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Influence of 4 weeks' intervention by exercise and diet on low-density lipoprotein subfractions in obese men with type 2 diabetes.

Insulin resistance is associated with dyslipoproteinemia characterized by increased serum triglycerides, reduced high-density lipoprotein 2 (HDL2) cholesterol, and increased small, dense low-density lipoprotein (LDL) subfraction particles. Physical activity and weight reduction are known to improve insulin resistance and dyslipoproteinemia, but their influence on LDL subfractions in diabetic patients is unknown. Therefore, we investigated the effect of a 4-week intervention program of exercise (2,200 kcal/wk) and diet (1,000 kcal/d: 50% carbohydrate, 25% protein, and 25% fat; polyunsaturated/saturated fat ratio, 1.0) on glycemic control and HDL and LDL subfractions in 34 obese patients with non-insulin-dependent diabetes (age, 49 +/- 9 years; body mass index [BMI], 33.1 +/- 5.1 kg/m2). Reductions in body weight (P < .001) and improvements in fasting blood glucose, insulin, fructosamine (P < .001), and free fatty acids (P < .01) by intervention were associated with reductions in serum cholesterol and apolipoprotein B (apo B) concentrations in very-low-density lipoprotein (VLDL) (P < .01), intermediate-density lipoprotein (IDL), and small, dense (>1.040 g/mL) LDL particles (P < .001). These data underlie the positive influence of weight reduction induced by exercise and diet on insulin resistance and lipoprotein metabolism in obese diabetic patients, particularly showing improvements of the LDL subfraction profile with a decrease of small, dense LDL particles. This is of particular importance, as these particles have been shown to be associated with coronary artery disease.

Adult↗

Depletion of total antioxidant capacity in type 2 diabetes.

The purpose of the study was to examine the relationship between antioxidant depletion, glycemic control, and development of chronic complications in a controlled population of type 2 diabetic patients. Fifty age-matched type 2 diabetic patients receiving sulfonylureas but not insulin treatment were screened and assigned to two groups based on the presence or absence of proteinuria. A third group of normal subjects without diabetes were also enrolled in the study. All subjects in the three groups were Egyptians who were matched for body weight, and the two diabetic groups were also age-matched. Plasma glucose and fructosamine levels were higher in the two groups of diabetic patients versus the control group, but lipid peroxide levels were higher only in the patients with proteinuria. Compared with the control group, the total antioxidant capacity was depleted in the two diabetic groups, but the depletion was more severe in patients with proteinuria. Thus, the mean Trolox equivalent antioxidant capacity (TEAC) of the control group was 2.7+/-0.45, versus 1.7+/-0.5 (P < .001) in the patients without proteinuria. Furthermore, the TEAC measured in patients with proteinuria, who also had more diabetic complications, was lower (1.4+/-0.5, P < .001) than the TEAC in patients without urinary protein. In conclusion, a depletion of the total antioxidant capacity is associated with a higher incidence of diabetic complications.

Adult↗

Effects of gliclazide versus metformin on the clinical profile and lipid peroxidation markers in type 2 diabetes.

The sulfonylurea gliclazide and the biguanide metformin have different mechanisms to reduce glycemia. We performed a randomized study to compare these two agents with respect to glycemic control and effects on lipid peroxidation markers in 36 adult patients with type 2 diabetes. Both agents significantly decreased glycosylated hemoglobin ([HbA1c] P < .05), fructosamine (P < .05), and the glucose-excursion curve during the oral glucose tolerance test ([OGTT] P < .01). With regard to the insulin curve during this test, no significant change was observed with metformin and a significant increase was measured with gliclazide (P < .05). Considering the small number of events, no significant difference was detected in the number of hypoglycemic episodes between the two agents. More upper-gastrointestinal (GI) symptoms were observed with metformin compared with gliclazide (P < .05). Even with no change in the standard lipid profile, both agents increased serum vitamin E (P < .01 for gliclazide and P < .05 for metformin) and decreased the level of lipid peroxidation markers in low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particles (P < .05). Despite different mechanisms of action, gliclazide and metformin demonstrated comparable levels of efficacy and complementary effects on lipid peroxidation markers.

Aged↗

The amylin analog pramlintide improves glycemic control and reduces postprandial glucagon concentrations in patients with type 1 diabetes mellitus.

To explore further the effects of the human amylin analog pramlintide on overall glycemic control and postprandial responses of circulating glucose, glucagon, and metabolic intermediates in type 1 diabetes mellitus, 14 male type 1 diabetic patients were examined in a double-blind, placebo-controlled, crossover study. Pramlintide (30 microg four times daily) or placebo were administered for 4 weeks, after which a daytime blood profile (8:30 AM to 4:30 PM) was performed. Serum fructosamine was decreased after pramlintide (314+/-14 micromol/L) compared with placebo (350+/-14 micromol/L, P = .008). On the profile day, the mean plasma glucose (8.3+/-0.7 v 10.2+/-0.8 mmol/L, P = .04) and postprandial concentrations (incremental areas under the curve [AUCs] from 0 to 120 minutes) were significantly decreased during pramlintide administration (P < .01 for both) despite comparable circulating insulin levels (359+/-41 v 340+/-35 pmol/L). Mean blood glycerol values were reduced (0.029+/-0.004 v 0.040+/-0.004 mmol/L, P = .01) and blood alanine levels were elevated (0.274+/-0.012 v 0.246+/-0.008 mmol/L, P = .03) after pramlintide versus placebo. Blood lactate concentrations did not differ during the two regimens. During pramlintide administration, the AUC (0 to 120 minutes) for plasma glucagon after breakfast was diminished (P = .02), and a similar trend was observed following lunch. In addition, peak plasma glucagon concentrations 60 minutes after breakfast (45.8+/-7.3 v 72.4+/-8.0 ng/L, P = .005) and lunch (47.6+/-9.0 v 60.9+/-8.2 ng/L, P = .02) were both decreased following pramlintide. These data indicate that pramlintide (30 microg four times daily) is capable of improving metabolic control in type 1 diabetics. This may relate, in part, to suppression of glucagon concentrations. Longer-term studies are required to ascertain whether these findings are sustained over time.

Adult↗

Proinflammatory activity on rat carotid endothelium of albumins obtained by different procedures.

To investigate whether the proinflammatory activity of intravenously administered albumins is related to their preparation method, we compared bovine albumins obtained by alcohol precipitation and by heat shock. This last procedure produced a notable increase in monocyte adhesion/mm2 in rat carotid endothelium (48 +/- 31, n = 32 rats, vs 7 +/- 6, n = 24 rats, mean +/- S.D., P < 0.001). We found no changes in fluorescence emission in these two groups, and no correlation was observed between leukocyte adhesion and the contents of free fatty acids, free -SH groups, fructosamine, dimers and polymers. The inhibition profile of the proinflammatory activity by polyanionic molecules (fucoidan and dextran sulfate 500 kD) was compatible with the recognition of heat-shocked albumins by scavenger receptors. Thiol disulfide exchange in albumins was produced by ageing with cysteine and by incubation with protein disulfide isomerase. Albumins thus modified increased the adhesion of leukocytes to the endothelium, which indicates that some isomeric forms of albumin generated by thiol disulfide exchange may acquire proinflammatory behavior.

Alcohols↗

Glycation in diabetic neuropathy: characteristics, consequences, causes, and therapeutic options.

Glycation is the nonenzymatic reaction of glucose, alpha-oxoaldehydes, and other saccharide derivatives with proteins, nucleotides, and lipids. Early glycation adducts (fructosamines) and advanced glycation adducts (AGEs) are formed. "Glycoxidation" is a term used for glycation processes involving oxidation. Sural, peroneal, and saphenous nerves of human diabetic subjects contained AGEs in the perineurium, endothelial cells, and pericytes of endoneurial microvessels and in myelinated and unmyelinated fibres localized to irregular aggregates in the cytoplasm and interstitial collagen and basement membranes. Pentosidine content was increased in cytoskeletal and myelin protein extracts of the sural nerve of human subjects and cytoskeletal proteins of the sciatic nerve of streptozotocin-induced diabetic rats. AGEs in the sciatic nerve of diabetic rats were decreased by islet transplantation. Improved glycemic control of diabetic patients may be expected to decrease protein glycation in the nerve. Protein glycation may decrease cytoskeletal assembly, induce protein aggregation, and provide ligands for cells surface receptors. The receptor for advanced glycation and products (RAGE) was expressed in peripheral neurons. It is probable that high intracellular glucose concentration is an important trigger for increased glycation, leading to increased formation of methylglyoxal, glyoxal, and 3-deoxyglucosone that glycate proteins to form AGEs intracellularly and extracellularly. Oxidative stress enhances these processes and is, in turn, enhanced by AGE/RAGE interactions. An established therapeutic strategy to prevent glycation is the use of alpha-oxoaldehyde scavengers. Available therapeutic options for trial are high-dose nicotinamide and thiamine therapies to prevent methylglyoxal formation. Future possible therapeutic strategies are RAGE antagonists and inducers of the enzymatic antiglycation defense. More research is required to understand the role of glycation in the development of diabetic neuropathy.

Animals↗

Combined metformin and insulin therapy for patients with type 2 diabetes mellitus.

OBJECTIVE: This study was undertaken to assess the effects of combined treatment with insulin and metformin in patients with type 2 diabetes mellitus in whom dietary measures, weight control, and oral antihyperglycemic therapy had failed. BACKGROUND: Insulin resistance in peripheral tissues, increased hepatic gluconeogenesis, and impaired insulin secretion are the underlying factors in the development of type 2 diabetes. Metformin is a biguanide antihyperglycemic agent that increases peripheral insulin sensitivity, reduces hepatic gluconeogenesis, and decreases intestinal glucose absorption. METHODS: Thirty-one patients (24 women, 7 men; mean age, 61.8 years; mean body mass index [BMI], 28.0 kg/m2) were enrolled in this randomized, double-blind, 2-way, crossover, placebo-controlled study. Patients with type 2 diabetes who were treated previously with insulin or oral hypoglycemic agents and who had a glycosylated hemoglobin (HbA1c) level >9% or a fasting blood glucose level >8 mmol/L were included. Patients who were being treated with oral agents were switched to insulin therapy and required to maintain stable blood glucose control for 2 months prior to randomization. Patients received insulin plus either metformin 1,700 mg/d or placebo for 5 months, followed by a 2-month washout period, and were then crossed over to the other treatment arm for 5 months of additional treatment (total treatment period: 12 months). RESULTS: Thirty patients completed the study; 1 patient withdrew early because of hypoglycemia. Compared with placebo, metformin produced significant reductions from overall baseline in mean daily insulin dose requirement (-8.69 units (17.2%], P < 0.001), HbA1c level (-0.74 [9.9%], P = 0.005), serum fructosamine level (-44.40 micromol/L, P = 0.026), 24-hour blood glucose profile (P = 0.008), and total cholesterol level (-0.42 mmol/L, P = 0.005). No treatment effects were observed on body weight, blood pressure, serum high-density lipoprotein cholesterol levels, or serum triglyceride levels. There was no correlation between BMI and reduction in HbA1C. No major side effects were reported. CONCLUSIONS: Combination therapy with metformin and insulin improves glycemic control and reduces insulin requirements. with no major side effects, in patients with type 2 diabetes and may improve the risk profile in this patient population.

Adult↗

Glycemic control in patients with type 2 diabetes mellitus switched from twice-daily immediate-release metformin to a once-daily extended-release formulation.

BACKGROUND: The extended-release formulation of metformin (MXR) prolongs drug absorption in the upper gastrointestinal tract and permits once-daily dosing in patients with type 2 diabetes mellitus. This newer formulation may enhance patient compliance with oral therapy and improve long-term control of diabetes compared with the conventional immediate-release formulation of metformin (MIR). OBJECTIVE: The goal of this study was to determine the effects on glycemic control of a switch to MXR therapy in patients with type 2 diabetes currently treated with MIR. METHODS: This was a multicenter, randomized, double-blind, parallel-group study in patients with established type 2 diabetes. Eligible patients were to have a glycated hemoglobin (HbA1c) value < or = 8.5% and mean fasting plasma glucose (FPG) concentrations < or = 200 mg/dL while receiving MIR 500 mg BID for at least 8 weeks. After a 2-week, single-blind lead-in period, patients were randomly assigned to receive MXR 1000 or 1500 mg QD for 24 weeks or to continue MIR 500 mg BID for 24 weeks. The primary efficacy variable was change in HbA1c from baseline to week 12. Other variables included change in FPG levels; change in HbA1c; distribution of HbA1c values; mean daily blood glucose concentrations (self-monitored); levels of fructosamine, serum insulin, and lipids; and body weight. RESULTS: Two hundred seventeen patients were randomized to treatment. The mean change from baseline in HbA1c values at weeks 12 and 24 were small and similar in the 3 treatment groups. At week 12, the mean change from baseline in HbA1c was 0.15% for MIR, 0.23% for MXR 1000 mg, and 0.04% for MXR 1500 mg. The corresponding mean changes at week 24 were 0.06%, 0.25%, and 0.14%. CONCLUSIONS: In this study, patients with type 2 diabetes who had been receiving twice-daily MIR achieved comparable glycemic control when therapy was switched to once-daily MXR at the same or a greater total daily dose.

Blood Glucose↗

A multicenter, randomized, open-label, comparative, two-period crossover trial of preference, efficacy, and safety profiles of a prefilled, disposable pen and conventional vial/syringe for insulin injection in patients with type 1 or 2 diabetes mellitus.

BACKGROUND: The accuracy and convenience of pen devices for insulin injection have improved quality of life for patients with insulin-treated diabetes mellitus (DM). Prefilled, disposable pens have the advantage of simplicity, with minimal training and attention required and no installation of new cartridges necessary. OBJECTIVE: The aim of this study was to assess patient preference, efficacy, and safety profiles of a prefilled, disposable pen (FlexPen) and conventional vial/syringe injection method for insulin injection therapy among patients with DM. METHODS: In a multicenter, randomized, open-label, crossover study, patients with type 1 or 2 DM were transferred from previous QD or BID conventional insulin therapy to a mixture of 70% insulin aspart protamine suspension and 30% insulin aspart injection (NovoLog Mix 7030) for 4 weeks of dose optimization using their usual type of syringe. Patients were then randomly assigned to use either vial/syringe or a prefilled, disposable pen to inject the biphasic insulin aspart 7030 mixture for the next 4 weeks, followed by 4 weeks of use of the other injection device. Efficacy, safety profiles, and patient preference for the delivery systems were compared. RESULTS: A total of 121 patients (mean [SD] age, 57.0 [12.4] years; age range, 28-81 years; mean [SD] body mass index, 31 [5.5] kg/m(2)) were enrolled. One hundred three patients completed the study. Seventy-four percent of patients (78105) indicated a preference for the pen over the vial/syringe method (95% CI, 71%-87%), compared with 20% (21105) who preferred the vial/syringe. Eighty-five percent (88104) considered the pen more discreet for use in public (compared with 9% [9104] for the vial/syringe), 74% (77104) considered it easier to use overall (compared with 21% [22104] for the vial/syringe), and 85% (89105) found the insulin dose scale on the pen easier to read (compared with 10% [10105] for the vial/syringe). Patients had statistically significant improvement in glycosylated hemoglobin values during the study (P < 0.05). No statistically significant differences in fasting plasma glucose, mean 4-point blood glucose profiles, or serum fructosamine values were found between groups. Overall, the safety profiles during treatment periods with the pen were comparable to those with the vial/syringe. CONCLUSIONS: In this trial, differences in efficacy and safety profiles between the vial/syringe and prefilled, disposable pen appeared negligible. However, more patients expressed a preference to continue use of the pen.

Adult↗

Diabetic retinopathy during pregnancy.

PURPOSE: The purpose of the study is to evaluate the incidence, prevalence, progression, and risk factors of diabetic retinopathy during pregnancy. METHODS: Sixty-five patients who were pregnant and had insulin-dependent diabetes mellitus were evaluated before pregnancy, in every trimester during the pregnancy, and 12 months postpartum. The medical data included age, diabetes duration, glycohemoglobin, fructosamine, hemoglobin, creatinine, uric acid, and systolic and diastolic blood pressure. RESULTS: Progression of the retinopathy occurred in 77.5% of the patients who presented with diabetic retinopathy at conception; proliferative diabetic retinopathy occurred in 22.5%. Only 26% of the patients who started the pregnancy without diabetic retinopathy had some progression of the retinopathy. Duration of the diabetes was longer in the progressive group compared with the nonprogressive group (P = 0.007). The glycohemoglobin was higher in the progressive group than in the nonprogressive group at each time point, but only in the third trimester was the difference statistically significant (P = 0.04). The hemoglobin level was lower in the progressive group than in the nonprogressive group (P < 0.01). The systolic blood pressure was higher in the progressive group (P < 0.005). CONCLUSION: Understanding the risk factors contributing to the aggravation of diabetic retinopathy during pregnancy is helpful in designing criteria for the team management of pregnant patients with diabetes.

Adult↗

Effects of aerobic physical exercise in the elderly with type 2 diabetes mellitus.

The objective of this study was to determine the impact of an aerobic physical exercise program in the treatment of a group of elderly patients with type 2 diabetes mellitus (DM) in relation to metabolic control, physical capacity, quality of life (QOL) and attitudes toward diabetes. Patients were randomly assigned to either an experimental (n=19) or a control (n=20) group. The following measurements were conducted at baseline and after week 16: glycosylated hemoglobin (hbA1c), fructosamine, 3 h oral glucose tolerance test, treadmill test (Balke-Naughton), and a questionnaire on QOL and attitudes toward DM. After the intervention, the experimental group showed a significant decrease of glucose excursion during the oral glucose tolerance test (OGTT) (area under the curve) (16.6+/-3.8 vs. 15.3+/-3.1, P<0.05) and an increase in total time on the treadmill (s) (423+/-207 vs. 471+/-230, P<0.05). An improvement in the attitudes toward DM was observed in the experimental group (P=0.01) but not in the control group. Female gender, higher body mass index and hbA1c were factors associated with a response to the intervention. This study suggests that physical exercise has significant effects on glucose excursion during an OGTT and exercise tolerance in elderly patients with type 2 DM.

Journal Article↗

Prediction of exercise-mediated changes in metabolic markers by gene polymorphism.

The effects of regular physical exercise on obesity-associated metabolic abnormalities vary for each individual. In this study, we investigated whether genotypes of genes associated with obesity can predict the effects of exercise on changes in metabolic markers in healthy men. Healthy Japanese men (n=106) performed the exercise program at 50% of their maximal heart rate for 20-60 min a day, 2-3 days each week for 3 months. The levels of fasting plasma glucose (FPG) and serum leptin significantly decreased after the exercise program. Polymorphisms of the beta3-adrenergic receptor (beta3AR) and uncoupling protein-1 (UCP-1) genes were analyzed with RFLP methods. In the Trp/Trp genotype of the beta3AR gene, the levels of serum leptin, FPG and fructosamine (FrAm) decreased significantly after the exercise program, but not in the Arg/Arg genotype. In the AG heterozygote and the GG homozygote of the UCP-1 gene, FPG and FrAm levels were significantly reduced, respectively. In conclusion, gene polymorphism of the beta3AR and UCP-1 was found to be associated with the exercise-mediated improvement in glucose tolerance and leptin resistance in healthy Japanese men.

Adult↗

Lipid peroxidation in type 2 normolipidemic diabetic patients.

Vascular complications, as a consequence of atherosclerosis, are the main causes of morbidity and mortality in diabetes. Low density lipoprotein (LDL) oxidation is accepted as a relevant pathogenic mechanism in atherogenesis. The aim of this work was to study the relationship between lipid peroxidation (LPO) and metabolic control. LPO was evaluated in 40 type 2 normolipidemic diabetic patients by measuring thiobarbituric acid reactive substances (TBARS), in the plasma, using malondialdehyde (MDA), end product of the oxidation of polyunsaturated fatty acids, as a standard. Fast blood glucose (FBG), serum total cholesterol (TC) and serum triglycerides (TG) were evaluated by routine methods. Fructosamine (FR) was measured by the nitroblue tetrazolium (NBT) colorimetric test. An elevated level of lipid peroxides (P < 0.001) was observed in the plasma of diabetic patients (4.51 +/- 1.29 nmol/ml) as compared to normal subjects (3.54 +/- 1.00 nmol/ml). Lipid peroxides did not correlate with the FR levels, nor with FBG, TC and TG. These results show an increase of LPO in type 2 normolipidemic diabetic patients. Probably the mechanism for higher lipid peroxide levels in diabetes is multifactorial. Our study supports the hypothesis of a role of oxidative stress in diabetes independently of the lipid serum content.

Aged↗

Alterations in serum levels of 1 alpha,25(OH)2 D3 and osteocalcin in patients with early diabetic nephropathy.

UNLABELLED: Serum levels of markers for bone remodeling and diabetic metabolic markers were measured in subjects with non-insulin-dependent diabetes mellitus (NIDDM) to investigate the relationship between early diabetic nephropathy and calcium/bone metabolism. 1 alpha,25(OH)2 D3 (Vit D), osteocalcin (OC), intact parathyroid hormone (PTH) and urine albumin excretion (UAE) were measured in all subjects. Serum levels of Vit D and OC were significantly decreased in diabetic subjects compared to age-matched, non-diabetic controls. In diabetic patients, a significant positive correlation was observed between intact PTH and OC. No significant correlation was found between levels of Vit D and OC. In early diabetic nephropathy without increased serum creatinine, Vit D decreased and OC increased with increasing UAE. Levels of hemoglobin Alc (HbAlc) and fructosamine (FRA) were not correlated with levels of Vit D or OC. Levels of Vit D were decreased and levels of OC were increased in diabetic subjects with proliferative retinopathy or with micro- or macro-albuminuria. CONCLUSIONS: Results of the present study indicate that changes in bone remodeling markers such as Vit D and OC levels are present in the early stages of diabetic nephropathy, and that circulating intact PTH is important in restoring the reduced OC levels in diabetic patients, probably as a reflection of bone remodeling.

Albuminuria↗

Damage of charge-dependent renal tubular reabsorption causes diabetic microproteinuria.

More negatively-charged proteins are harder to pass through the glomerular charge barrier (GCB) and to be reabsorbed by renal tubules. Although the glycation of albumin increases its negative charge compared to non-glycated albumin, the glycation of transferrin does not change its charge. This difference enabled us to examine the charge-dependent renal function in diabetic proteinuria. The percentage of urinary glycated transferrin (serum %G-transferrin) positively correlated with serum fructosamine concentrations and the percentage of serum glycated albumin (serum %G-albumin) in all subjects. Urinary concentrations of transferrin and beta 2-microglobulin strongly correlated in diabetic patients with microproteinuria, while no significant correlation was observed in subjects with diabetic macroproteinuria or non-diabetic proteinuria. Urine/serum (U/S) ratio of %G-albumin in the patients with diabetic proteinuria was significantly lower than that in subjects with non-diabetic proteinuria, while no difference of the U/S ratio of %G-transferrin was observed between any groups. Furthermore, U-%G-transferrin/U-%G-albumin ratio was highest in the diabetic patients with microproteinuria. These results lead to the conclusion that the initial damage in diabetic kidney causing microproteinuria starts with the dysfunction of charge-dependent tubular reabsorption prior to a loss of GCB.

Absorption↗

Diagnosis of diabetes mellitus in cats and dogs.

This article describes the clinical presentation of diabetes mellitus in cats and dogs, including the types of diabetes, signalment, history, physical examination findings, and laboratory diagnosis. Newer diagnostic tests such as serum fructosamine concentrations and arginine response rate are also briefly discussed.

Age Factors↗

Long-term monitoring of the diabetic dog and cat. Clinical signs, serial blood glucose determinations, urine glucose, and glycated blood proteins.

Management of diabetic dogs or cats requires the use of all available monitoring technology (Fig. 6). First, one should ask questions about the clinical control of DM. Are the clinical signs of DM resolved, and is the owner satisfied with insulin therapy? Other important questions would include: Is the dog or cat developing long-term complications of diabetes such as neuropathies or cataracts? Is body weight remaining stable? Is the dog or cat showing any signs of hypoglycemia? One should determine if the blood glucose curves are close to ideal for the type of insulin being administered. Urine glucose and ketones should be negative or trace as assessed by the at-home monitoring by the owner. In the problem diabetic, long-term glucose control can be assessed by serum fructosamine or glycosylated hemoglobin determinations. Regulation of the diabetic patient is accomplished when the owner is satisfied with the therapy and when the serum glucose monitoring parameters are acceptable.

Animals↗

Hematologic complications of diabetes mellitus.

In summary, hematologic abnormalities in diabetes affect the function, morphology, and metabolism of blood cells, and the coagulation system. These complications can contribute to the development of anemia, infection, and hypercoagulability in diabetic dogs and cats. Some hematologic changes, such as glycosylated hemoglobin and fructosamine, play an important role as markers of glycemic control. Hematologic changes also serve as important models for changes occurring in other tissues, such as cataract formation and nephropathy. Further study of blood alterations will enhance our knowledge of the biochemistry and pathophysiology of diabetes and diabetic complications and stimulate the development of effective preventative and therapeutic measures.

Animals↗