Hemoglobin Glycosylation Index is not related with blood glucose

OBJECTIVE: Accurate assessment of blood glucose control is essential to prevent chronic complications in diabetes. Hemoglobin Glycosylation Index (HGI) quantifies the degree to which individuals demonstrate a HbA(1C) higher or lower than average for the population. This study has aimed to assess the relationship between HGI and blood glucose. METHODS: 25 type 1 diabetes subjects (12 men and 13 women), 22.0+/-5.2 (17-34) years old, were instructed to self-monitor glucose with the One Touch Profile capillary glucose meter. HbA(1C) was determined and self-monitored blood glucose levels were studied every 3 months. Diabetic patients were monitored for 3-9 months and 62 measurements of HbA(1C) were included. HbA(1C) was measured by HPLC. Mean blood glucose (MBG) was calculated from self-monitored blood glucose records. A linear regression was calculated between HbA(1C) and MBG during the 60 days before sampling to determine HbA(1C). For each diabetic patient's MBG, a predicted HbA(1C) was calculated from the population regression equation. HGI was then calculated as HGI=observed HbA(1C)-predicted HbA(1C). Blood glucose was analyzed within target range (WTR), below target range (BTR) and above target range (ATR) according to The European Diabetes Policy Group Consensus for type 1 diabetes. RESULTS: A good linear regression between HbA(1C) and MBG was observed (r=.71, r(2)=.497, P=.000). No correlation was found between HGI and the percentage of WTR, BTR or ATR values. Moreover, the percentage of self-monitored blood glucose ATR and BTR was the same for high glycosylators (HGI<0 and ATR: 56.2+/-20.9%; HGI<0 and BTR: 34.5+/-17.5%) as for low glycosylators (HGI>0 and ATR: 52.8+/-25.5%; HGI>0 and BTR: 25.1+/-15.0%). CONCLUSIONS: HGI is determined for both physiological factors and blood glucose. A prospective study is necessary to assess whether HGI, together with HbA(1C), can predict the incidence and severity of chronic complications in diabetic patients.     

Periodontal disease severity is related to high levels of C-reactive protein in pre-eclampsia

OBJECTIVE: Recent studies have shown that pre-eclamptic women present a high prevalence of periodontitis, suggesting that active periodontal disease may play a role in the pathogenesis of pre-eclampsia. The present study analysed the effect of periodontal disease in the concentrations of serum high-sensitivity C-reactive protein (hs-CRP), and its association with pre-eclampsia. METHODS: A case-control study was carried out in Cali-Colombia, comprised of 398 pregnant women (145 cases and 253 controls) who were believed to have periodontal disease, between 28 and 36 weeks of gestational age. Pre-eclampsia cases were defined as blood pressure > or = 140/90 mmHg and proteinuria > or = 0.3 g/24 h. Controls were pregnant women with normal blood pressure, without proteinuria, matched by maternal age, gestational age and body mass index. Sociodemographic data, obstetric risk factors, periodontal state, subgingival microbial composition and hs-CRP levels were determined in both groups. RESULTS: The case and control groups were comparable for sociodemographic characteristics. In women with pre-eclampsia and confirmed periodontal disease (n = 138), hs-CRP levels increased according to the severity of the disease (gingivitis median 4.14 mg/dl; mild periodontitis median 4.70 mg/dl; moderate/severe periodontitis median 8.8 mg/dl; P = 0.01). A similar tendency was observed in controls with periodontal disease (n = 251), but it did not reach statistical significance (gingivitis median 5.10 mg/dl; mild periodontitis median 5.12 mg/dl; moderate/severe periodontitis median 6.90 mg/dl; P = 0.07). A significant difference in hs-CRP levels was observed in pre-eclamptic women with moderate/severe periodontitis compared to controls (P = 0.01). CONCLUSION: These findings suggest that chronic periodontitis may increase hs-CRP levels in pregnant women and lead to complications such as pre-eclampsia.     

Increased platelet reactivity in unstable angina patients is not related to C-reactive protein levels

Platelets are a major component of thrombi, and coronary thrombosis plays a key role in the pathogenesis of unstable angina (UA). Whether platelet aggregability is increased in UA patients however, is not known. Furthermore, no study has investigated the relationship between platelet reactivity and inflammation in UA patients In this study, venous blood samples were collected at admission in coronary care unit in 37 patients with unstable angina (Braunwald class IIIB) and in 37 sex- and age-matched patients with chronic stable angina (CSA). Patients taking thienopyridine or anticoagulant drugs were excluded from the study, as also were excluded patients with a history of acute myocardial infarction in the previous 12 months. Platelet aggregability was measured on flowing blood as time to occlude a ring coated with collagen-adenosine diphosphate (ADP), using the platelet function analyzer (PFA-100) system. By this method, the time to occlusion (closure time) is taken as a measure of platelet adhesion/aggregability, with shorter times indicating greater platelet reactivity.There were 23 men and 14 women in both groups, and age was 67.7?±?8 and 67.5?±?8 years in UA and SA, respectively (P?=?0.93). Closure time was significantly reduced in UA patients (78.8?±?14?s), compared to SA patients (93.3?±?19?s,?P?<?0.001). Among UA patients, serum C-reactive protein (CRP) levels had a median value of 5.1?mg/l (bottom and top quartile levels, 1.50–7.95). There was no significant correlation between closure time and CRP levels (r?=?0.22,?P?=?0.29). Our data show that, in patients with unstable angina there is an increase of platelet reactivity in response to ADP/collagen stimulation, which is not related to inflammation.     

Increased platelet reactivity in unstable angina patients is not related to C-reactive protein levels

Platelets are a major component of thrombi, and coronary thrombosis plays a key role in the pathogenesis of unstable angina (UA). Whether platelet aggregability is increased in UA patients however, is not known. Furthermore, no study has investigated the relationship between platelet reactivity and inflammation in UA patients In this study, venous blood samples were collected at admission in coronary care unit in 37 patients with unstable angina (Braunwald class IIIB) and in 37 sex- and age-matched patients with chronic stable angina (CSA). Patients taking thienopyridine or anticoagulant drugs were excluded from the study, as also were excluded patients with a history of acute myocardial infarction in the previous 12 months. Platelet aggregability was measured on flowing blood as time to occlude a ring coated with collagen-adenosine diphosphate (ADP), using the platelet function analyzer (PFA-100) system. By this method, the time to occlusion (closure time) is taken as a measure of platelet adhesion/aggregability, with shorter times indicating greater platelet reactivity.There were 23 men and 14 women in both groups, and age was 67.7 +/- 8 and 67.5 +/- 8 years in UA and SA, respectively (P = 0.93). Closure time was significantly reduced in UA patients (78.8 +/- 14 s), compared to SA patients (93.3 +/- 19 s, P < 0.001). Among UA patients, serum C-reactive protein (CRP) levels had a median value of 5.1 mg/l (bottom and top quartile levels, 1.50-7.95). There was no significant correlation between closure time and CRP levels (r = 0.22, P = 0.29). Our data show that, in patients with unstable angina there is an increase of platelet reactivity in response to ADP/collagen stimulation, which is not related to inflammation.     

Pentamidine-induced beta cell toxicity is not preventable by high glucose

The incidence of beta cell damage attributable to pentamidine treatment of pneumocystis pneumonia is increasing in frequency because of the AIDS epidemic. We carried out in vitro studies in perfused rat islets using insulin secretion as an index of beta cell damage to study the effects of pentamidine and to test whether glucose can prevent toxicity in this physiologic model. Isolated islets were cultured for 16-18 hours of static incubation, in a culture medium containing 100 mg/dl glucose, with or without pentamidine (10(-6) M, a therapeutic concentration). Islets were then perfused with media containing 60 mg/dl followed by 300 mg/dl glucose concentrations to study the insulin secretory response. Incubation of islets with pentamidine was associated with subsequent basal hypersecretion of insulin (0.40 +/- 0.05 microU/islet .5 minute vs. 0.18 +/- 0.04 microU/islet .5 minute, p less than .005), and an insulin secretory response to glucose which was completely abolished (0.05 +/- 0.04 microU/islet .5 minute versus 1.12 +/- 0.02 microU/islet .5 minute, p less than .005). To determine whether glucose may protect against the effects of pentamidine, islets were then exposed to high glucose concentrations during simultaneous incubation with pentamidine. Coincubation with high glucose did not prevent these insulin secretory defects. A more extended culture of pentamidine-treated islets in the absence of pentamidine and at a glucose concentration of 100 mg/dl did not result in any recovery of insulin secretion. We conclude that pentamidine-induced beta cell damage is irreversible, not preventable by incubation with high glucose concentrations, and may therefore result from a mechanism different to that of alloxan.     

Endomysial antibody production is not related to histological damage after in vitro gluten challenge

OBJECTIVE: To determine whether in vitro induction of endomysial antibodies is an in vitro marker of coeliac toxicity. DESIGN: To determine whether in vitro endomysial antibodies induced by gliadin incubation correlate with histological damage induced by in vitro gliadin challenge. METHODS: Small-bowel organ cultures from seven patients with treated coeliac disease were incubated in an organ culture system with gliadin; histological damage was morphometrically evaluated and endomysial antibodies were measured in the organ culture supernatant by indirect immunofluorescence. RESULTS: Although incubation with gliadin caused histological damage, there was no detectable production of endomysial antibody. CONCLUSIONS: In vitro, endomysial antibody induction cannot be used as a marker of coeliac toxicity. Endomysial antibodies are not necessary for generating the histological lesion of coeliac disease.     

Serum retinol binding protein 4 is related to insulin resistance and nonoxidative glucose metabolism in lean and obese women with normal glucose tolerance

CONTEXT: Retinol-binding protein (RBP) 4 is secreted by adipose tissue and is postulated to be a determinant of insulin sensitivity. The mechanisms of RBP4 insulin desensitizing action remain unclear. OBJECTIVE: The aim of the present study was to estimate the relationships between serum RBP4 concentration with insulin sensitivity and oxidative and nonoxidative glucose metabolism in lean and obese women. DESIGN AND PARTICIPANTS: The study group consisted of 67 women with normal glucose tolerance, 27 lean and 40 overweight or obese. Insulin sensitivity was estimated with the euglycemic hyperinsulinemic clamp. Glucose and lipid oxidation was measured with indirect calorimetry in the basal state and during the last 30 min of the clamp. Nonoxidative glucose metabolism was calculated in insulin-stimulated conditions by subtracting glucose oxidation from total glucose metabolism. RESULTS: There was no difference in serum RBP4 concentration between lean and obese women. Serum RBP4 was inversely related to insulin sensitivity and nonoxidative glucose metabolism in the entire group (r = -0.36, P =0.003 in both cases) and within the subgroups of lean (r = -0.41, P =0.034 and r = -0.41, P =0.031) and obese women (r = -0.41, P =0.009 and r = -0.40, P =0.01, respectively). These relationships were independent of potential confounding factors. RBP4 levels were not associated with oxidative metabolism of glucose or lipid. CONCLUSIONS: Our data indicate that serum RBP4 is related to decreased insulin sensitivity, mostly through its association with nonoxidative glucose metabolism.     

Synthetic salmon calcitonin is not diabetogenic in patients with normal or impaired glucose metabolism

The effects of short term administration of 200 MRC U of synthetic salmon calcitonin (sCT) daily on carbohydrate metabolism were investigated in 10 patients with various bone diseases, 3 of whom had type II diabetes mellitus and 3 of whom had impaired glucose tolerance. Blood glucose levels during the nocturnal postabsorptive period, blood glucose and blood insulin (IRI) levels and the ratio of the area under the insulin curve to the area under the glucose curve (AI/AG) after a mixed meal were determined before and after 15 days of treatment. The values before and after sCT treatment were not significantly different, suggesting that high doses of sCT are not diabetogenic and can be given to patients with impaired glucose tolerance or to diabetics, without any risk of deteriorating metabolic control.     

The change in one-hour postload plasma glucose levels,and an analysis of its related factors in abdominally obese Han Chinese men with normal glucose tolerance

ObjectiveThis study was to observe the difference in one-hour postload plasma glucose levels and analyze its related factors in abdominally obese men with normal glucose tolerance (NGT).DesignThis case–control study included 36 abdominally obese men (waist circumference ≥ 90 cm) and 31 non-abdominally obese men (waist circumference < 90 cm) aged 20–50 years with NGT. Cases and controls were matched in age. All subjects underwent oral glucose tolerance test with 75 g of oral anhydrous glucose.Results0.5 and 1-h postload plasma glucose levels were higher in abdominally obese group than in non-abdominally obese group (P < .05). Fasting plasma glucose (FPG), 2 and 3-h postload plasma glucose were similar in the two groups (P > .05). 1-h postload plasma glucose was positively correlated with body mass index (r = 0.454), waist circumference(WC) (r = 0.519), systolic blood pressure (r = 0.456), diastolic blood pressure (r = 0.338), triglycerides (r = 0.439), and negatively correlated with high density lipoprotein cholesterol (r = ? 0.391), 1/fasting insulin (r = ? 0.459), insulinogenic index (r = ? 0.357) and disposition index (r = ? 0.602) (P < .01). In multiple regression analysis, 1-h postload plasma glucose maintained an independent association with disposition index (β = ? 1.367, P = .000), WC (β = 0.103, P = .000) and triglycerides (β = 0.185, P = .017).ConclusionsThe present study demonstrated that the level of one-hour postload plasma glucose was elevated in abdominally obese men with NGT. Besides FPG and 2-h postload plasma glucose, we must also pay attention to the measurement of one-hour postload plasma glucose. Disposition index, WC and triglycerides were independently related factors for elevated one-hour postload plasma glucose.     

新疆维吾尔族空腹血糖受损人群血脂水平变化及低密度脂蛋白胆固醇升高的相关因素分析

目的 分析新疆维吾尔族（维族）IFG人群血脂代谢状况及LDL-C升高的危险因素。 方法 对新疆地区2053例30～80岁维族居民行横断面调查,筛查IFG人群,分析血脂代谢状况及LDL-C相关危险因素。 结果 该IFG人群中,血脂代谢异常的总患病率为99.8%（613/614）。高TG血症患病率为85.5%（525/614）,男女比较,差异无统计学意义（P〉0.05）;高TC血症、高LDL-C血症患病率为72.5%（445/614）和40.7%（250/614）,男性高于女性（75.0% vs 70.1%,52.4% vs 29.9%,P〈0.05）;低HDL-C血症患病率为29.8%（183/614）,男性低于女性（28.0% vs 31.4%,P〈0.05）。Logistic回归分析显示,LDL-C升高的危险因素为年龄、TC、2 hPG。 结论 维族IFG人群血脂代谢异常的总患病为99.8%,其中LDL-C升高的患病率为40.7%,其危险因素为年龄、TC和2 hPG。     

Beta cell desensitization to glucose induced by hyperglycemia is augmented by increased calcium

Chronic hyperglycemia has been shown to induce a decrease in beta cell sensitivity to a subsequent glucose challenge. Calcium is a necessary cofactor in the insulin secretory process and glucose elevates cytoplasmic levels. This study was designed to study whether chronic exposure to different extracellular calcium and glucose concentrations would affect the islets' subsequent response to regulatory stimuli. Islets were isolated and cultured in TC 199 plus 10% beta calf serum, glucose (5.5 or 27.5 mM) and calcium (0.5, 2.5 or 4.0 mM) for 48 h. Following culture, the islets were harvested and incubated a second time in the presence of glucose and/or arginine, theophylline, and trifluoperazine (TFP). Some islets were used for insulin content, protein synthesis studies and/or CO2 production from labelled glucose. Islets cultured in a normal glucose environment with low or normal calcium concentration maintained the capacity to respond to a subsequent glucose or arginine challenge. However, islets cultured in a high glucose or high calcium medium failed to respond to a second glucose or arginine stimulus. Theophylline stimulated insulin secretion from both glucose-sensitive and non-sensitive islets, while trifluoperazine inhibited glucose-stimulated insulin secretion in previously sensitive islets and increased insulin secretion in previously non-sensitive islets. The different culture conditions did not alter insulin content, protein synthesis or glucose conversion to labelled CO2. We conclude that chronic exposure to high glucose decreases beta cell responsiveness to glucose and amino acids. Increased extracellular calcium augmented this response. However, the beta cell remained sensitive to theophylline-induced insulin secretion, while TFP paradoxically increased insulin secretion in the glucose-insensitive beta cells. Protein synthesis and glucose oxidation were not affected by culture conditions. Thus we suggest that the glucose-induced desensitization of the beta cells may be due to alterations in the calcium-dependent release mechanism.     

Infection with Chlamydia pneumoniae but not Helicobacter pylori is related to elevated apolipoprotein B levels

OBJECTIVE: Results of many studies show that apolipoprotein B (apo B) is a better marker of risk of vascular disease than other lipid markers including LDL and HDL-cholesterol and triglycerides. We investigated the association between two infectious agents: C. pneumoniae and H. pylori, known to have an atherogenic effect, and apo B, to evaluate the effects of chronic infections on apo B levels. METHODS AND RESULTS: The study group consisted of 257 patients in whom diagnostic coronary angiography was performed. C. pneumoniae IgG and IgM and H. pylori IgG and IgA antibodies were measured by enzyme-linked immunosorbent assay and apo B levels were measured by the nephelometry method. Established risk factors of atherosclerosis were recorded. Of 257 patients recruited, 104 had normal vessels, 88 had 3 or more vessels obstructed and 65 had ectatic vessels without atherosclerosis. Mean apo B concentration was significantly higher in C. pneumoniae IgG and IgM positive healthy subjects compared with C. pneumoniae negatives (0.954 vs. 0.722 and 0.973 vs. 0.851, p < 0.001 and p = 0.007, respectively). Apo B levels were significantly higher in severe atherosclerotic patients (0.985 +/- 0.234 g/l) compared with control subjects (0.892 +/- 0.244 g/l) (p = 0.008), but the difference was not significant in ectatic subjects (0.946 +/- 0.272 g/l) when compared with controls (p = 0.18). Apo B levels were higher but not statistically significant in H. pylori antibody positive cases when compared with negatives. CONCLUSIONS: Apo B levels increased with C. pneumoniae infection. This finding supports the hypothesis that lipid profiles change to atherogenic lipid profile in chronic infections.     

Glucokinase mediates coupling of glycolysis to mitochondrial metabolism but not to beta cell damage at high glucose exposure levels

Aims/hypothesis  

Glucose is the main stimulus of insulin secretion in pancreatic beta cells. However, high glucose has also been considered to damage beta cells. In this study we examined, with special emphasis on the role of the glucose sensor enzyme glucokinase, whether elevated glucose metabolism evokes toxicity to beta cells.     

Hyperhomocysteinemia in ulcerative colitis is related to folate levels

AIM: To study the prevalence and clinical significance of hyperhomocysteinemia (hHcys), an independent factor for arterial and venous thrombosis, in a group of patients with ulcerative colitis (DC). METHODS: Fasting homocysteine (Hcys), folate, and vitamin B12 serum levels were measured in 40 DC patients and 50 healthy controls. Clinical data regarding DC were gathered. RESULTS: Median serum Hcys levels in DC patients were similar to those in controls (12.26 umol/L vs 12.32 μmol/ L), but the prevalence of hHcys was higher in UC patients than in controls (30% vs 10%, P= 0.028).UC significantly increased the risk of hHcys (adjusted odds ratio: 4.125; 95%CI: 1.26-13.44). Multivariate regression analysis showed that male sex, folate and vitamin B12 deficiency or lower serum values were significant independent predictors of higher Hcys levels in UC patients (r2=0.4;P<0.001). CONCLUSION: hHcys is common in UC patients and it is related to folate and vitamin B12 deficiency or lower serum values. It would be reasonable for patients with UC to receive folate and vitamin B complex supplements as a prophylactic measure.     

The normal insulin response to glucose

Summary Plasma insulin values during a 50 g. oral glucose tolerance test were measured by immuno-assay in 34 control subjects. Peak insulin levels occurred within the first 60 minutes and the fasting level was approached by 120 minutes. The insulin curve closely resembled the blood sugar curve and a significant correlation was found between the blood sugar and plasma insulin values at 60, 90 and 120 minutes after oral glucose. The results suggest that the wide range in plasma insulin response is due in part at least to variations in the blood sugar. The results also tend to confirm that immuno-reactive insulin is biologically significant.

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Die normale Insulinausschüttung nach GlukosegabenDie Beziehung zwischen Blutzucker und Plasma-Insulin

Zusammenfassung Die Plasma-Insulinwerte während der oralen Glukosebelastung mit 50 g Glukose wurden bei 34 Normalpersonen immunologisch gemessen. Die Höchstwerte wurden innerhalb der ersten 60 Minuten erreicht, nach 120 Minuten näherten sich die Spiegel wieder dem Nüchternwert. — Die Insulinkurve ähnelte der Blutzuckerkurve stark. Wir fanden eine signifikante Korrelation zwischen Blutzucker- und Plasmainsulinwerten 60, 90 und 120 Minuten nach der oralen Glukosezufuhr. Die Ergebnisse deuten darauf hin, daß die starken Unterschiede in der Insulinausschüttung zum Teil durch Schwankungen der Blutzuckerwerte bedingt sind. Sie stützen ferner die Anschauung, daß das immunologisch nachweisbare Insulin biologische Bedeutung hat.

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La réponse normale de l'insuline au glucoseRelation entre la glycémie et l'insuline plasmatique

Résumé On a mesuré les valeurs de l'insuline plasmatique, à l'aide du dosage immunologique, pendant un test de tolérance à 50 g de glucose administré par voie orale, chez 34 sujets témoins. Les taux maximums d'insuline se situaient dans les 60 premières minutes, et à 120 minutes les taux étaient proches de ceux à jeun. La courbe de l'insuline ressemblait étroitement à la courbe de la glycémie et on a trouvé une relation significative entre les valeurs de la glycémie et de l'insuline plasmatique, 60, 90 et 120 minutes après l'administration orale de glucose. Les résultats suggèrent que la large bande de variations dans la réponse de l'insuline plasmatique est due, au moins en partie, aux variations de la glycémie. Les résultats tendent également à confirmer que l'insuline immunoréactive est biologiquement significative.