Glycemic Control and Complications in Type 2 Diabetes Mellitus

https://doi.org/10.1016/j.amjmed.2009.12.004Get rights and content

Abstract

Current guidelines for treating patients with type 2 diabetes mellitus are based on glycemic standards derived from epidemiologic data; however, the course of the disease, from prediabetes to end-stage complications, is not the same in all patients. Microvascular complications, including nephropathy, retinopathy, and neuropathy, are strongly related to hemoglobin A1c (HbA1c). However, vascular complications may progress in patients who have HbA1c <7.0% and may appear even in undiagnosed patients owing to transient increases in plasma glucose concentrations. Concomitant atherosclerosis and occult macrovascular disease may follow an accelerated course in type 2 diabetes. Macrovascular complications may develop early, and, like microvascular complications, do not correlate linearly with HbA1c. Managing hyperglycemia in the later stages of type 2 diabetes does not appear to be associated with improved cardiovascular outcomes. The glucotoxicity and lipotoxicity that may precede prolonged hyperglycemia and β-cell dysfunction are early, reversible pathophysiologic events. This suggests that prompt management may modify the course of hyperglycemia and prevent or delay long-term complications. The challenge remains to identify patients with early type 2 diabetes who are at risk for rapid progression of β-cell decline and premature development of microvascular complications. Ongoing research into the mechanisms responsible for diabetic complications may provide new markers to help identify patients with type 2 diabetes who can benefit from earlier antidiabetes treatments.

Section snippets

The Current State of Diabetes Care

Approximately 24 million persons in the United States have diabetes, of which type 2 diabetes accounts for the vast majority of cases.1 Based on the National Health and Nutrition Examination Survey (NHANES) 1999 to 2002 data, ∼73 million Americans have diabetes or impaired fasting glucose (IFG), a condition that increases the risk for diabetes.2 A retrospective cohort study using the database of a healthcare maintenance organization, showed that nearly 25% of individuals with newly acquired

Glycemic Control and Microvascular Complications

The incidence and prevalence of neuropathy, retinopathy, and nephropathy increase with the duration of diabetes.16 The United Kingdom Prospective Diabetes Study (UKPDS) 35 demonstrated that HbA1c is strongly related to microvascular effects in patients with type 2 diabetes. Over a mean follow-up of 10 years, which was equivalent to the duration of type 2 diabetes in the study, a 1% reduction in HbA1c was associated with a 37% reduction in microvascular complications and a 43% reduction in

Hyperglycemia and Macrovascular Disease

Hyperglycemia, as measured by HbA1c, is a predictor of coronary heart disease (CHD) risk. In a Finnish study that followed elderly men and women (of whom ∼16% and ∼19% had type 2 diabetes, respectively, at baseline) for up to 3.5 years, HbA1c >7.9% were associated with a 21% incidence of CHD-related events and a 12% incidence of CHD mortality (P <0.05).28 In the Norfolk cohort of the European Prospective Investigation of Cancer and Nutrition (EPIC-Norfolk), 82% of the excess mortality

Diabetes Mellitus: Roles of Glucotoxicity and Glucolipotoxicity

Many clinicians believe that glucotoxicity plays a role in β-cell function, amplifies lipotoxicity, and reduces β-cell mass. Under current treatment models, glucotoxicity would not be considered a complication of type 2 diabetes because antidiabetes treatment is warranted only after a patient has reached a certain degree of β-cell dysfunction, as evidenced by fasting hyperglycemia. Just as microvascular and macrovascular complications begin before current treatment protocols prescribe

Summary

Almost 50% of patients with type 2 diabetes have HbA1c above the generally recommended goal of <7%. However, microvascular complications may occur in many patients whose HbA1c is below the current target. A recent understanding of the biochemical pathology of microvascular complications may lead to development of novel disease markers and treatments to help identify and manage patients before they are diagnosed with type 2 diabetes.

Macrovascular complications may represent the greatest cause of

Author Disclosures

The author of this article has disclosed the following industry relationships:

  • Mark Stolar, MD, is a member of Speakers' Bureaus of Amylin Pharmaceuticals, Inc., Novo Nordisk, and Takeda Pharmaceuticals North America, Inc.; and serves on the advisory board of Takeda Pharmaceuticals North America, Inc.

Acknowledgment

I thank Jonathan Wert, MD, of BlueSpark Healthcare Communications for literature research and editorial assistance.

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