Criteria diagnosis

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Medication Summary
Pharmacologic therapy has changed dramatically in the last 10 years. New drug classes and new drugs have become available for the treatment of type 2 diabetes.[231, 232] These drugs allow for the use of combination oral therapy, often with improvement in glycemic control that was previously beyond the reach of medical therapy. In 2012, the American College of Physicians (ACP) issued updated guidelines for the oral treatment of type 2 diabetes.[233] The recommendations, published in the Annals of Internal Medicine, include the following:

When diet, exercise, and weight loss fail to improve hyperglycemia in patients with diabetes, clinicians should add oral drug therapy. Metformin is the drug of choice for initial monotherapy unless contraindicated. If metformin and lifestyle modifications fail to control hyperglycemia, a second oral agent should be added. No combination therapy is recommended over another, but some studies indicate that metformin plus another agent generally has better efficacy than other monotherapies or combination therapies.

Traditionally, diet modification has been the cornerstone of diabetes management. Weight loss is more likely to control glycemia in patients with recent onset of the disease than in patients who are significantly insulinopenic. Medications that induce weight loss, such as orlistat, may be effective in highly selected patients but are not generally indicated in the treatment of the average patient with type 2 diabetes mellitus. Patients who are symptomatic at initial presentation with diabetes may require transient treatment with insulin to reduce glucose toxicity (which may reduce beta cell insulin secretion and worsen insulin resistance) or an insulin secretagogue to rapidly relieve symptoms such as polyuria and polydipsia. Dietary Modifications For most patients, the best diet is one consisting of the foods that they are currently eating. Attempts to calibrate a precise macronutrient composition of the diet to control diabetes, while time-honored, are generally not supported by the research, although studies are ongoing.[149] Caloric restriction is of first importance. After that, individual preference is reasonable. Modest restriction of saturated fats and simple sugars is also reasonable. However, some patients have remarkable short-term success with high-fat, low-carbohydrate diets of various sorts. Therefore, the author always stresses weight management in general and is flexible regarding the precise diet that the patient consumes. Also, the practitioner should advocate a diet using foods that are within the financial reach and cultural milieu of the patient. Ectopic fat deposition in liver and elsewhere adversely impacts insulin sensitivity. A weight loss strategy in children may help preserve insulin sensitivity.[150]

Modest weight losses of 5-10% were associated with significant improvements in cardiovascular disease risk factors (ie, decreased HbA1c levels, reduced blood pressure, increase in HDL cholesterol, and decrease in plasma triglycerides) in patients with type 2 diabetes mellitus. Risk factor reduction was even greater with losses of 10-15% of body weight.[151] Esposito et al reported greater benefit from a low-carbohydrate, Mediterranean-style diet compared with a low-fat diet in patients with newly diagnosed type 2 diabetes mellitus. [152] In a single-center, randomized trial, 215 overweight patients with newly diagnosed type 2 diabetes mellitus who had never been treated with antihyperglycemic drugs and whose HbA1c levels were less than 11% were assigned to either a Mediterranean-style diet (< 50% of daily calories from carbohydrates) or a low-fat diet (< 30% of daily calories from fat). After 4 years, participants assigned to the Mediterranean-style diet had lost more weight and had demonstrated more improvement in some measures of glycemic control and coronary risk than had participants consuming the low-fat diet; 44% of patients in the Mediterranean-style diet group required antihyperglycemic drug therapy, compared with 70% of those in the low-fat diet group. A study by Larsen et al concluded a high-protein diet offers no superior long-term therapeutic beneficial effect compared with a high-carbohydrate diet in the treatment of type 2 diabetes mellitus.[153] Already attenuated glucose disposal is not worsened by postprandial circulating amino acid concentration. Therefore, recommendations to restrict dietary proteins in patients with type 2 diabetes seem unwarranted.[154] A study by Lazo et al attested to the benefits of lifestyle intervention, which aimed at a minimum weight loss of 7%, on hepatic steatosis in those with type 2 diabetes.[155] Since there is no known treatment of nonalcoholic fatty liver disease, a weight loss strategy might help prevent progression to serious liver damage. In the Cardiovascular Health Study, phospholipid trans -palmitoleate levels were found to be associated with lower metabolic risk.[156] Trans -palmitoleate is principally derived from naturally occurring dairy and other ruminant trans -fats. Circulating trans -palmitoleate is associated with lower insulin resistance, incident of diabetes, and atherogenic dyslipidemia. Potential health benefits, therefore, need to be explored. Food-derived pro-oxidant advanced glycation end products may contribute to insulin resistance in clinical type 2 diabetes mellitus and may suppress protective mechanisms. Advanced glycation end product restriction may preserve native defenses and insulin sensitivity by maintaining a lower basal oxidative state.[157]

Management of Hypertension
The role of hypertension in increasing microvascular and macrovascular risk in patients with diabetes mellitus has been confirmed in the UKPDS and Hypertension Optimal Treatment (HOT) trials.[172, 173] The ADA suggests that the BP goal be below 130/80 mm Hg. In patients with greater than 1 g/d proteinuria and renal insufficiency, a more aggressive therapeutic goal (ie, 125/75 mm Hg) is advocated. According to the Veterans Affairs Diabetes Trial, a diastolic blood pressure of less than 70 mm Hg increases the risk of cardiovascular disease in patients with diabetes, even when systolic blood pressure is within the current guidelines (recommended range, < 140 mm Hg).[174] While ACE inhibitors, angiotensin receptor blockers (ARB), diuretics, beta blockers, and calcium channel blockers are all considered acceptable initial therapy, the author prefers inhibitors of the renin-angiotensin system (ie, ACE inhibitors, ARB) because of their proven renal protection effects in patients with diabetes. Many patients require multiple agents. Diuretics or calcium channel blockers frequently are useful as second and third agents. A study by Fogari et al found that, compared with amlodipine, the angiotensin II receptor antagonist losartan provided greater attenuation of left ventricular hypertrophy in hypertensive patients with type 2 diabetes.[175] A study by Hermado et al showed that treatment with antihypertensive medications taken at bedtime provide better ambulatory blood pressure control as well as significant reduction in cardiovascular morbidity and mortality when compared with taking medications upon waking.[176] The addition of the ARB telmisartan to usual care in patients at high risk for CVD did not prevent incident diabetes or lead to regression of IFG or IGT.[177]