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Glucose intolerance and serum aminotransferase activities in Japanese men.

BACKGROUND/AIMS: Elevated activities of serum aminotransferase are commonly observed in patients with diabetes mellitus. Few studies have addressed the relation between glucose intolerance and serum activities of aminotransferase in free-living populations. METHODS: Using a 75 g oral glucose tolerance test, we examined the association of impaired fasting glycemia (IFG), impaired glucose tolerance (IGT), and type 2 diabetes mellitus with serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyltransferase (GGT) among 4621 men aged 49-59 years of the Japan Self-Defense Forces. Statistical adjustment was made for body mass index, waist-hip ratio, and other possible confounding factors. RESULTS: Proportions of an elevated ALT (>50 IU/l) in men with normal glucose tolerance, IFG, IGT, and newly diagnosed diabetes mellitus were 3.5%, 9.5%, 7.7%, and 18.0%, respectively. Adjusted odds ratios of an elevated ALT for IFG, IGT, and newly diagnosed diabetes mellitus were 2.2 (95% confidence interval 1.1-4.3), 1.7 (1.2-2.4), and 4.4 (3.0-6.6), respectively. IGT and diabetes mellitus were also significantly positively associated with elevated AST (>40 IU/l) and GGT (>50 IU/l). CONCLUSIONS: Glucose intolerance is associated with elevated serum aminotransferase independent of obesity, but even a mildly elevated ALT is relatively uncommon in free-living men with glucose intolerance.

Alanine Transaminase↗

Comparative study on the preventing effects of oral vanadyl sulfate and dietary restriction on the age-related glucose intolerance in rats.

BACKGROUND AND AIMS: Aging is associated with a progressive impairment of glucose tolerance. The aim of this study was to explore the protective effects of the chronic oral administration of the insulino-mimetic agent vanadyl sulfate (VOSO4) as compared with those exerted by a long-lasting dietary restriction. METHODS: Male Sprague-Dawley rats, either fed ad libitum (AL) or subjected to 40% dietary restriction (DR), were used. VOSO4 (0.5 mg/mL drinking water) was administered to a subgroup of AL rats for two months, starting at 16 months of age. Rats were subjected to an intravenous glucose tolerance test (IVGTT) at 16 and 18 months of age. Finally, the beta-cell responsiveness to glucose was evaluated in vitro by the isolated perfused pancreas preparation. RESULTS: The IVGTT performed in 16-month-old rats showed that DR prevented the development of the moderate glucose intolerance observed in AL rats. The IVGTT performed at 18 months of age confirmed the beneficial effect of DR and showed that VOSO4 was able to prevent the further age-related progression of glucose intolerance observed in AL rats. Pancreas perfusion studies showed that no increase in insulin secretion occurred in both VOSO4-treated and DR rats with respect to the age-matched AL controls, consistently with the in vivo observation of post-loading insulinaemic changes. CONCLUSIONS: On the basis of these results, we conclude that the beneficial effect of both treatments is mostly related to an improvement of tissue sensitivity to insulin rather than to an insulinotropic effect.

Administration, Oral↗

Age-related glucose intolerance in hyperthyroid patients.

In an attempt to study age-related metabolic abnormalities, glucose intolerance and serum insulin were examined in normal subjects and hyperthyroid patients. For comparison, serum concentrations of thyroxine (T4), triiodothyronine (T3), and total cholesterol were also measured in normal subjects and hyperthyroid patients. Although serum T4 concentration remained unchanged, serum T3 concentration decreased significantly in an elderly group of normal subjects. Similarly, serum T4 did not change with age and serum T3 decreased slightly but progressively with age in hyperthyroid patients. In addition, serum total cholesterol concentration increased progressively with age in normal subjects. Oral glucose tolerance decreased with age in normal subjects despite the same timing, peak level attained, and total magnitude of insulin response for old and young subjects. Although the severity of hyperthyroidism decreases with age, age-related glucose intolerance was much more apparent in hyperthyroid patients because of the age-related decrease of basal concentration, the peak level attained, and the total magnitude of insulin response. It is suggested that age-related glucose intolerance is magnified by the hyperthyroid state.

Adolescent↗

Adverse effects of antihypertensive drug therapy on glucose intolerance.

Several antihypertensive drugs have an adverse effect on glucose tolerance that may partially or completely negate the beneficial effects of reducing blood pressure as it relates to the incidence of coronary heart disease and its complications. Diuretics (particularly high doses) and beta-blockers without intrinsic sympathomimetic activity have the greatest adverse effect on glucose intolerance. Central alpha-agonists, angiotensin-converting enzyme inhibitors, calcium channel blockers, and alpha-blockers do not adversely affect glucose and are preferred in diabetic hypertensive patients, selected hypertensive patients at risk for developing glucose intolerance, and probably most other patients with mild essential hypertension as initial and/or monotherapy compared with diuretics and beta-blockers.

Adrenergic alpha-Agonists↗

Glucose intolerance is associated with C-reactive protein and intima-media anatomy of the common carotid artery in patients with coronary heart disease.

AIMS: The purpose of this study was to examine the relationship between glucose intolerance and levels of hsCRP, calculated intima-media area (cIMa) of the carotid artery and flow-mediated dilation of the brachial artery in 122 patients with a myocardial infarction 1-12 months before inclusion and without known diabetes mellitus. METHODS: A standard oral glucose test (OGTT) was performed. Diabetes mellitus and impaired glucose tolerance (IGT) were defined according to the WHO criteria. Ultrasound measurement of cIMa of the carotid artery and flow-mediated dilation of the brachial artery were analyzed. RESULTS: Patients with diabetes mellitus had higher hs-CRP compared with patients with IGT and those patients with normal glucose tolerance (P < 0.05). The greater cIMa of the carotid artery in those with diabetes mellitus compared with normal subjects failed to reach conventional levels of significance (P = 0.058). hs-CRP and cIMa were associated with plasma glucose 120 min after the glucose load (P < 0.05). A multiple stepwise regression analysis, including all variables significantly associated with plasma-glucose 120 min after glucose ingestion as independent variables, revealed an independent and significant association between plasma-glucose 120 min after glucose ingestion in the OGTT and CRP (P < 0.05). No association was observed between glucose intolerance and endothelial function. CONCLUSION: Glucose intolerance was associated with hs-CRP and cIMa in patients with coronary heart disease without known diabetes mellitus. Thus, inflammation, atherosclerosis and impaired glucose tolerance are tightly interrelated disorders even in subjects without known diabetes mellitus.

Adult↗

Metabolic effects of physical training in subjects with oral glucose intolerance.

A group of normal weight subjects with oral glucose intolerance was studied for 4 months before, during, and after a physical training program (8 km/day/run). There were no significant differences in weight, basal blood glucose, lactate, and total cholesterol during and after training as compared with before training. Serum triglycerides significantly (P less than 0.05) decreased during the training period, and cholesterol-HDL significantly (P less than 0.01) increased during and after the physical program. Our data show that in previously inactive subjects with oral glucose intolerance physical training improves serum lipid patterns and thereby reduces atherosclerotic risk.

Adult↗

Triphenyltin chloride induces glucose intolerance by the suppression of insulin release from hamster pancreatic beta-cells.

UNLABELLED: We performed an intravenous glucose tolerance test (IVGTT) after the administration of triphenyltin chloride (TPTCl-Ad) in hamsters in order to confirm the presence of glucose intolerance and to clarify the pathogenesis of TPTCl-induced glucose intolerance. On the 1st, 2nd, 3rd, 4th and 7th days after TPTCl-Ad or the administration of sesame oil alone as a control, glucose was injected at a dose of 0.05 g glucose/100 g B.W., and then PG, IRI and TG were measured on 0, 1, 2, 3, 5 and 10 min after IVGTT. The TPT concentration in the pancreas was measured by gaschromatography and the morphological findings with a transmission electron microscope were compared between the TPTCl-Ad and the control hamsters. FPG on the 1st and the 2nd days after TPTCl-Ad were significantly higher than those in control, but those on the 4th and the 7th day recovered up to the control level. In contrast, basal IRI levels showed reciprocal results compared to the FPG levels. delta IRI/ delta PG on the 1st day after TPTCl-Ad was significantly reduced compared to the control. Fasting TG on the 1st day after TPTCl-Ad was much higher than the control. TPT-concentration on the 1st day after TPTCl-Ad showed peak values and its concentration gradually decreased. Electron microscopic findings in the pancreas after TPTCl-Ad indicated neither destruction nor lymphocyte infiltration of the pancreas. CONCLUSIONS: The present data suggest that the administration of TPTCl in hamsters induces a functional transient damage on islet cells but not a morphological disorder, which shows an essentially different nature from the change in the pancreas induced by viral infection or by a large amount of streptozotocin.

Animals↗

[Fasting or post-challenge blood glucose values for detection of glucose intolerance in screening for metabolic syndrome?].

INTRODUCTION: The normal-pathological threshold of fasting blood glucose values was modified by the new WHO diagnostic criteria (1999) and, in addition, impaired fasting glucose (IFG) was introduced as a new clinical entity. Nevertheless, the 2-h post-glucose challenge criteria and the concept of the impaired glucose tolerance (IGT) remained unchanged. There is no unequivocal agreement whether new fasting or unchanged post-challenge blood glucose criteria should be used for classification of glucose intolerance. AIMS: To assess the clinical-laboratory characteristics of metabolic syndrome a screening procedure was performed in hypertensive or obese subjects registered within primary health care and the reliability of the new fasting blood glucose criteria was analysed. PATIENTS AND METHODS: For inclusion, subjects of both sexes aged from 20 to 65 years exhibited at least one of the following clinical characteristics: hypertension (ongoing antihypertensive treatment or raised (> or = 140/90 mmHg) actual blood pressure), abnormal (> 30.0 kg/m2) body mass index [BMI] or elevated waist-hip ratio (> 0.85 in women, > 0.90 in men). Subjects with known diabetes were not involved. An oral glucose tolerance test (OGTT) with 75 g glucose was performed in each subject. Subjects with complete clinical and laboratory findings were statistically analysed (n = 944; women/men: 545/399; age: 46.1 +/- 7.3 years; BMI 32.2 +/- 5.4 kg/m2; waist-hip ratio 0.90 +/- 0.09; x +/- SD). RESULTS: In the total cohort newly diagnosed diabetes mellitus (based on the 120 min post-challenge glucose values) was found in 87 subjects (9.2%), IGT was detected in 136 cases (14.4%) while normal glucose tolerance was documented in 721 subjects (76.4%). Using fasting blood glucose values for classification, diabetes mellitus was detected in 79 subjects (8.4%), IFG was found in 124 cases (13.1%) while 741 subjects (78.5%) had normal glucose tolerance. Impaired glucoregulation (IGT + IFG) was found in 223 subjects (IGT alone 99 cases [44.4%], IFG alone 87 cases [39.0%], IGT and IFG in combination 37 cases [16.6%]). The sensitivity and specificity of fasting blood glucose criteria for detecting diabetes were 63.2% and 97.1%, respectively, while those for detecting glucose intolerance (IFG and diabetes as well as IGT and diabetes) were 52.9% and 88.2%, respectively. Clinical characteristics of subjects with abnormal post-challenge but normal fasting blood glucose values (n = 105) did not differ significantly from those of subjects with normal post-challenge but abnormal fasting blood glucose values (n = 85) (age: 46.7 +/- 6.9 years vs 46.7 +/- 6.1 years; BMI: 33.1 +/- 5.4 kg/m2 vs 32.3 +/- 4.5 kg/m2; waist-hip ratio: 0.91 +/- 0.09 vs 0.92 +/- 0.07; p > 0.05). CONCLUSION: OGTT and 2-h post-glucose challenge criteria should be used for the diagnosis of different categories of glucose intolerance in screening for metabolic syndrome.

Adult↗

Risk factors for glucose intolerance in Danish women with polycystic ovary syndrome.

BACKGROUND: Women with polycystic ovary syndrome (PCOS) are reported to be at risk for glucose intolerance. The aim of the study was to describe these risk factors in a population of Danish PCOS women attending a gynecologic clinic and to identify the parameters with the strongest correlation to the fasting blood glucose levels. In addition, we studied whether the oral glucose tolerance test (OGTT) diagnosed more cases of glucose intolerance in this PCOS population than the fasting plasma glucose value (FPG) alone. METHODS: Cross-sectional study of 91 women with oligomenorrhea or amenorrhea and elevated serum testosterone, followed by an OGTT in 27 of the women. RESULTS: Women with a FPG above normal were older and had a higher body mass index (BMI), cholesterol, and triglycerides and a lower sexual hormone binding globulin (SHBG). Of the 21 women older than 34, eight (38%) had a FPG above normal. The OGTT study showed that one of five with abnormal glucose tolerance would not have been diagnosed, if the FPG alone had been performed. CONCLUSIONS: In this study, 38% of women with symptoms of PCOS over the age of 34 had abnormal blood glucose values. These women should receive blood glucose testing regardless of BMI, testosterone levels and family history of type 2 diabetes mellitus. An OGTT may be necessary to find all cases of impaired glucose intolerance.

Adolescent↗

Sleep-disordered breathing, glucose intolerance, and insulin resistance.

Sleep-disordered breathing (SDB) is a common condition with prevalence estimates of 2-4% in the general population. Epidemiological data suggest that SDB is an independent risk factor for cardiovascular disease. Glucose intolerance and insulin resistance are also well-recognized risk factors for the development of cardiovascular disease. A number of recent clinic-based studies suggest that, independent of obesity, SDB may adversely affect glucose tolerance and insulin sensitivity. The purpose of this study was to systematically review the evidence for the link between SDB, glucose intolerance, and insulin resistance. A MEDLINE search for SDB and metabolic disorders was performed and 24 articles that met the inclusion criteria were identified. Population-based studies indicate that habitual snoring is independently associated with glucose intolerance and insulin resistance. Studies that have used objective measures of SDB (e.g. polysomnography) provide further support for an independent link between SDB, glucose intolerance, and insulin resistance. However, studies on the treatment of SDB with continuous positive airway pressure (CPAP) have yielded inconsistent results and overall do not reveal an improvement in the metabolic disturbance after treatment. Although population-based prospective data on the metabolic implications of SDB are still lacking, current data point to an independent association between SDB and impaired glucose homeostasis. Potential mediators of this association include altered adrenergic function, the direct effects of hypoxemia on glucose regulation, and release of proinflammatory cytokines that affect metabolism.

Databases, Bibliographic↗

Glucose intolerance and associated factors in the Fergana Valley, Uzbekistan.

Prevalence of glucose intolerance and other noncommunicable diseases has been examined in subjects aged 35 years and over in semirural and urban communities in the Fergana Valley in the eastern part of Uzbekistan, Central Asia. Diabetes and impaired glucose tolerance (IGT) were diagnosed according to the recommendations of the latest WHO Study Group on diabetes. Crude prevalence of diabetes was 9% and 5%, respectively, in semirural men and women, 13% and 9% in urban men and women. Crude prevalence of impaired glucose tolerance (IGT) was 6% and 9%, respectively, in semirural men and women, 9% and 8% in urban men and women. After adjustment for non-response, prevalence of diabetes was 5% and 4%, respectively, in semirural men and women and 8% in both urban men and women. Adjusted prevalence of IGT was 4% and 8%, respectively, in semirural men and women, 5% and 6% in urban men and women. The majority of subjects with a prior diagnosis of diabetes were being treated with oral hypoglycaemic agents. Almost one-half of subjects in both communities had body mass index of 25 kg m(-2) or greater. Central obesity (waist-hip ratio 0.95 or greater for men, 0.85 or greater for women) was observed in over one-quarter of subjects in both communities. Clinical hypertension was not frequent by international standards (9% in semirural subjects and 13% in urban subjects) but a number of subjects who were clinically normotensive claimed to be taking antihypertensive medication. It is concluded that glucose intolerance and central obesity are common in this region of Uzbekistan, about which there was previously little information.

Adult↗

Assessment of glucose intolerance and insulin sensitivity in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is associated with increased risk of impaired glucose tolerance and type 2 diabetes. PCOS has been considered as a major risk factor for the development of diabetes, and screening of women with PCOS for glucose intolerance is suggested. Detection of glucose intolerance in PCOS is best performed via 2-h oral glucose tolerance test rather than fasting plasma glucose alone, since it enables diagnosis of both impaired glucose tolerance and diabetes. Insulin resistance is a prominent feature of PCOS, although not all women with PCOS have insulin resistance. Measurement of insulin resistance is not included in the diagnostic criteria of the syndrome, and not required for the selection of treatments in current clinical practice. However, this measurement is undoubtedly of great interest for clinical research studies of PCOS. Several methods are available to the clinical investigator for the measurement of insulin resistance, yet there is no universally accepted and clinically useful definition, and no specific guidelines about how to measure it. While hyperinsulinaemic glucose clamp is considered to be the 'gold standard' for the measurement of insulin resistance, several alternative methods have been validated against the gold standard. Each method has its own merits and disadvantages. The choice of method for a particular study should be based on the specific aims, size, and type of that study. Variability in measurement of insulin resistance due to physiological factors, assay-related problems, and protocol differences in dynamic function tests deserves much more emphasis when interpreting the results of a study, or making comparisons between studies.

Female↗

Effect of protease inhibitor therapy on glucose intolerance in pregnancy.

OBJECTIVE: To determine if protease inhibitor use was associated with increased glucose intolerance in our population of pregnant women infected with the human immunodeficiency virus (HIV). METHODS: Women who were infected with HIV from January 1, 1998, to January 8, 2004, and who had a 1-hour and 3-hour glucola test were identified. Medical records were reviewed to obtain demographic characteristics and obstetric and laboratory data. Drug regimens at the time of glucola testing were determined. Human immunodeficiency virus-infected women were then matched 1:3 to HIV-noninfected gravidas by race, age, and year of delivery. RESULTS: One hundred seventy-one HIV-infected women had glucola results available. Twelve percent had an abnormal 1-hour glucola result and 3% had an abnormal 3-hour result. This was similar to the HIV-noninfected population. Forty-five percent of the HIV-infected cohort was on a protease inhibitor at the time of glucola testing. Protease inhibitor exposure had no effect on glucola test results. HIV infection itself also did not increase abnormal glucola test results. CONCLUSION: Glucose intolerance in this obstetric population was not associated with the diagnosis of HIV or with the use of protease inhibitors. Protease inhibitors should continue to be an option for the treatment of HIV in pregnancy.

Adult↗

Glycosylated haemoglobin and glucose intolerance in cystic fibrosis.

Sixty four patients, age range 1-20 years, with cystic fibrosis had their tolerance to glucose assessed according to their glycosylated haemoglobin (HbA1) concentrations. Raised concentrations were found in 24 (37.5%). Oral glucose tolerance tests were performed on 21 patients with raised HbA1 and 13 patients with normal HbA1 concentrations. C peptide responses were also measured to assess islet cell function. Patients with normal HbA1 had normal glucose tolerance and C peptide response. Seven of 21 patients with raised HbA1 concentrations were glucose intolerant. The remaining 14 patients with raised HbA1 concentrations had normal glucose tolerance but a reduced C peptide response, suggesting impaired islet cell function. There were no appreciable differences in the incidence of chest infections, respiratory function, and chest x-ray scores among patients with normal HbA1 concentrations, raised HbA1 concentrations, and normal oral glucose tolerant tests, and patients who were glucose intolerant. No correlation was found between HbA1 concentration and age or Shwachman score. Measuring HbA1 concentrations periodically is useful in detecting and monitoring glucose intolerance in patients with cystic fibrosis.

Adolescent↗

Long-term (5-year) effects of a reduced-fat diet intervention in individuals with glucose intolerance.

OBJECTIVE: To determine whether reducing dietary fat would reduce body weight and improve long-term glycemia in people with glucose intolerance. RESEARCH DESIGN AND METHODS: A 5-year Follow-up of a 1-year randomized controlled trial of a reduced-fat ad libitum diet versus a usual diet. Participants with glucose intolerance (2-h blood glucose 7.0-11.0 mmol/l) were recruited from a Workforce Diabetes Survey. The group that was randomized to a reduced-fat diet participated in monthly small-group education sessions on reduced-fat eating for 1 year. Body weight and glucose tolerance were measured in 136 participants at baseline 6 months, and 1 year (end of intervention), with follow-up at 2 years (n = l04), 3 years (n = 99), and 5 years (n = 103). RESULTS: Compared with the control group, weight decreased in the reduced-fat-diet group (P < 0.0001); the greatest difference was noted at 1 year (-3.3 kg), diminished at subsequent follow-up (-3.2 kg at 2 years and -1.6 kg at 3 years), and was no longer present by 5 years (1.1 kg). Glucose tolerance also improved in patients on the reduced-fat diet; a lower proportion had type 2 diabetes or impaired glucose tolerance at 1 year (47 vs. 67%, P < 0.05), but in subsequent years, there were no differences between groups. However, the more compliant 50% of the intervention group maintained lower fasting and 2-h glucose at 5 years (P = 0.041 and P = 0.026 respectively) compared with control subjects. CONCLUSIONS: The natural history for people at high risk of developing type 2 diabetes is weight gain and deterioration in glucose tolerance. This process may be ameliorated through adherence to a reduced fat intake

Blood Glucose↗

Treatment of glucose intolerance in pregnancy: staged diabetes management.

Current methods for the treatment of glucose intolerance first discovered in pregnancy are reviewed and a systematic data-based approach is introduced. Gestational diabetes mellitus (GDM) is a leading cause of adverse perinatal outcome in 5% of all pregnancies in the United States. Early detection and initiation of treatment meant to restore euglycemia will prevent many of the major complications associated with hyperglycemia. Staged Diabetes Management (SDM) is introduced in this paper as an innovative approach for the detection and treatment of GDM and glucose intolerance in pregnancy. Relying on self-monitored blood glucose data, SDM guides the primary care physician through increasingly more complex regimens until euglycemia is reached. Computer-based technologies assist the clinical decision-making by producing Ambulatory Glucose Profiles (AGP), which are graphic representations of glycemic control. SDM combined with AGP technology are meant to significantly reduce the threefold greater risk of adverse outcome in pregnancy experienced by women with GDM.

Diabetes, Gestational↗

Concordance between fasting and 2-h post-glucose challenge criteria for the diagnosis of diabetes mellitus and glucose intolerance in high risk individuals.

AIMS: To compare the new fasting with the 2-h post glucose challenge diagnostic criteria for diabetes mellitus in a high-risk Central European population. METHODS: The results of the 75-g oral glucose tolerance tests (OGTT) performed between 1st January 1990 and 31st December 1998 in patients at high risk of glucose metabolism disturbance were analysed. RESULTS: From 1554 patients with OGTT results available for the study, 1360 (759 women and 601 men, aged 65.5+/-6.9 years, body mass index 28.2 +/- 4.5 kg/m2) were included into the study. With the use of the post-challenge criteria, 41.3% of the analysed population had diabetes or impaired diabetes tolerance (IGT), whereas with the new fasting system only 16.6% would have been diagnosed with any type of glucose intolerance. Diabetes was significantly more often diagnosed with the post-challenge criteria than with the fasting ones: 16.2 vs. 5.3% (P < 0.0001). The subjects with diabetes diagnosed upon fasting glucose value were significantly younger than the subjects with diabetes diagnosed according to the 2-h glucose challenge: 65.7 +/- 6.2 vs. 68.8 +/- 7.0 years, respectively (P < 0.01). The sensitivity of the new criteria for the diagnosis of diabetes was 18.2%, and specificity 97.2%. A total of 77.8% of IGT cases would have been diagnosed as having normal glucose metabolism according to the fasting glucose. The sensitivity of the new criteria for the diagnosis of impaired glucose tolerance (IGT or impaired fasting glucose) was 14.6%, and specificity 89.8%. The overall kappa statistic (k) was low; 0.211 (95% confidence interval 0.149-0.27). CONCLUSIONS: The new lower fasting criteria might be too insensitive to identify a large proportion of individuals with diabetes or impaired glucose intolerance, particularly in a high-risk population.

Age Factors↗