American College of Physicians: Internal Medicine — Doctors for Adults ®


Type 2 diabetes mellitus

From the November ACP Observer, copyright 2005 by the American College of Physicians.

By any measure—clinical or financial—diabetes is a tremendously costly disease.

Asymptomatic while it becomes insidious, type 2 diabetes cost the U.S. economy $132 billion in 2002 in medical expenditures and lost productivity, according to the American Diabetes Association (ADA). That figure is expected to climb to $192 billion a year within 10 years if the American epidemics of obesity and hypertension remain unchecked.

And ADA officials last month warned that diabetes threatens to shorten Americans' life expectancy, reversing key life-span progress over the past century. As death rates for other killers—including stroke and heart disease—continue to fall, diabetes mortality rates are accelerating. (See "Age and diabetes diagnoses.")

Insulin crystals, as captured with a polarized light micrograph.

The prevalence and complications of diabetes also point to major gaps in the care of chronic disease. "Diabetes is not a terribly complicated disease to treat," said Nathaniel G. Clark, ACP Member, the ADA's national vice president for clinical affairs, "but it is generally poorly treated because there are so many factors to remember and because we lack a system of care."

Dr. Clark bluntly points to the need for information technology to help manage patients with the disease. "In a traditional office with no electronic capability, the chance of being able to render quality care is small," he said.

Until wider use of information technology is available, internists need to take current diabetes trends into account, he said, including the fact that type 2 diabetes is no longer just a problem for adults.

"Age can be very misleading," Dr. Clark said. "An increasing number of children, particularly adolescents, have type 2. And adults can develop type 1 diabetes."

Internists can look forward to new drugs as well as new drug classes and new delivery systems, such as inhaled forms of insulin. In the meantime, they need to continue to get help from other health care professionals, including nutritionists, nurse care managers and clinical pharmacists. (Also see, "Diabetes care innovations: group visits.")

"Clearly the old model of a doctor saying, 'You need to lose weight—why haven't you done that?' doesn't work," he said. "When doctors point out that a patient is too heavy, they have to be able to say, 'Let me have you talk to someone today who can give you some specific advice.'"

This edition of ACP Observer Special Focus is designed to help optimize your ability to diagnose, treat and manage patients with type 2 diabetes.


Diabetes has an asymptomatic phase that lasts between four to seven years during which complications can occur. It is often detected only through opportunistic testing.

There is no direct evidence indicating that universal screening for type 2 diabetes improves health outcomes or mortality rates. However, adults with risk factors for diabetes—including its most common complication, cardiovascular disease (CVD)—should be screened.

Other at-risk populations to screen include:

  • people age 45 years or older.

  • those with a family history of diabetes.

  • patients who are obese.

  • those with a history of gestational diabetes or who gave birth to a child weighing more than nine pounds.

  • patients with polycystic ovarian syndrome.

  • members of minority groups, likely due to genetic and environmental factors.

While no direct evidence supports specific screening intervals, expert panels have recommended screening at-risk patients every three years.

For patients with impaired fasting glucose—defined by the ADA as being between 100 mg/dL and 125 mg/dL—or impaired glucose tolerance, defined as a two-hour post-prandial value between 140 mg/dL and 199 mg/dL, recommend daily exercise and weight loss. Evidence also suggests that treating patients with impaired glucose tolerance with drugs like metformin delay onset of frank diabetes.


There are three ways to diagnose diabetes:

  • typical symptoms of hyperglycemia and a random blood glucose > 200 mg/dL.

  • a fasting plasma glucose > 126 mg/dL. If abnormal, repeat for confirmation.

  • a value at two hours on a glucose tolerance test > mg/dL after a 75 g oral glucose tolerance test.

Diagnosis also requires a careful evaluation for:

  • frequent urination, weight loss and fatigue
  • infections, particularly skin, foot, dental and genitourinary
  • visual problems, including acuity, central visual loss and eye pain
  • neuropathic complaints, such as burning, numbness and tingling in the extremities
  • diet and exercise history
  • medications, including oral hypoglycemic and antihypertensive agents
  • cardiovascular risk factors
  • other endocrine disorders, including polycystic ovarian syndrome and pituitary disorders
  • height, weight and blood pressure

Further testing will establish baselines and detect early diabetes complications. You should, for instance, give a dilated fundoscopic examination for retinopathy and urinary protein determination for early diabetic nephropathy, the leading cause of end-stage renal disease. Estimates show that the prevalence of retinopathy at the point of clinical diagnosis is between 10% and 37%, while 10% have nephropathy.

Follow-up tests include HA1c level, fasting lipid profile, serum creatinine, and urinary albumin-to-creatinine ratio or an equivalent measure to detect urinary protein.


Establish goals for glycemic control, with diet and exercise the cornerstones of diabetes therapy. Stress general diet principles including moderation and the use of complex carbohydrates and limited saturated fats.

All patients should be encouraged to quit smoking. You should also consider glucose monitoring as an adjunct to drug therapy. Although few data support the use of monitoring, it can help you adjust medications and guard against hypoglycemia.

Patients taking oral agents should use home blood glucose monitoring particularly after dose adjustments and during symptomatic hyper- or hypoglycemia. Patients taking insulin can use monitoring to prevent and document the timing and severity of hyper- and hypoglycemia.

Glucose monitoring should be done before meals and at bedtime to reflect fasting glucose levels as closely as possible. Also, have patients monitor post-meal levels, particularly if they have elevated HA1c despite normal fasting glucose levels.


Use drug therapy to prevent and treat micro- and macrovascular complications if diet and exercise don't adequately control hyperglycemia. All patients with type 2 diabetes should also take between 75 mg and 325 mg of aspirin a day unless they have specific contraindications.

When tailoring drug treatments, keep patient characteristics and preferences in mind and choose agents carefully. Avoid hypoglycemia and minimize patients' costs and weight gain.

Glycemic control

Target treatment to achieve an HA1c level of below 6.5 mg/dL or 7 mg/dL. Many different combinations of glucose-lowering agents are available, but consider metformin a first-line agent because it causes less hypoglycemia and weight gain and may improve cardiovascular risk. Side effects include nausea and diarrhea and possible lactive acidosis.

Other oral agents to consider are:

  • sulfonylureas, including glipizide and glimepiride. These stimulate insulin secretion in response to glucose. Watch for weight gain, and keep in mind that control may deteriorate over time.

  • nonsulfonylurea insulin secretagogues (repaglinide, nateglinide). These stimulate insulin production in response to post-meal hyperglycemia. Side effects include hypoglycemia, while repaglinide can bring on headaches.

  • alpha-glucosidase inhibitor (acarbose, miglitol). These reduce gastrointestinal carbohydrate absorption after a meal. Side effects include bloating and diarrhea.

  • thiazolidinediones (rosiglitazone, pioglitazone). These enhance muscle sensitivity to insulin. Side effects are weight gain and edema. Also check liver function tests at baseline and when clinically indicated thereafter.

Combinations of agents at lower doses may be more effective in lowering glucose levels with fewer side effects. Before adding additional agents, however, maximize the effects of existing therapy but be aware that patients often have a limited response when escalating from submaximal to maximal doses, particularly to sulfonylureas.

Exenatide is a new adjunctive therapy recently approved by the Food and Drug Administration. Consider prescribing this injectable drug when oral medications, such as metformin and sulfonylurea, do not achieve desired glucose control. During periods of hyperglycemia, exenatide stimulates first-phase response and insulin synthesis and moderates glucagon secretion. It also delays gastric emptying and has been shown to reduce food intake.

If oral agents do not achieve glycemic control, consider combining them with insulin. Options include:

  • Bedtime insulin plus daytime sulfonylurea. Use sulfonylurea in the morning and begin insulin NPH or insulin glargine, 10 units at bedtime. Titrate doses over time to achieve a target glycemic control of morning fasting glucose of between 90 mg/dL and 130 mg/dL.

  • Bedtime insulin plus metformin. Use metformin at 1,000 mg twice daily as well as NPH insulin at bedtime targeting the patient's fasting glucose level. You can titrate insulin rapidly with this combination because hypoglycemia is relatively uncommon.

If oral agents and bedtime insulin do not achieve glycemic control, consider other insulin regimens. Discontinue previous insulin secretagogue therapy before beginning multidose insulin treatments, and consider any of the following combinations:

  • daily injection of insulin glargine with rapid-acting insulin before meals.

  • multiple daily injections of regular insulin with NPH at bedtime.

  • twice-daily split-mixed (self-mixed NPH with regular) injection or insulin 75/25 before breakfast and dinner.

Start with a total daily dose of between 0.5 units/kg and 0.10 units/kg, and adjust dosages based on home glucose monitoring at two-week intervals. You can increase or decrease doses in 10% increments.

Pramlintide is another recently approved injectable therapy. It can be used before meals to help lower blood sugar levels in patients already on insulin. A synthetic analog of the human neuroendocrine hormone amylin, pramlintide is also secreted from beta cells with insulin. The drug slows gastric emptying and decreases appetite and glucagon secretion after meals.


Treat hypertension aggressively to reduce the risk of retinopathy and nephropathy, as well as macrovascular complications.

Treat to a target blood pressure of 130/80 mmHg. In patients with blood pressure above 130/80 mmHg but below 140/90 mmHg, lifestyle interventions should be used for a maximum of three months. If targets are not achieved, add pharmacologic agents. Patients with blood pressures above 140/90 mmHg should receive drug therapy in addition to lifestyle therapy from the start.

Start treatment with thiazide, angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs). Most patients with type 2 diabetes will need several agents—three or more is not uncommon—to achieve their target goal.

Consider thiazide diuretics, beta-blockers and calcium-channel blockers if ACE inhibitors and ARBs don't bring control or are not tolerated. Reserve alpha-blockers for patients who can't reach adequate control with other agents.

Consider patients' preferences, side effect profile and comorbidities when choosing treatments. Prescribe a beta-blocker to those with coronary heart disease; a diuretic, ACE inhibitor and beta-blocker to those with congestive heart failure; and an ACE-inhibitor or ARB to patients with proteinuria or overt nephropathy. Monitor this last group for proteinuria, serum creatinine and serum potassium while they're on therapy.


For primary prevention, consider statins for patients over age 40 who have one other cardiovascular risk factor, regardless of their baseline LDL level. For secondary prevention, begin all patients with diabetes on statins, regardless of their LDL and total cholesterol levels.

Maintain serum LDL cholesterol levels at less than 100 mg/dL. Patients with diabetes and CVD should try to reach an LDL cholesterol level of less than 70 mg/dL.

For patients with HDL cholesterol levels of less than 40 mg/dL and low or normal LDL levels, consider using fibrates to reduce macrovascular disease risk.

Watch for rhabdomyolysis and hepatitis in patients taking both a statin and gemfibrozil. And use niacin therapy cautiously because it can boost serum glucose.


Tailor treatment for painful neuropathy based on cost and patient preferences and comorbidities. Treatment options include:

  • Tricyclic antidepressants—such as 25 mg of nortriptyline—at bedtime, titrating based on pain relief. Watch for anticholinergic side effects, particularly in older patients.

  • Topical capsaicin cream, monitoring for burning sensation early in treatment.

  • Antiepileptics such as carbamazepine and gabapentin for patients who can't tolerate tricyclic antidepressants or topical medications.

Foot ulcers

Prevent foot ulcers with regular foot exams and patient education on scrupulous foot care. When necessary, initiate aggressive wound care and consider using antibiotics. Proper foot ulceration treatment can prevent amputation.


Teach patients and family members the signs, symptoms and treatment of hypoglycemia, and educate patients on smoking cessation and the importance of diet and exercise.

And encourage patients to keep information about their condition with them. Hypoglycemia may make them unable to communicate, so wearing a medical bracelet can help them get any necessary aid.

PIER modules for diabetes screening and treatment are online.


The information included herein should never be used as a substitute of clinical judgment and does not represent an official position of ACP.


Diabetes care innovations: group visits

Diabetes is often frustrating to treat because of its many potential complications. Marc Shalaby, FACP, an assistant professor of clinical medicine at Lehigh Valley Hospital in Allentown, Pa., has found a solution: group visits, a care innovation being increasingly implemented across the country.

For the past year and a half, Dr. Shalaby has held a two-hour diabetes education group meeting for eight to 12 patients every three to four months. His motivation? "It's tough to cover comprehensive diabetic care in the office, all in a 20-minute visit," he said. "Those who don't understand our decisions are the ones most likely not to change their therapy."

Dr. Shalaby spoke with Special Focus on the ins and outs of group visits:

On what happens during visits:

Everyone checks in so we see how patients are doing. We do physical exercises for about 15 minutes, then measure vital signs, refill prescriptions and do foot exams. We cover an educational topic for about 35 minutes, followed by a 15-minute question and answer period. My diabetes educator and I decide what we are going to cover, often with input from the group.

On results:

On average, everyone's numbers have improved significantly. For example, 60% of those participating are at blood pressure goal vs. 44% when we started. My subjective impression is that they have enjoyed the extra time spent with us and they like the socialization.

I like conducting the group visits because they let me focus on more intensive treatment during the regular office visits. Group visits count as a level three follow-up visit—so I break even, considering my time and that of my educator and nurse. You could make money if you have enough participants.

On the pros and cons:

For one, group visits get you out of the office. For another, you get insight into what works, and what doesn't.

On the downside, you may have to recruit regularly to keep the group from getting smaller and to maintain the break-even point. Also, we don't have electronic health records [EHRs], so we have to pull all those charts. Once we [have an EHR], it will be point and click.


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