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PubMed1988

Captopril does not alter metabolic control in elderly hypertensive diabetics during secondary failure.

In elderly patients diabetes and hypertension play an important and synergistic role in the development of cardiovascular complications. For this reason therapy must reduce blood pressure without compromising blood glucose control. We investigated the question of whether captopril, an angiotensin converting enzyme inhibitor, can be used without interference to glucose metabolism in diabetics with secondary failure. Ten elderly hypertensive diabetics (diastolic blood pressure greater than 95 mmHg), maintained in good metabolic control using oral hypoglycaemic agents and insulin, were studied before and after 30 days of captopril at 100 mg/day. We measured the following parameters: blood pressure, heart rate, fructosamine and a daily profile for blood glucose and c-peptide. There was a statistically significant reduction in systolic and diastolic blood pressure. No difference was observed in the levels of blood glucose and fructosamine. Insulin secretion as determined by c-peptide levels was not modified, in contrast with findings reported for the use of beta-blockers, diuretics or nifedipine. It seems that captopril is useful and without side effects, even in secondary-failure diabetic patients characterized by unstable metabolic control.

Aged↗
PubMed1988

[Indicators of glycated proteins in the diagnosis of diabetes. Use in populations with a high prevalence of hemoglobinopathies].

The authors compare the relative validity of HbA1c and fructosamine as indices of long-term blood glucose levels in population with a common occurrence of haemoglobinopathies. HbA1c levels in patients with haemoglobinopathies do not reflect the glucidic status of patients when compared to HbA1c levels in reference population. Validity of the fructosamine assay allows its potential use as a mass screening test for diabetes in these populations (USA, Africa, Caribbean...).

Blood Glucose↗
PubMed1995

Vitamin C and glycohemoglobin.

Three groups of 10 age- and sex-matched nondiabetic volunteers took 0, 750, or 1500 mg of vitamin C each day for 12 weeks. Glycohemoglobin (GHb) was measured by HPLC, electrophoresis, affinity chromatography, and immunoassay at baseline (-4 weeks and -1 day), during supplementation (6 weeks and 12 weeks), and after supplementation ended (6 and 12 weeks). Plasma vitamin C increased twofold during supplementation but, in contrast with the results of Davie et al. (Diabetes 1992; 41:167-73), there were no between-group differences in GHb, glucose, and fructosamine concentrations. Fructosamine may have increased with storage time. The net effects of vitamin C on absolute GHb at 12 weeks vs -1 day (and at 12 weeks vs 12 weeks after) in % GHb amounted to: HPLC -0.035 (-0.050); electrophoresis +0.005 (+0.035); affinity chromatography -0.070 (+0.015); and immunoassay -0.110 (+0.025). We conclude that supplementation of nondiabetics with 750 or 1500 mg of vitamin C daily for 12 weeks does not cause interference in GHb determinations by HPLC, electrophoresis, affinity chromatography, or immunoassay, and does not reduce in vivo Hb glycation.

Adult↗
PubMed1995

[Recent progress in evaluation of glycemic control by glycated protein and 1,5-AG].

The aim of treatment of diabetes is to prevent the progress of diabetic complications. A recent report by the DCCT (Diabetes Control and Complications Trial) clearly shows the importance of strict glycemic control for prevention of diabetic complications. For this purpose, some markers for long-term glycemic control other than glucose concentration will be helpful, because glucose levels fluctuate too severely to assess whether they are precise. HbA1c is the longest established marker for glycemic control but still large interlaboratory variation is present. The standardized procedure for measurement of HbA1c was just proposed by the Japan Diabetes Society. Fructosamine is measured by a simpler procedure but many deoxidizing materials in serum especially superoxide may interfere with the reaction. Glycated albumin should be more reliable than fructosamine but a standard method of measurement has not been established yet. Future measurement of advanced glycation end product (AGE) should prove to be good marker for not only glycemic control but also diabetic complications or diagnosis of diabetes. The decrease in serum 1,5-anhydro-D-glucitol(1,5-AG) is very sensitive to urinary glucose excretion and may be useful as a marker of glycemic control and diagnosis of diabetes.

Biomarkers↗
PubMed1994

[Prevalence estimates for non-insulin dependent diabetes mellitus (NIDDM) in Japan from National Survey of Circulatory Disorders 1990 data].

Prevalence of diabetes mellitus in Japan was estimated from fructosamine and hemoglobin A1c measurement data obtained from the National Survey of Circulatory Disorders 1990, using a previously reported method which used the results of a screening test for estimating true prevalence. The prevalence for males was higher than that for females. The prevalences were less than 10% for those 49 years or younger and approximately 20% for those 50 years or older. The estimated values derived from fructosamine or hemoglobin A1c did not vary considerably.

Adult↗
PubMed1994

Fluorescence-determined kinetics of plasma high oxidability in diabetic patients.

The peroxidative potential of whole plasma was studied in thirteen control subjects and twenty-three diabetic patients divided into two groups on the basis of their metabolic control, defined as good (n = 12) or poor (n = 11) according to the fasting blood glucose, glycated hemoglobin and fructosamine levels. The amounts of thiobarbituric reactive substances (TBARS) were determined before and after an exhaustive peroxidation induced by incubation with cupric sulfate; the kinetics of Cu-dependent plasma peroxidation, determined by the time course of endogenous fluorescence emission at 430 nm, were also evaluated. Our data indicate that in diabetic patients, and particularly in those with a long-lasting poor metabolic control, a significant increase in plasma susceptibility to peroxidative stress is evident only when we consider the lag-time of fluorescence emission in the course of Cu-induced plasma peroxidation. A good inverse correlation was observed between the lag-time and the blood glucose concentration, the glycated hemoglobin and the fructosamine blood levels. Furthermore a multivariate analysis, performed by Principal Component Analysis, strongly supports the relation between the extent and duration of the diabetic pathology, and the decrease in the lag-time of oxidation.

Aged↗
PubMed1993

Streptozotocin induced cardiomyopathy in diabetic rats.

Microscopic quantitative cardiomyopathy was previously reported in spontaneous diabetic biobreeding (BB) rats, but the nature of the lesions remains obscure. To further study the specificity of cardiomyopathy in streptozotocin-diabetic rats and discuss the existence of diabetic heart disease, we compared 40 streptozotocin-diabetic rats (D group) with 40 normal control rats (C group) at various durations in plasma glucose, fructosamine, plasma lipid, left ventricular enzyme contents and alterations of myocardial cells and coronary artery tree under electron and light microscope respectively. In 4 weeks, D rats showed myocardial mitochondrial swelling and degeneration, whereas at 8 weeks, myocardial enzyme contents markedly decreased, and myocardial lesions were more conspicuous with disruption of myocardial cells, formation of myocardial contraction bands, dilatation of intercalated discs, deposition of glycogen granules, etc. At 11 weeks, microscopic changes were essentially similar, whereas the decrease of enzyme contents became more conspicuous. During the 11 weeks, persistent and marked hyperglycemia and elevation of fructosamine were observed, however, no abnormalities were found along the coronary artery tree in the D rats. The results indicated that cardiomyopathy is diabetes specific, and exists independently as one of the three important components of diabetic heart disease.

Animals↗
PubMed1993

Selective determination of non-enzymatic glycosylated serum albumin as a medium term index of diabetic control.

Serum proteins are non-enzymatically glycosylated dependent on the concentration of free glucose and measurements of their concentration are used to control diabetic carbohydrate metabolism. Eight patients with insulin-dependent diabetes mellitus (IDDM) and 8 patients with non-insulin-dependent diabetes mellitus (NIDDM) with glycosylated hemoglobin levels of at least 10.5% were studied during a 6-week period of antidiabetic therapy. Glycosylated serum albumin (GSA) and glycosylated total serum proteins (GSP) were measured weekly using an affinity chromatography procedure. The fructosamine test (FA) and the measurement of mean blood glucose (MBG) were also carried out weekly. Glycosylated hemoglobin and its glucose adduct HbA1c were determined at 14-day intervals (HPLC-method). All measured parameters decreased during the period of the study. The correlation coefficients for the glycosylated proteins versus the MBG determined one week earlier were highest for GSA [IDDM: r(GSA/MBG-1) = 0.726, p < 0.001 for the single values and 0.984, p < 0.001 for the mean values; NIDDM: r (GSA/MBG-1) = 0.636, p < 0.001 for the single values and 0.986, p < 0.001 for the mean values]. The differences between the IDDM and NIDDM group probably occurred because 6 NIDDM patients were taking glibenclamide (7.0-10.5 mg/day) which is known to inhibit the glycosylation reaction of albumin. The fructosamine test is more prone to interferences than the selective determination of GSA. GSA determination therefore, gives precise data in medium term diabetic control.

Adult↗
PubMed1993

[Correlations of the levels of HbA1c with plasma apoproteins and plasma lipoproteins in type II diabetic patients].

Plasma apolipoproteins from VLDL, LDL and HDL lipoproteins were measured in 56 male patients with age range 50-60 years and noninsulin-dependent diabetes mellitus (type II) and 81 normal volunteers. Diabetic patients were further divided into two subgroups according to the HbA1c (glycated haemoglobin) concentrations, lower than 7% and higher than 7% respectively, after considering that HbA1c levels may be an appropriate index to monitor long-term blood glucose level. The studied groups, control and diabetic patients, were well matched with regard to age, % of smokers, % drinkers and % hypertensive and physical activity. The relationships between glucose, fructosamine and % HbA1c levels were investigated. In addition, the relationships between glucose, fructosamine, HbA1c levels and apolipoproteins from the lipoproteins were also studied. A significant correlation (p < 0.05) between glucose/fructosamine, glucose/HbA1c and fructosamine/HbA1c was found in both groups of diabetic patients with HbA1c lower than 7% and higher than 7% respectively. However HbA1c levels were positive and significantly (p < 0.05) correlated with the Apo-B and Apo-E and negative but significantly correlated (p < 0.05) with Apo-CII and Apo-CIII from VLDL particle in both groups of diabetic patients.

Apolipoproteins↗
PubMed1993

Glycated calmodulin from platelets as an index of glycemic control.

In an effort to test whether a significant fraction of calmodulin would become glycated within the life span of the platelet (10-14 days), we monitored the kinetics of calmodulin glycation in vitro. Under the conditions we used, the fraction of glycated calmodulin reached a maximum (approximately 21%) within 10 days. We then extended the studies to human subjects. The intraplatelet concentrations of calmodulin and glycated calmodulin from age-matched type I diabetic subjects were monitored by a combination of m-aminophenylboronate affinity chromatography and enzyme-linked immunosorbent assay. The results indicate that the concentrations of total intraplatelet calmodulin (nonglycated plus glycated) were not dependent on the glycemic state of the subjects. Data from control and diabetic subjects showed a poor correlation between the concentrations of glycohemoglobin and of glycated calmodulin. However, a better correlation was obtained when glycated calmodulin concentrations were compared with those of serum fructosamine. The fraction of glycated calmodulin in the control population (7.71% +/- 0.75%) was significantly (P < 0.05) different from that of the diabetic population (21.6% +/- 1.26%). Given that the clinical role of the fructosamine assay remains controversial, estimation of glycated calmodulin in platelets might be useful as a short time-window index of glycemic control.

Adolescent↗
PubMed1995

[Recent progress in diagnoses of diabetes and its complications].

Most of diabetics have no symptoms and chemical analyses may be sole way to diagnose the disease itself and its complications. Chemical analyses are also important to assess the propriety of glycemic control during every possible treatment of diabetes. Some markers for long-term glycemic control other than glucose concentration may be also used as a screening methods for glucose intolerance. HbA1c is established for long term as a marker for glycemic control but still large interlaboratory variation is present. Fructosamine is measured by a simpler procedure but many deoxidizing materials in serum especially superoxide may interfere with the reaction. Glycated albumin should be more reliable than fructosamine but a standard method of measurement has not been established yet. The decrease in serum 1,5-anhydro-D-glucitol(1,5-AG) is very sensitive to urinary glucose excretion and may be useful as a marker of glycemic control and diagnosis of diabetes. Discrimination of Type I(IDDM) from Type II(NIDDM) in Japanese diabetic patients is sometimes very difficult and evidences of autoimmunity by anti-glutamic acid decarboxylase(GAD) antibody and of exhaustion of insulin secretion by C-peptide measurement 6min after combined infusion of 1mg of glucagon and 20ml of 50% glucose are the few methods to diagnose. Early diagnosis of diabetic complication is another important point of clinico-chemical determinations. Usually, each diabetic complication progresses in parallel. Micro-measurement of urinary transferrin is one of the most sensitive methods likewise urinary microalbumin measurement. Future measurement of advanced glycation end product (AGE) may also tell us if patients are suffering from diabetic complications or if one is suffering from diabetes or not.

Biomarkers↗
PubMed1995

[Elevated plasma prekallikrein level in patients with diabetes].

The contact activation of intrinsic pathway in the coagulation system accompanied by plasma kallikrein-induced kinin generation is thought to be involved in the pathogenesis of diabetic retinopathy. Plasma prekallikrein (PPK), a proenzyme of plasma kallikrein, is a single-chain glycoprotein synthesized mainly in the liver. The aim of our study was to evaluate plasma prekallikrein level in diabetic patients and to examine the relationship between PPK and the metabolic control of diabetes and development of retinopathy. In 53 diabetic patients and 33 healthy subjects as controls the following parameters have been assessed: plasma prekallikrein, serum fructosamine, glycated haemoglobin HbA1c, prothrombin time, partial thromboplastin time and antithrombin III (AT III). Compared to the control group, PPK level was significantly higher in diabetics, especially in patients with proliferative retinopathy. The significant positive correlations have been found between PPK and HbA1c in diabetic patients and between PPK and serum fructosamine concentration but only in diabetics without retinopathy. No differences in prothrombin time and AT III have been observed between diabetics and healthy subjects. A suggestion is presented on increase of plasma prekallikrein level in diabetics due to hyperglycaemia-stimulated glycoprotein over-synthesis in the liver, what would confirm the role of kallikrein-kinin system in the pathogenesis of microangiopathy.

Adult↗
PubMed1996

Glucose monitoring as a guide to diabetes management. Critical subject review.

PURPOSE: To encourage a balanced approach to blood glucose monitoring in diabetes by a critical review of the history, power and cost of glucose testing. DATA SOURCES: The Cambridge Data Base was searched and was supplemented by a random review of other relevant sources, including textbooks, company pamphlets, and laboratory manuals. STUDY SELECTION: Keywords used were "glucosuria diagnosis," "blood glucose self-monitoring," "glycosylated hemoglobin," and "fructosamine" for the 10-year period ending 1992, restricted to English language and human. DATA EXTRACTION: About 200 titles were retrieved and reviewed according to the author's judgment of relevance. FINDINGS: "Snapshot tests" (venous and capillary blood glucose) and "memory tests" (urine glucose, glycated hemoglobin fractions and fructosamine) must be employed according to individual patients treatment goals. Day-to-day metabolic guidance is facilitated by capillary blood glucose testing for patients receiving insulin and by urine glucose testing for others. Capillary blood glucose testing is mandatory in cases of hypoglycemia unawareness (inability to sense hypoglycemia because of neuropathy) but is not a substitute for a knowledge of clinical hypoglycemia self-care. Criteria by reason (clinical judgement and cost effectiveness) must be separated from criteria by emotion (preoccupation with technology and marketing). No randomized studies show that any of these tests consistently improve clinical outcome. Optimal metabolic control and cost savings can be expected from a rational selection of tests.

Blood Glucose↗
PubMedDate not supplied

[Fluorescent products in the crystalline lens of type ii diabetic patients].

A body of evidence suggests that glycation of proteins and the resulting fluorescent products take part in the late complications of diabetes. The purpose of this study was to analyse the fluorescence of lens soluble proteins from diabetic patients. Soluble proteins were obtained from lens with cataract from 20 type II diabetic patients and from 21 non diabetic controls with similar age. The fluorescence of the soluble fraction (EX-360 nm, EM -454 nm) was quantified as a parameter for glycation end products. The glycation of plasma proteins was quantified by fructosamine levels. The fluorescence mean in the group of diabetics was about twice the non diabetic value (p < 0.01). The fluorescence in the diabetics with retinopathy was higher than that of diabetic without retinopathy (p < 0.01). Fructosamine levels were: diabetics 3.1 +/- 1.1 mM, non diabetics 1.9 +/- 0.8 mM (p < 0.001). The results suggest the involvement of fluorescent products, resulting from glycation of proteins, in lens opacification in diabetic patients.

Aged↗
PubMed1997

Variable glycation of serum proteins in patients with diabetes mellitus.

OBJECTIVE: To determine whether there were variations in vivo and in vitro in the glycation process among patients with diabetes mellitus and to assess the characteristics of patients with high and low glycation, if this was observed. PATIENTS: Patients (n = 185) attending a Diabetes Day Care Centre or Notre-Dame Hospital in Montreal participated in the in vivo study. Patients found to have high and low glycation were asked to allow the use of their serum for the in vitro part of the study. INTERVENTION: Capillary blood glucose levels were determined by nursing staff 4 times a day over 7.3 (standard deviation [SD]5.3) consecutive days with commercially available glucose oxydase reagent strips and meters. The ratio of the fructosamine concentration to the protein concentration (the F/P ratio) and the glycated hemoglobin were also determined at the same time as the capillary blood glucose level. Glycation was defined as the mean capillary blood glucose/F/P ratio. Patients with high and low glycation (higher or lower than [SD], of the mean) were compared. For the in vitro study, incorporation of carbon-14 glucose in serum proteins incubated with a 30-mmol/L glucose concentration was studied in some of the patients with low and high glycation. RESULTS: The mean capillary blood glucose/F/P ratio was a mean of 2.30 (SD 0.29) g/mL. Of the 185 subjects 31 had high glycation (1.46 [SD 0.19] g/mL) and 27 had low glycation (2.97 [SD 0.035] g/mL, p < 0.001). There was no significant difference in age, sex, diabetic treatment and glycated hemoglobin levels between the 2 groups. However, patients with low glycation had a greater body mass index (29.4 [SD 5.7] kg/m2 v. 26.4 [SD 4.3] kg/m2, p < 0.05). In vitro, incorporation of 14C glucose in serum proteins incubated with a 30mmol/L glucose concentration was higher in the 9 patients with high glycation than in that of the 7 with low glycation (0.031% [SD 0.03%] per gram of proteins v. 0.028% [SD 0.03%] per gram of proteins, p < 0.02). CONCLUSIONS: Glycation may vary among patients with diabetes mellitus who have similar capillary blood glucose concentrations. Glycation appears to be lower in patients with a greater body mass index. Furthermore, alternation in the glycation process itself may explain, in addition to the mean blood glucose level, the difference in fructosamine levels.

Adult↗
PubMed1997

[Glycosylated hemoglobin and glycosylated proteins for metabolic control of diabetes mellitus].

The target of therapy in patients with diabetes mellitus is preventing the development of late complications due to nearly normal blood glucose values. For the diagnosis and control of therapy in routine management of diabetes mellitus, determination of glycated haemoglobin (HbA1c) and fructosamine in addition to blood glucose values are of equal importance. This report stresses the clinical use, standard-determination methods and interpretation of glycated protein values. The problems of haemoglobin variants detected in Austria interfering with determination of HbA1c using the high performance liquid chromatography method and the suggestions of the American Diabetes Association for using glycated haemoglobin and fructosamine are discussed as well.

Blood Glucose↗
PubMed2003

Serum leptin levels in female patients with NIDDM.

OBJECTIVE: To compare serum leptin levels of diabetic and non-diabetic female subjects and also assess the relationship of hyperglycemia with serum insulin, C-peptide and leptin levels. DESIGN: It is a case control study. PLACE AND DURATION OF STUDY: The study was conducted at Medicare Hospital, Family Care Clinic and Baqai Institute of Diabetes and Endocrinology between December 1997 to September 1999. SUBJECT AND METHODS: One hundred and forty female subjects with different body mass indices and fasting blood sugar levels were selected from three different diabetic centers. A venous sample was drawn after an overnight fast (12 hours) for determination of blood parameters in all groups. Glycosylated hemoglobin, hexosamine, fructosamine, insulin and C-peptide were determined only in diabetic patients. Blood glucose, triacylglycerol (TAG), total cholesterol, HDL cholesterol, HbA1C, hexosamine and fructosamine were determined enzymatically. Serum leptin, C-peptide and insulin were measured using enzyme-linked immunoassay. RESULTS: Serum leptin levels of obese diabetic and non-diabetic subjects were significantly higher as compared with lean diabetic patients and non-diabetic subjects (P< 0.05). Leptin levels were positively correlated with serum insulin and C-peptide levels. Serum leptin increased with increase in body mass index and waist hip ratio was strongly related with insulin resistance in NIDDM. CONCLUSION: Leptin levels are increased in obesity and may play a role in development of insulin resistance and NIDDM.

Adult↗
PubMed2004

Serum concentrations of IGF-I, IGFBP-3 and c-peptide and risk of hyperplasia and cancer of the breast in postmenopausal women.

Experimental evidence suggests that insulin and insulin-related growth factors may play a role in breast pathology through their mitogenic and anti-apoptotic effects on breast cells. Our objective was to assess the relationship between serum concentrations of insulin-like growth factor-I (IGF-I), its major binding protein (IGFBP-3), the ratio IGF-I:IGFBP-3, c-peptide (a marker of insulin secretion) and the ratio c-peptide:fructosamine (a marker of insulin resistance) and the risk of epithelial hyperplasia (an established breast cancer risk factor) and localized breast cancer among postmenopausal women. Study subjects were patients who provided serum before breast biopsy or mastectomy in 3 hospitals in Grand Rapids, MI between 1977 and 1987. Two case groups, 186 subjects with epithelial hyperplasia of the breast and 185 subjects with localized breast cancer, were compared to 159 subjects with nonproliferative breast changes that have not been associated with increased breast cancer risk. Serum concentrations of IGF-I, IGFBP-3 and the ratio IGF-I:IGFBP-3 were not related to risk of either hyperplasia or breast cancer. For women in the highest quartile of c-peptide or of c-peptide:fructosamine compared to those in the lowest quartile, the odds ratios (ORs) for hyperplasia were 3.0 (95% confidence interval [CI] 1.4-6.5) and 3.3 (95% CI 1.5-7.3), respectively (p trend = 0.02 and 0.02, respectively). The corresponding ORs for breast cancer were 1.5 (95% CI 0.7-3.0) and 1.6 (95% CI 0.8-3.2), respectively (p trend = 0.35 and 0.25, respectively). Our results suggest that insulin and insulin resistance may play a role in breast pathology in postmenopausal women.

Adult↗