Risk Factors For Glucose Intolerance Research Articles

Bromocriptine reduces steatosis in obese rodent models

Obesity is a risk factor for glucose intolerance, steatosis, and oxidative stress, characteristics of nonalcoholic fatty liver disease. Bromocriptine may have anti-obesity, insulin-sensitizing, lipolytic, and antioxidant properties. We, therefore, hypothesized that bromocriptine would improve markers of nonalcoholic fatty liver disease in obese rodent models. We performed a randomized, controlled experiment in genetically obese fatty Zucker rats and diet-induced obese rats to assess for behavioral and peripheral anti-obesity actions of bromocriptine (10mg/kg) that would improve nonalcoholic fatty liver disease. Behaviorally, food intake decreased and locomotor activity increased in bromocriptine-treated fatty Zucker and dietary-induced obese rats. Peripherally, liver triglycerides were significantly reduced and hepatic manganese superoxide dismutase significantly increased in bromocriptine-treated fatty Zucker and diet-induced obese rats compared to controls. Blood glucose was significantly lower in bromocriptine-treated Zucker rats compared to fatty controls and was no different than that of lean controls. Improvements in obesigenic behaviors, glucose tolerance, hepatic lipid accumulation, and mitochondrial oxidative stress observed in genetically obese and diet-induced obese rodents indicate that bromocriptine may be promising as a broad-based therapy for nonalcoholic fatty liver disease.

Aging is an Inevitable Risk Factor for Insulin Resistance

The present work looks into the different aspects of glucose homeostasis in the elderly patients in comparison to healthy younger subjects and patients with type 2 diabetes mellitus, relying on intravenous glucose tolerance test. A clinicobiochemical study was carried out comprising forty apparently healthy non-diabetic non-obese old individuals (mean age 65 ± 4.8 years). Forty type 2 diabetic patients compared to thirty healthy young subjects. The senile group had no family history of diabetes. Cases with renal, hepatic, gastrointestinal, or endocrine abnormalities were excluded from the study. Intravenous glucose tolerance test (ivGTT) was done with sampling at 0, 5, 10, 15, 30, 45, and 60 min after glucose load and the following estimations were undertaken: glucose constant decay (K G ), glucose and insulin area under the curve, insulnogenic index, first phase insulin response, insulin resistance index and fractional insulin clearance. The senile and diabetic groups, when compared to the control, had non-significantly different fasting plasma glucose in senile group but it was higher in diabetic patients, while fasting serum insulin was significantly higher in the studied groups than in healthy control group. The senile group showed significant reduction in glucose tolerance (K G 1.36 ± 0.3%/min ) , decreased insulin sensitivity index (5.19 ± 1.4 10 -4 min -1 /[uU/ml]) and marked reduction of first phase insulin response (2.45 ± 0.78 uIU/ml per mg/dl), when compared with the control group. However, the degree of glucose intolerance and insulin insensitivity of the senile group was still significantly less than of type 2 diabetic patients. This study revealed that the insulin resistance seems to be characteristic feature of normal aging process and senility could be considered as an inevitable risk factor for glucose intolerance and metabolic syndrome with its accompanying health hazards. Insulin secretion, insulin clearance and interaction between insulin and target tissues are defective in elderly subjects. These functions are intermediate between healthy controls and type 2 diabetic patients and may predispose the elderly population to the risk of impaired glucose tolerance or diabetes mellitus with its attendant macrovascular and microvascular complications.

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

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. Cross-sectional study of 91 women with oligomenorrhea or amenorrhea and elevated serum testosterone, followed by an OGTT in 27 of the women. 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. 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.

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.

Circulating concentrations of insulin-like growth factor-I and development of glucose intolerance: a prospective observational study

Results of experimental and clinical studies suggest that insulin-like growth factor-I (IGF-I) and IGF binding protein-1 (IGFBP-1) could be important determinants of glucose homoeostasis. However, experimental models might also reflect compensatory and adaptive metabolic processes. We therefore prospectively examined the associations between circulating concentrations of IGF-I and IGFBP-1 and development of glucose tolerance. Participants in this cohort study were a random sample of 615 normoglycaemic men and women aged 45-65 years. Participants underwent oral glucose tolerance testing based on WHO definitions and criteria in 1990-92 and 1994-96. At the baseline visit, we measured serum concentrations of IGF-I and IGFBP-1, and assessed the relation between these peptides and subsequent glucose intolerance. At 4.5 years of follow-up, 51 (8%) of 615 participants developed impaired glucose tolerance or type-2 diabetes. After adjustment for correlates of IGF-I and risk factors for glucose intolerance, the odds ratio for risk of impaired glucose tolerance or type-2 diabetes for participants with IGF-I concentrations above the median (> or = 152 microg/L) compared with those with concentrations below the median (<152 microg/L) was 0.50 (0.26-0.95). Consistent with this finding, IGF-I also showed a significant inverse association with subsequent 2-h glucose concentrations, which was independent of correlates of IGF-I and risk factors for glucose tolerance (p for linear trend=0.026). We also found that this inverse association was independently modified by IGFBP-1 (p for interaction=0.011). These data show that circulating IGF-I and its interaction with IGFBP-1 could be important determinants of glucose homoeostasis and provide further evidence for the possible protective role of IGF-I against development of glucose intolerance.

Glucose intolerance with atypical antipsychotics.

Previous studies have suggested that the atypical antipsychotics clozapine and olanzapine may be associated with an increased risk of glucose intolerance and diabetes mellitus. Early studies have also suggested an association between use of conventional antipsychotics and the development of glucose intolerance. To examine quantitatively the association between glucose intolerance including diabetes mellitus and the use of the atypical antipsychotics clozapine, olanzapine or risperidone, and to identify possible risk factors for the development of glucose intolerance during treatment with these drugs. All reports suggestive of glucose intolerance for clozapine, olanzapine and risperidone were identified in the WHO database for adverse drug reactions. In the analyses of possible risk factors for glucose intolerance all other reports of adverse drug reactions for clozapine, olanzapine and risperidone were used as reference. Using the Bayesian Confidence Propagation Neural Network method, the strengths of the associations over time between glucose intolerance and the use of these drugs were analysed. For comparison, the strengths of the associations between glucose intolerance and the use of the conventional antipsychotics haloperidol and chlorpromazine were also analysed. Clozapine, olanzapine and risperidone were significantly associated with glucose intolerance. In contrast, chlorpromazine and haloperidol were not associated with glucose intolerance. For clozapine, olanzapine and risperidone grouped together, the following potential risk factors for glucose intolerance were identified: an underlying diabetic condition (odds ratio [OR] 10.22, 95% CI 8.20-12.73), an increase in weight (OR 2.36, 95% CI 1.76-3.17), male gender (OR 1.27, 95% CI 1.11-1.47), and concomitant use of valproic acid (OR 1.97, 95% CI 1.61-2.40), selective serotonin reuptake inhibitors (OR 1.63, 95% CI 1.33-1.99) or buspirone (OR 2.24, 95% CI 1.33-3.77). Treatment with clozapine, olanzapine or risperidone appears to be associated with an increased risk of glucose intolerance.

Risk factors for glucose intolerance in active acromegaly.

In the present retrospective study we determined the frequency of glucose intolerance in active untreated acromegaly, and searched for risk factors possibly supporting the emergence of the diabetic condition. Among 43 patients, 8 (19%; 95% CI: 8-33%) had diabetes mellitus and 2 (5%; 1-16%) impaired glucose tolerance. No impaired fasting glycemia was demonstrable. The frequency of diabetes was on average 4.5 times higher than in the general Slovak population. Ten factors suspected to support progression to glucose intolerance were studied by comparing the frequency of glucose intolerance between patients with present and absent risk factors. A family history of diabetes and arterial hypertension proved to have a significant promoting effect (P<0.05, chi-square test). A significant association with female gender was demonstrated only after pooling our data with literature data. Concomitant prolactin hypersecretion had a nonsignificant promoting effect. In conclusion, the association of active untreated acromegaly with each of the three categories of glucose intolerance (including impaired fasting glycemia, not yet studied in this connection) was defined as a confidence interval, thus permitting a sound comparison with the findings of future studies. Besides a family history of diabetes, female gender and arterial hypertension were defined as additional, not yet described risk factors.

Change of glycaemic status in Chinese subjects with impaired fasting glycaemia.

To examine the risk of progression to diabetes in Chinese subjects with impaired fasting glycaemia (IFG) or normal fasting glucose (NFG). Between 1988 and 1996, 657 Hong Kong Chinese subjects underwent annual screening, using an oral glucose tolerance test, until they had developed diabetes, or until June 1997, when the data were analysed. All subjects had a risk factor associated with the development of diabetes such as a history of gestational diabetes or a family history of diabetes. The follow-up interval for the subjects ranged from 0.87 to 8.54 years and of the 657, 319 had fasting plasma glucose levels of < 7.0 mmol/L where a fasting glucose level of > or = 7.0 mmol/L was used to diagnose diabetes Of the 319 nondiabetic subjects, 55 had IFG and 264 had NFG. After a median follow-up of 1.12 years (range: 0.87-8.54 years), 27 progressed to diabetes. The Kaplan-Meier analysis of progression to diabetes showed significant differences between subjects with IFG and subjects with NFG. Using Cox regression analysis, IFG (beta = 3.51, SE = 1.63, P = 0.032) and smoking (beta = 3.60, SE = 1.50, P = 0.017) were found to be independently associated with progression to diabetes. In Hong Kong Chinese with risk factors for glucose intolerance, IFG status is an independent risk factor for progression to diabetes.

A low socio-economic status is an additional risk factor for glucose intolerance in high risk Hong Kong Chinese.

To examine whether a low socio-economic status (SES) is an additional risk factor for glucose intolerance in Hong Kong Chinese with known risk factors for glucose intolerance, a total of 2847 Chinese subjects (473 men and 2374 women) were recruited from the community for assessment. They had known risk factors for glucose intolerance including a previous history of gestational diabetes, positive family history of diabetes in first degree relatives and equivocal fasting plasma glucose concentrations between 7 and 8 mmol/l or random plasma glucose concentrations between 8 and 11 mmol/l. The 2847 subjects were classified according to their education levels and occupations: education group 1 = high school or university, group 2 = middle school, group 3 = illiterate or up to elementary school; occupational group 1 = professional or managerial, group 2 = non-manual, group 3 = manual, group 4 = unskilled, group 5 = housewife or unemployed. Different socio-economic groups were well represented in this selected population. The distribution of educational groups in this study was similar to that recorded in the 1991 Hong Kong Census. When analysed according to education levels and after adjustment for age, women in the lowest social class had the highest prevalence of diabetes, body mass index, blood pressure and plasma glucose concentrations. Men with the lowest education level had the highest prevalence of diabetes after age adjustment. The age-adjusted odds ratio (95% confidence intervals) of having diabetes was 2.3 (1.3. 4.3) in female subjects and 2.5 (1.2, 5.4) in male subjects with the lowest SES compared to subjects with the highest SES. When categorised according to occupation and after adjustment for age, women in the lowest social class had the highest prevalence of diabetes and glycaemic indexes. The age-adjusted odds ratio of having diabetes was 4.5 (1.9, 10.9) in female subjects with the lowest SES compared to those with the highest SES. The corresponding age-adjusted odds ratio in male subjects was 1.9 (0.9, 3.9) but this was not statistically significant. In conclusion, a lower socio-economic class, categorised either by occupational or educational level, was an additional risk factor for diabetes in Hong Kong Chinese who had known risk factors for glucose intolerance. These subjects should have increased priority for health education and regular diabetes screening. Our findings further emphasise the complex relationships between societal affluence, personal income and educational level.

Pancreatic development and adult diabetes.

Low birth weight is an important risk factor for type 2 diabetes in later life. Maturity-onset diabetes of the young has been linked to genetic sequence abnormalities in transcription factors known to be involved in endocrine pancreatic development. These observations suggest that both the maternal environment and the fetal genome can influence the number and/or function of pancreatic beta cells in early life, and that this has life-long implications for postnatal diabetes. This article reviews the evidence that suggests that beta cells derive from a neogenic process within the pancreatic ductal epithelium, controlled by specific transcription factors and locally acting peptide growth factors. In rodents, many of the fetal phenotypes of beta cells are destroyed during neonatal life in a developmental apoptosis and are replaced by a second wave of neogenesis. This results in islets with insulin release characteristics suited to postnatal life. The timing and amplitude of these ontological events are altered by nutritional sufficiency, and this may be mediated by changes in pancreatic growth factor expression, particularly of the IGF axis. Because beta-cell plasticity after the perinatal period is limited, a dysfunctional programming of beta-cell ontogeny may present a long-term risk factor for glucose intolerance and type 2 diabetes. This critical window of pancreatic development is likely to occur in third trimester of human development.

Dietary Patterns in a High-Risk Population for Glucose Intolerance

We evaluated dietary habits as risk factor for glucose intolerance in a high risk population of Japanese-Brazilians enrolled in a study on the prevalence of diabetes (DM). Based on oral glucose tolerance test and WHO criteria, 331 had normal tolerance (NGT), 88 impaired tolerance (IGT) and 83 had type 2 DM (51 self-reported, 32 newly diagnosed diabetics). Clinical, laboratory and dietary data, assessed by food frequency questionnaire (FFQ), were compared between the NGT group and another composed of IGT and newly diagnosed DM (disturbed glucose tolerance or DGT group). Associations of total energy intake and nutrient intakes with glucose intolerance were analyzed by logistic regression. Also, subjects with NGT and DGT entered into separate models of multiple linear regression including BMI as the dependent variable, and total energy intake or each nutrient as independent variables. DGT group showed higher waist-to-hip ratio, blood pressure, plasma glucose and insulin levels and worse lipid profile. Total energy intake, macronutrients, fibers, alcohol and saturated fat intakes did not differ between groups; DGT was not associated with any nutrient intake in multivariate analyses. BMI of the subjects with DGT but not with NGT was associated with protein and cholesterol intakes in linear regression analysis. Our findings did not support an association between nutritional factors and glucose intolerance even in subjects who are unaware of their DGT, using FFQ to reflect current habits. However, we suggest that protein and cholesterol intakes may be markers of increased BMI. Despite assuming that obesity and insulin resistance precedes DM, FFQ may not be useful in the assessment of unfavorable dietary patterns among subjects at risk for glucose intolerance, such as Japanese-Brazilians with elevated BMI.

Fetal programming of the pancreatic β cells and the implications for postnatal diabetes

Infants born with low birth weight have a greatly increased risk of type-2 diabetes in later life. This can be reproduced in animal models where maternal nutritional restriction of rats limits fetal growth rate and can result in glucose intolerance when the offspring become adults. This is partly due to inadequate insulin release resulting from deficiencies in the number and/or function of pancreatic β cells. Evidence is presented which shows that β cells derive from a neogenic process within the pancreatic ductal epithelium, controlled by specific transcription factors and locally-acting peptide growth factors. Following birth, many of the fetal phenotype of β cells are destroyed in a developmental apoptosis, and replaced by a second wave of neogenesis. This results in islets with insulin release characteristics suited to postnatal life. The timing and amplitude of these ontological events are altered by nutritional sufficiency, and this may be mediated by changes in pancreatic growth factor expression, particularly of the insulin-like growth factor axis, and glucocorticoid presence. Since β cell plasticity following the perinatal period is limited, a dysfunctional programming of β cell ontogeny may present a long-term risk factor for glucose intolerance and type-2 diabetes.

The ageing entero-insular axis.

Ageing is one of the major risk factors for glucose intolerance including impaired glucose tolerance and Type II (non-insulin-dependent) diabetes mellitus. Reduced insulin secretion has been described as part of normal ageing although there is no information on age-related changes in the secretion of the major insulinotropic hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide (7-36 amide) (GLP-1). We assessed the entero-insular axis in 6 young premenopausal and 6 older postmenopausal women following treatment with oral carbohydrate. Insulin and glucose integrated responses were similar in the younger and older groups. Total integrated responses for GIP and GLP-1 were considerably greater in the older subjects. A positive correlation between age and total integrated responses for glucose (r = 0.65; p < 0.02) as well as GLP-1 (r = 0.85; p < 0.001) was seen. We hypothesise that an age-related impairment of insulin secretion to insulinotropic hormones, GIP and GLP-1, contributes to a reduction in glucose tolerance in this age group. The pronounced compensatory increase in postprandial secretion of GIP and GLP-1 provides further evidence not only for the negative feedback relation between incretin and insulin secretion but also for the importance of the entero-insular axis in the regulation of insulin secretion.

健診にみられた耐糖能異常の背景因子に関する検討 : 性、年齢、BMIとの関連について

健診にみられた耐糖能異常の背景因子に関する検討 : 性、年齢、BMIとの関連について

Vitamin D, glucose tolerance and insulinaemia in elderly men.

Vitamin D status was assessed in 142 elderly Dutchmen participating in a prospective population-based study of environmental factors in the aetiology of non-insulin-dependent diabetes mellitus. Of the men aged 70-88 years examined between March and May 1990, 39% were vitamin D depleted. After adjustment for confounding by age, BMI, physical activity, month of sampling, cigarette smoking and alcohol intake the 1-h glucose and area under the glucose curve during a standard 75-g oral glucose tolerance test (OGTT) were inversely associated with the serum concentration of 25-OH vitamin D (r = -0.23, p < 0.01; r = -0.26, p < 0.01, respectively). After excluding newly diagnosed diabetic patients total insulin concentrations during OGTT were also inversely associated with the concentration of 25-OH vitamin D (r = -0.18 to -0.23, p < 0.05). Hypovitaminosis D may be a significant risk factor for glucose intolerance.

Vitamin D Depletion as a Risk Factor for Glucose Intolerance in Elderly Dutchmen

Vitamin D Depletion as a Risk Factor for Glucose Intolerance in Elderly Dutchmen

Impaired glucose tolerance and insulin insensitivity in primary hyperparathyroidism

A high prevalence of diabetes mellitus has been shown in patients with primary hyperparathyroidism (PHPT). However, it is unclear whether this is related to the metabolic abnormalities in PHPT or to the presence of other risk factors for glucose intolerance in these patients. The aim of our study was to determine whether glucose intolerance and insulin insensitivity occur in subjects with PHPT who do not have other risk factors for diabetes mellitus. Cross-sectional study of glucose metabolism in PHPT patients without other risk factors for diabetes mellitus, compared to age and body mass index (BMI) matched healthy subjects. Nineteen non-obese, non-diabetic, normotensive patients with PHPT and 11 age and BMI matched healthy subjects. The continuous infusion of glucose test was used to assess glucose tolerance. Plasma glucose and insulin were measured during a 1-hour continuous infusion of glucose (5 mg/kg ideal body weight/min); insulin sensitivity and beta-cell function were derived from the glucose and insulin data by mathematical modelling. Fasting serum concentrations of parathyroid hormone, ionized calcium and 1,25-dihydroxyvitamin D (1,25(OH)2D) were measured in all subjects. PHPT patients attained higher plasma glucose levels at the end of the glucose infusion (median 9.0 (interquartile range 8.1-9.8) mmol/l) than did controls (7.9 (7.1-8.9) mmol/l, P < 0.05), and 8 (42%) PHPT patients had impaired glucose tolerance. Insulin sensitivity was lower in PHPT (60.3% (49.8-85.4)) than in controls (113.7% (89.3-149.2), P < 0.001); beta-cell function was not different in PHPT subjects. PHPT subjects with impaired glucose tolerance had reduced beta-cell function compared to PHPT subjects with normal glucose tolerance (89.9% (70.5-106.4) vs 120% (98.8-156.6) respectively, P < 0.05). No significant correlations were found between insulin sensitivity and PTH (rs = -0.21), 1,25(OH)2D (rs = -0.14), ionized calcium (rs = -0.11) and inorganic phosphate (rs = 0.34). Beta-cell function did not correlate with PTH (rs = 0.15), 1,25(OH)2D (rs = 0.04), ionized calcium (rs = 0.23) or inorganic phosphate (rs = -0.35). Insulin insensitivity is present in PHPT even in the absence of hypertension and obesity, and may be the cause of glucose intolerance and diabetes. PHPT subjects with reduced beta-cell function are more likely to develop glucose intolerance.

Food habits in Aborigines and persons of European descent of southeastern Australia

As part of a study of risk factors for glucose intolerance and heart disease in Australian Aborigines and persons of European descent, we elicited the prevalence of food habits that may be associated with high fat and high salt intakes. Interview data were gathered from population-based samples in country towns and visitors to an Aboriginal health service in a state capital city, all in southeastern Australia. Among persons aged 13 years and over, the frequency of eating takeaway food as a meal was categorised as monthly or less, weekly, more than once per week, and daily or more often. The prevalence of eating such meals was higher among city Aborigines than those living in the country town; the prevalence was lowest among the country-town Europeans (chi 2 = 184, 6 df, P < 0.001). The prevalence of adding salt during cooking and food consumption was higher among Aborigines compared with Europeans. Among country-town Aboriginal males aged 35 or under, 25 of 40 (63 per cent) added salt to cooked food 'most of the time', compared with 66 of 185 (36 per cent) Europeans (chi 2 = 9.8, P = 0.002). Among Aboriginal females, 47 of 64 (64 per cent) were in the highest category of salt use, compared with 35 of 190 (18 per cent) of Europeans (chi 2 = 66.3, P < 0.001). About one-third of country-town Aboriginal males used dripping to fry food, but in the other ethnicity, gender and location groups, vegetable oil was the most frequent choice. The main differences in food habits were associated with ethnicity, rather than location.(ABSTRACT TRUNCATED AT 250 WORDS)