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PubMed1994

Glomerular hyperfiltration in young Polynesians with type 2 diabetes.

An increase in glomerular filtration rate (hyperfiltration) may be an important early event in the initiation of diabetic nephropathy but the prevalence of hyperfiltration appears to vary between different populations with type 2 diabetes. We have measured glomerular filtration rate using 51Cr EDTA clearance in 15 young Polynesians (mean age 32 years), 1-30 months after the initial diagnosis of type 2 diabetes and 15 control Polynesian subjects of comparable age and sex distribution. The mean glomerular filtration rate in the diabetic subjects (216 ml/min) was 57% greater than that of the controls (137.5 ml/min, P < 0.0001). About one-third of their excess in glomerular filtration rate could be accounted for by the marked obesity of the diabetic subjects, but even after correcting for body size the diabetic subjects still had a significantly higher mean glomerular filtration rate than controls (165.6 vs. 119.6 ml/min per 1.73 m2, P < 0.001); 73% of the diabetic subjects had hyperfiltration (> 140 ml/min per 1.73 m2). The diabetic subjects were normotensive but nonetheless had increased rates of albumin excretion (median 61 versus 9 mg/day, P < 0.001). We conclude that hyperfiltration is common in young Polynesians with recently diagnosed type 2 diabetes. Prospective studies are needed to determine whether this early abnormality of renal function heralds the later development of overt nephropathy.

Adult↗
PubMed1994

Indications of reduced pulmonary function in type 1 (insulin-dependent) diabetes mellitus.

Abnormalities of pulmonary function tests have been described in type 1 (insulin-dependent) diabetes mellitus (IDDM). To better characterise such abnormalities and to verify whether these latter are associated with the presence of diabetic microvascular disease we compared 23 non-smoking patients who had IDDM with 24 non-smoking healthy control subjects strictly matched for sex, age, and body mass index. Compared with controls, diabetic patients had a reduced forced vital capacity (FVC) (87.5 +/- 13.1% vs. 96.4 +/- 13.6% of the predicted; P = 0.03) and forced expiratory volume in 1 s (FEV1) (90.5 +/- 17.7% vs. 101.2 +/- 13.2% of the predicted; P = 0.02). While within the group of patients the presence of retinopathy and autonomic neuropathy were not associated with modifications of pulmonary function tests, those with altered urinary albumin excretion rate (AER > or = 20 micrograms/min; range 21-589) (n = 7) had a significantly lower pulmonary diffusion capacity (DLCO) than the 16 normoalbuminuric subjects (62.6 +/- 7.2% vs. 88.7 +/- 20.1% of the predicted; P = 0.01). Moreover, in the group of patients, DLCO was inversely related with AER (r = -0.43; P = 0.04). In conclusion, IDDM is characterised by reduced FVC and FEV1, while a significant decrease in DLCO may be considered as selectively associated with renal disease.

Adult↗
PubMed1995

Metabolic control quality and free radical activity in diabetic patients.

The role of oxidative/reductive balance derangement in the pathogenesis of diabetic microangiopathy has often been discussed in the last few years. Therefore, we decided to evaluate the influence of intensive insulin therapy on selected indicators of free radical production. The levels of plasma hydrogen peroxide (H2O2) and serum malonyldialdehyde (MDA) were estimated in 15 patients with Type 1 and 15 with Type 2 diabetes before and after 2 weeks of intensive treatment. The initial H2O2 and MDA levels in all cases were significantly higher than in controls. After 2 weeks of treatment, the values for both estimated parameters were significantly lower; however, they were still higher than in the control group. Our results seem to confirm the previous suggestions concerning the relation between metabolic disturbances and oxidative stress in diabetic patients.

Adolescent↗
PubMed1995

Renin-aldosterone axis in normoalbuminuric insulin-dependent diabetes mellitus patients with glomerular hyperfiltration.

The renin-aldosterone axis was evaluated by captopril test in 22 normotensive normoalbuminuric insulin-dependent diabetes mellitus (IDDM) patients with and without glomerular hyperfiltration. Patients were divided into those with glomerular hyperfiltration (Hf-IDDM) and with normal glomerular filtration rate (GFR; Nf-IDDM) according to the upper limit of GFR (134.7 ml/min per 1.73 m2). Sixteen normal individuals were also studied. GFR was measured by the 51Cr-EDTA single injection method, extracellular fluid volume as the distribution volume of 51Cr-EDTA, and blood volume using 51Cr-sodium chromate-labelled red blood cells. Twenty-five mg of captopril were administered per os and plasma renin activity (PRA; RIA), plasma aldosterone (RIA) and blood pressure were measured at 0 and 120 min post-captopril. PRA at time zero (Hf-IDDM = 2.4 +/- 1.7; Nf-IDDM = 2.5 +/- 1.9; controls = 1.0 +/- 0.6 ng/ml/h) and at 120 min (Hf-IDDM = 9.9 +/- 8.3; Nf-IDDM = 11.2 +/- 8.9; controls = 5.4 +/- 5.7 ng/ml/h) was higher in IDDM patients than in controls (P = 0.01). The increase of PRA was similar in patients (Hf-IDDM = 7.5 +/- 7.3, and Nf-IDDM = 8.7 +/- 7.2 ng/ml/h) and controls (4.4 +/- 5.3 ng/ml/h). There was no difference in PRA levels between Hf-IDDM and Nf-IDDM patients. PRA did not correlate with GFR, aldosterone, blood pressure, blood volume, duration of diabetes, 24-h urinary sodium and metabolic control indexes. Plasma aldosterone and the magnitude of its decrease after captopril was similar among patients and controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Synthesis, structure-activity relationships and a reaction mechanism for mutagenic N-nitroso derivatives of glycosylamines and Amadori compounds--model substances for N-nitrosated early Maillard reaction products.

A series of nine glycosylamines and an Amadori compound were synthesized, together with their N-nitroso derivatives. Their structures were established by physico-chemical and spectroscopic data and elemental analyses. The N-nitroso compounds were further characterized by denitrosation with hydrogen bromide-acetic acid, followed by detection of the liberated NO by a chemiluminescence detector. N-Nitroso derivatives of N-p-nitrophenyl/p-methylphenyl/p-carboxyphenyl pentopyranosylamines, N-p-methylphenyl-1-deoxy-D-fructosylamine (the Amadori compound) and N-3-ethylindole-D-xylopyranosylamine were shown to be direct-acting mutagens in Salmonella typhimurium TA100. The activity of some of the compounds was similar to that of N-ethyl-N-nitrosourea. Their mutagenic activity was shown to depend on the structure of the amine and the sugar moieties and to require the presence of free hydroxyl groups in the sugar. The mutagenicity of N-nitrosoglycosylamines was attributed to their hydrolysis to arenediazonium cations. The formation of these compounds was detected by azo-coupling with N-ethyl-1-naphthylamine, using spectrophotometric and mass spectrometric analyses. These data implicate arene(alkyl)diazonium cations as the ultimate mutagens of N-nitrosoglycosylamines (and possibly of N-nitroso Amadori compounds), a little-explored class of N-nitroso compounds that may be formed in vivo.

Amino Sugars↗
PubMed1988

A colorimetric method for the estimation of serum glycated proteins based on differential reduction of free and bound glucose by sodium borohydride.

A new colorimetric method based on the phenol-sulfuric acid reaction is described for the estimation of serum glycated proteins by the differential reduction of free glucose and hexose bound nonenzymatically with 2.0 and 20 mg of NaBH4 in 0.02 ml of serum, respectively, at room temperature for 15 min. The values (microgram hexose/mg protein) in control subjects (n = 60) and diabetics (n = 90) were estimated to be 5.60 +/- 0.85 and 10.8 +/- 1.6, respectively. The increase was highly significant (P less than 0.001) in diabetics. The serum glycated protein levels correlate well with fasting blood sugar values (r = 0.77, P less than 0.001, n = 25). There was also a highly significant correlation between glycated protein level and glycated albumin value in individual serum samples (r = 0.85, P less than 0.001, n = 25). Values of borohydride reducible glyco-groups bound to serum proteins also correlated well with serum glycated protein levels (r = 0.96, p less than 0.001, n = 20) determined by the thiobarbituric acid assay method. The method is found to be simple and rapid, with a coefficient of variations of +/- 3.8%.

Blood Glucose↗
PubMed1994

Low-dose dietary L-arginine increases plasma interleukin 1 alpha but not interleukin 1 beta in patients with diabetes mellitus.

Oral high-dose arginine supplementation is used for the experimental immunotherapy of tissue trauma and sepsis. Yet the adequate dosage required for immunomodulation has to be established and the toxicity of high-dose arginine has not been fully elucidated. Following a protocol for the treatment of diabetic long-term complications (oral daily doses of 30 mg/kg BW; blind, placebo-controlled prospective study with crossing-over design) we studied plasma levels of interleukins 1 alpha (IL-1 alpha) and 1 beta reflecting immunostimulation. Arginine supplementation in 29 patients with diabetes mellitus prompted a 2-fold increase of IL-1 alpha from baseline levels (P < 0.001) while IL-1 beta was unaffected. Implications for the treated panel of diabetic patients could be a reduction of collagen accumulation by enhanced collagenolysis and clearance of advanced-stage non-enzymatic glycosylation products. Based upon our data, low-dose arginine protocols for further immunotherapeutical studies should be discussed.

Aged↗
PubMedDate not supplied

Does adequate control of diabetes in the preinfarction period improve the short-term postinfarction course?

It is uncertain whether adequate preinfarction diabetes control would alter the clinical outcome in diabetic patients once myocardial infarction has occurred. This study attempts an evaluation. Diabetic patients admitted successively to the cardiac intensive care unit with their first acute myocardial infarction were enrolled and followed throughout hospitalization. Every fourth consecutive patient with infarction, but not diabetic, was assigned to a control group. All patients were kept in the cardiac care unit for at least 48 h and vital signs and cardiac arrhythmias were continuously monitored. Radionuclide ventriculography was done within 24 h of admission and again upon discharge. When feasible, patients with postinfarction angina underwent coronary balloon angioplasty. During a 1-year period, 49 diabetic patients were studied, while 18 comparable nondiabetic patients served as controls. Diabetes was considered adequately controlled in 16 patients with glycosylated hemoglobin (HbA1c) of 8.8 +/- 0.7%, whereas in 33 patients diabetes was uncontrolled (HbA1c 14 +/- 3%), p < 0.001. No difference was found in the extent of infarct size, occurrence of heart failure, arrhythmias, and mortality when comparing the adequately with the inadequately controlled diabetics during a hospitalization period of 11 days. In diabetics, no differences were found in the short-term clinical course after acute myocardial infarction, whether the diabetes was adequately controlled or not in the preinfarction period.

Analysis of Variance↗
PubMed2006

Diphenyl diselenide reduces temporarily hyperglycemia: possible relationship with oxidative stress.

This study was designed to determine the effect of diphenyl diselenide and ebselen, synthetic organoselenium compounds with antioxidant properties, in diabetic rats. Diabetes was induced by the administration of streptozotocin (STZ) (45mg/kg, intravenous). In experimental trials, diphenyl diselenide, but not ebselen, caused a significant reduction in blood glucose levels of STZ-treated rats. This effect of diphenyl diselenide was accompanied by a reduction in the levels of glycated proteins. Diphenyl diselenide ameliorate superoxide dismutase activity (liver and erythrocytes) and Vitamin C levels (liver, kidney and blood), which were decreased in STZ-treated rats. In normal rats, diphenyl diselenide caused per se an increase in hepatic, renal and blood GSH levels. Similarly, treatment with diphenyl diselenide restored hepatic and renal GSH levels in STZ-treated rats. TBARS and protein carbonyl levels were not modified by STZ and/or diphenyl diselenide and ebselen treatments. Our findings suggest that diphenyl diselenide can be considered an anti-diabetogenic agent by exhibiting anti-hyperglycemic and antioxidant properties.

Alanine Transaminase↗
PubMed2004

Postprandial versus preprandial dosing of biphasic insulin aspart in elderly type 2 diabetes patients.

Preprandial dosing (within 5 min before meal) and postprandial dosing (15-20 min after meal onset) of NovoLog Mix 70/30 (BIAsp 30, a biphasic formulation of insulin aspart, 30% soluble and 70% protamine-crystallized) were compared in elderly (> or =65 years) type 2 diabetes patients in this open-label, 12-week, crossover study. Ninety-three patients were treated with b.i.d. preprandial injections of BIAsp 30 during a 2-week run-in period and subsequently randomized to a 4-week treatment with either pre- or postprandial b.i.d. BIAsp 30, followed by crossover to the other regimen for 4 weeks. Mean plasma glucose values during a 4-h mealtest at the end of each treatment were similar for pre- and postprandial BIAsp 30 (153 +/- 58 mg/dl and 161 +/- 59 mg/dl, respectively, difference not significant). However, the mean blood glucose increment from self-measured blood glucose values was slightly but significantly greater after postprandial injection than after preprandial injection (treatment difference: 16.3mg/dl; 95% CI: [0.5, 29.3]). Fifty-six percent of patients reported a hypoglycemic episode; postprandial injection did not increase the incidence of hypoglycemia as compared to preprandial injection (113 episodes versus 125 episodes, respectively). For some elderly type 2 diabetes patients, postprandial injection of BIAsp 30 may be an acceptable alternative to standard preprandial injection.

Aged↗
PubMed2005

Improvement in C-reactive protein and advanced glycosylation end-products in poorly controlled diabetics is independent of glucose control.

We studied the efficacy of four different treatment regimens (sulphonylurea and metformin+/-acarbose versus glimepiride and rosiglitazone versus glimepiride and bedtime NPH insulin versus multiple actrapid and NPH insulin injections) in poorly controlled type 2 diabetes subjects on hs-CRP, VCAM-1 and AGE at 4, 8 and 12 weeks of treatment. Multiple insulin injections rapidly improved HbA(1c) by 0.6+/-0.9% (p<0.005), 1.2+/-1.3% (p<0.0005) and 1.3+/-1.4% (p<0.0005) at week 4, at week 8 and week 12, respectively. Subjects who continued their existing combination treatment of sulphonylurea, metformin+/-acarbose also showed a significant reduction in HbA(1c) (p<0.05). Although effective in reducing glycemic parameters, there was no reduction in CRP levels in either treatment group. The treatment regimen consisting of rosiglitazone and glimepiride significantly lowered hs-CRP by -2.6 (3.9) mg/L (p<0.05) at week 12 in spite of no improvement in blood glucose. AGE improved in all groups irrespective of type of treatment, glycaemic control and CRP levels. Our data indicate rapid glycaemic control alone does not necessarily result in improvement in markers of inflammation in type 2 diabetes patients.

Administration, Oral↗
PubMed2004

Postmortem vitreous humor beta-hydroxybutyrate: its utility for the postmortem interpretation of diabetes mellitus.

Ketoacidotic coma is one of the most serious complications arising from diabetes mellitus, especially type I, and may be the cause of sudden death especially in diabetes type I. Since beta-hydroxybutyrate (beta-OHB) serum concentrations might provide more information on the severity of ketoacidosis, the aim of this study was to evaluate the concentrations of beta-OHB in vitreous humor and its correlation with other biochemical parameters during postmortem examination. We intended to ascertain the sensitivity and the specificity of these markers for diagnosing diabetes mellitus and the presence of ketoacidosis. This study involved 453 cadavers with a mean age of 57.6 years (S.D. 20.7) and a mean postmortem interval of 17.8 h (S.D. 9.6, range 2-61 h). Cases were assigned to two diagnostic groups according to the antemortem diagnosis of diabetes mellitus, based on the patients' medical records. In vitreous humor statistically significant differences were found in biochemical marker concentrations between the two diagnostic groups, the highest values being obtained in the group of subjects with a previous diagnosis of diabetes mellitus. The measurement of beta-OHB in vitreous humor may be a useful alternative to using blood during postmortem analysis. The presence of high levels of beta-OHB may help interpret the cause of death in diabetics when the autopsy result is negative.

3-Hydroxybutyric Acid↗
PubMedDate not supplied

Glycemic control with regular versus lispro insulin sliding scales in hospitalized Type 2 diabetics.

PURPOSE: The aim of this study was to compare glycemic control with either regular or lispro insulin sliding scales in hospitalized Type 2 diabetics who were not using insulin as outpatients. METHODS: Forty-three patients with Type 2 diabetes, who were taking oral agents only, were admitted to a medical inpatient service and randomized to receive either regular or lispro insulin sliding scale. Oral agents for diabetes were held upon admission and patients were followed throughout their hospital stay. RESULTS: There was no significant difference (P>.05) between the average finger-stick blood glucose (FSBG) in the regular insulin group (157.78+/-40.16 mg/dl) and the lispro insulin group (152.04+/-27.71 mg/dl). No significant difference was found between the daily dose of insulin (regular, 5.83+/-5.01 units; lispro, 4.27+/-3.40 units), total amount of insulin used during hospitalization (regular, 11.87+/-10.78 units; lispro, 12.77+/-14.39 units), glucose excursion (regular, 110.13+/-25.86 mg/dl; lispro, 106.77+/-52.65 mg/dl), or length of hospital stay (regular, 2.33+/-1.23 days; lispro, 2.69+/-1.59 days). CONCLUSION: No significant difference in glycemic control was found in hospitalized Type 2 diabetic patients who received either regular or lispro insulin sliding scales. Both insulin sliding scales used in this study are inadequate to achieve current recommended glycemic targets in this patient population, when used as the only inpatient treatment for diabetes.

Adult↗
PubMed2004

The role of adenosine triphosphate citrate lyase in the metabolism of acetyl coenzyme a and function of blood platelets in diabetes mellitus.

Diabetes is known to increase blood platelet activity. Activities of pyruvate dehydrogenase (PDH), adenosine triphosphate (ATP)-citrate lyase (ATPCL), acetyl-coenzyme A (acetyl-CoA) content, malonyl dialdehyde (MDA), synthesis, and platelet aggregation in resting conditions and after activation with thrombin were measured in diabetic subjects and in age- and sex-matched healthy subjects. Activities of ATPCL and PDH, acetyl-CoA content, and thrombin-evoked MDA synthesis as well as platelet aggregation in diabetes were 31%, 51%, 62%, 35%, and 21%, respectively, higher than in healthy subjects. In addition, activation of diabetic platelets caused 2 times greater release of acetyl-CoA from their mitochondria than in controls. Both 1.0 mmol/L (-)hydroxycitrate and 0.1 mmol/L SB-204490 decreased acetyl-CoA content in platelet cytoplasm along with suppression of MDA synthesis and platelet aggregation. These inhibitory effects were about 2 times greater in diabetic than in control platelets. The data presented indicate that the ATPCL pathway is operative in human platelets and may be responsible for provision of about 50% of acetyl units from their mitochondrial to cytoplasmic compartment. Increased acetyl-CoA synthesis in diabetic platelets may be the cause of their excessive activity in the course of the disease. ATPCL may be a target for its specific inhibitors as factors decreasing platelet activity.

ATP Citrate (pro-S)-Lyase↗
PubMed1994

Fetal liver length in diabetic pregnancy.

OBJECTIVES: Our purpose was to investigate whether liver size is increased in the fetuses of pregnant women with diabetes and whether there is any relationship between fetal liver size and maternal glycemic control. STUDY DESIGN: Eighty pregnant women with diabetes had ultrasonographic measurement of fetal liver length made at 18, 28, and 36 weeks' gestation. Twenty-four obese, nondiabetic women were studied at 36 weeks as controls. RESULTS: Fetal liver length measurements were significantly greater than normal by 18 weeks' gestation (12% above normal mean values; p < 0.001) and increased further (19%, p < 0.02) by 36 weeks. In the obese controls liver length was increased 9% and was significantly lower than in the diabetic subjects (p < 0.001). CONCLUSIONS: Fetal liver size in increased in pregnant women with diabetes and cannot be explained solely by maternal obesity. The major increase in liver size occurs early in pregnancy but appears to be modifiable by glycemic control later in gestation.

Adult↗
PubMed1998

Conversion of Amadori product of Maillard reaction to Nepsilon-(carboxymethyl)lysine in alkaline condition.

Nepsilon-(carboxymethyl)lysine (CML) is known to be formed by oxidative cleavage of Amadori products between C-2 and C-3 of the carbohydrate chain. We report here that CML formation from Amadori compounds is highly accelerated under alkaline conditions. Incubation of glycated human serum albumin (HSA) in 0.1 N NaOH led to the formation of CML whereas glycated HSA reduced by NaCNBH3 or non-glycated HSA did not generate CML. Nalpha-t-butyloxycarbonyl-Nepsilon-fructoselysine (Boc-FL), a model compound of Amadori product, was converted to CML under alkaline conditions. CML level of human sera (n=224) preincubated with 0.1 N NaOH correlated well with glycated albumin value (r=0.912) and hemoglobin A1c (r=0.797).

Amino Acids↗
PubMed2003

Physiological changes in circulating mannose levels in normal, glucose-intolerant, and diabetic subjects.

Mannose is an essential hexose that is required for glycoprotein synthesis. Although circulating mannose levels are known to be influenced by metabolic disorders, how physiological levels of mannose fluctuate in normal and diabetic subjects is largely unknown. We describe a new accurate and sensitive assay for determining circulating mannose levels, which we used to measure plasma mannose levels in 273 normal and diabetic (DM) subjects. Our results revealed a clear correlation (r = 0.754) between fasting plasma mannose (FPM) and fasting plasma glucose (FPG) levels. Our mannose assay showed sensitivity and specificity comparable to that seen for hemoglobin A(1c) (HbA(1c)) assay in subjects with impaired glucose tolerance (IGT) or DM whose FPG levels were normal. Mannose levels were found to increase less than glucose levels in response to an oral glucose tolerance test (OGTT). Furthermore, plasma mannose levels did not significantly change following a meal and more closely correlated with the coefficient of variation (CV) of daily glucose levels than did glucose itself. In conclusion, the close correlation between FPM and FPG levels taken together with the small fluctuations seen in plasma mannose in response to glucose suggests that the measurement of mannose using our assay could potentially play a supplementary role in the diagnosis and screening of patients with mild DM.

Adult↗