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Management of diabetes mellitus (DM) continues to undergo evolutionary changes with further refinements as a result of enhanced understanding of the pathophysiology, technologic advances in glucose monitoring techniques and equipment, and an abundance of new drugs and insulin administration devices. Clearly, the maintenance of near normal blood glucose levels remains the prime goal of therapy in both noninsulin-dependent diabetes mellitus (NIDDM) and insulin-dependent diabetes mellitus (IDDM) especially in the light of the recent diabetes control and complications trial. In addition, the data has always supported the role of sustained hyperglycemia in precipitating diabetic ketosis and hyperglycemic nonketotic state, as well as recurrent infections and changes in lipid levels leading to atherosclerosis in large-sized and medium-sized arteries. Basic therapeutic modalities to achieve euglycemia in NIDDM patients remain the diet, exercise, oral agents, and insulin. Optimal management of associated medical disorders, such as hypertension and obesity, also is important to prevent the onset or progress of angiopathic complications. Combination therapy with insulin and oral agents is a frequently used treatment strategy in the last decade to achieve optimal metabolic control in this population if the therapy with oral agents alone fails to achieve this objective. Furthermore, in patients with IDDM manifesting extreme excursion of diurnal glycemia, this approach deserves trial as suggested in recent studies. However, it is imperative to assess this modality in light of the knowledge of pathophysiology of DM.
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PMID:Combinations sulfonylurea and insulin therapy in diabetes mellitus. 878 38

Optimal blood glucose levels and normal insulin sensitivity are aims in the treatment of insulin-dependent diabetes mellitus (IDDM). Insulin sensitivity and insulin reserve are closely interrelated. It is essential to know more about both of these parameters at clinical diagnosis, because their preservation may delay the occurrence of diabetes-related complications. B-cell function is likely to be retained for a longer period in patients with adult onset of the disease compared with children. In this study, intensive insulin treatment was initiated in newly diagnosed adult patients to determine if it preserved endogenous insulin secretion longer than conventional therapy. Forty-nine patients with newly diagnosed diabetes were carefully categorized as having IDDM according to clinical and serological criteria. They were randomized to an intensive (I group) or conventional (C group) insulin therapy and evaluated for 5 years. Every 6 months, a check-up included glucagon-stimulated C-peptide (GSCP), hyperglycemic glucose clamp with arginine bolus, euglycemic-hyperinsulinemic clamp, and screening for microalbuminuria, retinopathy, and neuropathy. At the end of the study, hemoglobin A1c (HbA1c) was 6.3% +/- 1.9% in the I patients and 8.1% +/- 2.1% in the C patients (P < .001). Blood glucose concentrations less than 3.5 mmol/L were more frequent in the I group than in the C group (P < .05). Insulin sensitivity (M/I) and GSCP were higher in intensively treated patients after 5 years (M/I, I group 40 +/- 10 nmol x kg(-1) x min(-1) x pmol/L1 v C group 21 +/- 11, P < .005; GSCP, I group 0.6 +/- 0.2 nmol/L v C group 0.19 +/- 0.11, P < .005). The prevalence of peripheral neuropathy was significantly lower in the I group at the end of the study. In conclusion, intensive therapy is more effective in the preservation of insulin action and reserve. In our patients, no case of severe hypoglycemia was observed, indicating that intensive therapy was safe in these patients.
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PMID:Intensive therapy in adult insulin-dependent diabetes mellitus is associated with improved insulin sensitivity and reserve: a randomized, controlled, prospective study over 5 years in newly diagnosed patients. 896 84

The Precose Resolution of Optimal Titration to Enhance Current Therapies (PROTECT) study is an ongoing Phase IV clinical trial designed to assess the effectiveness, tolerability, and safety of acarbose tablets in patients with type II diabetes when the dosage is slowly titrated upward. This multicenter, open-label, 28-week trial will enroll approximately 7,000 type II diabetic patients. The present report describes the interim results for 2,139 patients who completed the trial as of November 1, 1996. Patients with type II diabetes enrolled in the study were inadequately controlled either with diet alone or with a sulfonylurea. The dosage of acarbose was titrated from 25 mg three times a day (TID) to 100 mg TID based on tolerability and efficacy. Efficacy of glycemic control was assessed by changes in glycated hemoglobin A1c (Hb A1c) and 1-hour postprandial plasma glucose (PPG) levels. Tolerability and safety were determined by patient reports of treatment-emergent adverse events and by review of laboratory tests. The PROTECT study confirms the previously demonstrated efficacy and safety of acarbose in improving glycemic control in patients with type II diabetes regardless of a patient's age, body weight, ethnic background, time since diagnosis, or severity of disease. mean 1-hour PPG levels declined throughout the entire treatment period, with a mean decrease from baseline of -47 mg/dL at the end of treatment. Hb A1c, the most reliable indicator of long-term glycemic control, decreased over the course of treatment, resulting in a mean decrease of -0.7% (P < 0.001). Although all patient types enrolled in the study responded positively to therapy, certain subgroups responded particularly well, such as those patients diagnosed with the disease less than 1 year ago, those treated with acarbose as monotherapy, and those with higher baseline Hb A1c levels. Adverse events were experienced by 36% of all patients and consisted primarily of gastrointestinal disturbances (flatulence, diarrhea, abdominal pain). Moderate renal insufficiency (serum creatinine levels between 1.5 and 2 mg/dL) was present in 259 patients, and no patients developed serum hepatic transaminase levels more than twice the normal range.
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PMID:PROTECT interim results: a large multicenter study of patients with type II diabetes. Precose Resolution of Optimal Titration to Enhance Current Therapies. 915 67

Optimal metabolic control is a primary management objective for adolescents with insulin-dependent diabetes mellitus. Nutrition therapy plays an important role in meeting this challenging treatment goal. This article presents broad nutrition goals, makes macronutrient recommendations, and describes their effect on blood glucose levels. Various meal-planning techniques and other developmentally appropriate approaches to assist adolescents in meeting these nutrition objectives are described. Finally, challenges in implementing nutrition therapy in an adolescent population are discussed.
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PMID:Nutrition strategies for adolescents with insulin-dependent diabetes mellitus. 923 49

The mortality rate after myocardial infarction is more than twice as large in diabetic patients than in patients without diabetes. Optimal blood sugar control in the acute phase and during follow-up might improve prognosis. The relative reduction in mortality and cardiac events after myocardial infarction by means of betablockers, ACE inhibitors and statins is the same for diabetics as for non-diabetes. However, because of the poorer prognosis, the absolute reduction in mortality is more than twice as high in diabetic as in non-diabetic patients. For this reason, diabetic patients comprise a target group for secondary prevention by means of betablockers, ACE inhibitors and statins after myocardial infarction.
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PMID:[Patients with diabetes mellitus--secodary prophylaxis after myocardial infarction]. 926 80

A wide range of dietary changes is likely to reduce the risk of macrovascular complications of diabetes. It is critically important to recommend a balance of macronutrients different from that currently consumed in most Western countries. Saturated fatty acids, especially myristic and palmitic acids, and trans fatty acids must be reduced to lower LDL cholesterol. Intake of polyunsaturated fatty acids should not be excessive (less than 10% total energy). Fiber-rich carbohydrate, derived from cereals, vegetables, and fruit with intact cell walls, and cis monounsaturated fatty acids should provide the bulk of total energy. These changes are likely to be associated with the most favorable lipoprotein profile and increase intake of dietary antioxidants and so reduce the level of oxidative stress. A reduction of sodium to below 6 g per day will help to reduce blood pressure levels. Optimal glycemic control has not yet been proved to reduce the risk of macrovascular complications, though this is a desirable goal for many other reasons. Ensuring appropriate energy balance (so that BMI is within the desirable range), using low glycemic index foods, and appropriately balancing carbohydrate intake with hypoglycemic drug therapy provide the best nutritional means of achieving satisfactory blood glucose levels. Successful implementation of nutritional recommendations requires the availability of dietitians capable of translating appropriate nutrition into appropriate foods acceptable to people with diabetes and their families. Clear food labeling and the availability of appropriate manufactured foods will further help patients with diabetes to achieve the dietary recommendations.
Diabetes 1997 Sep
PMID:The role of nutritional modifications in the prevention of macrovascular complications of diabetes. 928 14

The function of neutrophil can be evaluated by measuring oxidative metabolism using chemiluminescence, tetrazolium dye reduction or the others. Those results are not always satisfactory which would be caused by subtle difference in each preparation of the reagents and the lack of reproducibility. Recently, flow cytometric procedures for semi-quantitating superoxide production in neutrophils have been developed to evaluate their function. This procedure, which requires only small amount of whole blood, can easily and rapidly yield reproducible and reliable data. In this study, we optimized analytical conditions and then determined reference interval to evaluate neutrophil function of patients with various disorders. Optimal concentrations and incubation times of DCFH-DA and PMA were 5 mumol/l for 15 minutes and 25 micrograms/ml for 20 minutes, respectively. Production of superoxide in neutrophil was represented by relative fluorescence intensity(RFI) with assay coefficient of variance(CV) of 4.0-11.1%. Neutrophils had to be examined within 2 hours after venipuncture to obtain reliable data. Reference interval was determined as 170.4 +/- 58.7(mean +/- SD) RFI. Neutrophil function of patients with neutropenia, paroxysmal nocturnal hemoglobinuria(PNH), renal failure, systemic lupus erythematosus(SLE), myeloperoxidase deficiency, myelodysplastic syndrome(MDS), and diabetes mellitus were within the reference interval as evaluated by this method. Only neutrophils of chronic granulomatous disease, which is known to give clearly low superoxide production, showed actually decreased value. These results indicate that this procedure would be clinically useful for diagnosis of patient with impaired neutrophil function.
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PMID:[Determination of neutrophil function by measuring superoxide production with whole blood flow cytometry]. 939 45

The effect of improved glycemic control on the prevention or reversal of diabetic nephropathy has been optimally shown by the reduced incidence of albuminuria (accompanied by an increased risk of hypoglycemia) in the Diabetes Control and Complications Trial (DCCT). The earliest detection of the risk or of the presence of diabetic nephropathy continues to be elevated (and confirmed) levels of albuminuria. However, micro- and macroalbuminuria are frequently associated with increased glycated hemoglobin values, complicating attempts to separate the influence of glycemia from an inherent susceptibility for diabetic nephropathy. In the type 1 diabetic patient levels of c-peptide (co-secreted with insulin by the islets of Langerhans) in plasma reflect sustained islet function. C-peptide may be measured in plasma for as long as a decade after the clinical diagnosis of diabetes mellitus, and its presence may be prolonged with better management of diabetes. The consequent improved glycemic control afforded by sustained islet function will reduce the incidence of the retinopathic and nephropathic complications, uniquely accompanied by a lower risk of hypoglycemia. Optimal diabetic management (that is, normal glycemic indices for all diabetic subjects) remains the goal of diabetic therapy. However, failure to normalize glycemic control may remain a reality of contemporary diabetic management. Thus, renal function assays or genetic protocols (each proposed for the earliest detection of diabetic nephropathy) will need to identify individuals at risk against a broadly variable background of glycated hemoglobin levels.
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PMID:Glycemic control and the initiation and progression of the complications of diabetes mellitus. 940 18

Optimal T cell responsiveness requires signaling through the T cell receptor (TCR) and CD28 costimulatory receptors. Previously, we showed that T cells from autoimmune nonobese diabetic (NOD) mice display proliferative hyporesponsiveness to TCR stimulation, which may be causal to the development of insulin-dependent diabetes mellitus (IDDM). Here, we demonstrate that anti-CD28 mAb stimulation restores complete NOD T cell proliferative responsiveness by augmentation of IL-4 production. Whereas neonatal treatment of NOD mice with anti-CD28 beginning at 2 wk of age inhibits destructive insulitis and protects against IDDM by enhancement of IL-4 production by islet-infiltrating T cells, administration of anti-CD28 beginning at 5-6 wk of age does not prevent IDDM. Simultaneous anti-IL-4 treatment abrogates the preventative effect of anti-CD28 treatment. Thus, neonatal CD28 costimulation during 2-4 wk of age is required to prevent IDDM, and is mediated by the generation of a Th2 cell-enriched nondestructive environment in the pancreatic islets of treated NOD mice. Our data support the hypothesis that a CD28 signal is requisite for activation of IL-4-producing cells and protection from IDDM.
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PMID:Neonatal activation of CD28 signaling overcomes T cell anergy and prevents autoimmune diabetes by an IL-4-dependent mechanism. 941 Sep 2

It is not surprising that diabetes care has been a very active area for divisional projects and activities. Diabetes is prevalent in the community (up to one million Australians) and in general practice (1% of GP encounters). Optimal cost-effective diabetes management involves collaboration between general practice and public and private health services--one of the purposes for which divisions were created. Because diabetes is a multisystem chronic disease requiring multi-disciplinary interventions, it has also been a model for applying the health outcomes approach in general practice, especially in New South Wales.
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PMID:News from the divisions: diabetes shared care. 947 90


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