Showing papers by "Silvio E. Inzucchi published in 2002"

Oral Antihyperglycemic Therapy for Type 2 Diabetes: Scientific Review

Abstract: ContextCare of patients with type 2 diabetes has been revolutionized throughout the past several years—first, by the realization of the importance of tight glycemic control in forestalling complications, and second, by the availability of several unique classes of oral antidiabetic agents. Deciphering which agent to use in certain clinical situations is a new dilemma facing the primary care physician.ObjectiveTo systematically review available data from the literature regarding the efficacy of oral antidiabetic agents, both as monotherapy and in combination.Data SourcesA MEDLINE search was performed to identify all English-language reports of unique, randomized controlled clinical trials involving recently available oral agents for type 2 diabetes. Bibliographies were also reviewed to find additional reports not otherwise identified.Study Selection and Data ExtractionStudies (63) were included in the analysis if they had a study period of at least 3 months; if each group contained at least 10 subjects at the study's conclusion; and if hemoglobin A1c was reported. When multiple dosages of a drug were tested, the results of the highest approved dosage were used. In placebo-controlled trials, hemoglobin A1c data are presented as the difference between the change in treated vs placebo subjects.Data SynthesisFive distinct oral drug classes are now available for the treatment of type 2 diabetes. Compared with placebo treatment, most of these agents lower hemoglobin A1c levels approximately 1% to 2%. Equivalent efficacy is usually demonstrated when different agents are compared with one another in the same study population. When they are used in combination, there are additional glycemic benefits. Long-term vascular risk reduction has been demonstrated only with sulfonylureas and metformin.ConclusionsWith few exceptions, the available oral antidiabetic agents are equally effective at lowering glucose concentrations. Their mechanisms of action are different, however, and as a result they appear to have distinct metabolic effects. These are reflected in their adverse effect profiles and their effect on cardiovascular risk, which may influence drug choice.

Mechanism by which high-dose aspirin improves glucose metabolism in type 2 diabetes

Abstract: Recent studies have implicated fatty acid-dependent activation of the serine kinase IKKbeta, which plays a key role in tissue inflammation, in the pathogenesis of insulin resistance. High doses of salicylates have recently been shown to inhibit IKKbeta activity and might therefore ameliorate insulin resistance and improve glucose tolerance in patients with type 2 diabetes. To test this hypothesis, we studied nine type 2 diabetic subjects before and after 2 weeks of treatment with aspirin ( approximately 7 g/d). Subjects underwent mixed-meal tolerance tests and hyperinsulinemic-euglycemic clamps with [6,6-(2)H2]glucose to assess glucose turnover before and after treatment. High-dose aspirin treatment resulted in a approximately 25% reduction in fasting plasma glucose, associated with a approximately 15% reduction in total cholesterol and C-reactive protein, a approximately 50% reduction in triglycerides, and a approximately 30% reduction in insulin clearance, despite no change in body weight. During a mixed-meal tolerance test, the areas under the curve for plasma glucose and fatty acid levels decreased by approximately 20% and approximately 50%, respectively. Aspirin treatment also resulted in a approximately 20% reduction in basal rates of hepatic glucose production and a approximately 20% improvement in insulin-stimulated peripheral glucose uptake under matched plasma insulin concentrations during the clamp. In conclusion, these data support the hypothesis that IKKbeta represents a new target for treating type 2 diabetes mellitus.

The Effects of Rosiglitazone on Insulin Sensitivity, Lipolysis, and Hepatic and Skeletal Muscle Triglyceride Content in Patients With Type 2 Diabetes

Abstract: We examined the effect of three months of rosiglitazone treatment (4 mg b.i.d.) on whole-body insulin sensitivity and in vivo peripheral adipocyte insulin sensitivity as assessed by glycerol release in microdialysis from subcutaneous fat during a two-step (20 and 120 mU.m(-2).min(-1)) hyperinsulinemic-euglycemic clamp in nine type 2 diabetic subjects. In addition, the effects of rosiglitazone on liver and muscle triglyceride content were assessed by (1)H-nuclear magnetic resonance spectroscopy. Rosiglitazone treatment resulted in a 68% (P < 0.002) and a 20% (P < 0.016) improvement in insulin-stimulated glucose metabolism during the low- and high- dosage-insulin clamps, respectively, which was associated with approximately 40% reductions in plasma fatty acid concentration (P < 0.05) and hepatic triglyceride content (P < 0.05). These changes were associated with a 39% increase in extramyocellular lipid content (P < 0.05) and a 52% increase in the sensitivity of peripheral adipocytes to the inhibitory effects of insulin on lipolysis (P = 0.04). In conclusion, these results support the hypothesis that thiazolidinediones enhance insulin sensitivity in patients with type 2 diabetes by promoting increased insulin sensitivity in peripheral adipocytes, which results in lower plasma fatty acid concentrations and a redistribution of intracellular lipid from insulin responsive organs into peripheral adipocytes.

Insulin resistance and risk for stroke

Abstract: Background and purpose: Resistance to insulin-mediated glucose uptake by peripheral tissues is a cardinal defect in type 2 diabetes mellitus. Insulin resistance is also common among nondiabetic individuals, and may be an important risk factor for stroke in both populations. The authors review the definition, epidemiology, and treatment of insulin resistance. Methods: The authors searched Medline (1977–2001) and reviewed bibliographies to identify pertinent English-language publications. Results: Insulin resistance is present in most patients with type 2 diabetes. It is also common among elderly persons, certain ethnic groups, and persons with hypertension, obesity, physical deconditioning, and vascular disease. The principal pathophysiologic defect is impaired intracellular signaling in muscle tissue leading to defective glycogen synthesis. Insulin resistance is associated with numerous metabolic, hematologic, and cellular events that promote atherosclerosis and coagulation. The association between insulin resistance and risk for stroke has been examined in four case-control studies and five prospective observational cohort studies. Six of the nine studies are methodologically sound and provide evidence that insulin resistance is associated with risk for stroke. Conclusion: Insulin resistance may be a prevalent risk factor for stroke. New drugs can safely reduce insulin resistance and may have a role in stroke prevention.

Glargine and lispro: two cases of mistaken identity.

Abstract: Insulin glargine (Lantus; Aventis, Parsippany, NJ) is a recently available basal insulin analog that appears to have a more consistent activity profile than comparable long-acting insulin products (1). It is typically administered as a single injection before bedtime. Due to minor modification of the amino acid sequence in both the A- and B-chains of the insulin molecule, glargine is soluble only in an acidic pH (2). When injected, glargine precipitates in the neutral pH of subcutaneous tissues, prolonging its systemic absorption (2). Clinical trials have demonstrated that compared with NPH insulin, glargine improves fasting glucose in patients with type 1 diabetes (3) and results in less nocturnal hypoglycemia in patients with both type 1 (4) and type 2 (5) diabetes. It may be particularly useful in individuals who demonstrate labile blood glucose control with conventional insulin formulations. One immediately obvious difference between glargine and other long- (or intermediate-) acting insulins is that the product is a clear solution, similar to short-acting products, not a semi-opaque suspension. To avoid confusion …

Type 2 diabetes therapy. A pathophysiologically based approach.

Abstract: The dramatic increase in the number of classes of oral antidiabetic agents has provided physicians with more tools to help patients manage type 2 diabetes. Of course, glycemic control must remain paramount when choosing an oral agent. However, the mechanism of action of an agent, its side effect profile, and the potential for various nonglycemic benefits may help determine which is the best drug for an individual patient.

Glycemic management of diabetes in the perioperative setting.

Abstract: The patient with diabetes poses unique challenges in the perioperative setting. In addition to the increased risk of poor wound healing, postoperative infection, and vascular events, patients with diabetes are at ongoing risk of metabolic decompensation due to alteration in their antihyperglycemic regimens and to the stress of surgery itself. In the following pages, I review current approaches to glycemic control in patients with diabetes undergoing surgical procedures.