Overcoming psychological barriers to insulin use in type 2 diabetes

Type 2 diabetes mellitus (DM) is characterized by a gradual decrease in insulin sensitivity in peripheral tissues and the liver (insulin resistance), followed by a gradual decline in beta-cell function and insulin secretion. Given this decline, many patients with type 2 DM will require insulin therapy to achieve the glycemic target recommended by the American Diabetes Association of glycosylated hemoglobin (A1C) <7%. The combination of insulin plus oral antidiabetic drugs (OADs) has been shown to improve A1C values in patients who were not adequately controlled with OADs alone. Despite its established benefits, however, insulin therapy continues to be underused. The reluctance to initiate insulin therapy is often related to both provider and patient misperceptions about insulin's efficacy and side effects, as well as the perceived complexity of the treatment regimen. In addition, insulin therapy may be viewed as a "last resort" treatment option for severe disease or as "punishment" for patients' failure to manage their disease. However, patients should be made aware from the time of diagnosis that diabetes is a progressive disease and that it is likely that insulin therapy will be required at some point during the course of the disease. The subject of insulin therapy, therefore, should be approached positively and should be presented as an effective and flexible way to achieve glycemic goals for any patient at any time during therapy.     

The use of insulin to improve treatment in type 2 diabetes

Diabetes is a global problem of increasing proportions and requires adherence to tight treatment targets to prevent complications. This article focuses on the use of insulin to gain good glycaemia control in type 2 diabetes.     

Orlistat augments postprandial increases in glucagon-like peptide 1 in obese type 2 diabetic patients

OBJECTIVE: Orlistat leads to improved glycemic control in obese type 2 diabetic patients, which is attributed to decreased insulin resistance associated with weight loss. Glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are gut hormones that are secreted in response to food intake, and they both stimulate insulin secretion. Orlistat decreases fat absorption and increases intestinal fat content, which may lead to increased secretion of these peptides. In this pilot study, we tested the hypothesis that increased levels of these intestinal hormones may be involved in the improvement of postprandial hyperglycemia observed previously with orlistat in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: A total of 29 type 2 diabetic patients, who were not taking insulin or alpha-glucosidase inhibitors, were enrolled in the study. On a crossover and single-blind design, after an overnight fasting, the patients received 120-mg orlistat or placebo capsules, followed by a standard 600-kcal mixed meal that contained 38% fat. At baseline and 60 min after the meal, blood samples were obtained for the measurement of GLP-1, GIP, insulin, C-peptide, triglycerides, free fatty acids, and glucose. RESULTS: All measured parameters increased significantly in response to the mixed meal compared with baseline, both with orlistat or placebo. When compared with the placebo, the orlistat administration resulted in a significantly enhanced postprandial increase in GLP-1 and C-peptide levels and attenuated the postprandial rise in glucose and triglycerides. CONCLUSIONS: The results of this study suggest that apart from decreasing insulin resistance as a result of weight loss, orlistat may increase postprandial GLP-1 levels, thereby enhancing the insulin secretory response to the meal and blunting the postprandial rise in glucose in type 2 diabetic patients. Increased GLP-1 levels, which lead to decreased food intake, may also contribute to the weight loss that is associated with the use of this drug.     

Cardiovascular drug use and hospitalizations attributable to type 2 diabetes

OBJECTIVE: To investigate cardiovascular drug use and hospitalizations attributable to type 2 diabetes from 1 year before until 6 years after the start of oral antidiabetic therapy. RESEARCH DESIGN AND METHODS: In this cohort study, 2,584 patients with type 2 diabetes were selected from the PHARMO Record Linkage System, comprising pharmacy records and hospitalizations for all 320,000 residents of six Dutch cities. Patients with type 2 diabetes were identified as incident oral antidiabetic drug users between 1992 and 1997. Nondiabetic subjects were 1:1-matched for age, sex, pharmacy, and index date and received no insulin, oral antidiabetic drugs, or glucose-testing supplies. RESULTS: Patients with type 2 diabetes were more likely to use cardiovascular drugs (RR 1.28 [95% CI 1.23-1.34]) and to be hospitalized because of cardiovascular diseases (1.54 [1.33-1.78]) after the start of oral antidiabetic therapy than nondiabetic subjects. Differences between patients with type 2 diabetes and nondiabetic subjects lessened from 1 year before until 6 years after the start of oral antidiabetic therapy, reflected by decreasing attributable risks for diuretics, beta-blockers, calcium channel blockers, and cardiac and antithrombotic drugs. The difference in use of angiotensin-converting enzyme inhibitors and lipid-lowering drugs increased. Cardiovascular hospitalizations attributable to type 2 diabetes were approximately 50% in the years close to the start of oral antidiabetic treatment and decreased to approximately 33% in the following years. CONCLUSIONS: Although cardiovascular drug use and hospitalizations remained increased in patients with type 2 diabetes after the start of oral antidiabetic therapy, cardiovascular drug use attributable to type 2 diabetes decreased after the start of oral antidiabetic therapy, especially beta-blockers, whereas cardiovascular hospitalizations first decreased and then stabilized.     

Hypoglycemia in type 2 diabetes

Iatrogenic hypoglycemia is the limiting factor in the glycemic management of diabetes and a barrier to true glycemic control and becomes a progressively frequent clinical problem in advanced type 2 diabetes mellitus. As patients approach the insulin-deficient end of the spectrum of type 2, hypoglycemia results from the interplay of therapeutic insulin excess and compromised physiologic and behavioral defenses against falling plasma glucose concentrations.By practicing hypoglycemia risk reduction, applying the principles of aggressive glycemic therapy, and considering conventional risk factors and those indicative of compromised glucose counterregulation,it is possible to minimize the risk of hypoglycemia and improve glycemic control. Nonetheless, people with diabetes need better treatment regimens.     

Dyslipidemia in type 2 diabetes

Type 2 diabetes mellitus is associated with a cluster of lipid abnormalities:elevated plasma triglycerides, reduced high-density lipoprotein cholesterol, and smaller and denser low-density lipoproteins,which have been associated with an increased risk of cardiovascular disease. Insulin resistance may contribute to dyslipidemia associated with type 2 diabetes by increasing hepatic secretion of large,triglyceride-rich very low-density lipoprotein particles and by impairing the clearance of lipoprotein particles from plasma. Lifestyle interventions may be effective in improving the diabetic dyslipidemia syndrome. For patients who do not respond to lifestyle changes, pharmacologic therapies (lipid-lowering medications and anti-diabetic agents) are available. Clinical trials demonstrate that the use of such pharmaceutics to treat diabetic dyslipidemia concomitantly reduces the risk of coronary artery disease.     

The use of insulin secretagogues in the treatment of type 2 diabetes.

Secretatogues are a class of agents that achieve their hypoglycemic effects through stimulating insulin release. They include the sulfonylureas, repaglinide, and the investigational agent glucagon-like peptide. The secretagogue agents have been studied extensively as monotherapy and in conjunction with other classes of oral agents, including alpha-glucosidase inhibitors, bijuanides, and thiazolidinediones, for the treatment of type 2 diabetes. This article reviews the pharmacodynamic and pharmacokinetic differences of the secretagogues, as well as the most recent clinical trials. Such information should be helpful when deciding which agent or agents will yield the best glycemic control for an individual patient.     

Innovations in the treatment of type 2 diabetes mellitus: use of incretins

There is a new class of drugs used to treat diabetes mellitus (DM). It has come into existence after long-term studies of the fundamentally new hemostastic mechanism in glucose regulation via the gastrointestinal hormones incretins. With the advent of this class of drugs that minimize routine adverse reactions (weight gain, glycemic risk, nephro-, hepato-, and cardiotoxic effects, etc.), there is hope for a delay in the progressive increase of secretory function and beta-cell mass, which is inevitable during standard treatment (which presages the eventual need to initiate insulin therapy 7-10 years after the onset of the disease). The mechanism of action of incretins is considered. The place of novel agents (glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors) in the total pattern of treatment for type 2 DM, indications for and contraindications to their use, benefits versus traditional glucose-lowering therapy (the inestimable advantage of these drugs is no risk for hypoglycemia), and prospects for their future application are discussed.     

Symptom use and self-regulation in type II diabetes

A model of self-regulation that explains the health behavior of type II diabetic patients was tested by examining the use of symptoms as indicators of perceived blood glucose levels in 38 outpatients. Results of the study supported the self-regulation model by demonstrating that patients use symptoms to monitor blood glucose levels and to guide diabetes-related actions. Implications of the model for planning interventions with type II diabetes are discussed.     

Preventing type 2 diabetes

The rapid and often relentless progression of type 2 diabetes suggests that high-risk patients should be provided with an equally aggressive strategy to protect their remaining beta-cell function and endogenous insulin secretion. Management of patients with prediabetes should incorporate both lifestyle and pharmacologic intervention. Although no specific recommendations are published for the management of prediabetes, one can assume that preservation of pancreatic beta-cell function, improvement in peripheral insulin resistance and pancreatic insulin secretion, reducing pancreatic alpha-cell secretion of glucagon, preventing long- and short-term diabetes-related complications, and assisting patients to loose weight are beneficial. Aggressive, timely, and physiologic management of prediabetes should be advocated.     

Understanding type 2 diabetes

Practice profiles are reflective pieces written by nurses in practice and based on continuing professional development articles. This week Susan Ackroyd discusses type 2 diabetes.     

Insulin therapy in type 2 diabetes

Unlike type 1 diabetic patients, who have no significant insulin secretion and require insulin therapy from the disease onset, a prominent feature in the early stages of type 2 diabetes is insulin resistance with hyperinsulinemia. Therefore, improving insulin sensitivity by diet, exercise, and weight management will benefit type 2 diabetic patients. When these measures fail, glycemic goals may be achieved with oral agents. However, at the late stage of disease,most patients require exogenous insulin therapy to achieve optimal glucose control. The American Diabetes Association recommends that the objective of normalizing glycemia and glycosylated hemoglobin concentrations for patients with type 2 diabetes should be similar to that for type 1 diabetes.