fat patterning in this healthy population.

Adipose Tissue↗

PubMed1998

Chronic hyperglycemia increases arterial low-density lipoprotein metabolism and atherosclerosis in cynomolgus monkeys.

Diabetes mellitus confers a threefold to fivefold increased risk of mortality from vascular disease. The primary cause of this increased incidence of vascular disease is atherosclerosis, but the mechanisms accounting for the increase are unclear. Chronic hyperglycemia is a common feature of all forms of diabetes mellitus and may contribute greatly to the increased incidence of atherosclerosis, via promotion of both lipoprotein and tissue glycation, which may have atherogenic effects. The present study investigated the effect of chronic hyperglycemia on measures of low-density lipoprotein (LDL) metabolism and atherosclerosis in streptozotocin-induced diabetic (STZ-DM) and control cynomolgus monkeys after 6 months of study. Consistent with a chronic hyperglycemic state, diabetic monkeys had significant increases in glycated hemoglobin (GHb) and glycated plasma LDL concentrations, but had minimal changes in total plasma cholesterol (TPC) or triglyceride (TG) concentrations during the study. Forty-eight hours before necropsy, control and in vitro-glycated LDL were differentially radiolabeled and coinjected into diabetic and control monkeys. There was a significant increase in arterial LDL accumulation in femoral arteries from diabetic monkeys compared with controls, with similar trends in other arterial sites. The effect of LDL glycation on arterial LDL accumulation was minimal in both groups. Arterial segments from diabetic monkeys also had greater amounts of arterial cholesterol content compared with controls. Histomorphometric analyses showed that diabetic monkeys had significantly greater intimal areas in the femoral artery and abdominal aorta compared with controls. Diabetic monkeys also had reduced arterial remodeling, or compensation, in the femoral artery and abdominal aorta. However, there was no difference in advanced glycation end products (AGE) in arterial collagen between groups. In conclusion, experimentally induced diabetes mellitus increases arterial LDL accumulation and atherosclerosis extent in cynomolgus monkeys before changes in AGE formation. The increased atherogenesis may be due to changes in lipoproteins or direct effects of hyperglycemia on the artery wall.

Animals↗

PubMed1998

Caloric restriction in rhesus monkeys reduces low density lipoprotein interaction with arterial proteoglycans.

Caloric restriction (CR) has been shown to retard aging processes in many species. We investigated effects of CR on plasma low density lipoproteins (LDL), a major risk factor for the age-associated process of atherosclerosis. Studies emphasized effects of CR on LDL composition and their interaction with arterial proteoglycans (PG). Rhesus monkeys were fed a control diet (n=13) or subjected to CR (n=12 fed 30% less calories) for > 5 years. Plasma LDL cholesterol concentrations were similar for control and CR groups (82+/-8 vs 72+/-6 mg/dL, mean+/-SEM). LDL was isolated by ultracentrifugation and HPLC. LDL particles from CR animals had a lower molecular weight (2.9+/-0.1 vs 3.2+/-0.1 g/micromol, p < .05) and were depleted in triglyceride (249+/-16 vs 433+/-49 mol/particle, p < .005) and phospholipid (686+/-20 vs 837+/-33 mol/particle, p <.001). Lower PG binding was measured for LDL from CR animals (10.1+/-0.8 vs 15.6+/-1.1 microg LDL cholesterol/microg PG, p <.005). This was associated with the lower triglycerides (r=.76, p < .0005) and phospholipids (r=.48, p < .01). Thus, a dietary intervention which may retard aging inhibits a proposed mechanism of atherogenesis.

Animals↗

PubMed1998

Insulin sensitivity and cardiovascular risk factors in ovariectomized monkeys with estradiol alone or combined with nomegestrol acetate.

We have previously shown that medroxyprogesterone acetate (MPA), either alone or combined with conjugated equine estrogens (CEE), significantly decreased insulin sensitivity (SI), compared with both untreated controls and those treated with CEE alone. The purpose of this study was to determine the effects of estradiol (E2), with and without nomegestrol acetate (NA; a potent progestin that lacks androgenic activity), on SI and arterial antioxidant activity, as determined by F2-isoprostanes. Thirty-six adult female cynomolgus monkeys (Macaca fascicularis) were ovariectomized and fed a moderately atherogenic diet, with one of the following three treatments added to the diet, for 12 weeks: 1) no treatment (control); 2) E2; or 3) continuous combined E2 + NA (E2+NA). SI and glucose effectiveness were assessed by the frequently sampled i.v. glucose tolerance test using a third-phase insulin infusion after 10 weeks of treatment. Cholesterol content and F2-isoprostanes were measured in the thoracic aorta after 12 weeks of treatment. E2 treatment resulted in a significantly greater SI, compared with control or E2+NA-treated monkeys (10.03 +/- 0.91 vs. 6.35 and 6.49 x 10(-4) min(-1) microU(-1) mL; P < 0.05). In contrast to our studies of CEE and MPA, E2+NA treatment, though reducing the SI below that of the E2 group, did not reduce the SI below that of control monkeys. As expected, the short period of treatment resulted in no significant differences in aortic cholesterol content. There was no treatment effect on total F2-isoprostanes (representing F2-isoprostane formation caused primarily by autooxidation), suggesting minimal antioxidant activity. However, there was a treatment difference in the prostaglandin F2alpha (PGF2alpha) isomer (a prostaglandin (PG) isomer formed by both autooxidation of arachidonate and cyclooxygenase activity). PGF2alpha concentrations were 32% lower with E2 treatment, compared with controls, and 36% lower, compared with E2+NA treatment (0.48 +/- 0.08 vs. 0.71 +/- 0.12 and 0.75 +/- 0.06; P < 0.05), suggesting differences in PG synthesis between hormone treatments. In conclusion, NA, a progestin without androgenic activity, may still affect some cardiovascular risk factors differently than estrogen-only therapy. However, it seems to be less detrimental than MPA.

Administration, Oral↗

PubMed1998

Streptozotocin-induced diabetes mellitus in cynomolgus monkeys: changes in carbohydrate metabolism, skin glycation, and pancreatic islets.

Chronic hyperglycemia has been implicated in a number of diabetes mellitus-related conditions in the human population, including retinopathy, neuropathy, nephropathy, and vasculopathy. However, it has been difficult to evaluate the effect of long-term hyperglycemia in a research setting because of the disease's slow progression. In this study, we used streptozotocin (30 mg/kg of body weight, intravenously) to induce a state of chronic hyperglycemia in eight cynomolgus monkeys, and compared these monkeys with a matched control group (n = 8). Seven of eight monkeys with streptozotocin-induced diabetes required insulin therapy to avoid ketosis. After disease induction, all diabetic monkeys had significantly higher preprandial plasma glucose and glycated hemoglobin values, compared with their baseline values or values for control monkeys. Diabetic monkeys also had abnormal responses to an intravenous glucose tolerance test. Consistent with the chronic hyperglycemic state and formation of advanced glycation end products, diabetic monkeys had a significant increase in skin fluorescence over the course of the 6-month study. Plasma triglyceride and cholesterol concentrations increased, but not significantly so, in the diabetic monkeys after disease induction and were not significantly different from concentrations in control monkeys. Six months after disease induction, monkeys were necropsied, and immunohistochemical staining for insulin in the pancreatic islets indicated that diabetic monkeys had a significantly decreased amount of staining for the hormone. The percentage of islet insulin staining was significantly correlated with physiologic responses to the postinduction intravenous glucose tolerance test in all monkeys. Because cynomolgus monkeys are well-characterized models of atherosclerosis, this model may be useful for determining mechanisms whereby diabetes mellitus increases cardiovascular disease.

Animals↗

PubMed1997

Dietary soy protein and estrogen replacement therapy improve cardiovascular risk factors and decrease aortic cholesteryl ester content in ovariectomized cynomolgus monkeys.

Estrogen replacement therapy (ERT) decreases the progression of coronary artery atherosclerosis in monkeys. Dietary soy protein also retards the progression of atherosclerosis relative to animal proteins such as casein. Soy protein contains weakly estrogenic compounds called isoflavones or phytoestrogens that may be responsible for the cardioprotective effects. This study was designed as a 2 x 2 factorial to determine the magnitude of soy protein's effects on cardiovascular risk factors relative to casein and lactalbumin, with or without estradiol treatment. Ovariectomized female monkeys were randomized to four treatment groups based on past dietary cholesterol consumption, their origin, and past reproductive history, and studied for 7 months. The animals were divided into (1) a group fed casein and lactalbumin as the protein source (n = 14), (2) a group fed casein and lactalbumin as the protein source plus 17 beta-estradiol (E2) (n = 13), (3) a group fed soybean protein isolate as the protein source (n = 11), and (4) a group fed soybean protein isolate as the protein source plus E2 (n = 10). Soy protein compared with casein consumption resulted in a significant improvement in plasma lipid and lipoprotein concentrations, a significant improvement in insulin sensitivity and glucose effectiveness as determined by minimal-model analyses, and a decrease in arterial lipid peroxidation. E2-treated monkeys had a significant reduction in fasting insulin levels and insulin to glucose ratios, total body weight, and amounts of abdominal fat, and had smaller low-density lipoprotein (LDL) particles. In addition, E2 treatment resulted in a significant reduction (P = .001) in aortic cholesteryl ester content. A similar trend (P = .14) was found for soy protein compared with casein. There also was a significant interaction (P = .02) with soy and E2, such that animals consuming soy protein +E2 had the least arterial cholesteryl ester content. These results suggest that both ERT and dietary soybean protein have beneficial effects on cardiovascular risk factors. Interestingly, the two treatments affected different risk factors and together resulted in the greatest reduction in arterial cholesterol content. Further studies are needed to determine the active component of the soy protein and to assess its long-term effects on the cardiovascular system and other organ systems (such as the bones and reproductive system).

Aging↗

PubMed1997

A study of caloric restriction and cardiovascular aging in cynomolgus monkeys (Macaca fascicularis): a potential model for aging research.

Caloric restriction has been demonstrated to retard aging processes and extend maximal life span in rodents, and is currently being evaluated in several nonhuman primate trials. We initiated a study in 32 adult cynomolgus monkeys to evaluate the effect of caloric restriction on parameters contributing to atherosclerosis extent. Following pretrial determinations, at which time a baseline measure of ad libitum (ad lib) dietary intake was assessed, animals were randomized to an ad lib fed group (control) or a caloric restriction group (30% reduction from baseline intake). The animals are being evaluated for glycated proteins, insulin, glucose, insulin sensitivity measures, and specific measures of body fat composition by CT scans (e.g., intra-abdominal fat) over specified intervals. The results from the first year of observation demonstrate a significant diet effect on body weight, and specifically intra-abdominal fat. Further, insulin sensitivity has been significantly increased after 1 year of caloric restriction compared to the ad lib fed group. These studies indicate that caloric restriction has a marked effect on a pathologic fat depot, and this change is associated significantly with an improvement in peripheral tissue insulin sensitivity.

Aging↗

PubMed1996

The effects of hormone replacement therapy on carbohydrate metabolism and cardiovascular risk factors in surgically postmenopausal cynomolgus monkeys.

Controversy exists regarding the effects of estrogen and estrogen/progestin replacement therapies on glucose tolerance and insulin resistance. Also unknown are whether changes in glucose tolerance and insulin resistance with hormone therapy affect arterial glycation and atherosclerosis. We studied ovariectomized female monkeys fed a lipid-lowering diet and given either no hormone replacement therapy (n = 25) or conjugated equine estrogens (CEE) alone (n = 22) or combined with medroxyprogesterone acetate ([MPA] n = 21) for 30 months. Monkeys receiving combined hormone replacement had significantly higher fasting glucose and insulin levels and higher insulin responses to a glucose challenge compared with controls or those given estrogen alone. Monkeys given estrogen-only therapy had lower body weights, lower measures of abdominal adiposity, and decreased serum androgen concentrations. However, due to the effective dietary lipid decrease, there was no additional effect of hormone treatment on atherosclerosis. Also, there was no correlation between either arterial glycation or insulin levels and atherosclerosis extent. Thus, although there were adverse effects of combined hormone replacement therapy on carbohydrate metabolism, we were unable to determine whether these effects altered the extent of atherosclerosis.

Adipose Tissue↗

PubMed1996

Islet amyloid and islet amyloid polypeptide in cynomolgus macaques (Macaca fascicularis): an animal model of human non-insulin-dependent diabetes mellitus.

To further characterize spontaneous diabetes mellitus in cynomolgus macaques (Macaca fascicularis) as a model for human non-insulin-dependent diabetes mellitus (NIDDM), we evaluated the morphologic characteristics of the endocrine pancreas of 4 diabetic and 12 age-matched nondiabetic cynomolgus macaques. In addition, the cDNA-predicted amino acid sequence for islet amyloid polypeptide (IAPP) of this species was determined. Islet amyloid deposits exhibiting typical congophilia and green birefringence were found in 4/4 diabetic animals and in 8/12 nondiabetics. Islet amyloid deposits were significantly more extensive in the diabetic macaques (P = 0.001), in which they occupied a mean of 60% of the islet area. In contrast, in the nondiabetic group the maximum islet area occupied by amyloid was 24% (group mean = 6.8%), with four animals having no detectable islet amyloid. Amyloid deposits consistently showed immunoreactivity for IAPP but not for insulin. Comparisons between group means for diabetic versus nondiabetic macaques showed significantly greater islet area (P = 0.01, 85,390 versus 36,540 microns 2) and significantly greater islet area fraction (P = 0.02, 0.065 versus 0.032) for the diabetic group. The cDNA-predicted amino acid sequence for cynomolgus IAPP was identical to that previously reported for pig-tail macaques (M. nemestrina) and had 92%, 86%, and 84% amino acid sequence identity with human, domestic cat, and murine IAPPs, respectively. These findings support the use of cynomolgus macaques as an animal model of human NIDDM.

Amino Acid Sequence↗

PubMed1996

Treatment of type II diabetes: what options have been added to traditional methods?

Clinical goals in patients with non-insulin-dependent (type II) diabetes are to control glucose levels and prevent microvascular complications (eye, kidney, and nerve damage) while improving risk factors associated with cardiovascular disease (obesity, smoking, hyperlipidemia, hypertension, and hyperinsulinemia or insulin resistance). A wide array of medications and approaches is available to treat type II diabetes. Still, establishing an effective treatment regimen can be difficult, because patients have varying degrees of insulin secretory defects and insulin resistance and different conditions that must be factored in. Therefore, an individualized plan centered on self-management is the key to successful therapy in type II diabetes.

Clinical Trials as Topic↗

PubMed1996

Increased glycation of plasma lipoproteins in diabetic cynomolgus monkeys.

Hyperglycemia associated with diabetes mellitus increases glycation of hemoglobin and serum proteins in human and nonhuman primates. It also has been documented that numerous other circulating proteins may be glycated. In this study we found that most of the major subclasses of lipoproteins (low-density, very low-density, and high-density) from diabetic cynomolgus monkeys were significantly more glycated than were lipoproteins from age- and sex-matched controls. Correlations between levels of glycemic control and glycation of lipoproteins also were significant. Because glycation of lipoproteins has been shown to affect their normal metabolism, this animal model may be useful in determining the interaction between lipoproteins, diabetes mellitus, and the increased risk of atherosclerosis.

Animals↗

PubMed1996

Diabetes mellitus and islet amyloidosis in cynomolgus monkeys.

Six 15- to 20-year-old obese cynomolgus monkeys were determined to have diabetes mellitus. These monkeys were hyperglycemic and hypertriglyceridemic, yet remained nonketotic for several years before requiring clinical intervention. A significant decrease in glucose disappearance and an increased area under the glucose disappearance curve were found in response to intravenous glucose tolerance testing. Basal hyperinsulinemia was found in three animals that, in response to glucose stimulation, had a blunted insulin response, resulting in an overall decrease in the area under the insulin curve. Two animals died during the study and had extensive amyloid infiltration of pancreatic islets. The combined findings of old age, obesity, hyperinsulinemia, improvement in response to caloric restriction, and islet amyloidosis are consistent with type 2 diabetes mellitus.

Adipose Tissue↗

PubMed1995

Contribution of visceral fat mass to the insulin resistance of aging.

Recent studies have shown that central obesity (increased waist to hip ratio [WHR]) is related to insulin resistance and aging. Furthermore, in central-obesity states, the intraabdominal fat (IAF) depot has been postulated to contribute most to the development of insulin resistance. Therefore, the observed insulin resistance of aging may be related more to changes in body composition than to aging per se. The purpose of this study was to explore the association of IAF with age and insulin sensitivity (SI) after controlling for obesity. We examined 60 healthy nondiabetic subjects (normal 75-g oral glucose tolerance test, aged 23 to 83, 15 men and 45 women). We chose subjects so that those < or = 125% and greater than 125% of ideal body weight were equally represented in each age decade. We quantified total and subcutaneous abdominal fat and IAF at the umbilicus using a validated magnetic resonance imaging (MRI) scanning technique and determined SI using a modified minimal model. IAF correlated significantly with age (r = .49, P = .0001) in the group as a whole, as well as in men (r = .58, P = .022) and women (r = .48, P = .0008) separately. In all subjects, SI was significantly related to IAF (r = -.50, P < .0001) but was not related to age (r = .00, P = .98). In multivariate analysis for various combinations of age, sex, and measures of fat distribution, WHR accounted for 28% and IAF for 51% of the variance in SI, whereas age, sex, and interactions of age and sex accounted for only 1%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

PubMed1995

Doxazosin lowers blood pressure and improves insulin responses to a glucose load with no changes in tyrosine kinase activity or insulin binding.

alpha-Adrenergic blockers have shown favorable metabolic effects. We evaluated the glucose and insulin responses to a glucose load and lipid profiles in 36 diabetic hypertensive patients before and after 8 weeks of doxazosin administration. To evaluate insulin action at the cellular level, erythrocyte insulin binding and tyrosine kinase (TK) activity were measured in 12 of these patients. Systolic and diastolic blood pressures decreased significantly (P < .0001) after 8 weeks of doxazosin therapy. Doxazosin administration significantly reduced the integrated insulin response (area under the curve [AUC]-insulin: 6093 +/- 894 to 5260 +/- 807; P = .04) and the insulin/glucose index (I/G) at 90 and 120 min after a glucose load (at 90 min, 0.230 +/- 0.055 v 0.180 +/- 0.04, P < .05; at 120 min, 0.275 +/- 0.071 v 0.173 +/- 0.036, P < .05). HDL3 level increased from 31.1 +/- 1.5 mg% to 34 +/- 1.6 mg% (P < .05) after doxazosin. Erythrocyte insulin binding and tyrosine kinase activity were not significantly altered after doxazosin. No significant correlation was found between the insulin or glucose responses and the insulin receptor binding or tyrosine kinase activity before and after treatment.

Blood Glucose↗

PubMed1995

Caloric restriction decreases age-dependent accumulation of the glycoxidation products, N epsilon-(carboxymethyl)lysine and pentosidine, in rat skin collagen.

Nonenzymatic glycation of body proteins and subsequent advanced glycation reactions have been implicated in the aging process, while caloric restriction (CR) in rodents results in an increase in both mean and maximum life span. We have evaluated the effect of chronic (25 months) CR on glycation of blood proteins and accumulation of advanced glycation and oxidation (glycoxidation) products, N epsilon-(carboxymethyl)lysine (CML), and pentosidine, in skin collagen. Brown-Norway rats, fed ad libitum (AL) from birth, were divided into two equal groups at 4 months of age and placed on AL or CR diets (CR = 60% of AL diet). Cohorts of animals were sacrificed at 7, 13, and 25 months after the initiation of CR. At necropsy glycated hemoglobin was measured by affinity HPLC and glycated plasma protein by the fructosamine assay; extracts of skin collagen were analyzed by gas chromatography-mass spectrometry for CML and by reversed-phase HPLC for pentosidine. Glycation of hemoglobin, plasma proteins, and skin collagen was decreased significantly (18-33%) by CR. Concentrations of CML and pentosidine increased significantly with age in skin collagen in both AL and CR animals; however, CR significantly reduced levels of CML (25%), pentosidine (50%), and fluorescence (15%) in collagen in the oldest rats. We conclude that CR reduces the extent of glycation of blood and tissue proteins and the age-related accumulation of glycoxidation products in skin collagen.

Aging↗

PubMed1994

The effects of hormonal replacement therapy on insulin sensitivity in surgically postmenopausal cynomolgus monkeys (Macaca fascicularis).

OBJECTIVE: Our purpose was to evaluate the effect of hormone replacement therapy on insulin resistance in postmenopausal cynomolgus monkeys (Macaca fascicularis). STUDY DESIGN: We studied 37 surgically postmenopausal cynomolgus monkeys that were fed a moderately atherogenic diet for 12 weeks with either no treatment (control), conjugated equine estrogens, medroxyprogesterone acetate, combination conjugated equine estrogens and medroxyprogesterone acetate, or tamoxifen. Insulin sensitivity and glucose effectiveness were determined by the frequent-sampling intravenous tolerance test by means of the minimal model analysis. RESULTS: There were no differences in body weight, total plasma cholesterol, or body fat distribution between control and conjugated equine estrogens, medroxyprogesterone acetate, or combination treatment groups. However, compared with control animals (insulin sensitivity = 5.9 +2- 1.2 x 10(-4) min-1 microU-1 ml) or conjugated equine estrogens treatment (6.3 +/- 1.1 x 10(-4) min-1 microU-1 ml) insulin sensitivity was significantly decreased in animals treated with medroxyprogesterone acetate (2.9 +/- 0.4 x 10(-4) min-1 microU-1 ml, p < 0.001) or conjugated equine estrogens and medroxyprogesterone acetate (2.8 +/- 0.6 x 10(-4) min-1 microU-1 ml, p < 0.001). Although insulin sensitivity was shown to be decreased in the tamoxifen-treated animals (insulin sensitivity = 4.6 +/- 0.6 x 10(-4) min-1 microU -1 ml), the difference was not statistically significant compared with the control or conjugated equine estrogens-treated animals. No significant differences were seen for glucose effectiveness comparing control animals (glucose effectiveness = 0.043 +/- 0.006 min-1) to animals treated with medroxyprogesterone acetate (glucose effectiveness = 0.046 +/- 0.009 min-1), conjugated equine estrogens and medroxyprogesterone acetate (0.048 +/- 0.008 min-1) or tamoxifen (0.039 +/- 0.006 min-1). CONCLUSION: These results suggest that progestins alone or in combination with estrogens can induce insulin resistance in postmenopausal monkeys while having no effect on plasma lipid concentrations or glucose effectiveness.

Animals↗

PubMed1994

Glycohemoglobin measured by automated affinity HPLC correlates with both short-term and long-term antecedent glycemia.

We evaluated glycohemoglobin (GHb) and glycated plasma protein (GPP) by automated affinity HPLC for their ability to monitor both short-term and long-term antecedent glycemia in 70 diabetic subjects. We placed 30 subjects on an intervention protocol in which insulin and (or) dietary changes were made twice weekly to acutely decrease glycemia. We monitored 40 subjects at 6-week intervals; changes in the clinical regimen were made at that time only. Despite weekly changes in mean blood glucose in the subjects who received more intensive intervention. GHb concentrations correlated significantly with the weekly (r = 0.66, P < 0.001), 2-week (r = 0.70, P < 0.001), 3-week (r = 0.72, P < 0.001), and 6-week (r = 0.83, P < 0.001) mean glucose concentrations. GPP correlated significantly with measured glycated albumin determined by boronate affinity columns (r = 0.83, P < .001) and correlated best with the 1-week (r = 0.66, P < 0.001), 2-week (r = 0.64, P < .001) and 3-week (r = 0.60, P < 0.001) mean antecedent glucose concentration. Thus, GHb, traditionally considered a marker for only long-term diabetic control, correlated significantly with both short-term and long-term antecedent glycemia.

Adult↗

PubMed1993

Effect of obesity and fertility status on sex steroid levels in men.

Endocrine studies were performed on fertile and infertile obese men and compared with fertile and infertile nonobese men in order to determine the independent and codependent effects of obesity and fertility status on the male hypothalamic-pituitary gonadal axis. The obese infertile group exhibited significant endocrinologic changes as compared with fertile nonobese control group which was not observed in any of the other three groups. Serum testosterone was significantly lower. The testosterone/estradiol ratio was significantly lower despite a lack of significant change in serum estradiol levels. Serum steroid hormone binding globulin (SHBG) was significantly lower which correlated with elevated bioavailability of both testosterone and estradiol in the obese infertile group. Serum luteinizing hormone levels were no different, suggesting that free testosterone levels were unchanged. Obese infertile men exhibit endocrinologic changes that are not observed in men with either obesity or infertility alone. Reduction of serum SHBG, total testosterone, and testosterone/estradiol ratio appear to be a marker of infertility among obese men.

Biomarkers↗