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PubMed2002

Assay of advanced glycation endproducts (AGEs): surveying AGEs by chromatographic assay with derivatization by 6-aminoquinolyl-N-hydroxysuccinimidyl-carbamate and application to Nepsilon-carboxymethyl-lysine- and Nepsilon-(1-carboxyethyl)lysine-modified albumin.

Glycation of proteins leads to the formation of early glycation adducts (fructosamine derivatives) and advanced glycation endproducts (AGEs). Formation of AGEs has been linked to the development of cataract, diabetic complications, uraemia, Alzheimer's disease and other disorders. AGEs are a group of compounds of diverse molecular structure and biological function. To characterize AGE-modified proteins used in studies of structural and functional effects of glycation, an assay was developed that surveys the content of early and advanced glycation adducts in proteins. The assay procedure involved enzymic hydrolysis of protein substrate, derivatization of the hydrolysate with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) and HPLC of the resulting adducts with fluorimetric detection. Structural isomers of methylglyoxal-derived hydroimidazolone, glyoxal-derived hydroimidazolone, 3-deoxyglucosone-derived hydroimidazolone and N(delta)-(4-carboxy-4,6-dimethyl-5,6-dihydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)-ornithine (THP) were determined for the first time. AGEs with intrinsic fluorescence (argpyrimidine, pentosidine) were assayed without derivatization. Limits of detection were 2-17 pmol and levels of recovery were 50-99%, depending on the analyte. The AQC assay resolved structural and epimeric isomers of methylglyoxal-derived hydroimidazolones and THP. Hydroimidazolones, THP and argpyrimidine were AGEs of short-to-intermediate stability under physiological conditions, with half-lives of 1-2 weeks. Their measurement provides further insight into the glycation process. The assay was applied to the characterization of human serum albumin minimally and highly modified by N(epsilon)-carboxymethyl-lysine and N(epsilon)-(1-carboxyethyl)-lysine.

Aminoquinolines↗
PubMed2003

The enzymatic defence against glycation in health, disease and therapeutics: a symposium to examine the concept.

Glycation of proteins, nucleotides and basic phospholipids by glucose, glyoxal, methylglyoxal, 3-deoxyglucosone and other saccharide derivatives is potentially damaging to the proteome and mutagenic. It is now recognized that there is an enzymatic defence against glycation--a group of enzymes that suppress the physiological levels of potent glycating agents and repair glycated proteins: glyoxalase I, aldehyde reductases and dehydrogenases, amadoriase and fructosamine 3-phosphokinase. The enzymatic defence against glycation influences morbidity and the efficiency of drug therapy in certain diseases. Improved understanding of the balance between glycation and the enzymatic anti-glycation defence will advance disease diagnosis and therapy.

Glucose↗
PubMed2003

Quantitative screening of protein biomarkers of early glycation, advanced glycation, oxidation and nitrosation in cellular and extracellular proteins by tandem mass spectrometry multiple reaction monitoring.

Glycation of proteins forms fructosamines and AGEs (advanced glycation end products). Oxidative and nitrosative stress leads to the formation of oxidative and nitrosative modifications. The modified amino acid residues formed in these processes are biomarkers of protein damage: some are risk markers and some may be risk factors for disease development. We developed a method for the concurrent quantitative measurement of 16 biomarkers indicative of protein glycation, oxidation and nitrosation damage using LC-MS/MS (LC with tandem MS detection). Underivatized analytes were detected free in physiological fluids and in enzymatic hydrolysates of cellular and extracellular proteins. Hydroimidazolones were the most important glycation biomarkers, and methionine sulphoxide was the most important oxidative biomarker quantitatively; 3-nitrotyrosine was the biomarker of nitrosation. Quantitative screening showed high levels of AGEs in cellular protein and moderate levels in protein of blood plasma. Levels of 3-nitrotyrosine were typically 100-fold lower than this. The major glycation adducts in blood plasma had high renal clearances in normal healthy human subjects, whereas methionine sulphoxide and 3-nitrotyrosine had low renal clearances due to further metabolism. Physiological AGEs in blood plasma were eliminated from the circulation in the kidney and not in the liver. LC-MS/MS peptide mapping was also used to locate the protein biomarkers. These studies reveal that advanced glycation is a significant modification of cellular and extracellular protein. The enzymatic defences against glycation, antioxidants and proteasomal protein degradation inside cells are probable factors regulating biomarker levels of cellular protein.

Biomarkers↗
PubMed1993

Effect of posture and acute glycaemic control on the excretion of retinol-binding protein in normoalbuminuric insulin-dependent diabetic patients.

1. It has been suggested that tubular damage may precede glomerular damage at the onset of diabetic nephropathy. This may be reflected by increased urinary excretion of low-molecular-mass proteins, such as retinol-binding protein. 2. We have measured the urinary excretion rate of retinol-binding protein overnight, during orthostasis and during a hyperinsulinaemic euglycaemic clamp (blood glucose concentration 7.0 mmol/l) with stable diuresis in 34 normotensive, normoalbuminuric insulin-dependent diabetic patients and in 10 normal control subjects. Normal control subjects were not clamped. A further four normoalbuminuric insulin-dependent diabetic patients were rendered euglycaemic without a water load. 3. Overnight retinol-binding protein excretion rate was 58 (16-157) [median(range)] ng/min in patients with insulin-dependent diabetes and 32 (15-72) ng/min in control subjects (P < 0.01). The excretion rate did not change during orthostasis [patients with insulin-dependent diabetes, 67 (3-173) ng/min; control subjects, 23 (5-78) ng/min]. During the euglycaemic clamp retinol-binding protein excretion rate increased to 383 (78-4897) ng/min in patients with insulin-dependent diabetes (P < 0.01). An average increment in retinol-binding protein excretion rate of greater than 4000% was noted after acute euglycaemia in those patients with insulin-dependent diabetes who were not water-loaded. 4. In insulin-dependent diabetes, both overnight and orthostatic retinal-binding protein excretion was not correlated with fasting blood glucose concentration, HbA1, fructosamine or duration of diabetes. The absolute and incremental excretion rates of retinol-binding protein during the clamp were, however, correlated with both fasting blood glucose concentration and glucose excretion rate (rs = 0.41-0.48, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2003

Comparison of the micro- and macro-vascular effects of glimepiride and gliclazide in metformin-treated patients with Type 2 diabetes: a double-blind, crossover study.

AIMS: To compare the metabolic and vascular effects of two sulphonylureas (SU), gliclazide (specific for the pancreatic [SUR1] receptor) and glimepiride (a nonspecific agent that also binds to vascular and cardiac [SUR2] receptors), during chronic administration in metformin-treated patients with Type 2 diabetes (T2DM). METHODS: A randomized, double-blind, crossover study of gliclazide 80 mg BID and glimepiride 2 mg OD, each for 4 weeks as add-on therapy to metformin, with a 4-week washout period. Patients attended four study mornings after first dose and 4 weeks' SU treatment for measurements of arterial distensibility (Ax), pressor responsiveness to i.v. angiotensin II (ANGII), and cutaneous microvascular vasodilator responses to iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP). RESULTS: Glycaemic responses were similar (e.g. serum fructosamine was 315 vs 329 micro mol l-1 after 4 weeks), and there was no change in augmentation index during treatment with either SU (9.1 vs 9.8 mmHg after 4 weeks [95% confidence interval -8.1, 10.5]). Similarly, there were no differences between treatments in pressor responsiveness (e.g. PD10[dose of agonist required to increase mean BP by 10 mmHg] for ANGII was 1.37 vs 1.68 ng kg-1 min-1[-4.3, 6.9]) or cutaneous microvascular vasodilator responses (peak ACh response 68 +/- 36 vs 63 +/- 34 perfusion units [-82.7, 79.1]). CONCLUSIONS: There is no evidence that SUR1-specific and nonspecific SUs have differential effects on arterial distensibility, endothelial function or vasodilator mechanisms in metformin-treated patients with T2DM.

Aged↗
PubMed2003

Haemoglobin Etobicoke, an incidental finding in an Irish diabetic.

It is well recognized that haemoglobin variants can be detected during the measurement of HbA1c by high-performance liquid chromatography (HPLC). A number of variants have been reported as compromising the quantification of HbA1c, a marker used in the assessment of glycaemic control in diabetes. We describe a case of haemoglobin Etobicoke, a rare alpha chain variant detected in an Irish diabetic during HbA1c analysis. Its identity was confirmed using a series of investigations. These included haemoglobin electrophoresis at alkaline and acid pH, isoelectric focusing and globin chain electrophoresis. Ultimately mass spectrometry isolated the mutation at position alpha 84 (F5). Haemoglobin Etobicoke, first described in Canada in 1969 has not previously been detected on HbA1c analysis. In the presence of this rare variant, HbA1c, a standard method using HPLC to assess glycaemic control in diabetes is unreliable and alternatives such as fructosamine need to be considered. HbA1c measured by automated HPLC will effectively screen populations where haemoglobin variants were not previously known. Precise identity of these variants when they are detected is crucial to the reliable interpretation of HbA1c analyses.

Blood Protein Electrophoresis↗
PubMed2002

Five year results of a prospective very low calorie diet or conventional weight loss programme in type 2 diabetes.

AIMS: To complete 5-year follow-up of an intensive weight loss programme in established type 2 diabetic subjects. METHODS: Forty-five obese type 2 diabetic subjects, Body mass index (BMI) > 30, expressed interest in an intensive weight loss programme. Group 1 comprised 15 who selected very low calorie diet (VLCD), Group 2, 15 selected intensive conventional diet and exercise (ICD), 15 failed to follow either programme. Group sessions of eight to 15 subjects continued weekly for 6 months, then monthly for 12 months with prospective recording at 3, 6 and 12 months and then annually of quality of life, BMI, waist/hip ratio, blood pressure, fasting blood glucose, serum fructosamine and serum lipids. RESULTS: Weight loss was slower in the intensive conventional diet group than in the VLCD group, but better maintained at 5 years: group 1, 4.8 +/- 6 kg; group 2, 8.9 +/- 4 kg. In the intensive conventional diet group, 5 year high-density lipoprotein cholesterol was increased 1.78 +/- 0.26 mmol L-1 vs. 1.10 +/- 0.32 mmol L-1 at baseline, and diastolic blood pressure reduced 74.5 +/- 13.3 vs. 85.5 +/- 13.3 at baseline, both P < 0.05. CONCLUSIONS: Out-patient VLCD treatment proved safe and effective in overweight diabetic subjects but those who chose conventional diet and exercise had a slower but more sustained weight loss. Diabetic patients willing to attempt VLCD may safely lose sufficient weight to allow major surgery, but weight regain is inevitable. Patients willing to undertake a long-term group programme of conventional diet can sustain significant weight loss for 5 years, but still require antidiabetic medication.

Adult↗
PubMed2001

Effectiveness of changes in the delivery of diabetes care in a rural community.

Diabetes has a significant impact upon health in rural Maori communities. A diabetes club was established to support self-care and improve diabetes management in a rural community in Northland, New Zealand. A structured approach to care and an associated audit were also introduced. Patient involvement and ownership of the condition were considered important issues. Monitoring of care processes increased by 79%. The first year of audit was associated with a reduction in mean fructosamine from 369 +/- 85 micromol L-1 to 321 +/- 65 micromol L-1 and this was sustained for a further 3 years. The number of people using insulin increased from 15 to 22%. The audit process facilitated the implementation of changes in the delivery of care. We conclude that the data indicate that the enthusiastic delivery of care in general practice, with a devolution of power to the patient, linked to an audit service can result in improved management among patients with Type 2 diabetes.

Community Participation↗
PubMed2002

Antihyperglycaemic and anti-oxidant properties of Anoectochilus formosanus in diabetic rats.

1. In the present study, we investigated aqueous extracts of Anoectochilus formosanus (AFE) for antihyperglycaemic and anti-oxidant effects in diabetic rats induced by streptozotocin (STZ). 2. Diabetic rats were randomly divided into groups and treated orally by gavage with vehicle (distilled water) or AFE (1 and 2 g/kg), once a day for 21 days. 3. At the end of the 21 day period, AFE (2 g/kg) significantly reduced fasting blood glucose, serum fructosamine, triglycerides and total cholesterol compared with vehicle-treated diabetic rats. In vehicle-treated diabetic rats, levels of renal lipid peroxidation were increased, whereas glutathione concentrations were not affected. Renal lipid peroxidation levels were significantly lower and renal reduced glutathione (GSH) concentrations were significantly higher in AFE-treated diabetic rats compared with vehicle-treated diabetic rats. The diabetic kidney in the vehicle-treated group showed a decrease in catalase, but the activity of glutathione peroxidase (GSH-Px) was increased. 4. The activity of catalase, but not GSH-Px, was significantly reversed by AFE treatment. These results indicate that AFE (1 and 2 g/kg) not only possesses an antihyperglycemic effect, but that it may also reduce oxidative stress in diabetic rats.

Animals↗
PubMed2000

Neonatal hypoglycaemia in infants of diabetic mothers.

OBJECTIVE: To determine whether umbilical cord blood glucose correlates with subsequent hypoglycaemia after birth in infants of well-controlled diabetic mothers. METHODOLOGY: Thirty-eight term infants of well-controlled diabetic mothers were enrolled. Five mothers had pre-existing diabetes. Of the 33 gestational diabetic mothers, 16 were managed on insulin and 17 on diet. Maternal blood glucose was maintained between 4 and 8 mmol/L during labour and delivery. Infants' plasma glucose levels were measured from venous cord blood and serially, at less than 30 min, 1 h and 2 h of life by glucose hexokinase method. Blood glucose levels were further monitored by bedside Dextrostix for 24 h. RESULTS: Eighteen (47%) infants developed hypoglycaemia (blood glucose level less than 2 mmol/L) during the first 2 h of life. There was no difference in the cord blood glucose levels between infants with or without hypoglycaemia (3.7 +/- 1.1 vs 4.5 +/- 1.1 mmol/L, respectively). Infants of mothers with diabetes diagnosed prior to 28 weeks gestation were at a higher risk of developing hypoglycaemia (8 of 10 vs 10 of 28, OR 7.2, 95%CI 1.3-40.7). Hypoglycaemic infants were of significantly higher birthweight, and were more likely to be born to Caucasian mothers and by Caesarean section. Raised maternal fructosamine blood level, the need for insulin treatment or the infant's haematocrit were not different between infants with or without hypoglycaemia. CONCLUSIONS: In well-controlled diabetic mothers, the incidence of early hypoglycaemia in infants is still high, particularly in those mothers who had a longer duration of diabetes. Cord blood glucose level did not identify the infants with hypoglycaemia.

Birth Weight↗
PubMed1999

Antioxidant systems in polymorphonuclear leucocytes of Type 2 diabetes mellitus.

AIMS: To examine the effect of Type 2 diabetes mellitus (DM) on enzymes of importance for oxygen-dependent killing of microorganisms by leucocytes. METHODS: Twenty patients with Type 2 DM and 20 nondiabetic controls provided blood samples for analysis. RESULTS: The superoxide dismutase (SOD) activity was lower by 41% in polymorphonuclear leucocytes (PMNL) from patients with Type 2 DM than in controls (3.42+/-0.32 U/mg of protein vs. 5.79+/-0.71 U/mg of protein, P<0.005). Glutathione peroxidase (GSHPx) and glutathione reductase (GR) activities of Type 2 DM patients were 73.04% and 81.12% of control values (0.84+/-0.07 nkat/mg of protein vs. 1.15+/-0.10 nkat/mg of protein, P<0.003, and 2.02+/-0.12 nkat/mg of protein vs. 2.49+/-0.16 nkat/mg of protein, P < 0.023, respectively). The catalase activity showed no significant difference. A significant increase (141.37% of control) in the concentration of thiobarbituric acid reactive products was observed (9.91+/-0.78 miromol/l vs. 7.01+/-0.47 micromol/l, P<0.003). A positive correlation between thiobarbituric acid reactive products and glucose, glycated haemoglobin and fructosamine in the serum of diabetic patients was observed. CONCLUSION: These findings may explain some of the mechanisms underlying the increased susceptibility to certain infection in patients with Type 2 DM.

Adult↗
PubMed2000

Self-monitoring in Type 2 diabetes mellitus: a meta-analysis.

AIMS: Self-monitoring of blood or urine glucose is widely used by subjects with Type 2 diabetes mellitus. This study evaluated the effectiveness of the technique at improving blood glucose control through a systematic review and meta-analysis. METHODS: Randomized controlled trials were identified that compared the effects of blood or urine glucose monitoring with no self-monitoring, or blood glucose self-monitoring with urine glucose self-monitoring, on glycated haemoglobin as primary outcome in Type 2 diabetes. RESULTS: Eight reports were identified. These were rated for quality and data were abstracted. The mean (SD) quality score was 15.0 (1.69) on a scale ranging from 0 to 28. No study had sufficient power to detect differences in glycated haemoglobin (GHb) of less than 0.5%. One study was excluded because it was a cluster randomized trial of a complex intervention and one because fructosamine was used as the outcome measure. A meta-analysis was performed using data from four studies that compared blood or urine monitoring with no regular monitoring. The estimated reduction in GHb from monitoring was -0.25% (95% confidence interval -0.61 to 0.10%). Three studies that compared blood glucose monitoring with urine glucose monitoring were also combined. The estimated reduction in GHb from monitoring blood glucose rather than urine glucose was -0.03% (-0.52 to 0.47%). CONCLUSIONS: The results do not provide evidence for clinical effectiveness of an item of care with appreciable costs. Further work is needed to evaluate self-monitoring so that resources for diabetes care can be used more efficiently.

Blood Glucose Self-Monitoring↗
PubMed2003

Safety and efficacy of insulin glargine (HOE 901) versus NPH insulin in combination with oral treatment in Type 2 diabetic patients.

AIMS: A European, randomized, 29-centre, open-label study compared the safety and efficacy of two formulations of insulin glargine and neutral protamine Hagedorn (NPH) human insulin, in combination with oral agents, in patients with Type 2 diabetes mellitus (DM). METHODS: Two-hundred-and-four patients with Type 2 DM, in whom oral treatment alone was inadequate, were randomized to insulin glargine with 30 micro g/ml zinc [insulin glargine (30)], or insulin glargine with 80 micro g/ml zinc [insulin glargine (80)] or NPH insulin subcutaneously once daily. Insulin was titrated to aim for fasting blood glucose (FBG) values between 4 and 7 mmol/l. All participants received oral therapy during the 3-week titration phase and 1-week maintenance phase of the trial. RESULTS: No differences between treatment groups were observed in adjusted mean fasting plasma glucose; significant decreases of 3.4 mmol/l, 3.5 mmol/l and 3.1 mmol/l were observed within the insulin glargine (30), insulin glargine (80) and NPH insulin groups, respectively (P<0.0001 in each case). No differences between groups, but significant changes within groups, were observed in self-monitored FBG, mean FBG, blood glucose profile, stability of FBG, nocturnal blood glucose, fasting serum C-peptide, non-esterified fatty acids, haemoglobin A1c, fructosamine and fasting serum insulin. A significantly greater proportion of NPH insulin patients experienced symptomatic nocturnal hypoglycaemia (19.1 NPH group vs. 7.3% glargine groups; P=0.0123). Both insulins were well tolerated; one patient in each group experienced an injection site reaction. CONCLUSIONS: Insulin glargine is as safe and effective as NPH insulin given once daily and in this study caused fewer episodes of nocturnal hypoglycaemia.

Administration, Oral↗
PubMed2001

[Antioxidant and anti-AGE therapeutics: evaluation and perspectives].

Diabetic patients exhibit an oxidative stress status, that is an imbalance between reactive oxygen species and antioxidant defences, in favour of the first ones. This oxidative stress, together with formation of advanced glycation endproducts (AGEs), is involved in diabetic complications. It could thus be of great interest to propose antioxidant and/or anti-AGE therapeutics as complementary treatment in these patients. Antioxidants can be classical molecules such as vitamin E, lipoic acid or N-acetylcysteine. Thus, vitamin E supplementation can improve insulin efficiency and glycemic equilibrium, as shown by the decrease of glycaemia, glycated haemoglobin and fructosamine values. In addition, this kind of supplementation lowers plasma lipid peroxidation and oxidizability of low density lipoproteins, which is involved in the atherogenesis process. Moreover, it allows to fight against complications such as retinopathy. A second category is represented by molecules able to fight against the effects of glycation end-products (AGEs). They can act: either by preventing cellular action of AGEs; this is obtained with soluble receptors of advanced glycation endproducts (sRAGE); or by inhibiting AGE formation (scavenging of reactive carbonyl intermediates). Nucleophilic compounds such as pyridoxamine, tenilsetam, 2,3-diaminophenazone, OPB-9195 or aminoguanidine can act in this way. Aminoguanidine is able to limit the development of the main diabetes-associated complications in animals. A double-blind clinical assay has been conducted in type 2 diabetic patients in the United States and the Canada, in order to determine if aminoguanidine is able to slow down the progression of diabetes-induced nephropathy. We will discuss about another guanidic molecule, i.e. metformin, which is also able to scavenge AGEs, in the last part of this review. A third category of molecules is constituted by oral antidiabetic molecules exhibiting antioxidant properties. They are thiazolidinediones (troglitazone) and sulfonylureas (gliclazide). Troglitazone and gliclazide can thus decrease LDL oxidizability and monocyte adhesion to endothelial cells, which is an early step in the atherogenesis process and which is stimulated by oxidised LDLs. Finally, a prospective way is devoted to oral antidiabetic drugs exhibiting both antioxidant and anti-AGE properties. A very used antidiabetic drug of interest is metformin (dimethylbiguanide), since it can prevent diabetes complications not only by lowering glycaemia, but also by inhibiting AGE formation and by stimulating antioxidant defences. The latter therapeutic approach constitutes a future way in the diabetes area, in order both to obtain a better glycemic control and a least development of diabetic complications.

Antioxidants↗
PubMed2002

Long-term glycemic control measurements in diabetic patients receiving hemodialysis.

Cardiovascular morbidity is increased in patients with diabetes mellitus and there is a great prevalence of diabetes and cardiovascular disease among patients with end-stage renal disease (ESRD). Control of glycemia can decrease cardiovascular and end-organ damage. Because the validity of glycemic control tests have not been rigorously studied in patients with ESRD, we evaluated the value of various measures in these patients. The overall clinical goal was to investigate whether hemoglobin A1C (A1C) accurately reflects actual glycemic control as compared with other measures in light of the importance of attaining appropriately controlled blood glucose (BG). The commonly used tests of total glycated hemoglobin (GHb) and A1C may be unreliable in patients with ESRD because of the presence of anemia, shortened red blood cell (RBC) survival, and assay interferences from uremia. The primary aim of this study was to assess the relationship of capillary BG measurements to A1C, GHb, total glycated plasma proteins (GPP), and fructosamine (Fr) in diabetic patients receiving hemodialysis. Twenty-three patients were instructed to obtain BG evaluations twice daily for 7 days by using the Elite glucometer (Bayer Corporation, Elkhart, IN). These determinations included 6 fasting, 6 preprandial, and 3 separate 2-hour postprandial levels. Blood was obtained on day 7 for measurement of A1C, GHb, GPP, and Fr. A1C was analyzed by an immunoassay, GPP and GHb were assayed by affinity high-performance liquid chromatography (HPLC), and Fr by automated nitroblue colorimetric assay. Scatter plots were generated by plotting the average BG versus A1C, GHb, GPP, or Fr. Linear regression was performed for each plot showing the following relationships: A1C = 0.0174 (BG) + 4.76 (r = 0.58; P < 0.05): GHb = 0.0371 (BG) + 3.57 (r = 0.584; P < 0.05): GPP = 0.0083 (BG) + 26.13 (r = 0.065; P = 0.77): Fr = 0.6865 (BG) + 250 (r = 0.345; P = 0.11). Despite anemia and shortened RBC lifespan in patients with ESRD, A1C in the range of 6% to 7% estimates glycemic control similarly to patients without severe renal impairment. A1C values above 7.5% may overestimate hyperglycemia in patients with ESRD. Thus, diabetic patients receiving hemodialysis may have long-term BG that are more properly controlled than previously determined, reducing their risks of the macro- and microvascular complications of diabetes mellitus.

Blood Glucose↗
PubMed2002

Diabetes mellitus and bilateral cataracts in a kitten.

An 18-week-old male domestic long-hair kitten was presented with a history of polyuria and polydipsia for several weeks. The general condition was unremarkable, but the kitten was considerably smaller than expected for the age and showed cataracts in both eyes. Serum glucose concentrations were persistently elevated and based on clinical findings and an elevated serum fructosamine concentration, a diagnosis of diabetes mellitus was established. Diabetes mellitus is not commonly diagnosed in young kittens, nor are cataracts recognised as a frequent feature of this disease in cats. The cataracts progressed in spite of the insulin therapy and the kitten was euthanised 10 weeks after referral. Histopathological examination of the pancreas revealed few and small islets of Langerhans compared to the examination of pancreas from a healthy kitten of the same age. Histopathological changes in the eyes included cataracts affecting both cortex and nucleus.

Animals↗
PubMed2002

Some aspects of erythrocyte metabolism in insulin-treated diabetic dogs.

Insulin-dependent diabetes mellitus (IDDM) is a common metabolic disease often complicated by a number of pathological conditions among which are haematological changes and alterations in blood cell function. Human and feline diabetes mellitus patients have been reported to be associated with oxidative stress that can lead to membrane alterations and to reduced erythrocyte life-span. Erythrocyte function in dogs affected by IDDM has been investigated during insulin therapy, paying attention to antioxidant status, membrane resistance, enzyme activities and 2,3-diphosphoglycerate (2,3DPG) concentration. Thirteen diabetic and 36 healthy dogs were bled and haematology and blood chemistry assays were performed to evaluate the degree of compensation. Osmotic fragility, the activities of the enzymes glucose-6-phosphate dehydrogenase (G6PD) and pyruvate-kinase (PK) and the concentrations of reduced glutathione (GSH) and 2,3DPG were evaluated in the erythrocytes. Diabetic dogs did not differ from controls in terms of haematological parameters, except for higher numbers of platelets. Higher values of fructosamine, glucose, protein, plasma potassium and calculated osmolality were detected in the plasma from diabetic dogs. No differences were detected in osmotic fragility, GSH concentration and PK activity between the two groups but 2,3DPG concentration and G6PD activity were statistically significantly higher in the diabetic group. The results indicate minimal alterations in erythrocyte functions occur in insulin-treated diabetic dogs. This contrasts with what has been reported for IDDM humans and cats.

2,3-Diphosphoglycerate↗
PubMed2000

Possible effects of one week vitamin K (menaquinone-4) tablets intake on glucose tolerance in healthy young male volunteers with different descarboxy prothrombin levels.

To clarify the roles of vitamin K (VK) in the pancreas, twice oral, glucose tolerance tests were examined in 12 healthy young male volunteers before and after 1 week of VK tablet intake. Blood were collected by venipucture at 0, 30 and 120 min after 75 g oral glucose loading. They then took VK tablets (90 mg/d of menaquinone-4) for 1 week, and the second glucose tolerance test was examined. The subjects were divided into three groups by serum descarboxy prothrombin (DP) levels; four of lowest DP (L-DP), middle of DP (M-DP) and highest DP (H-DP) levels. They were compared by one-factor analysis of variance and Scheffè's F (group differences) and paired t -test (the effects of 1 week of VK intake). Age, body mass index and glucose status [plasma glucose (PG) and immunoreactive insulin (IRI), hemoglobin-Alc, fructosamine] of all groups were almost the same, but the IRI of the H-DP group was higher than that of the other groups at 120 min after the glucose loading (mean+/-SEM; L; 10.6+/-0.9, M-; 17.5+/-4.2, H-; 40.4+/-6.0 microU/ml). One week of VK intake tended to decrease the plasma DP levels of all groups and significantly reduced IRI of the H-DP at 120 min by half (before; 40.4+/-6.0 vs after: 18.4+/-4.6 microU/ml). The IRI/pG ratio in areas under the curve (AUC) of H-DP from 0 to 120 min after the loading was significantly decreased by 1 week of VK tablet intake (before: 31.0+/-7.4 vs after: 20/1+/-3.8 microU/g). These results suggested that there may be some relationship between pharmacological dose of vitamin K and insulin response.

Adult↗