Relationship Of Glucose Tolerance Research Articles

Sexual dimorphism in the peripheral metabolic homeostasis and behavior in the TgF344-AD rat model of Alzheimer's disease.

Alzheimer's disease (AD), a prevalent form of dementia, is characterized by the decline of cognitive abilities with age. Available treatment options for AD are limited, making it a significant public health concern. Recent research suggests that metabolic dysfunction plays a role in the development of AD. In addition, insulin therapy has been shown to improve memory in patients with cognitive decline. In this study, we report the first examination of body composition, peripheral insulin sensitivity, and glucose tolerance in relation to behavioral assessments of learning, memory, and anxiety in the TgF344-AD rat model of AD. Results from glucose and insulin tolerance tests show that female TgF344-AD rats exhibit impaired glucose clearance and reduced insulin sensitivity at both 9 and 12 months of age, while males display no differences at 9 months and even improved glucose clearance at 12 months. Results from the Morris Water Maze assessment of learning and memory reveal that male TgF344-AD rats display impairments at both 9 and 12 months of age, while female TgF344-AD rats only show impairments at 12 months. Furthermore, results from open field and elevated plus maze tests suggest that female TgF344-AD rats display increased anxiety at 9 months of age; however, no differences were detected in males or at 12 months of age. Overall, our findings suggest that impairments in metabolism, commonly associated with type 2 diabetes, occur before or simultaneously with cognitive decline and anxiety in a sexually dimorphic manner in the TgF344-AD rat model.

Glucose Tolerance is Linked to Postprandial Fuel Use Independent of Exercise Dose.

The optimal short-term exercise dose to improve glucose tolerance in relation to metabolic flexibility and/or insulin resistance is unknown. Therefore, we tested if short-term, work-matched continuous (CONT) versus interval (INT) exercise training improves glucose tolerance in part by reducing insulin resistance and increasing metabolic flexibility independent of clinically meaningful fat loss in adults with prediabetes. Subjects (age = 60.9 ± 1.4 yr, body mass index = 33.5 ± 1.1 kg·m) were screened for prediabetes using the American Diabetes Association criteria (75 g oral glucose tolerance test [OGTT] and/or HbA1c) and were randomized to 60 min·d of supervised CONT (n = 17, 70% HRpeak) or work-matched INT (n = 14; 90% HRpeak for 3 min and 50% HRpeak for 3 min) exercise for 12 bouts. Fitness (V˙O2peak) and body composition were assessed pre- and postintervention. A 180-min 75-g OGTT was performed, and glucose, insulin, and free fatty acids were collected to calculate glucose tolerance (tAUC180min) and whole-body as well as adipose tissue insulin resistance pre- and postintervention. RER (indirect calorimetry) was also measured at 0, 60, 120, and 180 min of the OGTT to assess fasting and postprandial metabolic flexibility. CONT and INT training improved V˙O2peak (L·min; P = 0.001) and glucose tolerance (P = 0.01) and reduced fasting RER (P = 0.006), as well as whole-body and adipose insulin resistance (both P = 0.02) with no effect on body fat (P = 0.18). Increased postprandial RER was correlated with reduced glucose tAUC180min (r = -0.38, P = 0.05) and increased 180-min RER related to decreased whole-body insulin resistance (r = -0.42, P = 0.03). Independent of exercise dose and fat loss, short-term training improves glucose tolerance in relation to enhanced postprandial fuel use.

Endocrine profile of β-thalassemia major patients followed from childhood to advanced adulthood in a tertiary care center.

Aim:Chronic iron overload resulting from frequent transfusions, poor compliance to efficient chelation therapy and chronic liver disease is basically responsible for the most severe complications of thalassemia major (TM). Before conventional treatment, TM was entirely childhood disease with a very short survival. Today, survival improved to 40–50 years and becomes a prevalent disease of adulthood and in the near future it will be one of senility. Furthermore, clinical phenotype of TM is changing with age and appearance of severe complications from the heart and endocrine glands that require special health care from well-informed specialists.Objectives:The aims of our study were to: (1) Imprint the clinical profile of long-lived TM patients; (2) evaluate retrospectively the cumulative incidence of endocrine diseases; (3) identify potential risk factors; and (4) orient the physicians in the modified clinical phenotype and the relative patients' health needs.Design:A retrospective cross-sectional study followed from childhood to adulthood by the same physician in a tertiary thalassemia clinic.Participants:Forty-three long-lived TM patients (mean age: 50.3 ± 10.8 years; range: 45.8–59.5 years; 23 females) were studied.Patients and Methods:An extensive medical history, with detailed clinical and laboratory data, endocrine complications, and current treatments, was obtained.Results:The data indicate that 88.4% of adult TM patients suffered from at least one endocrine complication. The majority of patients developed endocrine complications in the second decade of life when serum ferritin level was very high (12/23 TM female and 8/20 TM male patients, the serum ferritin levels at the diagnosis were above 5.000 ng/ml).Conclusions:These data underline that endocrine and bone complications in adult TM patients are highly prevalent and necessitate close monitoring, treatment, and follow-up. Physicians' strategies to optimize chelation therapy include identifying patients who are at risk for developing organ damage, developing chelation plans, promoting compliance, and educating patients. Several clinical aspects remain to be elucidated such as growth and impairment of glucose tolerance in relation to hepatitis C virus infection. Furthermore, affordable worldwide-established long-term treatment protocols for hypogonadism and osteoporosis are needed.

Cardiovascular disease in recent onset diabetes mellitus

Diabetes is associated with a marked increased risk of atherosclerotic vascular disorders, including coronary, cerebrovascular, and peripheral artery disease. Cardiovascular disease (CVD) could account for disabilities and high mortality rates in patients with diabetes. Conventional risk factors, including hyperlipidemia, hypertension, smoking, obesity, lack of exercise, and a positive family history, contribute similarly to macrovascular complications in type 2 diabetic patients and non-diabetic subjects. The levels of these factors in diabetic patients are certainly increased, but not enough to explain the exaggerated risk for macrovascular complications in the diabetic population. Furthermore, recently, macrovascular complications of diabetes have been shown to start before the onset of diabetes. Indeed, several clinical studies have confirmed the increased risk of CVD in patients with impaired glucose tolerance (IGT). Since insulin resistance-related postprandial metabolic derangements are thought to play a central role in the development and progression of CVD in patients with IGT, amelioration of postprandial metabolic disturbance is a therapeutic target for the prevention of CVD in these high-risk patients. Therefore, in this paper, we review the molecular mechanisms for the increased risk of CVD in recent onset diabetes mellitus, especially focusing on postprandial dysmetabolism. We also discuss here the potential therapeutic strategies that specially target the mechanisms responsible for vascular alterations in diabetes.

Metabolic, Hormonal, and Immunological Alterations in Subjects with Antecedent Mumps Infection

Since mumps virus seems to be one of the most likely candidates in viral etiology of insulin-dependent diabetes (IDDM) we studied the possible relationship of glucose tolerance (75 g oGTT), beta cell function, diabetes associated HLA antigens, haptoglobin phenotype, islet cell antibodies (ICA) and islet cell surface antibodies (ICSA) in 125 subjects with antecedent mumps infection. Impaired glucose tolerance (IGT) was diagnosed in 3.2% (n = 4) but onset of diabetes did not appear within 14 months after mumps infection. There was no relationship between glucose tolerance and complications of antecedent mumps infection (e.g. pancreatitis, meningitis, orchitis). The prevalence rate of ICA was 76%. ICSA were detectable in about 36% of children and 62% of the adults tested (p less than 0.01). There was no relationship between ICA/ICSA and diabetes-associated HLA antigens, haptoglobin phenotype or beta cell function (fasting C-peptide and insulin response to 75 g oGTT). However, adults with circulating ICA were characterized by a significantly lower insulin response to glucose. Fifty two "risk" subjects characterized by IGT, diabetes associated HLA antigen(s), ICA or ICSA either alone or combined were studied again 26 months after mumps infection. No symptomatic diabetes appeared and IGT was diagnosed in one case only. ICA and ICSA persisted in more than 50% of subjects in whom ICA or ICSA were present 14 months after mumps infection. Since the used immunological techniques do not clearly distinguish organ-specific from non-organ-specific antibodies the results must be interpreted with caution. To summarize, the preliminary results do not support a close temporal relationship between mumps infection and the onset of IDDM. The pathogenetic role of mumps virus and ICA/ICSA and their possible relation to a slow progressive beta cell destruction has still to be determined.

Relative glucose tolerance and subsequent development of hypertension in pregnancy

Objective: To test the hypothesis that relative carbohydrate tolerance, an indicator of insulin resistance, predicts subsequent risk for hypertension of pregnancy among previously normoglycemic, normotensive women. Methods: We conducted a nested case-control study in women enrolled at a large Colorado urban health maintenance organization. Subjects were previously healthy pregnant women who tested abnormal on their initial 50-g glucose screens and subsequently completed 3-hour, 100-g oral glucose tolerance tests. Cases were 54 previously normotensive women who subsequently developed hypertension and controls were 51 subjects with normotensive pregnancies, matched to cases on parity. Subjects diagnosed with gestational diabetes (17 cases, six controls) were excluded from the main analyses. Results: Among the 82 normoglycemic women (45 controls, 37 cases, 13 preeclampsia, 24 gestational hypertension), mean post-load glucose levels and total glucose area under the curve were significantly higher in cases than in controls ( P ≤ .04) and were positively correlated with peak mean arterial pressure. After adjustment for potential confounders, 2-hour post-load glucose levels remained strongly related to risk for hypertension (adjusted odds ratios = 1.48; 95% confidence interval 1.13, 1.92, per 10 mg/dL increase) and to peak mean arterial blood pressure ( r = .23, P = .04), as did total glucose area under the curve ( P ≤ .04). Cases were also more likely to have had one abnormal glucose tolerance test (28% versus 5%, P = .004). Stratifying analyses by case severity (preeclampsia and gestational hypertension) yielded similar results. Among all subjects, more cases than controls were also diagnosed with gestational diabetes (31% versus 12%, P = .008). Conclusion: These findings are consistent with the hypothesis that insulin resistance precedes the clinical onset of hypertension in pregnancy, and may be important in the etiology of hypertension.

Effects of physical activity on insulin action and glucose tolerance in obesity.

The purpose of this paper is to examine the effect of physical activity on glucose tolerance in relation to obesity. We reviewed current literature, with particular emphasis on randomized clinical trials, to prepare an evidence-based evaluation of the effects of physical activity on glucose intolerance in obesity. This literature review indicates that physical activity has favorable effects on reducing insulin resistance in obesity and among patients with type 2 diabetes mellitus. Improvement in glucose tolerance is less consistently observed and is related to intensity of exercise, collateral changes in adiposity, the interval between exercise and testing of glucose tolerance, and the baseline severity of glucose intolerance. A review of currently published clinical trial data supports the conclusion that physical activity can reduce insulin resistance and improve glucose intolerance in obesity.

Vascular dysfunction in diabetes mellitus

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Serum leptin in subjects with impaired glucose tolerance in relation to insulin sensitivity and first-phase insulin response.

It has been suggested that insulin could regulate the secretion of leptin, the ob gene product, but the findings have been contradictory. Therefore, we studied the association between leptin and insulin secretion and insulin sensitivity in impaired glucose tolerance (IGT). 39 obese subjects (17 men, 22 women, body mass index (BMI) 30.6 +/- 0.6 kg/m2, age 54 +/- 1 y, mean +/- s.e.m.) with IGT. Leptin, insulin sensitivity and first-phase insulin response (frequently sampled intravenous glucose tolerance test), anthropometry, infrared densitometric assay. Leptin correlated with BMI (r = 0.36, P = 0.022), fat percent (r = 0.74, P < 0.001) and fat mass (r = 0.53, P < 0.001). After adjustment for sex and fat mass, leptin showed no significant linear correlation with fasting insulin, insulin sensitivity or first-phase insulin response. In obese IGT subjects fat mass is the main correlate of serum leptin concentration. First-phase insulin response or the degree of insulin resistance are not associated with leptin in IGT.

Plasma islet amyloid polypeptide (Amylin) levels and their responses to oral glucose in Type 2 (non-insulin-dependent) diabetic patients

Fasting plasma islet amyloid polypeptide concentrations and their responses to an oral glucose load were determined in non-diabetic control subjects and patients with abnormal glucose tolerance in relation to the responses of insulin or C-peptide. Plasma islet amyloid polypeptide was measured by radioimmunoassay. In the non-diabetic control subjects, fasting plasma islet amyloid polypeptide was 6.4 +/- 0.5 fmol/ml (mean +/- SEM) and was about 1/7 less in molar basis than in insulin. The fasting islet amyloid polypeptide level rose in obese patients and fell in patients with Type 1 (insulin-dependent) diabetes mellitus. In non-obese patients with impaired glucose tolerance and Type 2 (non-insulin-dependent) diabetic patients without insulin therapy, the level was equal to that of the control subjects, but a low concentration of islet amyloid polypeptide relative to insulin or C-peptide was observed in the non-obese Type 2 diabetic group. The patterns of plasma islet amyloid polypeptide responses after oral glucose were similar to those of insulin or C-peptide. However, compared to non-obese patients, a hyper-response of islet amyloid polypeptide relative to C-peptide was noted in obese patients who had a hyper-response of insulin relative to C-peptide. This study suggests that basal hypo-secretion of islet amyloid polypeptide relative to insulin exists in non-obese Type 2 diabetes and that circulating islet amyloid polypeptide may act physiologically with insulin to modulate the glucose metabolism.

Development of Diabetes in Subjects with Normal or Impaired Glucose Tolerance in Relation to Insulin Response and Other Risk Factors

Development of Diabetes in Subjects with Normal or Impaired Glucose Tolerance in Relation to Insulin Response and Other Risk Factors

Natural history of glucose tolerance in relatives of diabetic patients: low prognostic value of the oral glucose tolerance test.

Seven hundred and fifty-one initially nondiabetic relatives of diabetic persons, in whom oral glucose tolerance tests (OGTT) have been performed, were followed for over 10 yr. Of these, 11.6% have died and no information was available from 13.7%. All other subjects were either retested (N = 369) or answered by questionnaire whether they are being treated for diabetes (N = 32) or not (N = 155). For test evaluation the sum of the 1- and the 2-h values during OGTT was used. The diagnosis of “diabetes” after 10 yr was made if the sum exceeded 500 mg/dl, which in 88% of cases coincides with fasting blood glucose values above 120 mg/dl. Among the retested individuals the results of OGTT showed a high degree of variation in both directions, which seems to represent just random variance rather than improvement or deterioration of biologic significance. These random changes in glucose tolerance do not correlate with changes in body weight. Sixty-three individuals have developed overt diabetes within the 10 yr. To optimize the discriminating value of the initial tests, the criteria dividing impaired glucose tolerance (IGT) from “normal” have been varied by a computer program. Sensitivity and specificity of the diagnosis IGT with respect to later development of diabetes depend on the criteria used and are inversely related. At the point where sensitivity and specificity are equal, both amount to 45%, and their sum never exceeds 90%. Using the criteria for IGT and diabetes recently proposed by members of an expert committee at the NIH, which are mainly based on the 2-h value and the fasting value, a sensitivity of 66% and a specificity of 19% are found. Thus, although a higher tendency toward the development of overt diabetes can be observed in the group of subjects with IGT compared with normal subjects, the prognostic value of the OGTT is very low when applied to individuals.

Glucose tolerance in relation to skeletal muscle enzyme activities in cancer patients

Glucose tolerance in relation to skeletal muscle enzyme activities in cancer patients

Glucose tolerance in relation to skeletal muscle enzyme activities in cancer patients

Glucose metabolism and skeletal muscle enzyme activities were studied in nineteen cancer patients and twelve matched controls. The fasting insulin values were normal but the fasting glucose values and the sum of glucose were increased and the sum of insulin was decreased during intravenous glucose tolerance test in the cancer patients. The elimination rate of glucose (k-value) during glucose challenge was, however, not significantly different in cancer patients as compared with that of appropriate controls. The activities of enzymes representative for glycogen turnover, glycolysis, citric acid cycle and respiratory chain were significantly lower in the muscle tissue of cancer patients, while the activity of 3-hydroxyacyl-CoA dehydrogenase, an enzyme in the beta-oxidation of fatty acids, was unchanged and the activity of glucose-6-phosphate dehydrogenase was significantly higher. Rate limiting enzyme activities in muscle tissue, phosphofructokinase and cytochrome c oxidase correlated signficantly with plasma insulin and glucose during glucose challenge. The results point at the possibility of covariating debilitation of pancreatic beta-cells and skeletal muscle enzymes caused by the malignant tumour.

One-hour glucose tolerance in relation to the use of contraceptive drugs

One-hour glucose tolerance tests on 4,815 women of reproductive age having multiphasic health checkups were cross-sectionally analyzed in relation to the use of contraceptive drugs. One-hour serum glucose levels were found to be higher in women taking a contraceptive drug than in others. The mean difference between pill users and nonusers of like age was 11 mg. per 100 ml. There was no observable variation in the glucose response of women taking oral contraceptives associated with the formulation and steroid components of the drug used or the duration of use. The effect of the contraceptive drugs on one-hour glucose tolerance was found to be additive to the effects of age, obesity, and a family history of diabetes. No discernible difference in glucose response was found between past users of contraceptive drugs and “never users,” regardless of the duration of use or the interval since discontinuation.

Glucose tolerance in relation to obesity and food intake.

Glucose tolerance tests were carried out on two strains of mice, one highly susceptible, the other only moderately susceptible to nutritional obesity. With glucose administered on the basis of body weight or fat-free weight, the highly susceptible strain disposed more rapidly of the administered glucose than did the moderately susceptible strain. Fasting blood sugar levels in both strains were found to increase with the logarithm of body weight. These observations are not readily explained in terms of the ‘glucostatic’ theory of the control of food intake.

Criteria for and interpretation of normal glucose tolerance tests.

Excerpt The old dictum that every diabetic has a high prolonged glucose tolerance curve, but that every high prolonged curve is not indicative of diabetes, still holds true. The lack of specificity...