Management of type 2 diabetes: oral agents, insulin, and injectables.

This article highlights the use of antidiabetic agents, including insulin. Medical nutrition therapy (MNT) and physical activity are the cornerstones of management of type 2 diabetes. The progressive nature of type 2 diabetes requires use of one or more oral agents and eventually insulin, along with MNT and physical activity. The American Association of Clinical Endocrinologists and the European Association for the Study of Diabetes have recommended a lower hemoglobin A1c target of <6.5%, and many health care providers strive to achieve normalization of blood glucose. Achievement of these goals often prompts providers to consider combination therapy to target different pathogenic mechanisms and manage both fasting and postprandial blood glucose levels. Maintenance of glycemic control over the lifespan of a patient with diabetes is overwhelmingly likely to require combination therapy with oral diabetes medications. The UK Prospective Diabetes Study reported that <50% of patients maintained glycemic control on MNT or monotherapy with oral agents at 3 years, and that number dropped to <25% at 9 years. Newer agents and insulins have become available since the UK Prospective Diabetes Study was completed and have enhanced our armamentarium of therapeutics for treatment of diabetes.

Identification and treatment of prediabetes to prevent progression to type 2 diabetes.

Overt type 2 diabetes is usually preceded by a condition known as prediabetes, which is characterized by impaired fasting glucose (IFG) and impaired glucose tolerance (IGT). Both IFG and IGT exhibit elevated glucose levels that are not sufficient to be classified as diabetes but that represent the development of insulin resistance. Achieving glycemic control in patients with prediabetes through lifestyle and pharmacologic interventions can effectively prevent or delay the development of diabetes and its associated complications. The first step, however, is to identify patients at risk. Although patients can be identified with an oral glucose tolerance test (OGTT) or a fasting plasma glucose (FPG) screening, a normal FPG does not preclude an elevated OGTT and, therefore, the presence of prediabetes. For patients who progress to type 2 diabetes, intensive therapy aimed at reducing and maintaining glycosylated hemoglobin (A1C) levels < 7% has been shown to reduce the risk of complications. An A1C level > or = 7% should signal the need to initiate or change therapy to achieve glycemic goals.

Identification and treatment of prediabetes to prevent progression to type 2 diabetes.

Overt type 2 diabetes is usually preceded by a condition known as prediabetes, which is characterized by impaired fasting glucose (IFG) and impaired glucose tolerance (IGT). Both IFG and IGT exhibit elevated glucose levels that are not sufficient to be classified as diabetes but that represent the development of insulin resistance. Achieving glycemic control in patients with prediabetes through lifestyle and pharmacologic interventions can effectively prevent or delay the development of diabetes and its associated complications. The first step, however, is to identify patients at risk. Although patients can be identified with an oral glucose tolerance test (OGTT) or a fasting plasma glucose (FPG) screening, a normal FPG does not preclude an elevated OGTT and, therefore, the presence of prediabetes. For patients who progress to type 2 diabetes, intensive therapy aimed at reducing and maintaining glycosylated hemoglobin (A1C) levels <7% has been shown to reduce the risk of complications. An A1C level > or =7% should signal the need to initiate or change therapy to achieve glycemic goals.

Management of hyperhomocysteinemia.

Hyperhomocysteinemia is an established risk factor for cardiovascular disease. The modification of traditional cardiovascular risk factors has resulted in better morbidity and mortality outcomes, so the treatment of hyperhomocysteinemia is explored for a similar benefit. Vitamin B(6), vitamin B(12) and folate, as co-factors in the metabolism of homosyteine, are used in the treatment of hyperhomocysteinemia. Betaine, a methyl-donor in a separate homocysteine metabolism pathway, is also used to treat hyperhomocysteinemia. These supplements have been used in various doses and combinations for different periods of time, with favorable outcomes. There is still no concensus whether hyperhomocysteinemia can be treated with folic acid alone, or in combination with vitamin B(6) and vitamin B(12). The dose of the supplements required to normalize fasting homocysteine remains to be determined, especially in diabetic nephropathy, hemodialysis and renal transplant patients. The benefits from lowering homocysteine levels have mainly been demonstrated in surrogate cardiovascular outcomes. The treatment of hyperhomocysteinemia cannot be firmly advocated until there are trials that demonstrate a beneficial clinical endpoint. In patients who have cardiovascular disease in the absence of more established risk factors, investigation and treatment of hyperhomocysteinemia should be considered.