Efficacy Of Glycemic Control Research Articles

Improvement in Glycemic Control and Outcome Corresponding to Intensive Insulin Therapy Protocol Development

Intensive insulin therapy (IIT) has been shown to reduce mortality and morbidity in longer stay, critically ill patients. However, this has been demonstrated in a single site, whereas two multicentric studies have been terminated prematurely mainly due to hypoglycemia. Other difficulties with IIT include efficacy of glycemic control. This report describes how IIT can be improved by protocol simplification and removal of glucose supplementation. A clinical information system established at each bedspace guided staff through the IIT algorithms. Time spent within predefined glycemic ranges was calculated assuming a linear trend between successive measurements. Three groups were investigated retrospectively: IIT1 protocol,(1) an updated IIT2 version, and intuitive nurse dosing of conventional insulin therapy (CIT). Fifty consecutive, critically ill patients were included in each study group. Patient characteristics were similar in each group. The frequency of CIT and IIT2 blood glucose measurements were 11.6 and 11.5 measurements per day, respectively, while the IIT1 measurements were more frequent (14.5 measurements per day). The mean proportion of time spent in the target glycemic range (4.4-6.1 mmol/liter) was highest in the IIT2 group (34.9%), as compared to the IIT1 (22.9%) and CIT groups (20.3%) (p <.001). Survival at 28 days was 74.5% for IIT2 (highest), 68% for IIT1, and 48% for CIT (p = .02). There were a similar number of those experiencing a severe hypoglycemic event in each group. IIT protocol optimization was associated with increased glycemic control and improved 28-day survival. The better optimized IIT2 protocol provided tighter control than either the IIT1 or CIT protocol, without increased sampling or incidence of hypoglycemia. The clinical effectiveness of the IIT algorithm appeared to be improved by simplifying the protocol to meet the needs of the critical care unit.

Evaluation of Treatment Satisfaction Associated with the Use of Insulin Aspart in Continuous Subcutaneous Insulin Infusion

The purpose of this study was to compare treatment satisfaction among people with type 1 and type 2 diabetes after switching from insulin lispro to insulin aspart in continuous subcutaneous insulin infusion (CSII). Efficacy of glycemic control between treatments was also investigated. Subjects using CSII with insulin lispro for 6 months or longer continued this therapy over a 4-week period and then switched to insulin aspart in CSII for 12 weeks. The Diabetes Treatment Satisfaction Questionnaire (DTSQ) and Insulin Treatment Satisfaction Questionnaire (ITSQ) were administered immediately prior to the switch and again at the end of 12 weeks of therapy with insulin aspart. Hemoglobin A(1c)(A1C) and fasting blood glucose (FBG) levels, insulin dose, and body weight were recorded at the same time points. Although average overall DTSQ score did not change significantly, average overall ITSQ score was significantly improved following the insulin aspart treatment. There was a small but statistically significant reduction in mean A1C and FBG following 12 weeks of CSII using insulin aspart. Both insulin aspart and insulin lispro are appropriate for CSII. ITSQ improvements suggest that aspects of CSII therapy with insulin aspart positively impact treatment satisfaction.

Glycemic control and insulin therapy in sepsis and critical illness

To review the literature about the pathophysiology of hyperglycemia and glycemic control in children and adults with sepsis and critical illness. Non-systematic survey of the medical literature using MEDLINE and terms hyperglycemia, glycemic control, intensive insulin therapy, sepsis and intensive care. Articles were selected according to their relevance based on the authors' opinion. Hyperglycemia is frequent in critically ill children and it is associated with worsened outcome. In adults, there is no consensus on the efficacy and safety of glycemic control. We describe the possible mechanisms involved in glucose toxicity and the beneficial effects of glycemic control. Initial studies showed that use of insulin to achieve glycemic control reduced morbidity and mortality in adult intensive care; however, recent studies have failed to confirm these findings. Importantly, it is evident that glycemic control is associated with increased incidence of hypoglycemia. The efficacy of glycemic control has not yet been studied in critically ill children. Glycemic control is a novel therapeutic option in critical care. Conflicting evidence in adults means that before we apply this approach to pediatrics it will need to be assessed in clinical trial.

Controle glicêmico e terapia insulínica em sepse e doença crítica

OBJETIVO: Revisar a literatura sobre a fisiopatologia de hiperglicemia e controle glicemico em criancas e adultos com sepse e doenca critica. FONTES DE DADOS: Pesquisa nao sistematica da literatura medica atraves da base de dados MEDLINE usando os termos hiperglicemia, controle glicemico, terapia insulinica intensiva, sepse e terapia intensiva. Os artigos foram selecionados de acordo com sua relevância, conforme a opiniao dos autores. SINTESE DOS DADOS: A hiperglicemia e frequente em criancas com doencas criticas e esta associada a desfecho negativo. Em adultos, nao ha um consenso sobre a eficacia e seguranca do controle glicemico. Descrevemos os possiveis mecanismos envolvidos em toxicidade da glicose e os efeitos beneficos do controle glicemico. Estudos iniciais demonstraram que o uso de insulina para atingir controle glicemico reduziu a morbimortalidade em terapia intensiva em adultos; no entanto, estudos recentes nao confirmaram esses achados. E importante destacar que o controle glicemico esta evidentemente associado a aumento da incidencia de hipoglicemia. A eficacia do controle glicemico ainda nao foi estudada em criancas criticamente doentes. CONCLUSAO: O controle glicemico e uma nova opcao terapeutica em terapia intensiva. Evidencias conflitantes em adultos significam que, antes de aplicar esta abordagem em pediatria, e necessario avalia-la em ensaio clinico.

Vildagliptin An Oral Dipeptidyl Peptidase-4 Inhibitor for Type 2 Diabetes

Vildagliptin is a member of a new class of oral antidiabetogenic agents known as dipeptidyl peptidase-4 (DDP-4) inhibitors.These drugs enhance islet function by improving α- and β-cell responsiveness to glucose. Mechanism of action studies in patients with type 2 diabetes show that vildagliptin increases plasma levels of active glucagon-like peptide-1, improves glucosedependent insulin secretion and β-cell function, improves insulin sensitivity, reduces inappropriate glucagon secretion, reduces fasting and postprandial glucose, and decreases HbA1c. Large-scale treatment trials with vildagliptin 50mg or 100mg per day as monotherapy or in combination in drug-naïve patients or as add-on therapy to on-going anti-diabetic treatment show that it is effective in reducing HbA1c (with greater decreases occurring in patients with higher initial HbA1c levels), maintains efficacy in glycemic control as monotherapy for at least 1 year, is associated with infrequent hypoglycemia, and does not cause weight gain.

Chronic complications in diabetes mellitus.

Diabetes mellitus is one of the most prevalent diseases among adult population in Japan. The persistent hyperglycemia is responsible for the appearance of various organ and tissue damage in diabetic subjects. Eyes, kidneys and peripheral nerves are frequently damaged due to diabetes-specific alteration in microvessels. Furthermore, large vessels are also damaged causing severe diseases such as myocardial infarction, cerebral infarction and gangrene. The pathogenesis of these alterations in small and large vessels has been extensively studied and various metabolic abnormalities induced by hyperglycemia are proposed to play a major role in the development of these diabetic vascular complications. Among those metabolic abnormalities, the activation of the diacyl glycerol-protein kinase C pathway has been proposed to play a pivotal role in the pathogenesis of not only microvascular complications but also macrovascular complications. The beneficial effect of a protein kinase C inhibitor on renal, retinal and atherosclerotic lesions in diabetic animal models may support this notion. The results of several large-scale clinical trials have confirmed the efficacy of glycemic control as well as blood pressure control in the management of diabetic complications. It is a prerequisite, therefore, to obtain near-normal glycemic and blood pressure control in order to prevent the appearance of diabetic complications and also suppress their progression. In this aspect nutritional consideration may be an important way to improve the quality of these managements.

The PROTECT study: final results of a large multicenter postmarketing study in patients with type 2 diabetes

The Precose ® Resolution of Optimal Titration to Enhance Current Therapies (PROTECT) trial was a nationwide postmarketing study designed to assess the effectiveness, tolerability, and safety of acarbose in patients with type 2 diabetes mellitus. This prospective, multicenter, open-label, 28-week trial enrolled 6142 patients who had type 2 diabetes that was inadequately controlled with either diet alone or diet plus a sulfonylurea. The dosage of acarbose was titrated from 25 mg TID to 50 mg TID (forced titration) and then titrated from 50 mg TID to 100 mg TID based on tolerability and efficacy. Efficacy of glycemic control was assessed by recording changes in glycated hemoglobin A 1c (Hb A 1c) and 1-hour postprandial plasma glucose (PPG) levels. Tolerability and safety were determined on the basis of patients' reports of treatment-emergent adverse events and by review of laboratory test results. Acarbose was safe and effective in improving glycemic control in patients with type 2 diabetes, regardless of their age, weight, ethnic background, time since diagnosis, or concomitant sulfonylurea therapy. HbA 1c levels declined throughout the treatment period, for a mean change in Hb A 1c of −0.66%. The mean change from baseline in 1-hour PPG levels was −41 mg/dL at the end of treatment. Although all types of patients enrolled in the study responded positively to acarbose therapy, certain subgroups responded particularly well, especially those who had been diagnosed with the disease for less than 1 year and those who were untreated at study entry. Adverse events consisted primarily of gastrointestinal disturbances

Estimated benefits of glycemic control in microvascular complications in type 2 diabetes.

The benefits of intensive glycemic control in patients with type 2 diabetes are not well quantified. It is therefore not clear which patients will benefit most from aggressive glycemic control. To evaluate the efficacy of glycemic control in type 2 diabetes. Markov decision model. Diabetic patients at a health maintenance organization. Risks for developing blindness and end-stage renal disease; number of patients and patient-years needed to treat to prevent complications. For a patient in whom diabetes developed before 50 years of age, reducing hemoglobin A1c levels from 9% to 7% results in an estimated 2.3-percentage point decrease (from 2.6% to 0.3%) in lifetime risk for blindness due to retinopathy. The same change in a patient with diabetes onset at 65 years of age would be expected to decrease the risk for blindness by 0.5 percentage points (from 0.5% to < 0.1%). However, the Markov model predicts substantially greater benefit when moving from poor to moderate glycemic control than when moving from moderate to almost-normal glycemic control. Targeting less than 20% of the patients at one health maintenance organization for intensified therapy may prevent more than 80% of the preventable patient-time spent blind. The risks for end-stage renal disease and the risk reduction provided by improved glycemic control are lower than those for blindness. This probability model, based on extrapolation from the experience with type 1 diabetes, suggests that patients with early onset of type 2 diabetes will accrue substantial benefit from almost-normal glycemic control. In patients with later onset, moderate glycemic control prevents most end-stage complications caused by microvascular disease. These results have important implications for informing patients and allocating health care resources.

PROTECT interim results: a large multicenter study of patients with type II diabetes

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 7000 type II diabetic patients. The present report describes the interim results for 2139 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 A 1c (Hb A 1c) 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 A 1c, 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 A 1c 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.

Metformin.

Metformin (dimethylbiguanide) is an orally administered drug used to lower blood glucose concentrations in patients with non-insulin-dependent diabetes mellitus (NIDDM).1 It improves insulin sensitivity and thus decreases the insulin resistance that is prevalent in NIDDM. The efficacy of glycemic control achieved with metformin is similar to that achieved with sulfonylureas, although their modes of action differ. Metformin can be used either as initial therapy or as an additional drug when sulfonylurea therapy alone is inadequate. In this article we shall discuss the pharmacology and clinical use of metformin, which is now available in the United States.The Burden of Non-Insulin-Dependent . . .