Disturbed Glucose Tolerance Research Articles

Predictive factors of non-deterioration of glucose tolerance following a 2-year behavioral intervention

AimTo identify predictive factors associated with non-deterioration of glucose metabolism following a 2-year behavioral intervention in Japanese-Brazilians.Methods295 adults (59.7% women) without diabetes completed 2-year intervention program. Characteristics of those who maintained/improved glucose tolerance status (non-progressors) were compared with those who worsened (progressors) after the intervention. In logistic regression analysis, the condition of non-progressor was used as dependent variable.ResultsBaseline characteristics of non-progressors (71.7%) and progressors were similar, except for the former being younger and having higher frequency of disturbed glucose tolerance and lower C-reactive protein (CRP). In logistic regression, non-deterioration of glucose metabolism was associated with disturbed glucose tolerance - impaired fasting glucose or impaired glucose tolerance - (p < 0.001) and CRP levels ≤ 0.04 mg/dL (p = 0.01), adjusted for age and anthropometric variables. Changes in anthropometry and physical activity and achievement of weight and dietary goals after intervention were similar in subsets that worsened or not the glucose tolerance status.ConclusionThe whole sample presented a homogeneous behavior during the intervention. Lower CRP levels and diagnosis of glucose intolerance at baseline were predictors of non-deterioration of the glucose metabolism after a relatively simple intervention, independent of body adiposity.

Risk factors for ischemic stroke and transient ischemic attack in patients under age 50.

To analyze risk factors for ischemic stroke and transient ischemic attack (TIA) in young adults under the age of 50. To make recommendations for additional research and practical consequences. From 97 patients with ischemic stroke or TIA under the age of 50, classical cardiovascular risk factors, coagulation disorders, history of migraine, use of oral contraceptives, cardiac abnormalities on ECG and echocardiography, and the results of duplex ultrasound were retrospectively analyzed. Literature was reviewed and compared to the results. 56.4% of the patients had hypertension, 12.1% increased total cholesterol, 20% hypertriglyceridemia, 31.5% an increased LDL-level, 32.6% a decreased HDL-level and 7.2% a disturbed glucose tolerance. Thrombophilia investigation was abnormal in 21 patients and auto-immune serology was abnormal in 15 patients. Ten of these patients were already known with a systemic disease associated with an increased risk for ischemic stroke (i.e. systemic lupus erythematosus). The ECG was abnormal in 16.7% of the cases, the echocardiography in 12.1% and duplex ultrasound of the carotid arteries was in 31.8% of the cases abnormal. Conventional cardiovascular risk factors are not only important in patients over the age of 50 with ischemic stroke or TIA, but also in this younger population under the age of 50. Thrombophilia investigation and/ or autoimmune serology should be restricted to patients without conventional cardiovascular risk factors and a history or other clinical symptoms associated with hypercoagulability and/ or autoimmune diseases.

CORRELATION BETWEEN SMOKING AND GLUCOSE METABOLISM IN PATIENTS WITH HYPERTENSION: PP.17.169

Objective: The smoking effect was appreciated in hypertension patients, depending on the glucose metabolism deviation degree. It is reminded that the smoking is related with the increase of resistance in the insulin in patients with diabetes Type 1, increasing the Glycosylated Hemoglobin (HbA1C). Design and Method: 135 individuals (69 smokers and 66 not smokers) with arterial hypertension, without further complications and with means age 56 ± 9,7 years, were studied. They were submitted in complete clinical and laboratorial examination. The fast glucose and the HbA1C values were determined in serum. The glucose value was measured again after oral administration of 75 gr glucose and their smoking habit were recorded. Results: As you can see at the table. Conclusions: 1) he mild deviations of glucose metabolism, like as the fast glucose disturbances, as well as the glucose tolerance disturbances, the smoking does not appear to influence the HbA1C levels. 2) The smoking effect of HbA1C level is enough important (p < 0,05) in hypertension patients with Type 2 diabetes. Consequently, the smoking habit of these patients should always are taken into consideration.

CD40L-CD40 fuel ignites obesity

Obesity and its metabolic complications like insulin resistance and type II diabetes with their continuously increasing morbidity and mortality represent a challenge for global health care (1). Yet, detailed mechanistic understanding of the pathogenesis of obesity and its metabolic complications as well as effective treatment options are still lacking. Inflammation is considered to have a pivotal role in the development of metabolic diseases (2–5). Obese adipose tissue shows hallmarks of chronic inflammation, with the involvement of T-cell subsets like Th1 and Th2 and regulatory T-cells (4–6), macrophage subsets (classically and alternatively activated macrophages) (7), but also other immune cells like mast cells (8). These immune cells, their cell-cell interactions, and their interactions with adipocytes have been found to alter adipose tissue function, thereby affecting insulin resistance and obesity. However, the exact immune cells and molecules involved, as well as the interplay between the different cell-types are still unclear (9). Especially T-cells have been proven to be important in the development of insulin resistance and obesity (4, 5). Recently, obesity has been associated with T-cell accumulation in adipose tissue, which apparently precedes the appearance of macrophages (3, 10). Surprisingly, Rag-/mice, which lack Tand B-cells, gain more weight, exhibit more visceral adiposity and have a more disturbed insulin and glucose tolerance when fed a high-fat diet than their wild type counterparts (4). Reconstitution of CD4+ T-cells improved their glucose tolerance, insulin sensitivity and lessened weight gain. These counterintuitive results can be explained by the shift in T-cell subsets: CD4+ reconstituted Rag-/mice exhibited a strong increase in the Th2 subset (4). Along this line, other papers show a detrimental role for CD4+ T-cells, especially the interferon γ-producing Th1 subset (6). These data suggest that CD4+ cells of the Th2 phenotype gradually fail to withhold the ever-expanding pro-inflammatory Th1 population, leading to a progressively pro-inflammatory environment, thereby promoting insulin resistance and obesity. In addition, Nishimura et al. showed a pivotal role for CD8+ T-cells in macrophage recruitment and tissue inflammation in obesity, indicating that also CD8+ T-cells have an essential role in initiation and propagation of adipose inflammation (3). T-cell proliferation, activation and subsequent adequate function of antigen presenting cells (APCs) require co-stimulation (11, 12). One of the co-stimulatory molecule dyads recently associated with obesity are the tumour necrosis factor (TNF)and TNF-receptor family members CD40L (CD154) and CD40 (13, 14). CD40L-CD40 interactions play a substantial, multifaceted role in immunity and inflammation, and are far more ubiquitously expressed than expected (15, 16). Not only are CD40L-CD40 interactions required for CD4+ cell proliferation and activation, and for inducing proper APC-function, they also induce endothelial cell activation, subsequent monocyte migration, as well as macrophageand smooth muscle cell activation, characterised by the production of chemokines, cytokines and proteolytic enzymes, and are therefore involved in a Correspondence to: Esther Lutgens Institute for Molecular Cardiovascular Research (IMCAR) Pauwelsstrase 30 52074 Aachen Germany Tel.: +49 241 808 0580, Fax: +49 241 808 2716 E-mail: elutgens@ukaachen.de

Phenotypic and pathomorphological characteristics of a novel mutant mouse model for maturity-onset diabetes of the young type 2 (MODY 2)

Several mutant mouse models for human diseases such as diabetes mellitus have been generated in the large-scale Munich ENU (N-ethyl-N-nitrosourea) mouse mutagenesis project. The aim of this study was to identify the causal mutation of one of these strains and to characterize the resulting diabetic phenotype. Mutants exhibit a T to G transversion mutation at nt 629 in the glucokinase (Gck) gene, leading to an amino acid exchange from methionine to arginine at position 210. Adult Munich Gck(M210R) mutant mice demonstrated a significant reduction of hepatic glucokinase enzyme activity but equal glucokinase mRNA and protein abundances. While homozygous mutant mice exhibited growth retardation and died soon after birth in consequence of severe hyperglycemia, heterozygous mutant mice displayed only slightly elevated blood glucose levels, present from birth, with development of disturbed glucose tolerance and glucose-induced insulin secretion. Additionally, insulin sensitivity and fasting serum insulin levels were slightly reduced in male mutant mice from an age of 90 days onward. While beta-cell mass was unaltered in neonate heterozygous and homozygous mutant mice, the total islet and beta-cell volumes and the total volume of isolated beta-cells were significantly decreased in 210-day-old male, but not female heterozygous mutant mice despite undetectable apoptosis. These findings indicate that reduced total islet and beta-cell volumes of male mutants might emerge from disturbed postnatal islet neogenesis. Considering the lack of knowledge about the pathomorphology of maturity-onset diabetes of the young type 2 (MODY 2), this glucokinase mutant model of reduced total islet and total beta-cell volume provides the opportunity to elucidate the impact of a defective glucokinase on development and maintenance of beta-cell mass and its relevance in MODY 2 patients.

Circulating asymmetric dimethylarginine, endothelin-1 and cell adhesion molecules in women with gestational diabetes

We measured plasma concentrations of asymmetric dimethylarginine (ADMA), endothelin-1 (ET-1), soluble vascular cell adhesion molecule-1 (sVCAM-1) and E-selectin in 56 patients with gestational diabetes (GDM), 68 pregnant women with normal glucose tolerance (NGT) and 36 healthy non-pregnant women. ADMA concentrations were markedly lower in NGT [0.48 (0.42-0.55) micromol/l] than in GDM subjects [0.50 (0.43-0.67) micromol/l] and healthy controls [0.57 (0.46-0.72) micromol/l, P = 0.005]. ET-1 levels were comparable between GDM [0.76 (0.58-0.90) pg/ml] and NGT women [0.75 (0.63-0.92) pg/ml] and significantly higher than in the non-pregnant subjects [0.62 (0.52-0.72) pg/ml, P = 0.007 and P = 0.005, respectively]. There were no differences in sVCAM-1 and E-selectin levels between the groups studied. ADMA levels were significantly associated with fasting glucose (beta = 0.23, P = 0.02) and gestational age (beta = 0.24, P = 0.01). Our results suggest that physiological adaptation to pregnancy is associated with a fall in circulating ADMA and an elevation of ET-1 concentrations, irrespective of the disturbances of glucose tolerance.

Glukokortikoide und Hypertonie

Severe arterial hypertension is a hallmark of Cushing syndrome which occurs in 80% of the patients. Additionally, persistent cortisol excess induces obesity, hyperinsulinemia with disturbed glucose tolerance and dyslipidemia which all contribute to the development of hypertension and its deleterious sequelae. Cortisol effects are mediated through diversely distributed intracellular glucocorticoid and mineralocorticoid receptors which are protected by the 11-beta-hydroxysteroiddehydrogenase type 2 in cells of some organs (i.e. kidney) but not in other. A highly complex clinical picture evolves in case of hypercortisolism due to the ubiquitous distribution of steroid receptors with different affinity and binding capacities for glucocorticoids. The present review focuses on the cortisol induced changes in blood pressure regulation which contribute to the development of hypertension.

High prevalence of undiagnosed diabetes and abnormal glucose tolerance in the Iranian urban population: Tehran Lipid and Glucose Study

BackgroundTo estimate the prevalence of diagnosed and undiagnosed diabetes mellitus, impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and combined IFG/IGT in a large urban Iranian population aged ≥ 20 years.MethodsThe study population included 9,489 participants of the Tehran Lipid and Glucose Study with full relevant clinical data. Age-standardized prevalence of diabetes and glucose intolerance categories were reported according to the 2003 American Diabetes Association definitions. Age-adjusted logistic regression models were used to estimate the numbers needed to screen (NNTS) to find one person with undiagnosed diabetes.ResultsThe prevalence of diagnosed and undiagnosed diabetes, isolated IFG, isolated IGT, and combined IFG/IGT were 8.1%, 5.1%, 8.7%, 5.4% and 4.0% in men and 10%, 4.7%, 6.3%, 7.6%, and 4.5% in women respectively. Participants with undiagnosed diabetes had higher age, body mass index (BMI), waist circumference, systolic and diastolic blood pressures, triglycerides (all p values <0.001) and lower HDL-cholesterol (only in women, p < 0.01) compared to normoglycemic subjects. Undiagnosed diabetes was associated with family history of diabetes, increased BMI (≥ 25 kg/m2), abdominal obesity, hypertriglyceridemia, hypertension and low HDL-cholesterol levels. Among men, a combination of increased BMI, hypertension, and family history of diabetes led to a NNTS of 1.6 (95% CI: 1.57–1.71) and among women a combination of family history of diabetes and abdominal obesity, yielded a NNTS of 2.2 (95% CI: 2.1–2.4).ConclusionIn conclusion, about one third of Tehranian adults had disturbed glucose tolerance or diabetes. One- third of total cases with diabetes were undiagnosed. Screening individuals with BMI ≥ 25 kg/m2 (men), hypertension (men), abdominal obesity (women) and family history of diabetes may be more efficient.

Oral glucose tolerance tests--with or without estimation of serum insulin? (author's transl)

Blood glucose and serum insulin values were determined after oral glucose tolerance tests in 528 persons with suspected pathological or disturbed glucose tolerance. Results were evaluated depending on sex, age, overweight, and familial diabetes. There were no differences of serum insulin secretion and behaviour of blood sugar between males and females. With increasing age there was a marked decrease of insulin secretion. In contrast there was increased hyperinsulinaemia with increasing overweight. This was particularly evident in persons with comparably reduced glucose tolerance but with different body weight. "Classical" changes of insulin secretion, as described for prediabetes and manifest diabetes in contrast to persons with normal metabolism, were only seen in selected groups of probands with normal weight. Serum insulin shows greater variability than blood glucose. Estimations of insulin are not necessary when assessing disturbances of glucose tolerance.

Impaired Insulin Secretion in Mice lacking Adenosine A1 Receptor

Introduction: Adenosine has been reported to participate in maintaining glucose homeostasis. Adenosine A1 receptor (A1AR) deficient mice present with a disturbed glucose tolerance and insulin resistance. Aim of this present study was to investigate the secretory insulin function in A1AR deficient mice. Methods: Experiments were performed in male C57Bl/6 mice of the Adenosine 1A Receptor strain generated previously in our lab. Mice received standard chow. Chemicals were injected intraperitoneally. Blood was sampled by tail vein puncture. Glucose was measured by glucometer. Insulin by ELISA. Impaired glucose tolerance was evidenced by modified Belfiore Insulin Sensitivity Index (ISI). Insulin tolerance (ITT), 1st phase insulin secretion and L-arginine-stimulated insulin secretion were tested according to published procedures. Data were analyzed by two tailed T-test. Results: tAUCs calculated from ITT data were significantly higher in A1AR-/- in two age groups ([min*mg-1*dl-1]: 8–9wk:17560±5608, n=8 vs. 7869±3238, n=5, p<0.01; 20–27 wk:17190±7398, n=6 vs. 9115±2537, n=9, p<0.01). The slope of linear decline of glucose after insulin stimulation (KITT [%/min]) was lower in A1AR-/- (Wt vs. A1AR-/-: 8–9wk 2.76±0.9, n=5 vs. 1.65±1.47%/min, n=8, n.s.; 20–27wk 2.0±1.6, n=9 vs. 1.15±0.29%/min, n=6, n.s.). Fasting plasma insulin was significantly higher in young A1AR-/- but not in mature mice (8 wk: 0.97±0.12 vs. 0.34±0.1ng/ml; 20 wk: 0.88±0.23 vs. 0.59±0.06ng/ml, n=12 vs. 22, n.s). A1AR-/- had a significantly decreased ISI compared to Wt (8wk: 0.3±1.1, n=5 vs. 1.5±0.52, n=6, p<0.01; 20wk: 0.07±0.02, n=12 vs. 0.72±0.12, n=5, p<0.001). A1AR had higher baseline and stimulated insulin plasma levels at 8 wk (Wt: n=5 vs. A1AR-/-: n=9; 0min: Wt: 0.56±0.45 vs. A1AR-/- 0.71±0.26ng/ml, n.s.; 2.5min: Wt: 0.76±0.59 vs. A1AR-/- 0.96±0.33ng/ml, n.s.; 5min: Wt: 0.83±0.64 vs. A1AR-/- 1.07±0.4ng/ml, n.s.). In contrast, at 20 wk A1AR-/- had a negative response after glucose stimulus with lower insulin levels, reaching significance after 5min (Wt: n=10, A1AR-/-: n=6; 0min: Wt: 0.56±0.25 vs. A1AR-/- 1.24±1.0ng/ml, n.s.; 2.5min: Wt: 1.21±0.9 vs. A1AR-/- 0.66±0.6ng/ml, n.s.; 5min: Wt: 1.35±0.65 vs. A1AR-/- 0.68±0.37ng/ml, p<0.05). Glucose-independent insulin secretion showed physiological response curves for both groups. Conclusion: A1AR-/- mice develop impaired glucose tolerance and insulin resistance with a more pronounced phenotype in mature mice. A1AR participates in glucose stimulated insulin release. Compensation for loss of A1AR fails to achieve sufficient insulin release in mature mice. Lack of A1AR-activation does not impair insulin exocytosis. The defunct insulin secretion in Adenosine 1A receptor deficiency might be caused by impaired Glucose uptake. Future studies should therefore investigate Glucose uptake pathways in A1AR-/-.

ACUTE CORONARY SYNDROME IN PATIENTS WITH DIABETES MELLITUS: ON THE WAY TO MUNICH-2008

Results of trials on the therapy of patients with acute myocardial infarction (MI) and glucose metabolism disturbances are discussed. According to author’s data, 67% of patients with MI have glucose tolerance disturbances including 44% of patient with these reaching the level of diabetes mellitus (DM). Mortality risk in patients with MI and DM is some times higher than this in patients with MI without glucose metabolism disturbances. Active glucose correction results in significant mortality risk reduction. It is necessary to reduce glucose blood level to normal one as soon as possible in patients with MI and DM. It can be managed with insulin, if the glucose blood level is intensively increased or with per oral glucose lowering medicines, if there is moderate hyperglycemia. In spite of wide usage of these class drugs, it is not still clear which medicine is mostly effective in patients with MI and glucose metabolism disturbances.

Validation of Prediction of the Score (Systematic Coronary Risk Evaluation) in Urban Population

P-778 Objectives: The premature death in highly developed countries is related mainly to cardiovascular atherosclerosis and malignant diseases, so the screening for subject in risk, primary prevention and early treatment should be a focus of the public health. Aim: The aim of the study was to assess validity of the SCORE risk estimation system in determining ten-year risk fatal cardiovascular disease (CVD) events in urban population. Material and Methods: The study was conducted in 2004–2005 as a part of the municipality sponsored program on Primary Prevention of the Atherosclerosis, Diabetes Type 2 and Hypertension. More than 40 000 subjects aged over 25 without any history of the CVD or diabetes type 2 participated in the study. The program was run in 42 general practitioners practices. In 13434 men and 27555 women anthropometric measurements, blood pressure, fasting total cholesterol and glycaemia tests were performed. Information about smoking status, family history of CVD and diabetes type 2 were collected by questionnaire. In subjects with elevated level of total cholesterol (> 5.2 mmol/l) HDL cholesterol and triglycerides tests were performed. Total cholesterol, systolic blood pressure and smoking status were used to assess 10-year risk of fatal cardiovascular disease event according to SCORE risk estimation system. Results: Among 40989 examined subjects 16,2% men and 40,9% women (p<0.05) were risk free. Risk below 5% was present in 53.1% of women and 51,.3% of men, risk between 6% and 14% in 30.4% men and 6% women. Very high risk (15% and over) was found in 8 women (0.03%) and 277 men (2.1%.). The applied logistic regression methods showed that the standard cardiovascular risk factors significantly underestimate the SCORE prediction: the highest risk factor was current smoking over 10 cigarettes daily (men: RR=12.4 95%CI: 10.3÷15.0 women: RR=9.1 95%CI: 7.5 11.÷1), obesity increased significantly the risk at 60% in men and 68% in women, glucose tolerance disturbances were also significant risk factors (diabetes mellitus: RR=1.57 for men and 1.43 for women, impaired glucose tolerance: RR=2.39 for both sexes) Conclusions: The SCORE outcome seems to be definite for health people exclusively while subjects with newly diagnosed diabetes mellitus, impaired glucose tolerance or obesity should be screened furthermore.

Gender differences in the metabolic syndrome and their role for cardiovascular disease

Women live longer than men and develop cardiovascular disease (CVD) at an older age. The metabolic syndrome represents a major risk factor for the development of CVD, and gender differences in this syndrome may contribute to gender differences in CVD. In recent years, the metabolic syndrome has been more prevalent in men than in women. Prevalence is increasing and this increase has been steeper in women, particularly in young women, during the last decade. The contributions of the different components of the metabolic syndrome differ between genders and in different countries. In a recent survey in Germany, 40% of the adult population had been diagnosed with disturbed glucose tolerance or type 2 diabetes. Undiagnosed diabetes was more frequent in men than in women, and risk factors for undiagnosed diabetes differed between the sexes. Worldwide, in individuals with impaired glucose tolerance, impaired fasting glucose was observed more frequently in men, whereas impaired glucose tolerance occurred relatively more often in women. Lipid accumulation patterns differ between women and men. Premenopausal women more frequently develop peripheral obesity with subcutaneous fat accumulation, whereas men and postmenopausal women are more prone to central or android obesity. In particular, android obesity is associated with increased cardiovascular mortality and the development of type 2 diabetes. Visceral adipocytes differ from peripheral adipocytes in their lipolytic activity and their response to insulin, adrenergic and angiotensin stimulation and sex hormones. Visceral fat is a major source of circulating free fatty acids and cytokines, which are directly delivered via the portal vein to the liver inducing insulin resistance and an atherogenic lipid profile. Inflammation increases cardiovascular risk particularly in women. A relatively greater increase in cardiovascular risk by the appearance of diabetes in women has been reported in many studies.Thus, the presently available data suggest that the pathophysiology of the metabolic syndrome and its contribution to the relative risk of cardiovascular events and heart failure show gender differences, which might be of potential relevance for prevention, diagnostics, and therapy of the syndrome.

Relations entre surcharges en fer et insulinorésistance

There is increasing evidence that moderately elevated body iron stores, below levels commonly found in genetic hemochromatosis, may be associated with adverse health outcomes. Genetic hemochromatosis, characterized by transferrin saturation (TS) greater than 45%, is most often linked to homozygosity of the HFE C282Y allele. The phenotype is also modulated by mutations of more recently discovered genes (including ferroportin, hemojuvelin, hepcidin, and transferrin receptor) and environmental factors (including alcohol, viruses, diet, blood loss). Iron overload without hemochromatosis is characterized by high levels of serum ferritin and normal TS, as seen in dysmetabolic hepatosiderosis. Elevated serum ferritin levels predict incident type 2 diabetes in prospective studies and have been associated with hypertension, dyslipidemia, glucose tolerance disturbances, central adiposity, and metabolic syndrome. High ferritin levels are not synonymous with iron overload and may in some cases be a simple marker of insulin resistance.

Endoneurial capillary abnormalities presage deterioration of glucose tolerance and accompany peripheral neuropathy in man.

To explore whether microangiopathy is associated with disturbed glucose tolerance and peripheral neuropathy, we assessed endoneurial capillary morphology in sural nerve biopsies from men with diabetes, impaired glucose tolerance (IGT), and normal glucose tolerance (NGT). Baseline morphology was related to glucose tolerance and neuropathy at baseline and at follow-up 6 years later. Capillary density (in number per millimeters squared) at baseline was higher in subjects with diabetes (n = 10) compared with those with NGT (n = 5) at follow-up (median [interquartile range]) (86.0 [24.3] vs. 54.9 [17.1]; P = 0.0200) and in those progressing from IGT to diabetes (n = 4) compared with those with persistent IGT (n = 4) (86.7 [25.2] vs. 54.1 [14.6]; P = 0.0433). The capillary luminal area (in micrometers squared) was lower in subjects with NGT progressing to IGT (n = 2) or subjects with IGT progressing to diabetes (n = 3) compared with subjects with constant NGT (n = 6) or constant IGT (n = 4) (11.9 [2.4] vs. 20.8 [7.8]; P = 0.0201). The capillary basement membrane area (in micrometers squared) was increased in patients with peripheral neuropathy (n = 10) compared with those without (n = 7) (114.6 [68.8] vs. 75.3 [28.7]; P = 0.0084). In conclusion, increased capillary density was associated with current or future diabetes, decreased capillary luminal area with future deterioration in glucose tolerance, and increased basement membrane area with peripheral neuropathy.

High prevalence of undiagnosed diabetes mellitus in Southern Germany: target populations for efficient screening. The KORA survey 2000.

To estimate the prevalence of undiagnosed diabetes mellitus, impaired glucose tolerance (IGT) and impaired fasting glucose (IFG), and their relations with cardiovascular risk factors in the general population aged 55 to 74 years in Southern Germany. Oral glucose tolerance tests were carried out in a random sample of 1353 subjects aged 55 to 74 years participating in the KORA (Cooperative Health Research in the Region of Augsburg) Survey 2000. Prevalences of glucose tolerance categories (1999 WHO criteria) were adjusted for sample probabilities. The numbers needed to screen (NNTS) to identify one person with undiagnosed diabetes were estimated from age-adjusted logistic regression models. Sample design-based prevalences of known and unknown diabetes, IGT, and IFG were 9.0%, 9.7%, 16.8%, 9.8% in men, and 7.9%, 6.9%, 16.0%, 4.5% in women, respectively. In both sexes, participants with undiagnosed diabetes had higher BMI, waist circumference, systolic blood pressure, triglycerides, uric acid, and lower HDL-cholesterol than normoglycaemic subjects. A combination of abdominal adiposity, hypertension, and parental diabetes in men resulted in a NNTS of 2.9 (95%CI: 2.0-4.6). In women, the combination of increased triglycerides, hypertension and parental diabetes history yielded a NNTS of 3.2 (95%CI: 2.2-5.1). About 40% of the population aged 55 to 74 years in the Augsburg region have disturbed glucose tolerance or diabetes. Half of the total cases with diabetes are undiagnosed. Cardiovascular risk factors worsen among glucose tolerance categories, indicating the need for screening and prevention. Screening for undiagnosed diabetes could be most efficient in individuals with abdominal adiposity (men), hypertriglyceridaemia (women), hypertension, and parental diabetes history.

The improvement of insulin resistance in patients with adrenal incidentaloma by surgical resection.

Several recent studies have indicated that patients with adrenal incidentaloma often have disturbed glucose tolerance or/and hypertension. It is unclear whether these metabolic conditions could be caused by adrenal incidentaloma. We investigated the prevalence of disturbed glucose tolerance, hypertension and insulin resistance in the patients with non-functioning adrenal incidentaloma and evaluated the changes of the parameters such as glucose tolerance, blood pressure and insulin sensitivity after adrenalectomy. Among 15 patients with incidentally discovered adrenal tumours in our department from 1996 to 1999, 4 patients were diagnosed as having pre-clinical Cushing's syndrome and the other 11 as having non-functioning tumours based on detailed endocrinological examinations including dexamethasone suppression testing. Four tumours with pre-clinical Cushing's syndrome and 8 tumours out of 11 patients with non-functioning tumours were diagnosed histopathologically as adrenocortical adenomas and the other 3 as of non-adrenal origin including a myelolipoma, an adrenal vascular cyst and an endothelioma. The prevalence of disturbed glucose tolerance was determined with an oral glucose tolerance test, and insulin sensitivity was evaluated by the method of steady state of plasma glucose (SSPG). All 12 patients with adrenocortical adenoma exhibited insulin resistance based on the SSPG (6.9-13.2 mmol/l). Before surgical removal of the tumours, the SSPG titre was relatively higher in the patients with pre-clinical Cushing's syndrome than in those with non-functioning with adrenocortical adenoma (mean value 11.65 vs. 8.99 mmol/l), whereas 2 of the 3 patients with non-adrenocortical tumours did not have insulin resistance. Among the 12 patients with adrenocortical adenoma, 7 (58%) and 9 (75%) patients exhibited hypertension and disturbed glucose tolerance, respectively. After removal of the tumours, SSPG of the patients with adrenocortical adenoma, but not that of the other 3 patients with non-cortical tumours, was significantly decreased compared to pre-adrenalectomy values. There are no significant differences in the changes of SSPG titres between in pre-clinical Cushing's syndrome and in non-functioning adrenocortical adenoma. Systolic blood pressure, but not diastolic blood pressure, was also significantly decreased in the patients with adrenocortical adenoma. High prevalences of disturbed glucose tolerance, insulin resistance and hypertension were found among the patients with non-functioning adrenocortical tumours. Adrenocortical adenoma may be one of the risk factors for insulin resistance that is believed to induce disturbed glucose tolerance and/or hypertension. Therefore, it is useful to evaluate insulin resistance for the patients with adrenal incidentalomas since results are likely to be helpful in deciding whether to remove the tumour by surgery.

Analysis of cortisol secretion in hormonally inactive adrenocortical incidentalomas: study of in vitro steroid secretion and immunohistochemical localization of steroidogenic enzymes.

Adrenal incidentalomas have recently increased in incidence, and thus it has become important to establish clinical management of these patients. It is also important to evaluate whether these tumors are different from preclinical or overt Cushing's syndrome in their steroidogenesis. In this study, we therefore examined steroidogenesis of hormonally inactive adrenal incidentalomas via short-term culture of tumor specimens, in addition to an immunohistochemical study of steroidogenic enzymes. Five patients (two men and three women) diagnosed with adrenocortical incidentaloma without any clinical signs of adrenocortical hormonal excess except for hypertension and disturbed glucose tolerance, were recruited for this study. Hormonal findings, including circadian rhythms for cortisol and ACTH secretion, the response of ACTH to CRH infusion and results of dexamethasone suppression test were all within normal limits in these patients. Immunoreactivity for all steroidogenic enzymes involved in cortisol production was detected in tumor cells in all cases examined. Results of in vitro steroidogenesis analysis using short-term culture revealed that levels of cortisol secretion varied among the cases. There were no differences in the immunolocalization of steroidogenic enzymes and/or the levels of cortisol secretion between these hormonally inactive tumors and preclinical and/or overt Cushing's syndrome. Dehydroepiandrosterone-sulfotransferase (DHEA-ST) immunoreactivity in nonneoplastic regions was suppressed in one case in which the tumor secreted cortisol similar to preclinical and/or overt Cushing's syndrome. These results demonstrate that the levels of in vitro steroid production and/or the immunolocalization of steroidogenic enzymes in hormonally inactive adrenocortical tumors vary markedly and are not overtly different from those of preclinical and/or overt Cushing's syndrome.

Störungen der Glukosetoleranz bei Thalassaemia major

Fragestellung und Hintergrund. Bei Patienten mit Thalassaemia major fuhrt die Hamosiderose haufig zu Endokrinopathien. Wir untersuchten die Entwicklung von Glukosetoleranzstorungen und den Einfluss therapeutischer Masnahmen wie intensivierter Chelattherapie und Diat. Methode und Patienten. 60 Patienten mit Thalassaemia major im Alter von 4–36 Jahren, die regelmasige subkutane Deferoxamininfusionen sowie Bluttransfusionen erhielten, wurden hinsichtlich moglicher Endokrinopathien untersucht. Zur Untersuchung der Insulinsekretion dienten orale und i.-v.-Glukosebelastungen sowie der i.-v.-Glukagontest. Bei Patienten mit gestorter Glukosetoleranz wurde der Einfluss einer intensivierten (i. v.) Deferoxamintherapie und diatetischer Masnahmen auf Blutglukose- und Seruminsulinkonzentrationen untersucht. Ergebnisse. Glukosetoleranzstorungen zahlen ab dem 2. Lebensjahrzehnt zu den 4 haufigsten Hormonerkrankungen bei Patienten mit Thalassaemia major. Storungen der Glukosetoleranz gehen in einem Fruhstadium mit einer Hyperinsulinamie einher, spater entwickelt sich ein Insulinmangeldiabetes durch Erschopfung der β-Zell-Aktivitat. In der Fruhphase der Erkrankung fuhrten bei einigen Patienten eine Intensivierung der Deferoxamintherapie oder alleinige diatetische Behandlung zu einer Verbesserung der Glukosetoleranz. Schlussfolgerungen. Storungen der Glukosetoleranz lassen sich im Fruhstadium durch Diat und Intensivierung der Chelattherapie bessern. Die Manifestation eines Diabetes mellitus kann damit moglicherweise aufgehalten werden. Im fortgeschrittenen Stadium der Glukosetoleranzstorung liegt ein Insulinmangel vor, weshalb eine Insulinsubstitution notwendig wird.

Different regulation of VLDL production in patients with disturbed glucose tolerance and in persons from FCHL families

Different regulation of VLDL production in patients with disturbed glucose tolerance and in persons from FCHL families